bluuebunny/crossref_metadata_2025_split huggingface dataset:
Why Pacing Frequency Affects the Production of Early Afterdepolarizations in Cardiomyocytes: An Explanation Revealed by Slow/Fast Analysis of a Minimal Model
Authors: Vo Theodore , Bertram Richard 
Published: January 2019

AbstractEarly afterdepolarizations (EADs) are pathological voltage oscillations in cardiomyocytes that have been observed in response to a number of pharmacological agents and disease conditions. Phase-2 EADs consist of small voltage fluctuations that occur during the plateau of an action potential, typically under conditions in which the action potential is elongated. Although a single-cell behavior, EADs can lead to tissue-level arrhythmias, including ventricular tachycardia. Much is currently known about the biophysical mechanisms (i.e., the roles of ion channels and intracellular Ca2+ stores) for the various forms of EADs, due partially to the development and analysis of mathematical models. This includes the application of slow/fast analysis, which takes advantage of timescale separation inherent in the system to simplify its analysis. We take this further, using a minimal 3D model to demonstrate that the phase-2 EADs are canards that are formed in the neighborhood of a folded node singularity. This knowledge allows us to determine the number of EADs that can be produced for a given parameter set without performing computer simulations, and provides guidance on parameter changes that can facilitate or inhibit EAD production. With this approach, we demonstrate why periodic stimulation, as would occur in an intact heart, preferentially facilitates EAD production when applied at low frequencies,. We also explain the origin of complex alternan dynamics that can occur with intermediate-frequency stimulation, in which varying numbers of EADs are produced with each stimulation. These revelations fall out naturally from an understanding of folded node singularities, but are hard or impossible to glean from a knowledge of the biophysical mechanism for EADs alone. Therefore, an understanding of the canard mechanism is a useful complement to an understanding of the biophysical mechanism that has been developed over years of experimental and computational investigations.
Removal of behavioural and electrophysiological signs of chronic pain byin vivomicrosections of rat somatosensory cortex with parallel X-ray microbeams
Authors: Zippo Antonio G. , Bertoli Gloria , Riccardi Maria Pia , Valente Maurizio , Bräuer-Krisch Elke , Caramenti Gian Carlo , Requardt Herwig , Grosso Veronica del , Coan Paola , Bravin Alberto , Biella Gabriele E. M. 
Published: January 2019

AbstractChronic pain (CP) is a condition characterized by a wide spectrum of clinical signs and symptoms, missing a sound modelling at the neuronal network scale. Recently, we presented a general theory showing common electrophysiological traits in different CP rat models, i.e. a collapse of relevant functional connectivity network properties, such as modularity, in the somatosensory thalamo-cortical (TC) network. In this work, we preliminary investigated by anin silicoaccurate simulator of the six-layer mammalian cortical networks that evidenced the crucial collapse of network modularity in CP simulated conditions and the consequent reduction of network adaptive processes. On this track, in studies on CP experimental animals affected by sciatic nerve multiple ligature (Bennett-Xie model), by synchrotron-generated X-ray microbeam (MB) irradiations (7 parallel beams, 100um width), we targetedin vivothe CP involved hindlimb somatosensory projection cortex that, because of the doses radiation (360 Gy, peak at each beam), non-invasively produced fast and precise tissue destruction along the 7 beam projections. These parcellated the cortical tissue and restored the cortical network statistics related to modularity and information processing efficiency as evidenced from post irradiationin vivoelectrophysiological recordings. In addition, by MB treatment there was an ensuing removal of behavioral signs of allodynia and hyperalgesia accompanied by recovered normal gait schemes yet preserving the normal sensory thresholds of the experimental rats up to three months after the MB irradiation. Finally, novel and unprecedented therapeutic appraisals for CP are devised.Significance StatementChronic pain (CP) is an excruciating condition with severe effects on patients’ life. Apart from many clinical and experimental studies no current theory on CP is generally accepted. Recently, we proposed a general theory of CP in experimental animals as characterized by strong alteration of the connections among neurons in different brain regions. We show here onin silicosimulations that specific connectivity changes in the somatosensory cortex recover the lost functional integrity. Concurrently, in experimental animals, we re-modulated,in vivo, some anatomical connections of the somatosensory cortex by extremely thin synchrotron generated X-ray microbeam irradiations. The resulting behavioral and electrophysiological signs of CP disappeared yet maintaining normal sensory responses. No adverse or pathological effects on blank animals were observable.
Bacterial and Archaeal Communities in Recycling Effluents from a Bauxite Flotation Plant
Authors: Liu Xinxing , Wu Yong-Hong , Liu Xi , Han-yan Wu , Xie Jianping , Wang Guohua , Qiu Guan-zhou , Huo Qiang 
Published: January 2019

AbstractRecycling effluent has become a bottleneck and an environmental risk associated with the regular production of bauxite via flotation and the sustainable development of the aluminum industry in China. To find a practical direction for biotreatment, the bacterial and archaeal communities in recycling effluents containing concentrate and tailings from bauxite flotation plants were investigated by a metagenomic sequencing method in association with the evaluated geochemical properties. The results showed that Paracoccus, Desulfomicrobium, Exiguobacterium, Tindallia, Ercella and Anoxynatronum were the primary bacterial genera and Methanothrix, Methanobacterium, Nitrososphaera and Methanosarcina were the dominant archaeal genera. Upon combining the microbial diversity and the geochemical properties of the two sample types, the microbial community containing Desulfomicrobium, Paracoccus, Tindallia, Methanobacterium, Methanothrix and Nitrososphaera was better adapted to the biodegradation of flotation collectors, and the microbial community consisting of Paracoccus, Exiguobacterium, Methanothrix and Methanobacterium was more efficient at hydrolyzed polyacrylamide (HPAM) biodegradation. In addition, a large proportion of unclassified OTUs has indicated that recycling effluent is a worthy resource for isolating new strains from the Firmicutes phylum.
Complex internationalization strategies and firm export performance during the great trade collapse
Authors: Córcoles David , Díaz-Mora Carmen , Gandoy Rosario 
Published: January 2019

PurposeFocusing on the global trade collapse and the subsequent recovery period, the purpose of this paper is to examine the export performance of firms that are involved in complex internationalization strategies.Design/methodology/approachThe authors use a random-effects probit model with panel data and a dynamic panel data model (GMM system) for Spanish manufacturing firms from 2006 to 2013 period.FindingsIt is found that, once firm characteristics are controlled for, complex internationalization plays an important role in continuing to export and, additionally, positively influences the level of exports. Firms active in a complex mix of internationalization strategies have an added advantage, which enables them to confront the uncertainty of foreign markets in better conditions and translates to a lower likelihood of ceasing exporting and to higher export values.Practical implicationsThe present paper throws light on this question by showing that the negative impact of trade collapse in 2009 on the export level was lower for firms inserted in complex internationalization strategies and the subsequent recovery was more intense.Originality/valueThe analysis goes one step further and investigates whether the impact is different during the trade collapse in 2009 and the following recovery. Here, previous empirical research at firm level on the role of complex internationalization strategies in trade is contradictory.
Harm-focused offender triage and prioritization: a Philadelphia case study
Authors: Ratcliffe Jerry H. , Kikuchi George 
Published: January 2019

PurposeThe purpose of this paper is to describe and test a quantitative harm-focused approach to offender selection for investigation and surveillance. The approach incorporates a measure of crime harm as well as a time-decay function that adjusts the score downward for offenders who desist from crime.Design/methodology/approachAcross 10 of 21 high-crime police districts in the city of Philadelphia, the authors compare the mean harm scores of 60 prolific offenders selected by district analysts, 60 prolific offenders selected citywide by detectives assigned to the Gun Violence Reduction Task Force and the top 60 prolific offenders chosen from a harm-score generated list of known offenders in the ten high-crime districts.FindingsThe offenders on the harm-focused list have significantly greater mean harm scores than the offenders identified by the crime analysts or task force personnel. They have a significantly greater mean number of gun crime episodes in their offending history as well.Research limitations/implicationsThe harm-focused approach uses arrest data that may not accurately reflect convictions and which miss undetected criminal activity. A leader of a criminal organization who orchestrates criminal activities but does not engage directly may have a low harm score. Arrest data may also suffer from some inherent bias. The approach also requires the creation of a crime harm index. Determining the operational impact on overall crime reduction by focusing on offenders with higher harm scores will require further research.Practical implicationsClinical methods of target selection based on officer intuition, opinion and experience may have limitations in terms of effectiveness and accuracy. They also lack transparency and may incorporate bias, a critical consideration given the current crisis in police-community trust and legitimacy. The actuarial method of weighing the harm of past offending with a crime harm score may be more acceptable and defendable to the community. It also identifies offenders with a higher frequency of involvement in gun crimes. Until methodological limitations are better understood, a compromise may be to start with the harm-score method (data-driven) and supplement this initial list through intelligence and investigative information.Originality/valueThe paper expands crime harm indices to quantify offender triage lists. The authors also empirically demonstrate through a case study that the approach is more effective at identifying harmful offenders than methods that solely rely on the experience or intuition of either crime analysts or detectives.
Spatial analysis of p63, K5 and K7 defines two groups of progenitor cells that differentially contribute to the maintenance of normal sebaceous glands, extraocular sebaceous carcinoma and benign sebaceous tumors
Authors: Boecker Werner , Reusch Michael , Mielke Volker , Reusch Ursula , Loening Thomas , Tiemann Markus , Buchwalow Igor 
Published: January 2019

AbstractThe histogenesis of extraocular sebaceous carcinomas is – in contrast to ocular sebaceous carcinomas – unclear, and information about the exact cellular architecture of these lesions and even of the normal sebaceous gland is still scarce. This study attempts to elucidate the histogenesis of sebaceous tumors, using multicolor immunofluorescence stainings to analyze 21 cases of sebaceous tumors (six each of extraocular sebaceous carcinoma, sebaceous adenoma and sebaceoma, and three cases of steatocystomas) and eight cases of normal sebaceous glands for p63, several keratins, androgen receptor, adipophilin, epithelial membrane antigen (EMA) and Ki‐67. The data of this observational study provide evidence for the existence of two subpopulations of progenitors in normal sebaceous glands: (i) p63+ K5+ progenitors which generate the K10+ luminal cells of sebaceous ducts; and (ii) p63+ K5+ K7+ progenitors which finally generate K7+ adipophilin+ EMA+ sebocytes. Without exception, all types of sebaceous tumors contained p63+ K5+ cells. Furthermore, these tumors showed a cellular hierarchy and differentiation to adipophilin+ and/or EMA+ mature sebocytes and to K10+ ductal cells through intermediary cells. Notably, a considerable number of sebaceous tumors lack the K7 pathway of cell maintenance in the normal sebaceous lobule. Based on our data, we propose a cellular algorithmic model of the hierarchy of normal sebaceous glands and of sebocytic tumors in which p63+ K5+ cells play a major role.
The phenology of migration in an unpredictable world
Authors: Schindler Daniel E. 
Published: January 2019

Abstract
In Focus: Freshwater, C., Trudel, M., Beacham, T. D., Gauthier, S., Johnson, S. C., Neville, C. & Juanes, F. (2016) . Journal of Animal Ecology, 88, 67–78. https://doi.org/10.1111/1365-2656.12852
Pacific salmon undertake arduous and risky migrations from their freshwater nursery grounds to the coastal ocean, northwards to their feeding grounds, and then back to their freshwater natal habitats to spawn. Understanding the phenology of such migrations has largely been viewed through the lens of microevolution producing optimal strategies that reflect local selection pressures; less emphasis has been placed on quantifying how variation in migration patterns can spread the risks associated with life in variable and unpredictable ecosystems. In this issue, Freshwater et al. use the information contained in ear stones (otoliths) and DNA of migrating juvenile sockeye salmon from the Fraser River of western Canada to quantify variation in the timing of their marine migrations. Not only were there population‐specific differences in migration phenology of fish from the same river, but there was substantial variation among individuals from specific populations. These patterns also varied from year to year. Data like these emphasize the risks involved in such migrations and suggest that variation in key migration traits are maintained because of the inherent unpredictability of ecosystems. Management and conservation efforts would be well‐served to consider actions that maintain such ecological variation to facilitate meta‐population persistence in a rapidly changing world.
Bullet Caliber and Type Categorization from Gunshot Wounds inSus Scrofa(Linnaeus) Long Bone
Authors: Henwood Bailey J. , Oost Tracy S. , Fairgrieve Scott I. 
Published: January 2019

AbstractStudies on ballistic trauma to the ribs and thorax, cranium, and long bones demonstrate the potential of obtaining a bullet caliber from an entrance wound. In order to validate prior research on caliber estimation in bone tissue and assess the viability of bullet type determination based on the macroscopic evidence at the entrance wound, thirty fleshed pork (Sus scrofa) shoulders (humeri) were shot with either lead or copper jacketed bullets in one of three calibers; 0.22, 9 mm, or 0.38. Overall, our findings are consistent with previous research indicating that calibers can be grouped into “small” and “large” categories. Bullet type, lead or copper jacket, can be ascertained based on cortical flaking and the analysis of materials deposited around the entry wound. The addition of this evidence holds value in cases where no firearm or ballistic evidence is recovered from a crime scene.
Revitalising Openness at Mozilla: A Mixed Method Research Approach
Authors: JENSEN RINA TAMBO 
Published: January 2019

This is a case about how Mozilla, the open source browser company, set out to reconnect with ‘collaborating in the open’ to regain its competitive advantage. This case describes how a multi‐disciplinary research team used ethnographic, market, and data analysis to articulate and clarify the problem, and build a strategy towards revitalizing Openness at Mozilla. It will aim to prove that the subsequent change achieved could only have been accomplished by a mixed method research approach. And importantly show, how the team used data to prove the distribution of findings, coupled with ethnography to shine light on the why and how of those findings. The case study will do this by discussing the key insights and how these fueled recommendation and subsequent change in the organisation.The project presented many problems: from convincing stakeholders of the need to fully explore the problem, to connecting widely different research methods and gleaning insights that built strongly on all strands of research. Overcoming these issues together, the team managed to outlay the key problems and opportunities for Mozilla and build a strategy which has affected real change in the company and is now being implemented by a team of 20 employees. We call this strategy Open by Design. Which, to us, means being open, purposefully.
Influence of molecular classification in anaplastic glioma for determining outcome and future approach to management
Authors: Back Michael , Jayamanne Dasantha T , Brazier David , Newey Alison , Bailey Dale , Schembri Geoffrey P , Hsiao Edward , Khasraw Mustafa , Wong Matthew , Kastelan Marina , Guo Linxin , Clarke Stephen , Wheeler Helen 
Published: January 2019

AbstractIntroductionAssess survival of patients with anaplastic glioma (AG) and the relationship to molecular subtype.MethodsPatients with AG managed with IMRT between 2008 and 2014 were entered into a prospective database assessing relapse‐free survival (RFS) and overall survival (OS). Isocitrate dehydrogenase (IDH) mutations were assessed prospectively from 2011, and subsequent testing of historical patients allowing categorisation under WHO 2016 classification as anaplastic astrocytoma IDH wild type (AAwt), anaplastic astrocytoma IDH mutated (AAmut), anaplastic oligodendroglioma (AOD) or other glial tumour (OTH). Kaplan‐Meier estimates of survival distribution were calculated for the primary endpoint of overall survival and Log‐rank test used to determine associated factors.ResultsOne hundred and fifty‐six patients were included with median follow‐up for survivors of 4.7 years. Fifty‐six per cent were managed after initial diagnosis, whilst 18% received IMRT at second or later relapse. Seventy‐three per cent had temozolomide as part of initial therapy. A total of 118 or 75% of patients had IDH mutated glioma, of which 61 were AOD and 57 AAmut. There were 68 relapses and 52 deaths for a 6yrRFS of 51.2% and 6yrOS of 62.5%. AAwt was associated with worse survival (P < 0.001); and delay of RT until second or later relapse (P = 0.03). Within the 118 patients with IDH mutated tumours, 6yrOS for AOD and AAmut were 90.0% and 62.5%, respectively (P = 0.003). Also two or more craniotomies (P < 0.001), delayed RT (P = 0.006) and age <40 years (P = 0.022) were associated with worse survival on univariate analysis but only AAmut subtype and number of craniotomies on multivariate analysis.ConclusionWithin AG, molecular classification predicts for survival, and should influence current decision‐making.
The micro elasticity of substitution and non‐neutral technology
Authors: Raval Devesh R. 
Published: January 2019

AbstractThis article provides evidence on the micro capital‐labor elasticity of substitution and the bias of technology. Using data on US manufacturing plants, I find several facts inconsistent with a Cobb‐Douglas production function, including large, persistent variation in capital shares. I then estimate the elasticity using variation in local wages, and several instruments for them, for identification. Estimates of the substitution elasticity using all plants range between 0.3 and 0.5, with similar estimates across industries. I use these elasticity estimates to measure labor augmenting productivity, and find that labor augmenting productivity is highly persistent, and correlated with exports, size, and growth.
Chronic obstructive pulmonary disease (COPD) among opioid‐dependent patients in agonist treatment. A diagnostic study
Authors: Grischott Thomas , Falcato Luis , Senn Oliver , Puhan Milo Alan , Bruggmann Philip 
Published: January 2019

AbstractAimsTo estimate the prevalence of chronic obstructive pulmonary disease (COPD) and related risk factors in people in opioid agonist treatment (OAT), to compare airflow limitation severity and age‐specific COPD prevalence rates with those in the general population, and to assess the OAT patients’ willingness to adopt life‐style changes and to use therapeutic offers for COPD management.DesignCross‐sectional study in a random sample of OAT patients.SettingOut‐patient centres for substance addiction medicine in Zurich, Switzerland.ParticipantsA total of 125 participants, recruited from November 2016 to April 2017 through invitation letters followed by phone or personal contact.MeasurementsStandardized questionnaires about drug use, smoking habits and medical history, completed during face‐to‐face interviews or from medical records. Spirometry without and—depending on the result—with bronchodilation.FindingsAlmost one‐third [30.3%; 95% confidence interval (CI) = 22.6–39.0%] of the 119 participants with valid spirometry tests were diagnosed with COPD. Among males aged 30–59 years, the age‐adjusted prevalence of at least moderate airflow limitation (GOLD grade ≥ 2) was 2.4 (95% CI = 1.3–4.4) times as high as in the ever‐smoking Swiss population in the same age group. Smoking tobacco (92.0%) and substance inhalation (cannabis = 97.6%, cocaine = 69.6%, heroin = 68.0%) were highly prevalent among all participants. The participants expressed considerable interest in life‐style changes and use of therapeutic offers for COPD management, with smoking cessation being least (20.2% of tobacco smokers interested) and pharmacological treatment to alleviate COPD symptoms most popular.ConclusionsIn Switzerland, COPD prevalence and multiple risk factors for COPD appear to be high among people in OAT compared with the general population. Individuals in OAT appear to develop COPD at a younger average age compared with the general population and are open to life‐style changes and other COPD management approaches.
Conductive electrospun scaffolds with electrical stimulation for neural differentiation of conjunctiva mesenchymal stem cells
Authors: Rahmani Ali , Nadri Samad , Kazemi Habib Sayed , Mortazavi Yousef , Sojoodi Mahdi 
Published: January 2019

AbstractAn electrical stimulus is a new approach to neural differentiation of stem cells. In this work, the neural differentiation of conjunctiva mesenchymal stem cells (CJMSCs) on a new 3D conductive fibrous scaffold of silk fibroin (SF) and reduced graphene oxide (rGo) were examined. rGo (3.5% w/w) was dispersed in SF‐acid formic solution (10% w/v) and conductive nanofibrous scaffold was fabricated using the electrospinning method. SEM and TEM microscopies were used for fibrous scaffold characterization. CJMSCs were cultured on the scaffold and 2 electrical impulse models (Current 1:115 V/m, 100‐Hz frequency and current 2:115 v/m voltages, 0.1‐Hz frequency) were applied for 7 days. Also, the effect of the fibrous scaffold and electrical impulses on cell viability and neural gene expression were examined using MTT assay and qPCR analysis. Fibrous scaffold with the 220 ± 20 nm diameter and good dispersion of graphene nanosheets at the surface of nanofibers were fabricated. The MTT result showed the viability of cells on the scaffold, with current 2 lower than current 1. qPCR analysis confirmed that the expression of β‐tubulin (2.4‐fold P ≤ 0.026), MAP‐2 (1.48‐fold; P ≤ 0.03), and nestin (1.5‐fold; P ≤ 0.03) genes were higher in CJMSCs on conductive scaffold with 100‐Hz frequency compared to 0.1‐Hz frequency. Collectively, we proposed that SF‐rGo fibrous scaffolds, as a new conductive fibrous scaffold with electrical stimulation are good strategies for neural differentiation of stem cells and the type of electrical pulses has an influence on neural differentiation and proliferation of CJMSCs.