User-centred design of flexible hypermedia for a mobile guide: Reflections on the hyperaudio experience

A user-centred design approach involves end-users from the very beginning. Considering users at the early stages compels designers to think in terms of utility and usability and helps develop the system on what is actually needed. This paper discusses the case of HyperAudio, a context-sensitive adaptive and mobile guide to museums developed in the late 90s. User requirements were collected via a survey to understand visitors’ profiles and visit styles in Natural Science museums. The knowledge acquired supported the specification of system requirements, helping defining user model, data structure and adaptive behaviour of the system. User requirements guided the design decisions on what could be implemented by using simple adaptable triggers and what instead needed more sophisticated adaptive techniques, a fundamental choice when all the computation must be done on a PDA. Graphical and interactive environments for developing and testing complex adaptive systems are discussed as a further step towards an iterative design that considers the user interaction a central point. The paper discusses how such an environment allows designers and developers to experiment with different system’s behaviours and to widely test it under realistic conditions by simulation of the actual context evolving over time. The understanding gained in HyperAudio is then considered in the perspective of the developments that followed that first experience: our findings seem still valid despite the passed time

Characteristics of de novo structural changes in the human genome

Small insertions and deletions (indels) and large structural variations (SVs) are major contributors to human genetic diversity and disease. However, mutation rates and characteristics of de novo indels and SVs in the general population have remained largely unexplored. We report 332 validated de novo structural changes identified in whole genomes of 250 families, including complex indels, retrotransposon insertions, and interchromosomal events. These data indicate a mutation rate of 2.94 indels (1–20 bp) and 0.16 SVs (>20 bp) per generation. De novo structural changes affect on average 4.1 kbp of genomic sequence and 29 coding bases per generation, which is 91 and 52 times more nucleotides than de novo substitutions, respectively. This contrasts with the equal genomic footprint of inherited SVs and substitutions. An excess of structural changes originated on paternal haplotypes. Additionally, we observed a nonuniform distribution of de novo SVs across offspring. These results reveal the importance of different mutational mechanisms to changes in human genome structure across generations

Anti-α-enolase Antibodies in Serum from Pediatric Patients Affected by Inflammatory Diseases: Diagnostic and Pathogenetic Insights

Human glycolytic enzyme α-enolase was associated with human diseases and with inflammation. An ELISA test was developed to measure anti-α-enolase AAE IgG and AAE IgA in the serum from patients affected by inflammatory diseases with the purpose to evaluate it as a novel diagnostic marker. 80 healthy blood donors and 194 paediatric patients affected by Juvenile idiopathic arthritis (JIA), celiac disease (CD), Crohn's Disease (CrD), hereditary periodic fever (HPF), and PFAPA syndrome were included in the study. HPF patients showed high levels of AAE antibodies, whereas JIA, CD, and CrD presented only partial results. Benign fevers such as PFAPA were almost negative for AAE Abs. These findings suggested that the genetic dysfunction of inflammasome associated with HPF could lead to the formation of AAE Abs that could be used for an early and easy diagnosis

Remarks on Limits on String Scale from Proton Decay and Low-Energy amplitudes in Braneworld Scenario

We discuss IR limit of four-fermion scattering amplitudes in braneworld models including intersecting-branes and SUSY SU(5) GUT version of it. With certain compactification where instanton effect is negligible, grand unification condition in D6-D6 intersecting-branes scenario subject to experimental constraint on proton decay provides possibility for upper limit on the string scale, $M_S$, through relationship between the string coupling, $g_s$, and the string scale. We discuss how IR divergence is related to number of twisted fields we have to introduce into intersection region and how it can change IR behaviour of tree-level amplitudes in various intersecting-branes models. Using number of twisted fields, we identify some intersecting-branes models whose tree-level amplitudes are purely stringy in nature and automatically proportional to $g_s/M^2_{S}$ at low energy. They are consequently suppressed by the string scale. For comparison, we also derive limit on the lower bound of the string scale from experimental constraint on proton decay induced from purely stringy contribution in the coincident-branes model, the limit is about $10^5$ TeV.Comment: 14 page

A global perspective on marine photosynthetic picoeukaryote community structure

A central goal in ecology is to understand the factors affecting the temporal dynamics and spatial distribution of microorganisms and the underlying processes causing differences in community structure and composition. However, little is known in this respect for photosynthetic picoeukaryotes (PPEs), algae that are now recognised as major players in marine CO2 fixation. Here, we analysed dot blot hybridisation and cloning–sequencing data, using the plastid-encoded 16S rRNA gene, from seven research cruises that encompassed all four ocean biomes. We provide insights into global abundance, α- and β-diversity distribution and the environmental factors shaping PPE community structure and composition. At the class level, the most commonly encountered PPEs were Prymnesiophyceae and Chrysophyceae. These taxa displayed complementary distribution patterns, with peak abundances of Prymnesiophyceae and Chrysophyceae in waters of high (25:1) or low (12:1) nitrogen:phosphorus (N:P) ratio, respectively. Significant differences in phylogenetic composition of PPEs were demonstrated for higher taxonomic levels between ocean basins, using Unifrac analyses of clone library sequence data. Differences in composition were generally greater between basins (interbasins) than within a basin (intrabasin). These differences were primarily linked to taxonomic variation in the composition of Prymnesiophyceae and Prasinophyceae whereas Chrysophyceae were phylogenetically similar in all libraries. These data provide better knowledge of PPE community structure across the world ocean and are crucial in assessing their evolution and contribution to CO2 fixation, especially in the context of global climate change

Improved imputation quality of low-frequency and rare variants in European samples using the ‘Genome of The Netherlands’

Although genome-wide association studies (GWAS) have identified many common variants associated with complex traits, low-frequency and rare variants have not been interrogated in a comprehensive manner. Imputation from dense reference panels, such as the 1000 Genomes Project (1000G), enables testing of ungenotyped variants for association. Here we present the results of imputation using a large, new population-specific panel: the Genome of The Netherlands (GoNL). We benchmarked the performance of the 1000G and GoNL reference sets by comparing imputation genotypes with ‘true’ genotypes typed on ImmunoChip in three European populations (Dutch, British, and Italian). GoNL showed s

230 Th normalization: new insights on an essential tool for quantifying sedimentary fluxes in the modern and quaternary ocean

© The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Costa, K. M., Hayes, C. T., Anderson, R. F., Pavia, F. J., Bausch, A., Deng, F., Dutay, J., Geibert, W., Heinze, C., Henderson, G., Hillaire-Marcel, C., Hoffmann, S., Jaccard, S. L., Jacobel, A. W., Kienast, S. S., Kipp, L., Lerner, P., Lippold, J., Lund, D., Marcantonio, F., McGee, D., McManus, J. F., Mekik, F., Middleton, J. L., Missiaen, L., Not, C., Pichat, S., Robinson, L. F., Rowland, G. H., Roy-Barman, M., Alessandro, Torfstein, A., Winckler, G., & Zhou, Y. 230 Th normalization: new insights on an essential tool for quantifying sedimentary fluxes in the modern and quaternary ocean. Paleoceanography and Paleoclimatology, 35(2), (2020): e2019PA003820, doi:10.1029/2019PA003820.230Th normalization is a valuable paleoceanographic tool for reconstructing high‐resolution sediment fluxes during the late Pleistocene (last ~500,000 years). As its application has expanded to ever more diverse marine environments, the nuances of 230Th systematics, with regard to particle type, particle size, lateral advective/diffusive redistribution, and other processes, have emerged. We synthesized over 1000 sedimentary records of 230Th from across the global ocean at two time slices, the late Holocene (0–5,000 years ago, or 0–5 ka) and the Last Glacial Maximum (18.5–23.5 ka), and investigated the spatial structure of 230Th‐normalized mass fluxes. On a global scale, sedimentary mass fluxes were significantly higher during the Last Glacial Maximum (1.79–2.17 g/cm2kyr, 95% confidence) relative to the Holocene (1.48–1.68 g/cm2kyr, 95% confidence). We then examined the potential confounding influences of boundary scavenging, nepheloid layers, hydrothermal scavenging, size‐dependent sediment fractionation, and carbonate dissolution on the efficacy of 230Th as a constant flux proxy. Anomalous 230Th behavior is sometimes observed proximal to hydrothermal ridges and in continental margins where high particle fluxes and steep continental slopes can lead to the combined effects of boundary scavenging and nepheloid interference. Notwithstanding these limitations, we found that 230Th normalization is a robust tool for determining sediment mass accumulation rates in the majority of pelagic marine settings (>1,000 m water depth).We thank Zanna Chase and one anonymous reviewer for valuable feedback. K. M. C. was supported by a Postdoctoral Scholarship at WHOI. L. M. acknowledges funding from the Australian Research Council grant DP180100048. The contribution of C. T. H., J. F. M., and R. F. A. were supported in part by the U.S. National Science Foundation (US‐NSF). G. H. R. was supported by the Natural Environment Research Council (grant NE/L002434/1). S. L. J. acknowledges support from the Swiss National Science Foundation (grants PP002P2_144811 and PP00P2_172915). This study was supported by the Past Global Changes (PAGES) project, which in turn received support from the Swiss Academy of Sciences and the US‐NSF. This work grew out of a 2018 workshop in Aix‐Marseille, France, funded by PAGES, GEOTRACES, SCOR, US‐NSF, Aix‐Marseille Université, and John Cantle Scientific. All data are publicly available as supporting information to this document and on the National Center for Environmental Information (NCEI) at https://www.ncdc.noaa.gov/paleo/study/28791

Population-specific genotype imputations using minimac or IMPUTE2

In order to meaningfully analyze common and rare genetic variants, results from genome-wide association studies (GWASs) of multiple cohorts need to be combined in a meta-analysis in order to obtain enough power. This requires all cohorts to have the same single-nucleotide polymorphisms (SNPs) in their GWASs. To this end, genotypes that have not been measured in a given cohort can be imputed on the basis of a set of reference haplotypes. This protocol provides guidelines for performing imputations

VITALAS at TRECVID-2009

This paper describes the participation of VITALAS in the TRECVID-2009 evaluation where we submitted runs for the High-Level Feature Extraction (HLFE) and Interactive Search tasks. For the HLFE task, we focus on the evaluation of low-level feature sets and fusion methods. The runs employ multiple low-level features based on all available modalities (visual, audio and text) and the results show that use of such features improves the retrieval eectiveness signicantly. We also use a concept score fusion approach that achieves good results with reduced low-level feature vector dimensionality. Furthermore, a weighting scheme is introduced for cluster assignment in the \bag-of-words" approach. Our runs achieved good performance compared to a baseline run and the submissions of other TRECVID-2009 participants. For the Interactive Search task, we focus on the evaluation of the integrated VITALAS system in order to gain insights into the use and eectiveness of the system's search functionalities on (the combination of) multiple modalities and study the behavior of two user groups: professional archivists and non-professional users. Our analysis indicates that both user groups submit about the same total number of queries and use the search functionalities in a similar way, but professional users save twice as many shots and examine shots deeper in the ranked retrieved list.The agreement between the TRECVID assessors and our users was quite low. In terms of the eectiveness of the dierent search modalities, similarity searches retrieve on average twice as many relevant shots as keyword searches, fused searches three times as many, while concept searches retrieve even up to ve times as many relevant shots, indicating the benets of the use of robust concept detectors in multimodal video retrieval. High-Level Feature Extraction Runs 1. A VITALAS.CERTH-ITI 1: Early fusion of all available low-level features. 2. A VITALAS.CERTH-ITI 2: Concept score fusion for ve low-level features and 100 concepts, text features and bag-of-words with color SIFT descriptor based on dense sampling. 3. A VITALAS.CERTH-ITI 3: Concept score fusion for ve low-level features and 100 concepts combined with text features. 4. A VITALAS.CERTH-ITI 4: Weighting scheme for bag-of-words based on dense sampling of the color SIFT descriptor. 5. A VITALAS.CERTH-ITI 5: Baseline run, bag-of-words based on dense sampling of the color SIFT descriptor. Interactive Search Runs 1. vitalas 1: Interactive run by professional archivists 2. vitalas 2: Interactive run by professional archivists 3. vitalas 3: Interactive run by non-professional users 4. vitalas 4: Interactive run by non-professional user

Combined Analysis of Methylation and Gene Expression Profiles in Separate Compartments of Small Bowel Mucosa Identified Celiac Disease Patients' Signatures

By GWAS studies on celiac disease, gene expression was studied at the level of the whole intestinal mucosa, composed by two different compartments: epithelium and lamina propria. Our aim is to analyse the gene-expression and DNA methylation of candidate genes in each of these compartments. Epithelium was separated from lamina propria in biopsies of CeD patients and CTRs using magnetic beads. Gene-expression was analysed by RT-PC; methylation analysis required bisulfite conversion and NGS. Reverse modulation of gene-expression and methylation in the same cellular compartment was observed for the IL21 and SH2B3 genes in CeD patients relative to CTRs. Bioinformatics analysis highlighted the regulatory elements in the genomic region of SH2B3 that altered methylation levels. The cREL and TNFAIP3 genes showed methylation patterns that were significantly different between CeD patients and CTRs. In CeD, the genes linked to inflammatory processes are up-regulated, whereas the genes involved in the cell adhesion/ integrity of the intestinal barrier are down-regulated. These findings suggest a correlation between gene-expression and methylation profile for the IL21 and SH2B3 genes. We identified a "gene-expression phenotype" of CeD and showed that the abnormal response to dietary antigens in CeD might be related not to abnormalities of gene structure but to the regulation of molecular pathways.This work was funded by the FC-Grant2013. Programma di mobilita nell'ambito delle reti di eccellenza POR Campania FSE 2007-2013 Asse V. The authors thank the European Laboratory for Food-induced Disease (ELFID). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript