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Tendon function and homeostasis rely on external loading. This study investigates the biological mechanisms behind tendon biomechanical function and how the mechanical performance is affected by reduced daily loading. The Achilles tendons of 16 weeks old female Sprague Dawley rats (n = 40) were unloaded for 5 weeks by inducing muscle paralysis with botulinum toxin injections in the right gastrocnemius and soleus muscles. The contralateral side was used as control. After harvest, the tendons underwent biomechanical testing to assess viscoelasticity (n = 30 rats) and small angle X-ray scattering to determine the structural properties of the collagen fibrils (n = 10 rats). Fourier transform infrared spectroscopy and histological staining (n = 10 rats) were performed to investigate the collagen and proteoglycan content. The results show that the stiffness increased in unloaded tendons, together with an increased collagen content. Creep and axial alignment of the collagen fibers were reduced. Stress-relaxation increased whereas hysteresis was reduced in response to unloading with botox treatment. Our findings indicate that altered matrix deposition relies on mechanical loading to reorganize the newly formed tissue, without which the viscoelastic behavior is impaired. The results demonstrate that reduced daily loading deprives tendons of their viscoelastic properties, which could increase the risk of injury., published version, peerReviewed

In highly organized tissues, such as cartilage, tendons and white matter, several quantitative MRI parameters exhibit dependence on the orientation of the tissue constituents with respect to the main imaging magnetic field (B0). In this study, we investigated the dependence of multiple relaxation parameters on the orientation of articular cartilage specimens in the B0. Bovine patellar cartilage-bone samples (n = 4) were investigated ex vivo at 9.4 Tesla at seven different orientations, and the MRI results were compared with polarized light microscopy findings on specimen structure. Dependences of T2 and continuous wave (CW)-T1ρ relaxation times on cartilage orientation were confirmed. T2 (and T2*) had the highest sensitivity to orientation, followed by TRAFF2 and adiabatic T2ρ. The highest dependence was seen in the highly organized deep cartilage and the smallest in the least organized transitional layer. Increasing spin-lock amplitude decreased the orientation dependence of CW-T1ρ. T1 was found practically orientation-independent and was closely followed by adiabatic T1ρ. The results suggest that T1 and adiabatic T1ρ should be preferred for orientation-independent quantitative assessment of organized tissues such as articular cartilage. On the other hand, based on the literature, parameters with higher orientation anisotropy appear to be more sensitive to degenerative changes in cartilage., published version, peerReviewed

Purpose The cortical characteristics of the iliac crest in male have rarely been investigated with quantitative histomorphometry. Also it is still unknown how cortical microarchitecture may vary between the iliac crest and fractures related sites at the proximal femur. We studied the microarchitecture of both external and internal cortices within the iliac crest, and compared the results with femoral neck and subtrochanteric femoral shaft sites. Methods Undecalcified histological sections of the iliac crest were obtained bicortically from cadavers (n = 20, aged 18–82 years, males). They were cut (7 μm) and stained using modified Masson-Goldner stain. Histomorphometric parameters of cortical bone were analysed with low (× 50) and high (× 100) magnification, after identifying cortical bone boundaries using our previously validated method. Within cortical bone area, only complete osteons with typical concentric lamellae and cement line were selected and measured. Results At the iliac crest, the mean cortical width of external cortex was higher than at the internal cortex (p < 0.001). Also, osteon structural parameters, e.g. mean osteonal perimeter, were higher in the external cortex (p < 0.05). In both external and internal cortices, pore number per cortical bone area was higher in young subjects (≤ 50 years) (p < 0.05) while mean pore perimeter was higher in the old subjects (> 50 years) (p < 0.05). Several cortical parameters (e.g. osteon area per cortical bone area, pore number per cortical area) were the lowest in the femoral neck (p < 0.05). The maximal osteonal diameter and mean wall width were the highest in the external cortex of the iliac crest (p < 0.05), and the mean cortical width, osteon number per cortical area were the highest in the subtrochanteric femoral shaft (p < 0.05). Some osteonal structural parameters (e.g. min osteonal diameter) were significantly positively correlated (0.29 ≤ R2 ≤ 0.45, p < 0.05) between the external iliac crest and the femoral neck. Conclusions This study reveals heterogeneity in cortical microarchitecture between the external and internal iliac crest cortices, as well as between the iliac crest, the femoral neck and the subtrochanteric femoral shaft. Standard iliac crest biopsy does not reflect accurately cortical microarchitecture of other skeletal sites., published version, peerReviewed

The terrestrial vegetation emits large amounts of volatile organic compounds (VOC) into the atmosphere, which on oxidation produce secondary organic aerosol (SOA). By acting as cloud condensation nuclei (CCN), SOA influences cloud formation and climate. In a warming climate, changes in environmental factors can cause stresses to plants, inducing changes of the emitted VOC. These can modify particle size and composition. Here we report how induced emissions eventually affect CCN activity of SOA, a key parameter in cloud formation. For boreal forest tree species, insect infestation by aphids causes additional VOC emissions which modifies SOA composition thus hygroscopicity and CCN activity. Moderate heat increases the total amount of constitutive VOC, which has a minor effect on hygroscopicity, but affects CCN activity by increasing the particles’ size. The coupling of plant stresses, VOC composition and CCN activity points to an important impact of induced plant emissions on cloud formation and climate., published version, peerReviewed

Ligaments provide stability to the human knee joint and play an essential role in restraining motion during daily activities. Compression-tension nonlinearity is a well-known characteristic of ligaments. Moreover, simpler material representations without this feature might give reasonable results because ligaments are primarily in tension during loading. However, the biomechanical role of different constitutive representations and their fibril-reinforced poroelastic properties is unknown. A numerical knee model which considers geometric and material nonlinearities of meniscus and cartilages was applied. Five different constitutive models for the ligaments (spring, elastic, hyperelastic, porohyperelastic, and fibril-reinforced porohyperelastic (FRPHE)) were implemented. Knee joint forces for the models with elastic, hyperelastic and porohyperelastic properties showed similar behavior throughout the stance, while the model with FRPHE properties exhibited lower joint forces during the last 50% of the stance phase. The model with ligaments as springs produced the lowest joint forces at this same stance phase. The results also showed that the fibril network contributed substantially to the knee joint forces, while the nonfibrillar matrix and fluid had small effects. Our results indicate that simpler material models of ligaments with similar properties in compression and tension can be used when the loading is directed primarily along the ligament axis in tension., published version, peerReviewed

Knee osteoarthritis (KOA) is most common in the medial tibial compartment. We present a novel method to study the effect of gait modifications and lateral wedge insoles (LWIs) on the stresses in the medial tibial cartilage by combining musculoskeletal (MS) modelling with finite element (FE) analysis. Subject’s gait was recorded in a gait laboratory, walking normally, with 5° and 10° LWIs, toes inward (‘Toe in’), and toes outward (‘Toe out wide’). A full lower extremity MRI and a detailed knee MRI were taken. Bones and most soft tissues were segmented from images, and the generic bone architecture of the MS model was morphed into the segmented bones. The output forces from the MS model were then used as an input in the FE model of the subject’s knee. During stance, LWIs failed to reduce medial peak pressures apart from Insole 10° during the second peak. Toe in reduced peak pressures by −11% during the first peak but increased them by 12% during the second. Toe out wide reduced peak pressures by −15% during the first and increased them by 7% during the second. The results show that the work flow can assess the effect of interventions on an individual level. In the future, this method can be applied to patients with KOA., published version, peerReviewed

We demonstrate in this study the potential of near infrared (NIR) spectroscopy as a tool for monitoring progression of cartilage degeneration in an animal model. Osteoarthritic degeneration was artificially induced in one joint in laboratory rats, and the animals were sacrificed at four time points: 1, 2, 4, and 6 weeks (3 animals/week). NIR spectra were acquired from both (injured and intact) knees. Subsequently, the joint samples were subjected to histological evaluation and glycosaminoglycan (GAG) content analysis, to assess disease severity based on the Mankin scoring system and to determine proteoglycan loss, respectively. Multivariate spectral techniques were then employed for classification (principal component analysis and support vector machines) and prediction (partial least squares regression) of the samples’ Mankin scores and GAG content from their NIR spectra. Our results demonstrate that NIR spectroscopy is sensitive to degenerative changes in articular cartilage, and is capable of distinguishing between mild (weeks 1&2; Mankin 3) cartilage degeneration. In addition, the spectral data contains information that enables estimation of the tissue’s Mankin score (error = 12.6%, R2 = 86.2%) and GAG content (error = 7.6%, R2 = 95%). We conclude that NIR spectroscopy is a viable tool for assessing cartilage degeneration post-injury, such as, post-traumatic osteoarthritis., published version, peerReviewed

Silicon is being increasingly studied as the next-generation anode material for Li-ion batteries because of its ten times higher gravimetric capacity compared with the widely-used graphite. While nanoparticles and other nanostructured silicon materials often exhibit good cyclability, their volumetric capacity tends to be worse or similar than that of graphite. Furthermore, these materials are commonly complicated and expensive to produce. An effortless way to produce nanostructured silicon is electrochemical anodization. However, there is no systematic study how various material properties affect its performance in LIBs. In the present study, the effects of particle size, surface passivation and boron doping degree were evaluated for the mesoporous silicon with relatively low porosity of 50%. This porosity value was estimated to be the lowest value for the silicon material that still can accommodate the substantial volume change during the charge/discharge cycling. The optimal particle size was between 10–20 µm, the carbide layer enhanced the rate capability by improving the lithiation kinetics, and higher levels of boron doping were beneficial for obtaining higher specific capacity at lower rates. Comparison of pristine and cycled electrodes revealed the loss of electrical contact and electrolyte decay to be the major contributors to the capacity decay., published version, peerReviewed

Economic costs of osteoarthritis (OA) are considerable. However, there are no clinical tools to predict the progression of OA or guide patients to a correct treatment for preventing OA. We tested the ability of our cartilage degeneration algorithm to predict the subject-specific development of OA and separate groups with different OA levels. The algorithm was able to predict OA progression similarly with the experimental follow-up data and separate subjects with radiographical OA (Kellgren-Lawrence (KL) grade 2 and 3) from healthy subjects (KL0). Maximum degeneration and degenerated volumes within cartilage were significantly higher (p, published version, peerReviewed

Measuring the lens gradient refractive index (GRIN) accurately and reliably has proven an extremely challenging technical problem. A fully automated laser ray tracing (LRT) system was built to address this issue. The LRT system captures images of multiple laser projections before and after traversing through an ex vivo lens. These LRT images, combined with accurate measurements of the lens geometry, are used to calculate the lens GRIN profile. Mathematically, this is an ill-conditioned problem; hence, it is essential to apply biologically relevant constraints to produce a feasible solution. The lens GRIN measurements were compared with previously published data. Our GRIN retrieval algorithm produces fast and accurate measurements of the lens GRIN profile. Experiments to study the optics of physiologically perturbed lenses are the future direction of this research., published version, peerReviewed

Research is ongoing to develop drug therapies to manage osteoarthritis (OA) and articular cartilage (AC) injuries. However, means to deliver drug to localized AC lesions are highly limited and not clinically available. This study investigates the capability of laser ultrasound (laser-induced plasma sound source) to deliver agents (methylene blue, MB, in PBS) into bovine AC. Treatment samples (n = 10) were immersed in MB solution simultaneously with LU exposure, while adjacent control 1 tissue (n = 10) was pre-treated with LU followed by immersion in MB and adjacent control 2 tissue (n = 10) was only immersed in MB. AC exposed (n = 22) or not exposed (n = 27) to LU were characterized for anomalies in structure, composition, viability or RNA expression. Optically detected MB content was significantly (p, published version, peerReviewed

Using reports of forest losses caused directly by large scale windstorms (or primary damage, PD) from the European forest institute database (comprising 276 PD reports from 1951–2010), total growing stock (TGS) statistics of European forests and the daily North Atlantic Oscillation (NAO) index, we identify a statistically significant change in storm intensity in Western, Central and Northern Europe (17 countries). Using the validated set of storms, we found that the year 1990 represents a change-point at which the average intensity of the most destructive storms indicated by PD/TGS > 0.08% increased by more than a factor of three. A likelihood ratio test provides strong evidence that the change-point represents a real shift in the statistical behaviour of the time series. All but one of the seven catastrophic storms (PD/TGS > 0.2%) occurred since 1990. Additionally, we detected a related decrease in September–November PD/TGS and an increase in December–February PD/TGS. Our analyses point to the possibility that the impact of climate change on the North Atlantic storms hitting Europe has started during the last two and half decades., published version, peerReviewed

Various types of DNA viruses are known to elicit the formation of a large nuclear viral replication compartment and marginalization of the cell chromatin. We used three-dimensional soft x-ray tomography, confocal and electron microscopy, combined with numerical modelling of capsid diffusion to analyse the molecular organization of chromatin in herpes simplex virus 1 infection and its effect on the transport of progeny viral capsids to the nuclear envelope. Our data showed that the formation of the viral replication compartment at late infection resulted in the enrichment of heterochromatin in the nuclear periphery accompanied by the compaction of chromatin. Random walk modelling of herpes simplex virus 1–sized particles in a three-dimensional soft x-ray tomography reconstruction of an infected cell nucleus demonstrated that the peripheral, compacted chromatin restricts viral capsid diffusion, but due to interchromatin channels capsids are able to reach the nuclear envelope, the site of their nuclear egress., published version, peerReviewed

Therapeutic treatment options for central nervous system diseases are greatly limited by the blood-brain barrier (BBB). Focused ultrasound (FUS), in conjunction with circulating microbubbles, can be used to induce a targeted and transient increase in BBB permeability, providing a unique approach for the delivery of drugs from the systemic circulation into the brain. While preclinical research has demonstrated the utility of FUS, there remains a large gap in our knowledge regarding the impact of sonication on BBB gene expression. This work is focused on investigating the transcriptional changes in dorsal hippocampal rat microvessels in the acute stages following sonication. Microarray analysis of microvessels was performed at 6 and 24 hrs post-FUS. Expression changes in individual genes and bioinformatic analysis suggests that FUS may induce a transient inflammatory response in microvessels. Increased transcription of proinflammatory cytokine genes appears to be short-lived, largely returning to baseline by 24 hrs. This observation may help to explain some previously observed bioeffects of FUS and may also be a driving force for the angiogenic processes and reduced drug efflux suggested by this work. While further studies are necessary, these results open up intriguing possibilities for novel FUS applications and suggest possible routes for pharmacologically modifying the technique., published version, peerReviewed

Conventional arthroscopic evaluation of articular cartilage is subjective and poorly reproducible. Therefore, implementation of quantitative diagnostic techniques, such as near infrared spectroscopy (NIRS) and optical coherence tomography (OCT), is essential. Locations (n = 44) with various cartilage conditions were selected from mature equine fetlock joints (n = 5). These locations and their surroundings were measured with NIRS and OCT (n = 530). As a reference, cartilage proteoglycan (PG) and collagen contents, and collagen network organization were determined using quantitative microscopy. Additionally, lesion severity visualized in OCT images was graded with an automatic algorithm according to International Cartilage Research Society (ICRS) scoring system. Artificial neural network with variable selection was then employed to predict cartilage composition in the superficial and deep zones from NIRS data, and the performance of two models, generalized (including all samples) and condition-specific models (based on ICRS-grades), was compared. Spectral data correlated significantly (p, published version, peerReviewed

Focal cartilage lesions can proceed to severe osteoarthritis or remain unaltered even for years. A method to identify high risk defects would be of utmost importance to guide clinical decision making and to identify the patients that are at the highest risk for the onset and progression of osteoarthritis. Based on cone beam computed tomography arthrography, we present a novel computational model for evaluating changes in local mechanical responses around cartilage defects. Our model, based on data obtained from a human knee in vivo, demonstrated that the most substantial alterations around the defect, as compared to the intact tissue, were observed in minimum principal (compressive) strains and shear strains. Both strain values experienced up to 3-fold increase, exceeding levels previously associated with chondrocyte apoptosis and failure of collagen crosslinks. Furthermore, defects at the central regions of medial tibial cartilage with direct cartilage-cartilage contact were the most vulnerable to loading. Also locations under the meniscus experienced substantially increased minimum principal strains. We suggest that during knee joint loading particularly minimum principal and shear strains are increased above tissue failure limits around cartilage defects which might lead to osteoarthritis. However, this increase in strains is highly location-specific on the joint surface., published version, peerReviewed

We present a novel algorithm combined with computational modeling to simulate the development of knee osteoarthritis. The degeneration algorithm was based on excessive and cumulatively accumulated stresses within knee joint cartilage during physiological gait loading. In the algorithm, the collagen network stiffness of cartilage was reduced iteratively if excessive maximum principal stresses were observed. The developed algorithm was tested and validated against experimental baseline and 4-year follow-up Kellgren-Lawrence grades, indicating different levels of cartilage degeneration at the tibiofemoral contact region. Test groups consisted of normal weight and obese subjects with the same gender and similar age and height without osteoarthritic changes. The algorithm accurately simulated cartilage degeneration as compared to the Kellgren-Lawrence findings in the subject group with excess weight, while the healthy subject group’s joint remained intact. Furthermore, the developed algorithm followed the experimentally found trend of cartilage degeneration in the obese group (R2 = 0.95, p 0.05). The proposed algorithm revealed a great potential to objectively simulate the progression of knee osteoarthritis., published version, peerReviewed

Article, The changes in chemical composition of human articular cartilage (AC) caused by osteoarthritis (OA) were investigated using Fourier transform infrared microspectroscopy (FTIR-MS). We demonstrate the sensitivity of FTIR-MS for monitoring compositional changes that occur with OA progression. Twenty-eight AC samples from tibial plateaus were imaged with FTIR-MS. Hyperspectral images of all samples were combined for K-means clustering. Partial least squares regression (PLSR) analysis was used to compare the spectra with the OARSI grade (histopathological grading of OA). Furthermore, the amide I and the carbohydrate regions were used to estimate collagen and proteoglycan contents, respectively. Spectral peak at 1338 cm−1 was used to estimate the integrity of the collagen network. The layered structure of AC was revealed using the carbohydrate region for clustering. Statistically significant correlation was observed between the OARSI grade and the collagen integrity in the superficial (r = −0.55) and the deep (r = −0.41) zones. Furthermore, PLSR models predicted the OARSI grade from the superficial (r = 0.94) and the deep (r = 0.77) regions of the AC with high accuracy. Obtained results suggest that quantitative and qualitative changes occur in the AC composition during OA progression, and these can be monitored by the use of FTIR-MS., published version, peerReviewed

Quantitative photoacoustic tomography is an imaging modality in which distributions of optical parameters inside tissue are estimated from photoacoustic images. This optical parameter estimation is an ill-posed problem and it needs to be approached in the framework of inverse problems. In this work, utilising surface light measurements in quantitative photoacoustic tomography is studied. Estimation of absorption and scattering is formulated as a minimisation problem utilising both internal quantitative photoacoustic data and surface light data. The image reconstruction problem is studied with two-dimensional numerical simulations in various imaging situations using the diffusion approximation as the model for light propagation. The results show that quantitative photoacoustic tomography augmented with surface light data can improve both absorption and scattering estimates when compared to the conventional quantitative photoacoustic tomography., published version, peerReviewed

Sea spray is one of the largest natural aerosol sources and plays an important role in the Earth’s radiative budget. These particles are inherently hygroscopic, that is, they take-up moisture from the air, which affects the extent to which they interact with solar radiation. We demonstrate that the hygroscopic growth of inorganic sea salt is 8–15% lower than pure sodium chloride, most likely due to the presence of hydrates. We observe an increase in hygroscopic growth with decreasing particle size (for particle diameters, Nature Communications, 8, ISSN:2041-1723