11. A novel dual-cytokine-antibody fusion protein for the treatment of CD38-positive malignanciesRoberto De Luca, Paul Kachel, Klara Kropivšek, Berend Snijder, Markus G. Manz, Dario Neri, 2018, izvirni znanstveni članek Opis: A novel dual-cytokine–antibody fusion protein, consisting of an antibody directed against CD38 [a tumor-associated antigen mainly expressed on the surface of multiple myeloma (MM) cells], simultaneously fused to both tumor necrosis factor ligand superfamily member 10 (TRAIL) and interleukin-2 (IL2), was designed, expressed and purified to homogeneity. The novel fusion protein, termed IL2-αCD38-αCD38-scTRAIL, was able to selectively recognize its cognate antigen expressed on the surface of MM and lymphoma cell lines, as evidenced by flow cytometry analysis. Moreover, the targeted version of TRAIL was able to induce cancer cell death in vitro, both with MM cell lines and with fresh isolates from the bone marrow of MM patients. The experiments provide a rationale for possible future applications of IL2-αCD38-αCD38-scTRAIL for the treatment of patients with MM or other CD38-positive malignancies.
Ključne besede: antibodies, dual-cytokine-antibody, CD38, multiple myeloma, TRAIL, IL2
Objavljeno v RUNG: 11.11.2024; Ogledov: 68; Prenosov: 0
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12. A roadmap of therapeutic strategies for patients with multiple myelomaBerend Snijder, Klara Kropivšek, 2023, drugi znanstveni članki Opis: Multiple myeloma is a rare and incurable cancer of plasma cells. To characterize this cancer, we developed an ex vivo drug screening method that combines imaging, deep learning and multiomics and applied it in an observational trial, uncovering new potential therapeutic strategies and underlying disease mechanisms.
Ključne besede: multiple myeloma, multiomics, deep learning, imaging, ex vivo drug screening
Objavljeno v RUNG: 11.11.2024; Ogledov: 64; Prenosov: 0
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13. 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, izvirni znanstveni članek Opis: 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.
Ključne besede: ultiple myeloma, precision medicine, ex-vivo, pharmacoscopy, proteotyping, oncology, hematology, microscopy, drug score
Objavljeno v RUNG: 11.11.2024; Ogledov: 65; Prenosov: 0
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14. Astrotop_X : razstavaNejc Trampuž, Dorotea Dolinšek, Peter Purg, Andreja Gomboc, 2024, razstava Opis: Medtem ko je velik del vesoljske industrije pa tudi družbenih ambicij in pripovedi usmerjen na iskanje življenju prijaznega planeta, se skupina umetnic_kov in znanstvenic_kov v projektu Astrotop_X sprašuje, kdo ali kaj je (ali so) subjekt(i), ki išče(jo) drugi dom v vesolju in kaj določa dejavnike, ki kozmično krajino opredelijo kot krajino ‘B.’ Izbrani ekosistem v kapsuli s pomočjo senzorske tehnologije ter računalniškega algoritma upira pogled v globoko vesolje, brska po podatkovni bazi eksoplanetov in presoja, kam – in če sploh – bi se kazalo preseliti v prihodnosti. Skrbno izbran del kraškega ekosistema v kapsuli Astrotop_X preko sporočanja stanja temperature in cirkadialnega ritma v realnem času analizirala bivanjski potencial na eksoplanetih.
Po premierni predstavitvi na pričujoči razstavi bo kapsula potovala v umetniško-znanstvenem laboratoriju xMobil, avtomobilski prikolici na sončne celice, ki predstavlja del zaprtokrožnega sistema, značilnega za vesoljska plovila. Tako se bodo v kapsuli naseljevali različni drugi prizadeti ekosistemi, medtem pa bodo teleskopi vsak dan odkrivali še kak morebitni planet B – ki pa bo seveda zmeraj predaleč, da bi tja tudi zares odpotovali ljudje. Morda pa bo to kdaj uspelo vsaj rastlinam?
Z vidika botanike je kraško rastlinstvo nedvomno že prilagojeno na trde življenjske pogoje, navajeno je na stres: zimski mraz, padavine, sušo, pomanjkanje zemlje in pregrevanje tal, sončno sevanje, burjo. Podobno, najbrž še huje bi bilo na eksoplanetu. Moralno-ekološka dilema: ali ne bi bila takšna rastlina, ki obišče ali se preseli na tuj planet preprosto invazivna vrsta? Tehnični problem: kako naj rastline preživijo tako dolgo pot? Prav možnost preživetja v takih razmerah je izziv tudi za raziskovalce, zato je izbor rastlin za potovanje prva, morda najpomembnejša odločitev. Poleg živih rastlin bi v tako kapsulo lahko dodali tudi t.i. “semensko bombico” ki potrpežljivo čaka na konec medzvezdnega potovanja…
Projekt Astrotop_X nasprotuje antropocentrističnemu dojemanju okolja in poudarja medsebojno soodvisnost vsega živega. V skladu z mislimi Donne Haraway in njenega “chthulucena” poziva k sobivanju večvrstnih skupnosti, kjer so nepremočrtna prepletenost in soodvisnost ključni za prihodnost Zemlje in njenih ekosistemov. Le na takšnem globokem sobivanju pa lahko temeljijo tudi tvorne spekulacije za prihodnost. Ali lahko rastline brez človeškega posredovanja postanejo zares avtonomni protagonisti medzvezdnih potovanj in
Skupina Astrotop_X:
Nejc Trampuž & Dorotea Dolinšek, umetnika
Andreja Gomboc, astronomija (UNG FN / CAK)
pETER Purg, znanost-umetnost (UNG FH/AU, GO! 2025)
Sodelujejo:
Programiranje: Saptashwa Bhattacharyya (UNG FN / CAK)
Botanika: Jože Bavcon ter Blanka Ravnjak (Botanični vrt, UL BF)
Tehnične rešitve: Dmitry Morozov
Grafično oblikovanje: Nejc Trampuž
Fotografiranje rastlin: Nejc Trampuž
Asistent fotograf: Jure Gubanc
Fotografija dogodkov: Gašper Rebernik (UNG AU)
Ekologija: Peter Trontelj (UL BF)
Skrb za jamo in okolje: Jamarski Klub Temnica
Produkcija: GO! 2025, Xcenter, Mojca Stubelj Ars
Astronomska opazovanja: Andrej Guštin, Eduardo Concepción
Produkcija GO! 2025 (Mojca Stubelj Ars, Xcenter) v okviru projektov PostMobilnost in xMobil (pETER Purg)
V sodelovanju z:
Univerza v Novi Gorici (ung.si), Fakulteta za naravoslovje (FN), Fakulteta za humanistiko (FH), Akademija umetnosti (AU)
Univerza v Ljubljani (uni-lj.si), Biotehniška fakulteta (BF) in Botanični vrt UL
Zavod Cosmolab
presežejo naše (človekove) fizične, fizikalne in nenazadnje geopolitične omejitve? V tem kontekstu Astrotop_X kritizira nenietzschejansko prečloveški tehnoeskapizem, ki poganja distopične fantazije kolonizacije vesolja. Opozarja na krhkost tuzemskih ekosistemov, ki so pogosto neupoštevani v dominantnih narativih o vesolju, tamkajšnjih vojaških in ekonomskih prestižih ter sci-fi pravljicah o lepi prihodnosti tam-nekje, vstran od grde in izčrpane krajine A. V algoritem kapsule je vključena podatkovna gesta, ki naposled priznava – da smo tukaj pravzaprav le ljudje (sami).
Tudi rastline so večplastne in nomadske enote, zato opirajoč se na posthumanistično misel Rosi Braidotti Astrotop_x spodbuja premik izven človeškega subjekta, s tem pa na novo opredeljuje in v fokus postavlja voljo ne-človeških dejavnikov. Četudi skozi nemara vendarle prečloveški umetniško-znanstveni pristop, kapsula Astrotop_X omogoča, da narava sama postane aktivna raziskovalka kozmične prihodnosti, s čimer razbija hierarhično ločnico med človekom in ne-človekom. Poziva k preučevanju ne le našega vpliva na planet, temveč tudi, kako lahko (tudi močno prizadeti) ekosistemi kot je (pred kratkim od ognja opustošen) Kras sami navigirajo skozi kompleksne čezresničnosti, kjer Zemlja morda ni več edino ali primarno domovanje živih bitij.
Ključne besede: znanost-umetnost, intermedijski, antropocen, medijski, astronomija, botanika, ekologija, interdisiplinaren, vesoljsko potovanje
Objavljeno v RUNG: 11.11.2024; Ogledov: 69; Prenosov: 0
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15. Cherenkov Telescope Array potential in the search for Galactic PeVatronsE.O. Angüner, Christopher Eckner, Gašper Kukec Mezek, Samo Stanič, Serguei Vorobiov, Lili Yang, Gabrijela Zaharijas, Danilo Zavrtanik, Marko Zavrtanik, Lukas Zehrer, 2019, objavljeni znanstveni prispevek na konferenci Opis: One of the major scientific objectives of the future Cherenkov Telescope Array (CTA) Observatory is the search for PeVatrons. PeVatrons are cosmic-ray factories able to accelerate nuclei at least up to the knee feature seen in the spectrum of cosmic rays measured near the Earth. CTA will perform a survey of the full Galactic plane at TeV energies and beyond with unprecedented sensitivity. The determination of efficient criteria to identify PeVatron candidates during the survey is essential in order to trigger further dedicated observations. Here, we present results from a study based on simulations to determine these criteria. The outcome of the study is a PeVatron figure of merit, defined as a metric that provides relations between spectral parameters and spectral cutoff energy lower limits. In addition, simulations of the PeVatron candidate HESS J1641−463 and its parental particle spectrum are presented and discussed. Eventually, our work is applied to simulated population of Galactic PeVatrons, with the aim to determine the sensitivity of CTA.
Ključne besede: Galactic cosmic rays, very-high-energy gamma rays, Galactic PeVatrons, Cherenkov Telescope Array (CTA) Observatory, Galactic plane survey, H.E.S.S. J1641−463 PeVatron candidate
Objavljeno v RUNG: 08.11.2024; Ogledov: 157; Prenosov: 5
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16. The gravitational wave follow-up program of the Cherenkov Telescope ArrayMonica Seglar-Arroyo, Christopher Eckner, Gašper Kukec Mezek, Samo Stanič, Serguei Vorobiov, Lili Yang, Gabrijela Zaharijas, Danilo Zavrtanik, Marko Zavrtanik, Lukas Zehrer, 2019, objavljeni znanstveni prispevek na konferenci Opis: The birth of gravitational-wave / electromagnetic astronomy was heralded by the joint observation of gravitational waves (GWs) from a binary neutron star (BNS) merger by Advanced LIGO and Advanced Virgo, GW170817, and of gamma-rays from the short gamma-ray burst GRB170817A by the Fermi Gamma-ray Burst Monitor (GBM) and INTEGRAL. This detection provided the first direct evidence that at least a fraction of BNSs are progenitors of short GRBs. GRBs are now also known to emit very-high-energy (VHE, > 100 GeV) photons as has been shown by recent independent detections of the GRBs 1901114C and 180720B by the ground-based gamma-ray detectors MAGIC and H.E.S.S. In the next years, the Cherenkov Telescope Array (CTA) will boost the searches for VHE counterparts thanks to its unprecedented sensitivity, rapid response and
capability to monitor large sky areas via survey-mode operation. In this contribution, we present the CTA program of observations following the detection of GW events. We discuss various follow-up strategies and links to multi-wavelength and multi-messenger observations. Finally we outline the capabilities and prospects of detecting VHE emission from GW counterparts.
Ključne besede: multi-messenger astrophysics, the Cherenkov Telescope Array (CTA) Observatory, gravitational waves, very-high-energy photons, gravitational-wave follow-up program
Objavljeno v RUNG: 08.11.2024; Ogledov: 167; Prenosov: 4
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17. Catalytic hydro(deoxy)genation of furfural and modelling of its reaction kineticsRok Šivec, 2024 Opis: In recent decades, there has been a growing interest in producing biofuels and biochemicals from renewable sources. Furfural stands as one of the ligno(hemi)cellulosic biomass derived platform chemical, which can be transformed into numerous value-added products.
The goal of this PhD was to systematically study hydrotreatment reactions of furfural under varying operating conditions and to gain insights into the reaction mechanism and kinetics. An extensive experimental and computational study of hydrogenation, hydrodeoxygenation, oligomerisation and etherification of furfural in a three-phase batch reactor was performed. The goals were divided into three consecutive objectives.
In the first part, hydrotreatment of furfural over Pd/C catalyst under various reaction conditions, including the solvent selection (solventless conditions, tetrahydrofuran, isopropanol), atmosphere (nitrogen, hydrogen), temperature (100–200 °C), pressure (25–75 bar) and stirring speed, was studied. A reaction pathway network and a micro-kinetic model were developed, incorporating thermodynamics (hydrogen solubility), mass transfer, adsorption, desorption, and surface reactions. These phenomena and their contribution to the surface coverages, TOF’s and global reaction rates were studied. The hydrogen presence on the catalyst surface was found to influence the main reaction pathway, leading to ring, aldehyde group or full hydrogenation.
In the second part, various monometallic catalysts (Pd/C, Pt/C, Re/C, Ru/C, Rh/C, Ni/C, Cu/C) were tested at 100 -200 °C with 60 bar of hydrogen and tetrahydrofuran as solvent. A generalized reaction pathway network was developed. H2 temperature-programmed reduction (H2-TPR) and CO temperature-programmed desorption (CO-TPD) were conducted, and a regression analysis of the results was subsequently performed by numerical modelling and optimisation. The obtained adsorption and desorption kinetic parameters for active metallic sites were further used in a generalized micro-kinetic model, applicable to all tested catalysts. Pd/C exhibited high activity and non-selective hydrogenation of furfural, while other catalysts showed selective aldehyde group hydrogenation followed by deoxygenation, consistent with density functional theory (DFT) calculations. Ru/C uniquely produced 2 methyltetrahydrofuran and ring-opening products at 200 °C. In silico optimization of reaction conditions for promising catalysts ((Pd/C, Pt/C, Re/C, Ni/C) aimed to maximize the yield of the target product.
In the third part, the influence of support on catalytic activity was studied. Hydrotreatment of furfural over Pd/Al2O3, Pd/SiO2, Ru/Al2O3, Ru/SiO2, Ni/Al2O3, and Ni/SiO2 was performed between 150 - 200 °C, using 60 bar of hydrogen and tetrahydrofuran as solvent. The strength and rate of adsorption and desorption to/from acidic, metallic and interface site structures were determined, using H2-TPR, CO-TPD and NH3-TPD and subsequent regression analysis of the results by numerical modelling and optimisation. The resulting parameters were sequentially used in the generalized micro-kinetic model to quantify the contribution of the active metal (Ni, Pd, or Ru), support (Al2O3 or SiO2), interphase sites and their relationship on catalyst activity and selectivity. Evaluation of morphological and structural characteristics, adsorption/desorption and intrinsic reaction kinetics has indicated that the coverage of acidic sites (on alumina or silica) facilitated yielding ring hydrogenation and inhibited deoxygenation, decarbonylation and cyclic compound opening. The rates for aromatics or aldehyde functional groups were, nonetheless, affected in a different order.
The used and developed methods and findings of this PhD offer useful guidelines for transforming furfural into high-value chemicals through catalytic hydrotreatment, with significant implications for future research and industrial applications.
Ključne besede: Lignocellulosic biomass, furfural, catalytic hydrogenation, micro-kinetic mass transfer model, reaction kinetics, first-principle methods, furfuryl alcohol, tetrahydrofurfuryl alcohol.
Objavljeno v RUNG: 08.11.2024; Ogledov: 145; Prenosov: 2
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18. REACTION MECHANISM AND MICROKINETICS OF HETEROGENEOUSLY CATALYSED LIGNIN DEPOLYMERISATION AND (DE)FUNCTIONALIZATION : DISSERTATIONTina Ročnik Kozmelj, 2024, doktorska disertacija Opis: Lignin, a complex aromatic polymer derived from lignocellulosic biomass, is a renewable resource for the production of aromatic-like chemicals and materials. However, its complex nature, depolymerisation and valorisation remain a major challenge for the bio-based community within biorefinery concepts. For this reason, lignin model compounds have been used to understand and design lignin depolymerisation, but insufficient attention has been paid to linking knowledge between simpler systems and applying it to a more complex problem. The objectives of this thesis were formulated accordingly to address the aforementioned gap in the literature. The objectives included a systematic approach correlating studies of lignin model compounds with lignin. Hydrodeoxygenation, cleavage of the β-O-4 bond and depolymerisation were investigated to evaluate the process- and structure-dependent correlations, effects on product distribution and kinetic parameters.
The catalytic reactions were carried out in batch reactor and the conditions were applied and intensified according to the knowledge gained during the experimental work. The liquid samples for monomer yield evaluation were analysed by GC-MS, while the structural characteristics of lignin and oligomeric fragments, e.g. molecular weight, functionality/reactivity and structural features, were examined by SEC, quantitative 31P and 2D-HSQC NMR. Kinetic modelling was performed to determine the kinetic parameters (e.g. kinetic constants and activation energies) describing defunctionalisation, β-O-4 bond cleavage and depolymerisation.
The study with monomeric lignin compounds contributed to the understanding of the key parameters leading to condensation during hydrotreatment. The unsaturated alkyl side-chain of eugenol and the reactive hydroxyl groups bound irreversibly and formed the carbonaceous species, while 4-propylphenol and 4-propylguaiacol provided important insights into the contribution of steric hindrances to a favourable reaction mechanism. An initial assessment of β-O-4 cleavage was performed with β-O-4-model compound, 2-phenoxy-1-phenylethanol, and linked to the lignin macromolecule by process- and structure-dependent correlations. Although the lignin model compound lacks the structural complexity of lignin, important insights into possible reaction processes were gained and accurate kinetic parameters were determined. Furthermore, lignin isolated in 50 vol% EtOH/H2O solutions was depolymerised and the optimal
reaction conditions were defined at a temperature of 275 °C and a pressure of 1.5 MPa with regard to the product distribution and the changes in the structural characteristics of the corresponding oligomeric fragments. Depolymerisation of lignins isolated in different EtOH/H2O solutions showed the importance of the structural features, especially ethoxylation degree and the content of β-O-4 or α-ethoxylated β-O-4 bonds. A higher ethoxylation degree of lignin reduced its potential to depolymerise and achieve the theoretical monomer yield. Therefore, the structural characteristics of lignin play the main role in designing and prediction of lignin depolymerisation.
The thesis represents a systematic approach of increasing the complexity of structures exposed to hydrodeoxygenation and depolymerisation. The approach contributed to incorporating the knowledge gained from less complex model compounds to real lignin samples by tailoring and designing lignin depolymerisation to exploit the potential of lignin for biorefinery concepts.
Ključne besede: model compounds, hydrodeoxygenation, organosolv lignin, depolymerisation, structural characteristics, kinetic modelling
Objavljeno v RUNG: 08.11.2024; Ogledov: 135; Prenosov: 0
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19. Magnetocaloric effect in amorphous and partially crystallized Fe[sub](40)Ni[sub](38)Mo[sub]4B[sub](18) alloysThanveer Thajudheen, R. V. Ramanujan, Senoy Thomas, 2016, izvirni znanstveni članek Opis: A study of magnetocaloric effect in amorphous and partially crystallized Fe40Ni38Mo4B18 alloys is reported. Amorphous Fe40Ni38Mo4B18, near its magnetic ordering temperature (600K) showed a magnetic entropy change ΔSM of 1.1 J/KgK and a relative cooling power of 36J/Kg in a field change of 10 kOe. Amorphous samples were partially crystallized by annealing at 700 K at different time intervals. Partially crystallized samples showed two distinct magnetic ordering temperature, one corresponding to the precipitated FeNi nanocrystals and the other one corresponding to the boron rich amorphous matrix. Magnetic ordering temperature of the residual amorphous matrix got shifted to the lower temperatures on increasing the annealing duration. Partially crystallised samples showed a magnetic entropy change of about 0.27J/kgK near the magnetic ordering temperature of the amorphous matrix (540K) in a field change of 10 kOe. The decrease in ΔSM on partial crystallisation is attributed to the biphasic magnetic nature of the s
Ključne besede: magnetism, phase transitions, entropy, equations of state, alloys, amorphous materials, annealing
Objavljeno v RUNG: 07.11.2024; Ogledov: 155; Prenosov: 3
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20. Testing cosmology and fundamental physics with the Cherenkov Telescope ArrayH. Martínez-Huerta, Christopher Eckner, Gašper Kukec Mezek, Samo Stanič, Serguei Vorobiov, Lili Yang, Gabrijela Zaharijas, Danilo Zavrtanik, Marko Zavrtanik, Lukas Zehrer, 2019, objavljeni znanstveni prispevek na konferenci Opis: The Cherenkov Telescope Array (CTA) is the next generation ground-based observatory for γ-ray astronomy at energies above 30 GeV. Thanks to its unique capabilities, CTA observations will
address a plethora of open questions in astrophysics, ranging from the origin of cosmic messengers to the exploration of the frontiers of physics. In this note, we present a comprehensive sensitivity study to assess the potential of CTA to measure the γ-ray absorption on the extragalactic background light (EBL), to constrain or detect intergalactic magnetic fields (IGMFs), and probe physics beyond the standard model such as axion-like particles (ALPs) and Lorentz invariance violation (LIV), which could modify the γ-ray spectra features expected from EBL absorption. Our results suggest that CTA will have unprecedented sensitivity to detect IGMF signatures and will probe so-far unexplored regions of the LIV and ALP parameter space. Furthermore, an indirect measurement of the EBL and of its evolution will be performed with unrivaled precision.
Ključne besede: very-high-energy gamma rays, the Cherenkov Telescope Array (CTA) Observatory, extragalactic background light (EBL), intergalactic magnetic fields (IGMFs), axion-like particles (ALPs), Lorentz invariance violation (LIV)
Objavljeno v RUNG: 07.11.2024; Ogledov: 166; Prenosov: 4
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