1. P856 : a single-cell functional precision medicine landscape of multiple myelomaKlara Kropivšek, Paul Kachel, Sandra Goetze, Rebekka Wegmann, Yannik Severin, Benjamin D. Hale, Yasmin Festl, Julien Mena, Audrey Van Drogen, Nadja Dietliker, 2022, published scientific conference contribution abstract Abstract: Multiple myeloma (MM) is a cancer of plasma cells, defined by complex genetics and extensive intra- and inter-patient heterogeneity. Despite improved patient survival driven by a plethora of treatment options, the disease remains incurable.
Molecularly-guided precision medicine to individualize treatment strategies in MM has had limited success, in part due to the genetic and molecular complexity of the disease. Functional precision medicine, a complementary approach in which patient treatment is guided by the ex vivo drug response of patient cells, has not yet been evaluated for MM systematically.
Keywords: mutliple myeloma, hematology, precision medicine, microscopy, deep learning, phenotyping, oncology, proteotype
Published in RUNG: 11.11.2024; Views: 366; Downloads: 2
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2. Ex vivo drug response heterogeneity reveals personalized therapeutic strategies for patients with multiple myelomaKlara Kropivšek, Paul Kachel, Sandra Goetze, Rebekka Wegmann, Yasmin Festl, Yannik Severin, Benjamin D. Hale, Julien Mena, Audrey Van Drogen, Nadja Dietliker, 2023, original scientific article Abstract: Abstract
Multiple myeloma (MM) is a plasma cell malignancy defined by complex genetics and extensive patient heterogeneity. Despite a growing arsenal of approved therapies, MM remains incurable and in need of guidelines to identify effective personalized treatments. Here, we survey the ex vivo drug and immunotherapy sensitivities across 101 bone marrow samples from 70 patients with MM using multiplexed immunofluorescence, automated microscopy and deep-learning-based single-cell phenotyping. Combined with sample-matched genetics, proteotyping and cytokine profiling, we map the molecular regulatory network of drug sensitivity, implicating the DNA repair pathway and EYA3 expression in proteasome inhibitor sensitivity and major histocompatibility complex class II expression in the response to elotuzumab. Globally, ex vivo drug sensitivity associated with bone marrow microenvironmental signatures reflecting treatment stage, clonality and inflammation. Furthermore, ex vivo drug sensitivity significantly stratified clinical treatment responses, including to immunotherapy. Taken together, our study provides molecular and actionable insights into diverse treatment strategies for patients with MM.
Keywords: ultiple myeloma, precision medicine, ex-vivo, pharmacoscopy, proteotyping, oncology, hematology, microscopy, drug score
Published in RUNG: 11.11.2024; Views: 377; Downloads: 4
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3. Insights into the single-particle composition, size, mixing state, and aspect ratio of freshly emitted mineral dust from field measurements in the Moroccan Sahara using electron microscopyAgnesh Panta, Konrad Kandler, Andrés Alastuey, Cristina González-Flórez, Adolfo Gonzalez-Romero, Martina Klose, Xavier Querol, Cristina Reche, Jesús Yus-Díez, Carlos Pérez García-Pando, 2023, original scientific article Abstract: Abstract. The chemical and morphological properties of mineral dust aerosols emitted by wind erosion from arid and semi-arid regions influence climate, ocean, and land ecosystems; air quality; and multiple socio-economic sectors. However, there is an incomplete understanding of the emitted dust particle size distribution (PSD) in terms of its constituent minerals that typically result from the fragmentation of soil aggregates during wind erosion. The emitted dust PSD affects the duration of particle transport and thus each mineral's global distribution, along with its specific effect upon climate. This lack of understanding is largely due to the scarcity of relevant in situ measurements in dust sources. To advance our understanding of the physicochemical properties of the emitted dust PSD, we present insights into the elemental composition and morphology of individual dust particles collected during the FRontiers in dust minerAloGical coMposition and its Effects upoN climaTe (FRAGMENT) field campaign in the Moroccan Sahara in September 2019. We analyzed more than 300 000 freshly emitted individual particles by performing offline analysis in the laboratory using scanning electron microscopy (SEM) coupled with energy-dispersive X-ray spectrometry (EDX). Eight major particle-type classes were identified with clay minerals making up the majority of the analyzed particles both by number and mass, followed by quartz, whereas carbonates and feldspar contributed to a lesser extent. We provide an exhaustive analysis of the PSD and potential mixing state of different particle types, focusing largely on iron-rich (Fe oxide-hydroxides) and feldspar particles, which are key to the effects of dust upon radiation and clouds, respectively. Nearly pure or externally mixed Fe oxide-hydroxides are present mostly in diameters smaller than 2 µm, with the highest fraction below 1 µm at about 3.75 % abundance by mass. Fe oxide-hydroxides tend to be increasingly internally mixed with other minerals, especially clays, as particle size increases; i.e., the volume fraction of Fe oxide-hydroxides in aggregates decreases with particle size. Pure (externally mixed) feldspar represented 3.2 % of all the particles by mass, of which we estimated about a 10th to be K-feldspar. The externally mixed total feldspar and K-feldspar abundances are relatively invariant with particle size, in contrast to the increasing abundance of feldspar-like (internally mixed) aggregates with particle size with mass fractions ranging from 5 % to 18 %. We also found that overall the median aspect ratio is rather constant across particle size and mineral groups, although we obtain slightly higher aspect ratios for internally mixed particles. The detailed information on the composition of freshly emitted individual dust particles and quantitative analysis of their mixing state presented here can be used to constrain climate models including mineral species in their representation of the dust cycle.
Keywords: mineral dust, Moroccan Sahara, electron microscopy
Published in RUNG: 13.05.2024; Views: 1196; Downloads: 8
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4. A framework for evaluating the performance of SMLM cluster analysis algorithmsDaniel J. Nieves, Jeremy A. Pike, Florian Levet, David J. Williamson, Mohammed Baragilly, Sandra Oloketuyi, Ario De Marco, Juliette Griffié, Daniel Sage, Edward A. K. Cohen, 2023, original scientific article Keywords: super resolution microscopy, functionalized nanobodies
Published in RUNG: 22.02.2023; Views: 2010; Downloads: 0
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5. Recent progress and applications of thermal lens spectrometry and photothermal beam deflection techniques in environmental sensingMladen Franko, Leja Goljat, Mingqiang Liu, Hanna Budasheva, Mojca Žorž, Dorota Korte, 2023, original scientific article Abstract: This paper presents recent development and applications of thermal lens microscopy (TLM) and beam deflection spectrometry (BDS) for the analysis of water samples and sea ice. Coupling of TLM detection to a microfluidic system for flow injection analysis (µFIA) enables the detection of microcystin-LR in waters with a four samples/min throughput (in triplicate injections) and provides an LOD of 0.08 µg/L which is 12-times lower than the MCL for microcystin-LR in water. µFIA-TLM was also applied for the determination of total Fe and Fe(II) in 3 µL samples of synthetic cloudwater.
The LODs were found to be 100 nM for Fe(II) and 70 nM for total Fe. The application of µFIA-TLM for the determination of ammonium in water resulted in an LOD of 2.3 µM for injection of a 5 µL sample and TLM detection in a 100 µm deep microfluidic channel. For the determination of iron
species in sea ice, the BDS was coupled to a diffusive gradient in the thin film technique (DGT). The 2D distribution of Fe(II) and total Fe on DGT gels provided by the BDS (LOD of 50 nM) reflected the distribution of Fe species in sea ice put in contact with DGT gels.
Keywords: thermal lens microscopy, beam deflection spectrometry, microfluidic system, microcystin-LR detection, iron species determination, ammonium detection
Published in RUNG: 03.01.2023; Views: 2914; Downloads: 41
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6. Electronic and chemical surface properties of Bi2Se3 derived compoundsZipporah Rini Benher, doctoral dissertation Keywords: Bismuth selenide derived compounds, surface chemical and electronic properties, topological insulators, single crystals, phase separation, inorganic bulk heterostructures, ix
Bridgman method, X-ray powder diffraction, scanning electron microscopy, photoelectron spectroscopy
Published in RUNG: 16.12.2022; Views: 2979; Downloads: 31
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7. Evolution of fractal dimension in pulsed laser deposited MoO3 film with ablation time and annealing temperatureMohanachandran Nair Sindhu Swapna, 2021, original scientific article Abstract: The multifractal analysis is a potential method for assessing thin flm surface morphology and its changes due to diferent
deposition conditions and post-deposition treatments. In this work, the multifractal analysis is carried out to understand the
surface morphology—root mean square (RMS) surface roughness—of nanostructured MoO3 flms prepared by pulsed laser
deposition technique by varying the ablation time and post-deposition annealing. The XRD analysis shows the evolution of
crystalline nature with annealing temperature. The XRD pattern of all the annealed flms shows the characteristic peak of
the orthorhombic MoO3 phase. The FESEM and AFM analysis reveals the morphological modifcation with ablation time
and annealing temperature. The multifractal analysis of the AFM images shows that the box—counting, information and
correlation dimension varies with the annealing temperature. The study also reveals the inverse relation between the fractal
dimension and the RMS surface roughness due to the annealing induced particle size variation and reorientation. The fractal
dimension’s evolution in the pulsed laser deposited MoO3 flm with ablation time and annealing temperature is also investigated. Thus, the study reveals the potential of multifractal analysis in the thin flm surface characterizatio
Keywords: Multifractal analysis · Pulsed laser deposition · Molybdenum oxide · Atomic force microscopy · Fractal
dimension
Published in RUNG: 04.07.2022; Views: 2204; Downloads: 0
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10. Unraveling the Role of Major Facilitator Superfamily (MFS) Transporters in Plant Abiotic Stress ToleranceChristina Paparokidou, 2014, final research report Abstract: The yields of worldwide crop production are negatively affected by adverse environmental conditions, such as drought, salinity, heavy metal contamination and nutrient depletion in cultivated soils (Yan et al., 2013; Golldack et al., 2011; Yadav, 2010; Kobayashi and Nishizawa, 2012). This reduced crop production constitutes a major problem for food sustainability world-wide (Spiertz, 2013). Indeed, one of the major challenges for plant biotechnology will be to satisfy the increased demand for food on one hand, and to compensate for the loss of crop production on the other. Thus, the discovery of new plant genes that are able to cope with these conditions is critical and expected not only to elucidate the molecular mechanisms underlying crop abiotic stress, but also to pioneer genetic engineering strategies for improved crop productivity.
The goal of this project was to identify novel genes belonging to the Major Facilitator Superfamily (MFS) of plant membrane transporters with potential major roles in conferring abiotic stress tolerance, namely to heavy metal, osmotic and iron deficiency stress. We selected three Arabidopsis thaliana MFS transporter genes, provisionally called MFS10, MFS11 and MFS12, which based on publicly available microarray data display specific expression patterns suggesting roles in plant tolerance to different abiotic stresses.
RT-PCR analyses showed that in fact the MFS10 gene is highly induced by cadmium (Cd), selenium (Se), salt and mannitol, while the MFS11 gene is upregulated by abscisic acid (ABA) and glucose, and the MFS12 gene by iron (Fe) deficiency, ABA and glucose. Furthermore, subcellular localization of fluorescent reporter fusions indicated that the MFS10 and MFS11 gene products are both plasma membrane localized transporters, while the encoded product of the MFS12 gene appears to be an endoplasmic reticulum localized transporter. Finally, reverse genetics using a null mutant allele for the MFS10 gene demonstrated that it functions as a regulator of plant responses to hyperosmotic (drought and salt) stress.
Keywords: Major Facilitator Superfamily (MFS), abiotic stress tolerance, heavy metals, osmotic stress, ABA stress, iron deficiency, T-DNA insertion lines, RT-PCR, confocal microscopy.
Published in RUNG: 03.05.2022; Views: 2380; Downloads: 0
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