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Abstract Canvas paintings are layered structures composed of canvas support sized with animal glue, a preparatory layer of the ground, and paint and varnish layers on the top. Preventing or limiting humidity-induced stresses in these structures requires an understanding of the relevant processes and risks. A three-dimensional model of a canvas painting was used to analyse stresses and crack development in the two-layer structure comprised of a glue-sized canvas on a wooden stretcher with a layer of stiff chalk-glue ground representing a pictorial layer in historic canvas paintings. The model was subjected to a large relative humidity fall which induced shrinkage of the glue-sized canvas. The modelling revealed that when a stretcher with flexible wooden bars is considered, high tensile stresses arise in the ground layer at the corners of the painting, and cracks are formed in these areas in the direction perpendicular to the painting’s diagonal. Ratios of critical distances between cracks to the ground layer thickness for which stresses in the midpoints between the cracks dropped to below the level inducing fracture in the material were estimated for various magnitudes of the relative humidity drop and thicknesses of the ground layer. Increasing ground layer thickness limits the hygric response of the sized canvas and makes the paintings less vulnerable to humidity variations. The ratio of stress along the diagonal calculated for painting with one crack to the solution without cracks was described by the double Lorentz function. A simple procedure of calculating stress variations along the diagonal—using the function—on a sequential addition of cracks was developed. Cracks in central parts of canvas painting were found to be induced by permanent cumulative drying shrinkage of the oil-based paints and grounds due to the evolution of the molecular composition of the oil binder. The outcome of the modelling indicated that the risk of cracking of the pictorial layers in canvas paintings due to drops in ambient relative humidity was small.

High-grade glioma is an aggressive cancer that occurs naturally in pet dogs. Canine high-grade glioma (cHGG) is treated with radiation, chemotherapy or surgery, but has no curative treatment. Within the past eight years, there have been advances in our imaging and histopathology standards as well as genetic charactereization of cHGG. However, there are only three cHGG cell lines publicly available, all of which were derived from astrocytoma and established using methods involving expansion of tumour cells in vitro on plastic dishes. In order to provide more clinically relevant cell lines for studying cHGG in vitro, the goal of this study was to establish cHGG patient-derived lines, whereby cancer cells are expanded in vivo by injecting cells into immunocompromized laboratory mice. The cells are then harvested from mice and used for in vitro studies. This method is the standard in the human field and has been shown to minimize the acquisition of genetic alterations and gene expression changes from the original tumour. Through a multi-institutional collaboration, we describe our methods for establishing two novel cHGG patient-derived lines, Boo-HA and Mo-HO, from a high-grade astrocytoma and a high-grade oligodendroglioma, respectively. We compare our novel lines to G06-A, J3T-Bg, and SDT-3G (traditional cHGG cell lines) in terms of proliferation and sensitivity to radiation. We also perform whole genome sequencing and identify an NF1 truncating mutation in Mo-HO. We report the characterization and availability of these novel patient-derived lines for use by the veterinary community.

Abstract Massive cultural objects made of wood are often situated in historic interiors in which they experience uncontrolled dynamic variations of relative humidity (RH). Although the objects usually have acclimatized to the natural climate variability, preventing risks related to any kind of modification of their environment requires an understanding of the object’s response to the expected changes. In the present study, an analysis of the risk of cracking related to continuous or intermittent heating, or the transfer to hypothetically ideal conditions in a conservation studio was performed for the case of elements of Veit Stoss’ altarpiece (1477–1489) preserved in St. Mary’s Basilica in Krakow, Poland. Massive sculptures carved in lime wood and approximately one meter in diameter were analysed. The study aimed at determining safe margins of environment modifications that would not cause propagation of cracks that are known to have accumulated in wood during centuries of the altarpiece’s existence. The mechanical properties of lime wood were determined experimentally to feed the numerical model. The energy release rates around the tips of cracks of various depths in a wooden sculpture were calculated using the finite element analysis and compared with the critical value of the parameter triggering the fracture propagation in the material, derived from the fracture energy measurement. It was shown that the church interior housing the altarpiece can be heated to 11 °C during the cold season to provide human comfort. The allowable duration of intermittent heating events to more comfortable 18 °C that would induce drops in RH of up to 40% was assessed as 12 h. The study demonstrated that moving the sculptures to the conservation studio would have to be done with extreme caution as it would be connected with risks depending on the depth of existing cracks and the duration of the RH change.

Abstract The fracture toughness in opening mode G Ic for selected oil paints from Mecklenburg's Paint Reference Collection after approximately 30 years of natural ageing was determined using the procedure adopted from the ASTM D5528–13 standard in which double cantilever beam specimens are split in tensile tests. The careful reglueing procedure allowed multiple fracturing tests to be carried out that not only improved statistics of the measurements but also provided insight into the variation of the fracture toughness across the paint film observed for some paints. The latter was due to pigment sedimentation or chemical change of the oil binder as a result of the easier access of oxygen from the side open to the air. For the lead white paint, used over centuries both in paint films and oil grounds, the G Ic values more than doubled from 18 to 39 J/m2 for three consecutive cracks formed at an increasing distance from one side of the paint film. The study demonstrated that fracture toughness corresponding to the first crack formation in aged oil paints ranged between 10 and 40 J/m2, relatively low values compared to the animal glue-based ground in paintings. In consequence, oil paints are more vulnerable to crack initiation and growth induced by tensile stress than the ground layer. The measurements filled the gap in the knowledge required for the analysis of fracturing or delamination processes in paintings.

Abstract Panel paintings are multi-layer structures composed of humidity-sensitive materials. Preventing or limiting stresses in these structures, generated by the loss or gain of moisture, requires an understanding of the relevant processes and risks. A three-dimensional elastic model of a panel painting was used to analyse surface stresses and understand how crack patterns are developed in the two-layer structure of the pictorial layer—the gesso and the paints. Two historically important paint types were considered—egg tempera and oil paints, laid on a gesso produced following historical procedures. Two scenarios of stress development were analysed: permanent cumulative drying shrinkage of paints or gesso, owing to gradual loss of water or evolution of the molecular composition of the binders, and moisture-induced cyclic swelling of the wood substrate. Ratios of distances between cracks in the tangential and longitudinal directions of a wood panel to the layer thickness were estimated for increasing magnitudes of materials’ dimensional change in the two scenarios. The critical values of the ratios for which stress in the midpoint between the cracks dropped below the value inducing strain at break in the materials and saturation of the crack patterns occurred, was approximately 3–4 or 5–6 for the paints and the gesso, respectively. The critical distance normalized to the gesso thickness between cracks parallel to the wood grain induced by cyclic swelling of the wood substrate due to relative humidity variation in the range of 50–70% was 6. The study demonstrated that crack spacings in the fully developed crack systems remain sensitive only to the thicknesses of paint or gesso layers which, therefore, can be derived from the crack pattern geometry. Existing flaws in gesso were found not to increase the risk of new crack development.

Abstract Mechanical properties—modulus of elasticity and strain at break, water vapour sorption, and hygroscopic expansion of selected egg tempera and distemper paints were determined as a function of relative humidity (RH) filling in this way a critical gap in the knowledge required for the analysis of fracturing processes in paintings. The experimental work was made possible by the preparation of several tempera paints, mimicking the historical materials, in the form of large specimens. Lead white, azurite, and yellow ochre were selected as pigments, and egg yolk and rabbit skin glue as binding media. The water vapour sorption and the moisture-related swelling of the paints were dominated by the proteinaceous components of the binders. The linear hygroscopic expansion coefficient of the dried egg yolk binder was approximately 1 × 10−4 per 1% RH, several times less than the coefficient of the collagen glue (4 × 10−4 per 1% RH). The moduli of elasticity of egg tempera paints at the RH mid-range were comparable to the moduli of aged oil paints, whilst the modulus of elasticity of the distemper paint was close to values measured for animal glue-based grounds. The paints experienced the transition from brittle to ductile states on increasing RH. The egg tempera paints were found to be more brittle than the distemper paint, gessoes, and, generally, aged oil paints. The observations modify a frequently used laminar model of panel paintings in which the mismatch in the response of glue-based ground layer and wood substrate to variations in RH has been identified as the worst-case condition for the fracturing of the entire pictorial layer. This study demonstrated that tempera could be more brittle than the ground layer and in consequence more vulnerable to cracking.

Abstract Background Ovarian carcinoma is the leading cause of mortality among gynecological cancers in the world. The high mortality rate is associated with lack of early diagnosis and development of drug resistance. The antitumor efficacy and mechanism of NCX-4040, a nitric oxide-releasing aspirin derivative, against ovarian cancer is studied. Methods NCX-4040, alone or in combination with cisplatin (cis-diamminedichloroplatinum, cDDP), was studied in cisplatin-sensitive (A2780 WT) and cisplatin-resistant (A2780 cDDP) cell lines as well as xenograft tumors grown in nude mice. Electron paramagnetic resonance (EPR) was used for measurements of nitric oxide and redox state. Immunoblotting analysis of A2780 cDDP tumor xenografts from mice was used for mechanistic studies. Results Cells treated with NCX-4040 (25 μM) showed a significant reduction of cell viability (A2780 WT, 34.9 ± 8.7%; A2780 cDDP, 41.7 ± 7.6%; p < 0.05). Further, NCX-4040 significantly enhanced the sensitivity of A2780 cDDP cells (cisplatin alone, 80.6 ± 11.8% versus NCX-4040+cisplatin, 26.4 ± 7.6%; p < 0.01) and xenograft tumors (cisplatin alone, 74.0 ± 4.4% versus NCX-4040+cisplatin, 56.4 ± 7.8%; p < 0.05), to cisplatin treatment. EPR imaging of tissue redox and thiol measurements showed a 5.5-fold reduction (p < 0.01) of glutathione in NCX-4040-treated A2780 cDDP tumors when compared to untreated controls. Immunoblotting analysis of A2780 cDDP tumor xenografts from mice treated with NCX-4040 and cisplatin revealed significant downregulation of pEGFR (Tyr845 and Tyr992) and pSTAT3 (Tyr705 and Ser727) expression. Conclusion The results suggested that NCX-4040 could resensitize drug-resistant ovarian cancer cells to cisplatin possibly by depletion of cellular thiols. Thus NCX-4040 appears to be a potential therapeutic agent for the treatment of human ovarian carcinoma and cisplatin-resistant malignancies.

Abstract Understanding how the evolving molecular composition of an oil paint layer on its transition to an aged solid film affects its dimensional change and mechanical properties is fundamental to the assessment of material durability and more broadly risk of degradation of oil paintings. Tensile properties—modulus of elasticity and strain at break—as well as cumulative shrinkage were determined for a selection of oil paints from Mecklenburg’s Paint Reference Collection now after approximately 30 years of drying. The oil paints were found to get stiffer and more brittle with diminishing plastic deformation and increasingly elastic behaviour. For some paints, the increases in stiffness and decreases in the strain at break were dramatic during the late stage of drying. The observations modify the current physical model of paintings in which the mismatch in the response of glue-based ground layer and unrestrained wood or canvas support to variations in relative humidity (RH) has been identified as the worst-case condition for the fracturing of the entire pictorial layer. This study demonstrated that some paints were more brittle than the glue-based ground layer and as a consequence more vulnerable to cracking. The shrinkage of paints due to molecular relocation and/or evaporation of organic medium as they dry and age was measured. This shrinkage can exceed their strain at break and lead to fracturing of the oil paint layer if it is restrained by a dimensionally stable substrate. Consequently, after long-term drying, the cumulative shrinkage can cause oil paints to crack even in absence of fluctuations in RH or temperature. An example of cracking developed in an oil paint layer on the top of an undamaged ground layer in a historic panel painting was made evident by the X-ray microtomography.

Abstract Understanding canvas paintings as physical systems is fundamental to develop evidence-based environmental specifications for museums. A number of tests were carried out to determine mechanical properties of canvas, canvas sized with animal glue and animal glue-based ground layer (gesso) as a function of relative humidity (RH). The mechanical properties of the canvas samples tested exhibited an anisotropy dependent on the measurement direction, being the stiffness corresponding to the weft direction greater than the warp and diagonal ones. Sizing the canvas with a layer of animal glue significantly increased its modulus of elasticity while the anisotropy of mechanical properties was kept in the composite material. The application of an animal glue-based ground layer on sized canvas increased the elasticity modulus of the system by another order of magnitude (~ 2 GPa) whereas the anisotropy of the material disappeared. The measurements were carried out in a wide range of RH from 30 to 90%. An increase in RH caused a decrease in the material stiffness. Cracking of the gesso layer, which is often responsible for the formation of cracks in paintings, was observed at strains of the order of a few thousandths. Swelling of glue sizing dominated the moisture-induced swelling of the composite material in the less stiff warp direction, completely overriding the shrinkage of the untreated canvas. In contrast, the swelling of the composite material in the stiffer weft direction was much smaller than for pure glue alone, being clearly affected by the textile.

Fire statistics indicate that fire, despite significant technical progress in the field of fire protection, is a significant risk to the long-term preservation of cultural property. Management of the risk requires tools which quantitatively relate the risk of fire to the characteristics of buildings and collections and the effectiveness of fire protection measures. Such tools must be accessible to, and useful for, conservation professionals and related decision-makers. To address the challenge, a module assessing fire risk for collections in museums has been developed on the HERIe online digital decision-supporting platform using the methodology proposed by Jean Tétreault transformed into a mathematical algorithm. It takes into account building characteristics and the proportion of the collection stored in showcases, as well as the vulnerability of the collection materials to heat, combustion, smoke, and water. This information is used to forecast loss to collection value over a selected time horizon. Fire likelihood is estimated from the fire statistics available in the user's country, area, or organization. Risks to collections associated with correct and unwanted activation of automatic fire suppression systems are also considered. [ABSTRACT FROM AUTHOR]

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Aromatase Inhibitors (AIs) block estrogen production and improve survival in patients with hormone-receptor-positive breast cancer. However, half of patients develop aromatase-inhibitor-induced arthralgia (AIIA), which is characterized by inflammation of the joints and the surrounding musculoskeletal tissue. To create a platform for future interventional strategies, our objective was to characterize a novel animal model of AIIA. Female BALB/C-Tg(NFκB-RE-luc)-Xen mice, which have a firefly luciferase NFκB reporter gene, were oophorectomized and treated with an AI (letrozole). Bioluminescent imaging showed significantly enhanced NFκB activation with AI treatment in the hind limbs. Moreover, an analysis of the knee joints and legs via MRI showed enhanced signal detection in the joint space and the surrounding tissue. Surprisingly, the responses observed with AI treatment were independent of oophorectomy, indicating that inflammation is not mediated by physiological estrogen levels. Histopathological and pro-inflammatory cytokine analyses further demonstrated the same trend, as tenosynovitis and musculoskeletal infiltrates were detected in all mice receiving AI, and serum cytokines were significantly upregulated. Human PBMCs treated with letrozole/estrogen combinations did not demonstrate an AI-specific gene expression pattern, suggesting AIIA-mediated pathogenesis through other cell types. Collectively, these data identify an AI-induced stimulation of disease pathology and suggest that AIIA pathogenesis may not be mediated by estrogen deficiency, as previously hypothesized.

BackgroundMedulloblastoma is the most common type of pediatric brain tumor. Although numerous factors influence patient survival rates, more than 30% of all cases will ultimately be refractory to conventional therapies. Current standards of care are also associated with significant morbidities, giving impetus for the development of new treatments. We have previously shown that oncolytic measles virotherapy is effective against medulloblastoma, leading to significant prolongation of survival and even cures in mouse xenograft models of localized and metastatic disease. Because medulloblastomas are known to be highly vascularized tumors, we reasoned that the addition of angiogenesis inhibitors could further enhance the efficacy of oncolytic measles virotherapy. Toward this end, we have engineered an oncolytic measles virus that express a fusion protein of endostatin and angiostatin, two endogenous and potent inhibitors of angiogenesis.MethodsOncolytic measles viruses encoding human and mouse variants of a secretable endostatin/angiostatin fusion protein were designed and rescued according to established protocols. These viruses, known as MV-hE:A and MV-mE:A respectively, were then evaluated for their anti-angiogenic potential and efficacy against medulloblastoma cell lines and orthotopic mouse models of localized disease.ResultsMedulloblastoma cells infected by MV-E:A readily secrete endostatin and angiostatin prior to lysis. The inclusion of the endostatin/angiostatin gene did not negatively impact the measles virus' cytotoxicity against medulloblastoma cells or alter its growth kinetics. Conditioned media obtained from these infected cells was capable of inhibiting multiple angiogenic factors in vitro, significantly reducing endothelial cell tube formation, viability and migration compared to conditioned media derived from cells infected by a control measles virus. Mice that were given a single intratumoral injection of MV-E:A likewise showed reduced numbers of tumor-associated blood vessels and a trend for increased survival compared to mice treated with the control virus.ConclusionsThese data suggest that oncolytic measles viruses encoding anti-angiogenic proteins may have therapeutic benefit against medulloblastoma and support ongoing efforts to target angiogenesis in medulloblastoma.

ObjectivesGout is the most prevalent inflammatory arthritis. To study the effects of regular physical activity and exercise intensity on inflammation and clinical outcome, we examined inflammatory pathogenesis in an acute model of murine gout and analyzed human gout patient clinical data as a function of physical activity.MethodsNF-κB-luciferase reporter mice were organized into four groups and exercised at 0 m/min (non-exercise), 8 m/min (low-intensity), 11 m/min (moderate-intensity), and 15 m/min (high-intensity) for two weeks. Mice subsequently received intra-articular monosodium urate (MSU) crystal injections (0.5mg) and the inflammatory response was analyzed 15 hours later. Ankle swelling, NF-κB activity, histopathology, and tissue infiltration by macrophages and neutrophils were measured. Toll-like receptor (TLR)2 was quantified on peripheral monocytes/neutrophils by flow cytometry and both cytokines and chemokines were measured in serum or synovial aspirates. Clinical data and questionnaires accessing overall physical activity levels were collected from gout patients.ResultsInjection of MSU crystals produced a robust inflammatory response with increased ankle swelling, NF-κB activity, and synovial infiltration by macrophages and neutrophils. These effects were partially mitigated by low and moderate-intensity exercise. Furthermore, IL-1β was decreased at the site of MSU crystal injection, TLR2 expression on peripheral neutrophils was downregulated, and expression of CXCL1 in serum was suppressed with low and moderate-intensity exercise. Conversely, the high-intensity exercise group closely resembled the non-exercised control group by nearly all metrics of inflammation measured in this study. Physically active gout patients had significantly less flares/yr, decreased C-reactive protein (CRP) levels, and lower pain scores relative to physically inactive patients.ConclusionsRegular, moderate physical activity can produce a quantifiable anti-inflammatory effect capable of partially mitigating the pathologic response induced by intra-articular MSU crystals by downregulating TLR2 expression on circulating neutrophils and suppressing systemic CXCL1. Low and moderate-intensity exercise produces this anti-inflammatory effect to varying degrees, while high-intensity exercise provides no significant difference in inflammation compared to non-exercising controls. Consistent with the animal model, gout patients with higher levels of physical activity have more favorable prognostic data. Collectively, these data suggest the need for further research and may be the foundation to a future paradigm-shift in conventional exercise recommendations provided by Rheumatologists to gout patients.