USE OF HISTORICAL AERIAL IMAGES FOR 3D MODELLING OF GLACIERS IN THE PROVINCE OF TRENTO

Abstract. Historical aerial images represent a source of information of great value for glacier monitoring, as they cover the area of interest at a well-defined epoch and allow for visual interpretation and metric analysis. Typically, the aerial images are used to produce orthophotos and manually digitize the perimeters of the glaciers for analysis of the surface extent of the glaciers, while the extraction of height information is more challenging due to data quality and characteristics. This article discusses the potential of historical aerial images for glacier modelling. More specifically, it analyses the impact of their coverage, radiometric- and geometric accuracy, state of preservation and completeness on the photogrammetric workflow. The data set used consists of scans of 300 (analog) aerial images acquired between August and October 1954 by the U.S. Air Force with a Fairchild KF7660 camera over the entire Province of Trento. For the modelling of the glaciers, different techniques such as manual stereoscopic measurement and dense image matching were tested on sample glaciers and the results were analysed in detail. Due to local radiometric saturation in a large part of the glacial surfaces and other disturbances affecting the historical images (e.g. scratches, scanning errors, dark shadows), dense image matching did not produce any valuable results, and stereo plotting could be used only on images (or image parts) with acceptable quality. The derived Digital Terrain Models (DTMs) were compared with a reference DTM obtained with dense image matching from digital aerial images acquired in September 2015 with an UltraCam Eagle sensor, and, for some glaciers, to a DTM obtained with dense image matching from scanned aerial images acquired in September 1983 with a RC30 analog camera. The differences between 1954 and 2015 DTMs showed values up to 70–80 m in height and a behaviour that is confirmed by the models employed by the glaciology experts in Trento

Clinical, laboratory and immunohistochemical characterization of in situ pulmonary arterial thrombosis in fatal COVID-19

Background: COVID-19 patients carry an increased rate of thrombosis. It is controversial to which extent thrombi in the pulmonary arterial tree really contribute to disease severity with hypoxemia secondary to microvascular/lung parenchymal damage with viral alveolitis considered to play the main role in critical disease. Objectives: The primary objective was to compare post-mortem lung disease from fatal COVID-19 pneumonia in patients with macroscopically evident pulmonary arterial tree thrombosis and patients without, by characterizing the immunohistochemical nature of thrombi, and by comparing clinical and laboratory features of these patients with other COVID-19 patients who died but without evidence of pulmonary arterial thrombosis (controls). Patients and methods: 13 COVID-19 pneumonia cases (mean age ± standard deviation: 74 ± 6.5 years) with macroscopically visible pulmonary arterial thrombosis were compared to 14 controls. Hematoxylin and Eosin stained slides were reviewed choosing those with visible pulmonary thrombi which were further characterized by immunohistochemistry, in particular for the inflammatory infiltrates. Ante mortem serum markers relevant to pulmonary embolism were evaluated in both groups. Results: Twenty arterial thrombi (5 cases with multiple thrombi) were selected for study and were composed by white blood cells (WBC) [median, IQR range: 10 % (5–12.25)], mainly neutrophils [58 % (35.2–64.5)]. Cases with thrombosis showed significantly higher levels of platelet count [median, IQR range: 195000/mmc (157750–274,500) vs 143,500 (113000–175,250), p = 0.011], LDH [854 U/L (731–1315) vs 539 (391.5–660), p = 0.003] at admission, and D-dimer at ICU transfer [25,072 FEU (6951–50,531) vs 1024 (620–5501), p = 0.003]. Conclusions: Immunothrombotically driven arterial thrombi in COVID-19 patients are associated with D-Dimer and LDH elevations, thus linking inflammation, coagulopathy and organ damage in fatal COVID-19

Exploring the boundaries in an interdisciplinary context through the Family Resemblance Approach: The Dialogue Between Physics and Mathematics

Among the relevant aspects of the family resemblance approach (FRA), our study focuses on the potential of the approach to elaborate on disciplinary identities in an interdisciplinary context, specifically regarding the interplay between physics and mathematics. We present and discuss how the FRA wheel can be used and intertwined with the framework of boundary objects and boundary crossing mechanisms (Akkerman & Bakker, Review of Educational Research, 81, 132–169, 2011), which is well-known in STEM education for dealing with interdisciplinarity. The role of the FRA discussed in the article is dual: both practical and theoretical. It is practical in that we show how its use, in combination with the Akkerman and Bakker framework, appears effective in fostering productive discussions among prospective teachers on disciplinary identities and interdisciplinarity in historical cases. It is theoretical in that the combination of the two frameworks provides the vocabulary to characterise the ‘ambiguous nature’ of interdisciplinarity: like boundaries, interdisciplinarity both separates disciplines, making their identities emerge, and connects them, fostering mechanisms of crossing and transgressing the boundaries. This empirical study reveals how the theoretical elaboration took advantage of the prospective teachers’ contributions. We initially presented the FRA to characterise disciplinary identities, but the prospective teachers highlighted its potential to characterise also the boundary zone and the dialogue between physics and mathematics. The data analysis showed that the combination of the two frameworks shaped a complex learning space where there was room for very different epistemic demands of the prospective teachers: from those who feel better within the identity cores of the disciplines, to those who like to inhabit the boundary zone and others who like to re-shape boundary spaces and move dynamically across them

Multiple Roles of Transforming Growth Factor Beta in Amyotrophic Lateral Sclerosis

Transforming growth factor beta (TGFB) is a pleiotropic cytokine, known to be dysregulated in many neurodegenerative disorders and particularly in amyotrophic lateral sclerosis (ALS). This motor neuronal disease is non-cell autonomous, as it affects not only motor neurons, but also their surrounding glial cells, and their target skeletal muscle fibers. Here, we analyze the multiple roles of TGFB in these cell types, and how TGFB signaling is altered in ALS tissues. Data reported support a crucial involvement of TGFB in the etiology and progression of ALS, leading us to hypothesize that an imbalance of TGFB signaling, diminished at the pre-symptomatic stage and then increased with time, could be linked to ALS progression. A reduced stimulation of the TGFB pathway at the beginning of disease blocks its neuroprotective effects and promotes glutamate excitotoxicity. At later disease stages, the persistent activation of the TGFB pathway promotes an excessive microglial activation and strengthens muscular dysfunction. The therapeutic potential of TGFB is discussed here, in order to foster new approaches to treat ALS

Autophagic and proteasomal mediated removal of mutant androgen receptor in muscle models of spinal and bulbar muscular atrophy

Spinal and bulbar muscular atrophy (SBMA) is an X-linked motoneuron disease (MND) caused by a mutant androgen receptor (AR) containing an elongated polyglutamine (polyQ) tract. ARpolyQ toxicity is triggered by androgenic AR ligands, which induce aberrant conformations (misfolding) of the ARpolyQ protein that aggregates. Misfolded proteins perturb the protein quality control (PQC) system leading to cell dysfunction and death. Spinal cord motoneurons, dorsal root ganglia neurons and skeletal muscle cells are affected by ARpolyQ toxicity. Here, we found that, in stabilized skeletal myoblasts (s-myoblasts), ARpolyQ formed testosterone-inducible aggregates resistant to NP-40 solubilization; these aggregates did not affect s-myoblasts survival or viability. Both wild type AR and ARpolyQ were processed via proteasome, but ARpolyQ triggered (and it was also cleared via) autophagy. ARpolyQ reduced two pro-autophagic proteins expression (BAG3 and VCP), leading to decreased autophagic response in ARpolyQ s-myoblasts. Overexpression of two components of the chaperone assisted selective autophagy (CASA) complex (BAG3 and HSPB8), enhanced ARpolyQ clearance, while the treatment with the mTOR independent autophagy activator trehalose induced complete ARpolyQ degradation. Thus, trehalose has beneficial effects in SBMA skeletal muscle models even when autophagy is impaired, possibly by stimulating CASA to assist the removal of ARpolyQ misfolded species/aggregates

Enhanced Clearance of Neurotoxic Misfolded Proteins by the Natural Compound Berberine and Its Derivatives

Background: Accumulation of misfolded proteins is a common hallmark of several neurodegenerative disorders (NDs) which results from a failure or an impairment of the proteinquality control (PQC) system. The PQC system is composed by chaperones and the degradative systems (proteasome and autophagy). Mutant proteins that misfold are potentially neurotoxic, thus strategies aimed at preventing their aggregation or at enhancing their clearance are emerging as interesting therapeutic targets for NDs. Methods: We tested the natural alkaloid berberine (BBR) and some derivatives for their capability to enhance misfolded protein clearance in cell models of NDs, evaluating which degradative pathway mediates their action. Results: We found that both BBR and its semisynthetic derivatives promote degradation of mutant androgen receptor (ARpolyQ) causative of spinal and bulbar muscular atrophy, acting mainly via proteasome and preventing ARpolyQ aggregation. Overlapping effects were observed on other misfolded proteins causative of amyotrophic lateral sclerosis, frontotemporal-lobar degeneration or Huntington disease, but with selective and specific action against each different mutant protein. Conclusions: BBR and its analogues induce the clearance of misfolded proteins responsible for NDs, representing potential therapeutic tools to counteract these fatal disorders

The role of extracellular vesicles in the removal of aggregated TDP43 responsible for ALS/FTD diseases

Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD) are two related neurodegenerative diseases. ALS is caused by the death of both upper and lower motoneurons, while FTD is characterized predominantly by circumscribed atrophy of the frontal and temporal lobes. ALS and FTD overlap each other. This is demonstrated by the presence of cognitive and behavioral dysfunction in up to 50% of ALS patients and by the presence of frontotemporal atrophy in patients with ALS. Moreover, these diseases are both characterize by the presence of TAR DNA binding protein 43 (TDP43) inclusions in affected cells. These inclusions, observed in 97% of patients with ALS and 50% of patients with FTD, are composed by TDP43 and its C-terminal fragments of 35 kDa (TDP35) and 25 kDa (TDP25). These fragments are highly aggregation-prone and probably neurotoxic. Thus, their removal is protective for cells. The mechanism responsible for the clearance of aggregates and misfolded proteins is the intracellular protein quality control (PQC) system. It consists of molecular chaperones/co- chaperones and the degradative pathways. PQC controls the folding status of proteins and prevents the aggregation of misfolded proteins by refolding them or degrading. Recent data demonstrated that also extracellular secretory pathway, represented especially by exosomes (EXOs) and microvesicles (MVs), might be involved in the removal of misfolded proteins from affected cells. Thus, we evaluated the role of EXOs and MVs in the secretion of TDP43 and its C-terminal fragments, using neuronal cell models. We used ultracentrifugation, that allowed us to separate MVs from EXOs on the basis of their dimension. Then we analyzed them through i) Nanoparticle Tracking Analysis (NanoSight) to establish their number and sizes, and ii) western blot analysis, to characterize their protein content. Our preliminary results show that TDP43, TDP35 and TDP25 are all secreted, mainly by MVs. In particular, we found that MVs are enriched of insoluble forms of TDPs and also of superoxide dismutase 1 (SOD1), another ALS-related protein. Finally, both in EXOs and in MVs, we observed the presence of some important PQC-components, suggesting an interplay between the two pathways. GRANTS: Fondazione Cariplo, Italy (n. 2017_0747); Universit\ue0 degli Studi di Milano e piano di sviluppo UNIMI - linea B