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Background Previous studies by our group have shown that oxidative phosphorylation (OXPHOS) is the main pathway by which pancreatic cancer stem cells (CSCs) meet their energetic requirements; therefore, OXPHOS represents an Achille’s heel of these highly tumorigenic cells. Unfortunately, therapies that target OXPHOS in CSCs are lacking. Methods The safety and anti-CSC activity of a ruthenium complex featuring bipyridine and terpyridine ligands and one coordination labile position (Ru1) were evaluated across primary pancreatic cancer cultures and in vivo, using 8 patient-derived xenografts (PDXs). RNAseq analysis followed by mitochondria-specific molecular assays were used to determine the mechanism of action. Results We show that Ru1 is capable of inhibiting CSC OXPHOS function in vitro, and more importantly, it presents excellent anti-cancer activity, with low toxicity, across a large panel of human pancreatic PDXs, as well as in colorectal cancer and osteosarcoma PDXs. Mechanistic studies suggest that this activity stems from Ru1 binding to the D-loop region of the mitochondrial DNA of CSCs, inhibiting OXPHOS complex-associated transcription, leading to reduced mitochondrial oxygen consumption, membrane potential, and ATP production, all of which are necessary for CSCs, which heavily depend on mitochondrial respiration. Conclusions Overall, the coordination complex Ru1 represents not only an exciting new anti-cancer agent, but also a molecular tool to dissect the role of OXPHOS in CSCs. Results indicating that the compound is safe, non-toxic and highly effective in vivo are extremely exciting, and have allowed us to uncover unprecedented mechanistic possibilities to fight different cancer types based on targeting CSC OXPHOS.

Reducing the time for drying sawn timber to a certain moisture level without deteriorating its quality is increasingly important for an economic and energy-efficient industrial timber-drying process and to support the transition to a sustainable society. It is, however, crucial to ensure that the quality of the timber, i.e. the degree of distortion, cracking, discolouration, and moisture variation within and between the pieces in a drying batch, is not compromised. Drying-simulation software tend to be too conservative in drying-rate recommendations, which has been observed in practise particularly for large cross-section timber of Norway spruce. This study investigated the drying rate and checking occurrence of centre-yielded Norway spruce planks when dried with more aggressive schedules than normally used in practise, i.e. using higher dry-bulb temperatures and/or lower relative humidities than recommended in the conventional optimisation programmes used in the sawmill industry in Sweden. The objective was to investigate the possibility to considerably reduce the total drying time without compromising the quality of the dried timber. The quality of the planks was indirectly assessed by estimating their moisture-content distributions, calculating the moisture gradients and monitoring checking. This was achieved with 4D (3D + time) X-ray computed tomography and a recently developed image processing algorithm based on elastic image registration. The key findings in this study suggest that Norway spruce timber can be dried with significantly higher temperatures and lower relative humidities than suggested by simulations, leading to reduced total drying time without inducing checking. This methodology can help to improve the design of drying schedules to reduce drying time and energy consumption while maintaining timber quality at a level accepted by the customers., Validerad;2024;Nivå 2;2024-03-25 (hanlid);Full text license: CC BY 4.0This article has previously appeared as a manuscript in a thesis.

Determining moisture content (MC) distribution during the drying of porous materials such as wood is crucial for developing drying schedules and assessing their suitability to achieve optimised processes. This study aimed to determine the causes of the unique drying behaviour and the well-known unusual longer drying time of western hemlock compared to other similar softwoods. In situ X-ray computed tomography (CT) was used to study the evolution of MC in timber during the drying process. The drying behaviour of western hemlock (Tsuga heterophylla (Raf.) Sarg.) was compared with Norway spruce (Picea abies (L.) Karst.) and Scots pine (Pinus sylvestris L.) from green to oven-dried condition with industry-proposed drying schedules used for steering a custom-made experimental kiln combined with a CT scanner. CT scanning was performed at 30 min intervals during the complete drying period of 30 h, and the CT images were processed to calculate the MC evolution within the specimen. Western hemlock showed a considerably slower capillary-phase drying and did not go into the transition and diffusion phases when a schedule adapted to pine and spruce drying was applied for its drying. CT images and MC gradient calculations showed a lower drying rate and severe non-uniformity in MC distribution, which could be due to the effect of higher green MC and the presence of wet pockets. Furthermore, the evaporation front at the first 5 h of drying receded faster into the hemlock specimen, and as drying proceeded, it slowed down compared to other specimens., Godkänd;2023;Nivå 0;2023-10-12 (joosat);Konferensartikel i tidskrift;Part of special Issue: International Conference Wood Science and Engineering in the Third Millennium - ICWSE 2023CC BY 4.0 License

Drying green sawn timber to a specific moisture content is needed for further processing. Large batch kilns of approx. 100 cubic meters of timber loads are commonly used with heated air blowing across the packages. When the air reaches the end of the blow depth, it has considerably increased its relative humidity by the evaporation from the wet timber. To even out the climate at the beginning and end of the blow depth, the direction of air circulation is reversed periodically. This exposes timber at those locations to fluctuations in climate while the middle packages are exposed to a more even climate. This study aimed to find the influence of the location of timber along the blow depth in liquid-water-flow behavior during the initial stages of drying. A research drying kiln combined with a CT-scanner was used to mimic this environment across the load and obtain CT images simultaneously, which were used to study the moisture content evolution. The results found that the transition between the capillary and the diffusion regimes can be identified with this method. Additionally, the transition regime was entered earlier for specimens drying in the more even climate which modeled the middle of a drying kiln, but with larger water pockets nearer to the surface of the specimens., Validerad;2024;Nivå 1;2024-05-02 (hanlid);Full text license: "All content is freely available without charge to any user or his/her institution. Users are allowed to read, download, copy, distribute, print, search, or link to the full texts of the articles in this journal without asking prior permission from the publisher or the author."

Most of the physical, mechanical, and esthetic properties of wood products are affected by the drying of sawn timber. A better understanding of moisture transport in wood during kiln drying is necessary to obtain better quality products, shorter drying schedules, lower energy consumption, and a more sustainable process. Four-dimensional X-ray computed tomography (4DCT) (three-dimensional in space and one in time) with image processing techniques can be used to study the moisture content (MC) of sawn timber during kiln drying. The development of the technique is however made difficult by computational complexity and a lack of accurate experimental validation. In this study, a method relying on 4DCT has been developed using state-of-the-art image processing techniques. The method was validated by a regression analysis of the predicted MC against gravimetric measurements for different timber cross sections and differentinitial MC distributions on a significantly smaller scale than has previously been investigated. It is concluded that the MC can be estimated with an average uncertainty of ±4.8 percentage points on a 10 mm scale. Sawmills could ultimately benefit from a better understanding of wood-water interactions and dry sawn timber more efficiently.

Funder: Republic of Slovenia; Slovenian Research Agency ARRS (J4-3087); CT WOOD

Thermo-hydro-mechanical (THM)-densified timber is rarely used in construction, although its mechanical properties are in many cases excellent. The main reason for its rare use is set-recovery, which reduces the degree of densification over time so that the mechanical properties deteriorate. Our knowledge of the long-term creep of densified timber is insufficient and a full understanding of its long-term behaviour is still lacking. The purpose of this study was to examine the behaviour under long-term loading of Scots pine sapwood densified in an open system at 170–200 °C. The influence of the THM densification process on the creep properties was studied on (1) unmodified specimens, (2) THM-densified specimens, (3) THM-densified specimens that had been further thermally treated, and (4) low-molecular-weight phenol-formaldehyde resin-impregnated and THM-densified specimens. All specimens were loaded at 20 ± 2 °C and 65 ± 5% relative humidity for 14 days under 3-point bending at 35% of the short-term ultimate load, and the bending deformation was registered. The THM densification doubled the density, causing a significant increase in the modulus of rupture but no change in the modulus of elasticity, and reduced the equilibrium moisture content and creep compliance. Post-thermal modification and resin impregnation improved the dimensional stability and further reduced the creep compliance in bending. The results demonstrate that THM densification combined with resin-impregnation or thermal modification reduces the creep of Scots pine timber under a long-term bending load in a constant climate., Validerad;2022;Nivå 2;2022-05-16 (joosat);Funder: Republic of Slovenia, European Regional Development Fund, Slovenian Research Agency ARRS (J4-3087); CT WOOD, Luleå University of Technology

A partir de la noción central de trauma –tanto en su sentido individual como en su sentido colectivo– y del marco conceptual y metodológico de la psicología analítica –según el modelo teórico propuesto por C.G. Jung–, esta investigación propone una interpretación psicológica de algunos de los escritos más importantes e influyentes del cristianismo primitivo. Al menos durante el período correspondiente a las dos primeras generaciones, el cristianismo fue una facción más dentro del judaísmo, y se desarrolló tomando como referencia muchos conceptos y nociones de las Escrituras hebreas. De ahí que en primer lugar se interpreten tanto algunos pasajes concretos como algunas características generales de la Biblia hebrea que parecen remitir al afrontamiento y a la elaboración de experiencias traumáticas. Tomando como referencia la destrucción del Templo de Jerusalén del año 587 a.C. y la consiguiente deportación a Babilonia, se analizan las posibles repercusiones, individuales y colectivas, así como sus huellas en las Escrituras, de esta experiencia profundamente traumática. Las consecuencias de Babilonia, y de otras muchas vivencias traumáticas con características análogas, dejaron su impronta no sólo en las Escrituras hebreas, sino también en las Escrituras cristianas como una memoria traumática colectiva..., Starting from the central notion of trauma –both in its individual and its collective sense– and the conceptual and methodological framework of Analytical Psychology –according to the theoretical model proposed by C.G. Jung–, this research proposes a psychological interpretation of some of the most influential writings of early Christianity. At least for the period corresponding to the first two generations, Christianity was one more faction within Judaism, and developed by reference to many concepts and notions from the Hebrew Scriptures. For this reason, some concrete passages and some general characteristics of the Hebrew Bible that seem to refer to coping with and the elaboration of traumatic experiences are interpreted. Based on the destruction of the Jerusalem Temple in 587 B.C. and the consequent deportation to Babylon, the possible repercussions of this deeply traumatic experience for the Jewish people, both individual and collective, as well as its traces in the Scriptures, are analyzed. The consequences of Babylon, and of many other traumatic experiences with analogous characteristics, left their mark not only in the Hebrew Scriptures, but also in the Christian Scriptures as a collective traumatic memory...

Tailored ruthenium sandwich complexes bearing photoresponsive arene ligands can efficiently promote azide–thioalkyne cycloaddition (RuAtAC) when irradiated with UV light. The reactions can be performed in a bioorthogonal manner in aqueous mixtures containing biological components. The strategy can also be applied for the selective modification of biopolymers, such as DNA or peptides. Importantly, this ruthenium-based technology and the standard copper-catalyzed azide–alkyne cycloaddition (CuAAC) proved to be compatible and mutually orthogonal

Tailored ruthenium sandwich complexes bearing photoresponsive arene ligands can efficiently promote azide-thioalkyne cycloaddition (RuAtAC) when irradiated with UV light. The reactions can be performed in a bioorthogonal manner in aqueous mixtures containing biological components. The strategy can also be applied for the selective modification of biopolymers, such as DNA or peptides. Importantly, this ruthenium-based technology and the standard copper-catalyzed azide-alkyne cycloaddition (CuAAC) proved to be compatible and mutually orthogonal.