bluuebunny/crossref_metadata_2025 huggingface dataset:
Dynamics and fate of beneficial mutations under lineage contamination by linked deleterious mutations
Authors: Pénisson Sophie , Singh Tanya , Sniegowski Paul , Gerrish Philip
Published: August 2016

Beneficial mutations drive adaptive evolution, yet their selective advantage does not ensure their fixation. Haldane’s application of single-type branching process theory showed that genetic drift alone could cause the extinction of newly-arising beneficial mutations with high probability. With linkage, deleterious mutations will affect the dynamics of beneficial mutations and might further increase their extinction probability. Here, we model the lineage dynamics of a newly-arising beneficial mutation as a multitype branching process; this approach allows us to account for the combined effects of drift and the stochastic accumulation of linked deleterious mutations, which we calllineage contamination. We first study the lineage contamination phenomenon in isolation, deriving extinction times and probabilities of beneficial lineages. We then put the lineage contamination phenomenon into the context of an evolving population by incorporating the effects of background selection. We find that the survival probability of beneficial mutations is simply Haldane’s classical formula multiplied by the correction factor, whereUis deleterious mutation rate,is mean selective advantage of beneficial mutations,κ∈ (1,ε], andε= 2 –e−1. We also find there exists a genomic deleterious mutation rate,, that maximizes the rate of production of surviving beneficial mutations, and that. Both of these results, and others, are curiously independent of the fitness effects of deleterious mutations. We derive critical mutation rates above which: 1) lineage contamination alleviates competition among beneficial mutations, and 2) the adaptive substitution process all but shuts down.
Population structure reduces the benefits from partner choice in mutualism
Authors: Akçay Erol
Published: August 2016

Mutualisms are key drivers of evolutionary and ecological processes. Understanding how different species can evolve to interact in mutually beneficial ways is an important goal of evolutionary theory, especially when the benefits require costly investments by the partners. For such costly investments to evolve, some sort of fitness feedback mechanism must exist that more than recoups the direct costs. Several such feedback mechanisms have been explored both theoretically and empirically, yet we know relatively little how they might act together, as they probably do in nature. In this paper, I model the joint action of three of the main mechanisms that can maintain symbiotic cooperation: partner choice by hosts, population structure amongst symbionts, and undirected rewards from hosts to symbionts. My results show that population structure reduces the benefit from partner choice to hosts. It may help or hinder beneficial symbionts and create positive or negative frequency dependence depending on the nature of host rewards to the symbiont. Strong population structure also makes it less likely that host choosiness and symbiont cooperation will be jointly maintained in a population. The intuition behind my results is that all else being equal, population structure reduces local variation available to the host to choose from. Thus, population structure is not always beneficial for the evolution of cooperation between species. My results also underscore the need to do full analyses of multiple mechanisms of social evolution to uncover their interactions to uncover the interactions between them.
Into the Evening: Complex Interactions in theArabidopsiscircadian clock
Authors: Huang He , Nusinow Dmitri A.
Published: August 2016

InArabidopsis thaliana, an assembly of proteins named the evening complex (EC) has been established as an essential component of the circadian clock with conserved functions in regulating plant growth and development. Recent studies identifying EC-regulated genes and EC-interacting proteins have expanded our understanding of EC function. In this review, we focus on new progress uncovering how the EC contributes to the circadian network through the integration of environmental inputs and the direct regulation of key clock genes. We also summarize new findings of how the EC directly regulates clock outputs, such as day-length dependent and thermoresponsive growth, and provide new perspectives on future experiments to address unsolved questions related to the EC.
Crystal structure ofPlasmodium falciparumproplasmepsin IV: the plasticity of proplasmepsins
Authors: Recacha Rosario , Jaudzems Kristaps , Akopjana Inara , Jirgensons Aigars , Tars Kaspars
Published: August 2016

Plasmepsin IV fromPlasmodium falciparum(PM IV) is a promising target for the development of novel antimalarial drugs. Here, the crystal structure of the truncated zymogen of PM IV (pPM IV), consisting of the mature enzyme plus a prosegment of 47 residues, has been determined at 1.5 Å resolution. pPM IV presents the fold previously described for studied proplasmepsins, displaying closer similarities to proplasmepin IV fromP. vivax(pPvPM) than to the other two proplasmepsins fromP. falciparum. The study and comparison of the pPM IV structure with the proplasmepsin structures described previously provide information about the similarities and differences in the inactivation–activation mechanisms among the plasmepsin zymogens.
Structural analysis of point mutations at theVaccinia virusA20/D4 interface
Authors: Contesto-Richefeu Céline , Tarbouriech Nicolas , Brazzolotto Xavier , Burmeister Wim P. , Peyrefitte Christophe N. , Iseni Frédéric
Published: August 2016

TheVaccinia viruspolymerase holoenzyme is composed of three subunits: E9, the catalytic DNA polymerase subunit; D4, a uracil-DNA glycosylase; and A20, a protein with no known enzymatic activity. The D4/A20 heterodimer is the DNA polymerase cofactor, the function of which is essential for processive DNA synthesis. The recent crystal structure of D4 bound to the first 50 amino acids of A20 (D4/A201–50) revealed the importance of three residues, forming a cation–π interaction at the dimerization interface, for complex formation. These are Arg167 and Pro173 of D4 and Trp43 of A20. Here, the crystal structures of the three mutants D4-R167A/A201–50, D4-P173G/A201–50and D4/A201–50-W43A are presented. The D4/A20 interface of the three structures has been analysed for atomic solvation parameters and cation–π interactions. This study confirms previous biochemical data and also points out the importance for stability of the restrained conformational space of Pro173. Moreover, these new structures will be useful for the design and rational improvement of known molecules targeting the D4/A20 interface.
The quorum-quenching lactonase fromGeobacillus caldoxylosilyticus: purification, characterization, crystallization and crystallographic analysis
Authors: Bergonzi Celine , Schwab Michael , Elias Mikael
Published: August 2016

Lactonases are enzymes that are capable of hydrolyzing various lactones such as aliphatic lactones or acyl-homoserine lactones (AHLs), with the latter being used as chemical signaling molecules by numerous Gram-negative bacteria. Lactonases therefore have the ability to quench the chemical communication, also known as quorum sensing, of numerous bacteria, and in particular to inhibit behaviors that are regulated by this system, such as the expression of virulence factors or the production of biofilms. A novel representative from the metallo-β-lactamase superfamily, dubbed GcL, was isolated from the thermophilic bacteriumGeobacillus caldoxylosilyticus. Because of its thermophilic origin, GcL may constitute an interesting candidate for the development of biocontrol agents. Here, we show that GcL is a thermostable enzyme with a half-life at 75°C of 152.5 ± 10 min. Remarkably, it is also shown that GcL is among the most active lactonases characterized to date, with catalytic efficiencies (kcat/Km) against AHLs of greater than 106 M−1 s−1. The structure of GcL is expected to shed light on the catalytic mechanism of the enzyme and the molecular determinants for the substrate specificity in this class of lactonases. Here, the expression, purification, characterization, crystallization and X-ray diffraction data collection to 1.6 Å resolution of GcL are reported.
An integer-coded differential evolution algorithm for simple assembly line balancing problem of type 2
Authors: Zhang Haijun , Yan Qiong , Liu Yuanpeng , Jiang Zhiqiang
Published: August 2016

Purpose

This paper aims to develop a new differential evolution algorithm (DEA) for solving the simple assembly line balancing problem of type 2 (SALBP-2).

Design/methodology/approach

Novel approaches of mutation operator and crossover operator are presented. A self-adaptive double mutation scheme is implemented and an elitist strategy is used in the selection operator.

Findings

Test and comparison results show that the proposed IDEA obtains better results for SALBP-2.

Originality/value

The presented DEA is called the integer-coded differential evolution algorithm (IDEA), which can directly deal with integer variables of SALBP-2 on a discrete space without any posterior conversion. The proposed IDEA will be an alternative in evolutionary algorithms, especially for various integer/discrete-valued optimization problems.
The impact of middle management commitment on improvement initiatives in public organisations
Authors: Alhaqbani Abdullah , Reed Deborah M , Savage Barbara M , Ries Jana
Published: August 2016

Purpose

– Top management commitment is considered a significant factor in improvement programmes, and many papers have been written about the role of top management commitment in implementing a quality management system. However, not considering other management levels’ commitment, such as middle management, may lead to issues in achieving organisational development. Public organisations that work through vertical structures may face a lack of middle management commitment, which might have a negative impact on lower and non-management staff commitment to improvement programmes. In this regard, the purpose of this paper is to examine the impact of middle management’s commitment towards improvement initiatives in public organisations.

Design/methodology/approach

– Empirical research with a mixed-method design used semi-structured interviews and a questionnaire to explore the current practices of continuous improvement (CI) and examine employees’ views from different management levels of the implications of current improvements in a Saudi public service organisation.

Findings

– The analysis indicated that the lower managers and non-management staff agree that, after the implementation of the quality management system, the organisation’s middle management showed a lack of commitment to that system. Moreover, this lack of commitment is recognised in the analysis of participants’ views of CI practices recorded in the questionnaire and interviews. This lack of commitment has caused poor employee commitment and thus a lack of problem solving in organisational departments. It is also responsible for a lack of employee involvement, the centralisation of decisions, deficiencies in terms of determining and applying training, inequality between employees and a lack of trust between employees and their managers. These issues could be managed and resolved through middle management and their commitment.

Practical implications

– Increasing middle managers’ awareness of the importance of their commitment to improvement initiatives can have an impact on employees’ commitment towards improvement initiatives, especially in those public organisations that have vertical/hierarchical structures. The level of commitment towards the implementation of improvement programmes needs further in-depth analyses to identify which factors influence public organisation leaders’ commitment to improvement programmes.

Originality/value

– The results of this study could motivate middle managers in public organisations to review their policies and to facilitate CI initiatives.
Effectiveness of QFD in a municipal administration process
Authors: Ocampo Jimenez Narda B. , Baeza Serrato Roberto
Published: August 2016

Purpose

– The purpose of this paper is to document the results of an implementation of the quality function deployment (QFD) tool in a process of a municipal administration involving: request for component support: family farming, urban and backyard agriculture that are part of the Rural Development Directorate of the Moroleón City Hall in the state of Guanajuato, México.

Design/methodology/approach

– The work is an exploratory study where the application of different quantitative techniques, database analysis, sample collection, field notes, participant observation, workshops and direct interviews were held and conducted to collect data.

Findings

– From the analysis of the requirements of quality characteristics are identified, simplified, response time reduced, assertiveness maintained and transparency in the resource allocations were assured. According to the calculations, customer expectations were clearly identified.

Originality/value

– The implementation of quality management methods such as QFD, in a municipal administration was used aimed at improving the services offered to citizens according to their expectations. It is expressed that mayors should be primarily concerned about giving the officials under their direction the necessary training to make their employment joyful with the help and use of the best tools available to provide quality results.
Empirical study on quality management for product-service systems in industrial environment
Authors: Pasch Florian , Rybski Christoffer , Jochem Roland
Published: August 2016

Purpose

– To achieve long-term customer retention a comprehensive and individual performance is increasingly important for companies from the manufacturing industry. A possibility to meet this challenge is given by Industrial Product-Service Systems (IPS2). The purpose of this paper is to discuss the results of a current study on quality management for IPS².

Design/methodology/approach

– After a short introduction to the topic of IPS² the paper takes the study design as its structure. It gives an overview of the demography and results of the study and ends with a conclusion.

Findings

– Concerning the choice of products and services the results show that customer individual performances prevail. Closely related to that is the tender of services, which are meanwhile a part of the performance offer in all industries. All in all there are already first types of IPS². The quality perception exceeds the conformance of specific requirements. Reliability and perceived quality are becoming increasingly important. An integration of customers into the quality management is the exception. Regarding the quality management in value creation chains it can be outlined that quality goals are mostly company-wide but not for the entire value creation chain. Cross-company standardized processes exist in least cases. This also applies to cross-linked CAQ-systems. Communication of quality problems is handled mainly via e-mail. Quality management in value creation chains needs a common buildup of competencies by joint trainings. In practice it is barely there. Even if the potential is seen, partners and suppliers mostly will not be considered.

Originality/value

– The paper considers the study results from different angles and shows the potentials of the IPS² approach. Thereby it investigates different approaches to offer a combined product-service system.
A new approach to construction of extended kit for M-Sequence UWB sensor system based on LTCC
Authors: Ruman Kornel , Pietrikova Alena , Galajda Pavol , Vehec Igor , Rovensky Tibor , Kmec Martin
Published: August 2016

Purpose

The purpose of this paper is to introduce modified in–phase and quadrature components (I–Q) demodulator based on low temperature co-fired ceramics (LTCC) dielectric substrate GreenTape 951PX for M-Sequence ultra-wide band (UWB) sensor system.

Design/methodology/approach

Microstrip low pass (LP) and band pass (BP) filters for UWB sensor systems with required properties (for both filters, minimum attenuation is −40dB in stopband, bandwidth of pass band is 6 to 8.5 GHz for BP filter and cutoff frequency is 2.5 GHz for LP filter) were designed, simulated, fabricated and measured using dielectric substrates Du Pont GreenTape 951 PX. The developed microstrip filters were integrated with all parts of I–Q demodulator on one multilayer structure based on LTCC substrate Du Pont GreenTape 951 PX.

Findings

Both type of microstrip filters integrated in the I– Q demodulator achieved better transmission characteristics in comparison with commercial available filters. It was shown that LTCC technology based on GreenTape 951PX proves good stability in gigahertz frequency and suitability for fabrication of I–Q demodulator with a multilayer approach.

Originality/value

The novelty of this work lies in substituting commercially available LP and BP filters used in I– Q demodulator by microstrip LP and BP filters with better performance and furthermore the I– Q demodulator is fabricated based on LTCC instead of previously used PCB.
Influence of ITO layer application on electrical parameters of silicon solar cells with screen printed front electrode
Authors: Drabczyk Kazimierz , Domaradzki Jaroslaw , Kulesza-Matlak Grazyna , Lipinski Marek , Kaczmarek Danuta
Published: August 2016

Purpose

The purpose of this paper was investigation and comparison of electrical and optical properties of crystalline silicon solar cells with ITO or TiO2 coating. The ITO, similar to TiO2, is very well transparent in the visible part of optical radiation; however, its low resistivity (lower that 10-3 Ohm/cm) makes it possible to use simultaneously as a transparent electrode for collection of photo-generated electrical charge carriers. This might also invoke increasing the distance between screen-printed metal fingers at the front of the solar cell that would increase of the cell’s active area. Performed optical investigation showed that applied ITO thin film fulfill standard requirements according to antireflection properties when it was deposited on the surface of silicon solar cell.

Design/methodology/approach

Two sets of samples were prepared for comparison. In the first one, the ITO thin film was deposited directly on the crystalline silicon substrate with highly doped emitter region. In the second case, the TCO film was deposited on the same type of silicon substrate but with additional ultrathin SiO2 passivation. The fingers lines of 80 μm width were then screen-printed on the ITO layer with two different spaces between fingers for each set. The influence of application of the ITO electrode and the type of metal electrodes patterns on the electrical performance of the prepared solar cells was investigated through optical and electrical measurements.

Findings

The electrical parameters such as short-circuit current (Jsc), open circuit voltage (Voc), fill factor (FF) and conversion efficiency were determined on a basis of I-V characteristics. Short-circuit current density (Jsc) was equal to 32 mA/cm2 for a solar cell with a typical antireflection layer and 31.5 mA/cm2 for the cell with ITO layer, respectively. Additionally, electroluminescence of prepared cells was measured and analysed.

Originality/value

The influence of the properties of ITO electrode on the electrical performance of crystalline silicon solar cells was investigated through complex optical, electrical and electroluminescence measurements.
Bank social responsibility and the use of money
Authors: Ferreira Gilciney , Mattoso Cecilia Queirós
Published: August 2016

Purpose

The purpose of the present research is first to assess the financial education’s effectiveness, examining how a specific communication regarding the use of money could help new consumers from low-income families avoid insolvency. The second is to analyse the impact of this corporate social responsibility (CSR) activity on a Brazilian bank’s image.

Design/methodology/approach

The research used a qualitative methodology based on in-depth interviews using three advertising films, which served as an enhanced element to prompt students to evaluate the discourse of sensible use of money and credit and the bank’s image.

Findings

The results showed that the students are very receptive to the ideas shown by the bank advertising films. Nevertheless, the interviewees showed a certain degree of suspicion toward the initiative and intentions of the bank. The perceived corporate image was clearly ambiguous, with the financial institution showing its advertising film about the careful use of money in complete contrast to actual bank branch practices in which employees offer and encourage young students from low-income families to get loans and credit cards. The bank became more socially responsible merely to cut costs and as a consequence did not improve its image.

Practical implications

For CSR in banks to be real and have a positive impact on society, the authors suggest that the bank enter into a cooperation or sponsorship agreement with the federal government or any public sector institution or non-governmental organizations. The form, the arguments and the language of the bank’s financial education campaign examined in this article seemed to be capable of serving social purposes or benefiting society.

Social implications

Educating consumers in the conscious use of money reduces delinquency rates and increases banks’ profits while, at the same time, benefiting society economically. The bank’s positive experience in terms of financial education could help the Brazilian government and other institutions with the same purpose. The advertising campaign provides some insights for the Brazilian government financial education program to which it has given high priority (BCB, 2015).

Originality/value

The article expands studies on CSR in developing countries and of attitudes toward it in the emerging middle class, two issues that have received scant attention. The study reinforces Carroll and Shabana’s view (2010) that companies are becoming more socially responsible merely to cut costs and Porter and Kramer’s call that to be really strategic the action must not appear to be mitigating the very harm it has caused.
Thinking inside the basin: scale in transboundary water management
Authors: Holmatov Bunyod , Lautze Jonathan
Published: August 2016

While transboundary waters are widely advocated to be best managed at the basin level, practical experience in transboundary waters at the basin vis‐à‐vis other scales has not been systematically examined. To understand past experiences in transboundary water management at alternate scales, this paper: (i) determines the relative abundance of water treaties at different scales and (ii) elucidates how transboundary water law varies according to the scale to which it applies. The paper developed a scale typology with six groups, and systematically applied it to stratify transboundary water treaties. Treaty contents were then compared across scales according to the following set of parameters: primary issue area, temporal development, and important water management attributes. Results of this work reveal: (i) treaties tend to focus on hydropower and flood control at smaller scales, and organizations and policies at larger scales; (ii) a temporal trend toward treaties concluded at larger scales; and (iii) a higher proportion of treaties is at larger scales in Africa and Asia than in Europe and the Americas. These findings suggest that smaller scale cooperation may constitute a more constructive scale in which to achieve development‐oriented cooperation. Further, scope may exist to complement basin scale cooperation with cooperation at smaller scales, in order to optimize transboundary water management. In the context of basin‐wide management frameworks, Africa and Asia may benefit from greater emphasis on small‐scale transboundary water cooperation.
The Genus Heracleum: A Comprehensive Review on Its Phytochemistry, Pharmacology, and Ethnobotanical Values as a Useful Herb
Authors: Bahadori Mir Babak , Dinparast Leila , Zengin Gokhan
Published: August 2016

Heracleum species, also known as hogweed, are traditionally used as food additives, spices, and flavoring agents. Moreover, these plants are widely used in folklore medicine for the treatment of many disorders such as inflammation, flatulence, stomachache, epilepsy, psoriasis, and as carminative, wound healing, antiseptic, antidiarrheal, tonic, digestive, pain killer, analgesic, and anticonvulsant agents. The genus Heracleum has broad pharmacological activities: anti‐inflammatory, antimicrobial, anticholinesterase, anti‐oxidant, antiviral, cytotoxic, and anticarcinogenic. A total of 94 compounds have been isolated from plants of the Heracleum genus, all indicating vital biological activities. Also, about 50 compounds have been identified as major components in their essential oils. The genus is rich in several types of bioactive coumarin compounds, with huge potential for the discovery of new coumarins. Various parts of these plants produce essential oils (mainly aliphatic esters and monoterpenes) with a wide spectrum of biological activities. Heracleum species have great potential for applications in the food, cosmetics, perfumery, and pharmaceutical industries due to their broad ethnobotanical uses and pharmacological properties. Accordingly, this review aims to categorize updated and comprehensive information on ethnobotanical uses, phytochemistry, and pharmacology of Heracleum species in order to open new perspectives for future studies, including possible uses as functional ingredients in food products.
CYNICAL STREETS: NEIGHBORHOOD SOCIAL PROCESSES AND PERCEPTIONS OF CRIMINAL INJUSTICE*
Authors: BERG MARK T. , STEWART ERIC A. , INTRAVIA JONATHAN , WARREN PATRICIA Y. , SIMONS RONALD L.
Published: August 2016

Studies have found that African Americans are more likely to perceive racial biases in the criminal justice system than are those from other racial groups. There is a limited understanding of how neighborhood social processes affect variation in these perceptions. This study formulates a series of hypotheses focused on whether perceived racial biases in the criminal justice system or perceptions of injustice vary as a function of levels of moral and legal cynicism as well as of adverse police–citizen encounters. These hypotheses are tested with multilevel regression models applied to data from a sample of 689 African Americans located in 39 neighborhoods. Findings from the regression models indicate that the positive association between structural disadvantage and perceptions of injustice is accounted for by moral and legal cynicism. Furthermore, adverse police encounters significantly increase perceptions of injustice; controlling for these encounters reduces the strength of the association between cynicism and injustice perceptions. Finally, the findings reveal that cynicism intensifies the association between adverse police encounters and perceptions of criminal injustice. The results are discussed in terms of their implications for research regarding perceived biases in the criminal justice system and neighborhood social processes.
Prognostic factors for long‐term infliximab treatment in Crohn's disease patients: a 20‐year single centre experience
Authors: Billiet T. , Cleynen I. , Ballet V. , Ferrante M. , Van Assche G. , Gils A. , Vermeire S.
Published: August 2016

Background

The long‐term efficacy of infliximab in patients with Crohn's disease is suboptimal.

Aim

To study prognostic factors for real‐life long‐term effcacy of infliximab in Crohn's disease.

Methods

All consecutive Crohn's disease patients treated with infliximab at a tertiary centre were retrospectively analysed. Only patients who received scheduled infliximab maintenance treatment were considered. Patient‐ and disease‐related factors were used to identify independent predictors of infliximab failure‐free survival using Cox proportional hazards regression.

Results

Of 1031 patients with Crohn's disease, 261 were eligible for inclusion. Median time on infliximab was 2.4 [IQR 1.4–4.7] years, and 65 (24.9%) patients experienced infliximab failure. Estimated 5‐year infliximab failure‐free survival was 65.9% (95% CI 58.3–73.5). Multivariate Cox regression identified disease duration ≥1 year (HR 2.5 (95% CI 1.2–5.2), P = 0.02), L1 disease location [HR 2.0 (1.1–3.5), P = 0.02], prior anti‐TNF use [HR 2.3 (1.1–4.8), P = 0.03], haemoglobin <13.5 g/dL [HR 2.3 (1.2–4.4), P = 0.02], not using therapeutic drug monitoring [HR 8.0 (4.1–15.6), P = 1 × 10−9], and first dose optimisation within first year [HR 3.7 (2.1–6.6), P = 5 × 10−6] as independent predictors of infliximab failure‐free survival. Stratifying patients into risk groups resulted in estimated 3‐year infliximab failure‐free survival rates ranging from 95.3% (94.2–96.4) to 26.3% (8.6–44.0) depending on the number of risk factors (P = 8 × 10−13).

Conclusions

This study identified several easy to obtain predictors of infliximab failure in patients with Crohn's disease, and these are in line with previous reports. Those with a high‐risk profile for infliximab failure in whom infliximab initiation is considered, should be treated as early as possible making use of therapeutic drug monitoring.
Ecoregionalization classification of wetlands based on a cluster analysis of environmental data
Authors: Lechner Alex M. , McCaffrey Nic , McKenna Phill , Venables William N. , Hunter John T.
Published: August 2016

Aim

Effective vegetation conservation requires reasonable certainty regarding the distribution, extent and classification of plant communities and ecoregions for assessing rarity. In this paper we describe a multivariate clustering approach based on environmental data for objectively defining temperate treeless palustrine wetland communities.

Location

New South Wales (NSW), Australia.

Methods

In NSW no comprehensive state‐wide map of wetland vegetation exists, with more than 200 vegetation maps produced by local and state governments at a range of spatial resolutions and extents. Using the available vegetation spatial data, we produced a composite map which identified 6323 wetlands >1 ha. We then used the partitioning around medoids cluster analysis method for grouping wetlands based on 12 climate, topography, geology and soils spatial data layers and the wetland locations. We tested a range of cluster numbers from three to 20, and assessed the stability of the clustering by calculating mean silhouette widths. The derived classes were then characterized in terms of number of individual wetlands and their area, and also the number and area of individual wetlands found within protected areas such as national parks.

Results

We found a peak in the mean silhouette width at 11 clusters, indicating that this was the optimal number of clusters for classifying the wetland data. We produced maps of wetland density for each of the 11 clusters and described the mean and mode environmental characteristics of each cluster. Each cluster represented a unique combination of environmental variables. For example, wetlands in cluster 2 are typically in the south, in areas of low evaporation and low average temperatures. An assessment of rarity found that wetlands in the largest cluster class had an areal extent of 14 644 ha, compared to 1414 ha for the smallest cluster. All but one of the clusters had part of their range within protected areas.

Conclusions

Clustering environmental variables is an important but underutilized method for characterizing vegetation communities/ecoregions such as wetlands spatially. This approach can be used to produce objective, repeatable and defensible wetland community maps for assessing rarity.
Quantitative model for the blood pressure‐lowering interaction of valsartan and amlodipine
Authors: Heo Young‐A , Holford Nick , Kim Yukyung , Son Mijeong , Park Kyungsoo
Published: August 2016

Aims

The objective of this study was to develop a population pharmacokinetic (PK) and pharmacodynamic (PD) model to quantitatively describe the antihypertensive effect of combined therapy with amlodipine and valsartan.

Methods

PK modelling was used with data collected from 48 healthy volunteers receiving a single dose of combined formulation of 10 mg amlodipine and 160 mg valsartan. Systolic (SBP) and diastolic blood pressure (DBP) were recorded during combined administration. SBP and DBP data for each drug alone were gathered from the literature. PKPD models of each drug and for combined administration were built with NONMEM 7.3.

Results

A two‐compartment model with zero order absorption best described the PK data of both drugs. Amlodipine and valsartan monotherapy effects on SBP and DBP were best described by an Imax model with an effect compartment delay. Combined therapy was described using a proportional interaction term as follows: (D1 + D2) +ALPHA×(D1 × D2). D1 and D2 are the predicted drug effects of amlodipine and valsartan monotherapy respectively. ALPHA is the interaction term for combined therapy. Quantitative estimates of ALPHA were −0.171 (95% CI: −0.218, −0.143) for SBP and −0.0312 (95% CI: −0.07739, −0.00283) for DBP. These infra‐additive interaction terms for both SBP and DBP were consistent with literature results for combined administration of drugs in these classes.

Conclusion

PKPD models for SBP and DBP successfully described the time course of the antihypertensive effects of amlodipine and valsartan. An infra‐additive interaction between amlodipine and valsartan when used in combined administration was confirmed and quantified.
Children's supernatural thinking as a signalling behaviour in early childhood
Authors: Hernández Blasi Carlos , Bjorklund David F. , Ruiz Soler Marcos
Published: August 2016

In this study, we analysed the reaction times of 137 college students when making decisions on pairs of hypothetical children verbalizing different types of vignettes and/or exhibiting different physical appearance (photographs of faces). Vignettes depicted immature and mature versions of both supernatural (e.g., ‘The sun's not out today because it's mad’ vs. ‘The sun's not out today because the clouds are blocking it’) and natural (‘I can remember all 20 cards!’ vs. ‘I can remember 6 or 7 cards’) explanations to ordinary phenomena. Photographs of children's faces were morphed with a physical appearance of approximately 4–7 years old or approximately 8–10 years old. In earlier research, immature supernatural thinking produced positive‐affect reactions from adults and older adolescents (14–18 years old) towards young children, with cognitive cues being more important than physical‐appearance cues in influencing adults’ judgements. Reaction times to make decisions varied for the Supernatural and Natural vignettes and for the immature and mature vignettes/faces, reflecting the differential cognitive effort adults used for making decisions about aspects of children's physical appearance and verbal expressions. The findings were interpreted in terms of the critical role that young children's immature supernatural thinking has on adults’ perception, analogous to the evolved role of immature physical features on adults’ perception of infants.
Positional plagiocephaly reduces parental adherence to SIDS Guidelines and inundates the health system
Authors: Martiniuk A. , Jacob J. , Faruqui N. , Yu W.
Published: August 2016

Background

This study sought to better understand parent, grandparent and clinician views of prevention, treatment and costs of plagiocephaly.

Methods

A qualitative study was conducted using focus groups and semi‐structured interviews. A grounded theory approach was taken to build theories from the qualitative data collected. A subjectivist epistemological orientation was taken under the paradigm of positivism.

Results

Ninety‐one parents, 6 grandparents and 24 clinicians were recruited from the community as well as primary and tertiary care clinics. Plagiocephaly worried most parents because it could permanently affect their child's ‘looks’ and some thought it would affect a child's development. Parents were ‘willing to do anything’ to prevent plagiocephaly including using products or sleeping positions that are contraindicated under sudden infant death syndrome guidelines. Parents found the care pathway convoluted and inconsistent messages were given from different health providers. For clinicians, the high prevalence of flat head is ‘clogging up their patient pool’, taking up time they used to spend with children with more severe conditions.

Conclusion

There is a need to re‐emphasize sudden infant death syndrome guidelines for families when they present with an infant with plagiocephaly. Stronger messaging regarding the lack of safety of current pillows marketed to prevent flat head may be useful to decrease their use. Increasing education for all health professionals including general practitioners, allied health and complementary health providers and standardizing assessment and referral criteria may allow the majority of diagnosis and treatment of positional plagiocephaly to occur at points of first contact (e.g. general practitioners, community nurse) and may prevent further burden on the health care system.
‘Remind‐to‐move’ treatment versus constraint‐induced movement therapy for children with hemiplegic cerebral palsy: a randomized controlled trial
Authors: Dong Vicky Anqin , Fong Kenneth N K , Chen Yun‐Feng , Tseng Stella S W , Wong Louisa M S
Published: August 2016

Aim

To evaluate ‘remind‐to‐move’ (RTM) treatment by comparing it with constraint‐induced movement therapy (CIMT) and conventional rehabilitation of the upper extremity in children with hemiplegic cerebral palsy (CP).

Method

Seventy‐three children (44 males, 29 females; mean age 11y 8mo, standard deviation [SD] 3y 1mo) – with 20, 38, and 15 in Manual Ability Classification System levels I,II, andIIIrespectively – were recruited from three special schools and randomly selected for anRTM(n=25) orCIMT(n=24) programme (for 75h over 3wks) or for conventional rehabilitation (n=24). The Jebsen–Taylor Hand Function Test, the Bruininks–Oseretsky Test of Motor Proficiency (Subtest 3), the Caregiver Functional Use Survey, and arm movement duration captured by accelerometers were used at the baseline, post‐test, and 1‐month and 3‐month follow‐ups.

Results

Both theRTMandCIMTtreatments achieved significant gains in manual capacities and spontaneous hand use immediately after the intervention compared with conventional rehabilitation, but there were no significant differences between the two interventions.

Interpretation

TheRTMtreatment demonstrated similar therapeutic effects withCIMTin manual dexterity and functional hand use, but both interventions were superior to conventional rehabilitation.RTMis recommended as an alternative treatment for the hemiplegic upper extremity in children withCP.
Trends in diabetes and obesity in Samoa over 35 years, 1978–2013
Authors: Lin S. , Naseri T. , Linhart C. , Morrell S. , Taylor R. , McGarvey S. T. , Magliano D. J. , Zimmet P.
Published: August 2016

Aims

Population surveys of Type 2 diabetes mellitus and obesity conducted in Samoa over three decades have used varying methodologies and definitions. This study standardizes measures, and trends of Type 2 diabetes mellitus and obesity for 1978–2013 are projected to 2020 for adults aged 25–64 years.

Methods

Unit records from eight surveys (n = 12 516) were adjusted to the previous census for Division of residence, sex and age to improve national representativeness. Type 2 diabetes mellitus is defined as a fasting plasma glucose ≥ 7.0 mmol/l and/or on medication. Obesity is defined as BMI ≥ 30 kg/m2. Random effects meta‐regression was employed to assess time trends following logit transformation. Poisson regression from strata was used to assess the effects of mean BMI changes on Type 2 diabetes mellitus period trends.

Results

Over 1978–2013, Type 2 diabetes mellitus prevalence increased from 1.2% to 19.6% in men (2.3% per 5 years), and from 2.2% to 19.5% in women (2.2% per 5 years). Obesity prevalence increased from 27.7% to 53.1% in men (3.6% per 5 years) and from 44.4% to 76.7% (4.5% per 5 years) in women. Type 2 diabetes mellitus and obesity prevalences increased in all age groups. From period trends, Type 2 diabetes mellitus prevalence in 2020 is projected to be 26% in men and women. Projected obesity prevalence is projected to be 59% in men and 81% in women. Type 2 diabetes mellitus period trends attributable to BMI increase are estimated as 31% (men) and 16% (women), after adjusting for age.

Conclusion

This is the first study to produce trends of Type 2 diabetes mellitus and obesity in Samoa based on standardized data from population surveys. Type 2 diabetes mellitus is equally prevalent in both sexes, and obesity is widespread. Type 2 diabetes mellitus prevalence in Samoa is likely to continue to increase in the near future.
Differences in the pre‐diapause and pre‐oviposition accumulation of critical nutrients in adult females of the beetle Colaphellus bowringi
Authors: Tan Qian‐Qian , Feng Lian , Liu Wen , Zhu Li , Lei Chao‐Liang , Wang Xiao‐Ping
Published: August 2016

In many insect species, the differentiation of development between diapause and reproduction first becomes obvious during the diapause preparation (pre‐diapause) and pre‐oviposition phases. However, the differentiation of nutrient accumulation between these two phases remains unclear. We compared the weights of pre‐diapause and reproductive adult female Colaphellus bowringi Baly (Coleoptera: Chrysomelidae), and measured their triacylglycerol (TAG), protein, and carbohydrate content from emergence until they had fed for 4 days post‐eclosion. We also compared the ovarian development and accumulation of lipid droplets between pre‐diapause and reproductive adult females in order to determine whether we could visually detect differences in nutrient allocation. The weights of both pre‐diapause and reproductive females increased with duration of feeding. The fresh weight and water content of pre‐diapause females was significantly lower than that of reproductive females after feeding for 3 days post‐eclosion. Pre‐diapause females channeled their reserves into TAG in the fat body, whereas reproductive females converted nutrients into proteins and carbohydrates for egg development. These results quantify differences in nutrient accumulation between pre‐diapause and reproductive adult female C. bowringi, and provide clues for understanding the molecular mechanisms underlying differences in the allocation of nutrients between diapause and reproduction in insects.
Dispersal of diapausing Tetranychus urticae and T. kanzawai
Authors: Ghazy Noureldin Abuelfadl , Otsuki Hatsune , Sekido Tomoe , Yano Shuichi , Amano Hiroshi
Published: August 2016

The spider mites Tetranychus urticae Koch and Tetranychus kanzawai Kishida (Acari: Tetranychidae) overwinter mostly as mated adult diapausing females. Their overwintering survival depends in part on their dispersal towards suitable habitats. We investigated the dispersal behaviour of diapausing females of T. urticae and T. kanzawai with respect to factors known to affect the dispersal of non‐diapausing mites: light, population density, gravity, and humidity. In general, diapausing females of T. urticae showed a stronger tendency to disperse than did those of T. kanzawai under all test conditions. High population density promoted the dispersal of diapausing T. urticae, but not of T. kanzawai. Dispersal of diapausing females of both species was not significantly affected by gravity, humidity, or whether feeding damage was caused by conspecifics or heterospecifics. On plants, more T. urticae than T. kanzawai moved downward. We propose that dispersal after the onset of diapause may be an important life‐history strategy in T. urticae, but not in T. kanzawai.
Lipoprotein lipase in chronic lymphocytic leukemia: function and prognostic implications
Authors: Rombout Ans , Verhasselt Bruno , Philippé Jan
Published: August 2016

Chronic lymphocytic leukemia (CLL) is a clinically heterogeneous disease characterized by the accumulation of a clonal population of B cells in peripheral blood, bone marrow, and lymphoid organs. More than 10 years ago, lipoprotein lipase (LPL) mRNA was identified as being strongly expressed in patients experiencing a more aggressive phenotype, while CLL patients with an indolent disease course lack expression of this marker. Since then, several reports confirmed the capability of LPL to predict CLL disease evolution at the moment of diagnosis. In contrast, data on the functional implications of LPL in CLL are scarce. LPL exerts a central role in overall lipid metabolism and transport, but plays additional, non‐catalytic roles as well. Which of those is more important in the pathogenesis of CLL remains largely unclear. Here, we review the current knowledge on the prognostic and biological relevance of LPL in CLL.
Crystal structures of spleen tyrosine kinase in complex with novel inhibitors: structural insights for design of anticancer drugs
Authors: Lee Sang Jae , Choi Jang‐Sik , Han Byeong‐Gu , Kim Hyoun Sook , Song Ho‐Juhn , Lee Jaekyoo , Nam Seungyoon , Goh Sung‐Ho , Kim Jung‐Ho , Koh Jong Sung , Lee Byung Il
Published: August 2016

Spleen tyrosine kinase (SYK) is a cytosolic nonreceptor protein tyrosine kinase that mediates key signal transduction pathways following the activation of immune cell receptors. SYK regulates cellular events induced by the B‐cell receptor and Fc receptors with high intrinsic activity. Furthermore, SYK has been regarded as an attractive target for the treatment of autoimmune diseases and cancers. Here, we report the crystal structures of SYK in complex with seven newly developed inhibitors (G206, G207, O178, O194, O259, O272, and O282) to provide structural insights into which substituents of the inhibitors and binding regions of SYK are essential for lead compound optimization. Our kinase inhibitors exhibited high inhibitory activities against SYK, with half‐maximal inhibitory concentrations (IC50) of approximately 0.7–33 nm, but they showed dissimilar inhibitory activities against KDR, RET, JAK2, JAK3, and FLT3. Among the seven SYK inhibitors, O272 and O282 exhibited highly specific inhibitions against SYK, whereas O194 exhibited strong inhibition of both SYK and FLT3. Three inhibitors (G206, G207, and O178) more efficiently inhibited FLT3 while still substantially inhibiting SYK activity. The binding mode analysis suggested that a highly selective SYK inhibitor can be developed by optimizing the functional groups that facilitate direct interactions with Asn499.

Database

The atomic coordinates and structure factors for human SYK are in the Protein Data Bank under accession codes 4XG2 (inhibitor‐free form), 4XG3 (G206), 4XG4 (G207), 5GHV (O178), 4XG6 (O194), 4XG7 (O259), 4XG8 (O272), and 4XG9 (O282).