bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cutting Edge: Regulatory T Cells Facilitate Cutaneous Wound Healing
Authors: Nosbaum Audrey , Prevel Nicolas , Truong Hong-An , Mehta Pooja , Ettinger Monika , Scharschmidt Tiffany C. , Ali Niwa H. , Pauli Mariela L. , Abbas Abul K. , Rosenblum Michael D. 
Published: January 2016

Abstract
Foxp3-expressing regulatory T cells (Tregs) reside in tissues where they control inflammation and mediate tissue-specific functions. The skin of mice and humans contain a large number of Tregs; however, the mechanisms of how these cells function in skin remain largely unknown. In this article, we show that Tregs facilitate cutaneous wound healing. Highly activated Tregs accumulated in skin early after wounding, and specific ablation of these cells resulted in delayed wound re-epithelialization and kinetics of wound closure. Tregs in wounded skin attenuated IFN-γ production and proinflammatory macrophage accumulation. Upon wounding, Tregs induce expression of the epidermal growth factor receptor (EGFR). Lineage-specific deletion of EGFR in Tregs resulted in reduced Treg accumulation and activation in wounded skin, delayed wound closure, and increased proinflammatory macrophage accumulation. Taken together, our results reveal a novel role for Tregs in facilitating skin wound repair and suggest that they use the EGFR pathway to mediate these effects.
Overlapping IgG4 Responses to Self- and Environmental Antigens in Endemic Pemphigus Foliaceus
Authors: Qian Ye , Jeong Joseph S. , Ye Jian , Dang Bim , Abdeladhim Maha , Aoki Valeria , Hans-Filhio Gunter , Rivitti Evandro A. , Valenzuela Jesus G. , Diaz Luis A. 
Published: January 2016

Abstract
The etiology of human autoimmune diseases in general remains largely unknown, although the genetic and environmental interplay may be relevant. This applies to the autoimmune diseases of the skin such as the pemphigus phenotypes and others. In this group, there is an endemic form of pemphigus foliaceus (also known as fogo selvagem [FS]) in which the pathogenic IgG4 autoantibody response to the self-antigen desmoglein 1 (Dsg1) cross-reacts with the LJM11 sand fly salivary gland Ag. In this investigation, we dissected the IgG4 autoantibody repertoires used by FS patients in response to endogenous self-Dsg1 and exogenous LJM11 sand fly Ag. Based on analyses of the genetic clonal signatures of these Abs, our results indicate that there is a significant overlap between these two responses, as all identified IgG4 mAbs cross-react to both Dsg1 and LJM11 Ags. Germline H- and L-chain V gene Abs generated according to mutated cross-reactive mAbs preserved their reactivity to both Ags. Our findings suggest that both Dsg1 autoantigen and LJM11 environmental Ag could be the initial antigenic stimulants for the IgG4 autoimmune responses in FS. These results support our hypothesis that LJM11 Ag plays a substantial role in triggering the IgG4 autoantibody development in FS and provide new insights on how noninfectious environmental Ag(s) may drive the generation of autoantibodies in IgG4-related autoimmune diseases.
Vitamin C Facilitates Demethylation of the Foxp3 Enhancer in a Tet-Dependent Manner
Authors: Sasidharan Nair Varun , Song Mi Hye , Oh Kwon Ik 
Published: January 2016

Abstract
Demethylation of CpG motifs in the Foxp3 intronic element, conserved noncoding sequence 2 (CNS2), is indispensable for the stable expression of Foxp3 in regulatory T cells (Tregs). In this study, we found that vitamin C induces CNS2 demethylation in Tregs in a ten-eleven-translocation 2 (Tet2)-dependent manner. The CpG motifs of CNS2 in Tregs generated in vitro by TGF-β (iTregs), which were methylated originally, became demethylated after vitamin C treatment. The conversion of 5-methylcytosin into 5-hydroxymethylcytosin was more efficient, and the methyl group from the CpG motifs of Foxp3 CNS2 was erased rapidly in iTregs treated with vitamin C. The effect of vitamin C disappeared in Tet2−/− iTregs. Furthermore, CNS2 in peripheral Tregs in vivo, which were demethylated originally, became methylated after treatment with a sodium-dependent vitamin C transporter inhibitor, sulfinpyrazone. Finally, CNS2 demethylation in thymic Tregs was also impaired in Tet2−/− mice, but not in wild type mice, when they were treated with sulfinpyrazone. Collectively, vitamin C was required for the CNS2 demethylation mediated by Tet proteins, which was essential for Foxp3 expression. Our findings indicate that environmental factors, such as nutrients, could bring about changes in immune homeostasis through epigenetic mechanisms.
Del tweet a la fotografía, la evolución de la comunicación política en Twitter hacia la imagen. El caso del debate del estado de la nación en España (2015)
Authors: Ruiz del Olmo Francisco Javier , Bustos Díaz Javier 
Published: January 2016

Este estudio analiza el uso de Twitter en la política y su evolución hacia un modelo comunicativo basado más en la imagen que en el contenido. Metodología. Esta investigación realiza un análisis cualitativo que tiene como objeto las imágenes publicadas en la red social Twitter por los principales partidos y líderes políticos españoles, durante el debate del estado de la nación que tuvo lugar entre el 24 y el 25 de febrero de 2015. Resultados. Los datos muestran el progresivo aumento de imágenes en la comunicación política en Twitter y visualizan sus categorías. Conclusiones. La investigación establece que las imágenes tienen una mayor relevancia que el propio texto y en muchos casos, la imagen se convierte en el principal vehículo de la comunicación política.
The Machine, the Mayor, and the Marine:
Authors: Leichtman Ellen C. 
Published: January 2016

ABSTRACT
The Republican machine, the mayor of Philadelphia, and the head of public safety all had input with regard to the enforcement of Prohibition in Philadelphia in 1924–25. W. Freeland Kendrick, a member of the Philadelphia machine, had won the mayoralty overwhelmingly in 1923 because he was the choice of machine head William S. Vare. The Republican machine did not support Prohibition and Vare expected Kendrick to turn a blind eye to the Prohibition laws. Kendrick, however, decided to appoint a Marine brigadier general, Smedley D. Butler, as the head of the Department of Public Safety. It was Butler's belief that all laws had to be upheld, including the Prohibition laws. Butler's methods of Prohibition enforcement were not popular with either the machine or the populace. Kendrick found himself between Vare and Butler. The result was that Kendrick fired Butler, and the machine destroyed Kendrick's future in politics.
Intimate Enemies:
Authors: Hornor Elizabeth 
Published: January 2016

ABSTRACT
During the mid-eighteenth century, relations between British Americans and Indians in North America were defined by the events of the Seven Years' War and Pontiac's War. A critical component of the relationship was the Native American capture of European American civilians, particularly those living on land simultaneously claimed by competing groups. Native American captivity had a long history in the colonies and continues to be studied by historians. This article concludes that the strict separation introduced by the Proclamation Line of 1763 was ineffective because it did not take into account the complexity of white-Indian relations at mid-century, but the ideology behind the Line's implementation resolved the tension that had been the defining character of life on simultaneously claimed land. That resolution had far-ranging effects, pointing to the lasting importance of Pontiac's War as well as the impact of those events on the continuing relationship between Native Americans and Americans.
The Mid-Atlantic and the American Revolution
Authors: Bodle Wayne 
Published: January 2016

ABSTRACT
This essay explores the mutual effects of the American Revolution and the Mid-Atlantic region on each other, with its principal emphasis on how the Revolution impacted the region, and somewhat less on the obverse consequences. Reviewing previously published and forthcoming arguments about how New York, New Jersey, Pennsylvania, and Delaware were a “fabricated” regional entity—a construct of political, economic, and social intention as much as or perhaps more than spatial imagination and geographical expression—it suggests that the cumulative impacts of the Seven Years' War, the British “imperial crisis” from 1763 to 1775, and the war of the American Revolution itself, uprooted and otherwise destroyed much of the spatial framing systems of the earlier colonial era. Notwithstanding these consequences, the article argues that the region's structural and functional integrity, as a shaper of both elite and more ordinary experience, largely survived the collapse and peeling away of this colonial “scaffolding.” It offers some tentative suggestions about how that improbable outcome may have obtained, and proposes some areas to which future research attention to the Mid-Atlantic should be paid.
The Only Things You Will Find in the Middle of the Road Are Double Yellow Lines, Dead Frogs, and Electoral Leverage:
Authors: Heineman Kenneth J. 
Published: January 2016

ABSTRACT
The Mid-Atlantic region of the United States, from its very inception, attracted visionaries, exiles, pacifists, and warriors—often united only by their suspicion of an overly assertive government. Over the course of the past four centuries, the Mid-Atlantic engendered melting-pot politics and a spirit of private initiative—allowing for partnerships with government when necessary. The middle of the Eastern Seaboard ultimately influenced the political culture of the middle of America—helping to bind the North together during the Civil War, laying the foundation for the New Deal, and continuing to influence national elections through the twenty-first century.
In Search of a Useable—and Hopeful—Environmental Narrative in the Mid-Atlantic
Authors: Magoc Chris J. 
Published: January 2016

ABSTRACT
Beyond a survey of some of the most recent traditional and public environmental history scholarship and trends in the Mid-Atlantic, this article—drawing from and reinterpreting the Turner Frontier Thesis—argues that the region both embodies broad currents of US environmental history and helped to establish American attitudes and patterns of behavior that migrated westward and shaped the course of national development. The article suggests that a Mid-Atlantic environmental history marked by such stories as mountaintop removal coal mining, urbanization, industrial disaster, environmental injustice, and the despoliation and ongoing recovery of rivers and watersheds like the Chesapeake and the Hudson is not only “typically” but “exceptionally” American. Further, the author notes that geography, environment, and natural resource history have shaped and informed heritage areas and other important recent work in public history, seeing in those trends the genesis of an era in which regional and subbioregional environmental histories can help inform and inspire new directions toward a more hopeful and sustainable future.
A Labored Mid-Atlantic Region Defined, Not Discovered:
Authors: Batch Rachel A. 
Published: January 2016

ABSTRACT
Despite expansive agendas in labor and working-class history, a Mid-Atlantic regional perspective has not been, and likely will not be, deemed useful in discerning historical change and causation for core questions in the field. Following a brief survey of labor historiography and its emerging directions, the author considers diverse ways of “finding” a region and regional identities through routes of work and place, and suggests that a Mid-Atlantic labor identity might be found in the “drama and debris” of the Great Strike of 1877 and during deindustrialization in the 1970s.
The Pennsylvania Historical and Museum Commission and the Papers of the Harmony Society:
Authors: Mattern Eleanor 
Published: January 2016

ABSTRACT
Among archivists and manuscript collectors, the term “replevin” commonly describes efforts by government archives to recover public records that are in private hands. At times, such efforts can provoke friction, raising questions about the line between public and private property rights. This article chronicles an atypical replevin case in Pennsylvania, one that focuses on the struggles over the ownership of papers of a private origin, but which became government property with their transfer to the Commonwealth in 1937. This is a custodial history of a collection of papers documenting the Harmony Society, a religious separatist society once located in western Pennsylvania and in southwest Indiana. It is a story that involves a former Harmonist, a scholar, misplaced trust, and recovery that highlights the complex psychology of ownership.
Occupational Mobility and Social Status: The Welsh Experience in Sharon, Pennsylvania, 1880–1930
Authors: Tyler Robert Llewellyn 
Published: January 2016

ABSTRACT
This article identifies the Welsh as a distinct ethnolinguistic community in Sharon, Mercer County, during the late nineteenth and early twentieth centuries and provides an analysis of intragenerational and intergenerational changes in socioeconomic status, as indicated by occupational shifts. The study provides a clearer picture than the images promulgated by contemporary Welsh leaders who strove to emphasize the industry and upward mobility of their fellow countrymen.
The Quaker Exiles: “The Cause of Every Inhabitant”
Authors: Whidbee Paige L. 
Published: January 2016

ABSTRACT
In 1777 twenty-two Philadelphia Quakers were arrested by the new American government, who suspected the Quakers harbored loyalist sentiments. They were unable to support any charges against them with evidence. To keep these Quakers incarcerated, the government denied them a hearing, removed them from Pennsylvania, and had them imprisoned at a farm in Virginia. Far from home and denied a hearing, the exiled Quakers resorted to publishing petitions, letters, and pamphlets to argue for their release. This article will show that these arguments succeeded because they employed the same rhetoric and ideals that the Revolution's leaders used to justify the fight for Independence. Quaker use of this rhetoric forced the Revolution's leaders to meaningfully confront the contradictions between their promises about liberty and their actions, and established the Friends' response strategy as an effective tool for similar groups to use in the future.
Alginate-Encapsulation for the Improved Hypothermic Preservation of Human Adipose-Derived Stem Cells
Authors: Swioklo Stephen , Constantinescu Andrei , Connon Che J. 
Published: January 2016

Abstract

Despite considerable progress within the cell therapy industry, unmet bioprocessing and logistical challenges associated with the storage and distribution of cells between sites of manufacture and the clinic exist. We examined whether hypothermic (4°C–23°C) preservation of human adipose-derived stem cells could be improved through their encapsulation in 1.2% calcium alginate. Alginate encapsulation improved the recovery of viable cells after 72 hours of storage. Viable cell recovery was highly temperature-dependent, with an optimum temperature of 15°C. At this temperature, alginate encapsulation preserved the ability for recovered cells to attach to tissue culture plastic on rewarming, further increasing its effect on total cell recovery. On attachment, the cells were phenotypically normal, displayed normal growth kinetics, and maintained their capacity for trilineage differentiation. The number of cells encapsulated (up to 2 × 106 cells per milliliter) did not affect viable cell recovery nor did storage of encapsulated cells in a xeno-free, serum-free,current Good Manufacturing Practice-grade medium. We present a simple, low-cost system capable of enhancing the preservation of human adipose-derived stem cells stored at hypothermic temperatures, while maintaining their normal function. The storage of cells in this manner has great potential for extending the time windows for quality assurance and efficacy testing, distribution between the sites of manufacture and the clinic, and reducing the wastage associated with the limited shelf life of cells stored in their liquid state.

Significance
Despite considerable advancement in the clinical application of cell-based therapies, major logistical challenges exist throughout the cell therapy supply chain associated with the storage and distribution of cells between the sites of manufacture and the clinic. A simple, low-cost system capable of preserving the viability and functionality of human adipose-derived stem cells (a cell with substantial clinical interest) at hypothermic temperatures (0°C–32°C) is presented. Such a system has considerable potential for extending the shelf life of cell therapy products at multiple stages throughout the cell therapy supply chain.
A Detailed Assessment of Varying Ejection Rate on Delivery Efficiency of Mesenchymal Stem Cells Using Narrow-Bore Needles
Authors: Amer Mahetab H. , Rose Felicity R.A.J. , White Lisa J. , Shakesheff Kevin M. 
Published: January 2016

Abstract

As the number of clinical trials exploring cell therapy rises, a thorough understanding of the limits of cell delivery is essential. We used an extensive toolset comprising various standard and multiplex assays for the assessment of cell delivery postejection. Primary human mesenchymal stem cell (hMSC) suspensions were drawn up into 100-µl Hamilton syringes with 30- and 34-gauge needles attached, before being ejected at rates ranging from 10 to 300 µl/minute. Effects of ejection rate, including changes in viability, apoptosis, senescence, and other key aspects of cellular health, were evaluated. Ejections at slower flow rates resulted in a lower percentage of the cell dose being delivered, and apoptosis measurements of samples ejected at 10 µl/minute were significantly higher than control samples. Immunophenotyping also revealed significant downregulation of CD105 expression in samples ejected at 10 µl/minute (p &lt; .05). Differentiation of ejected hMSCs was investigated using qualitative markers of adipogenesis, osteogenesis, and chondrogenesis, which revealed that slower ejection rates exerted a considerable effect upon the differentiation capacity of ejected cells, thereby possibly influencing the success of cell-based therapies. The findings of this study demonstrate that ejection rate has substantial impact on the percentage of cell dose delivered and cellular health postejection.

Significance
There are a growing number of clinical trials using mesenchymal stem cells (MSCs) for cellular therapy in a multitude of clinical targets. Numerous cell-therapy procedures use injection-based administration to deliver high-density cell preparations to the target site, either systemically or directly. However, there is growing evidence in the literature of a problem with cell injection methods in various cellular therapy applications. Because a thorough understanding of the limits of cell delivery is essential, an extensive toolset comprising various standard and multiplex assays was used for the assessment of cell delivery post-ejection. The effects of clinically relevant ejection rates and needles were assessed in terms of different aspects of cellular health of ejected human MSCs and their differentiation capacity. Our study emphasizes the potential impact of the administration protocol of cell suspensions and the importance of optimization of delivery parameters according to the nature and cellular responses of cells post-ejection. Our novel findings and comprehensive assessment of different parameters of cellular health and differentiation potential may be used to improve cell delivery using fine needles.
PCR‐Based Analysis of Mitochondrial DNA Copy Number, Mitochondrial DNA Damage, and Nuclear DNA Damage
Authors: Gonzalez‐Hunt Claudia P. , Rooney John P. , Ryde Ian T. , Anbalagan Charumathi , Joglekar Rashmi , Meyer Joel N. 
Published: February 2016

AbstractBecause of the role that DNA damage and depletion play in human disease, it is important to develop and improve tools to assess these endpoints. This unit describes PCR‐based methods to measure nuclear and mitochondrial DNA damage and copy number. Long amplicon quantitative polymerase chain reaction (LA‐QPCR) is used to detect DNA damage by measuring the number of polymerase‐inhibiting lesions present based on the amount of PCR amplification; real‐time PCR (RT‐PCR) is used to calculate genome content. In this unit, we provide step‐by‐step instructions to perform these assays in Homo sapiens, Mus musculus, Rattus norvegicus, Caenorhabditis elegans, Drosophila melanogaster, Danio rerio, Oryzias latipes, Fundulus grandis, and Fundulus heteroclitus, and discuss the advantages and disadvantages of these assays. © 2016 by John Wiley & Sons, Inc.
Plasma neurofilament light chain predicts progression in progressive supranuclear palsy
Authors: Rojas Julio C. , Karydas Anna , Bang Jee , Tsai Richard M. , Blennow Kaj , Liman Victor , Kramer Joel H. , Rosen Howard , Miller Bruce L. , Zetterberg Henrik , Boxer Adam L. 
Published: February 2016

AbstractObjectiveBlood‐based biomarkers for neurodegenerative conditions could improve diagnosis and treatment development. Neurofilament light chain (NfL), a marker of axonal injury, is elevated in cerebrospinal fluid (CSF) of patients with progressive supranuclear palsy (PSP). The goal of this study was to determine the diagnostic and prognostic value of plasma NfL in patients with PSP.MethodsPlasma NfL was measured with ultrasensitive digital immunoassay‐based technology at baseline and 1‐year follow‐up in a pilot cohort of 15 PSP patients and 12 healthy controls, and a validation cohort of 147 PSP patients. Mixed linear models tested the ability of plasma NfL to predict neurological, cognitive and functional decline, and brain atrophy.ResultsBaseline mean plasma NfL levels were elevated in PSP patients (31 ± 4 pg/mL, vs. control, 17.5 ± 1 pg/mL, P < 0.05) and this difference persisted at follow‐up. A cutoff value of 20 pg/mL related to the diagnosis of PSP with a sensitivity of 0.80 and specificity of 0.83 (positive likelihood ratio = 4.7 and a negative likelihood radio of 0.24). Patients with higher NfL levels had more severe neurological (PSPRS, −36.9% vs. −28.9%, P = 0.04), functional (SEADL, −38.2% vs. −20%, P = 0.03), and neuropsychological (RBANS, −23.9% vs. −12.3%, P = 001) deterioration over 1 year. Higher baseline NfL predicted greater whole‐brain and superior cerebellar peduncle volume loss. Plasma and CSF NfL were significantly correlated (r = 0.74, P = 0.002).InterpretationPlasma NfL is elevated in PSP and could be of value as a biomarker both to assist clinical diagnosis and to monitor pharmacodynamic effects on the neurodegenerative process in clinical trials.
Identification of NARMAX Hammerstein models with performance assessment using brain storm optimization algorithm
Authors: Pal Partha S. , Kar Rajib , Mandal Durbadal , Ghoshal Sakti P. 
Published: February 2016

SummaryIn this paper, brain storm optimization (BSO)‐based efficient identification approach has been applied to different types of stable and practically useful Nonlinear Auto Regressive Moving Average with exogenous noise (NARMAX) Hammerstein models with various performance criteria‐based assessments. Different performance measures of the estimation process like accuracy, precision and consistency have been established to ensure the general applicability and practical usefulness of the proposed approach. The accuracy and the precision of the parameter estimation are established with the corresponding bias and variance information, while the consistency has been justified with the help of hypothesis test results. BSO‐based optimum values of the output mean square errors and the parameters and their corresponding convergences ensure the stability and robustness of the proposed identification scheme. The comparative studies of the performance of the BSO algorithm with the other basic evolutionary algorithms have been reported with optimum values of the mean square errors, estimated values of the parameters, corresponding computational times and hypothesis test outcomes. Copyright © 2016 John Wiley & Sons, Ltd.