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Somaattisten mutaatiosignatuurien ja ituradan polygeenisten riskisummien yhteys rintasyövissä
No full textMutational signatures in cancer reflect somatic mutational processes active throughout an individual’s lifetime and provide insights into cancer etiology. While some signatures are well-characterized, arising from environmental and endogenous processes, many remain poorly characterized and new signatures are frequently identified. Germline genetic factors, such as polygenic risk scores (PRS) combining genetic effects across the genome, impact cancer predisposition, but their role in shaping somatic mutational profiles remains largely unexplored. Understanding the interplay between germline predispositions and somatic mutational processes could provide new insights into cancer development.
This thesis explores the relationship between somatic mutational profiles and PRSs. Using data of 218 breast cancer patients of Finnish ancestry provided by the iCAN flagship project, we evaluated the associations between somatic mutational signatures and PRS for breast cancer and 30 common blood biomarkers by using Spearman’s correlation and beta regression. Mutational signature profiles of single base substitutions (SBS) were constructed from tumor whole-exome sequencing data and PRSs were computed in previous publications.
We observed in total of 20 associations (pSyövän mutaatiosignatuurit kuvaavat somaattisia mutaatioprosesseja, jotka ovat olleet aktiivisia yksilön elämän aikana. Vaikka osa näistä signatuureista ja niiden endo- tai eksogeenisista taustatekijöistä tunnetaankin hyvin, monien alkuperä on jäänyt pimentoon. Ituradan geenivarianttien on havaittu olevan yhteydessä myös somaattisten mutaatioiden syntyyn, mutta tämä yhteys ei ole vielä kovin hyvin tunnettu. Tätä yhteyttä lisää tutkimalla voisimme lisätä ymmärrystämme syövän synnystä ja kehittymisestä.
Tässä diplomityössä tutkimme lisää tätä yhteyttä löytääksemme assosiaatioita mutaatiosignatuurien ja ituradan geneettisten varianttien välille käyttämällä polygeenisia riskisummia (PRS) jotka summaavat ituradan geneettisten varianttien yhteisvaikutuksen. Tutkimme mutaatiosignatuurien ja rintasyövän PRS:n sekä 30 yleisen veren biomarkkerin PRS:ien välisiä assosiaatioita korrelaatioiden ja beta-regression avulla, käyttäen iCAN-lippulaivahankkeen dataa 218 suomalaisesta rintasyöpäpotilaasta. Mutaatiosignatuurit määritettiin tuumorien eksomisekvensointi-datasta, ja PRS:t olivat aiemmissa tutkimuksissa määritettyjä.
Havaitsimme kokonaisuudessaan 20 assosiaatiota (p<0.05) mutaatiosignatuuritasojen ja PRS:ien välillä. Esimerkiksi, havaitsimme reumafaktorin PRS:n ja signatuurin 13 (p=0.002) sekä apolipoproteiini A:n ja signatuurin 3 (p=0.006) välillä käänteisen yhteyden. Positiivinen yhteys havaittiin muun muassa konjugoituneen bilirubiinin PRS:n ja signatuurin 30 välillä (p=0.012). Lisäksi havaitsimme useita jo aiemmissa tutkimuksissa ilman genetiikkaa määriteltyjä yhteyksiä, kuten käänteisen yhteyden apolipoproteiini-B:n PRS:n ja signatuurin 13 välillä. Nämä assosiaatiot eivät kuitenkaan säilyneet merkittävinä monitestauskorjauksen jälkeen.
Tämän analyysin avulla löysimme uusia yhteyksiä ituradan geneettisten varianttien ja somaattisten mutaatiosignatuurien välille rintasyövissä. Nämä löydökset auttavat meitä ymmärtämään syövän kehittymistä, ja niitä lisää tutkimalla voimme vahvistaa ymmärrystämme aihealueesta. Parhaimmillaan tämä voisi johtaa uusien rintasyövän juuritekijöiden löytymiseen tai jopa uusien hoitomuotojen kehittämiseen
Data-efficient optimization of thermally-activated polymer actuators through machine learning
No full textPublisher Copyright: © 2025 The Author(s) | openaire: EC/H2020/949648/EU//ModelComFor applications in soft robotics and smart textiles, thermally-activated, twisted, and coiled polymer actuators can offer high mechanical actuation with proper optimization of their processing conditions. However, optimization is often aggravated by the potentially high number of processing variables and the time-consuming nature of materials synthesis and characterization. To overcome these problems, we employed an active machine learning workflow using Bayesian optimization. We subsequently used this approach to optimize the actuation of polymer coils based on three common processing conditions consisting of ply number, applied twisting and coiling stresses. Since the experimental parameters are discrete and not continuous as in conventional Bayesian optimization tasks, a discrete Bayesian optimization workflow was developed. An actuation strain of 1.25 was achieved by optimizing the processing conditions, which required the fabrication of only 62 sample combinations out of 1089 possible ones. Our results highlight the potential of Bayesian optimization in actuator design problems, thereby opening up possibilities for tackling more complex challenges by considering a broader range of processing conditions or addressing multi-objective tasks.Peer reviewe
A Shift Toward Supercritical Brain Dynamics Predicts Alzheimer’s Disease Progression
No full textPublisher Copyright: Copyright © 2024 Javed et al.Alzheimer’s disease (AD) is the most common form of dementia with continuum of disease progression of increasing severity from subjective cognitive decline (SCD) to mild cognitive impairment (MCI) and lastly to AD. The transition from MCI to AD has been linked to brain hypersynchronization, but the underlying mechanisms leading to this are unknown. Here, we hypothesized that excessive excitation in AD disease progression would shift brain dynamics toward supercriticality across an extended regime of critical-like dynamics. In this framework, healthy brain activity during aging preserves operation at near the critical phase transition at balanced excitation–inhibition (E/I). To test this hypothesis, we used source-reconstructed resting-state MEG data from a cross-sectional cohort (N = 343) of individuals with SCD, MCI, and healthy controls (HC) as well as from a longitudinal cohort (N = 45) of MCI patients. We then assessed brain criticality by quantifying long-range temporal correlations (LRTCs) and functional EI (fE/I) of neuronal oscillations. LRTCs were attenuated in SCD in spectrally and anatomically constrained regions while this breakdown was progressively more widespread in MC. In parallel, fE/I was increased in the MCI but not in the SC cohort. Both observations also predicted the disease progression in the longitudinal cohort. Finally, using machine learning trained on functional (LRTCs, fE/I) and structural (MTL volumes) features, we show that LRTCs and f/EI are the most informative features for accurate classification of individuals with SCD while structural changes accurate classify the individuals with MCI. These findings establish that a shift toward supercritical brain dynamics reflects early AD disease progression.Peer reviewe
Biobased Antimicrobial Coatings: Layer-by-Layer Assemblies Based on Natural Polyphenols
No full textPublisher Copyright: © 2025 The Authors. Published by American Chemical Society.Natural polyphenols possess inherent defensive properties against pathogens. This study investigated the radical scavenging and antimicrobial activity of biobased polyphenol nanoparticles (PNPs) derived from grape seeds. Scanning electron micrographs and dynamic light scattering confirmed the synthesized nanoparticles’ spherical shape, showing an average hydrodynamic radius of 93.9 ± 4.0 nm. The PNPs exhibited radical scavenging activity at about 433 mg Trolox per gram and a microbial inhibitory effect against Micrococcus luteus and Escherichia coli. The negatively charged PNPs were used to prepare thin multilayer films combined with positively charged polyelectrolytes such as poly(allylamine hydrochloride), poly-l-lysine, poly(diallyldimethylammonium chloride), or polyethylenimine. The viscoelastic properties of polyelectrolyte/PNP films were monitored using a quartz crystal microbalance with dissipation. The PNPs showed the best interface compatibility with poly-l-lysine (PLL), enabling the preparation of mechanically stable thin multilayer films. The antioxidant activity of PLL/PNP films was 72 ± 6 μg Trolox per cm2 at pH 10. The PLL/PNP films displayed antimicrobial activity against M. luteus and E. coli, with growth inhibition of 50.7 ± 0.6% and 12.1 ± 0.6%, respectively. The prepared biobased PLL/PNP Layer-by-Layer assemblies can potentially prevent biofilm formation on a large spectrum of materials.Peer reviewe
The role of personalised marketing communication on brand experience in omnichannel marketing
No full textPersonalised marketing communication (PMC) has been a prominent tool for marketers to connect and build relationships with customers. Yet, among previous studies, little was done to investigate the role of personalised marketing in brand experience. Moreover, previous studies focused on the PMC of a single channel rather than evaluating the synergy across channels. Although attention is expected to be paid to brand experience on all channels and touchpoints in omnichannel marketing, the digital channel faces more challenges in carrying out brand experience. Therefore, this research attempts to discover the consumers' perspectives on PMC, explore PMC in the top prominent channels (email, website, and mobile app notifications), and examine its role in brand experience.
This paper draws on relevant literature in personalised marketing and brand experience. It adopts the brand experience scale to explain the role of PMC in brand experience, studies the influence of elements such as involvement, product category, data privacy, and channel synergy on PMC and brand experience in omnichannel marketing. Based on 13 in-depth interviews focusing on a group of young consumers in Finland, the study shows that branded cues related to sense, emotion, behaviour, and cognition in PMC trigger responses in customers more effectively than relational, social, and pragmatic dimensions. Although the general perceptions towards personalised marketing communication are positive because of the benefits that consumers receive, their perceptions deviate at the channel level and in the forms that PMC takes. Mixed attitudes toward PMC appear in email and mobile apps due to the overwhelming quantity of PMC and a lack of perceived control for customers. While no product category restriction for PMC is found, the synergy is not strong between online-offline channels or among online channels, which impedes the stimulation of brand experience. The threat from data privacy can be controlled by data transparency, but the linkage to overconsumption is more concerning. The findings also suggest that brands have a sensible timing for PMC to match the level of involvement of customers, as well as moderate and review their PMC strategy to deliver more dimensions of brand experience effectively
Biodegradation of Lignocellulose-Polyester Composite Films in Freshwater and Seawater Conditions
No full textPublisher Copyright: © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2024.Developing biodegradable material alternatives is crucial to address the fossil-based plastic pollution in marine ecosystems. Natural biodegradable polymers like cellulose exhibit potential plastic alternatives. However, their susceptibility to water and moisture poses challenges when blending with hydrophobic polymers. Thus, chemical modification is often required to enhance cellulose dispersion in hydrophobic polymer matrices, which may hinder its inherent biodegradability. In this study, the aquatic biodegradation and degradation mechanisms of lignocellulose-polyester composite films under aerobic conditions were for the first time explored in simulated freshwater and real seawater environments. The composite films were produced by blending cellulose nanofibrils (CNFs) with polycaprolactone (PCL), a hydrophobic polyester, using lignin nanoparticles (LNPs) as an interfacial compatibilizer. The structural and morphological changes of the composite films were studied using Fourier transform infrared (FTIR), X-ray photoelectron spectroscopy (XPS), thermal gravimetric analysis (TGA), and scanning electron microscopy (SEM). Despite the use of LNPs (poorly degradable in aquatic conditions) and the composite films’ hydrophobicity, the presence of up to 25 wt% PCL and 5wt% LNPs did not prevent the composites from achieving > 85% biodegradation within 42 days, in both fresh water and seawater conditions. The incorporation of CNFs increased the water uptake capability of PCL which helped to increase the films’ porosity, in turn enhancing the film degradation process. This study confirmed that hydrophobizing nanocellulose with biodegradable polyesters and LNPs can preserve the nanocellulose’s inherent coveted biodegradability. Hence, this sustainable approach to developing bio-based composites supports responsible material development, disposal, and end-of-life management. Graphical abstract: (Figure presented.)Peer reviewe
Development and characterization of pomegranate peel extract-infused carboxymethyl cellulose composite films for functional, sustainable food packaging
No full textOur study explores the development and characterization of carboxymethyl cellulose (CMC)-based composite films integrated with clay particles and pomegranate peel extract (PE), aiming to inspire the films with natural antimicrobial and antioxidant properties for potential applications in food packaging. We conducted a comprehensive examination of the mechanical, barrier, surface, and degradation properties of these composite films, considering the impacts of incorporating clay particles and PE on their overall performance. Our findings reveal that the inclusion of clay particles enhances the mechanical strength and barrier properties of the films, while PE contributes to antioxidant and antibacterial effects. Namely, after the integration of 3 wt% clay, the tensile strength exhibited a remarkable increase of approximately 300%, accompanied by a notable reduction of 60% in water vapor permeability and 30% in oxygen transmission rate. Furthermore, the integration of PE into CMC films promoted antibacterial activity against 2 g-positive bacterial species, Staphylococcus aureus and Listeria monocytogenes. Additionally, we conducted a life cycle assessment (LCA) to quantify the cradle-to-gate environmental impacts of the developed bio-based active films. When normalized to the functional properties of the films, including mechanical and barrier performance, we observed significant benefits, with reductions of up to 59% after the concurrent incorporation of PE and clay nanosheets. Overall, our study underscores the potential of CMC-based composite films augmented with PE as a promising solution for sustainable food packaging, offering enhanced functionality while reducing environmental impact and increasing food safety.Peer reviewe
Atomic and Molecular Layer Deposition of Functional Thin Films Based on Rare Earth Elements
No full text| openaire: EC/HE/101097815/EU//UniEn-MLDHigh-quality rare earth element (R) based thin films are in demand for applications ranging from (opto)electronics and energy conversion/storage to medical diagnostics, imaging and security technologies. Atomic layer deposition (ALD) offers large-area homogeneous and conformal ultrathin films and is uniquely suited to address the requirements set by the potential applications of R-based thin films. The history starts from the 1990s, when the first electroluminescent R-doped thin films were grown with ALD. The interest soon expanded to rare earth element oxide layers as high-k gate dielectrics in semiconductor devices, and later to complex ternary and quaternary perovskite oxides with novel functional properties. The most recent advancements related to the combined atomic/molecular layer deposition (ALD/MLD) have rapidly expanded the family of R-organic hybrid materials with intriguing luminescence and up-conversion properties. This review provides up-to-date insights to the current state of ALD and ALD/MLD research of R-based thin films and highlights their application potential.Peer reviewe
Enhanced Electrochemical Hydrogenation of Benzaldehyde to Benzyl Alcohol on Pd@Ni-MOF by Modifying the Adsorption Configuration
No full textPublisher Copyright: © 2024 American Chemical Society.Electrocatalytic hydrogenation (ECH) approaches under ambient temperature and pressure offer significant potential advantages over thermal hydrogenation processes but require highly active and efficient hydrogenation electrocatalysts. The performance of such hydrogenation electrocatalysts strongly depends not only on the active phase but also on the architecture and surface chemistry of the support material. Herein, Pd nanoparticles supported on a nickel metal-organic framework (MOF), Ni-MOF-74, are prepared, and their activity toward the ECH of benzaldehyde (BZH) in a 3 M acetate (pH 5.2) aqueous electrolyte is explored. An outstanding ECH rate up to 283 μmol cm-2 h-1 with a Faradaic efficiency (FE) of 76% is reached. Besides, higher FEs of up to 96% are achieved using a step-function voltage. Materials Studio and density functional theory calculations show these outstanding performances to be associated with the Ni-MOF support that promotes H-bond formation, facilitates water desorption, and induces favorable tilted BZH adsorption on the surface of the Pd nanoparticles. In this configuration, BZH is bonded to the Pd surface by the carbonyl group rather than through the aromatic ring, thus reducing the energy barriers of the elemental reaction steps and increasing the overall reaction efficiency.Peer reviewe
PyBDR: Set-Boundary Based Reachability Analysis Toolkit in Python
No full textPublisher Copyright: © The Author(s) 2025.We present PyBDR, a Python reachability analysis toolkit based on set-boundary analysis, which centralizes on widely-adopted set propagation techniques for formal verification, controller synthesis, state estimation, etc. It employs boundary analysis of initial sets to mitigate the wrapping effect during computations, thus improving the performance of reachability analysis algorithms without significantly increasing computational costs. Beyond offering various set representations such as polytopes and zonotopes, our toolkit particularly excels in interval arithmetic by extending operations to the tensor level, enabling efficient parallel interval arithmetic computation and unifying vector and matrix intervals into a single framework. Furthermore, it features symbolic computation of derivatives of arbitrary order and evaluates them as real or interval-valued functions, which is essential for approximating behaviours of nonlinear systems at specific time instants. Its modular architecture design offers a series of building blocks that facilitate the prototype development of reachability analysis algorithms. Comparative studies showcase its strengths in handling verification tasks with large initial sets or long time horizons. The toolkit is available at https://github.com/ASAG-ISCAS/PyBDR.Peer reviewe