bluuebunny/crossref_metadata_2025_split huggingface dataset:
Computational design of treatment strategies for proactive therapy on atopic dermatitis using optimal control theory
Authors: Christodoulides Panayiotis , Hirata Yoshito , Domínguez-Hüttinger Elisa , Danby Simon G. , Cork Michael J. , Williams Hywel C. , Aihara Kazuyuki , Tanaka Reiko J. 
Published: May 2017

Atopic dermatitis (AD) is a common chronic skin disease characterized by recurrent skin inflammation and a weak skin barrier, and is known to be a precursor to other allergic diseases such as asthma. AD affects up to 25% of children worldwide and the incidence continues to rise. There is still uncertainty about the optimal treatment strategy in terms of choice of treatment, potency, duration and frequency. This study aims to develop a computational method to design optimal treatment strategies for the clinically recommended ‘proactive therapy’ for AD. Proactive therapy aims to prevent recurrent flares once the disease has been brought under initial control. Typically, this is done by using an anti-inflammatory treatment such as a potent topical corticosteroid intensively for a few weeks to ‘get control’, followed by intermittent weekly treatment to suppress subclinical inflammation to ‘keep control’. Using a hybrid mathematical model of AD pathogenesis that we recently proposed, we computationally derived the optimal treatment strategies for individual virtual patient cohorts, by recursively solving optimal control problems using a differential evolution algorithm. Our simulation results suggest that such an approach can inform the design of optimal individualized treatment schedules that include application of topical corticosteroids and emollients, based on the disease status of patients observed on their weekly hospital visits. We demonstrate the potential and the gaps of our approach to be applied to clinical settings.
This article is part of the themed issue ‘Mathematical methods in medicine: neuroscience, cardiology and pathology’.
Dynamics of the cell-mediated immune response to tumour growth
Authors: López Álvaro G. , Seoane Jesús M. , Sanjuán Miguel A. F. 
Published: May 2017

Using a hybrid cellular automaton, we investigate the transient and asymptotic dynamics of the cell-mediated immune response to tumour growth. We analyse the correspondence between this dynamics and the three phases of the theory of immunoedition: elimination, equilibrium and escape. Our results demonstrate that the immune system can keep a tumour dormant for long periods of time, but that this dormancy is based on a frail equilibrium between the mechanisms that spur the immune response and the growth of the tumour. Thus, we question the capacity of the cell-mediated immune response to sustain long periods of dormancy, as those appearing in recurrent disease. We suggest that its role might be rather to synergize with other types of tumour dormancy.This article is part of the themed issue ‘Mathematical methods in medicine: neuroscience, cardiology and pathology’.
Multiscale ordinal network analysis of human cardiac dynamics
Authors: McCullough M. , Small M. , Iu H. H. C. , Stemler T. 
Published: May 2017

In this study, we propose a new information theoretic measure to quantify the complexity of biological systems based on time-series data. We demonstrate the potential of our method using two distinct applications to human cardiac dynamics. Firstly, we show that the method clearly discriminates between segments of electrocardiogram records characterized by normal sinus rhythm, ventricular tachycardia and ventricular fibrillation. Secondly, we investigate the multiscale complexity of cardiac dynamics with respect to age in healthy individuals using interbeat interval time series and compare our findings with a previous study which established a link between age and fractal-like long-range correlations. The method we use is an extension of the symbolic mapping procedure originally proposed for permutation entropy. We build a Markov chain of the dynamics based on order patterns in the time series which we call an ordinal network, and from this model compute an intuitive entropic measure of transitional complexity. A discussion of the model parameter space in terms of traditional time delay embedding provides a theoretical basis for our multiscale approach. As an ancillary discussion, we address the practical issue of node aliasing and how this effects ordinal network models of continuous systems from discrete time sampled data, such as interbeat interval time series.
This article is part of the themed issue ‘Mathematical methods in medicine: neuroscience, cardiology and pathology’.
Pulsatile flow in ventricular catheters for hydrocephalus
Authors: Giménez Á. , Galarza M. , Thomale U. , Schuhmann M. U. , Valero J. , Amigó J. M. 
Published: May 2017

The obstruction of ventricular catheters (VCs) is a major problem in the standard treatment of hydrocephalus, the flow pattern of the cerebrospinal fluid (CSF) being one important factor thereof. As a first approach to this problem, some of the authors studied previously the CSF flow through VCs under time-independent boundary conditions by means of computational fluid dynamics in three-dimensional models. This allowed us to derive a few basic principles which led to designs with improved flow patterns regarding the obstruction problem. However, the flow of the CSF has actually a pulsatile nature because of the heart beating and blood flow. To address this fact, here we extend our previous computational study to models with oscillatory boundary conditions. The new results will be compared with the results for constant flows and discussed. It turns out that the corrections due to the pulsatility of the CSF are quantitatively small, which reinforces our previous findings and conclusions.
This article is part of the themed issue ‘Mathematical methods in medicine: neuroscience, cardiology and pathology’.
Mathematical methods in medicine: neuroscience, cardiology and pathology
Authors: Amigó José M. , Small Michael 
Published: May 2017

The application of mathematics, natural sciences and engineering to medicine is gaining momentum as the mutual benefits of this collaboration become increasingly obvious. This theme issue is intended to highlight the trend in the case of mathematics. Specifically, the scope of this theme issue is to give a general view of the current research in the application of mathematical methods to medicine, as well as to show how mathematics can help in such important aspects as understanding, prediction, treatment and data processing. To this end, three representative specialties have been selected: neuroscience, cardiology and pathology. Concerning the topics, the 12 research papers and one review included in this issue cover biofluids, cardiac and virus dynamics, computational neuroscience, functional magnetic resonance imaging data processing, neural networks, optimization of treatment strategies, time-series analysis and tumour growth. In conclusion, this theme issue contains a collection of fine contributions at the intersection of mathematics and medicine, not as an exercise in applied mathematics but as a multidisciplinary research effort that interests both communities and our society in general.
This article is part of the themed issue ‘Mathematical methods in medicine: neuroscience, cardiology and pathology’.
KKL-35 exhibits potent antibiotic activity againstLegionellaspecies independently of trans-translation inhibition
Authors: Brunel Romain , Descours Ghislaine , Durieux Isabelle , Doublet Patricia , Jarraud Sophie , Charpentier Xavier 
Published: May 2017

AbstractTrans-translation is a ribosome rescue system that is ubiquitous in bacteria. Small molecules defining a new family of oxadiazole compounds that inhibit trans-translation have been found to have broad-spectrum antibiotic activity. We sought to determine the activity of KKL-35, a potent member of the oxadiazole family, against the human pathogenLegionella pneumophilaand other related species that can also cause Legionnaires disease (LD). Consistent with the essential nature of trans-translation inL. pneumophila, KKL-35 inhibits growth of all tested strains at sub-micromolar concentrations. KKL-35 is also active against other LD-causingLegionellaspecies. KKL-35 remains equally active againstL. pneumophilamutants that have evolved resistance to macrolides. KKL-35 inhibits multiplication ofL. pneumophilain human macrophages at several stages of infection. No resistant mutants could be obtained, even during extended and chronic exposure. Surprisingly, KKL-35 is not synergistic with other ribosome-targeting antibiotics and does not induce the filamentation phenotype observed in cells defective for trans-translation. Importantly, KKL-35 remains active againstL. pneumophilamutants expressing an alternate ribosome-rescue system and lacking tmRNA, the essential component of trans-translation. These results indicate that the antibiotic activity of KKL-35 is not related to the specific inhibition of trans-translation and its mode of action remains to be identified. In conclusion, KKL-35 is an effective antibacterial agent against the intracellular pathogenL. pneumophilaand with no detectable resistance. However, further studies are needed to better understand its mechanism of action and to assess further the potential of oxadiazoles in treatment.
Gene expression variability across cells and species shapes innate immunity
Authors: Hagai Tzachi , Chen Xi , Miragaia Ricardo J , Gomes Tomás , Rostom Raghd , Kunowska Natalia , Proserpio Valentina , Donati Giacomo , Bossini-Castillo Lara , Naamati Guy , Emerton Guy , Trynka Gosia , Kondova Ivanela , Denis Mike , Teichmann Sarah A 
Published: May 2017

SummaryAs the first line of defence against pathogens, cells mount an innate immune response, which is highly variable from cell to cell. The response must be potent yet carefully controlled to avoid self-damage. How these constraints have shaped the evolution of innate immunity remains poorly understood. Here, we characterise this programme’s transcriptional divergence between species and expression variability across cells. Using bulk and single-cell transcriptomics in primate and rodent fibroblasts challenged with an immune stimulus, we reveal a striking architecture of the innate immune response. Rapidly diverging genes, including cytokines and chemokines, also vary across cells and have distinct promoter structures. Conversely, genes involved in response regulation, such as transcription factors and kinases, are conserved between species and display low cell-to-cell variability. We suggest that this unique expression pattern, observed across species and conditions, has evolved as a mechanism for fine-tuned regulation, to achieve an effective but balanced response.
High-quality rice RNA-seq-based co-expression network for predicting gene function and regulation
Authors: Yu Hua , Jiao Bingke , Liang Chengzhi 
Published: May 2017

AbstractInferring the genome-scale gene co-expression network is important for understanding genetic architecture underlying the complex and various biological phenotypes. The recent availability of large-scale RNA-seq sequencing-data provides great potential for co-expression network inference. In this study, for the first time, we presented a novel heterogeneous ensemble pipeline integrating three frequently used inference methods, to build a high-quality RNA-seq-based Gene Co-expression Network (GCN) in rice, an important monocot species. The quality of the network obtained by our proposed method was first evaluated and verified with the curated positive and negative gene functional link datasets, which obviously outperformed each single method. Secondly, the powerful capability of this network for associating unknown genes with biological functions and agronomic traits was showed by enrichment analysis and case studies. Particularly, we demonstrated the potential applications of our proposed method to predict the biological roles of long non-coding RNA (lncRNA) and circular RNA (circRNA) genes. Our results provided a valuable data source for selecting candidate genes to further experimental validation during rice genetics research and breeding. To enhance identification of novel genes regulating important biological processes and agronomic traits in rice and other crop species, we released the source code of constructing high-quality RNA-seq-based GCN and rice RNA-seq-based GCN, which can be freely downloaded online athttps://github.com/czllab/NetMiner.
Predicting drug resistance evolution: insights from antimicrobial peptides and antibiotics
Authors: Yu Guozhi , Baeder Desiree Y , Regoes Roland R , Rolff Jens 
Published: May 2017

AbstractAntibiotic resistance constitutes one of the most pressing public health concerns. Antimicrobial peptides of multicellular organisms are considered part of a solution to this problem, and AMPs produced by bacteria such as colistin are last resort drugs. Importantly, antimicrobial peptides differ from many antibiotics in their pharmacodynamic characteristics. Here we implement these differences within a theoretical framework to predict the evolution of resistance against antimicrobial peptides and compare it to antibiotic resistance. Our analysis of resistance evolution finds that pharmacodynamic differences all combine to produce a much lower probability that resistance will evolve against antimicrobial peptides. The finding can be generalized to all drugs with pharmacodynamics similar to AMPs. Pharmacodynamic concepts are familiar to most practitioners of medical microbiology, and data can be easily obtained for any drug or drug combination. Our theoretical and conceptual framework is therefore widely applicable and can help avoid resistance evolution if implemented in antibiotic stewardship schemes or the rational choice of new drug candidates.
Mitochondrial genetic effects on reproductive success: signatures of positive intra-sexual, but negative inter-sexual pleiotropy
Authors: Camus M. Florencia , Dowling Damian K. 
Published: May 2017

AbstractMitochondria contain their own DNA, and numerous studies have reported that genetic variation in this (mt)DNA sequence modifies the expression of life-history phenotypes. Maternal inheritance of mitochondria adds a layer of complexity to trajectories of mtDNA evolution, because theory predicts the accumulation of mtDNA mutations that are male-biased in effect. While it is clear that mitochondrial genomes routinely harbor genetic variation that affects components of reproductive performance, the extent to which this variation is sex-biased, or even sex-specific in effect, remains elusive. This is because nearly all previous studies have failed to examine mitochondrial genetic effects on both male and female reproductive performance within the one-and-the-same study. Here, we show that variation across naturally-occurring mitochondrial haplotypes affects components of reproductive success in both sexes, inDrosophila melanogaster. However, while we uncovered evidence for positive pleiotropy, across haplotypes, in effects on separate components of reproductive success when measured within the same sex, such patterns were not evident across sexes. Rather, we found a pattern of sexual antagonism across haplotypes on some reproductive parameters. This suggests the pool of polymorphisms that delineate global mtDNA haplotypes is likely to have been partly shaped by maternal transmission of mtDNA and its evolutionary consequences.
Disaster recovery planning and business continuity for informaticians
Authors: Cervone H. Frank 
Published: May 2017

Purpose
The purpose of this paper is to address the problems associated with informatics and analytics projects that are developed in an “organic” manner. As such, this often circumvents formal project management principles and practices. The decision to do this is determined by organizational factors; however, even in an informal environment, ensuring that adequate disaster recovery and business continuity plans are in place for all mission-critical applications is vital to ensure the long-term survival prospects of an organization in the event of a disaster.

Design/methodology/approach
By adapting the principles and techniques of traditional disaster recovery and business continuity planning, an informatician can develop plans that integrate the requirements of their projects into a larger, organization-wide plan to recover from incidents and ensure continuity of business operations.

Findings
The use of disaster recovery planning and business continuity planning can help ensure the long-term viability of informatics and analytics projects within an organization.

Originality/value
Most business continuity planning is focused on projects that are formally developed and relatively large in scale. This paper applies these principles and practices to informatics and analytics projects that are developed informally and managed casually. Thorough an example, the point that more traditional disaster recovery and continuity practices can and should be applied in this less-formal environment is demonstrated.
Cultivate, assess, advocate, implement, and sustain
Authors: Mannheimer Sara , Cote Conor 
Published: May 2017

Purpose
For libraries with limited resources, digital preservation can seem like a daunting responsibility. Forming partnerships can help build collective knowledge and maximize combined resources to achieve digital preservation goals. This paper aims to provide guidance to help libraries with limited resources achieve digital preservation goals by forming partnerships to build collective knowledge and maximize combined resources.

Design/methodology/approach
In 2015, librarians from four Montana institutions formed the Digital Preservation Working Group (DPWG), a collaboration to increase digital preservation efforts statewide. The group’s immediate goals were to promote digital preservation best-practices at each individual institution, and to learn about and support each other’s work. The group’s long-term goal was to implement a shared digital preservation service that would fill gaps in existing digital preservation efforts.

Findings
Beyond the cost savings gained by sharing a digital preservation service, the members of DPWG benefitted from shared knowledge and expertise gained during the partnership. The group also functioned as a sounding board as each institution built its digital preservation program, and it became a system of support when challenges arose.

Practical/implications
This paper proposes a five-point plan for creating digital preservation partnerships: cultivate a foundation of knowledge and identify a shared vision; assess the current digital preservation landscape at each institution; advocate for the value of digital preservation activities; implement shared digital preservation services; and sustain group activities and establish structures for ongoing support.

Originality/value
The activities of DPWG provide a model for institutions seeking to collaborate to meet digital preservation challenges. This paper shows that by implementing a structured plan, institutions can build and sustain digital preservation partnerships, thus positioning themselves to achieve digital preservation success.
Finding access and digital preservation solutions for a digitized oral history project
Authors: Matusiak Krystyna K. , Tyler Allison , Newton Catherine , Polepeddi Padma 
Published: May 2017

PurposeThe purpose of this paper is to examine affordable access and digital preservation solutions for digital collections developed by under-resourced small- and mid-sized cultural heritage organizations.Design/methodology/approachThe paper presents a case study ofJeffco Stories, a collection of digitized oral histories created by the Jefferson County Public Library in Colorado.FindingsThis paper describes how the Jefferson County Public Library undertook a migration project of its oral history digital collection into an open-access platform, Omeka, and selected DuraCloud as a hosted digital preservation service.Research limitations/implicationsAs a case study, this paper is limited to one institution’s experience with selecting access and digital preservation solutions.Practical/implicationsThis paper is relevant to librarians and archivists who are exploring access and preservation solutions for digital collections and to those who are considering migrating to open-access content management systems and cloud-based digital preservation solutions.Originality/valueThis paper presents a case of a public library and the challenges in finding affordable access and digital preservation solutions for small digital collections.
Rethinking digital preservation: definitions, models, and requirements
Authors: Wilson Thomas C. 
Published: May 2017

Purpose
This paper aims to clarify a mechanism for determining the robustness of digital preservation options given that the field has matured and contains a number of alternatives.

Design/methodology/approach
By examining the component activities of digital preservation, the open archival information system (OAIS) reference model and the trustworthy repository certification process, this paper outlines a possible new model for evaluating the caliber of any particular digital preservation mechanism.

Findings
This paper offers a more ordered and prescriptive model for evaluating digital preservation efforts.

Research limitations/implications
As a review of the OAIS reference model is underway, this paper seeks to contribute to that ongoing discussion to address several issues lacking in the current model and its effect on the certification process.

Originality/value
This paper identifies weaknesses in current practices and offers a model for addressing them.
veraPDF: building an open source, industry supported PDF/A validator for cultural heritage institutions
Authors: Wilson Carl , McGuinness Rebecca , Jung Joachim 
Published: May 2017

Purpose
This paper describes the development of the veraPDF validator. The objective of veraPDF is to build an industry supported, open source validator for all parts and conformance levels of the PDF/A specification for archival PDF documents. The project is led by the Open Preservation Foundation and the PDF Association and is funded by the EU PREFORMA project.

Design/methodology/approach
veraPDF is designed to meet the needs of the digital preservation community and the PDF industry alike. The technology is subject to the review of and acceptance by the PDF Association’s PDF Validation Technical Working Group, including many participants of the relevant ISO working groups. Cultural heritage institutions are collecting ever-increasing volumes of digital information, which they have a mandate to preserve for the long term. However, in many cases, they need to ensure their content has been produced to the specifications of a standard file format, as well as any acceptance criteria stated in their institutional policy.

Findings
With increasing knowledge and experience of processes and policies, cultural heritage institutions are influencing the production and development of digital preservation software. The product development funded by the PREFORMA project shows how such cooperation can benefit the community as a whole.

Originality/value
This paper describes the value of an open source approach to developing a PDF/A validator for cultural heritage organisations.