Reboot

I am an artist that works with technologically obsolete materials in order to elevate them to have purely aesthetic, sublime qualities. Creating my art this way has led me to profile and understand hoarders; those who collect materials that are otherwise socially useless. They collect these objects to the point where the collection act becomes an obsessive psychological disorder. This thesis will prove that while I identify with those who struggle with this disorder, my own collection tendencies lend themselves to being more related to the processes of contemporary artists and their need to reconfigure the original use of objects in multitude

Utilization of granular solidification during terrestrial locomotion of hatchling sea turtles

Biological terrestrial locomotion occurs on substrate materials with a range of rheological behaviour, which can affect limb-ground interaction, locomotor mode and performance. Surfaces like sand, a granular medium, can display solid or fluid-like behaviour in response to stress. Based on our previous experiments and models of a robot moving on granular media, we hypothesize that solidification properties of granular media allow organisms to achieve performance on sand comparable to that on hard ground. We test this hypothesis by performing a field study examining locomotor performance (average speed) of an animal that can both swim aquatically and move on land, the hatchling Loggerhead sea turtle (Caretta caretta). Hatchlings were challenged to traverse a trackway with two surface treatments: hard ground (sandpaper) and loosely packed sand. On hard ground, the claw use enables no-slip locomotion. Comparable performance on sand was achieved by creation of a solid region behind the flipper that prevents slipping. Yielding forces measured in laboratory drag experiments were sufficient to support the inertial forces at each step, consistent with our solidification hypothesis

Snow accumulation and ablation measurements in a midlatitude mountain coniferous forest (Col de Porte, France, 1325 m altitude): the Snow Under Forest (SnoUF) field campaign data set

Forests strongly modify the accumulation, metamorphism and melting of snow in midlatitude and high-latitude regions. Recently, snow routines in hydrological and land surface models were improved to incorporate more accurate representations of forest snow processes, but model intercomparison projects have identified deficiencies, partly due to incomplete knowledge of the processes controlling snow cover in forests. The Snow Under Forest (SnoUF) project was initiated to enhance knowledge of the complex interactions between snow and vegetation. Two field campaigns, during the winters 2016–2017 and 2017–2018, were conducted in a coniferous forest bordering the snow study at Col de Porte (1325 m a.s.l., French Alps) to document the snow accumulation and ablation processes. This paper presents the field site, the instrumentation and the collection and postprocessing methods. The observations include distributed forest characteristics (tree inventory, lidar measurements of forest structure, subcanopy hemispherical photographs), meteorology (automatic weather station and an array of radiometers), snow cover and depth (snow pole transect and laser scan) and snow interception by the canopy during precipitation events. The weather station installed under dense canopy during the first campaign has been maintained since then and has provided continuous measurements throughout the year since 2018. Data are publicly available from the repository of the Observatoire des Sciences de l'Univers de Grenoble (OSUG) data center at https://doi.org/10.17178/SNOUF.2022 (Sicart et al., 2022).</p

The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer

Abstract: Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors

A non-internalised CD38-binding radiolabelled single-domain antibody fragment to monitor and treat multiple myeloma.

peer reviewedBACKGROUND: Antibody-based therapies targeting CD38 are currently used as single agents as well as in combination regimens for multiple myeloma, a malignant plasma cell disorder. In this study, we aimed to develop anti-CD38 single-domain antibodies (sdAbs) that can be used to trace CD38(+) tumour cells and subsequently used for targeted radionuclide therapy. SdAbs are derived from Camelidae heavy-chain antibodies and have emerged as promising theranostic agents due to their favourable pharmacological properties. METHODS: Four different anti-CD38 sdAbs were produced, and their binding affinities and potential competition with the monoclonal antibody daratumumab were tested using biolayer interferometry. Their binding kinetics and potential cell internalisation were further studied after radiolabelling with the diagnostic radioisotope Indium-111. The resulting radiotracers were evaluated in vivo for their tumour-targeting potential and biodistribution through single-photon emission computed tomography (SPECT/CT) imaging and serial dissections. Finally, therapeutic efficacy of a lead anti-CD38 sdAb, radiolabelled with the therapeutic radioisotope Lutetium-177, was evaluated in a CD38(+) MM xenograft model. RESULTS : We retained anti-CD38 sdAb #2F8 as lead based on its excellent affinity and superior stability, the absence of competition with daratumumab and the lack of receptor-mediated internalisation. When intravenously administered to tumour-xenografted mice, radiolabelled sdAb #2F8 revealed specific and sustained tumour retention with low accumulation in other tissues, except kidneys, resulting in high tumour-to-normal tissue ratios. In a therapeutic setting, myeloma-bearing mice received three consecutive intravenous administrations of a high (18.5 MBq) or a low radioactive dose (9.3 MBq) of (177)Lu-DTPA-2F8 or an equal volume of vehicle solution. A dose-dependent tumour regression was observed, which translated into a prolonged median survival from 43 days for vehicle-treated mice, to 62 days (p = 0.027) in mice receiving the low and 65 days in mice receiving the high (p = 0.0007) radioactive dose regimen, respectively. CONCLUSIONS: These results highlight the theranostic potential of radiolabelled anti-CD38 sdAbs for the monitoring and treatment of multiple myeloma

Radiotheranostic Agents in Hematological Malignancies.

peer reviewedRadioimmunotherapy (RIT) is a cancer treatment that combines radiation therapy with tumor-directed monoclonal antibodies (Abs). Although RIT had been introduced for the treatment of CD20 positive non-Hodgkin lymphoma decades ago, it never found a broad clinical application. In recent years, researchers have developed theranostic agents based on Ab fragments or small Ab mimetics such as peptides, affibodies or single-chain Abs with improved tumor-targeting capacities. Theranostics combine diagnostic and therapeutic capabilities into a single pharmaceutical agent; this dual application can be easily achieved after conjugation to radionuclides. The past decade has seen a trend to increased specificity, fastened pharmacokinetics, and personalized medicine. In this review, we discuss the different strategies introduced for the noninvasive detection and treatment of hematological malignancies by radiopharmaceuticals. We also discuss the future applications of these radiotheranostic agents

The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer

Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PAM, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and pArg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM(-/-) patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors