The Ongoing Challenge of Hematopoietic Stem Cell-Based Gene Therapy for β-Thalassemia

β-thalassemia is characterized by reduced or absence of β-globin production, resulting in anemia. Current therapies include blood transfusion combined with iron chelation. BM transplantation, although curative, is restricted by the matched donor limitation. Gene therapy, on the other hand, is promising, and its success lies primarily on designing efficient globin vectors that can effectively and stably transduce HSCs. The major breakthrough in β-thalassemia gene therapy occurred a decade ago with the development of globin LVs. Since then, researchers focused on designing efficient and safe vectors, which can successfully deliver the therapeutic transgene, demonstrating no insertional mutagenesis. Furthermore, as human HSCs have intrinsic barriers to HIV-1 infection, attention is drawn towards their ex vivo manipulation, aiming to achieve higher yield of genetically modified HSCs. This paper presents the current status of gene therapy for β-thalassemia, its success and limitations, and the novel promising strategies available involving the therapeutic role of HSCs

Hydrogen-Bonded Networks Based on Cobalt(II), Nickel(II), and Zinc(II) Complexes of N,N'-Diethylurea

N,N'-diethylurea (DEU) was employed as a ligand to form the octahedral complexes [M(DEU)6]2+ (M=Co, Ni and Zn). Compounds [Co(DEU)6](BF4)2 (1), [Co(DEU)6](CIO4)2 (2), [Ni(DEU)6](CIO4)2 (3), and [Zn(DMU)6](CIO4)2 (4) have been prepared from the reactions of DEU and the appropriate hydrated metal(II) salts in EtOH in the presence of 2,2-dimethoxypropane. Crystal structure determinations demonstrate the existence of [M(DEU)6]2+ cations and CIO4− (in 2–4) or BF4− (in 1) counterions. The [M(DEU)6]2+ cations in the solid state are stabilized by a pseudochelate effect due to the existence of six strong intracationic N-H ⋯ O(DEU) hydrogen bonds. The [M(DEU)6]2+ cations and counterions self-assemble to form hydrogen-bonded 2D architectures in 2–4 that conform to the kgd (kagome dual) network, and a 3D hydrogen-bonded rtl (rutile) network in 1. The nature of the resulting supramolecular structures is influenced by the nature of the counter-ion. The complexes were also characterized by vibrational spectroscopy (IR)

Habitus emerging : the development of hybrid logics and collaborative business models in the Irish craft beer sector

This article analyses data from 25 Irish craft beer entrepreneurs supplemented by associated web and press material, to explore how habitus emerges in a nascent entrepreneurial field. Welter's frame of entrepreneurial contexts – business, social, spatial, and institutional – is combined with Bourdieusian theory to explain the emergence of habitus. Findings show that emerging habitus is enacted through hybridization of diverse global and local field logics, via the adoption, development and extension of their logics. It is also path-dependent upon the life and career histories of a critical mass of habitus members, previously exposed to these fields. The study shows both local and global strategies of collective resource sharing - a novel approach to tackling the resource paucity typically faced by partitioned specialists facing large scale generalists

Assessment of the environmental status in Hellenic coastal waters (Eastern Mediterranean): from the Water Framework Directive to the Marine Strategy Water Framework Directive.

A  methodology is presented to assess the environmental status sensu the Marine Strategy Water Framework Directive (MSFD) based on data obtained from the monitoring of water quality in the Hellenic coastal waters within the Water Framework Directive (WFD).   An adapted decision tree used for integrating the results of the WFD in the Basque country was applied. Modifications lie to the evaluation of the physicochemical status based on a eutrophication index developed for Eastern Mediterranean waters. Results on hydromorphological, physicochemical and biological elements are presented. The chemical status was evaluated based on measurements of heavy metals in water. The evaluation of the biological quality was based on the use of metrics developed for phytoplankton biomass, benthic macroinvertebrates and macroalgae updated to accommodate MSFD needs. Results on the integrative status of the water bodies were validated by correlating classification results with a pressure index and environmental indicators in water column and sediment. Following this decision tree the majority of stations expected to be at risk of achieving the good status were found in moderate status. Benthos was found to be the element with the closest agreement with the integrated final status having an increased weighting in the decision tree. The quality of benthos and in some  limited cases  the eutrophication index determined largely the final status. The highest disagreement with the integrative classification was produced by macroalgae. All indicators used correlated with water and sediment parameters but benthos correlated better with sediment factors while phytoplankton and eutrophication index with water column parameters

GEOMORPHOLOGY, SEDIMENTOLOGY AND GEOCHEMISTRY IN THE MARINE AREA BETWEEN SIFNOS AND KIMOLOS ISLANDS, GREECE

Στην ελάχιστα μελετημένη θαλάσσια περιοχή μεταξύ των νησιών Σίφνου και Κιμώλου πραγματοποιήθηκε μια εκτεταμένη ωκεανογραφική μελέτη, με σκοπό την καταγραφή της υποθαλάσσιας μορφολογίας και των χαρακτηριστικών των επιφανειακών ιζημάτων, καθώς και της πηγής προέλευσης αυτών. Έγιναν καταγραφές με πολυδεσμικό βυθόμετρο και δειγματοληψίες επιφανειακών ιζημάτων με box corer με το Ω/Κ Αιγαίο και ακολούθησαν αναλύσεις μεγέθους κόκκων, ορυκτολογίας και γεωχημείας. Ένα μεγάλο βαθυμετρικό βύθισμα εντοπίστηκε βόρεια της Κιμώλου, με μέγιστο βάθος 743 μ., που συγκεντρώνει λεπτόκοκκα ιζήματα. Η κατανομή των ιζημάτων ως προς το μέγεθος κόκκων χαρακτηρίζεται από σταδιακή μείωση του μεγέθους από νότο προς βορρά. Η ορυκτολογική σύσταση περιλαμβάνει ασβεστίτη, Mg-ασβεστίτη, αραγωνίτη, δολομίτη, χαλαζία, Κ-άστριους, πλαγιόκλαστα, αμφίβολους και αργιλικά ορυκτά. Οι κύριες ιζηματολογικές επαρχίες που αναγνωρίστηκαν είναι 1) η ρηχή περιοχή πλησίον της Κιμώλου, με υψηλό περιεχόμενο σε Si, Al, K, Rb και Ba, 2) η βαθιά περιοχή δυτικά της Σίφνου, όπου εμφανίζεται και το μεγάλο βύθισμα, που χαρακτηρίζεται από υψηλό περιεχόμενο σε Fe, Ti, Na, Mg, S, Cr, Cu, Ni, V, Zn και 3) το στενό μεταξύ Σίφνου και Κιμώλου, με υψηλότερο περιεχόμενο σε Ca, S και Sr. Στο βύθισμα αυτό, παρατηρήθηκε σημαντικός εμπλουτισμός των ιζημάτων σε μαγγάνιο, ενώ τα οξείδια του Mn φαίνεται να προσροφούν διάφορα μέταλλα.An extensive oceanographic survey was conducted in the marine area between Kimolos and Sifnos Islands, a rather poorly-studied sector of the Aegean Sea, in order to gain better understanding of submarine geomorphological features and associated sediment provenance. Multi-beam bathymetry and surface sediment sampling with a box corer were carried out on board R/V Aegaeo, followed by grain-size analysis, XRD and XRF measurements. A large circular depression was identified north of Kimolos reaching a water depth of 743 m, filled with fine grained sediments. Surface sediment distribution is characterized by gradual decrease in grain-size from silty sand to silt in a S-N direction. The mineralogical composition comprises calcite, Mgcalcite, aragonite, dolomite, quartz, K feldspars, plagioclase, amphiboles and clay minerals. Major sediment provinces identified were: (i) the shallow sector proximal to Kimolos, characterized by higher contents in Si, Al, K, Rb and Ba; (ii) the deep area west of Sifnos, including the large depression, characterized by higher contents in Fe, Ti, Na, Mg, S, Cr, Cu, Ni, V, Zn; and (iii) the south passage between Kimolos and Sifnos, which exhibits higher Ca, S, and Sr contents. Manganese enrichment was observed in and around the bathymetric depression, where Mn oxides act efficiently as scavengers of a suite of metals

"We can remember it for you": location, memory, and commodification in social networking sites

This article explores the spatial self through the performative aspects of location sharing and geotagging in the process of self-representation on social networking sites (SNSs). Based on the legacy of early experimentations with location-based technologies for social interaction, the article asserts that the representation of location in SNSs has more temporal than spatial attributes. The article explores the immediacy of networks and the different kinds of temporality encountered in SNSs to address the commodification of geotagged content uploaded on SNSs. Location-based data are valuable commodities bought and sold in the market. Therefore, the act of archiving memories on SNSs is commodified and performed within the predetermined functions and actions set within the SNSs’ interfaces. SNSs devise ways to keep users constantly interacting with the present moment in time and simultaneously create memories of the recent past while disclosing personal data that companies use for profit

TITUS: the Tokai Intermediate Tank for the Unoscillated Spectrum

68 pages.38 figures68 pages.38 figures68 pages.38 figures70 pages, 41 figuresThe TITUS, Tokai Intermediate Tank for Unoscillated Spectrum, detector, is a proposed Gd-doped Water Cherenkov tank with a magnetised muon range detector downstream. It is located at J-PARC at about 2 km from the neutrino target and it is proposed as a potential near detector for the Hyper-Kamiokande experiment. Assuming a beam power of 1.3 MW and 27.05 x 10^{21} protons-on-target the sensitivity to CP and mixing parameters achieved by Hyper-Kamiokande with TITUS as a near detector is presented. Also, the potential of the detector for cross sections and Standard Model parameter determination, supernova neutrino and dark matter are shown

Hyper-Kamiokande Design Report

On the strength of a double Nobel prize winning experiment (Super)Kamiokande and an extremely successful long baseline neutrino programme, the third generation Water Cherenkov detector, Hyper-Kamiokande, is being developed by an international collaboration as a leading worldwide experiment based in Japan. The Hyper-Kamiokande detector will be hosted in the Tochibora mine, about 295 km away from the J-PARC proton accelerator research complex in Tokai, Japan. The currently existing accelerator will be steadily upgraded to reach a MW beam by the start of the experiment. A suite of near detectors will be vital to constrain the beam for neutrino oscillation measurements. A new cavern will be excavated at the Tochibora mine to host the detector. The experiment will be the largest underground water Cherenkov detector in the world and will be instrumented with new technology photosensors, faster and with higher quantum efficiency than the ones in Super-Kamiokande. The science that will be developed will be able to shape the future theoretical framework and generations of experiments. Hyper-Kamiokande will be able to measure with the highest precision the leptonic CP violation that could explain the baryon asymmetry in the Universe. The experiment also has a demonstrated excellent capability to search for proton decay, providing a significant improvement in discovery sensitivity over current searches for the proton lifetime. The atmospheric neutrinos will allow to determine the neutrino mass ordering and, together with the beam, able to precisely test the three-flavour neutrino oscillation paradigm and search for new phenomena. A strong astrophysical programme will be carried out at the experiment that will also allow to measure precisely solar neutrino oscillation