bluuebunny/crossref_metadata_2025 huggingface dataset:
A Polanyian Perspective on C.S. Lewis’s The Abolition of Man
Authors: Fennell Jon
Published: December 2017

The Abolition of Man is sometimes viewed as an attack on science. This interpretation is, of course, erroneous. Anticipating this criticism, Lewis states that his remarks are not an attack on science but instead a defense of value—the value, among other things, of science. Lewis goes on to suggest that science might itself be the remedy for the dark moral malady that The Abolition of Man accounts for and describes. The purpose of this study is to show that, in the work of Michael Polanyi, Lewis’s aspirations regarding the curative powers of science are in fact realized. Polanyi not only demonstrates the bankruptcy of scientism, but he does so in a manner that, while revealing the inspiring character of genuine science, greatly clarifies Lewis’s project. Polanyi deepens and broadens Lewis’s analysis in The Abolition of Man , thereby offering an indispensable service to those who have learned to respect this very important work.
C. S. Lewis and J. R. R. Tokien as I knew them (never well)
Authors: Stanley Eric
Published: December 2017

I attended all the lectures C. S. Lewis and J. R. R. Tolkien gave in 1948 to 1951. My own teaching of English Renaissance literature at Birmingham University was informed by Lewis’s volume in the Oxford History of English Literature (1954), parts of which I had heard him give as lectures. At Birmingham we started a series of Medieval and Renaissance texts, and I wrote to Lewis and ask him if he would be our General Editor; he said, yes. He asked me to meet him, correspondence followed, and I quote from a long, witty, and wise letter about an edition of mine, and about another edition which Lewis disliked and I also quote from that sharper letter.

I knew Tolkien because, as an undergraduate I attended his weekly seminars. At that time he himself was greatly interested in Ancrene Wisse and the Katherine Group. He lectured on Sir Gawain and the Green Knight. Much later, in 1972, I met Tolkien again, at a book-launch party. I ventured to speak to him. I gave my name, and in his charming way he said he remembered me. I wondered at that, but took it as evidence of his kindness.
Owen Barfield’s Orpheus
Authors: Hipolito Jeffrey
Published: December 2017

This essay examines Owen Barfield’s reworking of Virgil’s account of the Orpheus myth in the fourth Georgic. It finds that while Barfield retains Virgil’s nesting-doll form he dramatically shifts the thematic focus. In particular, where Virgil’s Stoicism compels him to see Orpheus’s romantic longing for Eurydice as a failure of character, Barfield’s rendering suggests that romantic love both a reflection of and step in the direction of the selfless love towards which each character wittingly or unwittingly strives.
Recovering Mrs Fidget: An Analysis of the Rise, Fall, and Restoration of Storge as Envisioned in The Four Loves and Lewis’ Fiction
Authors: Litz Duane
Published: December 2017

It is often observed that The Four Loves serves as a resource for reading Lewis’s fictional work. Scholarship admits that The Four Loves may even be used as a ‘roadmap’ for understanding love in his novels. However, previous treatments have yet to expose the particularly descriptive and comprehensive nature of Storge that runs through Lewis’s literature. This study adequately proves that the reader may use The Four Loves as a guide in order to define and understand natural Affection as it emerges in his narrative passages. Simultaneously, numerous examples from Lewis’s fictional corpus are offered in order to clarify concepts that will eventually coalesce in The Four Loves. Through careful analysis, it is evident that Lewis’s fiction illustrates the grandeur of Storge when it is crafted by artful Charity; the diabolical nature of Storge when it is corrupted by self-absorption; and the re-emergence of Storge when it is reordered by a journey of transformation. Therefore, using Lewis’s Mrs Fidget as a model to engage various facets of Storge, and utilizing The Four Loves as a guide to reading Lewis’s fiction, this study demonstrates that Lewis establishes a methodology for the rise, fall, and restoration of affectionate love in his writings.
Warren Lewis, Mrs Janie King Moore, and The Kilns
Authors: King Don
Published: December 2017

Warren Lewis’s antipathy for Mrs. Janie King Moore (1872-1951), his brother’s longtime companion and adopted “mother” is well-documented. Accordingly, it is not entirely surprising that as the years passed, Warren kept a record of Moore’s dogmatic, selfish, and condescending statements and dialogues. To these he added other examples of ‘wheezes’ that he overheard while living in The Kilns, eventually compiling what he called Mens Humana, or Kilns Table Talk. In what follows I mine Warren’s Mens Humana, offer explanatory comments, and focus in particular upon his comments regarding Moore, her daughter, Maureen, and Vera Henry, Moore’s goddaughter and occasional Kilns housekeeper. I conclude with several observations about Warren as a member of The Kilns household and as a writer.
A Subjectivist Account of Life’s Meaning
Authors: Svensson Frans
Published: December 2017

In this paper, I propose and defend a particular desire-based theory of what makes a person’s life meaningful. Desire-based theories avoid the problems facing other theories of meaning in life: in contrast to objectivist theories (both consequentialist and non-consequentialist ones), they succeed in providing a necessary link between what makes a person’s life meaningful and the person’s own set of attitudes or concerns; in contrast to hybrid theories (or subjectivist theories with a value requirement), they avoid the elitism or exclusivism inherent in the former; and in contrast to mental-state theories, they avoid the problem of not taking the state of the world properly into account when determining whether someone’s life is meaningful. However, meaningfulness does not plausibly depend on the satisfaction of just any desires—perhaps especially not on the satisfaction of desires that we experience as alien to ourselves. I therefore suggest that the meaning in your life depends on the extent to which your categorical desires (i.e. those desires that are partly constitutive of your practical identity) are satisfied or fulfilled. In the final section of the paper, I respond to at least four possible objections to this view.
What Good is Meaning in Life?
Authors: Woodard Christopher
Published: December 2017

Most philosophers writing on meaning in life agree that it is a distinct kind of final value. This consensus view has two components: the ‘final value claim’ that meaning in life is a kind of final value, and the ‘distinctness claim’ that it is distinct from all other kinds of final value. This paper discusses some difficulties in vindicating both claims at once. One way to underscore the distinctness of meaning, for example, is to retain a feature of our pre-theoretical concept of meaning in life, according to which the least possible quantity of meaning is meaninglessness. Unfortunately, this makes it harder to defend the claim that meaning is a kind of final value. On the other hand, revising the concept to allow for negative meaning renders meaning closer in structure to other kinds of final value, but also makes it harder to defend the distinctness claim. In light of these difficulties, the paper explores the prospects of a theory of meaning in life which departs from the consensus view by rejecting the final value claim. On such a view, the value of meaning in life is entirely instrumental.
Selection of Meat Inspection Data for an Animal Welfare Index in Cattle and Pigs in Denmark
Authors: Nielsen Søren Saxmose , Denwood Matthew James , Forkman Björn , Houe Hans
Published: December 2017

National welfare indices of cattle and pigs are constructed in Denmark, and meat inspection data may be used to contribute to these. We select potentially welfare-relevant abattoir recordings and assess the sources of variation within these with a view towards inclusion in the indices. Meat inspection codes were pre-selected based on expert judgement of having potential animal welfare relevance. Random effects logistic regression was then used to determine the magnitude of variation derived at the level of the farm or abattoir, of which farm variation might be associated with welfare, whereas abattoir variation is most likely caused by differences in recording practices. Codes were excluded for use in the indices based on poor model fit or a large abattoir effect. There was a large abattoir effect for most of the codes modelled and these codes were deemed to be not appropriate to be carried forward to the welfare index. A few were found to be potentially useful for a welfare index: Eight for slaughter pigs, 15 for sows, five for cattle <18 months of age, and six for older cattle. The absolute accuracy of each code/combination could not be assessed, only the relative variation between farms and abattoirs.
Dual Regulation of the Small RNA MicC and the Quiescent Porin OmpN in Response to Antibiotic Stress in Escherichia coli
Authors: Dam Sushovan , Pagès Jean-Marie , Masi Muriel
Published: December 2017

Antibiotic resistant Gram-negative bacteria are a serious threat for public health. The permeation of antibiotics through their outer membrane is largely dependent on porin, changes in which cause reduced drug uptake and efficacy. Escherichia coli produces two major porins, OmpF and OmpC. MicF and MicC are small non-coding RNAs (sRNAs) that modulate the expression of OmpF and OmpC, respectively. In this work, we investigated factors that lead to increased production of MicC. micC promoter region was fused to lacZ, and the reporter plasmid was transformed into E. coli MC4100 and derivative mutants. The response of micC–lacZ to antimicrobials was measured during growth over a 6 h time period. The data showed that the expression of micC was increased in the presence of β-lactam antibiotics and in an rpoE depleted mutant. Interestingly, the same conditions enhanced the activity of an ompN–lacZ fusion, suggesting a dual transcriptional regulation of micC and the quiescent adjacent ompN. Increased levels of OmpN in the presence of sub-inhibitory concentrations of chemicals could not be confirmed by Western blot analysis, except when analyzed in the absence of the sigma factor σE. We suggest that the MicC sRNA acts together with the σE envelope stress response pathway to control the OmpC/N levels in response to β-lactam antibiotics.
Tempol Supplementation Restores Diaphragm Force and Metabolic Enzyme Activities in mdx Mice
Authors: Burns David , Ali Izza , Rieux Clement , Healy James , Jasionek Greg , O’Halloran Ken
Published: December 2017

Duchenne muscular dystrophy (DMD) is characterized by striated muscle weakness, cardiomyopathy, and respiratory failure. Since oxidative stress is recognized as a secondary pathology in DMD, the efficacy of antioxidant intervention, using the superoxide scavenger tempol, was examined on functional and biochemical status of dystrophin-deficient diaphragm muscle. Diaphragm muscle function was assessed, ex vivo, in adult male wild-type and dystrophin-deficient mdx mice, with and without a 14-day antioxidant intervention. The enzymatic activities of muscle citrate synthase, phosphofructokinase, and lactate dehydrogenase were assessed using spectrophotometric assays. Dystrophic diaphragm displayed mechanical dysfunction and altered biochemical status. Chronic tempol supplementation in the drinking water increased diaphragm functional capacity and citrate synthase and lactate dehydrogenase enzymatic activities, restoring all values to wild-type levels. Chronic supplementation with tempol recovers force-generating capacity and metabolic enzyme activity in mdx diaphragm. These findings may have relevance in the search for therapeutic strategies in neuromuscular disease.
In Vitro and In Vivo Antioxidant and Anti-Hyperglycemic Activities of Moroccan Oat Cultivars
Authors: Marmouzi Ilias , Karym El , Saidi Nezha , Meddah Bouchra , Kharbach Mourad , Masrar Azlarab , Bouabdellah Mounya , Chabraoui Layachi , El Allali Khalid , Cherrah Yahia , Faouzi My
Published: December 2017

Improvement of oat lines via introgression is an important process for food biochemical functionality. This work aims to evaluate the protective effect of phenolic compounds from hybrid Oat line (F11-5) and its parent (Amlal) on hyperglycemia-induced oxidative stress and to establish the possible mechanisms of antidiabetic activity by digestive enzyme inhibition. Eight phenolic acids were quantified in our samples including ferulic, p-hydroxybenzoic, caffeic, salicylic, syringic, sinapic, p-coumaric and chlorogenic acids. The Oat extract (2000 mg/kg) ameliorated the glucose tolerance, decreased Fasting Blood Glucose (FBG) and oxidative stress markers, including Superoxide dismutase (SOD), Catalase (CAT), Glutathione peroxidase (GPx), Glutathione (GSH) and Malondialdehyde (MDA) in rat liver and kidney. Furthermore, Metformin and Oat intake prevented anxiety, hypercholesterolemia and atherosclerosis in diabetic rats. In vivo anti-hyperglycemic effect of Oat extracts has been confirmed by their inhibitory activities on α-amylase (723.91 μg/mL and 1027.14 μg/mL) and α-glucosidase (1548.12 μg/mL & 1803.52 μg/mL) enzymes by mean of a mixed inhibition.
Design and Implementation of Model Predictive Control for a Gyroscopic Inverted Pendulum
Authors: Chu Trung-Dung , Chen Chih-Keng
Published: December 2017

This study proposes the design of an active stabilizing system (ASAS) for a single-track vehicle. Using the gyroscopic effects of two flywheels, this system can generate control torque to stabilize the vehicle in cases where there is centrifugal force of turning. To control the flywheel gimbals to generate stabilizing torque, a model predictive controller (MPC) is applied to control the system. For the controller design and performance evaluations, a model of a gyroscopic inverted pendulum is developed. Control strategies are proposed to stabilize the vehicle in the cases of straight running, circular motion, and path following. The results of the proposed stratgies when controlling the gyroscopic inverted pendulum showed good performance even with physical limitations of the control torques. In order to evaluate the real-time performance and the feasibility of the MPC, a real-time simulator is employed, which includes two embedded STM32F407 boards. The dynamic system and the control algorithms are respectively embedded into two STM32F407 boards for real-time simulation. Implementations of the MPC in this study demonstrate that the proposed controllers are feasible for real-time applications.
Nonlinear Spectroscopy of Alkali Atoms in Cold Medium of Astrophysical Relevance
Authors: Efimov Dmitry , Bruvelis Martins , Bezuglov Nikolai , Dimitrijević Milan , Klyucharev Andrey , Srećković Vladimir , Gnedin Yurij , Fuso Francesco
Published: December 2017

The time-dependent population dynamics of hyperfine (HF) sublevels of n 2 p 3 / 2 atomic states upon laser excitation in a cold medium of alkali atoms is examined. We demonstrate some peculiarities of the absorption HF multiplet formation in D2-line resulting from a long interaction time (∼200 μ s) interaction between light and Na ( n = 3 ) and Cs ( n = 6 ) atoms in a cold and slow sub-thermal ( T ∼ 1 K) beam. We analytically describe a number of D2-line-shape effects that are of interest in spectroscopic studies of cold dusty white dwarfs: broadening by optical pumping, intensity redistribution within components of D2-line HF multiplet for partially closed transitions and asymmetry of absorption lines induced by AC Stark shifts for cyclic transitions.
Living Organisms Author Their Read-Write Genomes in Evolution
Authors: Shapiro James A.
Published: December 2017

Evolutionary variations generating phenotypic adaptations and novel taxa resulted from complex cellular activities altering genome content and expression: (i) Symbiogenetic cell mergers producing the mitochondrion-bearing ancestor of eukaryotes and chloroplast-bearing ancestors of photosynthetic eukaryotes; (ii) interspecific hybridizations and genome doublings generating new species and adaptive radiations of higher plants and animals; and, (iii) interspecific horizontal DNA transfer encoding virtually all of the cellular functions between organisms and their viruses in all domains of life. Consequently, assuming that evolutionary processes occur in isolated genomes of individual species has become an unrealistic abstraction. Adaptive variations also involved natural genetic engineering of mobile DNA elements to rewire regulatory networks. In the most highly evolved organisms, biological complexity scales with “non-coding” DNA content more closely than with protein-coding capacity. Coincidentally, we have learned how so-called “non-coding” RNAs that are rich in repetitive mobile DNA sequences are key regulators of complex phenotypes. Both biotic and abiotic ecological challenges serve as triggers for episodes of elevated genome change. The intersections of cell activities, biosphere interactions, horizontal DNA transfers, and non-random Read-Write genome modifications by natural genetic engineering provide a rich molecular and biological foundation for understanding how ecological disruptions can stimulate productive, often abrupt, evolutionary transformations.
Ubiquitin Specific Peptidase 22 Regulates Histone H2B Mono-Ubiquitination and Exhibits Both Oncogenic and Tumor Suppressor Roles in Cancer
Authors: Jeusset Lucile , McManus Kirk
Published: December 2017

Ubiquitin-Specific Peptidase 22 (USP22) is a ubiquitin hydrolase, notably catalyzing the removal of the mono-ubiquitin moiety from histone H2B (H2Bub1). Frequent overexpression of USP22 has been observed in various cancer types and is associated with poor patient prognosis. Multiple mechanisms have been identified to explain how USP22 overexpression contributes to cancer progression, and thus, USP22 has been proposed as a novel drug target in cancer. However, gene re-sequencing data from numerous cancer types show that USP22 expression is frequently diminished, suggesting it may also harbor tumor suppressor-like properties. This review will examine the current state of knowledge on USP22 expression in cancers, describe its impact on H2Bub1 abundance and present the mechanisms through which altered USP22 expression may contribute to oncogenesis, including an emerging role for USP22 in the maintenance of genome stability in cancer. Clarifying the impact aberrant USP22 expression and abnormal H2Bub1 levels have in oncogenesis is critical before precision medicine therapies can be developed that either directly target USP22 overexpression or exploit the loss of USP22 expression in cancer cells.
Study of Anisotropic Plastic Behavior in High Pressure Torsion of Aluminum Single Crystal by Crystal Plasticity Finite Element Method
Authors: Wei Peitang , Lu Cheng , Liu Huaiju , Su Lihong , Deng Guanyu , Tieu Kiet
Published: December 2017

In this study, a crystal plasticity finite element method (CPFEM) model has been developed to investigate the anisotropic plastic behavior of (001) aluminum single crystal during high-pressure torsion (HPT). The distributions of equivalent plastic strain and Mises stress recorded on the sample surface are presented. The directional variations of plastic strain and Mises stress with the development of four-fold symmetry pattern are observed along the sample circumference. The crystallographic orientation evolution along the tangential direction is studied, and the corresponding lattice rotation and slip trace are predicted, respectively. The plastic anisotropy mechanism is discussed in detail based on the theory of crystal plasticity. The simulation results reveal that the differences in slip systems activation (dominant slip and multiple slips) are responsible for the anisotropic plastic deformation in HPT.
Suitability of Soil Erosion Models for the Evaluation of Bladed Skid Trail BMPs in the Southern Appalachians
Authors: Vinson J. , Barrett Scott , Aust W. , Bolding M.
Published: December 2017

This project measured soil erosion rates from bladed skid trails in the mountains of Virginia following a timber harvest, and compared measured erosion to four erosion model predictions produced by Universal Soil Loss Equation—Forest (USLE-Forest), Revised Universal Soil Loss Equation, v.2 (RUSLE2), Water Erosion Prediction Project—Road (WEPP-Road) using default files, and WEPP-Road using modified files in order to assess the utility of the models for these conditions. Skid trails were segregated into six blocks where each block had similar trail slopes and soils. Each block contained four skid trail closure treatments: (1) bare soil (Control); (2) residual limbs and tops (Slash); (3) grass seed (Seed); and (4) fertilizer, seed, and straw mulch (Mulch). All treatments had waterbars, the minimum trail closure best management practice (BMP), to provide upslope and downslope borders of experimental units. Site cover characteristics on each experimental unit were collected quarterly as input parameters for erosion models. The suitability of soil erosion models were evaluated based upon statistical summaries, linear relationships with measured erosion rates, Nash-Sutcliffe Model Efficiency, and a nonparametric analysis. Treatments were measured to have erosion rates of 15.2 tonnes ha−1 year−1 (Control), 5.9 tonnes ha−1 year−1 (Seed), 1.1 tonnes ha−1 year−1 (Mulch), and 0.8 tonnes ha−1 year−1 (Slash). It was determined that WEPP-Road: Modified (p-value = 0.643) and USLE-Forest (p-value = 0.307) were the most suitable models given their accuracy; however USLE-Forest may be better for making management decisions given its practicality.
By 2050 the Mitigation Effects of EU Forests Could Nearly Double through Climate Smart Forestry
Authors: Nabuurs Gert-Jan , Delacote Philippe , Ellison David , Hanewinkel Marc , Hetemäki Lauri , Lindner Marcus
Published: December 2017

In July 2016, the European Commission (EC) published a legislative proposal for incorporating greenhouse gas emissions and removals due to Land Use, Land Use Change and Forestry (LULUCF) into its 2030 Climate and Energy Framework. The Climate and Energy Framework aims at a total emission reduction of 40% by 2030 for all sectors together as part of the Paris Agreement. The LULUCF proposal regulates a “no debit” target for LULUCF (Forests and Agricultural soils), and regulates the accounting of any additional mitigation potential that might be expected of it. We find that the forest share of the LULUCF sector can achieve much more than what is in the regulation now. We elaborate a strategy for unlocking European Union (EU) forests and forest sector potential based on the concept of “climate smart forestry” (CSF). We find that to-date, European policy has not firmly integrated forest potential into the EU climate policy framework. Nor have climate objectives been firmly integrated into those of the forest and forest sector at either the EU or national level. Yet a wide range of measures can be applied to provide positive incentives for more firmly integrating these climate objectives into the forest and forest sector framework. With the right set of incentives in place at EU and Member States levels, we find the current literature supports the view that the EU has the potential to achieve an additional combined mitigation impact through CSF of 441 Mt CO2/year by 2050. In addition, CSF, through reducing and/or removing greenhouse gas emissions, adapting and building forest resilience, and sustainably increasing forest productivity and incomes, tackles multiple policy goals.
Use, Utilization, Productivity and Fuel Consumption of Purpose-Built and Excavator-Based Harvesters and Processors in Italy
Authors: Magagnotti Natascia , Pari Luigi , Spinelli Raffaele
Published: December 2017

Annual use, utilization, productivity and fuel consumption of three purpose-built and three excavator-based harvesters and processors were monitored for one work year. All machines were owned and operated by private contractors and were representative of the Italian machine fleet. Despite challenging mountain terrain, annual use ranged from 675 to 1525 h per year, and production from 3200 to 27,400 m3 per year. Productivity was lower for excavator-based units, and for machines working under a yarder, due to limited yarder capacity. Purpose-built machines offered higher utilization, productivity and fuel efficiency compared with excavator-based machines. Fuel consumption per m3 was 2.4 times greater for excavator-based units, compared with purpose-built machines. Excavator-based units offered financial and technical advantages, but their long-term market success will likely depend on future improvements in fuel efficiency, in the face of increasing fuel prices.
Comprehensive Analysis of the Cork Oak (Quercus suber) Transcriptome Involved in the Regulation of Bud Sprouting
Authors: Usié Ana , Simões Fernanda , Barbosa Pedro , Meireles Brígida , Chaves Inês , Gonçalves Sónia , Folgado André , Almeida Maria , Matos José , Ramos António
Published: December 2017

Cork oaks show a high capacity of bud sprouting as a response to injury, which is important for species survival when dealing with external factors, such as drought or fires. The characterization of the cork oak transcriptome involved in the different stages of bud sprouting is essential to understanding the mechanisms involved in these processes. In this study, the transcriptional profile of different stages of bud sprouting, namely (1) dormant bud and (2) bud swollen, vs. (3) red bud and (4) open bud, was analyzed in trees growing under natural conditions. The transcriptome analysis indicated the involvement of genes related with energy production (linking the TCA (tricarboxylic acid) cycle and the electron transport system), hormonal regulation, water status, and synthesis of polysaccharides. These results pinpoint the different mechanisms involved in the early and later stages of bud sprouting. Furthermore, some genes, which are involved in bud development and conserved between species, were also identified at the transcriptional level. This study provides the first set of results that will be useful for the discovery of genes related with the mechanisms regulating bud sprouting in cork oak.
Health Co-Benefits of Green Building Design Strategies and Community Resilience to Urban Flooding: A Systematic Review of the Evidence
Authors: Houghton Adele , Castillo-Salgado Carlos
Published: December 2017

Climate change is increasingly exacerbating existing population health hazards, as well as resulting in new negative health effects. Flooding is one particularly deadly example of its amplifying and expanding effect on public health. This systematic review considered evidence linking green building strategies in the Leadership in Energy and Environmental Design® (LEED) Rating System with the potential to reduce negative health outcomes following exposure to urban flooding events. Queries evaluated links between LEED credit requirements and risk of exposure to urban flooding, environmental determinants of health, co-benefits to public health outcomes, and co-benefits to built environment outcomes. Public health co-benefits to leveraging green building design to enhance flooding resilience included: improving the interface between humans and wildlife and reducing the risk of waterborne disease, flood-related morbidity and mortality, and psychological harm. We conclude that collaborations among the public health, climate change, civil society, and green building sectors to enhance community resilience to urban flooding could benefit population health.
Promoting Long-Term Health among People with Spinal Cord Injury: What’s New?
Authors: McColl Mary , Gupta Shikha , Smith Karen , McColl Alexander
Published: December 2017

A key ingredient to successful health promotion is a primary care provider who can offer an informed first response to lifestyle issues, emerging problems and chronic challenges. This article aims to assist family physicians to play their role in promoting the health of people with SCI, by summarizing the latest evidence in the management of spinal cord injury in primary care. This study used a scoping review methodology to survey peer-reviewed journal articles and clinical guidelines published between January 2012 to June 2016. This search strategy identified 153 articles across 20 topics. A prevention framework is used to identify five primary, nine secondary, four tertiary, and two quaternary prevention issues about which family physicians require current information. Major changes in the management of SCI in primary care were noted for 8 of the 20 topics, specifically in the areas of pharmacological management of neuropathic pain and urinary tract infection; screening for bowel and bladder cancer; improvements in wound care; and clarification of dietary fibre recommendations. All of these changes are represented in the 3rd edition of Actionable Nuggets—an innovative tool to assist family physicians to be aware of the best practices in primary care for spinal cord injury.
Exploratory Data Analysis of Synthetic Aperture Radar (SAR) Measurements to Distinguish the Sea Surface Expressions of Naturally-Occurring Oil Seeps from Human-Related Oil Spills in Campeche Bay (Gulf of Mexico)
Authors: Carvalho Gustavo , Minnett Peter , De Miranda Fernando , Landau Luiz , Paes Eduardo
Published: December 2017

An Exploratory Data Analysis (EDA) aims to use Synthetic Aperture Radar (SAR) measurements for discriminating between two oil slick types observed on the sea surface: naturally-occurring oil seeps versus human-related oil spills—the use of satellite sensors for this task is poorly documented in scientific literature. A long-term RADARSAT dataset (2008–2012) is exploited to investigate oil slicks in Campeche Bay (Gulf of Mexico). Simple Classification Algorithms to distinguish the oil slick type are designed based on standard multivariate data analysis techniques. Various attributes of geometry, shape, and dimension that describe the oil slick Size Information are combined with SAR-derived backscatter coefficients—sigma-(σo), beta-(βo), and gamma-(γo) naught. The combination of several of these characteristics is capable of distinguishing the oil slick type with ~70% of overall accuracy, however, the sole and simple use of two specific oil slick’s Size Information (i.e., area and perimeter) is equally capable of distinguishing seeps from spills. The data mining exercise of our EDA promotes a novel idea bridging petroleum pollution and remote sensing research, thus paving the way to further investigate the satellite synoptic view to express geophysical differences between seeped and spilled oil observed on the sea surface for systematic use.
Characterization of the Asiatic Acid Glucosyltransferase, UGT73AH1, Involved in Asiaticoside Biosynthesis in Centella asiatica (L.) Urban
Authors: Kim Ok , Jin Mei , Lee Dae , Jetter Reinhard
Published: December 2017

Centella asiatica (L.) Urban contains two ursane-type triterpene saponins, asiaticoside and madecassoside, as major secondary metabolites. In order to select candidate genes encoding UDP-glucosyltransferases (UGTs) involved in asiaticoside biosynthesis, we performed transcriptomic analysis of leaves elicited by methyl jasmonate (MeJA). Among the unigenes, 120 isotigs and 13 singletons of unique sequences were annotated as UGTs, including 37 putative full-length cDNAs, and 15 of the putative UGT genes were named according to the UGT committee nomenclature protocols. One of them, UGT73AH1, was characterized by heterologous expression in Escherichia coli BL21 (DE3) cells. After induction with IPTG, a total protein extract was assayed with UDP-glucose and asiatic acid. UPLC-QTOF/MS analysis showed that UGT73AH1 catalyzes the glycosylation of asiatic acid to its monoglucoside. It remains unclear whether glycosylation occurs on the triterpene C-2α, C-3β, C-23, or C-28 position. However, it is very likely that UGT73AH1 glucosylates the C-28 position, because only C-28 bears a glucose moiety in the final pathway product of asiatic acid, while C-2α, C-3β, and C-23 remain un-conjugated.
Pan-Domain Analysis of ZIP Zinc Transporters
Authors: Lehtovirta-Morley Laura , Alsarraf Mohammad , Wilson Duncan
Published: December 2017

The ZIP (Zrt/Irt-like protein) family of zinc transporters is found in all three domains of life. However, little is known about the phylogenetic relationship amongst ZIP transporters, their distribution, or their origin. Here we employed phylogenetic analysis to explore the evolution of ZIP transporters, with a focus on the major human fungal pathogen, Candida albicans. Pan-domain analysis of bacterial, archaeal, fungal, and human proteins revealed a complex relationship amongst the ZIP family members. Here we report (i) a eukaryote-wide group of cellular zinc importers, (ii) a fungal-specific group of zinc importers having genetic association with the fungal zincophore, and, (iii) a pan-kingdom supercluster made up of two distinct subgroups with orthologues in bacterial, archaeal, and eukaryotic phyla.
Frequency-Dependent Multi-Well Cardiotoxicity Screening Enabled by Optogenetic Stimulation
Authors: Rehnelt Susanne , Malan Daniela , Juhasz Krisztina , Wolters Benjamin , Doerr Leo , Beckler Matthias , Kettenhofen Ralf , Bohlen Heribert , Bruegmann Tobias , Sasse Philipp
Published: December 2017

Side effects on cardiac ion channels causing lethal arrhythmias are one major reason for drug withdrawals from the market. Field potential (FP) recording from cardiomyocytes, is a well-suited tool to assess such cardiotoxic effects of drug candidates in preclinical drug development, but it is currently limited to the spontaneous beating of the cardiomyocytes and manual analysis. Herein, we present a novel optogenetic cardiotoxicity screening system suited for the parallel automated frequency-dependent analysis of drug effects on FP recorded from human pluripotent stem cell-derived cardiomyocytes. For the expression of the light-sensitive cation channel Channelrhodopsin-2, we optimised protocols using virus transduction or transient mRNA transfection. Optical stimulation was performed with a new light-emitting diode lid for a 96-well FP recording system. This enabled reliable pacing at physiologically relevant heart rates and robust recording of FP. Thereby we detected rate-dependent effects of drugs on Na+, Ca2+ and K+ channel function indicated by FP prolongation, FP shortening and the slowing of the FP downstroke component, as well as generation of afterdepolarisations. Taken together, we present a scalable approach for preclinical frequency-dependent screening of drug effects on cardiac electrophysiology. Importantly, we show that the recording and analysis can be fully automated and the technology is readily available using commercial products.
Pharmacokinetics, Pharmacodynamics, Tolerability, and Food Effect of Cenerimod, a Selective S1P1 Receptor Modulator in Healthy Subjects
Authors: Juif Pierre-Eric , Baldoni Daniela , Reyes Maribel , Wilbraham Darren , Febbraro Salvatore , Vaclavkova Andrea , Hoch Matthias , Dingemanse Jasper
Published: December 2017

The pharmacokinetics, pharmacodynamics, tolerability, and food effect of cenerimod, a potent sphingosine-1-phosphate subtype 1 receptor modulator, were investigated in three sub-studies. Two double-blind, placebo-controlled, randomised studies in healthy male subjects were performed. Cenerimod was administered either as single dose (1, 3, 10 or 25 mg; Study 1) or once daily for 35 days (0.5, 1, 2 or 4 mg; Study 2). A two-period cross-over, open-label study was performed to assess the food effect (1 mg, Study 3). The pharmacokinetic profile of cenerimod was characterised by a tmax of 5.0–6.2 h. Terminal half-life after single and multiple doses ranged from 170 to 199 h and 283 to 539 h, respectively. Food had no relevant effect on the pharmacokinetics of cenerimod. A dose-dependent decrease in lymphocyte count was observed after initiation of cenerimod and reached a plateau (maximum change from baseline: −64%) after 20–23 days of treatment. Lymphocyte counts returned to baseline values at end-of-study examination. One serious adverse event of circulatory collapse (25 mg dose group, maximum tolerated dose: 10 mg) and adverse events of mild-to-moderate intensity were reported. Treatment initiation was associated with transient decreases in heart rate and blood pressure at doses >1 and ≥10 mg, respectively.
Lipopolysaccharide-Induced Nitric Oxide, Prostaglandin E2, and Cytokine Production of Mouse and Human Macrophages Are Suppressed by Pheophytin-b
Authors: Lin Chun-Yu , Wang Wen-Hung , Chen Shin-Huei , Chang Yu-Wei , Hung Ling-Chien , Chen Chung-Yi , Chen Yen-Hsu
Published: December 2017

Sepsis is an overwhelming systemic response to infection that frequently results in tissue damage, organ failure, and even death. Nitric oxide (NO), prostaglandin E2 (PGE2), and cytokine overproduction are thought to be associated with the immunostimulatory cascade in sepsis. In the present study, we analyzed the anti-inflammatory efficacy of the pheophytin-b on both RAW 264.7 murine macrophage and purified human CD14+ monocytes stimulated with lipopolysaccharide (LPS) and elucidated the mechanisms by analyzing the cell signaling pathways known to be activated in sepsis. Pheophytin-b suppressed the overexpression of NO, PGE2, and cytokines in LPS-stimulated macrophages without inducing cytotoxicity. It also reduced NOS2 and COX-2 mRNA and protein levels. The inhibitory effects on NO, PGE2, and cytokine overproduction arose from the suppression of STAT-1 and PI3K/Akt pathways; no changes in NF-κB, MAPK, and AP-1 signaling were detected. Thus, pheophytin-b may represent a potential candidate to beneficially modulate the inflammatory response in sepsis.
Charomers—Interleukin-6 Receptor Specific Aptamers for Cellular Internalization and Targeted Drug Delivery
Authors: Hahn Ulrich
Published: December 2017

Interleukin-6 (IL-6) is a key player in inflammation and the main factor for the induction of acute phase protein biosynthesis. Further to its central role in many aspects of the immune system, IL-6 regulates a variety of homeostatic processes. To interfere with IL-6 dependent diseases, such as various autoimmune diseases or certain cancers like multiple myeloma or hepatocellular carcinoma associated with chronic inflammation, it might be a sensible strategy to target human IL-6 receptor (hIL-6R) presenting cells with aptamers. We therefore have selected and characterized different DNA and RNA aptamers specifically binding IL-6R. These IL-6R aptamers, however, do not interfere with the IL-6 signaling pathway but are internalized with the receptor and thus can serve as vehicles for the delivery of different cargo molecules like therapeutics. We succeeded in the construction of a chlorin e6 derivatized aptamer to be delivered for targeted photodynamic therapy (PDT). Furthermore, we were able to synthesize an aptamer intrinsically comprising the cytostatic 5-Fluoro-2′-deoxy-uridine for targeted chemotherapy. The α6β4 integrin specific DNA aptamer IDA, also selected in our laboratory is internalized, too. All these aptamers can serve as vehicles for targeted drug delivery into cells. We call them charomers—in memory of Charon, the ferryman in Greek mythology, who ferried the deceased into the underworld.
sCwc/sLcc: Highly Scalable Feature Selection Algorithms
Authors: Shin Kilho , Kuboyama Tetsuji , Hashimoto Takako , Shepard Dave
Published: December 2017

Feature selection is a useful tool for identifying which features, or attributes, of a dataset cause or explain the phenomena that the dataset describes, and improving the efficiency and accuracy of learning algorithms for discovering such phenomena. Consequently, feature selection has been studied intensively in machine learning research. However, while feature selection algorithms that exhibit excellent accuracy have been developed, they are seldom used for analysis of high-dimensional data because high-dimensional data usually include too many instances and features, which make traditional feature selection algorithms inefficient. To eliminate this limitation, we tried to improve the run-time performance of two of the most accurate feature selection algorithms known in the literature. The result is two accurate and fast algorithms, namely sCwc and sLcc. Multiple experiments with real social media datasets have demonstrated that our algorithms improve the performance of their original algorithms remarkably. For example, we have two datasets, one with 15,568 instances and 15,741 features, and another with 200,569 instances and 99,672 features. sCwc performed feature selection on these datasets in 1.4 seconds and in 405 seconds, respectively. In addition, sLcc has turned out to be as fast as sCwc on average. This is a remarkable improvement because it is estimated that the original algorithms would need several hours to dozens of days to process the same datasets. In addition, we introduce a fast implementation of our algorithms: sCwc does not require any adjusting parameter, while sLcc requires a threshold parameter, which we can use to control the number of features that the algorithm selects.
Imaging Characteristics of Malignant Sinonasal Tumors
Authors: Kawaguchi Masaya , Kato Hiroki , Tomita Hiroyuki , Mizuta Keisuke , Aoki Mitsuhiro , Hara Akira , Matsuo Masayuki
Published: December 2017

Malignancies of the nasal cavity and paranasal sinuses account for 1% of all malignancies and 3% of malignancies of the upper aerodigestive tract. In the sinonasal tract, nearly half of all malignancies arise in the nasal cavity, whereas most of the remaining malignancies arise in the maxillary or ethmoid sinus. Squamous cell carcinoma is the most common histological subtype of malignant tumors occurring in this area, followed by other epithelial carcinomas, lymphomas, and malignant soft tissue tumors. Although many of these tumors present with nonspecific symptoms, each tumor exhibits characteristic imaging features. Although complex anatomy and various normal variants of the sinonasal tract cause difficulty in identifying the origin and extension of large sinonasal tumors, the invasion of vital structures such as the brain, optic nerves, and internal carotid artery affects patients’ prognosis. Thus, diagnostic imaging plays a key role in predicting the histological subtype and in evaluating a tumor extension into adjacent structures. This article describes the computed tomography and magnetic resonance imaging findings for malignant sinonasal tumors.
Preliminary Results of Clover and Grass Coverage and Total Dry Matter Estimation in Clover-Grass Crops Using Image Analysis
Authors: Mortensen Anders , Karstoft Henrik , Søegaard Karen , Gislum René , Jørgensen Rasmus
Published: December 2017

The clover-grass ratio is an important factor in composing feed ratios for livestock. Cameras in the field allow the user to estimate the clover-grass ratio using image analysis; however, current methods assume the total dry matter is known. This paper presents the preliminary results of an image analysis method for non-destructively estimating the total dry matter of clover-grass. The presented method includes three steps: (1) classification of image illumination using a histogram of the difference in excess green and excess red; (2) segmentation of clover and grass using edge detection and morphology; and (3) estimation of total dry matter using grass coverage derived from the segmentation and climate parameters. The method was developed and evaluated on images captured in a clover-grass plot experiment during the spring growing season. The preliminary results are promising and show a high correlation between the image-based total dry matter estimate and the harvested dry matter ( R 2 = 0.93 ) with an RMSE of 210 kg ha − 1 .
The Cell Wall Integrity Signaling Pathway and Its Involvement in Secondary Metabolite Production
Authors: Valiante Vito
Published: December 2017

The fungal cell wall is the external and first layer that fungi use to interact with the environment. Every stress signal, before being translated into an appropriate stress response, needs to overtake this layer. Many signaling pathways are involved in translating stress signals, but the cell wall integrity (CWI) signaling pathway is the one responsible for the maintenance and biosynthesis of the fungal cell wall. In fungi, the CWI signal is composed of a mitogen-activated protein kinase (MAPK) module. After the start of the phosphorylation cascade, the CWI signal induces the expression of cell-wall-related genes. However, the function of the CWI signal is not merely the activation of cell wall biosynthesis, but also the regulation of expression and production of specific molecules that are used by fungi to better compete in the environment. These molecules are normally defined as secondary metabolites or natural products. This review is focused on secondary metabolites affected by the CWI signal pathway with a special focus on relevant natural products such as melanins, mycotoxins, and antibacterial compounds.
Sociodemographic Factors on Contraceptive Use among Ever-Married Women of Reproductive Age: Evidence from Three Demographic and Health Surveys in Bangladesh
Authors: Haq Iqramul , Sakib Saifullah , Talukder Ashis
Published: December 2017

Contraceptive use among married women of reproductive age has showed a substantial progress over the last few decades in Bangladesh. This study explores the sociodemographic factors associated with contraceptive use among ever-married women of reproductive age in Bangladesh by utilizing the information extracted from three of the Bangladesh Demographic and Health Surveys (BDHSs) in 1993–1994, 2004 and 2014. Bivariate analysis was conducted by performing chi-squared test of independence to explore the relationship between selected sociodemographic factors and dependent variables. To know the adjusted effects of covariates, a popular binary logistic regression model was considered. Respondents’ current age, place residence, division religion, education, age at first marriage, family planning (FP) media exposure, ideal number of children and fertility preferences are the significant determinants according to the most recent survey, BDHS 2014. However, wealth index and a respondent’s current working status were found to be significant factors only in BDHS 2004. The results of the study strongly recommend efforts to increase the education level among poor people, particularly among women in Bangladesh. Program interventions, including health behavior education and family planning services and counselling, are especially needed for some categories of the population, including those living in rural areas, Sylhet, Chittagong and Dhaka divisions, as well as illiterate and Muslim ever-married women.
Detection of Capillary-Mediated Energy Fields on a Grain Boundary Groove: Solid–Liquid Interface Perturbations
Authors: Glicksman Martin , Ankit Kumar
Published: December 2017

Grain boundary grooves are common features on polycrystalline solid–liquid interfaces. Their local microstructure can be closely approximated as a “variational” groove, the theoretical profile for which is analyzed here for its Gibbs–Thomson thermo-potential distribution. The distribution of thermo-potentials for a variational groove exhibits gradients tangential to the solid–liquid interface. Energy fluxes stimulated by capillary-mediated tangential gradients are divergent and thus capable of redistributing energy on real or simulated grain boundary grooves. Moreover, the importance of such capillary-mediated energy fields on interfaces is their influence on stability and pattern formation dynamics. The capillary-mediated field expected to be present on a stationary grain boundary groove is verified quantitatively using the multiphase-field approach. Simulation and post-processing measurements fully corroborate the presence and intensity distribution of interfacial cooling, proving that thermodynamically-consistent numerical models already support, without any modification, capillary perturbation fields, the existence of which is currently overlooked in formulations of sharp interface dynamic models.