bluuebunny/crossref_metadata_2025 huggingface dataset:
Is land condition a useful indicator of soil organic carbon stock in Australia’s northern grazing land?
Authors: Bray S. G. , Allen D. E. , Harms B. P. , Reid D. J. , Fraser G. W. , Dalal R. C. , Walsh D. , Phelps D. G. , Gunther R.
Published: June 2016

The grazing lands of northern Australia contain a substantial soil organic carbon (SOC) stock due to the large land area. Manipulating SOC stocks through grazing management has been presented as an option to offset national greenhouse gas emissions from agriculture and other industries. However, research into the response of SOC stocks to a range of management activities has variously shown positive, negative or negligible change. This uncertainty in predicting change in SOC stocks represents high project risk for government and industry in relation to SOC sequestration programs. In this paper, we seek to address the uncertainty in SOC stock prediction by assessing relationships between SOC stocks and grazing land condition indicators. We reviewed the literature to identify land condition indicators for analysis and tested relationships between identified land condition indicators and SOC stock using data from a paired-site sampling experiment (10 sites). We subsequently collated SOC stock datasets at two scales (quadrat and paddock) from across northern Australia (329 sites) to compare with the findings of the paired-site sampling experiment with the aim of identifying the land condition indicators that had the strongest relationship with SOC stock. The land condition indicators most closely correlated with SOC stocks across datasets and analysis scales were tree basal area, tree canopy cover, ground cover, pasture biomass and the density of perennial grass tussocks. In combination with soil type, these indicators accounted for up to 42% of the variation in the residuals after climate effects were removed. However, we found that responses often interacted with soil type, adding complexity and increasing the uncertainty associated with predicting SOC stock change at any particular location. We recommend that caution be exercised when considering SOC offset projects in northern Australian grazing lands due to the risk of incorrectly predicting changes in SOC stocks with change in land condition indicators and management activities for a particular paddock or property. Despite the uncertainty for generating SOC sequestration income, undertaking management activities to improve land condition is likely to have desirable complementary benefits such as improving productivity and profitability as well as reducing adverse environmental impact.
Use of business analysis in beef businesses to direct management practice change for climate adaptation outcomes
Authors: Broad Kiri C. , Sneath Roger J. , Emery Timothy M. J.
Published: June 2016

Beef businesses in northern Australia are facing increased pressure to be productive and profitable with challenges such as climate variability and poor financial performance over the past decade. Declining terms of trade, limited recent gains in on-farm productivity, low profit margins under current management systems and current climatic conditions will leave little capacity for businesses to absorb climate change-induced losses. In order to generate a whole-of-business focus towards management change, the Climate Clever Beef project in the Maranoa-Balonne region of Queensland trialled the use of business analysis with beef producers to improve financial literacy, provide a greater understanding of current business performance and initiate changes to current management practices. Demonstration properties were engaged and a systematic approach was used to assess current business performance, evaluate impacts of management changes on the business and to trial practices and promote successful outcomes to the wider industry. Focus was concentrated on improving financial literacy skills, understanding the business’ key performance indicators and modifying practices to improve both business productivity and profitability. To best achieve the desired outcomes, several extension models were employed: the ‘group facilitation/empowerment model’, the ‘individual consultant/mentor model’ and the ‘technology development model’. Providing producers with a whole-of-business approach and using business analysis in conjunction with on-farm trials and various extension methods proved to be a successful way to encourage producers in the region to adopt new practices into their business, in the areas of greatest impact. The areas targeted for development within businesses generally led to improvements in animal performance and grazing land management further improving the prospects for climate resilience.
Longitudinal multiparameter assay of lymphocyte interactions from onset by microfluidic cell pairing and culture
Authors: Dura Burak , Servos Mariah M. , Barry Rachel M. , Ploegh Hidde L. , Dougan Stephanie K. , Voldman Joel
Published: June 2016

Significance

Many immune responses are mediated by direct cell–cell interactions and develop over multiple timescales. A mechanistic understanding of how diverse outcomes arise during these interactions entails identifying the relationships between various responses occurring at different stages by correlated measurements. Typical approaches that rely on population-wide correlations, however, reveal these connections broadly and mask the fine details that might be discernible only at the single-cell level. Here, we present a microfluidics-based cell–cell interaction assay that allows defined generation, real-time imaging, and longitudinal assay of lymphocyte interactions, thereby permitting direct correlative studies within each single cell. Our studies using this platform indicate a possible role for the strength of calcium signaling in selective regulation of cytotoxicity and interferon-gamma production of natural killer cells.
Magnesium isotope geochemistry in arc volcanism
Authors: Teng Fang-Zhen , Hu Yan , Chauvel Catherine
Published: June 2016

Significance

Arc lavas from Martinique have nonmidocean ridge basalt Mg isotopic composition, which is consistent with the incorporation of subducted Mg. This is, to our knowledge, the first report of mantle-derived lavas with Mg isotopic composition heavier than oceanic basalts, heretofore shown to be isotopically homogenous. More importantly, our results provide insight into the strongly debated origins of Martinique arc lavas and suggest that contributions of Mg from fluids supplied by the subducted slab may play a significant control in the Mg isotopic systematics of arc lavas.
Maternally supplied S-acyl-transferase is required for crystalloid organelle formation and transmission of the malaria parasite
Authors: Santos Jorge M. , Duarte Neuza , Kehrer Jessica , Ramesar Jai , Avramut M. Cristina , Koster Abraham J. , Dessens Johannes T. , Frischknecht Friedrich , Chevalley-Maurel Séverine , Janse Chris J. , Franke-Fayard Blandine , Mair Gunnar R.
Published: June 2016

Significance

The malaria parasite requires the formation of a stage-specific, enigmatic organelle—the crystalloid—for mosquito invasion. Perhaps acting as storage for proteins and lipids, the crystalloid is generated during ookinete formation and dissolved during sporogony in the oocyst. We show here that
Plasmodium berghei
expresses an S-acyl-transferase DHHC10 that localizes to the crystalloid. Parasites depleted of
dhhc10
produce ookinetes that successfully establish oocysts but fail to produce sporozoites; knockout parasites are characterized by the absence of the crystalloid and the mislocalization of a crystalloid-resident protein.
Normocyte-binding protein required for human erythrocyte invasion by the zoonotic malaria parasite
Plasmodium knowlesi
Authors: Moon Robert W. , Sharaf Hazem , Hastings Claire H. , Ho Yung Shwen , Nair Mridul B. , Rchiad Zineb , Knuepfer Ellen , Ramaprasad Abhinay , Mohring Franziska , Amir Amirah , Yusuf Noor A. , Hall Joanna , Almond Neil , Lau Yee Ling , Pain Arnab , Blackman Michael J. , Holder Anthony A.
Published: June 2016

Significance

Plasmodium knowlesi
is a parasite that naturally infects cynomolgus monkeys but is also a major cause of severe zoonotic malaria in humans in South East Asia. Comparing the genomes of parasites restricted to growth in culture with cynomolgus RBCs and those adapted to growth in human RBCs identified a gene specifically required for invasion of human RBCs, a process that is critical for parasite replication. This gene encodes normocyte-binding protein Xa, a protein previously shown to bind human RBCs and implicated in invasion. Disruption of this gene blocks invasion of human but not cynomolgus RBCs, thus confirming a key mediator of human infection and a potential target for inclusion in vaccines to prevent human infection.
Polymers in the gut compress the colonic mucus hydrogel
Authors: Datta Sujit S. , Preska Steinberg Asher , Ismagilov Rustem F.
Published: June 2016

Significance

Hydrogels are critical components of biological systems; however, how these structures are affected by polymers abundant in their environments (e.g., dietary fiber in the gut and soluble glycoproteins in tissues) remains unknown. Here we find that the colonic mucus hydrogel (a protective barrier and mediator of microbe–host interactions) is compressed by gut polymers. Surprisingly, the predictions of a simple thermodynamic model are able to describe our experiments on this complex biological system, providing insight into the underlying physics. Moreover, we find that gut microbes modulate mucus structure by degrading dietary polymers into smaller, noncompressing fragments. These findings reveal a mechanism of mucus restructuring and illustrate an unexpected interplay between diet, gut microbiota, and the biological structures that protect a host.
Spatiotemporal Spawning Patterns of Smallmouth Bass at Its Upstream Invasion Edge
Authors: S. Rubenson Erika , Olden Julian D.
Published: June 2016

Climate change and land‐use practices are causing widespread warming of streams, forcing resident species to adapt or migrate. For instance, in the John Day River, Oregon (Columbia River basin), rising temperatures are facilitating the range expansion of Smallmouth Bass Micropterus dolomieu into critical salmon rearing habitat. Understanding Smallmouth Bass reproductive ecology at its range boundaries is integral to understanding and ultimately predicting its upstream range expansion. We addressed this knowledge gap by exploring potential temperature‐mediated effects on Smallmouth Bass reproduction at the leading edge of its nonnative riverine distribution in the Pacific Northwest. We used continuous snorkel surveys to characterize its upstream extent in the North Fork John Day River, where we observed spawning patterns and measured adult nest‐guarding male size, fecundity, brood development, habitat attributes, and nest success over 2 years (2014, 2015). We found a pattern of asynchronous and protracted spawn timing across the leading invasion edge, >90% nest success, and few changes in reproductive attributes (e.g., fecundity, brood development) as the thermal regime became increasingly colder. We also found increased selectivity of nest substrata and decreased guarding requirements in upstream habitats. These results suggest that reproductive success does not limit the upstream range expansion of Smallmouth Bass and highlight potential ecological benefits that may offset the energetic demands associated with dispersing upstream. Overall, our findings enhance the current understanding of how reproduction influences range expansion of nonnative Smallmouth Bass populations in streams, enabling us to better guide managers tasked with minimizing the spread of this nonnative species in the future.

Received November 2, 2015; accepted February 1, 2016 Published online June 15, 2016
Novel Signaling Pathways in Pulmonary Arterial Hypertension (2015 Grover Conference Series)
Authors: Awad Keytam S. , West James D. , de Jesus Perez Vinicio , MacLean Margaret
Published: June 2016

The proliferative endothelial and smooth muscle cell phenotype, inflammation, and pulmonary vascular remodeling are prominent features of pulmonary arterial hypertension (PAH). Mutations in bone morphogenetic protein type 2 receptor (BMPR2) have been identified as the most common genetic cause of PAH and females with BMPR2 mutations are 2.5 times as likely to develop heritable forms of PAH than males. Higher levels of estrogen have also been observed in males with PAH, implicating sex hormones in PAH pathogenesis. Recently, the estrogen metabolite 16α‐OHE1 (hydroxyestrone) was implicated in the regulation of miR29, a microRNA involved in modulating energy metabolism. In females, decreased miR96 enhances serotonin's effect by upregulating the 5‐hydroxytryptamine 1B (5HT1B) receptor. Because PAH is characterized as a quasi‐malignant disease, likely due to BMPR2 loss of function, altered signaling pathways that sustain this cancer‐like phenotype are being explored. Extracellular signal–regulated kinases 1 and 2 and p38 mitogen‐activated protein kinases (MAPKs) play a critical role in proliferation and cell motility, and dysregulated MAPK signaling is observed in various experimental models of PAH. Wnt signaling pathways preserve pulmonary vascular homeostasis, and dysregulation of this pathway could contribute to limited vascular regeneration in response to injury. In this review, we take a closer look at sex, sex hormones, and the interplay between sex hormones and microRNA regulation. We also focus on MAPK and Wnt signaling pathways in the emergence of a proproliferative, antiapoptotic endothelial phenotype, which then orchestrates an angioproliferative process of vascular remodeling, with the hope of developing novel therapies that could reverse the phenotype.
Enhancement of runaway production by resonant magnetic perturbation on J-TEXT
Authors: Chen Z.Y. , Huang D.W. , Izzo V.A. , Tong R.H. , Jiang Z.H. , Hu Q.M. , Wei Y.N. , Yan W. , Rao B. , Wang S.Y. , Ma T.K. , Li S.C. , Yang Z.J. , Ding D.H. , Wang Z.J. , Zhang M. , Zhuang G. , Pan Y.
Published: June 2016

The suppression of runaways following disruptions is key for the safe operation of ITER. The massive gas injection (MGI) has been developed to mitigate heat loads, electromagnetic forces and runaway electrons (REs) during disruptions. However, MGI may not completely prevent the generation of REs during disruptions on ITER. Resonant magnetic perturbation (RMP) has been applied to suppress runaway generation during disruptions on several machines. It was found that strong RMP results in the enhancement of runaway production instead of runaway suppression on J-TEXT. The runaway current was about 50% pre-disruption plasma current in argon induced reference disruptions. With moderate RMP, the runway current decreased to below 30% pre-disruption plasma current. The runaway current plateaus reach 80% of the pre-disruptive current when strong RMP was applied. Strong RMP may induce large size magnetic islands that could confine more runaway seed during disruptions. This has important implications for runaway suppression on large machines.
The locus of plane quartics with a hyperflex
Authors: Hu Xuntao
Published: June 2016

Using the results of a work by Dalla Piazza, Fiorentino and Salvati Manni, we determine an explicit modular form defining the locus of plane quartics with a hyperflex among all plane quartics. As a result, we provide a direct way to compute the divisor class of the locus of plane quartics with a hyperflex within

M

3

¯

\overline {\mathcal {M}_{3}}

, first obtained by Cukierman. Moreover, the knowledge of such an explicit modular form also allows us to describe explicitly the boundary of the hyperflex locus in

M

3

¯

\overline {\mathcal {M}_{3}}

. As an example we show that the locus of banana curves (two irreducible components intersecting at two nodes) is contained in the closure of the hyperflex locus. We also identify an explicit modular form defining the locus of Clebsch quartics and use it to recompute the class of this divisor, first obtained in a work by Ottaviani and Sernesi.
On the Wiener-Hopf compactification of a symmetric cone
Authors: Sundar S.
Published: June 2016

LetVVbe a finite dimensional real Euclidean Jordan algebra with the identity element11. LetQQbe the closed convex cone of squares. We show that the Wiener-Hopf compactification ofQQis the interval{x∈V:−1≤x≤1}\{x \in V: -1 \leq x \leq 1\}. As a consequence, we deduce that theKK-groups of the Wiener-HopfC∗C^{*}-algebra associated toQQare trivial.
Equivalence and stable isomorphism of groupoids, and diagonal-preserving stable isomorphisms of graph 𝐶*-algebras and Leavitt path algebras
Authors: Carlsen Toke , Ruiz Efren , Sims Aidan
Published: June 2016

We prove that ample groupoids with

σ
\sigma

-compact unit spaces are equivalent if and only if they are stably isomorphic in an appropriate sense, and relate this to Matui’s notion of Kakutani equivalence. We use this result to show that diagonal-preserving stable isomorphisms of graph

C
∗

C^*

-algebras or Leavitt path algebras give rise to isomorphisms of the groupoids of the associated stabilised graphs. We deduce that the Leavitt path algebras

L

Z

(

E
2

)

L_{\mathbb {Z}}(E_2)

and

L

Z

(

E

2
−

)

L_{\mathbb {Z}}(E_{2-})

are not stably

∗

^*

-isomorphic.
Davies’ method for anomalous diffusions
Authors: Murugan Mathav , Saloff-Coste Laurent
Published: June 2016

Davies’ method of perturbed semigroups is a classical technique to obtain off-diagonal upper bounds on the heat kernel. However Davies’ method does not apply to anomalous diffusions due to the singularity of energy measures. In this note, we overcome the difficulty by modifying the Davies’ perturbation method to obtain sub-Gaussian upper bounds on the heat kernel. Our computations closely follow the seminal work of Carlen, Kusuoka and Stroock (1987). However, a cutoff Sobolev inequality due to Andres and Barlow (2015) is used to bound the energy measure.
The self-shrinker in warped product space and the weighted Minkowski inequality
Authors: Wu Guoqiang
Published: June 2016

This paper consists of two parts. One is that for a kind of self-shrinker in a manifold with warped product metric, we prove that under some conditions on ambient space, the mean convex self-shrinker must have parallel second fundamental form. The other one is a generalization of Brendle’s Minkowski inequality for weighted mean curvature.
Vanishing viscosity limits for the 3D Navier-Stokes equations with a slip boundary condition
Authors: Zhong Xin
Published: June 2016

The solvability and vanishing viscosity limit for three dimensional incompressible Navier-Stokes equations with a slip boundary condition were obtained. The proof of these results is based on standard energy estimates.
What time is it? Deep learning approaches for circadian rhythms
Authors: Agostinelli Forest , Ceglia Nicholas , Shahbaba Babak , Sassone-Corsi Paolo , Baldi Pierre
Published: June 2016

Motivation: Circadian rhythms date back to the origins of life, are found in virtually every species and every cell, and play fundamental roles in functions ranging from metabolism to cognition. Modern high-throughput technologies allow the measurement of concentrations of transcripts, metabolites and other species along the circadian cycle creating novel computational challenges and opportunities, including the problems of inferring whether a given species oscillate in circadian fashion or not, and inferring the time at which a set of measurements was taken.

Results: We first curate several large synthetic and biological time series datasets containing labels for both periodic and aperiodic signals. We then use deep learning methods to develop and train BIO_CYCLE, a system to robustly estimate which signals are periodic in high-throughput circadian experiments, producing estimates of amplitudes, periods, phases, as well as several statistical significance measures. Using the curated data, BIO_CYCLE is compared to other approaches and shown to achieve state-of-the-art performance across multiple metrics. We then use deep learning methods to develop and train BIO_CLOCK to robustly estimate the time at which a particular single-time-point transcriptomic experiment was carried. In most cases, BIO_CLOCK can reliably predict time, within approximately 1 h, using the expression levels of only a small number of core clock genes. BIO_CLOCK is shown to work reasonably well across tissue types, and often with only small degradation across conditions. BIO_CLOCK is used to annotate most mouse experiments found in the GEO database with an inferred time stamp.

Availability and Implementation: All data and software are publicly available on the CircadiOmics web portal: circadiomics.igb.uci.edu/.

Contacts:  fagostin@uci.edu or pfbaldi@uci.edu

Supplementary information  :  Supplementary data are available at Bioinformatics online.
A convex optimization approach for identification of human tissue-specific interactomes
Authors: Mohammadi Shahin , Grama Ananth
Published: June 2016

Motivation: Analysis of organism-specific interactomes has yielded novel insights into cellular function and coordination, understanding of pathology, and identification of markers and drug targets. Genes, however, can exhibit varying levels of cell type specificity in their expression, and their coordinated expression manifests in tissue-specific function and pathology. Tissue-specific/tissue-selective interaction mechanisms have significant applications in drug discovery, as they are more likely to reveal drug targets. Furthermore, tissue-specific transcription factors (tsTFs) are significantly implicated in human disease, including cancers. Finally, disease genes and protein complexes have the tendency to be differentially expressed in tissues in which defects cause pathology. These observations motivate the construction of refined tissue-specific interactomes from organism-specific interactomes.

Results: We present a novel technique for constructing human tissue-specific interactomes. Using a variety of validation tests (Edge Set Enrichment Analysis, Gene Ontology Enrichment, Disease-Gene Subnetwork Compactness), we show that our proposed approach significantly outperforms state-of-the-art techniques. Finally, using case studies of Alzheimer’s and Parkinson’s diseases, we show that tissue-specific interactomes derived from our study can be used to construct pathways implicated in pathology and demonstrate the use of these pathways in identifying novel targets.

Availability and implementation:  http://www.cs.purdue.edu/homes/mohammas/projects/ActPro.html

Contact:  mohammadi@purdue.edu
Fast metabolite identification with Input Output Kernel Regression
Authors: Brouard Céline , Shen Huibin , Dührkop Kai , d'Alché-Buc Florence , Böcker Sebastian , Rousu Juho
Published: June 2016

Motivation: An important problematic of metabolomics is to identify metabolites using tandem mass spectrometry data. Machine learning methods have been proposed recently to solve this problem by predicting molecular fingerprint vectors and matching these fingerprints against existing molecular structure databases. In this work we propose to address the metabolite identification problem using a structured output prediction approach. This type of approach is not limited to vector output space and can handle structured output space such as the molecule space.

Results: We use the Input Output Kernel Regression method to learn the mapping between tandem mass spectra and molecular structures. The principle of this method is to encode the similarities in the input (spectra) space and the similarities in the output (molecule) space using two kernel functions. This method approximates the spectra-molecule mapping in two phases. The first phase corresponds to a regression problem from the input space to the feature space associated to the output kernel. The second phase is a preimage problem, consisting in mapping back the predicted output feature vectors to the molecule space. We show that our approach achieves state-of-the-art accuracy in metabolite identification. Moreover, our method has the advantage of decreasing the running times for the training step and the test step by several orders of magnitude over the preceding methods.

Availability and implementation :

Contact:  celine.brouard@aalto.fi

Supplementary information:  Supplementary data are available at Bioinformatics online.
Analysis of aggregated cell–cell statistical distances within pathways unveils therapeutic-resistance mechanisms in circulating tumor cells
Authors: Schissler A. Grant , Li Qike , Chen James L. , Kenost Colleen , Achour Ikbel , Billheimer D. Dean , Li Haiquan , Piegorsch Walter W. , Lussier Yves A.
Published: June 2016

Motivation: As ‘omics’ biotechnologies accelerate the capability to contrast a myriad of molecular measurements from a single cell, they also exacerbate current analytical limitations for detecting meaningful single-cell dysregulations. Moreover, mRNA expression alone lacks functional interpretation, limiting opportunities for translation of single-cell transcriptomic insights to precision medicine. Lastly, most single-cell RNA-sequencing analytic approaches are not designed to investigate small populations of cells such as circulating tumor cells shed from solid tumors and isolated from patient blood samples.

Results: In response to these characteristics and limitations in current single-cell RNA-sequencing methodology, we introduce an analytic framework that models transcriptome dynamics through the analysis of aggregated cell–cell statistical distances within biomolecular pathways. Cell–cell statistical distances are calculated from pathway mRNA fold changes between two cells. Within an elaborate case study of circulating tumor cells derived from prostate cancer patients, we develop analytic methods of aggregated distances to identify five differentially expressed pathways associated to therapeutic resistance. Our aggregation analyses perform comparably with Gene Set Enrichment Analysis and better than differentially expressed genes followed by gene set enrichment. However, these methods were not designed to inform on differential pathway expression for a single cell. As such, our framework culminates with the novel aggregation method, cell-centric statistics (CCS). CCS quantifies the effect size and significance of differentially expressed pathways for a single cell of interest. Improved rose plots of differentially expressed pathways in each cell highlight the utility of CCS for therapeutic decision-making.

Availability and implementation:  http://www.lussierlab.org/publications/CCS/

Contact:  yves@email.arizona.edu or piegorsch@math.arizona.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
BioASF: a framework for automatically generating executable pathway models specified in BioPAX
Authors: Haydarlou Reza , Jacobsen Annika , Bonzanni Nicola , Feenstra K. Anton , Abeln Sanne , Heringa Jaap
Published: June 2016

Motivation: Biological pathways play a key role in most cellular functions. To better understand these functions, diverse computational and cell biology researchers use biological pathway data for various analysis and modeling purposes. For specifying these biological pathways, a community of researchers has defined BioPAX and provided various tools for creating, validating and visualizing BioPAX models. However, a generic software framework for simulating BioPAX models is missing. Here, we attempt to fill this gap by introducing a generic simulation framework for BioPAX. The framework explicitly separates the execution model from the model structure as provided by BioPAX, with the advantage that the modelling process becomes more reproducible and intrinsically more modular; this ensures natural biological constraints are satisfied upon execution. The framework is based on the principles of discrete event systems and multi-agent systems, and is capable of automatically generating a hierarchical multi-agent system for a given BioPAX model.

Results: To demonstrate the applicability of the framework, we simulated two types of biological network models: a gene regulatory network modeling the haematopoietic stem cell regulators and a signal transduction network modeling the Wnt/β-catenin signaling pathway. We observed that the results of the simulations performed using our framework were entirely consistent with the simulation results reported by the researchers who developed the original models in a proprietary language.

Availability and Implementation: The framework, implemented in Java, is open source and its source code, documentation and tutorial are available at http://www.ibi.vu.nl/programs/BioASF.

Contact:  j.heringa@vu.nl
Influence maximization in time bounded network identifies transcription factors regulating perturbed pathways
Authors: Jo Kyuri , Jung Inuk , Moon Ji Hwan , Kim Sun
Published: June 2016

Motivation: To understand the dynamic nature of the biological process, it is crucial to identify perturbed pathways in an altered environment and also to infer regulators that trigger the response. Current time-series analysis methods, however, are not powerful enough to identify perturbed pathways and regulators simultaneously. Widely used methods include methods to determine gene sets such as differentially expressed genes or gene clusters and these genes sets need to be further interpreted in terms of biological pathways using other tools. Most pathway analysis methods are not designed for time series data and they do not consider gene-gene influence on the time dimension.

Results: In this article, we propose a novel time-series analysis method TimeTP for determining transcription factors (TFs) regulating pathway perturbation, which narrows the focus to perturbed sub-pathways and utilizes the gene regulatory network and protein–protein interaction network to locate TFs triggering the perturbation. TimeTP first identifies perturbed sub-pathways that propagate the expression changes along the time. Starting points of the perturbed sub-pathways are mapped into the network and the most influential TFs are determined by influence maximization technique. The analysis result is visually summarized in TF-Pathway map in time clock . TimeTP was applied to PIK3CA knock-in dataset and found significant sub-pathways and their regulators relevant to the PIP3 signaling pathway.

Availability and Implementation: TimeTP is implemented in Python and available at http://biohealth.snu.ac.kr/software/TimeTP/ .

Supplementary information:  Supplementary data are available at Bioinformatics online.

Contact:  sunkim.bioinfo@snu.ac.kr
RapMap: a rapid, sensitive and accurate tool for mapping RNA-seq reads to transcriptomes
Authors: Srivastava Avi , Sarkar Hirak , Gupta Nitish , Patro Rob
Published: June 2016

Motivation: The alignment of sequencing reads to a transcriptome is a common and important step in many RNA-seq analysis tasks. When aligning RNA-seq reads directly to a transcriptome (as is common in the de novo setting or when a trusted reference annotation is available), care must be taken to report the potentially large number of multi-mapping locations per read. This can pose a substantial computational burden for existing aligners, and can considerably slow downstream analysis.

Results: We introduce a novel concept, quasi-mapping, and an efficient algorithm implementing this approach for mapping sequencing reads to a transcriptome. By attempting only to report the potential loci of origin of a sequencing read, and not the base-to-base alignment by which it derives from the reference, RapMap—our tool implementing quasi-mapping—is capable of mapping sequencing reads to a target transcriptome substantially faster than existing alignment tools. The algorithm we use to implement quasi-mapping uses several efficient data structures and takes advantage of the special structure of shared sequence prevalent in transcriptomes to rapidly provide highly-accurate mapping information. We demonstrate how quasi-mapping can be successfully applied to the problems of transcript-level quantification from RNA-seq reads and the clustering of contigs from de novo assembled transcriptomes into biologically meaningful groups.

Availability and implementation: RapMap is implemented in C ++11 and is available as open-source software, under GPL v3, at https://github.com/COMBINE-lab/RapMap .

Contact:  rob.patro@cs.stonybrook.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
A novel algorithm for calling mRNA m
6
A peaks by modeling biological variances in MeRIP-seq data
Authors: Cui Xiaodong , Meng Jia , Zhang Shaowu , Chen Yidong , Huang Yufei
Published: June 2016

Motivation:   N 6 -methyl-adenosine (m 6 A) is the most prevalent mRNA methylation but precise prediction of its mRNA location is important for understanding its function. A recent sequencing technology, known as Methylated RNA Immunoprecipitation Sequencing technology (MeRIP-seq), has been developed for transcriptome-wide profiling of m 6 A. We previously developed a peak calling algorithm called exomePeak. However, exomePeak over-simplifies data characteristics and ignores the reads’ variances among replicates or reads dependency across a site region. To further improve the performance, new model is needed to address these important issues of MeRIP-seq data.

Results: We propose a novel, graphical model-based peak calling method, MeTPeak, for transcriptome-wide detection of m 6 A sites from MeRIP-seq data. MeTPeak explicitly models read count of an m 6 A site and introduces a hierarchical layer of Beta variables to capture the variances and a Hidden Markov model to characterize the reads dependency across a site. In addition, we developed a constrained Newton’s method and designed a log-barrier function to compute analytically intractable, positively constrained Beta parameters. We applied our algorithm to simulated and real biological datasets and demonstrated significant improvement in detection performance and robustness over exomePeak. Prediction results on publicly available MeRIP-seq datasets are also validated and shown to be able to recapitulate the known patterns of m 6 A, further validating the improved performance of MeTPeak.

Availability and implementation: The package ‘MeTPeak’ is implemented in R and C ++, and additional details are available at https://github.com/compgenomics/MeTPeak

Contact:  yufei.huang@utsa.edu or xdchoi@gmail.com

Supplementary information:  Supplementary data are available at Bioinformatics online.
On tests of general relativity with binary radio pulsars
Authors: Del Pozzo W. , Vecchio A.
Published: June 2016

The timing of radio pulsars in binary systems provides a superb testing ground of general relativity. Here we propose a Bayesian approach to carry out these tests, and a relevant efficient numerical implementation, that has several conceptual and practical advantages with respect to traditional methods based on least-squares fit that have been used so far: (i) it accounts for the actual structure of the likelihood function – and it is not predicated on the Laplace approximation which is implicitly built in least-squares fit that can potentially bias the inference – (ii) it provides the ratio of the evidences of any two models under consideration as the statistical quantity to compare different theories, and (iii) it allows us to put joint constraints from the monitoring of multiple systems, that can be expressed in terms of ratio of evidences or probability intervals of global (thus not system-dependent) parameters of the theory, if any exists. Our proposed approach optimally exploits the progress in timing of radio pulsars and the increase in the number of observed systems. We demonstrate the power of this framework using simulated data sets that are representative of current observations.
Hard X-ray luminosity function of tidal disruption events: First results from the MAXI extragalactic survey
Authors: Kawamuro Taiki , Ueda Yoshihiro , Shidatsu Megumi , Hori Takafumi , Kawai Nobuyuki , Negoro Hitoshi , Mihara Tatehiro
Published: June 2016

We derive the first hard X-ray luminosity function (XLF) of stellar tidal disruption events (TDEs) by supermassive black holes (SMBHs), which gives an occurrence rate of TDEs per unit volume as a function of peak luminosity and redshift, utilizing an unbiased sample observed by the Monitor of All-sky X-ray Image (MAXI). On the basis of the light curves characterized by a power-law decay with an index of −5/3, a systematic search using the MAXI data detected four TDEs in the first 37 months of observations, all of which have been found in the literature. To formulate the TDE XLF, we consider the mass function of SMBHs, that of disrupted stars, the specific TDE rate as a function of SMBH mass, and the fraction of TDEs with relativistic jets. We perform an unbinned maximum likelihood fit to the MAXI TDE list and check the consistency with the observed TDE rate in the ROSAT all-sky survey. The results suggest that the intrinsic fraction of the jet-accompanying events is 0.0007%–34%. We confirm that at z ≲ 1.5 the contamination of the hard X-ray luminosity functions of active galactic nuclei by TDEs is not significant and hence that their contribution to the growth of SMBHs is negligible at the redshifts.
A History of Psychosis in Bipolar Disorder is Associated With Gray Matter Volume Reduction
Authors: Ekman Carl Johan , Petrovic Predrag , Johansson Anette G. M. , Sellgren Carl , Ingvar Martin , Landén Mikael
Published: June 2016

Psychotic symptoms are prevalent in schizophrenia, bipolar disorder, and other psychiatric and neurological disorders, yet the neurobiological underpinnings of psychosis remain obscure. In the last decade, a large number of magnetic resonance imaging studies have shown differences in local gray matter volume between patients with different psychiatric syndromes and healthy controls. Few studies have focused on the symptoms, which these syndromes are constituted of. Here, we test the association between psychosis and gray matter volume by using a sample of 167 subjects with bipolar disorder, with and without a history of psychosis, and 102 healthy controls. Magnetic resonance images were analyzed on group level using a voxel-wise mass univariate analysis (Voxel-Based Morphometry). We found that patients with a history of psychosis had smaller gray matter volume in left fusiform gyrus, the right rostral dorsolateral prefrontal cortex, and the left inferior frontal gyrus compared with patients without psychosis and with healthy controls. There was no volume difference in these areas between the no-psychosis group and healthy controls. These areas have previously been structurally and functionally coupled to delusions and hallucinations. Our finding adds further evidence to the probability of these regions as key areas in the development of psychotic symptoms.
Impact of a new sampling buffer on faecal haemoglobin stability in a colorectal cancer screening programme by the faecal immunochemical test
Authors: Grazzini Grazia , Ventura Leonardo , Rubeca Tiziana , Rapi Stefano , Cellai Filippo , Di Dia Pietro P. , Mallardi Beatrice , Mantellini Paola , Zappa Marco , Castiglione Guido
Published: June 2016

Haemoglobin (Hb) stability in faecal samples is an important issue in colorectal cancer screening by the faecal immunochemical test (FIT) for Hb. This study evaluated the performance of the FIT-Hb (OC-Sensor Eiken) used in the Florence screening programme by comparing two different formulations of the buffer, both in an analytical and in a clinical setting. In the laboratory simulation, six faecal pools (three in each buffer type) were stored at different temperatures and analysed eight times in 10 replicates over 21 days. In the clinical setting, 7695 screenees returned two samples, using both the old and the new specimen collection device (SCD). In the laboratory simulation, 5 days from sample preparation with the buffer of the old SCD, the Hb concentration decreased by 40% at room temperature (25°C, range 22–28°C) and up to 60% at outside temperature (29°C, range 16–39°C), whereas with the new one, Hb concentration decreased by 10%. In the clinical setting, a higher mean Hb concentration with the new SCD compared with the old one was found (6.3 vs. 5.0 µg Hb/g faeces, respectively, P<0.001); no statistically significant difference was found in the probability of having a positive result in the two SCDs. Better Hb stability was observed with the new buffer under laboratory conditions, but no difference was found in the clinical performance. In our study, only marginal advantages arise from the new buffer. Improvements in sample stability represent a significant target in the screening setting.
Assessment of Computer Literacy of Nurses in Lesotho
Authors: Mugomeri Eltony , Chatanga Peter , Maibvise Charles , Masitha Matseliso
Published: June 2016

Health systems worldwide are moving toward use of information technology to improve healthcare delivery. However, this requires basic computer skills. This study assessed the computer literacy of nurses in Lesotho using a cross-sectional quantitative approach. A structured questionnaire with 32 standardized computer skills was distributed to 290 randomly selected nurses in Maseru District. Univariate and multivariate logistic regression analyses in Stata 13 were performed to identify factors associated with having inadequate computer skills. Overall, 177 (61%) nurses scored below 16 of the 32 skills assessed. Finding hyperlinks on Web pages (63%), use of advanced search parameters (60.2%), and downloading new software (60.1%) proved to be challenging to the highest proportions of nurses. Age, sex, year of obtaining latest qualification, computer experience, and work experience were significantly (P < .05) associated with inadequate computer skills in univariate analysis. However, in multivariate analyses, sex (P = .001), year of obtaining latest qualification (P = .011), and computer experience (P < .001) emerged as significant factors. The majority of nurses in Lesotho have inadequate computer skills, and this is significantly associated with having many years since obtaining their latest qualification, being female, and lack of exposure to computers. These factors should be considered during planning of training curriculum for nurses in Lesotho.
New paradigms in the diagnosis and management of endometriosis
Authors: Kavoussi Shahryar K. , Lim Courtney S. , Skinner Bethany D. , Lebovic Dan I. , As-Sanie Sawsan
Published: June 2016

Purpose of review

Endometriosis is a common gynecologic condition estimated to affect 10–15% of reproductive-aged women, 30% of women with subfertility, and 80% of women with chronic pelvic pain. Although mainstays of diagnosis and treatment are still commonly applied, there have been various advances in the modalities of diagnosis and management of this complex condition. This article provides an updated review of novel findings regarding the diagnosis and management of this challenging disease.

Recent findings

Despite an abundance of studies on noninvasive diagnostic markers for endometriosis, there is no single imaging study, biomarker or panel of biomarkers that has been validated for clinical diagnosis. New technologies, such as use of indocyanine green and fluorescence, which visualize neovascularization often associated with endometriosis may improve diagnostic detection of endometriosis at the time surgery, but have not been demonstrated to improve pain outcomes after surgery. Hormone suppression remains the mainstay therapy prior to and following surgery. Although most methods demonstrate similar efficacy in reducing endometriosis-associated pain, newer pharmacologic agents that may prove advantageous include oral gonadotropin receptor antagonists, selective progesterone receptor modulators, and angiogenesis inhibitors.

Although there have been some advances in the study of noninvasive imaging and biomarkers, more investigation into effective modalities are being conducted and are needed.
Patient experience and hospital profitability: Is there a link?
Authors: Richter Jason P. , Muhlestein David B.
Published: June 2016

Background:

Patient experience has had a direct financial impact on hospitals since value-based purchasing was instituted by the Centers for Medicare & Medicaid Services in 2013 as a method to reward or punish hospitals based on performance on various measures, including patient experience. Although other industries have shown an indirect impact of customer experience on overall profitability, that link has not been well established in the health care industry. Return-to-provider rate and perceptions of health quality have been associated with profitability in the health care industry.

Purpose:

Our aims were to assess whether, independent of a direct financial impact, a more positive patient experience is associated with increased profitability and whether a more negative patient experience is associated with decreased profitability.

Methodology/Approach:

We used a sample of 19,792 observations from 3767 hospitals over the 6-year period 2007–2012. The data were sourced from Centers for Medicare & Medicaid Services and Hospital Consumer Assessment of Healthcare Providers and Systems. Using generalized estimating equations to account for repeated measures, we fit four separate models for three dependent variables: net patient revenue, net income, and operating margin. Each model included one of the following independent variables of interest: percentage of patients who definitely recommend the hospital, percentage of patients who definitely would not recommend the hospital, percentage of patients who rated the hospital 9 or 10, and percentage of patients who rated the hospital 6 or lower.

Findings:

We identified that a positive patient experience is associated with increased profitability and a negative patient experience is even more strongly associated with decreased profitability.

Practice Implications:

Management should have greater justification for incurring costs associated with bolstering patient experience programs. Improvements in training, technology, and staffing can be justified as a way to improve not only quality but now profitability as well.
RESOLUTION OF TREATMENT-RESISTANT SUBRETINAL FLUID IN A PATIENT WITH EXUDATIVE AGE-RELATED MACULAR DEGENERATION FOLLOWING ENDOPHTHALMITIS
Authors: Kally Peter M. , Sidikaro Yossi , McCannel Colin A.
Published: June 2016

Purpose:

This is the first report to the best of the authors' knowledge to show resolution of subretinal fluid and treatment requirement in a case of exudative age-related macular degeneration (eAMD) with persistent fluid despite treatment that resolved following an episode of culture-positive bacterial endophthalmitis.

Methods:

A 73-year-old man with history of eAMD of the right eye presented with acute postinjection bacterial endophthalmitis 3 days after injection. He had a history of only partially treatment-responsive eAMD that had been treated over a period of 8 years.

Results:

After tap-and-inject treatment of endophthalmitis with ceftazidime, vancomycin, and dexamethasone, the patient returned for follow-up with visual improvement and resolution of the subretinal fluid. The previously treatment-resistant eAMD remains quiescent without further treatment after 10 months of follow-up.

Conclusion:

It is possible that some aspect of the infection, inflammation, or treatment of endophthalmitis had a disease-modifying impact on the eAMD. Further research into the components of endophthalmitis and its treatment may result in the discovery of new treatment approaches or treatment targets.