Preparing DARIAH

In this paper, a preparatory project for an integrated European research infrastructure in the humanities is presented. This project, Preparing for the construction of the Digital Research Infrastructure for the Arts and Humanities - or Preparing DARIAH for short, is part of the ESFRI e-infrastructures programme and supports the emergence of a new collaborative framework in which researchers are able to maximise the impact of their work on the international stage and aims at providing the foundations for the timely construction of the infrastructure requisite for the arts, humanities and cultural heritage communities in the digital age. DARIAH uses an interdisciplinary approach and involves tackling a number of interrelated issues such as strategic, organisational, financial, technical and conceptual in order to facilitate long-term access to and use of all European humanities and cultural heritage information for the purposes of enhancing and expanding research, thereby increasing our knowledge and understanding of our histories, heritage, languages and cultures. The DARIAH network will act as a place where the incubation of new ideas and ways of working can be facilitated and developed, and then transitioned into established organisations thus ensuring long-term sustainability and stability and the integration of these methods and techniques into everyday research practice. DARIAH will support research practitioners at all stages in the research process, and at differing levels of sophistication, from beginners through to those employing advanced techniques and methodologies

Selective CO₂ capture in metal-organic frameworks with azine-functionalized pores generated by mechanosynthesis

Two new three-dimensional porous Zn(II)-based metal-organic frameworks, containing azine-functionalized pores, have been readily and quickly isolated via mechanosynthesis, by using a nonlinear dicarboxylate and linear N-donor ligands. The use of nonfunctionalized and methyl-functionalized N-donor ligands has led to the formation of frameworks with different topologies and metal-ligand connectivities and therefore different pore sizes and accessible volumes. Despite this, both metal-organic frameworks (MOFs) possess comparable BET surface areas and CO₂ uptakes at 273 and 298 K at 1 bar. The network with narrow and interconnected pores in three dimensions shows greater affinity for CO compared to the network with one-dimensional and relatively large pores-attributable to the more effective interactions with the azine groups

Immunological Outcomes of Allergen-Specific Immunotherapy in Food Allergy

IgE-mediated food allergies are caused by adverse immunologic responses to food proteins. Allergic reactions may present locally in different tissues such as skin, gastrointestinal and respiratory tract and may result is systemic life-threatening reactions. During the last decades, the prevalence of food allergies has significantly increased throughout the world, and considerable efforts have been made to develop curative therapies. Food allergen immunotherapy is a promising therapeutic approach for food allergies that is based on the administration of increasing doses of culprit food extracts, or purified, and sometime modified food allergens. Different routes of administration for food allergen immunotherapy including oral, sublingual, epicutaneous and subcutaneous regimens are being evaluated. Although a wealth of data from clinical food allergen immunotherapy trials has been obtained, a lack of consistency in assessed clinical and immunological outcome measures presents a major hurdle for evaluating these new treatments. Coordinated efforts are needed to establish standardized outcome measures to be applied in food allergy immunotherapy studies, allowing for better harmonization of data and setting the standards for the future research. Several immunological parameters have been measured in food allergen immunotherapy, including allergen-specific immunoglobulin levels, basophil activation, cytokines, and other soluble biomarkers, T cell and B cell responses and skin prick tests. In this review we discuss different immunological parameters and assess their applicability as potential outcome measures for food allergen immunotherapy that may be included in such a standardized set of outcome measures

The influence of haemoglobin and iron on in vitro mycobacterial growth inhibition assays.

The current vaccine against tuberculosis, live attenuated Mycobacterium bovis BCG, has variable efficacy, but development of an effective alternative is severely hampered by the lack of an immune correlate of protection. There has been a recent resurgence of interest in functional in vitro mycobacterial growth inhibition assays (MGIAs), which provide a measure of a range of different immune mechanisms and their interactions. We identified a positive correlation between mean corpuscular haemoglobin and in vitro growth of BCG in whole blood from healthy UK human volunteers. Mycobacterial growth in peripheral blood mononuclear cells (PBMC) from both humans and macaques was increased following the experimental addition of haemoglobin (Hb) or ferric iron, and reduced following addition of the iron chelator deferoxamine (DFO). Expression of Hb genes correlated positively with mycobacterial growth in whole blood from UK/Asian adults and, to a lesser extent, in PBMC from South African infants. Taken together our data indicate an association between Hb/iron levels and BCG growth in vitro, which may in part explain differences in findings between whole blood and PBMC MGIAs and should be considered when using such assays

A LOFAR prompt search for radio emission accompanying X-ray flares in GRB 210112A

© The Author(s) 2023. Published by Oxford University Press on behalf of Royal Astronomical Society. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/).The composition of relativistic gamma-ray burst (GRB) jets and their emission mechanisms are still debated, and they could be matter or magnetically dominated. One way to distinguish these mechanisms arises because a Poynting flux dominated jet may produce low-frequency radio emission during the energetic prompt phase, through magnetic reconnection at the shock front. We present a search for radio emission coincident with three GRB X-ray flares with the LOw Frequency ARray (LOFAR), in a rapid response mode follow-up of long GRB 210112A (at z~2) with a 2 hour duration, where our observations began 511 seconds after the initial swift-BAT trigger. Using timesliced imaging at 120-168 MHz, we obtain upper limits at 3 sigma confidence of 42 mJy averaging over 320 second snapshot images, and 87 mJy averaging over 60 second snapshot images. LOFAR's fast response time means that all three potential radio counterparts to X-ray flares are observable after accounting for dispersion at the estimated source redshift. Furthermore, the radio pulse in the magnetic wind model was expected to be detectable at our observing frequency and flux density limits which allows us to disfavour a region of parameter space for this GRB. However, we note that stricter constraints on redshift and the fraction of energy in the magnetic field are required to further test jet characteristics across the GRB population.Peer reviewe

HIV-1 Infection in Cyprus, the Eastern Mediterranean European Frontier: A Densely Sampled Transmission Dynamics Analysis from 1986 to 2012

Since HIV-1 treatment is increasingly considered an effective preventionstrategy, it is important to study local HIV-1 epidemics to formulate tailored preventionpolicies. The prevalence of HIV-1 in Cyprus was historically low until 2005. To investigatethe shift in epidemiological trends, we studied the transmission dynamics of HIV-1 in Cyprususing a densely sampled Cypriot HIV-1 transmission cohort that included 85 percent ofHIV-1-infected individuals linked to clinical care between 1986 and 2012 based on detailedclinical, epidemiological, behavioral and HIV-1 genetic information. Subtyping andtransmission cluster reconstruction were performed using maximum likelihood and Bayesianmethods, and the transmission chain network was linked to the clinical, epidemiological andbehavioral data. The results reveal that for the main HIV-1 subtype A1 and B sub-epidemics,young and drug-naïve HIV-1-infected individuals in Cyprus are driving the dynamics of thelocal HIV-1 epidemic. The results of this study provide a better understanding of thedynamics of the HIV-1 infection in Cyprus, which may impact the development of preventionstrategies. Furthermore, this methodology for analyzing densely sampled transmissiondynamics is applicable to other geographic regions to implement effective HIV-1 preventionstrategies in local settings

Immune-Complex Mimics as a Molecular Platform for Adjuvant-Free Vaccine Delivery

Protein-based vaccine development faces the difficult challenge of finding robust yet non-toxic adjuvants suitable for humans. Here, using a molecular engineering approach, we have developed a molecular platform for generating self-adjuvanting immunogens that do not depend on exogenous adjuvants for induction of immune responses. These are based on the concept of Immune Complex Mimics (ICM), structures that are formed between an oligomeric antigen and a monoclonal antibody (mAb) to that antigen. In this way, the roles of antigens and antibodies within the structure of immune complexes are reversed, so that a single monoclonal antibody, rather than polyclonal sera or expensive mAb cocktails can be used. We tested this approach in the context of Mycobacterium tuberculosis (MTB) infection by linking the highly immunogenic and potentially protective Ag85B with the oligomeric Acr (alpha crystallin, HspX) antigen. When combined with an anti-Acr monoclonal antibody, the fusion protein formed ICM which bound to C1q component of the complement system and were readily taken up by antigen-presenting cells in vitro. ICM induced a strong Th1/Th2 mixed type antibody response, which was comparable to cholera toxin adjuvanted antigen, but only moderate levels of T cell proliferation and IFN-γ secretion. Unfortunately, the systemic administration of ICM did not confer statistically significant protection against intranasal MTB challenge, although a small BCG-boosting effect was observed. We conclude that ICM are capable of inducing strong humoral responses to incorporated antigens and may be a suitable vaccination approach for pathogens other than MTB, where antibody-based immunity may play a more protective role

HIV-1 Infection in Cyprus, the Eastern Mediterranean European Frontier: A Densely Sampled Transmission Dynamics Analysis from 1986 to 2012

Since HIV-1 treatment is increasingly considered an effective preventionstrategy, it is important to study local HIV-1 epidemics to formulate tailored preventionpolicies. The prevalence of HIV-1 in Cyprus was historically low until 2005. To investigatethe shift in epidemiological trends, we studied the transmission dynamics of HIV-1 in Cyprususing a densely sampled Cypriot HIV-1 transmission cohort that included 85 percent ofHIV-1-infected individuals linked to clinical care between 1986 and 2012 based on detailedclinical, epidemiological, behavioral and HIV-1 genetic information. Subtyping andtransmission cluster reconstruction were performed using maximum likelihood and Bayesianmethods, and the transmission chain network was linked to the clinical, epidemiological andbehavioral data. The results reveal that for the main HIV-1 subtype A1 and B sub-epidemics,young and drug-naïve HIV-1-infected individuals in Cyprus are driving the dynamics of thelocal HIV-1 epidemic. The results of this study provide a better understanding of thedynamics of the HIV-1 infection in Cyprus, which may impact the development of preventionstrategies. Furthermore, this methodology for analyzing densely sampled transmissiondynamics is applicable to other geographic regions to implement effective HIV-1 preventionstrategies in local settings