DMRcaller: a versatile R/Bioconductor package for detection and visualization of differentially methylated regions in CpG and non-CpG contexts

DNA methylation has been associated with transcriptional repression and detection of differential methylation is important in understanding the underlying causes of differential gene expression. Bisulfite-converted genomic DNA sequencing is the current gold standard in the field for building genome-wide maps at a base pair resolution of DNA methylation. Here we systematically investigate the underlying features of detecting differential DNA methylation in CpG and non-CpG contexts, considering both the case of mammalian systems and plants. In particular, we introduce DMRcaller, a highly efficient R/Bioconductor package, which implements several methods to detect Differentially Methylated Regions (DMRs) between two samples. Most importantly, we show that different algorithms are required to compute DMRs and the most appropriate algorithm in each case depends on the sequence context and levels of methylation. Furthermore, we show that DMRcaller outperforms other available packages and we propose a new method to select the parameters for this tool and for other available tools. DMRcaller is a comprehensive tool for differential methylation analysis which displays high sensitivity and specificity for the detection of DMRs and performs entire genome wide analysis within a few hours

Tänka,snabbt och långsamt vid bedömning av förmåga

Räddningstjänsten genomför regelbundet förmågebedömning i syfte att möta olika samhällsstörningar. I lagen (2003:778) om skydd mot olyckor (LSO) 1 kap. 3 § fastställs att ”räddningstjänsten skall planeras och organiseras så att räddningsinsatserna kan påbörjas inom godtagbar tid och genomföras på ett effektivt sätt”. Förmågebedömning bör därför genomföras både vid en räddningsinsats, men också vid planering för beredskap eftersom ”räddningstjänsten skall planeras och organiseras”. Detta examensarbete syftar till att undersöka hur beslutsfattarna inom Räddningstjänsten Syd genomför förmågebedömning dels vid en räddningsinsats, dels vid planering för beredskap. Vid en räddningsinsats har beslutsfattarna mindre tid att fatta beslut medan tiden vid planering för beredskap är relativt lång. Intressanta frågeställningar i denna studie är att undersöka hur tidsaspekten påverkar beslutsfattarnas förmågebedömning. Vilka parametrar är viktiga vid en räddningsinsats respektive vid planering för beredskap? Är parametrarna samma i båda fallen? För att kunna besvara frågeställningen genomfördes scoping- och intervjustudie. Scopingstudien bestod av sökning i databasen Scopus, sökning i referenslistor av identifierade publikationer, sökning i grå litteratur samt övrig litteratursökning. En semistrukturerad intervjustudie genomfördes med beslutsfattare inom Räddningstjänsten Syd. Kartläggning av viktiga parametrar kunde sedan jämföras dels vid en räddningsinsats, dels vid planering för beredskap. En del av förmågebedömningen är att fatta beslut om förmåga. Kahneman (2013) beskriver två system för beslutsfattande, System 1 och System 2. System 1 är den snabba beslutsfattarprocessen som sker automatiserat och följer den mänskliga intuitionen medan system 2 är den långsamma tankeverksamheten vilken följs av en ansträngande beslutsfattarprocess. System 1 och System 2 kan integreras i andra beslutsteorier såsom rationellt beslutsfattande och naturalistiskt beslutsfattande. Denna studie visar att en räddningsinsats består av minst två faser, nämligen uppstartsfasen och genomförandefasen. Vid uppstartsfasen verkar beslutsfattarna i högre utsträckning förlita sig på naturalistiskt beslutsfattande dvs. igenkänning genom mental simulering (RPD-modellen). Integrerat inom RPD-modellen kan både System 1 och System 2 användas beroende på uppgiftens komplexitet. Vid genomförandefasen däremot verkar tillvägagångssättet i högre utsträckning vara baserat på System 2, där gruppens åsikter tas i beaktning då beslutsfattarna planerar för uthållighet. Vid planering för beredskap verkar beslutsfattarna i högre utsträckning förlita sig på rationellt beslutsfattande vilken kan betraktas som System 2. Planering för beredskap genomförs både inför varje pass och inför längre tidshorisont där händelser identifieras som kan utgöra ett hot för samhället. Kartläggningen har påvisat att information, planering, gruppen och resurser är samma i båda fallen, dels vid räddningsinsats, dels vid planering för beredskap. Övriga viktiga parametrar som skiljer sig åt i båda fallen identifierades till kommunikation, skadeplatsfaktorer, situationsmedvetenhet, övningar, överblickbarhet, omvärldsbevakning och statistik

Allosteric signalling in the outer membrane translocation domain of PapC usher

PapC ushers are outer-membrane proteins enabling assembly and secretion of P pili in uropathogenic E. coli. Their translocation domain is a large β-barrel occluded by a plug domain, which is displaced to allow the translocation of pilus subunits across the membrane. Previous studies suggested that this gating mechanism is controlled by a β-hairpin and an α-helix. To investigate the role of these elements in allosteric signal communication we developed a method combining evolutionary and molecular dynamics studies of the native translocation domain and mutants lacking the β-hairpin and/or α-helix. Analysis of a hybrid residue interaction network suggests distinct regions (residue 'communities') within the translocation domain (especially around β12-β14) linking these elements, thereby modulating PapC gating. Antibiotic sensitivity and electrophysiology experiments on a set of alanine-substitution mutants confirmed functional roles for four of these communities. This study illuminates the gating mechanism of PapC ushers and its importance in maintaining outer-membrane permeability

Comparison of Quantities of Information in the Human Memory

A mathematical model of changing the amount of information in the abstract human memory is proposed in the presence of the subsequent "external discrete" training (filling the information). Under this model, the amount of information is a solution of impulsive differential equation with fixed moments of impulsive effects and variable structure. Sufficient conditions are proposed related to the moments and magnitudes of  the impulsive effects (i.e., to the moments of discrete training and the volume of the received information), where the quantities of information in two different models of learning can be compared

Marketing Strategies for Promoting Medical Tourism in Thailand / Jutamas Rerkrujipimol and Ilian Assenov

Thailand is considered to be among the global leaders in the medical tourism market which has grown rapidly in recent years but has faced formidable competition from Singapore, India and other countries. This exploratory research was intended to evaluate the current marketing strategies of healthcare providers and intermediaries through interviews with stakeholders and observation, and to propose effective marketing strategies for preserving and enhancing Thailand's position as a leading medical tourism destination. The paper identifies the strengths of Thailand's healthcare service providers and points to a number of problems that may reduce the growth opportunity of this industry. These include lack of practical government policies with regard to medical tourism and of other supporting regulations, lack of organization as a cooperation centre aimed at promoting the medical tourism industry as a whole, remaining low awareness of the opportunities presented by the industry among potentialfbreign patients, and a shortage of doctors and qualified medical staff. Measures for improvement are suggested

Strategies for analyzing bisulfite sequencing data

DNA methylation is one of the main epigenetic modifications in the eukaryotic genome; it has been shown to play a role in cell-type specific regulation of gene expression, and therefore cell-type identity. Bisulfite sequencing is the gold-standard for measuring methylation over the genomes of interest. Here, we review several techniques used for the analysis of high-throughput bisulfite sequencing. We introduce specialized short-read alignment techniques as well as pre/post-alignment quality check methods to ensure data quality. Furthermore, we discuss subsequent analysis steps after alignment. We introduce various differential methylation methods and compare their performance using simulated and real bisulfite sequencing datasets. We also discuss the methods used to segment methylomes in order to pinpoint regulatory regions. We introduce annotation methods that can be used for further classification of regions returned by segmentation and differential methylation methods. Finally, we review software packages that implement strategies to efficiently deal with large bisulfite sequencing datasets locally and we discuss online analysis workflows that do not require any prior programming skills. The analysis strategies described in this review will guide researchers at any level to the best practices of bisulfite sequencing analysis

Strategies for analyzing bisulfite sequencing data

DNA methylation is one of the main epigenetic modifications in the eukaryotic genome and has been shown to play a role in cell-type specific regulation of gene expression, and therefore cell-type identity. Bisulfite sequencing is the gold-standard for measuring methylation over the genomes of interest. Here, we review several techniques used for the analysis of high-throughput bisulfite sequencing. We introduce specialized short-read alignment techniques as well as pre/post-alignment quality check methods to ensure data quality. Furthermore, we discuss subsequent analysis steps after alignment. We introduce various differential methylation methods and compare their performance using simulated and real bisulfite-sequencing datasets. We also discuss the methods used to segment methylomes in order to pinpoint regulatory regions. We introduce annotation methods that can be used further classification of regions returned by segmentation or differential methylation methods. Lastly, we review software packages that implement strategies to efficiently deal with large bisulfite sequencing datasets locally and also discuss online analysis workflows that do not require any prior programming skills. The analysis strategies described in this review will guide researchers at any level to the best practices of bisulfite sequencing analysis

Beach and Coastal Survey of Thailand: What Future for Surf Tourism / Steven Andrew Martin and Ilian Assenov

There are surfers on vacation looking for waves. Surfing and surf tourism run parallel: they are focused upon location-specific destinations where natural resources and phenomena occur conducive to the sport; and travelling for the sake of surfing new places is as old as the sport itself. This research serves to improve the overall understanding of surf tourism in Thailand and to offer recommendations for sustainability and quality of experience. As an investigation, three ideas within the broad environment of Thailand have been rationalized: to survey and assess the coastal resource in order to determine the plausibility and practicability of surf tourism in Thailand (including the discovery and documentation of surf breaks); to interpret the surf tourist characteristics of Phuket, Thailand, through unstructured and semi-structured personal interviews; and to answer the question: "What future for surf tourism in Thailand?" This research has idented and assessed five of Thailand's provincial areas most suited for surf tourism, and has identified that contrary to popular belief there are a large number of areas suitablefor surfing and surf tourism, including those for advanced, intermediate, and beginner surfers. In all, 80 surfing areas were surveyed. A refined Thailand-specific definition for surf tourism is suggested, reflecting the natural environment and the characteristics of the current surf tourists. The paper concludes by identiffing the future prospects, challenges, and related issues for sustainable surf tourism in Thailand