bluuebunny/crossref_metadata_2025_split huggingface dataset:
Critical Components of the Pluripotency Network Are Targets for the p300/CBP Interacting Protein (p/CIP) in Embryonic Stem Cells
Authors: Chitilian J.M. , Thillainadesan G. , Manias J.L. , Chang W.Y. , Walker E. , Isovic M. , Stanford W.L. , Torchia J. 
Published: October 2013

Abstract
p/CIP, also known as steroid receptor coactivator 3 (SRC-3)/Nuclear Receptor Coactivator 3 (NCoA3), is a transcriptional coactivator that binds liganded nuclear hormone receptors, as well as other transcription factors, and facilitates transcription through direct recruitment of accessory factors. We have found that p/CIP is highly expressed in undifferentiated mouse embryonic stem cells (mESCs) and is downregulated during differentiation. siRNA-mediated knockdown of p/CIP decreased transcript levels of Nanog, but not Oct4 or Sox2. Microarray expression analysis showed that Klf4, Tbx3, and Dax-1 are significantly downregulated in mESCs when p/CIP is knocked down. Subsequent chromatin immunoprecipitation (ChIP) analysis demonstrated that Tbx3, Klf4, and Dax-1 are direct transcriptional targets of p/CIP. Using the piggyBac transposition system, a mouse ESC line that expresses Flag-p/CIP in a doxycycline-dependent manner was generated. p/CIP overexpression increased the level of target genes and promoted the formation of undifferentiated colonies. Collectively, these results indicate that p/CIP contributes to the maintenance of ESC pluripotency through direct regulation of essential pluripotency genes. To better understand the mechanism by which p/CIP functions in ESC pluripotency, we integrated our ChIP and transcriptome data with published protein-protein interaction and promoter occupancy data to draft a p/CIP gene regulatory network. The p/CIP gene regulatory network identifies various feed-forward modules including one in which p/CIP activates members of the extended pluripotency network, demonstrating that p/CIP is a component of this extended network. Stem Cells 2014;32:204–215
An Osteopontin-Integrin Interaction Plays a Critical Role in Directing Adipogenesis and Osteogenesis by Mesenchymal Stem Cells
Authors: Chen Qing , Shou Peishun , Zhang Liying , Xu Chunliang , Zheng Chunxing , Han Yanyan , Li Wenzhao , Huang Yin , Zhang Xiaoren , Shao Changshun , Roberts Arthur I. , Rabson Arnold B. , Ren Guangwen , Zhang Yanyun , Wang Ying , Denhardt David T. , Shi Yufang 
Published: October 2013

Abstract
An imbalance between normal adipogenesis and osteogenesis by mesenchymal stem cells (MSCs) has been shown to be related to various human metabolic diseases, such as obesity and osteoporosis; however, the underlying mechanisms remain elusive. We found that the interaction between osteopontin (OPN), an arginine-glycine-aspartate-containing glycoprotein, and integrin αv/β1 plays a critical role in the lineage determination of MSCs. Although OPN is a well-established marker during osteogenesis, its role in MSC differentiation is still unknown. Our study reveals that blockade of OPN function promoted robust adipogenic differentiation, while inhibiting osteogenic differentiation. Re-expression of OPN restored a normal balance between adipogenesis and osteogenesis in OPN−/− MSCs. Retarded bone formation by OPN−/− MSCs was also verified by in vivo implantation with hydroxyapatite-tricalcium phosphate, a bone-forming matrix. The role of extracellular OPN in MSC differentiation was further demonstrated by supplementation and neutralization of OPN. Blocking well-known OPN receptors integrin αv/β1 but not CD44 also affected MSC differentiation. Further studies revealed that OPN inhibits the C/EBPs signaling pathway through integrin αv/β1. Consistent with these in vitro results, OPN−/− mice had a higher fat to total body weight ratio than did wild-type mice. Therefore, our study demonstrates a novel role for OPN-integrin αv/β1 in regulating MSC differentiation. Stem Cells 2014;32:327–337
Concise Review: The Immune Status of Mesenchymal Stem Cells and Its Relevance for Therapeutic Application
Authors: Knaän-Shanzer Shoshan 
Published: October 2013

AbstractMultipotentiality and anti-inflammatory activity, the two main properties of mesenchymal stem cells (MSCs), underlie their therapeutic prospective. During the past decade, numerous studies in animal models and clinical trials explored the potential of MSCs in the treatment of diseases associated with tissue regeneration and inflammatory control. Other qualities of MSCs: ready accessibility in bone marrow and fat tissue and rapid expansion in culture make the therapeutic use of patients’ own cells feasible. The prevailing belief that MSCs are nonimmunogenic encouraged the use of unrelated donor cells in immune-competent recipients. The data emerging from studies performed with immune-incompatible cells in animal models for a wide-range of human diseases show, however, conflicting results and cast doubt on the immune privileged status of MSCs. Our analysis of the preclinical literature in this review is aimed to gain a better understanding of the therapeutic potential of immune-incompatible MSCs. Emphasis was laid on applications for enhancement of tissue repair in the absence of immune-suppressive therapy. Stem Cells 2014;32:603–608
Loss of Spastin Function Results in Disease-Specific Axonal Defects in Human Pluripotent Stem Cell-Based Models of Hereditary Spastic Paraplegia
Authors: Denton Kyle R. , Lei Ling , Grenier Jeremy , Rodionov Vladimir , Blackstone Craig , Li Xue-Jun 
Published: October 2013

Abstract
Human neuronal models of hereditary spastic paraplegias (HSP) that recapitulate disease-specific axonal pathology hold the key to understanding why certain axons degenerate in patients and to developing therapies. SPG4, the most common form of HSP, is caused by autosomal dominant mutations in the SPAST gene, which encodes the microtubule-severing ATPase spastin. Here, we have generated a human neuronal model of SPG4 by establishing induced pluripotent stem cells (iPSCs) from an SPG4 patient and differentiating these cells into telencephalic glutamatergic neurons. The SPG4 neurons displayed a significant increase in axonal swellings, which stained strongly for mitochondria and tau, indicating the accumulation of axonal transport cargoes. In addition, mitochondrial transport was decreased in SPG4 neurons, revealing that these patient iPSC-derived neurons recapitulate disease-specific axonal phenotypes. Interestingly, spastin protein levels were significantly decreased in SPG4 neurons, supporting a haploinsufficiency mechanism. Furthermore, cortical neurons derived from spastin-knockdown human embryonic stem cells (hESCs) exhibited similar axonal swellings, confirming that the axonal defects can be caused by loss of spastin function. These spastin-knockdown hESCs serve as an additional model for studying HSP. Finally, levels of stabilized acetylated-tubulin were significantly increased in SPG4 neurons. Vinblastine, a microtubule-destabilizing drug, rescued this axonal swelling phenotype in neurons derived from both SPG4 iPSCs and spastin-knockdown hESCs. Thus, this study demonstrates the successful establishment of human pluripotent stem cell-based neuronal models of SPG4, which will be valuable for dissecting the pathogenic cellular mechanisms and screening compounds to rescue the axonal degeneration in HSP. Stem Cells 2014;32:414–423
A Site-Specific Genetic Modification for Induction of Pluripotency and Subsequent Isolation of Derived Lung Alveolar Epithelial Type II Cells
Authors: Yan Qing , Quan Yuan , Sun Huanhuan , Peng Xinmiao , Zou Zhengyun , Alcorn Joseph L. , Wetsel Rick A. , Wang Dachun 
Published: October 2013

Abstract
Human induced pluripotent stem cells (hiPSCs) have great therapeutic potential in repairing defective lung alveoli. However, genetic abnormalities caused by vector integrations and low efficiency in generating hiPSCs, as well as difficulty in obtaining transplantable hiPSC-derived cell types are still major obstacles. Here we report a novel strategy using a single nonviral site-specific targeting vector with a combination of Tet-On inducible gene expression system, Cre/lox P switching gene expression system, and alveolar epithelial type II cell (ATIIC)-specific NeomycinR transgene expression system. With this strategy, a single copy of all of the required transgenes can be specifically knocked into a site immediately downstream of β-2-microglobulin (B2M) gene locus at a high frequency, without causing B2M dysfunction. Thus, the expression of reprogramming factors, Oct4, Sox2, cMyc, and Klf4, can be precisely regulated for efficient reprogramming of somatic cells into random integration-free or genetic mutation-free hiPSCs. The exogenous reprogramming factor transgenes can be subsequently removed after reprogramming by transient expression of Cre recombinase, and the resulting random integration-free and exogenous reprogramming factor-free hiPSCs can be selectively differentiated into a homogenous population of ATIICs. In addition, we show that these hiPSC-derived ATIICs exhibit ultrastructural characteristics and biological functions of normal ATIICs. When transplanted into bleomycin-challenged mice lungs, hiPSC-derived ATIICs efficiently remain and re-epithelialize injured alveoli to restore pulmonary function, preventing lung fibrosis and increasing survival without tumorigenic side effect. This strategy allows for the first time efficient generation of patient-specific ATIICs for possible future clinical applications. Stem Cells 2014;32:402–413
The Transition from Stem Cell to Progenitor Spermatogonia and Male Fertility Requires the SHP2 Protein Tyrosine Phosphatase
Authors: Puri Pawan , Phillips Bart T. , Suzuki Hitomi , Orwig Kyle E. , Rajkovic Aleksandar , Lapinski Philip E. , King Philip D. , Feng Gen-Sheng , Walker William H. 
Published: October 2013

AbstractSHP2 is a widely expressed protein tyrosine phosphatase required for signal transduction from multiple cell surface receptors. Gain and loss of function SHP2 mutations in humans are known to cause Noonan and LEOPARD syndromes, respectively, that are characterized by numerous pathological conditions including male infertility. Using conditional gene targeting in the mouse, we found that SHP2 is required for maintaining spermatogonial stem cells (SSCs) and the production of germ cells required for male fertility. After deleting SHP2, spermatogenesis was halted at the initial step during which transit-amplifying undifferentiated spermatogonia are produced from SSCs. In the absence of SHP2, proliferation of SSCs and undifferentiated spermatogonia was inhibited, thus germ cells cannot be replenished and SSCs cannot undergo renewal. However, germ cells beyond the undifferentiated spermatogonia stage of development at the time of SHP2 knockout were able to complete their maturation to become sperm. In cultures of SSCs and their progeny, inhibition of SHP2 activity reduced growth factor-mediated intracellular signaling that regulates SSC proliferation and cell fate. Inhibition of SHP2 also decreased the number of SSCs present in culture and caused SSCs to detach from supporting cells. Injection of mice with an SHP2 inhibitor blocked the production of germ cells from SSCs. Together, our studies show that SHP2 is essential for SSCs to maintain fertility and indicates that the pathogenesis of infertility in humans with SHP2 mutations is due to compromised SSC functions that block spermatogenesis. Stem Cells 2014;32:741–753
A generalized fault location method based on voltage sags for distribution network
Authors: Awalin Lilik Jamilatul , Mokhlis Hazlie , Abu Bakar AbHalim , Mohamad Hasmaini , Illias Hazlee A. 
Published: October 2013

AbstractAn enhanced fault location method based on voltage sag profiles for distribution networks is presented in this paper. In other previous methods, only a single measurement has been used. The proposed method can be used with any number of measurements in the network, making it more general. A new ranking approach that addresses multiple possibilities of the faulted section is proposed. Different case studies with various numbers of measurements are performed on a large 11‐kV network with the main feeder consisting of 42 buses to validate the method. The test results show that there is an improvement in terms of accuracy in detecting the faulted section in the first attempt for each additional measurement. Therefore, by utilizing the average value of each measurement, a better accuracy of fault location can be achieved. © 2013 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc.
Design of freely configurable safety light curtain using hemispherical mirrors
Authors: Lu Huimin , Serikawa Seiichi 
Published: October 2013

AbstractSafety light curtains provide reliable and cost‐effective protection against access into hazardous points or areas. However, in practice, peopl still need to adjust the light detection element accurately in order to receive the safe amount of irradiating laser light. In our proposed system, we utilized light emitting diodes (LEDs) as the light source, and designed two hemispherical mirrors to receive the LED light, and used PSoC microcomputer to determine the threshold voltage value. Compared with recent market products, the proposed system is freely configurable, and with no dead zone detection. In addition, compared to the laser light, the LED light has the advantages of no radiation, small electropult, low‐cost, and high efficiency. After conducting sufficient experiments, the proposed system has been found to successfully detect the intruder with 100% recognition rate, which can meet the needs of industrialization. © 2013 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc.
Development and external validation of new ultrasound‐based mathematical models for preoperative prediction of high‐risk endometrial cancer
Authors: Van Holsbeke C. , Ameye L. , Testa A. C. , Mascilini F. , Lindqvist P. , Fischerova D. , Frühauf F. , Fransis S. , de Jonge E. , Timmerman D. , Epstein E. 
Published: October 2013

ABSTRACTObjectivesTo develop and validate strategies, using new ultrasound‐based mathematical models, for the prediction of high‐risk endometrial cancer and compare them with strategies using previously developed models or the use of preoperative grading only.MethodsWomen with endometrial cancer were prospectively examined using two‐dimensional (2D) and three‐dimensional (3D) gray‐scale and color Doppler ultrasound imaging. More than 25 ultrasound, demographic and histological variables were analyzed. Two logistic regression models were developed: one ‘objective’ model using mainly objective variables; and one ‘subjective’ model including subjective variables (i.e. subjective impression of myometrial and cervical invasion, preoperative grade and demographic variables). The following strategies were validated: a one‐step strategy using only preoperative grading and two‐step strategies using preoperative grading as the first step and one of the new models, subjective assessment or previously developed models as a second step.ResultsOne‐hundred and twenty‐five patients were included in the development set and 211 were included in the validation set. The ‘objective’ model retained preoperative grade and minimal tumor‐free myometrium as variables. The ‘subjective’ model retained preoperative grade and subjective assessment of myometrial invasion. On external validation, the performance of the new models was similar to that on the development set. Sensitivity for the two‐step strategy with the ‘objective’ model was 78% (95% CI, 69–84%) at a cut‐off of 0.50, 82% (95% CI, 74–88%) for the strategy with the ‘subjective’ model and 83% (95% CI, 75–88%) for that with subjective assessment. Specificity was 68% (95% CI, 58–77%), 72% (95% CI, 62–80%) and 71% (95% CI, 61–79%) respectively. The two‐step strategies detected up to twice as many high‐risk cases as preoperative grading only. The new models had a significantly higher sensitivity than did previously developed models, at the same specificity.ConclusionTwo‐step strategies with ‘new’ ultrasound‐based models predict high‐risk endometrial cancers with good accuracy and do this better than do previously developed models. Copyright © 2013 ISUOG. Published by John Wiley & Sons Ltd.
The expanding tropics: a critical assessment of the observational and modeling studies
Authors: Lucas Christopher , Timbal Bertrand , Nguyen Hanh 
Published: October 2013

This review provides comprehensive coverage of the tropical expansion literature to date. The primary focus is on the annual‐ and zonal‐mean behavior of the phenomenon. An idealized model that identifies the mean meridional circulation as a hemisphere‐wide structure with significant tropical–extratropical interaction is introduced as background for the understanding of the expansion and the methodologies used for detection. A variety of metrics from different data sources have been used to identify an expansion of the global tropics since 1979 by 1°–3° latitude in each hemisphere, an average trend of approximately 0.5°–1.0° decade−1. The symmetry of this expansion—whether Northern and Southern hemispheres are expanding at the same rate—is unclear. Limitations of observational datasets, including reanalyses, prevent a more precise determination at this time. General circulation models are able to qualitatively reproduce this expansion, but generally underestimate its magnitude. Multiple factors have been identified as potential drivers of the expansion, including increasing greenhouses gases, stratospheric ozone depletion, and anthropogenic aerosols. No single factor by itself appears to explain the full expansion, perhaps a shortcoming of the models or experiment design. It may be that some combination of these forcings is producing the change, but the relative contribution of each forcing to the expansion is currently unknown. The key issues remaining to be resolved are briefly summarized at the end. WIREs Clim Change 2014, 5:89–112. doi: 10.1002/wcc.251This article is categorized under:

Paleoclimates and Current Trends > Modern Climate Change
Climate Models and Modeling > Knowledge Generation with Models
A compound event framework for understanding extreme impacts
Authors: Leonard Michael , Westra Seth , Phatak Aloke , Lambert Martin , van den Hurk Bart , McInnes Kathleen , Risbey James , Schuster Sandra , Jakob Doerte , Stafford‐Smith Mark 
Published: October 2013

Climate and weather variables such as rainfall, temperature, and pressure are indicators for hazards such as tropical cyclones, floods, and fires. The impact of these events can be due to a single variable being in an extreme state, but more often it is the result of a combination of variables not all of which are necessarily extreme. Here, the combination of variables or events that lead to an extreme impact is referred to as a compound event. Any given compound event will depend upon the nature and number of physical variables, the range of spatial and temporal scales, the strength of dependence between processes, and the perspective of the stakeholder who defines the impact. Modeling compound events is a large, complex, and interdisciplinary undertaking. To facilitate this task we propose the use of influence diagrams for defining, mapping, analyzing, modeling, and communicating the risk of the compound event. Ultimately, a greater appreciation of compound events will lead to further insight and a changed perspective on how impact risks are associated with climate‐related hazards. WIREs Clim Change 2014, 5:113–128. doi: 10.1002/wcc.252This article is categorized under:

Climate Models and Modeling > Knowledge Generation with Models
Assessing Impacts of Climate Change > Representing Uncertainty
A channel reservation and preemption model using overlapping regions in sector‐based cellular networks
Authors: Sheu Tsang‐Ling , Lin Chia‐Nan , Hwang Jenq‐Neng 
Published: October 2013

AbstractThis paper presents a channel reservation and preemption (CRP) model using overlapping regions in a cellular network with multiple sectors. To fully exploit and reuse the frequencies, directional antennas are installed on base stations (BSs) to divide the coverage into a number of equal‐sized sectors. When traffic is unevenly distributed across the sectors in a BS, channel utilization in every sector may become very different; low‐traffic sectors may be underutilized while high‐traffic sectors may be overutilized. A CRP scheme is thus proposed to more efficiently utilize free channels among sectors. CRP aims at reducing the dropping probabilities of handoff calls. Specifically, when free channels in a sector are not available, a handoff call, instead of being dropped, is allowed to preempt an ongoing call residing in the overlapping region of two adjacent sectors or two neighbor cells. Under CRP, the preempted ongoing call will not be disconnected, because it can switch over its service to the BS of a neighbor cell or to another directional antenna of an adjacent sector. For the purpose of evaluation, we build an analytical model for the proposed CRP using six‐tuple Markov chains. Analytical results show that the proposed CRP can significantly reduce the dropping probabilities of inter‐sector handoff calls, particularly when traffic between two sectors is not evenly distributed. Copyright © 2013 John Wiley & Sons, Ltd.
Subsystem density‐functional theory
Authors: Jacob Christoph R. , Neugebauer Johannes 
Published: October 2013

Subsystem density‐functional theory (subsystem DFT) has developed into a powerful alternative to Kohn–Sham DFT for quantum chemical calculations of complex systems. It exploits the idea of representing the total electron density as a sum of subsystem densities. The optimum total density is found by minimizing the total energy with respect to each of the subsystem densities, which breaks down the electronic‐structure problem into effective subsystem problems. This enables calculations on large molecular aggregates and even (bio‐)polymers without system‐specific parameterizations. We provide a concise review of the underlying theory, typical approximations, and embedding approaches related to subsystem DFT such as frozen‐density embedding (FDE). Moreover, we discuss extensions and applications of subsystem DFT and FDE to molecular property calculations, excited states, and wave function in DFT embedding methods. Furthermore, we outline recent developments for reconstruction techniques of embedding potentials arising in subsystem DFT, and for using subsystem DFT to incorporate constraints into DFT calculations.This article is categorized under:Structure and Mechanism > Computational Materials Science