bluuebunny/crossref_metadata_2025_split huggingface dataset:
p300 and cAMP response element‐binding protein‐binding protein in skeletal muscle homeostasis, contractile function, and survival
Authors: Svensson Kristoffer , LaBarge Samuel A. , Sathe Abha , Martins Vitor F. , Tahvilian Shahriar , Cunliffe Jennifer M. , Sasik Roman , Mahata Sushil K. , Meyer Gretchen A. , Philp Andrew , David Larry L. , Ward Samuel R. , McCurdy Carrie E. , Aslan Joseph E. , Schenk Simon 
Published: January 2020

AbstractBackgroundReversible ε‐amino acetylation of lysine residues regulates transcription as well as metabolic flux; however, roles for specific lysine acetyltransferases in skeletal muscle physiology and function are unknown. In this study, we investigated the role of the related acetyltransferases p300 and cAMP response element‐binding protein‐binding protein (CBP) in skeletal muscle transcriptional homeostasis and physiology in adult mice.MethodsMice with skeletal muscle‐specific and inducible knockout of p300 and CBP (PCKO) were generated by crossing mice with a tamoxifen‐inducible Cre recombinase expressed under the human α‐skeletal actin promoter with mice having LoxP sites flanking exon 9 of the Ep300 and Crebbp genes. Knockout of PCKO was induced at 13–15 weeks of age via oral gavage of tamoxifen for 5 days to both PCKO and littermate control [wildtype (WT)] mice. Body composition, food intake, and muscle function were assessed on day 0 (D0) through 5 (D5). Microarray and tandem mass tag mass spectrometry analyses were performed to assess global RNA and protein levels in skeletal muscle of PCKO and WT mice.ResultsAt D5 after initiating tamoxifen treatment, there was a reduction in body weight (−15%), food intake (−78%), stride length (−46%), and grip strength (−45%) in PCKO compared with WT mice. Additionally, ex vivo contractile function [tetanic tension (kPa)] was severely impaired in PCKO vs. WT mice at D3 (~70–80% lower) and D5 (~80–95% lower) and resulted in lethality within 1 week—a phenotype that is reversed by the presence of a single allele of either p300 or CBP. The impaired muscle function in PCKO mice was paralleled by substantial transcriptional alterations (3310 genes; false discovery rate < 0.1), especially in gene networks central to muscle contraction and structural integrity. This transcriptional uncoupling was accompanied by changes in protein expression patterns indicative of impaired muscle function, albeit to a smaller magnitude (446 proteins; fold‐change > 1.25; false discovery rate < 0.1).ConclusionsThese data reveal that p300 and CBP are required for the control and maintenance of contractile function and transcriptional homeostasis in skeletal muscle and, ultimately, organism survival. By extension, modulating p300/CBP function may hold promise for the treatment of disorders characterized by impaired contractile function in humans.
Water–fat separation in spiral magnetic resonance fingerprinting for high temporal resolution tissue relaxation time quantification in muscle
Authors: Koolstra Kirsten , Webb Andrew G. , Veeger Thom T. J. , Kan Hermien E. , Koken Peter , Börnert Peter 
Published: January 2020

PurposeTo minimize the known biases introduced by fat in rapid T1 and T2 quantification in muscle using a single‐run magnetic resonance fingerprinting (MRF) water–fat separation sequence.MethodsThe single‐run MRF acquisition uses an alternating in‐phase/out‐of‐phase TE pattern to achieve water–fat separation based on a 2‐point DIXON method. Conjugate phase reconstruction and fat deblurring were applied to correct for B0 inhomogeneities and chemical shift blurring. Water and fat signals were matched to the on‐resonance MRF dictionary. The method was first tested in a multicompartment phantom. To test whether the approach is capable of measuring small in vivo dynamic changes in relaxation times, experiments were run in 9 healthy volunteers; parameter values were compared with and without water–fat separation during muscle recovery after plantar flexion exercise.ResultsPhantom results show the robustness of the water–fat resolving MRF approach to undersampling. Parameter maps in volunteers show a significant (P < .01) increase in T1 (105 ± 94 ms) and decrease in T2 (14 ± 6 ms) when using water–fat‐separated MRF, suggesting improved parameter quantification by reducing the well‐known biases introduced by fat. Exercise results showed smooth T1 and T2 recovery curves.ConclusionWater–fat separation using conjugate phase reconstruction is possible within a single‐run MRF scan. This technique can be used to rapidly map relaxation times in studies requiring dynamic scanning, in which the presence of fat is problematic.
Enhanced multi‐index Monte Carlo by means of multiple semicoarsened multigrid for anisotropic diffusion problems
Authors: Robbe Pieterjan , Nuyens Dirk , Vandewalle Stefan 
Published: January 2020

SummaryIn many models used in engineering and science, material properties are uncertain or spatially varying. For example, in geophysics and porous media flow, in particular, the uncertain permeability of the material is modeled as a random field. These random fields can be highly anisotropic. Efficient solvers, such as the multiple semicoarsened multigrid (MSG) method are required to compute solutions for various realizations of the uncertain material. The MSG method is an extension of the classic multigrid method, which uses additional coarse grids that are coarsened in only a single coordinate direction. In this sense, it closely resembles the extension of multilevel Monte Carlo to multi‐index Monte Carlo (MIMC). We present an unbiased MIMC method that reuses the MSG coarse solutions. Our formulation of the estimator can be interpreted as the problem of learning the unknown distribution of the number of samples across all indices and unifies the previous work on adaptive MIMC and unbiased estimation. We analyze the cost of this new estimator theoretically and present numerical experiments with various anisotropic random fields, where the unknown coefficients in the covariance model are considered as hyperparameters. We illustrate its robustness and superiority over unbiased MIMC without sample reuse.
Impact of EMA regulatory label changes on systemic diclofenac initiation, discontinuation, and switching to other pain medicines in Scotland, England, Denmark, and The Netherlands
Authors: Morales Daniel R. , Morant Steve V. , MacDonald Thomas M. , Mackenzie Isla S. , Doney Alexander S. F. , Mitchell Lyn , Bennie Marion , Robertson Chris , Hallas Jesper , Pottegard Anton , Ernst Martin Thomsen , Wei Li , Nicholson Lizzie , Morris Carole , Herings Ron M. C. , Overbeek Jetty A. , Smits Elisabeth , Flynn Robert W. V. 
Published: January 2020

AbstractPurposeIn June 2013 a European Medicines Agency referral procedure concluded that diclofenac was associated with an elevated risk of acute cardiovascular events and contraindications, warnings, and changes to the product information were implemented across the European Union. This study measured the impact of the regulatory action on the prescribing of systemic diclofenac in Denmark, The Netherlands, England, and Scotland.MethodsQuarterly time series analyses measuring diclofenac prescription initiation, discontinuation and switching to other systemic nonsteroidal anti‐inflammatory (NSAIDs), topical NSAIDs, paracetamol, opioids, and other chronic pain medication in those who discontinued diclofenac. Absolute effects were estimated using interrupted time series regression.ResultsOverall, diclofenac prescription initiations fell during the observation periods of all countries. Compared with Denmark where there appeared to be a more limited effect, the regulatory action was associated with significant immediate reductions in diclofenac initiation in The Netherlands (−0.42%, 95% CI, −0.66% to −0.18%), England (−0.09%, 95% CI, −0.11% to −0.08%), and Scotland (−0.67%, 95% CI, −0.79% to −0.55%); and falling trends in diclofenac initiation in the Netherlands (−0.03%, 95% CI, −0.06% to −0.01% per quarter) and Scotland (−0.04%, 95% CI, −0.05% to −0.02% per quarter). There was no significant impact on diclofenac discontinuation in any country. The regulatory action was associated with modest differences in switching to other pain medicines following diclofenac discontinuation.ConclusionsThe regulatory action was associated with significant reductions in overall diclofenac initiation which varied by country and type of exposure. There was no impact on discontinuation and variable impact on switching.
Identification of functional single nucleotide polymorphism of Populus trichocarpa PtrEPSP‐TF and determination of its transcriptional effect
Authors: Xie Meng , Zhang Jin , Singan Vasanth R. , McGranahan Melissa J. , LaFayette Peter R. , Jawdy Sara S. , Engle Nancy , Doeppke Crissa , Tschaplinski Timothy J. , Davis Mark F. , Lindquist Erika , Barry Kerrie , Schmutz Jeremy , Parrott Wayne A. , Chen Feng , Tuskan Gerald A. , Chen Jin‐Gui , Muchero Wellington 
Published: January 2020

AbstractIn plants, the phenylpropanoid pathway is responsible for the synthesis of a diverse array of secondary metabolites that include lignin monomers, flavonoids, and coumarins, many of which are essential for plant structure, biomass recalcitrance, stress defense, and nutritional quality. Our previous studies have demonstrated that Populus trichocarpa PtrEPSP‐TF, an isoform of 5‐enolpyruvylshikimate 3‐phosphate (EPSP) synthase, has transcriptional activity and regulates phenylpropanoid biosynthesis in Populus. In this study, we report the identification of single nucleotide polymorphism (SNP) of PtrEPSP‐TF that defines its functionality. Populus natural variants carrying this SNP were shown to have reduced lignin content. Here, we demonstrated that the SNP‐induced substitution of 142nd amino acid (PtrEPSP‐TFD142E) dramatically impairs the DNA‐binding and transcriptional activity of PtrEPSP‐TF. When introduced to a monocot species rice (Oryza sativa) in which an EPSP synthase isoform with the DNA‐binding helix‐turn‐helix (HTH) motif is absent, the PtrEPSP‐TF, but not PtrEPSP‐TFD142E, activated genes in the phenylpropanoid pathway. More importantly, heterologous expression of PtrEPSP‐TF uncovered five new transcriptional regulators of phenylpropanoid biosynthesis in rice. Collectively, this study identifies the key amino acid required for PtrEPSP‐TF functionality and provides a strategy to uncover new transcriptional regulators in phenylpropanoid biosynthesis.
Association between immunosuppressive cytokines and PSA progression in biochemically recurrent prostate cancer treated with intermittent hormonal therapy
Authors: Hawley Jessica E. , Pan Samuel , Figg William D. , Lopez‐Bujanda Zoila A. , Strope Jonathan D. , Aggen David H. , Dallos Matthew C. , Lim Emerson A. , Stein Mark N. , Hu Jianhua , Drake Charles G. 
Published: January 2020

AbstractBackgroundImmunosuppressive cytokines have the potential to promote prostate cancer progression. Assessing their longitudinal changes may implicate mechanisms of progression, treatment resistance, and suggest new therapeutic targets.MethodsThirty‐seven men with biochemically recurrent (BCR) prostate cancer who received 6 months of androgen deprivation therapy (ADT) and were monitored until the time to prostate‐specific antigen progression (TTPP) were identified from a completed phase III trial (NCT00020085). Serum samples were archived at baseline, 3 months after ADT, and at TTPP. Cytokine concentrations were quantified using a 36‐parameter electrochemiluminescence assay. The Wilcoxon signed‐rank sum test was used to compare observations between time points. Kaplan‐Meier analysis was used to calculate TTPP dichotomized by cytokine values above or below the median. Pearson's rank correlation coefficient was used to compare continuous variables.ResultsMedian TTPP was 399 days (range, 114‐1641). Median prostate‐specific antigen (PSA) at baseline and progression were 8.5 and 5.3 ng/mL, respectively. Twenty‐three patients (62%) achieved undetectable PSA with ADT. Castrate levels of testosterone (<50 ng/dL) after 3 months of ADT occurred in 35 patients (95%). TNF‐α (P = .002), IL‐23 (P = .002), and CXCL10 (P = .001) significantly increased from baseline to post ADT. Certain cytokines correlated longitudinally: TNF‐α correlated with IL‐23 (r = .72; P < .001) and IL‐8 (r = .59; P < .001) from baseline to post ADT and to PSA progression. Neutrophil‐to‐lymphocyte ratio correlated with IL‐27 (r = .57; P < .001) and MIP‐3α (r = .56; P < .001). Patients with a detectable PSA after ADT had elevated levels of IL‐6 (P = .049) and IL‐8 (P = .013) at PSA progression as compared with those with an undetectable PSA. There was a trend toward shorter TTPP in patients with TNF‐α levels above the median (P = .042).ConclusionsSeveral innate cytokines were associated with biochemically recurrent prostate cancer.
A protocol for using attenuated total reflection Fourier‐transform infrared spectroscopy for pre‐screening ancient bone collagen prior to radiocarbon dating
Authors: Naito Yuichi I. , Yamane Masako , Kitagawa Hiroyuki 
Published: January 2020

RationalePre‐screening of bone collagen quality is important to reduce the cost for analyses such as radiocarbon (14C) dating with accelerator mass spectrometry in archaeological studies. We developed a pre‐screening protocol based on attenuated total reflection (ATR) Fourier‐transform infrared spectroscopy (FTIR) for assessing the chemical composition and mineralogy of ancient bone samples.MethodsATR‐FTIR measurements were performed on bulk bones of diverse origin and age before collagen extraction. The percentage nitrogen of bulk bones, as well as the weight percentage, and the percentage carbon and nitrogen of extracted organic matter were noted. Several machine learning algorithms were applied to the spectral data and compared for their efficacy in screening for well preserved collagen.ResultsThe results showed that (a) the first derivative of the spectral data was better suited to screening than the raw FTIR data, especially for a wider spectral range and (b) certain classification algorithms [e.g. gradient boosting machine (GBM)] were able to efficiently predict the degree of preservation in bone samples.ConclusionsThis pre‐screening protocol can serve as a fast, concise and inexpensive pre‐screening tool for determining relative degrees of preservation before collagen extraction and subsequent 14C dating. The screening power based on the machine learning techniques can be further improved by accumulating the FTIR spectral data of bones.
Towards reliable digital forensics investigations through measurement science
Authors: Hughes Nicolas , Karabiyik Umit 
Published: January 2020

AbstractValidation is the scientifically accepted methodology for demonstrating the accuracy and reliability of a process. Currently, digital forensics discipline does not conduct the sort of validation testing needed to develop statistical confidence in tool performance, or to generate the empirical data needed to bring objectivity to examiner conclusions. Recently recommended standards provide more reliable results, and tool testing programs provide a better understanding of tools' limitations. However, these efforts do not constitute testing over the full range of expected target device conditions, product functionality, and target device configurations which are needed for validation testing. Several major impediments to validation testing include a lack of validation methods, a lack of reference data, and a lack of the definitional precision and low‐level specificity needed to establish a system of measurement in digital forensics. This study attempts to identify the remaining needs that prevent comprehensive validation in digital forensics and identify potential solutions to address those needs.This article is characterized under:Digital and Multimedia Science > Cyber Threat IntelligenceJurisprudence and Regulatory Oversight > Interdisciplinary Collaboration
Introduction: Historical Trajectories of Education and Development in (Post)Colonial Africa
Authors: Matasci Damiano , Jerónimo Miguel Bandeira , Dores Hugo Gonçalves 
Published: January 2020

AbstractThis chapter addresses the historical trajectories of education and development in the twentieth century (post)colonial Africa, framing the main goals of this collective book. It discusses the three key phases during which the economic and social goals of education were profoundly reconfigured. The first phase, spanning the period between 1900 and 1930, coincided with the introduction of the first “native” educational systems in the wake of the “scramble for Africa.” Debates on colonial education subsequently evolved starting from the 1930s. The effects of the Great Depression and the Second World War encouraged more attention being paid to economic and social repercussions of education in colonial contexts. Finally, the independence wave sweeping over the early 1960s opened up a third phase marked by the political aspirations of the new independent states and Cold War rivalries.
The Fabric of Academic Communities at the Heart of the British Empire’s Modernization Policies
Authors: Charton Hélène 
Published: January 2020

Abstract
This chapter considers the role played by education reforms in the new social and political agenda launched in the British Empire at the beginning of the 1940s. Setting up colonial universities in African British colonies as well as increasing the number of scholarships granted to Africans to study at British universities were policies at the heart of educational modernization. These training programs strongly contributed to the shaping of extended imperial communities which embodied the new links London was trying to establish within the Empire. The East African case shows that these new communities were built on a common set of values, practices, and references spread by British higher education institutions at home and in the colonies, meant to replace prevailing race distinctions underlying the former colonial order. The development of an imperial elite was far from easy as evidenced by the many types of resistance that arose both in the colonies and Great Britain.
Welfare and Education in British Colonial Africa, 1918–1945
Authors: Kallaway Peter 
Published: January 2020

AbstractThe current discussions about the decolonization of education and its relationship to issues of development raise important questions about the nature of colonial education and require us to avoid the reification of such notions if we are to gain an ample understanding of their meaning. It is important therefore to understand the complexities of educational discourse, policy and practices in colonial contexts, and how they were transferred to the “development debates” of the post-colonial era. The key theme that runs through all of these policy issues is the complexity of the issues involved and the need for a nuanced understanding of the ambiguities of educational theory and practice in an era of unprecedented radical political, social and economic change globally on the African and South African context.
Kinematik und Dynamik räumlicher Stöße von Kugeln
Authors: Willert Emanuel 
Published: January 2020

ZusammenfassungDie dreidimensionale Dynamik allgemeiner, zusammenstoßender Körper ist kompliziert und erlaubt im Zusammenhang mit der jeweiligen Kontaktmechanik des Stoßes in der Regel weder eine analytische Behandlung noch eine auch nur ansatzweise überschaubare Darstellung der vollständigen Lösung.
Die Methode der Dimensionsreduktion in der Kontaktmechanik
Authors: Willert Emanuel 
Published: January 2020

ZusammenfassungSehr viele rotationssymmetrische Kontaktprobleme können exakt auf Kontakte zwischen einem entsprechend zu wählenden starren ebenen Profil und einer eindimensionalen Bettung von linearen, unabhängigen verallgemeinerten Federelementen abgebildet werden. Der mathematische und numerische Aufwand zur Behandlung solcher Kontakte ist deutlich geringer als im Fall des rotationssymmetrischen Originals; mathematisch durch die Rückführung des mehrdimensionalen Randwertproblems auf einfache algebraische Operationen und die Analysis einer einzigen Veränderlichen, numerisch durch die Reduktion der Freiheitsgrade und (was noch wichtiger ist) deren Entkopplung. Den Abbildungsschritt von dem dreidimensionalen, axialsymmetrischen Original auf das ebene Ersatzsystem leistet die Methode der Dimensionsreduktion (MDR), die in den letzten 10 Jahren am Fachgebiet für Systemdynamik und Reibungsphysik der TU Berlin entwickelt und in einer Vielzahl von Publikationen dokumentiert wurde und auf deren Grundlage der überwiegende Teil der numerischen Rechnungen dieses Buches entstanden ist.
Ausgewählte Anwendungen von Stoßproblemen
Authors: Willert Emanuel 
Published: January 2020

ZusammenfassungNach der Darstellung der dynamischen und kontaktmechanischen Grundlagen und der ausführlichen Untersuchung des Stoßproblems unter verschiedenen Bedingungen stehen in diesem Kapitel Anwendungsbereiche aus Physik, Technik und Medizin im Mittelpunkt, für die die in den früheren Kapiteln gezeigten Ergebnisse von Bedeutung sind. Die Gebiete, in denen die gezeigten kontaktmechanischen Grundlagen und Lösungen von Stoßproblemen Relevanz haben, sind teilweise selbst riesige Forschungszweige, die in jeweils kurzen Unterkapiteln natürlich nicht annähernd erschöpfend dargestellt werden können. Der Stil des Kapitels unterscheidet sich daher von dem der früheren Teile dieses Buches: Die behandelten Themen werden nicht mehr umfassend und mathematisch detailliert entwickelt; stattdessen wird „nur“ beschrieben, welche Fragestellungen in welchen Anwendungsgebieten auftreten und wie man eventuell die in den früheren Kapiteln hergeleiteten Ergebnisse zur Behandlung dieser Fragen verwenden kann.
The Commercialisation of Rice Farming in Cambodia
Authors: Cramb Rob , Sareth Chea , Vuthy Theng 
Published: January 2020

AbstractIn this and the next five chapters the focus is on the commercialisation of rice farming in the Central Plain of Cambodia. Particularly since 2010, rice has come to be seen as more than merely a subsistence crop or a staple for domestic consumption but as “white gold”—a commodity with major commercial, including export potential. This chapter sets the scene for the in-depth studies on the commercialisation of rice farming in Cambodia by describing the rice-growing environment in Cambodia as a whole, outlining the history of rice production in Cambodia, examining the role of the rice sector in the rapid agricultural and economic growth in Cambodia since 1993, highlighting the changes at the farm level that have underpinned this agricultural growth, and providing a profile of Takeo Province within this larger context. Cambodia has a long history and comparative advantage in rice production. With relative political stability and access to improved varieties and other inputs, farmers have been able to increase the area cultivated and especially per-hectare yields so that total production has grown at over 5% since 1990. From being a rice-deficit country in the 1980s, the country has achieved self-sufficiency and, since 2010, become a serious exporter of paddy and milled rice. Rice farmers in Takeo Province have long made an important contribution to Cambodia’s rice production and currently contribute 8% of wet season output and 19% of dry season output, as well as a major share of exports.