bluuebunny/crossref_metadata_2025 huggingface dataset:
Logging, exotic plant invasions, and native plant reassembly in a lowland tropical rain forest
Authors: Döbert Timm F. , Webber Bruce L. , Sugau John B. , Dickinson Katharine J. M. , Didham Raphael K.
Published: December 2017

Habitat modification and biological invasions are key drivers of global environmental change. However, the extent and impact of exotic plant invasions in modified tropical landscapes remain poorly understood. We examined whether logging drives exotic plant invasions and whether their combined influences alter understory plant community composition in lowland rain forests in Borneo. We tested the relationship between understory communities and local‐ and landscape‐scale logging intensity, using leaf area index (LAI) and aboveground biomass (AGB) data from 192 plots across a logging‐intensity gradient from primary to repeatedly logged forests. Overall, we found relatively low levels of exotic plant invasions, despite an intensive logging history. Exotic species were more speciose, had greater cover, and more biomass in sites with more local‐scale canopy loss. Surprisingly, though, exotic species invasion was not related to either landscape‐scale canopy loss or road configuration. Moreover, logging and invasion did not seem to be acting synergistically on native plant composition, except that seedlings of the canopy‐dominant Dipterocarpaceae family were less abundant in areas with higher exotic plant biomass. Current low levels of invasion, and limited association with native understory community change, suggest there is a window of opportunity to manage invasive impacts. We caution about potential lag effects and the possibly severe negative impacts of exotic plant invasions on the long‐term quality of tropical forest, particularly where agricultural plantations function as permanent seed sources for recurrent dispersal along logging roads. We therefore urge prioritization of strategic management plans to counter the growing threat of exotic plant invasions in modified tropical landscapes.
Design, synthesis, and antiprotozoal evaluation of new 2,9‐bis[(substituted‐aminomethyl)phenyl]‐1,10‐phenanthroline derivatives
Authors: Guillon Jean , Cohen Anita , Das Rabindra Nath , Boudot Clotilde , Gueddouda Nassima Meriem , Moreau Stéphane , Ronga Luisa , Savrimoutou Solène , Basmaciyan Louise , Tisnerat Camille , Mestanier Sacha , Rubio Sandra , Amaziane Sophia , Dassonville‐Klimpt Alexandra , Azas Nadine , Courtioux Bertrand , Mergny Jean‐Louis , Mullié Catherine , Sonnet Pascal
Published: December 2017

A series of new 2,9‐bis[(substituted‐aminomethyl)phenyl]‐1,10‐phenanthroline derivatives was synthesized, and the compounds were screened in vitro against three protozoan parasites (Plasmodium falciparum, Leishmania donovani, and Trypanosoma brucei brucei). Biological results showed antiparasitic activity with IC50 values in the μm range. The in vitro cytotoxicity of these molecules was assessed by incubation with human HepG2 cells; for some derivatives, cytotoxicity was observed at significantly higher concentrations than antiparasitic activity. The 2,9‐bis[(substituted‐aminomethyl)phenyl]‐1,10‐phenanthroline 1h was identified as the most potent antimalarial candidate with ratios of cytotoxic‐to‐antiparasitic activities of 107 and 39 against a chloroquine‐sensitive and a chloroquine‐resistant strain of P. falciparum, respectively. As the telomeres of the parasite P. falciparum are the likely target of this compound, we investigated stabilization of the Plasmodium telomeric G‐quadruplexes by our phenanthroline derivatives through a FRET melting assay. The ligands 1f and 1m were noticed to be more specific for FPf8T with higher stabilization for FPf8T than for the human F21T sequence.
Antibacterial activities and molecular mechanism of amino‐terminal fragments from pig nematode antimicrobial peptide CP‐1
Authors: Dong Na , Wang Zhihua , Chou Shuli , Zhang Licong , Shan Anshan , Jiang Junguang
Published: December 2017

High manufacturing costs and weak cell selectivity have limited the clinical application of naturally occurring peptides when faced with an outbreak of drug resistance. To overcome these limitations, a set of antimicrobial peptides was synthesized with the general sequence of (WL)n, where n = 1, 2, 3, and WL was truncated from the N‐terminus of Cecropin P1 without initial serine residues. The antimicrobial peptide WL3 exhibited stronger antimicrobial activity against both Gram‐negative and Gram‐positive microbes than the parental peptide CP‐1. WL3 showed no hemolysis even at the highest test concentrations compared to the parental peptide CP‐1. The condition sensitivity assays (salts, serum, and trypsin) demonstrated that WL3 had high stability in vitro. Fluorescence spectroscopy and electron microscopy indicated that WL3 killed microbes by means of penetrating the membrane and causing cell lysis. In a mouse model, WL3 was able to significantly reduce the bacteria load in major organs and cytokines (TNF‐α, IL‐6, and IL‐1β) levels in serum. In summary, these findings suggest that WL3, which was modified from a natural antimicrobial peptide, has enormous potential for application as a novel antibacterial agent.
Filaggrin mutations increase allergic airway disease in childhood and adolescence through interactions with eczema and aeroallergen sensitization
Authors: Chan Adrian , Terry William , Zhang Hongmei , Karmaus Wilfried , Ewart Susan , Holloway John W. , Roberts Graham , Kurukulaaratchy Ramesh , Arshad Syed Hasan
Published: December 2017

Background

Filaggrin loss‐of‐function (FLG‐LOF) mutations are an established genetic cause of eczema. These mutations have subsequently been reported to increase the risk of aeroallergen sensitization and allergic airway disease. However, it is unclear whether FLG variants require both eczema and aeroallergen sensitization to influence airway disease development long‐term outcomes.

Objective

To examine the effects of FLG‐LOF mutations on allergic airway disease outcomes, with eczema and aeroallergen sensitization as intermediate variables, using the Isle of Wight birth cohort.

Methods

Study participants were evaluated at ages 1, 2, 4, 10 and 18 years to ascertain the development of allergic diseases (eczema, asthma and allergic rhinitis) and aeroallergen sensitization (determined by skin prick tests). FLG‐LOF mutations were genotyped in 1150 subjects. To understand the complex associations between FLG mutations, intermediate variables (eczema and aeroallergen sensitization) and airway disease, path analysis was performed.

Results

There were significant total effects of FLG‐LOF mutations on both asthma and allergic rhinitis at all ages as well as on aeroallergen sensitization up till 10 years old. In the filaggrin‐asthma analysis, a direct effect of FLG‐LOF mutations was observed on early childhood eczema (age 1 and 2 years) (relative risk (RR) 2.01, 95% CI: 1.74‐2.31, P < .001), and all significant indirect pathways on asthma outcomes passed through eczema at these ages. In contrast, for the filaggrin‐rhinitis model, FLG‐LOF mutations exerted significant direct effects on early eczema as well as rhinitis at 10 years (RR 1.99; 95% CI: 1.72‐2.29, P = .002).

Conclusion

FLG‐LOF mutations are a significant risk factor for later childhood asthma and rhinitis. However, the pathway to asthma is only through early childhood eczema while a direct effect was observed for childhood rhinitis.
Therapeutic potential of phages in autoimmune liver diseases
Authors: Górski A , Jończyk-Matysiak E , Łusiak-Szelachowska M , Weber-Dąbrowska B , Międzybrodzki R , Borysowski J
Published: December 2017

Autoimmune liver disease (ALD) poses a difficult medical challenge, as there is a significant number of patients in whom current therapy offers questionable or no benefit, yet its side effects may be serious, including the development of malignancy. Bacterial viruses (phages) have been recognized increasingly as immunomodulators contributing to immune homeostasis and curbing inflammation. Accumulating data suggest that phages may be useful in immunotherapy of ALD. Phages have been shown to down-regulate the expression and/or production and activity of factors associated with hepatic injury [reactive oxygen species, Toll-like receptor (TLR)-4 activation, nuclear factor kappa B (NF-κB) activation, proinflammatory and procoagulant activities of platelets] and up-regulate the expression and/or production of factors demonstrated as playing a protective role [interleukin (IL)-10, IL-1 receptor antagonist].
Randomized open‐label crossover assessment of Prograf vs Advagraf on immunosuppressant pharmacokinetics and pharmacodynamics in simultaneous pancreas‐kidney patients
Authors: Cattral Mark , Luke Sean , Knauer Michael J. , Norgate Andrea , Schiff Jeffrey , Muirhead Norman , Luke Patrick P.
Published: December 2017

Introduction

We assessed the pharmacokinetic and pharmacodynamic impact of converting stable simultaneous pancreas‐kidney (SPK) recipients from standard tacrolimus (Prograf) to long‐acting tacrolimus (Advagraf).

Methods

In a randomized prospective crossover study, stable SPK recipients on Prograf were assigned to Prograf with 1:1 conversion to Advagraf or vice versa. Demographics, tacrolimus, mycophenolic acid levels, and Cylex CD4 + ATP levels were taken at specified intervals in addition to standard blood work.

Results

Twenty‐one patients, who were a minimum of 1 year post‐transplant, were entered into the study. No difference in tacrolimus or mycophenolic acid levels was noted between patients who were first assigned to Prograf or Advagraf. Additionally, Cylex levels as well as serum creatinine, lipase, and blood sugar levels were unchanged. There were no episodes of rejection during the 6‐month study.

Conclusions

It is safe to convert between Prograf and Advagraf 1:1, without major impact on pharmacokinetics or pharmacodynamics in SPK recipients.
Global health inequalities and the need for solidarity: a view from the Global South
Authors: Tosam Mbih J. , Chi Primus Che , Munung Nchangwi Syntia , Oukem‐Boyer Odile Ouwe Missi , Tangwa Godfrey B.
Published: December 2017

Although the world has experienced remarkable progress in health care since the last half of the 20th century, global health inequalities still persist. In some poor countries life expectancy is between 37‐40 years lower than in rich countries; furthermore, maternal and infant mortality is high and there is lack of access to basic preventive and life‐saving medicines, as well a high prevalence of neglected diseases, HIV/AIDS, tuberculosis, and malaria. Moreover, globalization has made the world more connected than before such that health challenges today are no longer limited within national or regional boundaries, making all persons equally vulnerable. Because of this, diseases in the most affluent countries are closely connected with diseases in the poorest countries. In this paper, we argue that, because of global health inequalities, in a situation of equal vulnerability, there is need for global solidarity not only as a means of reducing health inequalities, but also as a way of putting up a united force against global health challenges. We argue for an African approach to solidarity in which the humanity of a person is not determined by his/her being human or rational capacity, but by his/her capacity to live a virtuous life. According to this view of solidarity, because no one is self‐sufficient, no individual can survive alone. If we are to collectively flourish in a world where no individual, nation or region has all the health resources or protection needed for survival, we must engage in solidarity where we remain compassionate and available to one another at all times.
Evaluation of peer‐generated MCQs to assess and support learning in a problem‐based learning programme
Authors: Botelho MG , Lam OLT , Watt RM , Leung DYP , Kember D
Published: December 2017

Purpose

Problem‐based learning (PBL) students report uncertainty on the depth and breadth of learning required, and this is a significant stressor and challenge. Student‐generated MCQ questions were trialled and evaluated as a way to support depth and breadth of learning.

Methods

Students set MCQs relating to specified learning issues, and an analysis and evaluation of setting and answering the MCQs were performed. The Revised Study Process Questionnaire (R‐SPQ‐2F) and final written examination scores were correlated to question setting and answering. Students were asked to rate the impact of the MCQs on their learning in PBL.

Results

A total of 147 questions were created and 2373 answered. Students reported challenges with setting questions, although these made them think more deeply and helped their learning and affirming their learning progress. MCQs authored indicated significant associations with Understanding, and examination scores were associated with MCQs authored. Students reported a moderate response to how the MCQs supported their depth and breadth of learning.

Conclusions

While MCQ setting was perceived as a useful learning exercise, students engaged to different levels and experienced challenges. Students were uncertain whether the MCQs helped clarify the depth and breadth of learning in PBL, as they were not clear whether the questions set by their peers were relevant to the required learning outcomes.
Interactive life‐history traits predict sensitivity of plants and animals to temporal autocorrelation
Authors: Paniw Maria , Ozgul Arpat , Salguero‐Gómez Roberto
Published: December 2017

Temporal autocorrelation in demographic processes is an important aspect of population dynamics, but a comprehensive examination of its effects on different life‐history strategies is lacking. We use matrix population models from 454 plant and animal populations to simulate stochastic population growth rates (log λs) under different temporal autocorrelations in demographic rates, using simulated and observed covariation among rates. We then test for differences in sensitivities, or changes of log λs to changes in autocorrelation among two major axes of life‐history strategies, obtained from phylogenetically informed principal component analysis: the fast‐slow and reproductive‐strategy continua. Fast life histories exhibit highest sensitivities to simulated autocorrelation in demographic rates across reproductive strategies. Slow life histories are less sensitive to temporal autocorrelation, but their sensitivities increase among highly iteroparous species. We provide cross‐taxonomic evidence that changes in the autocorrelation of environmental variation may affect a wide range of species, depending on complex interactions of life‐history strategies.
Impact of an early respiratory care programme with non‐invasive ventilation adaptation in patients with amyotrophic lateral sclerosis
Authors: Vitacca M. , Montini A. , Lunetta C. , Banfi P. , Bertella E. , De Mattia E. , Lizio A. , Volpato E. , Lax A. , Morini R. , Paneroni M. ,   the ALS RESPILOM Study Group
Published: December 2017

Background and purpose

Forced vital capacity (FVC) <80% is one of the key indications for starting non‐invasive ventilation (NIV) in amyotrophic lateral sclerosis (ALS). It was hypothesized that a very early start of NIV could lengthen the free interval before death compared to later‐start NIV; as a secondary outcome, the survival rate of patients on NIV without tracheotomy was also evaluated.

Methods

This retrospective study was conducted on 194 ALS patients, divided into a later group (LG) with FVC <80% at NIV prescription (n = 129) and a very early group (VEG) with FVC ≥80% at NIV prescription (n = 65). Clinical and respiratory functional data and time free to death between groups over a 3‐year follow‐up were compared.

Result

At 36 months from diagnosis, mortality was 35% for the VEG versus 52.7% for the LG (P = 0.022). Kaplan−Meier survival curves adjusted for tracheotomy showed a lower probability of death (P = 0.001) for the VEG as a whole (P = 0.001) and for the non‐bulbar (NB) subgroup (P = 0.007). Very early NIV was protective of survival for all patients [hazard ratio (HR) 0.45; 95% confidence interval (CI) 0.28–0.74; P = 0.001] and for the NB subgroup (HR 0.43; 95% CI 0.23–0.79; P = 0.007), whilst a tracheotomy was protective for all patients (HR 0.27; 95% CI 0.15–0.50; P = 0.000) and both NB (HR 0.26; 95% CI 0.12–0.56; P = 0.001) and bulbar subgroups (HR 0.29; 95% CI 0.11–0.77; P = 0.013). Survival in VEG patients on NIV without tracheotomy was three times that for the LG (43.1% vs. 14.7%).

Conclusion

Very early NIV prescription prolongs the free time from diagnosis to death in NB ALS patients whilst tracheotomy reduces the mortality risk in all patients.
Tolerance Versus Support: Perceptions of Residential Community Climate Among LGB Parents
Authors: Oswald Ramona Faith , Routon Jasmine M. , McGuire Jenifer K. , Holman Elizabeth Grace
Published: December 2017

Objective

To understand which aspects of residential communities are most salient for determining whether sexual minority parents classify their residential community climates as tolerant versus supportive.

Background

Metropolitan hubs for lesbian, gay, and bisexual (LGB) parents are well established, but less is known about nonmetropolitan community climates for LGB parents. Residential community climate toward nonmetropolitan LGB persons may be particularly important to LGB parents because of the potential influences on child and family well‐being.

Method

Open‐ and closed‐ended survey data from a sample of 55 LGB parents were collected along with publically available data regarding their residential communities. Self‐reported residential community climate (tolerant vs. supportive) and community involvement, as well as objective county and municipal climate were analyzed.

Results

Compared with LGB parents who perceived their communities to be tolerant (n = 38), parents who considered their residential communities to be supportive (n = 17) were more likely to live in counties characterized by legal support and broad social acceptance, were personally more likely to participate in LGB‐focused social and political activities, had children with more exposure to other LGB families, and attended church less frequently.

Conclusion

Having basic features of equity such as city ordinances and LGB organizations provides a foundation for tolerance in a community; however, individuals in a community must access personal and social supports and activities beyond work and church to feel truly supported.

Implications

LGB parents' perceptions of climate reveal specific community features that need to be strengthened to promote family well‐being.
A unified damage factor model for ductile fracture of steels with different void growth and shrinkage rates
Authors: Li C. , Zhou Z. , Zhu Y. , Lu L.
Published: December 2017

Micromechanical fracture modelling is an effective method to predict ductile fracture in steel structures. This paper aims to establish a simplified and general fracture model for various loading conditions, which is convenient to calculate the instantaneous damage index. With the concept of the ductile damage factor, a unified ductile damage factor model considering the difference of rates between void growth and shrinkage has been proposed. Based on experiment results and finite element analysis, the model parameters for Q235B Chinese structural steel were calibrated. The ductile damage factor and equivalent plastic strain at fracture initiation were investigated. Comparison among the proposed model, experimental results, and the cyclic void growth model demonstrated the effectiveness and accuracy of the proposed model. A parametric study was conducted to investigate the influence of cyclic constitutive parameters on the accuracy of fracture prediction. The predicted results are acceptable while reducing those calibrated cyclic constitutive parameters by 20%.
Productivity Risk and Industry Momentum
Authors: Misirli Efdal Ulas
Published: December 2017

A productivity shock identified through a vector autoregression model is a priced risk factor for one‐month industry momentum portfolios and commands a positive risk premium. Stocks in winning industries have greater sensitivity to productivity news, thereby earning higher average returns than stocks in losing industries. This evidence lends support to an Intertemporal Capital Asset Pricing Model (ICAPM) with human wealth. In many specifications, exposure to productivity risk captures more than half of the observed industry momentum profits. This paper studies the sources of profits and attributes the risks of industry momentum portfolios to the behavior of their underlying cash flows.
Factors affecting grazing preference by sheep in a breeding population of tall fescue (Festuca arundinacea Schreb.)
Authors: Cougnon M. , Shahidi R. , Schoelynck J. , Van Der Beeten I. , Van Waes C. , De Frenne P. , Van Labeke M.‐C. , Reheul D.
Published: December 2017

A disadvantage of tall fescue (Festuca arundinacea Schreb.) is its low voluntary intake, resulting in suboptimal performance under grazing. Ideally, selection for this trait is done using grazing animals, but their use in plant breeding programmes is costly and laborious. Repeatable, stable and quantifiable traits linked to animal preference could ease tall fescue breeding. We established a trial to find relationships between the grazing preference of sheep and sward‐ and plant‐related traits. Seventeen genotypes were studied in swards. Sheep grazing preference, pre‐grazing sward height (SH), leaf softness, leaf blade length, width, colour and shear strength, and concentration of fibre, silica, digestible organic matter (DOM) and water‐soluble carbohydrate (WSC) were quantified throughout the growing season. The traits with the strongest correlation with sheep preference were DOM, SH, leaf colour, leaf width and WSC. Leaf softness, silica content and leaf shear strength were not correlated with sheep preference. We conclude that DOM is the trait that offers the best prospects for contributing to progress in tall fescue plant breeding for both intake and feeding value.
Empowering people to help speak up about safety in primary care: Using codesign to involve patients and professionals in developing new interventions for patients with multimorbidity
Authors: Knowles Sarah , Hays Rebecca , Senra Hugo , Bower Peter , Locock Louise , Protheroe Jo , Sanders Caroline , Daker‐White Gavin
Published: December 2017

Background

Multimorbidity, defined as the presence of two or more long‐term conditions, is increasingly common in primary care, and patients with multimorbidity may face particular barriers to quality of care and increased safety risks due to the complexity of managing multiple conditions. Consistent with calls to directly involve service users in improving care, we aimed to use design materials to codesign new interventions to improve safety in primary care.

Design

We drew on two established methods—accelerated experience‐based codesign and the future workshop approach. We synthesized design materials based on research into the patient experience of safety and multimorbidity in primary care to enable both patients, service users and carers, and primary health‐care professionals to propose interventions to improve care.

Results

Both patients and professionals prioritized polypharmacy as a threat to safety. Their recommendations for supportive interventions were consistent with Burden of Treatment theory, emphasizing the limited capacity of patients with multimorbidity and the need for services to proactively offer support to reduce the burden of managing complex treatment regimes.

Discussion & Conclusions

The process was feasible and acceptable to participants, who valued the opportunity to jointly propose new interventions. The iterative workshop approach enabled the research team to better explore and refine the suggestions of attendees. Final recommendations included the need for accessible reminders to support medication adherence and medication reviews for particularly vulnerable patients conducted with pharmacists within GP practices.
Submarine slope–fan sedimentation in an ancient forearc related to contemporaneous magmatism: The Upper Cretaceous Izumi Group, southwestern Japan
Authors: Noda Atsushi , Sato Daisuke
Published: December 2017

The Izumi Group in southwestern Japan is considered to represent deposits in a forearc basin along an active volcanic arc during the late Late Cretaceous. The group consists mainly of felsic volcanic and plutonic detritus, and overlies a Lower to Upper Cretaceous plutono‐metamorphic complex (the Ryoke complex). In order to reconstruct the depositional environments and constrain the age of deposition, sedimentary facies and U–Pb dating of zircon grains in tuff were studied for a drilled core obtained from the basal part of the Izumi Group. On the basis of the lithofacies associations, the core was subdivided into six units from base to top, as follows: mudstone‐dominated unit nonconformably deposited on the Ryoke granodiorite; tuffaceous mudstone‐dominated unit; tuff unit; tuffaceous sandstone–mudstone unit; sandstone–mudstone unit; and sandstone‐dominated unit. This succession suggests that the depositional system changed from non‐volcanic muddy slope or basin floor, to volcaniclastic sandy submarine fan. Based on a review of published radiometric age data of the surrounding region of the Ryoke complex and the Sanyo Belt which was an active volcanic front during deposition of the Izumi Group, the U–Pb age (82.7 ±0.5 Ma) of zircon grains in the tuff unit corresponds to those of felsic volcanic and pyroclastic rocks in the Sanyo Belt.
Inclusive or Exclusive? How Contact with Host Nationals May Change Immigrants' Boundary Perceptions and Foster Identity Compatibility
Authors: Simonsen Kristina Bakkær
Published: December 2017

While immigrants may value their ethnic identities, the symbolic boundaries in many European nations are drawn in an exclusive manner, presenting ethnic identification as incompatible with host national belonging. Combining boundary drawing and contact theory, this article examines whether — in a context of exclusive boundary drawing — contact can lead to more inclusive boundary perceptions and foster identity compatibility. The analysis employs survey and interview data from Denmark, which is taken as a case of exclusive boundary drawing. Demonstrating both positive effects and the limits of contact in such a context, the article offers a critical assessment of contact's potential and contributes to nuancing our understanding of macro and micro conditions of immigrant identity.
Factors associated with physical activity levels in people with venous leg ulcers: A multicentre, prospective, cohort study
Authors: Smith Daisy , Team Victoria , Barber Georgina , O'Brien Jane , Wynter Karen , McGinnes Rosemary , Tsiamis Ellie , Weller Carolina D
Published: December 2017

Increasing levels of physical activity among people with venous leg ulcers (VLUs) can potentially reduce the health cost burden, improve functional aspects of patients’ lives and increase ulcer healing rates. The aim of this study was to investigate factors associated with physical activity levels in patients with VLUs. Data from 2016 to 2017 Aspirin for Venous Leg Ulcer cohort study were analysed for the present study. Ninety participants were recruited from 5 outpatient specialist wound clinics across Victoria, Australia between August 2016 and April 2017. There was a statistically significant association between diabetes and physical activity, with a higher proportion of people with type 2 diabetes in the sedentary category. Further, there was a statistically significant association between patient‐reported VLU education and physical activity levels. An indirect advantage of relevant, easy‐to‐understand education about VLUs may increase physical activity levels, which may facilitate improved time to healing of VLUs.
Fundamental principles that govern the copper doping behavior in complex clinker system
Authors: Tao Yong , Zhang Wenqin , Li Neng , Shang Dechen , Xia Zhongsheng , Wang Fazhou
Published: December 2017

Understanding the doping behavior of impurity ions in clinker phases is crucial for controlling the doping effect on clinker compounds, which, however, has not yet been fully demonstrated due to the composition complexity. Herein, we employ the state‐of‐the‐art ab initio calculation to uncover the substitution mechanism of Cu ions in 4 dominant clinker crystals. The defect formation energies indicate Cu ions energetically prefer to substitute Fe ions in ferrite, which is in accord with the experiments. The bond order difference is innovatively postulated to interpret the energy barriers of Cu substitution in comparison with the ionic radius criterion. The high potential barriers of Cu substituting Ca, Si, and Al ions are ascribed to their bond order mismatch, while the tendency of Cu replacing Fe is due to their bond order similarity. Namely, the Cu doping in clinker phases follows the “bond order conformity” principle. In‐depth electronic structure analysis reveals that the bond order is more effective than the ionic radius to estimate potential barriers of Cu substitution in complex clinker system mainly because the latter underestimates the influence of electronic structure differences while the bond order directly measures the bonding structure related to interatomic charge transfer.
Role of silica nanoparticle in multi‐component epoxy composites for electrical insulation with high thermal conductivity
Authors: Lee Dae Ho , Lee Nakyung , Park Hoyyul
Published: December 2017

Multicomponent epoxy micro/nano‐composites containing micro‐alumina, micro‐quartz, and nano‐silica were fabricated to develop electrical insulation materials with high thermal conductivity. Simply changing the ratio between the alumina and quartz microparticles caused a trade‐off relationship between the thermal conductivity and electrical insulation. Increasing the alumina content in the epoxy‐alumina/quartz micro‐composites enhanced the thermal conductivity but deteriorated the dielectric strength. An increase in the thermal conductivity without incurring a loss in the dielectric strength was achieved by incorporating silica nanoparticles in the epoxy micro‐composites. Adding silica nanoparticles to the epoxy micro‐composites was found to be more efficient in improving the thermal conductivity compared to increasing the alumina ratio, especially at low alumina/quartz ratios. This behavior corresponded to theoretical models. Therefore, we provide a useful insight, both practical and theoretical, into the more advanced optimization of designing multicomponent epoxy composites for electrical insulation with high thermal conductivity.
Geostatistical interpolation can reliably extend coverage of a very high‐resolution model of temperature‐dependent sex determination
Authors: Carter Anna L. , Kearney Michael R. , Hartley Stephen , Porter Warren P. , Nelson Nicola J.
Published: December 2017

Aim

Recognition that statistical models do not always reliably predict habitat suitability under future climate scenarios is leading increasingly to explicit incorporation of the physiological constraints that underlie species’ distributions into spatially explicit predictions. However, computational intensity constrains the use of high‐resolution, process‐explicit models. We examined whether geostatistical analysis can effectively interpolate a biophysical model, reducing the computational investment typically required for using mechanistic methods to inform physiological predictions.

Location

New Zealand [40°40′00″ S 174°00′00″ E].

Methods

We used a spatially explicit, mechanistic microclimate model to predict hourly temperatures at five soil depths under two scenarios of climate warming. Using the predicted soil temperatures as input to a biophysical model of temperature‐dependent embryonic development, we estimated incubation temperatures and corresponding hatchling sex ratios for tuatara, a reptile with temperature‐dependent sex determination, at a submetre horizontal spatial resolution. We then applied ordinary kriging, a robust method of geostatistical interpolation, to estimate predictions throughout the full extent of our study location, an additional 480,000+ microsites, and validated the interpolation against an independent set of predictions.

Results

Ordinary kriging accurately predicted spatial variability in incubation temperatures. Mean predictions were similar between methods, and error in the geospatial model generally decreased with increasing soil depth. Error was higher for the geospatial model of the ‘maximum warming’, compared with the ‘minimum warming’, scenario of climate change.

Main conclusions

Our results show that ordinary kriging can be a reliable method for interpolating variability in high‐resolution predictions. However, the effects of error on the accuracy of interpolated predictions will become more severe as values approach a physiological threshold, such as the minimum and maximum incubation temperatures that result in extreme sex ratio bias. For distribution models, the widths of geographic areas predicted to be suitable for, in this case, maintaining balanced sex ratios, compared to those predicted to be unsuitable, may be narrower than in reality.
Gallic acid attenuates calcium calmodulin‐dependent kinase II‐induced apoptosis in spontaneously hypertensive rats
Authors: Jin Li , Piao Zhe Hao , Liu Chun Ping , Sun Simei , Liu Bin , Kim Gwi Ran , Choi Sin Young , Ryu Yuhee , Kee Hae Jin , Jeong Myung Ho
Published: December 2017

Hypertension causes cardiac hypertrophy and leads to heart failure. Apoptotic cells are common in hypertensive hearts. Ca2+/calmodulin‐dependent protein kinase II (CaMKII) is associated with apoptosis. We recently demonstrated that gallic acid reduces nitric oxide synthase inhibition‐induced hypertension. Gallic acid is a trihydroxybenzoic acid and has been shown to have beneficial effects, such as anti‐cancer, anti‐calcification and anti‐oxidant activity. The purpose of this study was to determine whether gallic acid regulates cardiac hypertrophy and apoptosis in essential hypertension. Gallic acid significantly lowered systolic and diastolic blood pressure in spontaneously hypertensive rats (SHRs). Wheat germ agglutinin (WGA) and H&E staining revealed that gallic acid reduced cardiac enlargement in SHRs. Gallic acid treatment decreased cardiac hypertrophy marker genes, including atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), in SHRs. The four isoforms, α, β, δ and γ, of CaMKII were increased in SHRs and were significantly reduced by gallic acid administration. Gallic acid reduced cleaved caspase‐3 protein as well as bax, p53 and p300 mRNA levels in SHRs. CaMKII δ overexpression induced bax and p53 expression, which was attenuated by gallic acid treatment in H9c2 cells. Gallic acid treatment reduced DNA fragmentation and the TUNEL positive cells induced by angiotensin II. Taken together, gallic acid could be a novel therapeutic for the treatment of hypertension through suppression of CaMKII δ‐induced apoptosis.
LncRNA‐DANCR contributes to lung adenocarcinoma progression by sponging miR‐496 to modulate mTOR expression
Authors: Lu Qing‐chun , Rui Zhuang‐hua , Guo Zhong‐liang , Xie Wang , Shan Shan , Ren Tao
Published: December 2017

Long non‐coding RNAs (lncRNAs) have emerged as new and important regulators of pathological processes including tumour development. In this study, we demonstrated that differentiation antagonizing non‐protein coding RNA (DANCR) was up‐regulated in lung adenocarcinoma (ADC) and that the knockdown of DANCR inhibited tumour cell proliferation, migration and invasion and restored cell apoptosis rescued; cotransfection with a miR‐496 inhibitor reversed these effects. Luciferase reporter assays showed that miR‐496 directly modulated DANCR; additionally, we used RNA‐binding protein immunoprecipitation (RIP) and RNA pull‐down assays to further confirm that the suppression of DANCR by miR‐496 was RISC‐dependent. Our study also indicated that mTOR was a target of miR‐496 and that DANCR could modulate the expression levels of mTOR by working as a competing endogenous RNA (ceRNA). Furthermore, the knockdown of DANCR reduced tumour volumes in vivo compared with those of the control group. In conclusion, this study showed that DANCR might be an oncogenic lncRNA that regulates mTOR expression through directly binding to miR‐496. DANCR may be regarded as a biomarker or therapeutic target for ADC.
Functional assessment of the BMPR2 gene in lymphoblastoid cell lines from Graves’ disease patients
Authors: Pousada Guillermo , Lago‐Docampo Mauro , Prado Sonia , Varela‐Calviño Rubén , Mantiñán Beatriz , Valverde Diana
Published: December 2017

In this study, we analysed the possible influence of the c.419‐43delT BMPR2 variant in patients with Graves’ disease (GD), in a molecular basis, focusing our efforts on possible alterations in the mRNA processing and synthesis. The molecular assessment of this variant in patients with GD would shed light on the association between the BMPR2 gene and the disease. The variant was detected in 18%, 55% and 10% of patients with pulmonary arterial hypertension, GD and in general population, respectively. Patients with GD fold change showed increased BMPR2 expression when matched against the controls, with a mean of 4.21 ± 1.73 (P = 0.001); BMPR2 was overexpressed in the analysed cell cycle stages. Fold change analysis of variant carriers and non‐carriers showed slight overexpression and differences between phases, but none of them were statistically significant. BMPR2 expression was confirmed in the lymphoblastoid cell lines (LCLs) with a molecular weight of 115 kD, and no differences between variant carriers and non‐carriers were detected. To conclude, the BMPR2 variant c.419‐19delT appears in high frequency in patients with GD, and independently of its presence, BMPR2 is overexpressed in the LCLs from the GD patients tested. This increase could be paired with the described decreased expression of transforming growth factor‐β1 in thyroid tissue from patients with GD.
Profile of common prostate cancer risk variants in an unscreened Romanian population
Authors: Iordache Paul D. , Mates Dana , Gunnarsson Bjarni , Eggertsson Hannes P. , Sulem Patrick , Guðmundsson Júlíus , Benónísdóttir Stefania , Csiki Irma Eva , Rascu Stefan , Radavoi Daniel , Ursu Radu , Staicu Catalin , Calota Violeta , Voinoiu Angelica , Jinga Mariana , Rosoga Gabriel , Danau Razvan , Sima Sorin Cristian , Badescu Daniel , Suciu Nicoleta , Radoi Viorica , Manolescu Andrei , Rafnar Thorunn , Halldórsson Bjarni V. , Jinga Viorel , Stefánsson Kári
Published: December 2017

To find sequence variants affecting prostate cancer (PCA) susceptibility in an unscreened Romanian population we use a genome‐wide association study (GWAS). The study population included 990 unrelated pathologically confirmed PCA cases and 1034 male controls. DNA was genotyped using Illumina SNP arrays, and 24.295.558 variants were imputed using the 1000 Genomes data set. An association test was performed between the imputed markers and PCA. A systematic literature review for variants associated with PCA risk identified 115 unique variants that were tested in the Romanian sample set. Thirty of the previously reported SNPs replicated (P‐value < 0.05), with the strongest associations observed at: 8q24.21, 11q13.3, 6q25.3, 5p15.33, 22q13.2, 17q12 and 3q13.2. The replicated variants showing the most significant association in Romania are rs1016343 at 8q24.21 (P = 2.2 × 10−4), rs7929962 at 11q13.3 (P = 2.7 × 10−4) and rs9364554 at 6q25.2 (P = 4.7 × 10−4). None of the variants tested in the Romanian GWAS reached genome‐wide significance (P‐value <5 × 10−8) but 807 markers had P‐values <1 × 10−4. Here, we report the results of the first GWAS of PCA performed in a Romanian population. Our study provides evidence that a substantial fraction of previously validated PCA variants associate with risk in this unscreened Romanian population.
Combination of arsenic trioxide and Dasatinib: a new strategy to treat Philadelphia chromosome‐positive acute lymphoblastic leukaemia
Authors: Wang Tao , Cheng Chunyan , Peng Lijun , Gao Mengqing , Xi Mengping , Rousseaux Sophie , Khochbin Saadi , Wang Jin , Mi Jianqing
Published: December 2017

Tyrosine kinase inhibitors (TKIs) have significantly improved the prognosis of Philadelphia chromosome‐positive acute lymphoblastic leukaemia (Ph+ ALL), one of the most common and aggressive forms of haematological malignancies. However, TKI resistance has remained an unsolved issue. In this study, we investigate the impact of adding arsenic trioxide (ATO) on the action of Dasatinib, a second‐generation TKI, in Ph+ ALL. We show that ATO cooperates with Dasatinib in both TKI‐sensitive and resistant Ph+ ALL cell lines to increase apoptosis and we unravel the underlying mechanisms. Indeed, combining ATO and Dasatinib leads to severe cell apoptosis by activating the UPR apoptotic IRE1/JNK/PUMA axis, while neutralizing the UPR ATF4‐dependent anti‐apoptotic axis, activated by ATO alone. Additionally, ATO and Dasatinib in combination repress the expression of several genes, which we previously showed to be associated with shorter survival probability in ALL patients. Overall these data support the use of ATO in combination with Dasatinib as a novel therapeutic regimen for Ph+ ALL patients.
A matching framework to improve causal inference in interrupted time‐series analysis
Authors: Linden Ariel
Published: December 2017

Rationale, aims, and objectives

Interrupted time‐series analysis (ITSA) is a popular evaluation methodology in which a single treatment unit's outcome is studied over time and the intervention is expected to “interrupt” the level and/or trend of the outcome, subsequent to its introduction. When ITSA is implemented without a comparison group, the internal validity may be quite poor. Therefore, adding a comparable control group to serve as the counterfactual is always preferred. This paper introduces a novel matching framework, ITSAMATCH, to create a comparable control group by matching directly on covariates and then use these matches in the outcomes model.

Method

We evaluate the effect of California's Proposition 99 (passed in 1988) for reducing cigarette sales, by comparing California to other states not exposed to smoking reduction initiatives. We compare ITSAMATCH results to 2 commonly used matching approaches, synthetic controls (SYNTH), and regression adjustment; SYNTH reweights nontreated units to make them comparable to the treated unit, and regression adjusts covariates directly. Methods are compared by assessing covariate balance and treatment effects.

Results

Both ITSAMATCH and SYNTH achieved covariate balance and estimated similar treatment effects. The regression model found no treatment effect and produced inconsistent covariate adjustment.

Conclusions

While the matching framework achieved results comparable to SYNTH, it has the advantage of being technically less complicated, while producing statistical estimates that are straightforward to interpret. Conversely, regression adjustment may “adjust away” a treatment effect. Given its advantages, ITSAMATCH should be considered as a primary approach for evaluating treatment effects in multiple‐group time‐series analysis.
Recent Advances in Halophilic Protozoa Research
Authors: Harding Tommy , Simpson Alastair G. B.
Published: December 2017

Most research on microorganisms adapted to hypersaline habitats has focused on Archaea and Bacteria, with microbial eukaryotes receiving much less attention. Over the past 15 yr, our knowledge of phagotrophic microbial eukaryotes, i.e. protozoa, from hypersaline habitats has greatly improved through combinations of microscopy, molecular phylogenetics, environmental sequencing, transcriptomics and growth experiments. High salinity waters from salterns, other landlocked water masses and deep hypersaline anoxic basins contain unique and diverse halophilic protozoan assemblages. These have the potential to exert substantial grazing pressure on prokaryotes and other eukaryotes. They represent many separate evolutionary lineages; species of Heterolobosea, Bicosoecida, and Ciliophora have been most intensively characterized, with several proven to be extreme (or borderline extreme) halophiles. Transcriptomic examinations of the bicosoecid Halocafeteria (and the heteroloboseid Pharyngomonas) indicate that high‐salt adaptation is associated with a subtle shift in protein amino acid composition, and involves the differential expression of genes participating in ion homeostasis, signal transduction, stress management, and lipid remodeling. Instances of gene duplication and lateral transfer possibly conferring adaptation have been documented. Indirect evidence suggests that these protozoa use “salt‐out” osmoadaptive strategies.
Influence of Poor Oral Health on Physical Frailty: A Population‐Based Cohort Study of Older British Men
Authors: Ramsay Sheena E. , Papachristou Efstathios , Watt Richard G. , Tsakos Georgios , Lennon Lucy T. , Papacosta A. Olia , Moynihan Paula , Sayer Avan A. , Whincup Peter H. , Wannamethee S. Goya
Published: December 2017

Objectives

To investigate the associations between objective and subjective measures of oral health and incident physical frailty.

Design

Cross‐sectional and longitudinal study with 3 years of follow‐up using data from the British Regional Heart Study.

Setting

General practices in 24 British towns.

Participants

Community‐dwelling men aged 71 to 92 (N = 1,622).

Measurements

Objective assessments of oral health included tooth count and periodontal disease. Self‐reported oral health measures included overall self‐rated oral health; dry mouth symptoms; sensitivity to hot, cold, and sweet; and perceived difficulty eating. Frailty was defined using the Fried phenotype as having 3 or more of weight loss, grip strength, exhaustion, slow walking speed, and low physical activity. Incident frailty was assessed after 3 years of follow‐up in 2014.

Results

Three hundred three (19%) men were frail at baseline (aged 71–92). Having fewer than 21 teeth, complete tooth loss, fair to poor self‐rated oral health, difficulty eating, dry mouth, and more oral health problems were associated with greater likelihood of being frail. Of 1,284 men followed for 3 years, 107 (10%) became frail. The risk of incident frailty was higher in participants who were edentulous (odds ratio (OR) = 1.90, 95% confidence interval (CI) = 1.03–3.52); had 3 or more dry mouth symptoms (OR = 2.03, 95% CI = 1.18–3.48); and had 1 (OR = 2.34, 95% CI = 1.18–4.64), 2 (OR = 2.30, 95% CI = 1.09–4.84), or 3 or more (OR = 2.72, 95% CI = 1.11–6.64) oral health problems after adjustment for age, smoking, social class, history of cardiovascular disease or diabetes mellitus, and medications related to dry mouth.

Conclusion

The presence of oral health problems was associated with greater risks of being frail and developing frailty in older age. The identification and management of poor oral health in older people could be important in preventing frailty.