Effects of fiber layout on strength and failure of 3D printed notched composites

This study investigates the effect of printing strategies on the strength of additively manufactured notched fiber reinforced composite specimens. Specimens with varying notch geometries (two radii and two opening angles) and fiber layouts (unreinforced, unidirectional, quasi-isotropic and concentric) were 3D printed and tested under tension. Digital image correlation provided surface strain field data. Results showed that fiber deposition patterns significantly impact notch sensitivity, failure loads and mechanisms, with notch geometry being of secondary importance. The unidirectional layout achieved the highest strength but with progressive failure, while quasiisotropic specimens failed abruptly from the notch. The concentric layout shielded the notch region but induced premature failure away from the notch due to transverse stress. Stress concentration factor approaches, which work well for conventional laminates, have limitations for 3D printed composites due to local differences and complex interactions. Optimizing fiber deposition, instead of geometry, emerges as a promising design route. Combining unidirectional and contouring algorithms may improve performance. However, further studies utilizing multiscale modelling and local failure analyses are needed to fully understand failure mechanisms and guide optimal notch designs for 3D printed composites. With improved understanding and design methods, 3D printing promises to unlock new possibilities for structurally efficient notched composite parts

Effect of slow-moving landslides on a vaulted masonry building: The case of San Carlo Borromeo church in Cassingheno (Genova)

This paper presents the structural analysis of San Carlo Borromeo church, a masonry building located in Cassingheno (Genoa, Italy) in an area affected by a slow-moving landslide. A deep knowledge of the building in terms of geometry, structural configuration, history and construction phases was acquired by means of on-site surveys and archival research. The crack patterns were surveyed in detail and the deformations were studied through a point cloud obtained from a LIDAR survey. The comparison between the landslide direction and the damage observed showed discrepancies and suggested the presence of foundation settlements due to other phenomena. To identify the actual causes of damage, a finite element model (FEM) of the building in its hypothetical undeformed configuration was created. The geometry of such configuration was reconstructed starting from the point cloud obtained from the LIDAR survey and removing geometrical defects such as leaning of walls, deformation of vaults and inclination of tie-rods. To simulate the effects produced by the landslide and the foundation settlements on the building over time, nonlinear analyses were performed by imposing different displacement fields at the foundation plane in multiple steps. The damage predicted numerically was then compared with the one experienced by the building, showing good agreement

Autophagy-related protein LC3 and Beclin-1 in the first trimester of pregnancy

Autophagy is a degradation process that acts in response to environmental stressors. Recently, autophagy has been detected in normal term, preeclamptic and intrauterine growth-restricted placentas. The object of this work was to investigate the presence of autophagy in first trimester voluntary interruption of pregnancy placental villi by the expression of autophagy-related proteins, light chain 3 (LC3), and Beclin-1. In first trimester placental villi laser scanning confocal microscopy (LSCM) analysis revealed LC3 and Beclin-1 immunoreactivity prevalently located in villous cytotrophoblasts. Using LSCM, LC3, and Beclin-1 were localized to the cytoplasm of the trophoblast layer in human full-term placentas. Beclin-1 expression and LC3 activation were confirmed by western blotting. These data emphasize that autophagy activation is different among cytotrophoblasts and syncytiotrophoblasts depending on the gestational age and thus we speculate that autophagy might play a prosurvival role throughout human pregnancy

The role of preclinical models in creatine transporter deficiency: Neurobiological mechanisms, biomarkers and therapeutic development

Creatine (Cr) Transporter Deficiency (CTD) is an X-linked metabolic disorder, mostly caused by missense mutations in the SLC6A8 gene and presenting with intellectual disability, autistic behavior, and epilepsy. There is no effective treatment for CTD and patients need lifelong assistance. Thus, the research of novel intervention strategies is a major scientific challenge. Animal models are an excellent tool to dissect the disease pathogenetic mechanisms and drive the preclinical development of therapeutics. This review illustrates the current knowledge about Cr metabolism and CTD clinical aspects, with a focus on mainstay diagnostic and therapeutic options. Then, we discuss the rodent models of CTD characterized in the last decade, comparing the phenotypes expressed within clinically relevant domains and the timeline of symptom development. This analysis highlights that animals with the ubiquitous deletion/mutation of SLC6A8 genes well recapitulate the early onset and the complex pathological phenotype of the human condition. Thus, they should represent the preferred model for preclinical efficacy studies. On the other hand, brain-and cell-specific conditional mutants are ideal for understanding the basis of CTD at a cellular and molecular level. Finally, we explain how CTD models might provide novel insight about the pathogenesis of other disorders, including cancer

Interplay between PFBC-associated SLC20A2 and XPR1 phosphate transporters requires inositol polyphosphates for control of cellular phosphate homeostasis

Solute carrier family 20 member 2 (SLC20A2) and xenotropic and polytropic retrovirus receptor 1 (XPR1) are transporters with phosphate uptake and efflux functions, respectively. Both are associated with primary familial brain calcification (PFBC), a genetic disease characterized by cerebral calcium-phosphate deposition and associated with neuropsychiatric symptoms. The association of the two transporters in the same disease suggests that they jointly regulate phosphate fluxes and cellular homeostasis, but direct evidence is missing. Here, we found that cross-talk between SLC20A2 and XPR1 regulates phosphate homeostasis and identify XPR1 as a key inositol polyphosphate (IP)-dependent regulator of this process. We found that overexpression of wildtype SLC20A2 increases phosphate uptake as expected, but also unexpectedly increases phosphate efflux, whereas PFBC-associated SLC20A2 variants did not. Conversely, SLC20A2 depletion decreased phosphate uptake only slightly, most likely compensated for by the related SLC20A1 transporter, but strongly decreased XPR1-mediated phosphate efflux. The SLC20A2-XPR1 axis maintained constant intracellular phosphate and ATP levels, which both increased in XPR1-KO cells. Elevated ATP is a hallmark of altered inositol pyrophosphate (PP-IP) synthesis, and basal ATP levels were restored after phosphate efflux rescue with wildtype XPR1, but not with XPR1 harboring a mutated PP-IP-binding pocket. Accordingly, inositol hexakisphosphate kinase 1-2 (IP6K1-2) gene inactivation or IP6K inhibitor treatment abolished XPR1-mediated phosphate efflux regulation and homeostasis. Our findings unveil an SLC20A2-XPR1 interplay that depends on IPs such as PP-IPs and controls cellular phosphate homeostasis via the efflux route, and that alteration of this interplay likely contributes to PFBC

KNOWLEDGE-BASED MODELLING FOR AUTOMATIZING HBIM OBJECTS. THE VAULTED CEILINGS OF PALAZZO DUCALE IN URBINO

Vault modelling in HBIM poses a significant challenge due to the geometrical complexity and lack of standardization of those elements. Starting from the definition of an ontology able to describe and manage different typologies of Italian Renaissance vaults, this paper presents two methods for their representation in the context of Ducal Palace of Urbino HBIM implementation. The first method is a simplified semi-automated scan-to-BIM procedure relying on Revit adaptive families; the second is a more complex parametric scripting in Dynamo VPL. The paper proposes a library of suitable vault families for the parametric modelling of Renaissance architecture and offers a comparison between the models generated and their respective surveyed point-clouds, with the aim of assessing the procedure. Revit adaptive families appeared to be the easiest to implement and the most efficient solution, while Dynamo allowed for greatest complexity thought showing limitations and implementation difficulties

Clinical, molecular and glycophenotype insights in SLC39A8-CDG

Background: SLC39A8, a gene located on chromosome 4q24, encodes for the manganese (Mn) transporter ZIP8 and its detrimental variants cause a type 2 congenital disorder of glycosylation (CDG). The common SLC39A8 missense variant A391T is associated with increased risk for multiple neurological and systemic disorders and with decreased serum Mn. Patients with SLC39A8-CDG present with different clinical and neuroradiological features linked to variable transferrin glycosylation profile. Galactose and Mn supplementation therapy results in the biochemical and clinical amelioration of treated patients. Results: Here, we report clinical manifestations, neuroradiological features and glycophenotypes associated with novel SLC39A8 variants (c.1048G > A; p.Gly350Arg and c.131C > G; p.Ser44Trp) in two siblings of the same Italian family. Furthermore, we describe a third patient with overlapping clinical features harbouring the homozygous missense variant A391T. The clinical phenotype of the three patients was characterized by severe developmental disability, dystonic postural pattern and dyskinesia with a more severe progression of the disease in the two affected siblings. Neuroimaging showed a Leigh syndrome-like pattern involving the basal ganglia, thalami and white matter. In the two siblings, atrophic cerebral and cerebellum changes consistent with SLC39A8-CDG were detected as well. Serum transferrin isoelectric focusing (IEF) yielded variable results with slight increase of trisialotransferrin isoforms or even normal pattern. MALDI-MS showed the presence of hypogalactosylated transferrin N-glycans, spontaneously decreasing during the disease course, only in one affected sibling. Total serum N-glycome depicted a distinct pattern for the three patients, with increased levels of undergalactosylated and undersialylated precursors of fully sialylated biantennary glycans, including the monosialo-monogalacto-biantennary species A2G1S1. Conclusions: Clinical, MRI and glycosylation features of patients are consistent with SLC39A8-CDG. We document two novel variants associated with Leigh syndrome-like disease presentation of SLC39A8-CDG. We show, for the first time, a severe neurological phenotype overlapping with that described for SLC39A8-CDG in association with the homozygous A391T missense variant. We observed a spontaneous amelioration of transferrin N-glycome, highlighting the efficacy of MS-based serum glycomics as auxiliary tool for the diagnosis and clinical management of therapy response in patients with SLC39A8-CDG. Further studies are needed to analyse more in depth the influence of SLC39A8 variants, including the common missense variant, on the expression and function of ZIP8 protein, and their impact on clinical, biochemical and neuroradiological features

Variazioni stagionali di indicatori di benessere in allevamenti lombardi di bovine da latte in aree di pianura, collinari e pedemontane

One of the main priorities of the agricultural EU policies is to set up valid, reliable and feasible indicators for on-farm welfare assessment. The EU Welfare Quality\uae project has developed a set of valid and feasible indicators, that have also been tested for inter-observer repeatability. For those indicators, repeatability between different times of survey has already been tested, but always within limited time spans; therefore, we have no information about their long-term repeatability, e.g. in extremely different seasonal conditions. We can hypothesize that more or less marked seasonal variations can occur, depending on farms\u2019 geographical location. In order to verify this hypothesis, we collected some welfare indicators, derived from the Welfare Quality\uae protocol, in 22 dairy farms located in plain, hilly and piedmont areas in Lumbardy, both in summer and in winter. No differences between seasons were found for presence of hairless patch areas, lameness, avoidance distance at the feeding rack (used to evaluate human-animal relationship) and for the other behavioural indicators. The percentage of cow that are too lean was higher in winter, especially in piedmont farms, where the climate is more severe. In fact, a long cold period, with rain, snow and wind, may cause an increase of energy consumption that, in turn, can make cows loose weight. The percentage of cows with diarrhoea was higher in winter, probably due to a reduction of digestion efficiency, induced by low environmental temperatures, that increased the sensibility of cows to enteric pathologies. We may conclude that the geographic location of the farms affected the repeatability of some welfare indicators in different seasons. The present study was carried out in the frame of the EULAT project, supported by Lumbardy Region, and that aims at the valorization of an excellent production chain \u2013 in terms of environmental sustainability, animal welfare and nutritional quality for the production of milk and dairy products

Cyclocreatine treatment ameliorates the cognitive, autistic and epileptic phenotype in a mouse model of Creatine Transporter Deficiency

Creatine Transporter Deficiency (CTD) is an inborn error of metabolism presenting with intellectual disability, behavioral disturbances and epilepsy. There is currently no cure for this disorder. Here, we employed novel biomarkers for monitoring brain function, together with well-established behavioral readouts for CTD mice, to longitudinally study the therapeutic efficacy of cyclocreatine (cCr) at the preclinical level. Our results show that cCr treatment is able to partially correct hemodynamic responses and EEG abnormalities, improve cognitive deficits, revert autistic-like behaviors and protect against seizures. This study provides encouraging data to support the potential therapeutic benefit of cyclocreatine or other chemically modified lipophilic analogs of Cr

Zukunftskonzept Harz : eine Untersuchung zur zukünftigen Anpassung des Wintertourismus an den Klimawandel

Der Harz ist ein deutsches Mittelgebirge dessen Haupterwerbsquelle der Tourismus ist. Diese Arbeit befasst sich mit dem Umgang der durch den Klimawandel verursachten Gefährdung des Wintertourismus. Die steigenden Temperaturen und Niederschlagsveränderungen führen zu immer häufigeren schneefreien Tagen während der Wintersaison und stellen eine große Gefahr für die Erhaltung des Wintertourismus im Harz dar. Anpassungsmaßnahmen- und Strategien wie der Einsatz von Schneekanonen werden stark diskutiert. Viele sehen den Gebrauch von künstlichem Schnee als einzige Möglichkeit auch in Zukunft eine gute Wintersaison und somit auch eine wichtige Einnahmequelle erhalten zu können. Kunstschneegegner hingegen sehen dieser Entwicklung mit großer Besorgnis entgegen. Hohe Kosten, ein maßloser Wasserverbrauch und der rücksichtslose Eingriff in die Natur werden hingenommen und das Ergebnis wird auf den Schulter der nächsten Generationen ausgetragen. Ein Blick auf die tatsächlichen Möglichkeiten des Harzes Kunstschnee zu benutzen und auch die Aussicht auf die demografische Entwicklung bezüglich der zukünftigen Zielgruppen zeigen, dass künstlicher Schnee die Zukunft des Harzer Wintertourismus nicht sichern kann