bluuebunny/crossref_metadata_2025 huggingface dataset:
Diffusion Tensor Imaging of Lumbar Nerve Roots
Authors: Manoliu Andrei , Ho Michael , Nanz Daniel , Piccirelli Marco , Dappa Evelyn , Klarhöfer Markus , Del Grande Filippo , Kuhn Felix Pierre
Published: February 2016

Objectives

The aim of this study was to compare the quality of recently emerged advanced diffusion tensor imaging (DTI) techniques with conventional single-shot echo-planar imaging (EPI) in a functional assessment of lumbar nerve roots.

Materials and Methods

The institutional review board approved the study including 12 healthy volunteers. Diffusion tensor imaging was performed at 3 T (MAGNETOM Skyra; Siemens Healthcare) with b-values of 0 and 700 s/mm2 and an isotropic spatial resolution for subsequent multiplanar reformatting. The nerve roots L2 to S1 were imaged in coronal orientation with readout-segmented EPI (rs-DTI) and selective-excitation EPI (sTX-DTI) with an acquisition time of 5 minutes each, and in axial orientation with single-shot EPI (ss-DTI) with an acquisition time of 12 minutes (scan parameters as in recent literature). Two independent readers qualitatively and quantitatively assessed image quality.

Results

The interobserver reliability ranged from “substantial” to “almost perfect” for all examined parameter and all 3 sequences (κ = 0.70–0.94). Overall image quality was rated higher, and artifact levels were scored lower for rs-DTI and sTX-DTI than for ss-DTI (P = 0.007–0.027), while fractional anisotropy and signal-to-noise ratio values were similar for all sequences (P ≥ 0.306 and P ≥ 0.100, respectively). Contrast-to-noise ratios were significantly higher for rs-DTI and ss-DTI than for sTX-DTI (P = 0.004–0.013).

Conclusions

Despite shorter acquisition times, rs-DTI and sTX-DTI produced images of higher quality with smaller geometrical distortions than the current standard of reference, ss-DTI. Thus, DTI acquisitions in the coronal plane, requiring fewer slices for full coverage of exiting nerve roots, may allow for functional neurography in scan times suitable for routine clinical practice.
Single Breath-Hold T1ρ-Mapping of the Heart for Endogenous Assessment of Myocardial Fibrosis
Authors: van Oorschot Joep W.M. , Visser Fredy , Eikendal Anouk L.M. , Vonken Evert-jan P.A. , Luijten Peter R. , Chamuleau Steven A.J. , Leiner Tim , Zwanenburg Jaco J.M.
Published: February 2016

Objectives

In this study, we propose a method to acquire high spatial-resolution T1ρ-maps, which allows bright and black-blood imaging, in a single breath-hold. To validate this innovative method, the reproducibility was tested in phantoms and volunteers. Lastly, the sensitivity and specificity for infarct detection was compared with the criterion standard late gadolinium enhancement (LGE).

Methods

T1ρ-mapping was performed using a T1ρ-prepared balanced steady-state free precession sequence at 1.5 T and 3 T. Five images with increasing spin-lock preparation times (spin-lock = 0, 10, 20, 30, 40 milliseconds, amplitude = 500 Hz) were acquired with an interval of 3 beats. Black-blood imaging was performed using a double inversion pulse sequence. The method was tested in 2 times 10 healthy volunteers at 1.5 and 3 T and in 9 myocardial infarction patients at 1.5 T. T1ρ-maps, and LGE images were scored for presence and extent of myocardial scarring.

Results

Phantom results show that the proposed T1ρ-mapping method gives accurate T1ρ-values. The mean T1ρ-relaxation time of the myocardium in healthy controls was 52.8 ± 1.8 milliseconds at 1.5 T and 46.4 ± 1.8 milliseconds at 3 T. In patients, the T1ρof infarcted myocardium was (82.4 ± 5.2 milliseconds), and the T1ρof remote myocardium was (54.2 ± 2.8 milliseconds;P< 0.0001). Sensitivity of infarct detection on a T1ρ-map was 70%, with a specificity of 94%, compared with LGE.

Conclusions

In this study, we have investigated a method to acquire high spatial-resolution T1ρ-maps of the heart in a single breath-hold. This method proved to be reproducible and had high specificity compared with LGE and can thus be used for the endogenous detection of myocardial fibrosis in patients with ischemic cardiomyopathy.
Requirements for multi-level systems pharmacology models to reach end-usage: the case of type 2 diabetes
Authors: Nyman Elin , Rozendaal Yvonne J. W. , Helmlinger Gabriel , Hamrén Bengt , Kjellsson Maria C. , Strålfors Peter , van Riel Natal A. W. , Gennemark Peter , Cedersund Gunnar
Published: February 2016

We are currently in the middle of a major shift in biomedical research: unprecedented and rapidly growing amounts of data may be obtained today, from
in vitro
,
in vivo
and clinical studies, at molecular, physiological and clinical levels. To make use of these large-scale, multi-level datasets, corresponding multi-level mathematical models are needed, i.e. models that simultaneously capture multiple layers of the biological, physiological and disease-level organization (also referred to as quantitative systems pharmacology—QSP—models). However, today's multi-level models are not yet embedded in end-usage applications, neither in drug research and development nor in the clinic. Given the expectations and claims made historically, this seemingly slow adoption may seem surprising. Therefore, we herein consider a specific example—type 2 diabetes—and critically review the current status and identify key remaining steps for these models to become mainstream in the future. This overview reveals how, today, we may use models to ask scientific questions concerning, e.g., the cellular origin of insulin resistance, and how this translates to the whole-body level and short-term meal responses. However, before these multi-level models can become truly useful, they need to be linked with the capabilities of other important existing models, in order to make them ‘personalized’ (e.g. specific to certain patient phenotypes) and capable of describing long-term disease progression. To be useful in drug development, it is also critical that the developed models and their underlying data and assumptions are easily accessible. For clinical end-usage, in addition, model links to decision-support systems combined with the engagement of other disciplines are needed to create user-friendly and cost-efficient software packages.
Improving the physiological realism of experimental models
Authors: Vinnakota Kalyan C. , Cha Chae Y. , Rorsman Patrik , Balaban Robert S. , La Gerche Andre , Wade-Martins Richard , Beard Daniel A. , Jeneson Jeroen A. L.
Published: February 2016

The Virtual Physiological Human (VPH) project aims to develop integrative, explanatory and predictive computational models (C-Models) as numerical investigational tools to study disease, identify and design effective therapies and provide anin silicoplatform for drug screening. Ultimately, these models rely on the analysis and integration of experimental data. As such, the success of VPH depends on the availability of physiologically realistic experimental models (E-Models) of human organ function that can be parametrized to test the numerical models. Here, the current state of suitable E-models, ranging fromin vitronon-human cell organelles toin vivohuman organ systems, is discussed. Specifically, challenges and recent progress in improving the physiological realism of E-models that may benefit the VPH project are highlighted and discussed using examples from the field of research on cardiovascular disease, musculoskeletal disorders, diabetes and Parkinson's disease.
Understanding the physiology of the ageing individual: computational modelling of changes in metabolism and endurance
Authors: van Beek Johannes H. G. M. , Kirkwood Thomas B. L. , Bassingthwaighte James B.
Published: February 2016

Ageing and lifespan are strongly affected by metabolism. The maximal possible uptake of oxygen is not only a good predictor of performance in endurance sports, but also of life expectancy. Figuratively speaking, healthy ageing is a competitive sport. Although the root cause of ageing is damage to macromolecules, it is the balance with repair processes that is decisive. Reduced or intermittent nutrition, hormones and intracellular signalling pathways that regulate metabolism have strong effects on ageing. Homeostatic regulatory processes tend to keep the environment of the cells within relatively narrow bounds. On the other hand, the body is constantly adapting to physical activity and food consumption. Spontaneous fluctuations in heart rate and other processes indicate youth and health. A (homeo)dynamic aspect of homeostasis deteriorates with age. We are now in a position to develop computational models of human metabolism and the dynamics of heart rhythm and oxygen transport that will advance our understanding of ageing. Computational modelling of the connections between dietary restriction, metabolism and protein turnover may increase insight into homeostasis of the proteins in our body. In this way, the computational reconstruction of human physiological processes, the Physiome, can help prevent frailty and age-related disease.
Succinct Colored de Bruijn Graphs
Authors: Belk Keith , Boucher Christina , Bowe Alexander , Gagie Travis , Morley Paul , Muggli Martin D. , Noyes Noelle R. , Puglisi Simon J. , Raymond Rober
Published: February 2016

Iqbal et al. (Nature Genetics, 2012) introduced thecolored de Bruijn graph, a variant of the classic de Bruijn graph, which is aimed at “detecting and genotyping simple and complex genetic variants in an individual or population”. Because they are intended to be applied to massive population level data, it is essential that the graphs be represented efficiently. Unfortunately, current succinct de Bruijn graph representations are not directly applicable to the colored de Bruijn graph, which require additional information to be succinctly encoded as well as support for non-standard traversal operations. Our data structure dramatically reduces the amount of memory required to store and use the colored de Bruijn graph, with some penalty to runtime, allowing it to be applied in much larger and more ambitious sequence projects than was previously possible.
Local joint testing improves power and identifies missing heritability in association studies
Authors: Brown Brielin C. , Price Alkes L. , Patsopoulos Nikolaos A. , Zaitlen Noah
Published: February 2016

There is mounting evidence that complex human phenotypes are highly polygenic, with many loci harboring multiple causal variants, yet most genetic association studies examine each SNP in isolation. While this has lead to the discovery of thousands of disease associations, discovered variants account for only a small fraction of disease heritability. Alternative multi-SNP methods have been proposed, but issues such as multiple testing correction, sensitivity to genotyping error, and optimization for the underlying genetic architectures remain. Here we describe a local joint testing procedure, complete with multiple testing correction, that leverages a genetic phenomenon we call linkage masking wherein linkage disequilibrium between SNPs hides their signal under standard association methods. We show that local joint testing on the original Wellcome Trust Case Control Consortium dataset leads to the discovery of 29% more associated loci that were later found in followup studies containing thousands of additional individuals. These loci double the heritability explained by genome-wide significant associations in the WTCCC dataset, implicating linkage masking as a novel source of missing heritability. Furthermore, we show that local joint testing in acis-eQTL study of the gEUVADIS dataset increases the number of genes discovered by 10.7% over marginal analyses. Our multiple hypothesis correction and joint testing framework are available in a python software package calledjester, available atgithub.com/brielin/Jester.
A Family of Interaction-Adjusted Indices of Community Similarity
Authors: Benedikt Schmidt Thomas Sebastian , Matias Rodrigues João Frederico , von Mering Christian
Published: February 2016

Interactions between taxa are essential drivers of ecological community structure and dynamics, but they are not taken into account by traditional indices of diversity. In this study, we propose a novel family of indices that quantify community similarity in the context of taxa interaction networks. Using publicly available datasets, we assess the performance of two specific indices which areTaxa INteraction-Adjusted(TINA, based on taxa co-occurrence networks), andPhylogenetic INteraction-Adjusted(PINA, based on phylogenetic similarities). TINA and PINA outperformed traditional indices when partitioning human-associated microbial communities according to habitat, even for extremely downsampled datasets, and when organising ocean micro-eukaryotic plankton diversity according to geographical and physicochemical gradients. We argue that interaction-adjusted indices capture novel aspects of diversity outside the scope of traditional approaches, highlighting the biological significance of ecological association networks in the interpretation of community similarity.
Exploiting single-cell quantitative data to map genetic variants having probabilistic effects
Authors: Chuffart Florent , Richard Magali , Jost Daniel , Duplus-Bottin Hélène , Ohya Yoshikazu , Yvert Gaël
Published: February 2016

Despite the recent progress in sequencing technologies, genome-wide association studies (GWAS) remain limited by a statistical-power issue: many polymorphisms contribute little to common trait variation and therefore escape detection. The small contribution sometimes corresponds to incomplete penetrance, which may result from probabilistic effects on molecular regulations. In such cases, genetic mapping may benefit from the wealth of data produced by single-cell technologies. We present here the development of a novel genetic mapping method that allows to scan genomes for single-cell Probabilistic Trait Loci that modify the statistical properties of cellular-level quantitative traits. Phenotypic values are acquired on thousands of individual cells, and genetic association is obtained from a multivariate analysis of a matrix of Kantorovich distances. No prior assumption is required on the mode of action of the genetic loci involved and, by exploiting all single-cell values, the method can reveal non-deterministic effects. Using both simulations and yeast experimental datasets, we show that it can detect linkages that are missed by classical genetic mapping. A probabilistic effect of a single SNP on cell shape was detected and validated. The method also detected a novel locus associated with elevated gene expression noise of the yeast galactose regulon. Our results illustrate how single-cell technologies can be exploited to improve the genetic dissection of certain common traits.

AUTHOR SUMMARY

Genetic association studies are usually conducted on phenotypes measured at the scale of whole tissues or individuals, and not at the scale of individual cells. However, some common traits, such as cancer, can result from a minority of cells that adopted a special behavior. From one individual to another, DNA variants can modify the frequency of such cellular behaviors. The body of one of the individuals then harbours more misbehaving cells and is therefore predisposed to a macroscopic phenotypic change, such as disease. Such genetic effects are probabilistic, they contribute little to trait variation at the macroscopic level and therefore largely escape detection in classical studies. We have developed a novel statistical method that uses single-cell measurements to detect variants of the genome that have non-deterministic effects on cellular traits. The approach is based on a comparison of distributions of single-cell traits. We applied it to colonies of yeast cells and showed that it can detect mutations that change cellular morphology or molecular regulations in a probabilistic manner. This opens the way to study multicellular organisms from a novel angle, by exploiting single-cell technologies to detect genetic variants that predispose to certain diseases or common traits.
Conserved gene clusters in the scrambled plastomes of IRLC legumes (Fabaceae: Trifolieae and Fabeae)
Authors: Sveinsson Saemundur , Cronk Quentin
Published: February 2016

The plastid genome retains several features from its cyanobacterial-like ancestor, one being the co-transcriptional organization of genes into operon-like structures. Some plastid operons have been identified but undoubtedly many more remain undiscovered. Here we utilize the highly variable plastome structure that exists within certain legumes of the inverted repeat lost clade (IRLC) to find conserved gene clusters. These plastomes exhibit an unusually high frequency of translocations and inversions. We analysed the plastomes of 23 legume species and identified 32 locally collinear blocks (LCBs), which are regions within the plastid genomes that occur in different orientation and/or order among the plastid genomes but are themselves free from internal rearrangements. Several represent gene clusters that have previously been recognized as plastid operons. It appears that the number of LCBs has reached saturation in our data set, suggesting that these LCBs are not random, but likely represent legume plastid operons protected from internal rearrangement by functional constraint. Some of the LCBs we identify, such aspsbD/C/Z, are previously known plastid operons. Others, such asrpl32-ndhF-psbA-matK-rbcL-atpB-atpE, may represent novel polycistronic operons in legumes.
Introgression maintains the genetic integrity of the mating-type determining chromosome of the fungus Neurospora tetrasperma
Authors: Corcoran Pádraic , Anderson Jennifer L. , Jacobson David J. , Sun Yu , Ni Peixiang , Lascoux Martin , Johannesson Hanna
Published: February 2016

Genome evolution is driven by a complex interplay of factors, including selection, recombination, and introgression. The regions determining sexual identity are particularly dynamic parts of eukaryotic genomes that are prone to molecular degeneration associated with suppressed recombination. In the fungus Neurospora tetrasperma, it has been proposed that this molecular degeneration is counteracted by the introgression of nondegenerated DNA from closely related species. In this study, we used comparative and population genomic analyses of 92 genomes from eight phylogenetically and reproductively isolated lineages of N. tetrasperma, and its three closest relatives, to investigate the factors shaping the evolutionary history of the genomes. We found that suppressed recombination extends across at least 6 Mbp (∼63%) of the mating-type (mat) chromosome in N. tetrasperma and is associated with decreased genetic diversity, which is likely the result primarily of selection at linked sites. Furthermore, analyses of molecular evolution revealed an increased mutational load in this region, relative to recombining regions. However, comparative genomic and phylogenetic analyses indicate that the mat chromosomes are temporarily regenerated via introgression from sister species; six of eight lineages show introgression into one of their mat chromosomes, with multiple Neurospora species acting as donors. The introgressed tracts have been fixed within lineages, suggesting that they confer an adaptive advantage in natural populations, and our analyses support the presence of selective sweeps in at least one lineage. Thus, these data strongly support the previously hypothesized role of introgression as a mechanism for the maintenance of mating-type determining chromosomal regions.
Optimization of the design for beamline with fast polarization switching elliptically polarized undulators
Authors: Cao Jiefeng , Wang Yong , Zou Ying , Zhang Xiangzhi , Wu Yanqing , Tai Renzhong
Published: February 2016

Fast switching of X-ray polarization with a lock-in amplifier is a good method for acquiring weak signals from background noise for X-ray magnetic circular dichroism (XMCD) experiments. The usual way to obtain a beam with fast polarization switching is to use two series of elliptically polarized undulators (tandem twin EPUs). The two EPUs generate two individual beams. Each beam has a different polarization and is fast switched into the beamline. It is very important to ensure that the energy resolution, the flux and the spot size at the sample of the two beams are equal in XMCD experiments. However, it is difficult in beamline design because the distances from the two EPUs to the beamline optics are different and the beamline is not switchable. In this work, a beamline design without an entrance slit for fast polarization switching EPUs is discussed. The energy resolution of the two beams can be tuned to be equal by minor rotation of the optics in the monochromator. The flux of the two beams can be balanced through separation bladesX, Yin the exit slit, and by adjusting the position of theXblades along the beam. The spot size of the two beams can be adjusted to be equal by shifting the sample as well.
Purification, crystallization and X-ray crystallographic analysis of a putative exopolyphosphatase fromZymomonas mobilis
Authors: Zhang Aili , Guo Erhong , Qian Lanfang , Tang Nga-Yeung , Watt Rory M. , Bartlam Mark
Published: February 2016

Exopolyphosphatase (PPX) enzymes degrade inorganic polyphosphate (poly-P), which is essential for the survival of microbial cells in response to external stresses. In this study, a putative exopolyphosphatase fromZymomonas mobilis(ZmPPX) was crystallized. Crystals of the wild-type enzyme diffracted to 3.3 Å resolution and could not be optimized further. The truncation of 29 amino acids from the N-terminus resulted in crystals that diffracted to 1.8 Å resolution. The crystals belonged to space groupC2, with unit-cell parametersa= 122.0,b= 47.1,c= 89.5 Å, α = γ = 90, β = 124.5°. An active-site mutant that crystallized in the same space group and with similar unit-cell parameters diffracted to 1.56 Å resolution. One molecule was identified per asymmetric unit. Analytical ultracentrifugation confirmed that ZmPPX forms a dimer in solution. It was confirmed that ZmPPX possesses exopolyphosphatase activity against a synthetic poly-P substrate.
An unlikely hero? Challenging stigma through community engagement
Authors: Best David
Published: February 2016

Purpose

– The purpose of this paper is to describe a high-profile social enterprise in Blackpool, England, called Jobs, Friends and Houses (JFH) that has created a visible social identity of recovery and meaningful activity, to assess how stigma is challenged through active and visible community engagement.

Design/methodology/approach

– Case study based on in-depth individual interview and focus group, supplemented by participant in-depth interviews.

Findings

– The paper describes one particular incident in which a worker at JFH intervened in a violent attack, possibly saving a woman’s life. The paper describes the experiences of internalised stigma and external exclusion being challenged by the development of a positive social identity and a pro-social community role that has high visibility. Data are presented showing the strong social identity experienced by participants and recognised by external stakeholders.

Research limitations/implications

– This is a pilot study which uses an opportunistic design and much stronger longitudinal designs will be needed to address the issues raised in the paper.

Social implications

– The paper argues that the visibility of the pro-social identity has been central to challenging stereotypes and discriminating attitudes and suggests that a social identity approach may be central to generating and sustaining a recovery community and to confronting and reversing long-held stigmatised attitudes.

Originality/value

– The paper is important as it discusses the impact of recovery through engagement in meaningful activities that challenge stigma and exclusion through work. The paper is framed in terms of a social identity model of recovery.
Experimental public administration from 1992 to 2014
Authors: Bouwman Robin , Grimmelikhuijsen Stephan
Published: February 2016

Purpose

– Based on previous inventories, the purpose of this paper is to extend the knowledge on public administration experiments by focusing on their experimental type, design, sample type and realism levels and external validity. The aim is to provide an overview of experimental public administration and formulate potential ways forward.

Design/methodology/approach

– The authors examine the current state of experimental public administration, by looking at a systematic selection of ISI ranked experimental publications in major public administration journals (1992-2014) and recommend ways forward based on this review.

Findings

– The review indicates a rise in experimentation in public administration in recent years, this can be attributed mostly to some subfields of public administration. Furthermore, most experiments in public administration tend to have relatively simple designs, high experimental realism and a focus on external validity. Experimental public administration can be strengthened by increasing diversification in terms of samples, experimental designs, experimental types and substantive scope. Finally, the authors recommend to better utilize experiments to generate usable knowledge for practitioners and to replicate experiments to improve scientific rigour.

Originality/value

– This paper contributes to experimental public administration by drawing on a systematic selection of papers and assessing them in depth. By means of a transparent and systematic selection of publications, various venues or ways forward are presented.
Crowdsourcing for a better world
Authors: Choy Katherine , Schlagwein Daniel
Published: February 2016

Purpose

– The purpose of the paper is to better understand the relation between information technology (IT) affordances and donor motivations in charitable crowdfunding.

Design/methodology/approach

– This paper reports the findings from a comparative case study of two charitable crowdfunding campaigns.

Findings

– The affordances of crowdfunding platforms support types of donor motivation that are not supported effectively, or at all, in offline charity.

Research limitations/implications

– For future researchers, the paper provides a theoretical model of the relation between IT affordances and motivations in the context of charitable crowdfunding.

Practical/implications

– For practitioners in the charity space, the paper suggests why they may wish to consider the use of charitable crowdfunding and how they may go about its implementation.

Originality/value

– Based on field research at two charitable crowdfunding campaigns, the paper provides a new theoretical model.
The dual impact of online communication on older adults’ social connectivity
Authors: Hage Eveline , Wortmann Hans , van Offenbeek Marjolein , Boonstra Albert
Published: February 2016

Purpose

– In today’s aging world online communication is often viewed as a means to enhance social connectivity, and therefore well-being, of older adults. However, previous research on the influence of online communication on social connectivity largely disregards older adults, yields conflicting results and fails to assess the – debatable − causal direction of relationship. The purpose of this paper is to overcome these issues by developing four hypotheses related to who uses what, how, with whom.

Design/methodology/approach

– The authors use a panel data study to test the hypotheses, including 302 older adults. Response rates are between 62 and 75 percent.

Findings

– The authors find, first, that older adults differentiate between social connectivity with other village members, i.e., village connectivity, and connectivity with friends. Second, the impact of online communication varies among these two types of social connectivity. Where e-mail use has a negative impact on village connectivity, it does not affect connectivity with friends. Facebook use on the other hand has a negative impact on connectivity with friends, but not on village connectivity. The negative effects were not found among those older adults that were already well-connected on forehand, indicating a buffer effect.

Practical/implications

– Policy makers’ implementing online communication tools to strengthen social connectivity of older adults, may want to carefully select tools based on the type of connectivity they aim to enhance. Impact needs to be monitored.

Originality/value

– The authors contribute by analyzing how characteristics of online communication tools, i.e., information richness and privacy protection, as well as social connectivity, i.e., geographical proximity and emotional closeness jointly shape older adults’ social connectivity.
The Internet of Things and its impact on the library
Authors: Massis Bruce
Published: February 2016

Purpose

– The purpose of this paper is to consider the Internet of Things (IOT) and its potential impact on libraries.

Design/methodology/approach

– This paper presents a literature review and a commentary on this topic that have been addressed by professionals, researchers and practitioners.

Findings

– In communicating the issues when comprehending the scope of the IOT, libraries need not succumb to the sometimes near-hysteria that surrounds the rhetoric regarding security and privacy. But, librarians must actively engage in the conversation and its subsequent actions to respond to patrons who use library networks and devices with calm, logical and transparent answers to those questions concerning what they are doing to ensure that security and privacy vulnerabilities are regularly addressed.

Originality/value

– The value in concentrating on this topic is to provide background and suggest several approaches to security and privacy concerns regarding the IOT.
Symptoms and their recognition in adult haemodialysis patients: Interactions with quality of life
Authors: Raj Rajesh , Ahuja Kiran DK , Frandsen Mai , Jose Matthew
Published: February 2016

Aim

We investigated the symptom burden in adults on haemodialysis, the recognition of symptoms by nurses and nephrologists, and the relationship between symptoms and quality of life.

Methods

In this cross‐sectional observational study, symptoms and quality of life in haemodialysis patients were determined using validated surveys. Nurses and nephrologists independently estimated their patients' symptoms, and these estimates were compared with patient responses (sensitivity; kappa values for interrater agreement). Associations between symptoms and quality of life were assessed using multi‐level regression.

Results

Forty‐three patients, 18 nurses and 3 nephrologists participated. The commonest symptoms (95%CI) reported by patients were weakness, 69% (53 to 82); poor mobility, 44% (29 to 60); and drowsiness, 44% (29 to 60). Sensitivity less than 50% was seen towards 11 of 17 symptoms in nurse ratings compared with 15 of 17 in nephrologist ratings. Agreement with patient symptom ratings was mostly ‘fair’ (0.21–0.4), with nurses' scores showing greater agreement than nephrologists'. Physical, mental and kidney disease component summary scores of quality of life were negatively associated with total symptom score and the number of ‘major’ symptoms (r2 values 0.3–0.36); while with multivariate regression, 50% to 60% of the variance in these scores was accounted for by parsimonious models containing symptoms such as pain and poor mobility.

Conclusion

Symptom burden worsened quality of life scores in haemodialysis patients. Clinician recognition of symptom burden was inaccurate, although nurses were more accurate than nephrologists. Using patient‐completed surveys or including dialysis nurse feedback in routine outpatient settings may help improve symptom recognition by nephrologists.
Does plant apparency matter? Thirty years of data provide limited support but reveal clear patterns of the effects of plant chemistry on herbivores
Authors: Smilanich Angela M. , Fincher R. Malia , Dyer Lee A.
Published: February 2016

According to the plant‐apparency hypothesis, apparent plants allocate resources to quantitative defenses that negatively affect generalist and specialist herbivores, while unapparent plants invest more in qualitative defenses that negatively affect nonadapted generalists. Although this hypothesis has provided a useful framework for understanding the evolution of plant chemical defense, there are many inconsistencies surrounding associated predictions, and it has been heavily criticized and deemed obsolete.

We used a hierarchical Bayesian meta‐analysis model to test whether defenses from apparent and unapparent plants differ in their effects on herbivores. We collected a total of 225 effect sizes from 158 published papers in which the effects of plant chemistry on herbivore performance were reported.

As predicted by the plant‐apparency hypothesis, we found a prevalence of quantitative defenses in woody plants and qualitative defenses in herbaceous plants. However, the detrimental impacts of qualitative defenses were more effective against specialists than generalists, and the effects of chemical defenses did not significantly differ between specialists and generalists for woody or herbaceous plants.

A striking pattern that emerged from our data was a pervasiveness of beneficial effects of secondary metabolites on herbivore performance, especially generalists. This pattern provides evidence that herbivores are evolving effective counteradaptations to putative plant defenses.
Time-of-flight secondary ion mass spectrometry as a tool for evaluating the plasma-induced hydrogenation of graphene
Authors: Wallace Joshua S. , Quinn Austin , Gardella Joseph A. , Hu Jing , Kong Eric Siu-Wai , Joh Han-Ik
Published: February 2016

Bandgap modification in graphene has received immense attention in the quest to develop postsilicon electronic materials. Hydrogenation of graphene has largely been the focus of bandgap modification; however, current research has relied solely upon the appearance of structural defects in Raman spectroscopy to evaluate the extent of hydrogenation. Here, the authors present time-of-flight secondary ion mass spectrometry (ToF-SIMS) as a complementary tool to Raman in determining the chemical changes occurring concurrently with structural defects. Multivariate analysis, through the use of principal component analysis (PCA) is coupled to ToF-SIMS analysis for the rapid determination of differences in surface chemistry between samples. Untreated graphene was found to exhibit a minimal defect intensity in the Raman with the most prominent ion intensities in the ToF-SIMS originating from unsaturated, graphene-like carbon fragments. However, exposure to H2 plasma results in the evolution of a structural defect in the Raman which coincides with a mass shift toward ions representing hydrogen-rich, saturated hydrocarbons in addition to aliphatic oxides. The use of PCA on the resultant ion images and spectra allowed for rapid differentiation between samples based upon chemical species, rather than the intensity of a lattice defect alone, with high intra- and intersample reproducibility.
Dynamic fractal signature dissimilarity analysis for therapeutic response assessment using dynamic contrast‐enhanced MRI
Authors: Wang Chunhao , Subashi Ergys , Yin Fang‐Fang , Chang Zheng
Published: February 2016

Purpose:

To develop a dynamic fractal signature dissimilarity (FSD) method as a novel image texture analysis technique for the quantification of tumor heterogeneity information for better therapeutic response assessment with dynamic contrast‐enhanced (DCE)‐MRI.

Methods:

A small animal antiangiogenesis drug treatment experiment was used to demonstrate the proposed method. Sixteen LS‐174T implanted mice were randomly assigned into treatment and control groups (n = 8/group). All mice received bevacizumab (treatment) or saline (control) three times in two weeks, and one pretreatment and two post‐treatment DCE‐MRI scans were performed. In the proposed dynamic FSD method, a dynamic FSD curve was generated to characterize the heterogeneity evolution during the contrast agent uptake, and the area under FSD curve (AUCFSD) and the maximum enhancement (MEFSD) were selected as representative parameters. As for comparison, the pharmacokinetic parameter Ktrans map and area under MR intensity enhancement curve AUCMR map were calculated. Besides the tumor's mean value and coefficient of variation, the kurtosis, skewness, and classic Rényi dimensions d1 and d2 of Ktrans and AUCMR maps were evaluated for heterogeneity assessment for comparison. For post‐treatment scans, the Mann–Whitney U‐test was used to assess the differences of the investigated parameters between treatment/control groups. The support vector machine (SVM) was applied to classify treatment/control groups using the investigated parameters at each post‐treatment scan day.

Results:

The tumor mean Ktrans and its heterogeneity measurements d1 and d2 values showed significant differences between treatment/control groups in the second post‐treatment scan. In contrast, the relative values (in reference to the pretreatment value) of AUCFSD and MEFSD in both post‐treatment scans showed significant differences between treatment/control groups. When using AUCFSD and MEFSD as SVM input for treatment/control classification, the achieved accuracies were 93.8% and 93.8% at first and second post‐treatment scan days, respectively. In comparison, the classification accuracies using d1 and d2 of Ktrans map were 87.5% and 100% at first and second post‐treatment scan days, respectively.

Conclusions:

As quantitative metrics of tumor contrast agent uptake heterogeneity, the selected parameters from the dynamic FSD method accurately captured the therapeutic response in the experiment. The potential application of the proposed method is promising, and its addition to the existing DCE‐MRI techniques could improve DCE‐MRI performance in early assessment of treatment response.
Resource Letter SW1: Space Weather
Authors: Baker Daniel N. , Lanzerotti Louis J.
Published: February 2016

This Resource Letter describes the phenomena and effects on technological systems that are known collectively as space weather. A brief history of the topic is provided, and the scientific understandings of drivers for such phenomena are discussed. The impacts of space disturbances are summarized, and the strategies for dealing with space weather threats are examined. The Resource Letter concludes with description of approaches that have been proposed to deal with threats to our increasingly technological society.
Differential dynamic microscopy to characterize Brownian motion and bacteria motility
Authors: Germain David , Leocmach Mathieu , Gibaud Thomas
Published: February 2016

We have developed a lab module for undergraduate students, which involves the process of quantifying the dynamics of a suspension of microscopic particles using Differential Dynamic Microscopy (DDM). DDM is a relatively new technique that constitutes an alternative method to more classical techniques such as dynamic light scattering (DLS) or video particle tracking (VPT). The technique consists of imaging a particle dispersion with a standard light microscope and a camera and analyzing the images using a digital Fourier transform to obtain the intermediate scattering function, an autocorrelation function that characterizes the dynamics of the dispersion. We first illustrate DDM in the textbook case of colloids under Brownian motion, where we measure the diffusion coefficient. Then we show that DDM is a pertinent tool to characterize biological systems such as motile bacteria.
Physical Activity Coparticipation and Independent Mobility as Correlates of Objectively Measured Nonschool Physical Activity in Different School Grades: The UP&DOWN Study
Authors: Garcia-Cervantes Laura , D’Haese Sara , Izquierdo-Gomez Rocio , Padilla-Moledo Carmen , Fernandez-Santos Jorge R. , Cardon Greet , Veiga Oscar Luis
Published: February 2016

Background:

The aim was to investigate the association of (i) parental, sibling, and friend coparticipation in physical activity (PA); and (ii) independent mobility (IM) for walking, cycling, and taking public transport with objectively measured nonschool PA on week- and weekend days in different school grades.

Methods:

A total of 1376 Spanish youngsters (50.8% boys; mean age 11.96 ± 2.48 years) participated in the study. Participants reported the frequency of their parental, sibling, and best friend coparticipation in PA with them and their IM for walking, cycling, and taking public transport. PA was objectively measured by accelerometry.

Results:

Coparticipation in PA and IM were more frequently related to nonschool PA among adolescents than among children. Friend coparticipation in PA was positively associated with higher levels of nonschool PA in adolescents. IM for walking and IM for cycling in adolescents were related to nonschool PA on weekdays.

Conclusions:

Our results highlight the need for age-focused interventions and the integration of family and friends to promote PA in youth.
Pocket DNA sequencers make real-time diagnostics a reality
Authors: Pennisi Elizabeth
Published: February 2016

Advances in accuracy of nanopore sequencing help pave the way for on-the-spot DNA tests.
The next big eye
Authors: Clery Daniel
Published: February 2016

The pressure is on the builders of the James Webb Space Telescope to ensure that NASA's $8 billion gamble pays off.
Comment on “Cortical folding scales universally with surface area and thickness, not number of neurons”
Authors: de Lussanet Marc H. E.
Published: February 2016

The cerebrum of large mammals is convoluted, whereas that of small mammals is smooth. Mota and Herculano-Houzel (Reports, 3 July 2015, p. 74) inspired a model on an old theory that proposed a fractal geometry. I show that their model reduces to the product of gray-matter proportion times the folding index. This proportional relation describes the available data even better than the fractal model.
Molecular architecture of the human U4/U6.U5 tri-snRNP
Authors: Agafonov Dmitry E. , Kastner Berthold , Dybkov Olexandr , Hofele Romina V. , Liu Wen-Ti , Urlaub Henning , Lührmann Reinhard , Stark Holger
Published: February 2016

A human spliceosomal subcomplex

The spliceosome is an RNA and protein molecular machine that cuts out introns from messenger RNAs. Agafonov
et al.
used cryo-electron microscopy to determine the structure of the largest intermediate subcomplex on the assembly pathway for the human spliceosome (see the Perspective by Cate). The structure shows substantial differences from the equivalent yeast complex. It also reveals how the subcomplex must dock onto the rest of the spliceosome and hints at the structural changes the complex must go through to form the mature spliceosome.

Science
, this issue p.
1416
; see also p.
1390
DNA-controlled dynamic colloidal nanoparticle systems for mediating cellular interaction
Authors: Ohta Seiichi , Glancy Dylan , Chan Warren C. W.
Published: February 2016

Dynamic DNA clustering of nanoparticles

The size and shape of nanoparticles can increase the cellular uptake and delivery of contrast agents and therapeutics. Ohta
et al.
created gold nanoparticles partly covered with DNA chains and with folic acid as the targeting molecule (see the Perspective by Parak). The particles could link together to hide the folic acid or to expose it on the surface, depending on the hybridization and overall particle configuration. The addition of complementary DNA allowed switching between structures, thus changing the way the particles interacted with cells.

Science
, this issue p.
841
; see also p.
814
Beyond Ebola
Authors: Currie Janet , Grenfell Bryan , Farrar Jeremy
Published: February 2016

The Ebola epidemic provides lessons for how to respond to future epidemics
Lactobacillus plantarum
strain maintains growth of infant mice during chronic undernutrition
Authors: Schwarzer Martin , Makki Kassem , Storelli Gilles , Machuca-Gayet Irma , Srutkova Dagmar , Hermanova Petra , Martino Maria Elena , Balmand Severine , Hudcovic Tomas , Heddi Abdelaziz , Rieusset Jennifer , Kozakova Hana , Vidal Hubert , Leulier François
Published: February 2016

Microbiota and infant development

Malnutrition in children is a persistent challenge that is not always remedied by improvements in nutrition. This is because a characteristic community of gut microbes seems to mediate some of the pathology. Human gut microbes can be transplanted effectively into germ-free mice to recapitulate their associated phenotypes. Using this model, Blanton
et al.
found that the microbiota of healthy children relieved the harmful effects on growth caused by the microbiota of malnourished children. In infant mammals, chronic undernutrition results in growth hormone resistance and stunting. In mice, Schwarzer
et al.
showed that strains of
Lactobacillus plantarum
in the gut microbiota sustained growth hormone activity via signaling pathways in the liver, thus overcoming growth hormone resistance. Together these studies reveal that specific beneficial microbes could potentially be exploited to resolve undernutrition syndromes.

Science
, this issue p.
10.1126/science.aad3311
, p.
854
Rpn1 provides adjacent receptor sites for substrate binding and deubiquitination by the proteasome
Authors: Shi Yuan , Chen Xiang , Elsasser Suzanne , Stocks Bradley B. , Tian Geng , Lee Byung-Hoon , Shi Yanhong , Zhang Naixia , de Poot Stefanie A. H. , Tuebing Fabian , Sun Shuangwu , Vannoy Jacob , Tarasov Sergey G. , Engen John R. , Finley Daniel , Walters Kylie J.
Published: February 2016

The yin and yang of proteasomal regulation

The ubiquitin-proteasome pathway regulates myriad proteins through their selective proteolysis. The small protein ubiquitin is attached, typically in many copies, to the target protein, which is then recognized and broken down by the proteasome. Shi
et al.
found a repeat structure in the proteasome for recognizing ubiquitin as well as ubiquitin-like (UBL) proteins. Tandem binding sites allow the proteasome to dock multiple proteins. One of the bound UBL proteins is an enzyme that cleaves ubiquitin-protein conjugates, which antagonizes degradation. Thus, the repetition of related binding sites with distinct specificity achieves a balance of positive and negative regulation of the proteasome.

Science
, this issue p.
10.1126/science.aad9421
Differences among astrocytes
Authors: Stevens Beth , Muthukumar Allie K.
Published: February 2016

Neurons determine the specificity of local astrocytes

[Also see Report by

Farmer
et al.

]
Genome Sequence of a Gram-Positive Diazotroph, Paenibacillus durus Type Strain ATCC 35681
Authors: Halim Mardani Abdul , Rahman Ahmad Yamin , Sim Kee-Shin , Yam Hok-Chai , Rahim Ainihayati Abdul , Ghazali Amir Hamzah Ahmad , Najimudin Nazalan
Published: February 2016

Here, we report the complete genome sequence of
Paenibacillus durus
type strain ATCC 35681, which can fix atmospheric nitrogen even in the presence of nitrate.