bluuebunny/crossref_metadata_2025_split huggingface dataset:
Histone chaperone APLF regulates induction of pluripotency in murine fibroblasts
Authors: Syed Khaja Mohieddin , Joseph Sunu , Mukherjee Ananda , Majumder Aditi , Teixeira Jose M. , Dutta Debasree , Pillai Madhavan Radhakrishna 
Published: November 2016

ABSTRACT
Induction of pluripotency in differentiated cells through the exogenous expression of the transcription factors Oct4, Sox2, Klf4 and cellular Myc involves reprogramming at the epigenetic level. Histones and their metabolism governed by histone chaperones constitute an important regulator of epigenetic control. We hypothesized that histone chaperones facilitate or inhibit the course of reprogramming. For the first time, we report here that the downregulation of histone chaperone Aprataxin PNK-like factor (APLF) promotes reprogramming by augmenting the expression of E-cadherin (Cdh1), which is implicated in the mesenchymal-to-epithelial transition (MET) involved in the generation of induced pluripotent stem cells (iPSCs) from mouse embryonic fibroblasts (MEFs). Downregulation of APLF in MEFs expedites the loss of the repressive MacroH2A.1 (encoded by H2afy) histone variant from the Cdh1 promoter and enhances the incorporation of active histone H3me2K4 marks at the promoters of the pluripotency genes Nanog and Klf4, thereby accelerating the process of cellular reprogramming and increasing the efficiency of iPSC generation. We demonstrate a new histone chaperone (APLF)–MET–histone modification cohort that functions in the induction of pluripotency in fibroblasts. This regulatory axis might provide new mechanistic insights into perspectives of epigenetic regulation involved in cancer metastasis.
A blinded randomised placebo-controlled trial investigating the efficacy of morphine analgesia for procedural pain in infants: Trial protocol
Authors: Slater Rebeccah , Hartley Caroline , Moultrie Fiona , Adams Eleri , Juszczak Ed , Rogers Richard , Norman Jane E. , Patel Chetan , Stanbury Kayleigh , Hoskin Amy , Green Gabrielle ,   Poppi Trial Team
Published: November 2016

Infant pain has both immediate and long-term negative consequences, yet in clinical practice it is often undertreated. To date, few pain-relieving drugs have been tested in infants. Morphine is a potent analgesic that provides effective pain relief in adults, but there is inconclusive evidence for its effectiveness in infants. The purpose of this study is to establish whether oral morphine provides effective analgesia for procedural pain in infants. A blinded, placebo-controlled, parallel-group randomized, phase II, clinical trial will be undertaken to determine whether morphine sulphate administered orally prior to clinically-required retinopathy of prematurity (ROP) screening and heel lancing provides effective analgesia.  156 infants between 34 and 42 weeks’ gestational age who require a clinical heel lance and ROP screening on the same test occasion will be included in the trial. Infants will be randomised to receive either a single dose of morphine sulphate (100 μg/kg) or placebo. Each infant will be monitored for 48 hours and safety data will be collected during the 24 hours following drug administration. The primary outcome will be the Premature Infant Pain Profile–revised (PIPP-R) score 30 seconds after ROP screening. The co-primary outcome will be the magnitude of nociceptive-specific brain activity evoked by a clinically-required heel lance. Infant clinical stability will be assessed by comparing the number of episodes of bradycardia, tachycardia, desaturation and apnoea, and changes in respiratory support requirements in the 24-hour periods before and after the clinical intervention. In addition, drug safety will be assessed by considering the occurrence of apnoeic and hypotensive episodes requiring intervention in the 24-hour period following drug administration. This study has been published as an Accepted Protocol Summary by The Lancet.
Cerebral lateralisation of first and second languages in bilinguals assessed using functional transcranial Doppler ultrasound
Authors: Grabitz Clara R. , Watkins Kate E. , Bishop Dorothy V. M. 
Published: November 2016

Background: Lateralised representation of language in monolinguals is a well-established finding, but the situation is much less clear when there is more than one language. Studies to date have identified a number of factors that might influence the brain organisation of language in bilinguals. These include proficiency, age of acquisition and exposure to the second language. The question as to whether the cerebral lateralisation of first and second languages are the same or different is as yet unresolved. Methods: We used functional transcranial Doppler sonography (FTCD) to measure cerebral lateralisation in the first and second languages in 26 high proficiency bilinguals with German or French as their first language (L1) and English as their second language (L2). FTCD was used to measure task-dependent blood flow velocity changes in the left and right middle cerebral arteries during word generation cued by single letters. Language history measures and handedness were assessed through self-report questionnaires. Results:The majority of participants were significantly left lateralised for both L1 and L2, with no significant difference in the size of asymmetry indices between L1 and L2. Asymmetry indices for L1 and L2 were not related to language history, such as proficiency of the L2. Conclusion: In highly proficient bilinguals, there is strong concordance for cerebral lateralisation of first and second languages.
COMPASS: Continuous Open Mouse Phenotyping of Activity and Sleep Status
Authors: Brown Laurence A. , Hasan Sibah , Foster Russell G. , Peirson Stuart N. 
Published: November 2016

Background: Disruption of rhythms in activity and rest occur in many diseases, and provide an important indicator of healthy physiology and behaviour. However, outside the field of sleep and circadian rhythm research, these rhythmic processes are rarely measured due to the requirement for specialised resources and expertise. Until recently, the primary approach to measuring activity in laboratory rodents has been based on voluntary running wheel activity. By contrast, measuring sleep requires the use of electroencephalography (EEG), which involves invasive surgical procedures and time-consuming data analysis. Methods: Here we describe a simple, non-invasive system to measure home cage activity in mice based upon passive infrared (PIR) motion sensors. Careful calibration of this system will allow users to simultaneously assess sleep status in mice. The use of open-source tools and simple sensors keeps the cost and the size of data-files down, in order to increase ease of use and uptake. Results: In addition to providing accurate data on circadian activity parameters, here we show that extended immobility of >40 seconds provides a reliable indicator of sleep, correlating well with EEG-defined sleep (Pearson’s r >0.95, 4 mice). Conclusions: Whilst any detailed analysis of sleep patterns in mice will require EEG, behaviourally-defined sleep provides a valuable non-invasive means of simultaneously phenotyping both circadian rhythms and sleep. Whilst previous approaches have relied upon analysis of video data, here we show that simple motion sensors provide a cheap and effective alternative, enabling real-time analysis and longitudinal studies extending over weeks or even months. The data files produced are small, enabling easy deposition and sharing. We have named this system COMPASS - Continuous Open Mouse Phenotyping of Activity and Sleep Status. This simple approach is of particular value in phenotyping screens as well as providing an ideal tool to assess activity and rest cycles for non-specialists.
Highly variable penetrance of abnormal phenotypes in embryonic lethal knockout mice
Authors: Wilson Robert , Geyer Stefan H. , Reissig Lukas , Rose Julia , Szumska Dorota , Hardman Emily , Prin Fabrice , McGuire Christina , Ramirez-Solis Ramiro , White Jacqui , Galli Antonella , Tudor Catherine , Tuck Elizabeth , Mazzeo Cecilia Icoresi , Smith James C. , Robertson Elizabeth , Adams David J. , Mohun Timothy , Weninger Wolfgang J. 
Published: November 2016

Background: Identifying genes that are essential for mouse embryonic development and survival through term is a powerful and unbiased way to discover possible genetic determinants of human developmental disorders. Characterising the changes in mouse embryos that result from ablation of lethal genes is a necessary first step towards uncovering their role in normal embryonic development and establishing any correlates amongst human congenital abnormalities. Methods: Here we present results gathered to date in the Deciphering the Mechanisms of Developmental Disorders (DMDD) programme, cataloguing the morphological defects identified from comprehensive imaging of 220 homozygous mutant embryos from 42 lethal and subviable lines, analysed at E14.5. Results: Virtually all embryos show multiple abnormal phenotypes and amongst the 42 lines these affect most organ systems. Within each mutant line, the phenotypes of individual embryos form distinct but overlapping sets. Subcutaneous edema, malformations of the heart or great vessels, abnormalities in forebrain morphology and the musculature of the eyes are all prevalent phenotypes, as is loss or abnormal size of the hypoglossal nerve. Conclusions: Overall, the most striking finding is that no matter how profound the malformation, each phenotype shows highly variable penetrance within a mutant line. These findings have challenging implications for efforts to identify human disease correlates.
The LonDownS adult cognitive assessment to study cognitive abilities and decline in Down syndrome
Authors: Startin Carla M. , Hamburg Sarah , Hithersay Rosalyn , Davies Amy , Rodger Erin , Aggarwal Nidhi , Al-Janabi Tamara , Strydom André 
Published: November 2016

Background:Down syndrome (DS), the most common genetic cause of intellectual disability, is associated with an ultra-high risk of developing Alzheimer’s disease. However, there is individual variability in the onset of clinical dementia and in baseline cognitive abilities prior to decline, particularly in memory, executive functioning, and motor coordination. The LonDownS Consortium aims to determine risk and protective factors for the development of dementia and factors relating to cognitive abilities in people with DS. Here we describe our cognitive test battery and related informant measures along with reporting data from our baseline cognitive and informant assessments.Methods:We developed a cognitive test battery to assess general abilities, memory, executive function, and motor coordination abilities in adults with DS, with informant ratings of similar domains also collected, designed to allow for data on a broad range of participants. Participants (n=305) had a range of ages and abilities, and included adults with and without a clinical diagnosis of dementia.Results:Results suggest the battery is suitable for the majority of adults with DS, although approximately half the adults with dementia were unable to undertake any cognitive task. Many test outcomes showed a range of scores with low floor and ceiling effects. Non-verbal age-adjusted IQ scores had lower floor effects than verbal IQ scores. Before the onset of any cognitive decline, females aged 16-35 showed better verbal abilities compared to males. We also identified clusters of cognitive test scores within our battery related to visuospatial memory, motor coordination, language abilities, and processing speed / sustained attention.Conclusions:Our further studies will use baseline and longitudinal assessments to explore factors influencing cognitive abilities and cognitive decline related to ageing and onset of dementia in adults with DS.
The Eastern waterfront area of Lisbon: progress, decline and regeneration.
Authors: Nevado Ana 
Published: November 2016

Urban regeneration represents the future of contemporary cities, seeking for better life conditions of populations and environment. As a strategy, process and political instrument, it is inserted in strategic guidelines of international communitarian development, implying, on one hand, a constant updating/revision of the legal diplomas of urban planning and management, and, on the other hand, new models of territorial development based on economic competitiveness, globalization, sustainability and social cohesion. The rapid European and Portuguese urban development focus urban regeneration as a priority. In the case of Lisbon, the expansion and the subsequent industrial dislocation shaped new and external urban centralities that are currently inserted in the Lisbon Metropolitan Area, requiring specific technical-political organizations. Analysing the complex evolution of post-industrial areas, from expansion/progress until the decline and regeneration, the matter of heritage is one of the most challenging elements in the territory. Since in port and post-industrial areas it is hence notorious, the presence of History, preservation, conservation and/or demolition are present and future challenges to Architects. We highlight the case of the Eastern waterfront area of Lisbon due to its historic and urban evolution – marked by successive and complex urban and infrastructural transformations – and by its current situation of urban decline that introduces problems, challenges and opportunities of intervention to the technicians that are involved in urban regeneration processes. In the case study, we are able to find many examples of rural and industrial legacy, that reveal the past of that territory. Considering that the past justifies and supports the intervention in the contemporary city and the current scarcity of funds/in times of crisis, it is now crucial to question ways of regenerate declined areas. We conclude that the territory must be social and economic active and productive, renting pre-existing elements. Especially in the current context of public financial unavailability, it urges to globally rethink urban management strategies - highlighting factors as cooperation, connection and public participation -, and stimulating the intervention departing from the pre-existences, history and heritage.
The Topology of Marble: The Matter of Estremoz’s Built Heritage
Authors: Silva Cidalia Ferreira , Esteves Luis Duarte 
Published: November 2016

This paper addresses built heritage from the perspective of marble as a cross-scale legacy between distant and close places. Through Estremoz marble we make visible that heritage is not only a static element to preserve but a matter continuously in motion across time and space. Topology of marble brings to the fore this awareness of seeing the interconnection between its geological formation, the extraction and the constructive processes, in a multiplicity of cycles still in transformation. The article is structured by the simultaneity of in-here and out-here interconnections: (a) Here and In-here, maps the motion of marble from the quarries with the built urban heritage of Estremoz; (b) Here and Out-here, renders visible the intimate connection with distant places, such as Europe, Africa, and South America.
Notes towards a project for the quarries landscape of Estremoz Anticline
Authors: Baganha Pedro 
Published: November 2016

The area known as Estremoz anticline, in central Alentejo, Portugal, is well known for its marble quarries since the roman period. The industrial activity since mid 20th century resulted in a violently humanized landscape. Until recently the investigation regarding these marble quarries has been typically related with the rationalization of the industrial activity or the environmental issues that arise. This paper will try to take a different perspective on the subject, using the concepts of cultural landscape and industrial heritage.The validation of the hypothesis that this landscape is part of the cultural heritage of its local community must start with the analysis of similar examples worldwide. This paper address three such examples: Caserta's quarries, the Balearic Islands, and Edward Butynsky's photographic investigation. Finally the article proposes a conceptual framework to further research about the subject, aimed at a territorial architectural project for the area.
Hybride Modellierung intrakranieller Pulswellen unter Berücksichtigung der kardiovaskulären Kopplung
Authors: Misgeld Berno Johannes Engelbert , Mondal Rajib , Leonhardt Steffen 
Published: November 2016

Zusammenfassung
Intrakranielle P-Wellen werden durch das pulsatil einströmende Blutvolumen in das Gehirn verursacht. Die Morphologie der
P-Welle unterscheidet sich allerdings von der Pulswelle in der Aorta durch das Auftreten von Oberwellen. Die
charakteristische Form der Pulswelle wird heutzutage für die Hydrozephalus-Diagnostik verwendet, da diese je nach
pathologischem Zustand und Schwere der Erkrankung in charakteristischer Weise variiert. Ein genaues Modell könnte dabei
in Zukunft in der Diagnose von Normaldruckhydrozephalus eingesetzt werden. Allerdings ist die genaue
Übertragungscharakteristik und Beeinflussung der P-Welle durch den Zustand des intrakraniellen Raumes bis heute
unbekannt. In diesem Beitrag wird daher ein neues Modell verteilter Parameter für das vaskuläre System abgeleitet und mit
einem Modell konzentrierter Parameter des intrakraniellen Raumes gekoppelt. Hierdurch wird erstmalig die Generierung
intrakranieller P-Wellen auf Basis aortaler Druckpulse möglich. Zudem werden über Parametervariationen des Modells
verschiedene P-Wellenklassen, zugehörig zu verschiedenen pathologischen Hydrozephaluszuständen, nachgestellt. Das
vorgeschlagene Modell ist dabei in der Lage, einen Großteil der pathologischen P-Wellen-Klassen von klinischen
Referenzdaten nachzustellen. Die Beeinflussung der P-Welle durch den Zustand des intrakraniellen Raumes wird durch die
Linearisierung der Modelldynamik und Überführung in die Übertragungsfunktion verdeutlicht.
Modeling and closed-loop control of a medical flow generator appliance
Authors: Scheel Mathias , Berndt Andreas , Simanski Olaf 
Published: November 2016

Abstract
The CPAP (Continuous Positive Airway Pressure) therapy is the most common therapy to treat the obstructive sleep apnoea
syndrome. If the upper respiratory tracts collapse, it may lead to breathing interrupts during sleep. The CPAP-device
provides a positive pressure to splint the airways. The influence on the pressure is different from patient to patient and
their medical condition. It has been shown that many CPAP-devices can not maintain the required pressure set points,
because the mask pressure is seriously influenced by the patient's breathing. In this work the electromechanic part and
pneumatic part of the breathing therapy system is modeled to provide an opportunity for a model-based control
approach. Based on the physical chain of effect an existing control strategy is extended. In the end some control results
are shown and a conclusion is made.
Sorus formation on the holdfast haptera of the kelp Ecklonia radicosa (Phaeophyceae, Laminariales)
Authors: Akita Shingo , Yamada Hirokazu , Ito Madoka , Graham Michael H. , Fujita Daisuke 
Published: November 2016

AbstractKelps usually form sori on their vegetative blades or sporophylls, and occasionally on stipes, with a notable exception being the primitive kelp
Morning sickness of pregnancy: more than meets the eye
Authors: Arsad Noorazizah , Chew Kah Teik , Abdul Ghani Nur Azurah , Tan Hui Jan , Wahab Norasyikin A. , Mohd Ismail Nor Azlin 
Published: November 2016

Abstract
Wernicke’s encephalopathy (WE) is a rare life-threatening complication following severe hyperemesis gravidarum. Early recognition of this condition and prompt thiamine administration is the key to preventing devastating sequelae. We report a successful delivery of a small-for-gestational-age (SGA) baby by a patient with WE and thyrotoxicosis in pregnancy.
Lump-Type Solutions to the (3+1)-Dimensional Jimbo-Miwa Equation
Authors: Ma Wen-Xiu 
Published: November 2016

Abstract:
Taking advantage of the Hirota bilinear form, four classes of lump-type solutions to the (3+1)-dimensional Jimbo-Miwa equation are presented through symbolic computation with Maple. Special choices of the involved parameters guaranteeing analyticity of the fourth solution are given, together with two particular lump-type solutions.
A Causal Inference Approach to Network Meta-Analysis
Authors: Schnitzer Mireille E , Steele Russell J , Bally Michèle , Shrier Ian 
Published: November 2016

Abstract:While standard meta-analysis pools the results from randomized trials that compare two treatments, network meta-analysis aggregates the results of randomized trials comparing a wider variety of treatment options. However, it is unclear whether the aggregation of effect estimates across heterogeneous populations will be consistent for a meaningful parameter when not all treatments are evaluated on each population. Drawing from counterfactual theory and the causal inference framework, we define the population of interest in a network meta-analysis and define the target parameter under a series of nonparametric structural assumptions. This allows us to determine the requirements for identifiability of this parameter, enabling a description of the conditions under which network meta-analysis is appropriate and when it might mislead decision making. We then adapt several modeling strategies from the causal inference literature to obtain consistent estimation of the intervention-specific mean outcome and model-independent contrasts between treatments. Finally, we perform a reanalysis of a systematic review to compare the efficacy of antibiotics on suspected or confirmed methicillin-resistantStaphylococcus aureusin hospitalized patients.
Meaning and inconsistencies of meaning – exploring the perspectives of Norwegian veterans in Afghanistan
Authors: Lien Roger , Firing Kristian , Bendixen Mons , Kennair Leif Edward Ottesen 
Published: November 2016

Abstract
This qualitative study explores the meaning-making process of veterans to address the positive aspects of military service in international operations. Thirteen veterans from a Force Protection Unit in Norway were interviewed about their deployment to Afghanistan. A thematic analysis revealed three main themes reflecting meaningful aspects of the service. “Confirmation of ability” refers to finding meaning by coping with stressful situations and being recognized for it. “Cohesion of peers” refers to finding meaning by belonging to a team and giving mutual support within the team, such as backing up each other and caring. “Significance of effort” refers to finding meaning by seeing their efforts as a contribution, as well as by receiving recognition and gaining status for their efforts. The analysis also revealed accompanying themes of inconsistencies, which in turn activated different coping strategies. The findings have been substantiated through a functional exposition of meaning: purpose, value, efficacy, and self-worth, as advocated by Baumeister (1991), and are discussed in the context of previous research and a theoretical concept of meaning making. Steps for future research are proposed.