Search results for: peroxide initiation

Authors: Michael R. Shurin, Galina Shurin, Vladimir A. Kirichenko

Abstract:

Background. Visibility of hepatic malignancies is poor on non-contrast imaging for daily verification of liver malignancies prior to radiation therapy on MRI-guided Linear Accelerators (MR-Linac). Ferumoxytol® (Feraheme, AMAG Pharmaceuticals, Waltham, MA) is a SPION agent that is increasingly utilized off-label as hepatic MRI contrast. This agent has the advantage of providing a functional assessment of the liver based upon its uptake by hepatic Kupffer cells proportionate to vascular perfusion, resulting in strong T1, T2 and T2* relaxation effects and enhanced contrast of malignant tumors, which lack Kupffer cells. The latter characteristic has been recently utilized for MRI-guided radiotherapy planning with precision targeting of liver malignancies. However potential radiotoxicity of SPION has never been addressed for its safe use as an MRI-contrast agent during liver radiotherapy on MRI-Linac. This study defines the radiomodulating properties of SPIONs in vitro on human monocyte and macrophage cell lines exposed to 60Go gamma-rays within clinical radiotherapy dose range. Methods. Human monocyte and macrophages cell line in cultures were loaded with a clinically relevant concentration of Ferumoxytol (30µg/ml) for 2 and 24 h and irradiated to 3Gy, 5Gy and 10Gy. Cells were washed and cultured for additional 24 and 48 h prior to assessing their phenotypic activation by flow cytometry and function, including viability (Annexin V/PI assay), proliferation (MTT assay) and cytokine expression (Luminex assay). Results. Our results reveled that SPION affected both human monocytes and macrophages in vitro. Specifically, iron oxide nanoparticles decreased radiation-induced apoptosis and prevented radiation-induced inhibition of human monocyte proliferative activity. Furthermore, Ferumoxytol protected monocytes from radiation-induced modulation of phenotype. For instance, while irradiation decreased polarization of monocytes to CD11b+CD14+ and CD11bnegCD14neg phenotype, Ferumoxytol prevented these effects. In macrophages, Ferumoxytol counteracted the ability of radiation to up-regulate cell polarization to CD11b+CD14+ phenotype and prevented radiation-induced down-regulation of expression of HLA-DR and CD86 molecules. Finally, Ferumoxytol uptake by human monocytes down-regulated expression of pro-inflammatory chemokines MIP-1α (Macrophage inflammatory protein 1α), MIP-1β (CCL4) and RANTES (CCL5). In macrophages, Ferumoxytol reversed the expression of IL-1RA, IL-8, IP-10 (CXCL10) and TNF-α, and up-regulates expression of MCP-1 (CCL2) and MIP-1α in irradiated macrophages. Conclusion. SPION agent Ferumoxytol increases resistance of human monocytes to radiation-induced cell death in vitro and supports anti-inflammatory phenotype of human macrophages under radiation. The effect is radiation dose-dependent and depends on the duration of Feraheme uptake. This study also finds strong evidence that SPIONs reversed the effect of radiation on the expression of pro-inflammatory cytokines involved in initiation and development of radiation-induced liver damage. Correlative translational work at our institution will directly assess the cyto-protective effects of Ferumoxytol on human Kupfer cells in vitro and ex vivo analysis of explanted liver specimens in a subset of patients receiving Feraheme-enhanced MRI-guided radiotherapy to the primary liver tumors as a bridge to liver transplant.

Keywords: superparamagnetic iron oxide nanoparticles, radioprotection, magnetic resonance imaging, liver

Procedia PDF Downloads 70

Authors: Paul J. McKay

Abstract:

Large-scale genome-wide association studies (GWAS) investigating genetic contributions to sexual orientation and gender identity are largely lacking and may reduce stigma experienced in the LGBTQ+ community by providing an underlying biological explanation for queerness. While there is a growing consensus within the scientific community that genetic makeup contributes – at least in part – to sexual orientation and gender identity, there is a marked lack of genomics research exploring polygenic contributions to queerness. Based on recent (2019) findings from a large-scale GWAS investigating the genetic architecture of same-sex sexual behavior, and various additional peer-reviewed publications detailing novel insights into the molecular mechanisms of sexual orientation and gender identity, we hypothesize that sexual orientation and gender identity are complex, multifactorial, and polygenic; meaning that many genetic factors contribute to these phenomena, and environmental factors play a possible role through epigenetic modulation. In recent years, large-scale GWAS studies have been paramount to our modern understanding of many other complex human traits, such as in the case of autism spectrum disorder (ASD). Despite possible benefits of such research, including reduced stigma towards queer people, improved outcomes for LGBTQ+ in familial, socio-cultural, and political contexts, and improved access to healthcare (particularly for trans populations); important risks and considerations remain surrounding this type of research. To mitigate possibilities such as invalidation of the queer identities of existing LGBTQ+ individuals, genetic discrimination, or the possibility of euthanasia of embryos with a genetic predisposition to queerness (through reproductive technologies like IVF and/or gene-editing in utero), we propose a community-engaged research (CER) framework which emphasizes the privacy and confidentiality of research participants. Importantly, the historical legacy of scientific research attempting to pathologize queerness (in particular, falsely equating gender variance to mental illness) must be acknowledged to ensure any future research conducted in this realm does not propagate notions of homophobia, transphobia or stigma against queer people. Ultimately, in a world where same-sex sexual activity is criminalized in 69 UN member states, with 67 of these states imposing imprisonment, 8 imposing public flogging, 6 (Brunei, Iran, Mauritania, Nigeria, Saudi Arabia, Yemen) invoking the death penalty, and another 5 (Afghanistan, Pakistan, Qatar, Somalia, United Arab Emirates) possibly invoking the death penalty, the importance of this research cannot be understated, as finding a biological basis for queerness would directly oppose the harmful rhetoric that “being LGBTQ+ is a choice.” Anti-trans legislation is similarly widespread: In the United States in 2022 alone (as of Oct. 13), 155 anti-trans bills have been introduced preventing trans girls and women from playing on female sports teams, barring trans youth from using bathrooms and locker rooms that align with their gender identity, banning access to gender affirming medical care (e.g., hormone-replacement therapy, gender-affirming surgeries), and imposing legal restrictions on name changes. Understanding that a general lack of knowledge about the biological basis of queerness may be a contributing factor to the societal stigma faced by gender and sexual orientation minorities, we propose the initiation of large-scale GWAS studies investigating the genetic basis of gender identity and sexual orientation.

Keywords: genome-wide association studies (GWAS), sexual and gender minorities (SGM), polygenicity, community-engaged research (CER)

Procedia PDF Downloads 67

Authors: M. M. Hassani, S. Ammann, F. K. Wittel, P. Niemz, H. J. Herrmann

Abstract:

Application of engineered wood, especially in the form of glued-laminated timbers has increased significantly. Recent progress in plywood made of high strength and high stiffness hardwoods, like European beech, gives designers in general more freedom by increased dimensional stability and load-bearing capacity. However, the strong hygric dependence of basically all mechanical properties renders many innovative ideas futile. The tendency of hardwood for higher moisture sorption and swelling coefficients lead to significant residual stresses in glued-laminated configurations, cross-laminated patterns in particular. These stress fields cause initiation and evolution of cracks in the bond-lines resulting in: interfacial de-bonding, loss of structural integrity, and reduction of load-carrying capacity. Subsequently, delamination of glued-laminated timbers made of hardwood elements can be considered as the dominant failure mechanism in such composite elements. In addition, long-term creep and mechano-sorption under changing environmental conditions lead to loss of stiffness and can amplify delamination growth over the lifetime of a structure even after decades. In this study we investigate the delamination process of adhesively bonded hardwood (European beech) elements subjected to changing climatic conditions. To gain further insight into the long-term performance of adhesively bonded elements during the design phase of new products, the development and verification of an authentic moisture-dependent constitutive model for various species is of great significance. Since up to now, a comprehensive moisture-dependent rheological model comprising all possibly emerging deformation mechanisms was missing, a 3D orthotropic elasto-plastic, visco-elastic, mechano-sorptive material model for wood, with all material constants being defined as a function of moisture content, was developed. Apart from the solid wood adherends, adhesive layer also plays a crucial role in the generation and distribution of the interfacial stresses. Adhesive substance can be treated as a continuum layer constructed from finite elements, represented as a homogeneous and isotropic material. To obtain a realistic assessment on the mechanical performance of the adhesive layer and a detailed look at the interfacial stress distributions, a generic constitutive model including all potentially activated deformation modes, namely elastic, plastic, and visco-elastic creep was developed. We focused our studies on the three most common adhesive systems for structural timber engineering: one-component polyurethane adhesive (PUR), melamine-urea-formaldehyde (MUF), and phenol-resorcinol-formaldehyde (PRF). The corresponding numerical integration approaches, with additive decomposition of the total strain are implemented within the ABAQUS FEM environment by means of user subroutine UMAT. To predict the true stress state, we perform a history dependent sequential moisture-stress analysis using the developed material models for both wood substrate and adhesive layer. Prediction of the delamination process is founded on the fracture mechanical properties of the adhesive bond-line, measured under different levels of moisture content and application of the cohesive interface elements. Finally, we compare the numerical predictions with the experimental observations of de-bonding in glued-laminated samples under changing environmental conditions.

Keywords: engineered wood, adhesive, material model, FEM analysis, fracture mechanics, delamination

Procedia PDF Downloads 429

Authors: Andrew Gennett

Abstract:

Designing for fungal development means embracing the symbiotic relationship between the living system and built environment. The potential of mycelium post-colonization is explored for the fabrication of advanced pure mycelium products, going beyond the conventional methods of aggregating materials. Fruiting induction imparts desired material properties such as enhanced environmental resistance. Production approach allows for simultaneous generation of multiple products while scaling up raw materials supply suitable for architectural applications. The following work explores the integration of fungal environmental perception with computational design of built fruiting chambers. Polyporales, are classified by their porous reproductive tissues supported by a wood-like context tissue covered by a hard waterproofing coat of hydrobpobins. Persisting for years in the wild, these species represent material properties that would be highly desired in moving beyond flat sheets of arial mycelium as with leather or bacon applications. Understanding the inherent environmental perception of fungi has become the basis for working with and inducing desired hyphal differentiation. Working within the native signal interpretation of a mycelium mass during fruiting induction provides the means to apply textures and color to the final finishing coat. A delicate interplay between meeting human-centered goals while designing around natural processes of living systems represents a blend of art and science. Architecturally, physical simulations inform model design for simple modular fruiting chambers that change as fungal growth progresses, while biological life science principles describe the internal computations occurring within the fungal hyphae. First, a form filling phase of growth is controlled by growth chamber environment. Second, an initiation phase of growth forms the final exterior finishing texture. Hyphal densification induces cellular cascades, in turn producing the classical hardened cuticle, UV protective molecule production, as well, as waterproofing finish. Upon fruiting process completion, the fully colonized spent substrate holds considerable value and is not considered waste. Instead, it becomes a valuable resource in the next cycle of production scale-up. However, the acquisition of new substrate resources poses a critical question, particularly as these resources become increasingly scarce. Pursuing a regenerative design paradigm from the environmental perspective, the usage of “agricultural waste” for architectural materials would prove a continuation of the destructive practices established by the previous industrial regime. For these residues from fields and forests serve a vital ecological role protecting the soil surface in combating erosion while reducing evaporation and fostering a biologically diverse food web. Instead, urban centers have been identified as abundant sources of new substrate material. Diverting the waste from secondary locations such as food processing centers, papers mills, and recycling facilities not only reduces landfill burden but leverages the latent value of these waste steams as precious resources for mycelium cultivation. In conclusion, working with living systems through innovative built environments for fungal development, provides the needed gain of function and resilience of mycelium products. The next generation of sustainable fungal products will go beyond the current binding process, with a focus upon reducing landfill burden from urban centers. In final considerations, biophilic material builds to an ecologically regenerative recycling production cycle.

Keywords: regenerative agriculture, mycelium fabrication, growth chamber design, sustainable resource acquisition, fungal morphogenesis, soil fertility

Procedia PDF Downloads 62

Authors: Krishna Raj Regmi

Abstract:

A “Climate change adaptation and disaster risk management for sustainable agriculture” project was implemented in Nepal, a Himalayan country during 2008 to 2013 sponsored jointly by Food and Agriculture Organization (FAO) and United Nations Development Programme (UNDP), Nepal. The paper is based on the results and findings of this joint pilot project. The climate change events such as increased intensity of erratic rains in short spells, trend of prolonged drought, gradual rise in temperature in the higher elevations and occurrence of cold and hot waves in Terai (lower plains) has led to flash floods, massive erosion in the hills particularly in Churia range and drying of water sources. These recurring natural and climate-induced disasters are causing heavy damages through sedimentation and inundation of agricultural lands, crops, livestock, infrastructures and rural settlements in the downstream plains and thus reducing agriculture productivity and food security in the country. About 65% of the cultivated land in Nepal is rainfed with drought-prone characteristics and stabilization of agricultural production and productivity in these tracts will be possible through adoption of rainfed and drought-tolerant technologies as well as efficient soil-water management by the local communities. The adaptation and mitigation technologies and options identified by the project for soil erosion, flash floods and landslide control are on-farm watershed management, sloping land agriculture technologies (SALT), agro-forestry practices, agri-silvi-pastoral management, hedge-row contour planting, bio-engineering along slopes and river banks, plantation of multi-purpose trees and management of degraded waste land including sandy river-bed flood plains. The stress tolerant technologies with respect to drought, floods and temperature stress for efficient utilization of nutrient, soil, water and other resources for increased productivity are adoption of stress tolerant crop varieties and breeds of animals, indigenous proven technologies, mixed and inter-cropping systems, system of rice/wheat intensification (SRI), direct rice seeding, double transplanting of rice, off-season vegetable production and regular management of nurseries, orchards and animal sheds. The alternate energy use options and resource conservation practices for use by local communities are installation of bio-gas plants and clean stoves (Chulla range) for mitigation of green house gas (GHG) emissions, use of organic manures and bio-pesticides, jatropha cultivation, green manuring in rice fields and minimum/zero tillage practices for marshy lands. The efficient water management practices for increasing productivity of crops and livestock are use of micro-irrigation practices, construction of water conservation and water harvesting ponds, use of overhead water tanks and Thai jars for rain water harvesting and rehabilitation of on-farm irrigation systems. Initiation of some works on community-based early warning system, strengthening of met stations and disaster database management has made genuine efforts in providing disaster-tailored early warning, meteorological and insurance services to the local communities. Contingent planning is recommended to develop coping strategies and capacities of local communities to adopt necessary changes in the cropping patterns and practices in relation to adverse climatic and disaster risk conditions. At the end, adoption of awareness raising and capacity development activities (technical and institutional) and networking on climate-induced disaster and risks through training, visits and knowledge sharing workshops, dissemination of technical know-how and technologies, conduct of farmers' field schools, development of extension materials and their displays are being promoted. However, there is still need of strong coordination and linkage between agriculture, environment, forestry, meteorology, irrigation, climate-induced pro-active disaster preparedness and research at the ministry, department and district level for up-scaling, implementation and institutionalization of climate change and disaster risk management activities and adaptation mitigation options in agriculture for sustainable livelihoods of the communities.

Keywords: climate change adaptation, disaster risk management, soil-water management practices, sustainable agriculture

Procedia PDF Downloads 504