Characterization of GAD-reaktive B cells and their B-cell receptor repertoire in the periphery and central nervous system

Antibodies (abs) against the intracellular cytoplasmic protein glutamic acid decarboxylase 65 (GAD65) occur in different neurological disorders. Hereby, patients with anti-GAD65 ab associated autoimmune neurological disorders (GAD-AIND) exhibit high levels of anti-GAD65 abs in the serum as well as in the cerebrospinal fluid (CSF). However, the sites of immunological dysregulation and the triggers for the production of auto-abs against GAD65 are unclear. Furthermore, investigations on the pathogenic relevance of anti-GAD65 abs and their producing cells have yielded conflicting results. In consequence, the treatment of patients with GAD-AIND remains challenging. Therefore, investigating the functional properties of GAD-reactive B cells and anti-GAD65 abs could help to gain insights into the pathophysiology of GAD-AIND and assist the development of new treatment strategies. To this end, we analyzed GAD-reactive B cells in peripheral blood of patients with GAD-AIND as well as bone marrow (bm) cells of one patient. As a next step, we generated monoclonal patient-derived abs from peripheral blood (PB) and CSF cells and characterized their reactivity to GAD in different assays. Moreover, we analyzed the auto-abs for sequence specificities, e.g., subclass distribution, and somatic hypermutations (SHMs). In the first study, we could detect anti-GAD65 ab producing cells derived from GAD-reactive B cells in the peripheral blood (PB) of fifteen patients with GAD-AIND. Compared to our healthy control group consisting of nineteen donors, cells producing anti-GAD65 abs were highly elevated. Furthermore, we could identify bm plasma cells as an additional source of anti-GAD65 abs. The frequency of GAD-reactive B cells was comparable to B cells reactive for common recall antigens (ags) e.g. tetanus toxoid. In a second study, we included six patients with GAD-AIND and were able to generate 30 monoclonal abs (mabs) with 25 mabs derived from CSF cells and 5 mabs derived from PB cells. Mabs could be generated in patients with a short disease duration at the time of sampling. Thereby, we identified 10 GAD65-reactive mabs (CSF: 6/25; PB: 4/5) with enzyme-linked-immunosorbent-assay (ELISA). Furthermore, we could demonstrate that the intrathecal anti-GAD65 response is polyclonal and that the mabs had undergone affinity maturation when being compared to non-GAD65-reactive mabs. By reverting the SHMs of three GAD-reactive mabs to their germline sequences, we could show that affinity maturation is essential for the reactivity towards GAD65. Taken together, our data characterize the B cell response in the CSF of patients with GAD-AIND, showing that the anti-GAD65 response is polyclonal and affinity maturation is necessary for the recognition of GAD65. Additionally, we could for the first time proof that anti-GAD65-ab-producing cells are present in the central nervous system. In addition, our data support the clinical observation that a B-cell depleting therapy might not be suitable for the treatment of long-standing GAD-AIND

Integrating human perception in 3D city models and urban digital twins

Urban digital twins, and 3D city models underpinning them, provide novel solutions to urban management but tend to overlook the human element. The trending research on human perception reveals people’s perspective towards interpreting and experiencing the built environment. Advancing the representation of building physics and descriptive information in 3D city models and urban digital twins, we establish the addition and integration of the notion of how humans perceive buildings. Unlocking a new dimension in our domain, this new concept can facilitate a broader adoption of semantic 3D data in socio-economic fields across various domains, and advance existing use cases in 3D GIS. This work is the first instance of integrating such attributes in 3D city models, which have traditionally been confined to physical and objective measures. The visual perception of each building is evaluated based on building images extracted from street view images. We add such information as new attributes to an existing CityJSON dataset representing thousands of 3D buildings in Amsterdam, the Netherlands. To facilitate a robust and sustainable integration, we develop a CityJSON Extension to accommodate the new data and validate its schema successfully, and we visualise the semantic 3D dataset. Further, we present two use cases to demonstrate the usability of our new data for downstream analysis. One is the concurrent clustering of buildings based on 3D morphology and human perception, while the other is conducting an attribute-based query that enables various stakeholders to identify a particular building of interest combining both traditional and perception attributes

INSPIRE i CROTIS kao upravljačke i temeljne komponente NSDI-a

U ovom radu popularno-znanstvenog karaktera su detaljno opisani temeljni principi INSPIRE-a s posebnim naglaskom na osnovne setove geopodataka. CROTIS, kao temeljni prostorni informacijski sustav, je osnova za hrvatski NSDI i jedna od budućih komponenti EU SDI. Rad detaljno i pregledno obrađuje odnos INSPIRE - CROTIS uz zaključke, temeljene na analitičkom pristupu, da se radi o visokoj razini usklađenosti i konfornosti

Važnost uvođenja vremenskih geoinformacija u pomorsku navigaciju

U ovom radu prikazuju se važnost i mogućnosti uvođenja vremena kao četvrte dimenzije u geoinformacije pomorske navigacije. Rad se temelji na radu Koncept pomorske četverodimenzionalne navigacije nagrađenog Rektorovom nagradom Sveučilišta u Zagrebu u svibnju 2006

Analysis of the advantage of using the SiRFStarIII architecture for navigational purposes in urban areas

Proteklih nekoliko godina tržište navigacijskih uređaja doživjelo je svoj najveći procvat - svakodnevna prisutnost navigacijskih uređaja nikad nije bila veća. Međutim, zbog sve većeg stupnja korištenja navigacijskih uređaja u urbanim sredinama, kao i građevinske ofenzive na iste, javlja se standardni problem GPS sustava - slabi signal koji vodi do manje točnosti i dugo vrijeme prvog fiksiranja rješenja pozicije (engl. Time To First Fix, TTFF). Radi poboljšanja situacije tvrtka SiRF Technology Holdings, Inc1 je proizvela novi čipset SiRFStarIII koji se odlikuje većom osjetljivošću, kratkim TTFF-om i predstavlja najnovije dostignuće u satelitskoj navigaciji. U radu se analizira prednost korištenja SiRFStarIII čipseta u urbanim sredinama kroz nekoliko praktičnih testova na području Grada Zagreba.In the last few years the market of navigational devices experienced it’s biggest boom – their everyday presense was never bigger. Meanwhile, because of a higher degree of use of navigational devices in urban ares as the engineering offensive on them some standard GPS problems are present – weak signal from satellites which leads to smaller accuracy and long Time To First Fix (TTFF). For a better situation, the company SiRF Technology Holdings, Inc. made a new chipset SiRFStarIII which accent is on higher sensitivity, short TTFF and represents the newest achievement in satellite navigation. This paper shows the analysis of the advantage of using the chipset SiRFStarIII in urban areas through few practical tests on the area of The City of Zagreb, Croati