Project Andvari: A Digital Portal to the Visual World of Early Medieval Northern Europe

Project Andvari is designed to provide integrated access to dispersed collections of northern European art and artifacts of the early medieval period (4th-12th centuries). Our goal is to create a digital portal offering aggregated search options and enhanced metadata. Funding is requested to convene an international workshop for humanities scholars, museum professionals, and technology experts to refine the conceptual design of the proposed research tool and identify its technological requirements in preparation for a pilot project. Ultimately, Project Andvari will facilitate interdisciplinary research in art, archaeology, history, and literary and religious studies of the northern periphery of medieval Europe. It will allow users to study visual culture across media and beyond traditional geographical and disciplinary boundaries. Its innovative application of search methods will promote analyses of relationships of artifacts and cultures, and help us discover the hitherto unnoticed

Ubic: Bridging the gap between digital cryptography and the physical world

Advances in computing technology increasingly blur the boundary between the digital domain and the physical world. Although the research community has developed a large number of cryptographic primitives and has demonstrated their usability in all-digital communication, many of them have not yet made their way into the real world due to usability aspects. We aim to make another step towards a tighter integration of digital cryptography into real world interactions. We describe Ubic, a framework that allows users to bridge the gap between digital cryptography and the physical world. Ubic relies on head-mounted displays, like Google Glass, resource-friendly computer vision techniques as well as mathematically sound cryptographic primitives to provide users with better security and privacy guarantees. The framework covers key cryptographic primitives, such as secure identification, document verification using a novel secure physical document format, as well as content hiding. To make a contribution of practical value, we focused on making Ubic as simple, easily deployable, and user friendly as possible.Comment: In ESORICS 2014, volume 8712 of Lecture Notes in Computer Science, pp. 56-75, Wroclaw, Poland, September 7-11, 2014. Springer, Berlin, German

Nanotailoring Stereolithography Resins for Unique Applications using Carbon Nanotubes

Nanostructured materials and exploiting their properties in stereolithography (SL) may open new markets for unique rapidly manufactured functional devices. Controlled amounts of multiwalled carbon nanotubes (MWCNTs) were successfully dispersed in SL epoxy-based resins and complex three-dimensional (3D) parts were successfully fabricated by means of a multi-material SL setup. The effect of the nanosized filler was evaluated using mechanical testing. Small dispersions of MWCNTs resulted in significant effects on the physical properties of the polymerized resin. A MWCNT concentration of .05 wt% (w/v) in DSM Somos® WaterShed™ 11120 resin increased the ultimate tensile stress and fracture stress an average of 17% and 37%, respectively. Electron microscopy was used to examine the morphology of the nanocomposite and results showed affinity between the MWCNTs and SL resin and identified buckled nanotubes that illustrated strong interfacial bonding. These improved physical properties may provide opportunities for using nanocomposite SL resins in end-use applications. Varying types and concentrations of nanomaterials can be used to tailor existing SL resins for particular applications.Mechanical Engineerin

Spatial Bloom Filters: Enabling Privacy in Location-Aware Applications

The wide availability of inexpensive positioning systems made it possible to embed them into smartphones and other personal devices. This marked the beginning of location-aware applications, where users request personalized services based on their geographic position. The location of a user is, however, highly sensitive information: the user's privacy can be preserved if only the minimum amount of information needed to provide the service is disclosed at any time. While some applications, such as navigation systems, are based on the users' movements and therefore require constant tracking, others only require knowledge of the user's position in relation to a set of points or areas of interest. In this paper we focus on the latter kind of services, where location information is essentially used to determine membership in one or more geographic sets. We address this problem using Bloom Filters (BF), a compact data structure for representing sets. In particular, we present an extension of the original Bloom filter idea: the Spatial Bloom Filter (SBF). SBF's are designed to manage spatial and geographical information in a space efficient way, and are well-suited for enabling privacy in location-aware applications. We show this by providing two multi-party protocols for privacy-preserving computation of location information, based on the known homomorphic properties of public key encryption schemes. The protocols keep the user's exact position private, but allow the provider of the service to learn when the user is close to specific points of interest, or inside predefined areas. At the same time, the points and areas of interest remain oblivious to the user

Activity and Process Stability of Purified Green Pepper (Capsicum annuum) Pectin Methylesterase

Pectin methylesterase (PME) from green bell peppers (Capsicum annuum) was extracted and purified by affinity chromatography on a CNBr-Sepharose-PMEI column. A single protein peak with pectin methylesterase activity was observed. For the pepper PME, a biochemical characterization in terms of molar mass (MM), isoelectric points (pI), and kinetic parameters for activity and thermostability was performed. The optimum pH for PME activity at 22 °C was 7.5, and its optimum temperature at neutral pH was between 52.5 and 55.0 °C. The purified pepper PME required the presence of 0.13 M NaCl for optimum activity. Isothermal inactivation of purified pepper PME in 20 mM Tris buffer (pH 7.5) could be described by a fractional conversion model for lower temperatures (55?57 °C) and a biphasic model for higher temperatures (58?70 °C). The enzyme showed a stable behavior toward high-pressure/temperature treatments. Keywords: Capsicum annuum; pepper; pectin methylesterase; purification; characterization; thermal and high-pressure stabilit

Protocol of the adaptive study of IL-2 dose frequency on regulatory T cells in type 1 diabetes (DILfrequency): a mechanistic, non-randomised, repeat dose, open-label, response-adaptive study.

INTRODUCTION: Type 1 diabetes (T1D) is caused by autoimmune destruction of the insulin-producing β cells in the pancreatic islets, leading to insulinopenia and hyperglycaemia. Genetic analyses indicate that alterations of the interleukin-2 (IL-2) pathway mediating immune activation and tolerance predispose to T1D, specifically the polymorphic expression of the IL-2 receptor-α chain (CD25) on T lymphocytes. Replacement of physiological doses of IL-2 could restore self-tolerance and prevent further autoimmunity by enhancing the function of CD4(+) T regulatory cells (Tregs) to limit the activation of auto reactive T effector cells (Teffs). In this experimental medicine study, we use an adaptive trial design to determine the optimal dosing regimen for IL-2 to improve Treg function while limiting activation of Teffs in participants with T1D. METHODS AND ANALYSIS: The Adaptive study of IL-2 dose frequency on Tregs in type 1 diabetes(DILfrequency) is a mechanistic, non-randomised, repeat dose open-label, response-adaptive study of 36 participants with T1D. The objective is to establish the optimal dose and frequency of ultra-low dose IL-2: to increase Treg frequency within the physiological range, to increase CD25 expression on Tregs, without increasing CD4(+) Teffs. DILfrequency has an initial learning phase where 12 participants are allocated to six different doses and frequencies followed by an interim statistical analysis. After analysis of the learning phase, the Dose and Frequency Committee will select the optimal targets for Treg frequency, Treg CD25 expression and Teff frequency. Three groups of eight participants will be treated consecutively in the confirming phase. Each dose and frequency selected will be based on statistical analysis of all data collected from the previous groups. ETHICS: Ethical approval for DILfrequency was granted on 12 August 2014. RESULTS: The results of this study will be reported, through peer-reviewed journals, conference presentations and an internal organisational report. TRIAL REGISTRATION NUMBERS: NCT02265809, ISRCTN40319192, CRN17571.This work is funded by The Sir Jules Thorn Award for Biomedical Research 2013 (13/JTA), the JDRF (9-2011-253), the Wellcome Trust (091157) and the National Institute for Health Research Cambridge Biomedical Research Centre. The Cambridge Institute for Medical Research is in receipt of a Wellcome Trust Strategic Award (100140). AM was supported by the Medical Research Council [grant number G0800860] and the National Institute for Health Research Cambridge Biomedical Research Centre.This is the final version of the article. It was first available from BMJ via http://dx.doi.org/10.1136/bmjopen-2015-00979

Enrichment analysis of Alu elements with different spatial chromatin proximity in the human genome

Transposable elements (TEs) have no longer been totally considered as “junk DNA” for quite a time since the continual discoveries of their multifunctional roles in eukaryote genomes. As one of the most important and abundant TEs that still active in human genome, Alu, a SINE family, has demonstrated its indispensable regulatory functions at sequence level, but its spatial roles are still unclear. Technologies based on 3C(chromosomeconformation capture) have revealed the mysterious three-dimensional structure of chromatin, and make it possible to study the distal chromatin interaction in the genome. To find the role TE playing in distal regulation in human genome, we compiled the new released Hi-C data, TE annotation, histone marker annotations, and the genome-wide methylation data to operate correlation analysis, and found that the density of Alu elements showed a strong positive correlation with the level of chromatin interactions (hESC: r=0.9, P<2.2×1016; IMR90 fibroblasts: r = 0.94, P < 2.2 × 1016) and also have a significant positive correlation withsomeremote functional DNA elements like enhancers and promoters (Enhancer: hESC: r=0.997, P=2.3×10−4; IMR90: r=0.934, P=2×10−2; Promoter: hESC: r = 0.995, P = 3.8 × 10−4; IMR90: r = 0.996, P = 3.2 × 10−4). Further investigation involving GC content and methylation status showed the GC content of Alu covered sequences shared a similar pattern with that of the overall sequence, suggesting that Alu elements also function as the GC nucleotide and CpG site provider. In all, our results suggest that the Alu elements may act as an alternative parameter to evaluate the Hi-C data, which is confirmed by the correlation analysis of Alu elements and histone markers. Moreover, the GC-rich Alu sequence can bring high GC content and methylation flexibility to the regions with more distal chromatin contact, regulating the transcription of tissue-specific genes

IL-21 production by CD4+ effector T cells and frequency of circulating follicular helper T cells are increased in type 1 diabetes patients.

AIMS/HYPOTHESIS: Type 1 diabetes results from the autoimmune destruction of insulin-secreting pancreatic beta cells by T cells. Despite the established role of T cells in the pathogenesis of the disease, to date, with the exception of the identification of islet-specific T effector (Teff) cells, studies have mostly failed to identify reproducible alterations in the frequency or function of T cell subsets in peripheral blood from patients with type 1 diabetes. METHODS: We assessed the production of the proinflammatory cytokines IL-21, IFN-γ and IL-17 in peripheral blood mononuclear cells from 69 patients with type 1 diabetes and 61 healthy donors. In an additional cohort of 30 patients with type 1 diabetes and 32 healthy donors, we assessed the frequency of circulating T follicular helper (Tfh) cells in whole blood. IL-21 and IL-17 production was also measured in peripheral blood mononuclear cells (PBMCs) from a subset of 46 of the 62 donors immunophenotyped for Tfh. RESULTS: We found a 21.9% (95% CI 5.8, 40.2; p = 3.9 × 10(-3)) higher frequency of IL-21(+) CD45RA(-) memory CD4(+) Teffs in patients with type 1 diabetes (geometric mean 5.92% [95% CI 5.44, 6.44]) compared with healthy donors (geometric mean 4.88% [95% CI 4.33, 5.50]). Consistent with this finding, we found a 14.9% increase in circulating Tfh cells in the patients (95% CI 2.9, 26.9; p = 0.016). CONCLUSIONS/INTERPRETATION: These results indicate that increased IL-21 production is likely to be an aetiological factor in the pathogenesis of type 1 diabetes that could be considered as a potential therapeutic target.This work was supported by the JDRF UK Centre for Diabetes - Genes, Autoimmunity and Prevention (D-GAP; 4-2007-1003) in collaboration with M. Peakman and T. Tree at King’s College London, the JDRF, the Wellcome Trust (WT; WT061858/091157 and 083650/Z/07/Z) and the National Institute for Health Research Cambridge Biomedical Research Centre (CBRC). The Cambridge Institute for Medical Research (CIMR) is in receipt of a Wellcome Trust Strategic Award (100140). RCF is funded by a JDRF post-doctoral fellowship (3-2011-374). CW is funded by the Wellcome Trust (088998). The funding organisations had no involvement with the design and conduct of the study; collection,management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript.This is the final published version. It first appeared at http://link.springer.com/article/10.1007%2Fs00125-015-3509-8

Integrating transposable elements in the 3D genome

Chromosome organisation is increasingly recognised as an essential component of genome regulation, cell fate and cell health. Within the realm of transposable elements (TEs) however, the spatial information of how genomes are folded is still only rarely integrated in experimental studies or accounted for in modelling. Whilst polymer physics is recognised as an important tool to understand the mechanisms of genome folding, in this commentary we discuss its potential applicability to aspects of TE biology. Based on recent works on the relationship between genome organisation and TE integration, we argue that existing polymer models may be extended to create a predictive framework for the study of TE integration patterns. We suggest that these models may offer orthogonal and generic insights into the integration profiles (or "topography") of TEs across organisms. In addition, we provide simple polymer physics arguments and preliminary molecular dynamics simulations of TEs inserting into heterogeneously flexible polymers. By considering this simple model, we show how polymer folding and local flexibility may generically affect TE integration patterns. The preliminary discussion reported in this commentary is aimed to lay the foundations for a large-scale analysis of TE integration dynamics and topography as a function of the three-dimensional host genome

Blockade of the Programmed Death-1 (PD1) Pathway Undermines Potent Genetic Protection from Type 1 Diabetes

Aims/Hypothesis Inhibition of PD1-PDL1 signaling in NOD mice accelerates onset of type 1 diabetes implicating this pathway in suppressing the emergence of pancreatic beta cell reactive T-cells. However, the molecular mechanism by which PD1 signaling protects from type 1 diabetes is not clear. We hypothesized that differential susceptibility of Idd mouse strains to type 1 diabetes when challenged with anti PDL1 will identify genomic loci that collaborate with PD1 signaling in suppressing type 1 diabetes. Methods: Anti PDL1 was administered to NOD and various Idd mouse strains at 10 weeks of age and onset of disease was monitored by measuring blood glucose levels. Additionally, histological evaluation of the pancreas was performed to determine degree of insulitis. Statistical analysis of the data was performed using Log-Rank and Student's t-test. Results: Blockade of PDL1 rapidly precipitated type 1 diabetes in nearly all NOD Idd congenic strains tested, despite the fact that all are moderately (Idd5, Idd3 and Idd10/18) or highly (Idd3/10/18 and Idd9) protected from spontaneous type 1 diabetes by virtue of their protective Idd genes. Only the Idd3/5 strain, which is nearly 100% protected from spontaneous disease, remained normoglycemic following PDL1 blockade. Conclusions: These results indicate that multiple Idd loci collaborate with PD1 signaling. Anti PDL1 treatment undermines a large portion of the genetic protection mediated by Idd genes in the NOD model of type 1 diabetes. Basal insulitis correlated with higher susceptibility to type 1 diabetes. These findings have important implications since the PD1 pathway is a target for immunotherapy