KTH Royal Institute of Technology

Clear cell renal cell carcinoma (ccRCC) presents substantial therapeutic challenges due to its molecular heterogeneity, limited response to conventional therapies, and widespread drug resistance. Recent advancements in molecular research have identified novel targets, such as BUB1B, which has been identified through global transcriptomic profiling and gene co-expression network analysis as critical in ccRCC progression. In this study, we synthesized 40 novel derivatives of TG-101209 to modulate BUB1B expression and activity, leading to the induction of apoptosis in Caki-1 cells. The molecular structures of all compounds were confirmed via 1H and 13C-NMR and mass spectrometry. Computational docking studies were conducted using Schrödinger Maestro software. The efficacy of the compounds on cell viability was screened using the MTT assay and further validated by the LDH assay. The expression of the target protein BUB1B and apoptosis-related proteins was analyzed via western blotting. BUB1B activity was assessed through an enzymatic assay, and compound binding efficacy was evaluated using a cellular thermal shift assay (CETSA). The results indicated that four compounds (7h, 8h, 8i, and 8j) demonstrate stronger molecular interactions and better conformational fit within the target cavity, leading to improved binding affinity. These compounds also exhibited more potency in reducing the viability of Caki-1 cells compared to TG-101209. In particular, compound 8h was identified as the most effective, exhibiting the strongest inhibitory effect on BUB1B and inducing apoptosis. Compound 8h demonstrated intracellular binding with BUB1B, similar to TG-101209, but through a different binding moiety that destabilizes the BUB1B protein structure, whereas TG-101209 stabilizes it. In conclusion, compound 8h, by destabilizing BUB1B and inducing apoptosis, shows promise as a potent therapeutic candidate for clear cell renal cell carcinoma (ccRCC) treatment.

Laminar airflow (LAF) is essential for maintaining a sterile environment in operating rooms, but its rapid unidirectional flow decay leads to low airflow efficiency and increases energy consumption. The objective of this study is to investigate the energy-saving and air quality benefits of using a low-turbulence air curtain around laminar airflow, which is referred to as protective laminar airflow (PLAF). Numerical simulations were used to model airflow and particle transport, and a series of experiments were conducted in a real operating room at St. Olavs Hospital, Norway, to validate the simulation results. The findings indicate that when the unidirectional airflow supply velocity is maintained at 0.25 m/s, combined with an air curtain that has the width of 2 cm and the velocity of 1.5 m/s, the PLAF system outperforms the conventional LAF system operating at a unidirectional airflow supply velocity of 0.30 m/s. This configuration results in a 17.3% energy saving, showing the potential of this airflow distribution strategy to enhance both cleanliness and energy efficiency.

Trust is essential for social interactions, including those between humans and social artificial agents, such as robots. Several factors and combinations thereof can contribute to the formation of trust and, importantly in the case of machines that work with a certain margin of error, to its maintenance and repair after it has been breached. In this paper, we present the results of a study aimed at investigating the role of robot voice and chosen repair strategy on trust formation and repair in a collaborative task. People helped a robot navigate through a maze, and the robot made mistakes at pre-defined points during the navigation. Via in-game behaviour and follow-up questionnaires, we could measure people's trust towards the robot. We found that people trusted the robot speaking with a state-of-the-art synthetic voice more than with the default robot voice in the game, even though they indicated the opposite in the questionnaires. Additionally, we found that three repair strategies that people use in human-human interaction (justification of the mistake, promise to be better, and denial of the mistake) work also in human-robot interaction.

The implicit boundary integral method (IBIM) provides a framework to construct quadrature rules on regular lattices for integrals over irregular domain boundaries. This work provides a systematic error analysis for IBIMs on uniform Cartesian grids for boundaries with different degrees of regularity. First, it is shown that the quadrature error gains an additional order of $\frac{d-1}{2}$ d - 1 2 from the curvature for a strongly convex smooth boundary due to the “randomness” in the signed distances. This gain is discounted for degenerated convex surfaces. Then the extension of error estimate to general boundaries under some special circumstances is considered, including how quadrature error depends on the boundary’s local geometry relative to the underlying grid. Bounds on the variance of the quadrature error under random shifts and rotations of the lattices are also derived.

Active suspensions encompass a wide range of complex fluids containing microscale energy-injecting particles, such as cells, bacteria or artificially powered active colloids. Because they are intrinsically non-equilibrium, active suspensions can display a number of fascinating phenomena, including turbulent-like large-scale coherent motion and enhanced diffusion. Here, using a recently developed active fast Stokesian dynamics method, we present a detailed numerical study of the hydrodynamic diffusion in apolar active suspensions of squirmers. Specifically, we simulate suspensions of active but non-self-propelling spherical squirmers (or ‘shakers’), of either puller type or pusher type, at volume fractions from 0.5 % to 55 %. Our results show little difference between pulling and pushing shakers in their instantaneous and long-time dynamics, where the translational dynamics varies non-monotonically with the volume fraction, with a peak diffusivity at around 10 % to 20 %, in stark contrast to suspensions of self-propelling particles. On the other hand, the rotational dynamics tends to increase with the volume fraction as is the case for self-propelling particles. To explain these dynamics, we provide detailed scaling and statistical analyses based on the activity-induced hydrodynamic interactions and the observed microstructural correlations, which display a weak local order. Overall, these results elucidate and highlight the different effects of particle activity versus motility on the collective dynamics and transport phenomena in active fluids.

A phenomenological description is presented to explain the intermediate and low-frequency/large-scale contributions to the wall-shear-stress ( ${\tau }_w$ ) and wall-pressure ( $\,{p}_w$ ) spectra of canonical turbulent boundary layers, both of which are well known to increase with Reynolds number, albeit in a distinct manner. The explanation is based on the concept of active and inactive motions (Townsend, J. Fluid Mech. , vol. 11, issue 1, 1961, pp. 97–120) associated with the attached-eddy hypothesis. Unique data sets of simultaneously acquired ${\tau }_w$ , ${p}_w$ and velocity-fluctuation time series in the log region are considered, across a friction-Reynolds-number ( $Re_{\tau }$ ) range of ${O}(10^3) \lesssim Re_{\tau } \lesssim {O}(10^6)$ . A recently proposed energy-decomposition methodology (Deshpande et al. , J. Fluid Mech. , vol. 914, 2021, A5) is implemented to reveal the active and inactive contributions to the ${\tau }_w$ - and $p_w$ -spectra. Empirical evidence is provided in support of Bradshaw's ( J. Fluid Mech. , vol. 30, issue 2, 1967, pp. 241–258) hypothesis that the inactive motions are responsible for the non-local wall-ward transport of the large-scale inertia-dominated energy, which is produced in the log region by active motions. This explains the large-scale signatures in the ${\tau }_w$ -spectrum, which grow with $Re_{\tau }$ despite the statistically weak signature of large-scale turbulence production, in the near-wall region. For wall pressure, active and inactive motions respectively contribute to the intermediate and large scales of the $p_w$ -spectrum. Both these contributions are found to increase with increasing $Re_{\tau }$ owing to the broadening and energization of the wall-scaled (attached) eddy hierarchy. This potentially explains the rapid $Re_{\tau }$ -growth of the $p_w$ -spectra relative to ${\tau }_w$ , given the dependence of the latter only on the inactive contributions.

In recent years, the development of biodegradable, cell-adhesive polymeric implants and minimally invasive surgery has significantly advanced healthcare. These materials exhibit multifunctional properties like self-healing, shape-memory, and cell adhesion, which can be achieved through novel chemical approaches. Engineering of such materials and their scalability using a classical polymer network without complex chemical synthesis and modification has been a great challenge, which potentially can be resolved using biobased dynamic covalent chemistry (DCC). Here, we report a scalable, self-healable, biodegradable, and cell-adhesive poly(ε-caprolactone) (PCL)-based vitrimer scaffold, using imine exchange, free from the limitations of melting transitions and supramolecular interactions in 4D-printed PCL. PCL's typical hydrophobicity hinders cell adhesion; however, our design, based on photopolymerization of PCL-dimethacrylate and methacrylate-terminated vanillin-based imine, achieves a water contact angle of 64°. The polymer network, fabricated in varying proportions, exhibited a co-continuous phase morphology, achieving optimal shape fixity (91 ± 1.7%) and shape recovery (92.5 ± 0.1%) at physiological temperature (37 °C). Additionally, the scaffold promoted cell adhesion and proliferation and reduced oxidative stress at the defect site. This multifunctional material shows the potential of DCC-based research in developing smart biomedical devices with complex geometries, paving the way for novel applications in regenerative medicine and implant design.

This article is a study of technological change in crosscountry (XC) skiing in Sweden from the late nineteenth century to the 1930s. While technological development in sport is usually seen as a linear and predetermined process, it is instead treated in this context as an arena where wills and intentions-grouped under the concepts of nostalgia and intensification-are negotiated. Nostalgia, in this sense, reflects a scepticism of innovation and change based on contemporary civilizational and rural-romantic concerns, whereas intensification represents the total mobilization of resources to improve sporting performance. The article shows that in its beginnings at the end of the nineteenth century, XC skiing expressed a romantic vision of a distinctive Swedish national landscape where skis were to be made using traditional and old-fashioned craftsmanship. In the early twentieth century, however, XC skiing changed and became progressive. The traditional Swedish skiing landscape was abandoned and the sport adapted to international conditions to enable Swedish athletes to compete successfully abroad. In other words, skiing was intensified because of the mobilization of resources by the Swedish Ski Association in close cooperation with the Swedish ski industry, which was then in an expansion phase.

Motivation Forecasting the synergistic effects of drug combinations facilitates drug discovery and development, especially regarding cancer therapeutics. While numerous computational methods have emerged, most of them fall short in fully modeling the relationships among clinical entities including drugs, cell lines, and diseases, which hampers their ability to generalize to drug combinations involving unseen drugs. These relationships are complex and multidimensional, requiring sophisticated modeling to capture nuanced interplay that can significantly influence therapeutic efficacy. Results We present a novel deep hypergraph learning method named Heterogeneous Entity Representation for MEdicinal Synergy prediction (HERMES) to predict the synergistic effects of anti-cancer drugs. Heterogeneous data sources, including drug chemical structures, gene expression profiles, and disease clinical semantics, are integrated into hypergraph neural networks equipped with a gated residual mechanism to enhance high-order relationship modeling. HERMES demonstrates state-of-the-art performance on two benchmark datasets, significantly outperforming existing methods in predicting the synergistic effects of drug combinations, particularly in cases involving unseen drugs. Availability and implementation The source code is available at https://github.com/Christina327/HERMES. Supplementary information Supplementary data are available at Bioinformatics online.

Terahertz (THz, 0.3–10 THz) radar systems have garnered significant attention due to their superior capabilities in high‐precision and robust sensing. However, the susceptibility to jamming, along with the sensing precision loss and ranging ambiguity induced by inflexible implementation of the conventional radar signal source, presents major challenges to the practical deployment of THz radars. Herein, a flexible photonic chaotic radar system is proposed at the THz band and investigate the ranging performance in precision and ambiguity. The photonic heterodyne detection scheme facilitates the generation of optoelectronic feedback loop‐based THz chaos at 300 GHz, achieving a seamless connection between THz domains and optical domains. The system is experimentally demonstrated its superior performance of sub‐centimeter resolution with 0.9345 cm and ranging unambiguity simultaneously. This work bridges the THz gap in the practical deployment of chaos theory and will pave the way for a new regime of THz radar empowered by chaos.

Biofilms constitute one of the most common forms of living matter, playing an increasingly important role in technology, health, and ecology. While it is well established that biofilm growth and morphology are highly dependent on the external flow environment, the precise role of fluid friction has remained elusive. We grew Bacillus subtilis biofilms on flat surfaces of a channel in a laminar flow at wall shear stresses spanning one order of magnitude ( τ w = 0.068 Pa to τ w = 0.67 Pa). By monitoring the three-dimensional distribution of biofilm over seven days, we found that the biofilms consist of smaller microcolonies, shaped like leaning pillars, many of which feature a streamer in the form of a thin filament that originates near the tip of the pillar. While the shape, size, and distribution of these microcolonies depend on the imposed shear stress, the same structural features appear consistently for all shear stress values. The formation of streamers occurs after the development of a base structure, suggesting that the latter induces a secondary flow that triggers streamer formation. Moreover, we observed that the biofilm volume grows approximately linearly over seven days for all shear stress values, with a growth rate inversely proportional to the wall shear stress. We develop a scaling model, providing insight into the mechanisms by which friction limits biofilm growth.

We study Hartree–Fock theory at half-filling for the 3D anisotropic Hubbard model on a cubic lattice with hopping parameter t in the x- and y-directions and a possibly different hopping parameter $t_z$ in the z-direction; this model interpolates between the 2D and 3D Hubbard models corresponding to the limiting cases $t_z=0$ and $t_z=t$, respectively. We first derive all-order asymptotic expansions for the density of states. Using these expansions and units such that t=1, we analyze how the Néel temperature and the antiferromagnetic mean field depend on the coupling parameter, U, and on the hopping parameter $t_z$. We derive asymptotic formulas valid in the weak coupling regime, and we study in particular the transition from the three-dimensional to the two-dimensional model as $t_z \rightarrow 0$. It is found that the asymptotic formulas are qualitatively different for $t_z = 0$ (the two-dimensional case) and $t_z > 0$ (the case of nonzero hopping in the z-direction). Our results show that certain universality features of the three-dimensional Hubbard model are lost in the limit $t_z \rightarrow 0$ in which the three-dimensional model reduces to the two-dimensional model.

In the dry-forming process, paper pulp is formed without adding water, making it more resource-effective than traditional papermaking. It is a relatively new technology, patented only in recent years, and very few material investigations exist in the literature; hence, little is known of the constitutive behaviour. The stress state during forming is highly complex, including multiaxial loading, extreme densification, friction, large strains, and fibre-joint formation. This paper studies dry-formed materials at different compression levels, from the sparse mat to the highly densified network. Three primary loading modes are investigated: in-plane tension, out-of-plane shear and out-of-plane compression. The results indicate that the tensile modulus and strength scale quadratically and cubically to the density, respectively, while the shear properties start developing after the density passes a threshold value. The compressive properties proved difficult to quantify, mainly because of the discrepancy between the density before and after the compressive test. The dry-formed material was compared to wet-formed paper materials in the literature. This showed that the in-plane (tensile) properties and the out-of-plane shear strength are visibly lower while the shear stiffness is similar, compared to wet-formed materials. Nonetheless, the findings set a starting point for numerical simulations of the dry-forming process.

The North Sea Basin has been covered by ice sheets originating from both the British Isles and Scandinavia at multiple times during the Pleistocene. The Witch Ground Basin (WGB) in the central northern North Sea is a critical location in terms of interpreting Late Pleistocene glacial to glacimarine history of the North Sea since it was the location of the Witch Ground Ice Stream that was active on multiple occasions during the Mid to Late Pleistocene. We map five mega‐scale glacial lineation flowsets corresponding to the changing ice flow direction of the Witch Ground Ice Stream and investigate the sedimentological fingerprint and corresponding subglacial depositional processes of this palaeo‐ice stream. We show that sorted sand layers within a subglacial traction till represent periodic hydraulic jacking and ice–bed decoupling at the base of the Witch Ground Ice Stream. In contrast to previous studies that have described glacitectonites deposited below the most recent grounded ice in the WGB, we present analysis of sediment cores that recovered primarily massive diamictons without any obvious deformation structures. The most recent ice cover in the WGB (~18–16 ka) was thought to have been sourced from a localized ice cap over Orkney and Shetland. The presence of chalk clasts sourced from NW of the WGB described in this study from the stratigraphically youngest till confirms this interpretation. The transition from subglacial to glacimarine deposition, while acoustically well defined (from opaque to laminated acoustic units), appears surprisingly uniform in the recovered sediment cores, but can be differentiated based on a change in colour including mottling and banding, presence of whole intact shells, and the increased number of silt and sand lenses. ¹⁴ C dating of glacimarine muds indicate high sedimentation rates of between 80 and 260 cm ka ⁻¹ . The transition from glacimarine to marine deposition is represented by a comparative decrease in sedimentation rate and deposition of Holocene age sandy mud. This study demonstrates a highly dynamic Witch Ground Ice Stream in the northern North Sea during the Late Pleistocene with evolving subglacial hydrology and depositional processes at the ice stream bed that left a distinct geomorphological and sedimentological fingerprint within the WGB.

The urban heat island (UHI) phenomenon is recognized as a main urban sustainability problem in the face of a changing climate, affecting human health, energy consumption, and other socio-economic considerations. The UHI can be mitigated by urban greenery, but it needs further investigation of detailed impacts across the urban landscape. The aim was to study UHI and model the relation to greenery in combination with urban grey structures, at a high spatiotemporal resolution across the urban landscape, in Stockholm. Temperature data was collected through opportunistic drive-by sensors on electric three-wheeled taxis. Data on greenview and skyview factors were used to inform on greenery and building density along the roads. During night and morning hours, the surface temperature was in general higher than air temperature, indicating that some densely built-up environments stored heat overnight. Hot zones were unevenly distributed throughout the city, while greenery had a cooling effect, especially when combined with skyview as an inverse measure of building density. Our results provide information on the spatiotemporal distribution of heat that can be used to inform efforts to use greenery for mitigating impacts of UHI on urban residents.

Energy poverty affects 550,000 homes in the Netherlands yet policy interventions to alleviate this issue are rare. Therefore, we test two energy coaching interventions in Amsterdam: a static information group (n = 67) which received energy efficient products and one energy-use report, and a smart information group (n = 50), which also had a display providing real-time feedback on energy-use. Results across both groups, show a 75% success rate for alleviating energy poverty. On average homes reduced monthly electricity consumption by 62 kWh (33%), gas by 41 m³ (42%), bills by €104 (53%) and percentage of income spent on energy from 10.1% to 5.3%.

Collisionless shock waves, found in supernova remnants, interstellar, stellar, and planetary environments, and laboratories, are one of nature’s most powerful particle accelerators. This study combines in situ satellite measurements with recent theoretical developments to establish a reinforced shock acceleration model for relativistic electrons. Our model incorporates transient structures, wave-particle interactions, and variable stellar wind conditions, operating collectively in a multiscale set of processes. We show that the electron injection threshold is on the order of suprathermal range, obtainable through multiple different phenomena abundant in various plasma environments. Our analysis demonstrates that a typical shock can consistently accelerate electrons into very high (relativistic) energy ranges, refining our comprehension of shock acceleration while providing insight on the origin of electron cosmic rays.