The intangibility of tangible objects: re-telling artefact stories through spatial multimedia annotations and 3D objects

An interdisciplinary team at the University of Cologne just released Kompakkt, an open-source online-tool for linking 3D objects to multimedia content and for gathering information through annotations in 3D space more generally. It enables users to share, explore, and collaboratively annotate objects in standard modern web browsers. The 3D representation of an object serves as the hub of an open-ended collection of heterogeneous information established through the use of multimedia annotations. The annotations are flexible (meta)data complementing what one usually finds in collection management systems in the GLAM sector. Through personalised and group level collections of 3D models, images, sounds and videos Kompakkt enables a novel solution for gathering and generating artefact information. The third dimension of objects highlights the perspective of annotations in a new way: annotations are not only linked to a specific location in space, the corresponding point of view chosen by the user is also relevant. Linking and ranking annotations leads to moving from one annotation (and a specific perspective) to another, which implies a movement through space in time. That allows new ways of annotation-based storytelling, where annotations can be used for presentations in which movement in VR- and AR-applications is embedded

Retinoic acid signaling acts via Hox1 to establish the posterior limit of the pharynx in the chordate amphioxus

In the invertebrate chordate amphioxus, as in vertebrates, retinoic acid (RA) specifies position along the anterior/posterior axis with elevated RA signaling in the middle third of the endoderm setting the posterior limit of the pharynx. Here we show that AmphiHox1 is also expressed in the middle third of the developing amphioxus endoderm and is activated by RA signaling. Knockdown of AmphiHox1 function with an antisense morpholino oligonucleotide shows that AmphiHox1 mediates the role of RA signaling in setting the posterior limit of the pharynx by repressing expression of pharyngeal markers in the posterior foregut/midgut endoderm. The spatiotemporal expression of these endodermal genes in embryos treated with RA or the RA antagonist BMS009 indicates that Pax1/9, Pitx and Notch are probably more upstream than Otx and Nodal in the hierarchy of genes repressed by RA signaling. This work highlights the potential of amphioxus, a genomically simple, vertebrate-like invertebrate chordate, as a paradigm for understanding gene hierarchies similar to the more complex ones of vertebrates

Accelerated large volume irradiation with dynamic Jaw/Dynamic Couch Helical Tomotherapy

BACKGROUND: Helical Tomotherapy (HT) has unique capacities for the radiotherapy of large and complicated target volumes. Next generation Dynamic Jaw/Dynamic Couch HT delivery promises faster treatments and reduced exposure of organs at risk due to a reduced dose penumbra. METHODS: Three challenging clinical situations were chosen for comparison between Regular HT delivery with a field width of 2.5 cm (Reg 2.5) and 5.0 cm (Reg 5.0) and DJDC delivery with a maximum field width of 5.0 cm (DJDC 5.0): Hemithoracic Irradiation, Whole Abdominal Irradiation (WAI) and Total Marrow Irradiation (TMI). For each setting, five CT data sets were chosen, and target coverage, conformity, integral dose, dose exposure of organs at risk (OAR) and treatment time were calculated. RESULTS: Both Reg 5.0 and DJDC 5.0 achieved a substantial reduction in treatment time while maintaining similar dose coverage. Treatment time could be reduced from 10:57 min to 3:42 min / 5:10 min (Reg 5.0 / DJDC 5.0) for Hemithoracic Irradiation, from 18:03 min to 8:02 min / 8:03 min for WAI and to 18:25 min / 18:03 min for TMI. In Hemithoracic Irradiation, OAR exposure was identical in all modalities. For WAI, Reg 2.5 resulted in lower exposure of liver and bone. DJDC plans showed a small but significant increase of ∼ 1 Gy to the kidneys, the parotid glans and the thyroid gland. While Reg 5.0 and DJDC were identical in terms of OAR exposure, integral dose was substantially lower with DJDC, caused by a smaller dose penumbra. CONCLUSIONS: Although not clinically available yet, next generation DJDC HT technique is efficient in improving the treatment time while maintaining comparable plan quality

An exciton-polariton laser based on biologically produced fluorescent protein

We thank A. Clemens (TU Dresden, Germany) for technical support with protein preparation and C. Murawski (U St Andrews, UK) for support with TDAF deposition. We acknowledge support from the ERC Starting Grant ABLASE (640012), the Scottish Funding Council (via SUPA), the European Union Marie Curie Career Integration Grant (PCIG12-GA-2012-334407), studentship funding through the EPSRC CM-DTC (EP/L015110/1) and the EPSRC Hybrid Polaritonics program grant (EP/M025330/1). S.H. gratefully acknowledges support by the Royal Society and the Wolfson Foundation and M.S. gratefully acknowledges support from a MSCA IF (659213).Under adequate conditions, cavity-polaritons form a macroscopic coherent quantum state, known as polariton condensate (PC). Compared to Wannier-Mott polaritons in inorganic semiconductors, the localized Frenkel polaritons in organic emitter materials show weaker interaction with each other but stronger coupling to light, which recently enabled the first realization of a PC at room temperature. However, this required ultrafast optical pumping which limits the applications of organic PCs. Here, we demonstrate room-temperature PCs of cavity-polaritons in simple laminated microcavities filled with the biologically produced enhanced green fluorescent protein (eGFP). The unique molecular structure of eGFP prevents exciton annihilation even at high excitation densities, thus facilitating PCs under conventional nanosecond pumping. Condensation is clearly evidenced by a distinct threshold, an interaction-induced blueshift of the condensate, long-range coherence and the presence of a second threshold at higher excitation density which is associated with the onset of photon lasing.Publisher PDFPeer reviewe

Self-reactive human CD4 T cell clones form unusual immunological synapses

Recognition of self–peptide-MHC (pMHC) complexes by CD4 T cells plays an important role in the pathogenesis of many autoimmune diseases. We analyzed formation of immunological synapses (IS) in self-reactive T cell clones from patients with multiple sclerosis and type 1 diabetes. All self-reactive T cells contained a large number of phosphorylated T cell receptor (TCR) microclusters, indicative of active TCR signaling. However, they showed little or no visible pMHC accumulation or transport of TCR–pMHC complexes into a central supramolecular activation cluster (cSMAC). In contrast, influenza-specific T cells accumulated large quantities of pMHC complexes in microclusters and a cSMAC, even when presented with 100-fold lower pMHC densities. The self-reactive T cells also maintained a high degree of motility, again in sharp contrast to virus-specific T cells. 2D affinity measurements of three of these self-reactive T cell clones demonstrated a normal off-rate but a slow on-rate of TCR binding to pMHC. These unusual IS features may facilitate escape from negative selection by self-reactive T cells encountering very small amounts of self-antigen in the thymus. However, these same features may enable acquisition of effector functions by self-reactive T cells encountering large amounts of self-antigen in the target organ of the autoimmune disease

Advancing electrochemical jet methods through manipulation of the angle of address

Electrochemical jet processing techniques have traditionally been considered to be limited to planar interactions with the electrolyte jet being maintained normal to the workpiece surface. In this study, the viability and resultant effects of articulating the nozzle relative to the work were investigated for the first time. Two machining conventions were defined, normal, where the jet is maintained perpendicular to the traverse direction, and push/pull, where the nozzle is rotated with respect to the direction of travel. It was found, with the normal convention that a range of differing resultant profile surface geometries could be created; unique to this process. This was demonstrated by the changing resultant side wall slopes found through the rotation of the head with up to 80% difference between the slopes of the cut walls. The adjacent wall to the nozzle slope decreasing as the jet angle approaches 90° whilst the opposite side wall slope increases. Predictable ratios of the differing slopes of the striation side walls were then able to be defined. The push/pull convention demonstrated that deeper, sharper cuts are possible due to the highly localising current density effect of nozzle inclination achieving a 35% increase in depth without requiring additional energy. Also, that resultant surface finish could be greatly improved, reducing the profile roughness (Ra) from 0.2 μm in the pull mode to 0.04 μm in the push mode achieving a mirror-like finish. The mechanics of these phenomena are investigated and defined. The influence of nozzle jet speed variation combined with inclining the jet was also studied. This was found to have no noticeable influence on the resultant profile when the nozzle is inclined. In contrast, when the nozzle is normal to the surface, jet velocity is seen to have a direct influence due to polarisation effects relating to the poor clearance of machining debris and the formation of oxides. It is shown that through variation of the angle of jet address an extra level of flexibility and performance is possible within electrochemical jet processes

What works to increase charitable donations? A meta-review with meta-meta-analysis

Many charities rely on donations to support their work addressing some of the world’s most pressing problems. We conducted a meta-review to determine what interventions work to increase charitable donations. We found 21 systematic reviews incorporating 1339 primary studies and over 2,139,938 participants. Our meta-meta-analysis estimated the average effect of an intervention on charitable donation size and incidence: r = 0.08 (95% CI [0.03, 0.12]). Due to limitations in the included systematic reviews, we are not certain this estimate reflects the true overall effect size. The most robust evidence found suggests charities could increase donations by (1) emphasising individual beneficiaries, (2) increasing the visibility of donations, (3) describing the impact of the donation, and (4) enacting or promoting tax-deductibility of the charity. We make recommendations for improving primary research and reviews about charitable donations, and how to apply the meta-review findings to increase charitable donations

Functional single-cell analysis of T-cell activation by supported lipid bilayer-tethered ligands on arrays of nanowells

Supported lipid bilayers are an important biomolecular tool for characterizing immunological synapses. Immobilized bilayers presenting tethered ligands on planar substrates have yielded both spatio-temporal and structural insights into how T cell receptors (TCRs) reorganize during the initial formation of synapses upon recognition of peptide antigens bound to major histocompatibility complex (MHC) molecules. The prototypical configuration of these assays, however, limits the extent to which the kinetics and structure of the supramolecular activation clusters of the synapse (that occur in seconds or minutes) can be related to subsequent complex cellular responses, such as cytokine secretion and proliferation, occurring over hours to days. Here we describe a new method that allows correlative measures of both attributes with single-cell resolution by using immobilized lipid bilayers and tethered ligands on the surface of dense arrays of subnanoliter wells. This modification allows each nanowell to function as an artificial antigen-presenting cell (APC), and the synapses formed upon contact can be imaged by fluorescence microscopy. We show that the lipid bilayers remain stable and mobile on the surface of the PDMS, and that modifying the ligands tethered to the bilayer alters the structure of the resulting synapses in expected ways. Finally, we demonstrate that this approach allows the subsequent characterization of secreted cytokines from the activated human T cell clones by microengraving in both antigen- and pan-specific manners. This new technique should allow detailed investigations on how biophysical and structural aspects of the synapse influence the activation of individual T cells and their complex functional responses.National Institute of Allergy and Infectious Diseases (U.S.) (5P01AI045757)National Cancer Institute (U.S.) (Cancer Center Support (Core) Grant P30-CA14051

Developing Recombinant Antibodies by Phage Display Against Infectious Diseases and Toxins for Diagnostics and Therapy

Antibodies are essential molecules for diagnosis and treatment of diseases caused by pathogens and their toxins. Antibodies were integrated in our medical repertoire against infectious diseases more than hundred years ago by using animal sera to treat tetanus and diphtheria. In these days, most developed therapeutic antibodies target cancer or autoimmune diseases. The COVID-19 pandemic was a reminder about the importance of antibodies for therapy against infectious diseases. While monoclonal antibodies could be generated by hybridoma technology since the 70ies of the former century, nowadays antibody phage display, among other display technologies, is robustly established to discover new human monoclonal antibodies. Phage display is an in vitro technology which confers the potential for generating antibodies from universal libraries against any conceivable molecule of sufficient size and omits the limitations of the immune systems. If convalescent patients or immunized/infected animals are available, it is possible to construct immune phage display libraries to select in vivo affinity-matured antibodies. A further advantage is the availability of the DNA sequence encoding the phage displayed antibody fragment, which is packaged in the phage particles. Therefore, the selected antibody fragments can be rapidly further engineered in any needed antibody format according to the requirements of the final application. In this review, we present an overview of phage display derived recombinant antibodies against bacterial, viral and eukaryotic pathogens, as well as microbial toxins, intended for diagnostic and therapeutic applications