Multiscale systems biology and systems pharmacology are powerful methodologies that are playing increasingly important roles in understanding the fundamental mechanisms of biological phenomena and in clinical applications. In this review, we summarize the state of the art in the applications of agent-based models (ABM) and hybrid modeling to the tumor immune microenvironment and cancer immune response, including immunotherapy. Heterogeneity is a hallmark of cancer; tumor heterogeneity at the molecular, cellular, and tissue scales is a major determinant of metastasis, drug resistance, and low response rate to molecular targeted therapies and immunotherapies. Agent-based modeling is an effective methodology to obtain and understand quantitative characteristics of these processes and to propose clinical solutions aimed at overcoming the current obstacles in cancer treatment. We review models focusing on intra-tumor heterogeneity, particularly on interactions between cancer cells and strom... [more]

The available energy can be effectively upgraded by adopting smart energy conversion measures. The biodegradability of biomass can be improved by employing pretreatment techniques; however, such methods result in reduced energy efficiency. In this study, microwave (MW) irradiation is used for green algae (Enteromorpha) pretreatment in combination with iron oxide nanoparticles (NPs) which act as a heterogeneous catalyst during anaerobic digestion process for biogas enhancement. Batch-wise anaerobic digestion was carried out. The results showed that MW pretreatment and its combination with Fe₃O₄ NPs produced highest yields of biogas and hydrogen as compared to the individual ones and control. The biogas amount and hydrogen % v/v achieved by MW pretreatment + Fe₃O₄ NPs group were 328 mL and 51.5%, respectively. The energy analysis indicated that synergistic application of MW pretreatment with Fe₃O₄ NPs produced added energy while consuming less input energy than MW pretreatment alone. The... [more]

Lemongrass is a plant that contains aromatic compounds (myrcene and limonene), powerful deodorants, and antimicrobial compounds (citral and geraniol). Identifying a suitable drying model for the material is crucial for establishing an initial step for the development of dried products. Convection drying is a commonly used drying method that could extend the shelf life of the product. In this study, a suitable kinetic model for the drying process was determined by fitting moisture data corresponding to four different temperature levels: 50, 55, 60 and 65 °C. In addition, the effect of drying temperature on the moisture removal rate, the effective diffusion coefficient and activation energy were also estimated. The results showed that time for moisture removal increases proportionally with the air-drying temperature, and that the Weibull model is the most suitable model for describing the drying process. The effective diffusion coefficient ranges from 7.64 × 10−11 m²/s to 1.48 × 10−10 m²... [more]

Excitable biological cells, such as cardiac muscle cells, can exhibit complex patterns of oscillations such as spiking and bursting. Moreover, it is well known that an enhancement in calcium currents may yield certain kind of cardiac arrhythmia, so-called early afterdepolarisations (EADs). The presence of EADs strongly correlates with the onset of dangerous cardiac arrhythmia. In this paper we study mathematically and numerically the dynamics of a cardiac muscle cell with respect to the calcium current by investigating a simplistic system of differential equations. For the study of this phenomena, we use bifurcation theory, numerical bifurcation analysis, geometric singular perturbation theory and computational methods to investigate a nonlinear multiple time scales system. It will turn out that EADs related to an enhanced calcium current are canard⁻induced and that we have to combine these theories to derive a better understanding of the dynamics behind EADs. Moreover, a suitable time... [more]

In earlier work (Silva et al., 2016; Soh et al., 2014a; Soh et al., 2015), the supercritical CO₂ transesterification of triolein to methyl-oleate using Nafion solid-acid catalyst and large methanol/triolein molar feed ratios was carried out. Herein, these ratios are adjusted (from 50⁻550) to evaluate the yield of fatty acid methyl esters in batch laboratory reactors as temperature is varied from 80⁻95 °C and pressure is varied from 8.0⁻9.65 MPa. Also, to better understand the effect of varying these operating parameters, batch reactor simulations using the Soave-Redlich-Kwong Equation of State (RK-ASPEN EOS) in ASPEN PLUS are carried-out. A single-reaction kinetic model is used and phase equilibrium is computed as the reactions proceed. Experimental data are compared with these results.

With the advent of effective immunotherapies to battle cancers and diseases, an obstacle in recovery has become the potential side effects, specifically cytokine release syndrome (CRS). As there is little quantitative understanding of risks for developing CRS and the degree of its severity, this work explored a model-based approach to produce a library of in silico patients through sensitivity analysis of cytokine interaction parameters and a Monte Carlo sampling. The objective of producing the in silico patients was to correlate a known grading system of cytokine release syndrome severity and thus design a new formula for grading CRS. Using our CRS grading system as the foundation, this work produced not only a formula which related the in silico patient data to the different grades, but we effectively demonstrated a selective approach to reduce the grade of CRS with sequential cytokine inhibition targets. We achieved the reduction of grades by applying the insight from the sensitivit... [more]

The effect of natural antibiotics Moringa oleifera seeds powder in cellulose acetate membranes as biofouling reducer agent was investigated. Mixed matrix membranes (MMM) were synthesized by adding 100 mesh M. oleifera seeds powder with variation of three concentrations (1 wt%, 2 wt%, and 3 wt%), into a mix polymer solution of CA (cellulose acetate) and two different solvents, i.e., DMF (dimethylformamide) and DMAc (dimethylacetamide). The synthesized membranes morphology was observed under scanning electron microscopy and from the images can be seen that the membranes made of DMAc formed rather large macrovoid as compared to DMF-based membranes. The microstructure affected the water flux through the membranes, in which the DMAc membranes provided a higher flux value and served as high-throughput microfiltration membranes. Antibacterial properties of MMM were tested using Escherichia coli adhesion onto membrane surfaces. The results showed that M. oleifera has been proven to eradicate E... [more]

Work on synthetic biology has largely used a component-based metaphor for system construction. While this paradigm has been successful for the construction of numerous systems, the incorporation of contextual design issues—either compositional, host or environmental—will be key to realising more complex applications. Here, we present a design framework that radically steps away from a purely parts-based paradigm by using aspect-oriented software engineering concepts. We believe that the notion of concerns is a powerful and biologically credible way of thinking about system synthesis. By adopting this approach, we can separate core concerns, which represent modular aims of the design, from cross-cutting concerns, which represent system-wide attributes. The explicit handling of cross-cutting concerns allows for contextual information to enter the design process in a modular way. As a proof-of-principle, we implemented the aspect-oriented approach in the Python tool, SynBioWeaver, which e... [more]

The regeneration of red blood cells (RBCs) after blood loss is an individual complex process. We present a novel simple compartment model which is able to capture the most important features and can be personalized using parameter estimation. We compare predictions of the proposed and personalized model to a more sophisticated state-of-the-art model for erythropoiesis, and to clinical data from healthy subjects. We discuss the choice of model parameters with respect to identifiability. We give an outlook on how extensions of this novel mathematical model could have an important impact for personalized clinical decision support in the case of polycythemia vera (PV). PV is a slow-growing type of blood cancer, where especially the production of RBCs is increased. The principal treatment targeting the symptoms of PV is bloodletting (phlebotomy), at regular intervals that are based on personal experiences of the physicians. Model-based decision support might help to identify optimal and ind... [more]

Regulatory T cells (Tregs) have an important role in self-tolerance. Understanding the functions of Tregs is important for preventing or slowing the progress of Type 1 Diabetes. We use a two-dimensional (2D) agent-based model to simulate immune response in mice and test the effects of Tregs in tissue protection. We compared the immune response with and without Tregs, and also tested the effects of Tregs from different sources or with different functions. The results show that Tregs can inhibit the proliferation of effector T cells by inhibiting antigens presenting via dendritic cells (DCs). Although the number and function of Tregs affect the inhibition, a small number of Tregs compared to CD4⁺ T cells can effectively protect islets in pancreatic tissue. Finally, we added Tregs to the system in the middle phase of the immune response. The simulation results show that Tregs can inhibit the production of effector CD8⁺ T cells and maintain a good environment for β cell regeneration.

Severe influenza infections are often characterized as having unique host responses (e.g., early, severe hypercytokinemia). Neuraminidase inhibitors can be effective in controlling the severe symptoms of influenza but are often not administered until late in the infection. Several studies suggest that immune modulation may offer protection to high risk groups. Here, we review the current state of mathematical models of influenza-induced host responses. Selecting three models with conserved immune response components, we determine if the immune system components which most affect virus replication when perturbed are conserved across the models. We also test each model’s response to a pre-induction of interferon before the virus is administered. We find that each model emphasizes the importance of controlling the infected cell population to control viral replication. Moreover, our work shows that the structure of current models does not allow for significant responses to increased interf... [more]

The antibacterial photocatalytic activity of TiO₂ supported over two types of substrates, borosilicate glass tubes (TiO₂/SiO₂-borosilicate glass tubes (BGT)) and low-density polyethylene pellets (TiO₂-LDPE pellets), which were placed in a compound parabolic collectors (CPC) reactor, was evaluated against Enterobacter cloacae and Escherichia coli under sunlight. Three solar photocatalytic systems were assessed, suspended TiO₂, TiO₂/SiO₂-BGT and TiO₂-LDPE pellets, at three initial bacterial concentrations, 1 × 10⁵; 1 × 10³; 1 × 10¹ CFU/mL of E. coli and total bacteria (E. cloacae and E. coli). The solar photo-inactivation of E. coli was achieved after two hours with 7.2 kJ/L of UV-A, while total bacteria required four hours and 16.5 kJ/L of UV-A. Inactivation order of E. coli was determined, as follows, suspended TiO₂/sunlight (50 mg/L) > TiO₂-LDPE pellets/sunlight (52 mg/L) > TiO₂/SiO₂-BGT/sunlight (59 mg/L), the best E. coli. inactivation rate was obtained with TiO₂-LDPE pellets/sunlig... [more]

Bioethanol is known as a viable alternative fuel to solve both energy and environmental crises. This study used response surface methodology based on the Box-Behnken experimental design to obtain the optimum conditions for and quality of bioethanol production. Enzymatic hydrolysis optimization was performed with selected hydrolysis parameters, including substrate loading, stroke speed, α-amylase concentration and amyloglucosidase concentration. From the experiment, the resulting optimum conditions are 23.88% (w/v) substrate loading, 109.43 U/g α-amylase concentration, 65.44 U/mL amyloglucosidase concentration and 74.87 rpm stroke speed, which yielded 196.23 g/L reducing sugar. The fermentation process was also carried out, with a production value of 0.45 g ethanol/g reducing sugar, which is equivalent to 88.61% of ethanol yield after fermentation by using Saccharomyces cerevisiae (S. cerevisiae). The physical and chemical properties of the produced ethanol are within the specifications... [more]

In light of possible future restrictions on the use of fossil fuel, due to climate change obligations and continuous depletion of global fossil fuel reserves, the search for alternative renewable energy sources is expected to be an issue of great concern for policy stakeholders. This study assessed the feasibility of bioenergy production under relatively low-intensity conservative, eco-agricultural settings (as opposed to those produced under high-intensity, fossil fuel based industrialized agriculture). Estimates of the net energy gain (NEG) and the energy return on energy invested (EROEI) obtained from a life cycle inventory of the energy inputs and outputs involved reveal that the energy efficiency of bioenergy produced in low-intensity eco-agricultural systems could be as much as much as 448.5⁻488.3 GJ·ha−1 of NEG and an EROEI of 5.4⁻5.9 for maize ethanol production systems, and as much as 155.0⁻283.9 GJ·ha−1 of NEG and an EROEI of 14.7⁻22.4 for maize biogas production systems. Thi... [more]

Yellow poplar (Liriodendron tulipifera) was chosen as the woody biomass for the production of charcoal for use in a liquid fuel slurry. Charcoal produced from this biomass resulted in a highly porous structure similar to the parent material. Micronized particles were produced from this charcoal using a multi-step milling process and verified using a scanning electron microscope and laser diffraction system. Charcoal particles greater than 50 µm exhibited long needle shapes much like the parent biomass while particles less than 50 µm were produced with aspect ratios closer to unity. Laser diffraction measurements indicated D10, D50, and D90 values of 4.446 µm, 15.83 µm, and 39.69 µm, respectively. Moisture content, ash content, absolute density, and energy content values were also measured for the charcoal particles produced. Calculated volumetric energy density values for the charcoal particles exceeded the No. 2 diesel fuel that would be displaced in a liquid fuel slurry.

In anaerobic digestion (AD), long-chain fatty acids (LCFAs) produced by hydrolysis of lipids, exhibit toxicity against microorganisms when their concentration exceeds several millimolar. An absorption detection system using a quartz crystal microbalance (QCM) was developed to monitor the LCFA concentration during an anaerobic digester’s operation treating oily organic waste. The dissociation of the LCFAs considerably improved the sensor response and, moreover, enabled it to specifically detect LCFA from the mixture of LCFA and triglyceride. Under alkaline conditions, the frequency-shift rates of the QCM sensor linearly increased in accordance with palmitic acid concentration in the range of 0⁻100 mg/L. Frequency changes caused by anaerobic digestate samples were successfully measured after removing suspended solids and adjusting the pH to 10.7. Finally, the QCM measurements for digestate samples demonstrated that frequency-shift rates are highly correlated with LCFA concentrations, whi... [more]

Biochar (BC) is increasingly applied in agriculture; however, due to its adsorption and degradation properties, biochar may also affect the efficacy of fumigant in amended soil. Our research is intended to study the effects of two types of biochars (BC-1 and BC-2) on the efficacy and emission of methyl isothiocyanate (MITC) in biochar amendment soil. Both types of biochars can significantly reduce MITC emission losses, but, at the same time, decrease the concentration of MITC in the soil. The efficacy of MITC for controlling soil-borne pests (Meloidogyne spp., Fusarium spp. Phytophthora spp., Abutilon theophrasti and Digitaria sanguinalis) was reduced when the biochar (BC-1 and BC-2) was applied at a rate of higher than 1% and 0.5% (on a weight basis) (on a weight basis), respectively. However, increased doses of dazomet (DZ) were able to offset decreases in the efficacy of MITC in soils amended with biochars. Biochars with strong adsorption capacity (such as BC-1) substantially reduce... [more]

This experimental work studies a small-scale biomass combustor (5⁻12 kW) with an underfed fixed bed using low air staging ratios (15%⁻30%). This document focuses on the influence of the operative parameters on the combustion process, so gaseous emissions and the distribution and concentration of particulate matter have also been recorded. The facility shows good stability and test repeatability. For the studied airflow ranges, the results show that increasing the total airflow rate does not increase the overall air excess ratio because the burning rate is proportionally enhanced (with some slight differences that depend on the air staging ratio). Consequently, the heterogeneous reactions at the bed remain in the so-called oxygen-limited region, and thus the entire bed operates under sub-stoichiometric conditions with regards of the char content of the biomass. In addition, tests using only primary air (no staging) may increase the fuel consumption, but in a highly incomplete way, appro... [more]

Italy, like every country member of the European Union (EU), will have to achieve the objectives required by the Energy Roadmap 2050. The purpose of the study was to evaluate the environmental impacts of residue recovery arising from the management of public and private green feedstocks, activity of the cooperative “Green City” in the Bologna district, and usage in a centralized heating system to produce thermal energy for public buildings. Results, obtained using the ReCipe impact assessment method, are compared with scores achieved by a traditional methane boiler. The study shows some advantages of the biomass-based system in terms of greenhouse gases (GHGs) emissions and consumption of non-renewable fuels, which affect climate change (−41%) and fossil resources depletion (−40%), compared to the use of natural gas (NG). Moreover, scores from network analysis denote the great contribution of feedstock transportation (98% of the cumulative impact). The main reason is attributable to al... [more]

In recent years, bioenergy has become a promising renewable energy source that can potentially reduce the greenhouse emissions and generate economic growth in rural areas. Gaining understanding and controlling biomass chemical composition contributes to an efficient biofuel generation. This paper presents a principal component analysis (PCA) that shows the influence and relevance of selected controllable factors over the chemical composition of switchgrass and, therefore, in the generation of biofuels. The study introduces the following factors: (1) storage days; (2) particle size; (3) wrap type; and (4) weight of the bale. Results show that all the aforementioned factors have an influence in the chemical composition. The number of days that bales have been stored was the most significant factor regarding changes in chemical components due to its effect over principal components 1 and 2 (PC1 and PC2, approximately 80% of the total variance). The storage days are followed by the particl... [more]

This study used thermal cracking with hydrogen (HTC) to produce bio-fuel oil (BFO) from jatropha oil (JO) and to improve its quality. We conducted HTC with different hydrogen pressures (PH2; 0⁻2.07 MPa or 0⁻300 psig), retention times (tr; 40⁻780 min), and set temperatures (TC; 623⁻683 K). By applying HTC, the oil molecules can be hydrogenated and broken down into smaller molecules. The acid value (AV), iodine value, kinematic viscosity (KV), density, and heating value (HV) of the BFO produced were measured and compared with the prevailing standards for oil to assess its suitability as a substitute for fossil fuels or biofuels. The results indicate that an increase in PH2 tends to increase the AV and KV while decreasing the HV of the BFO. The BFO yield (YBFO) increases with PH2 and tr. The above properties decrease with increasing TC. Upon HTC at 0.69 MPa (100 psig) H₂ pressure, 60 min time, and 683 K temperature, the YBFO was found to be 86 wt%. The resulting BFO possesses simulated di... [more]

In the context of environmental sustainability there has been an increasing interest in bioenergy production from renewable resources, and is expected that European biofuel production from energy crops will increase as a consequence of the achievement of policy targets. The aim of this paper is to assess the agronomic feasibility of biomass crop cultivation to provide profitable renewable feedstocks in a marginal and heavy-metal polluted area located in the Sulcis district, Sardinia (Italy). Results from literature review and unpublished data from field trials carried out in Sardinia were analysed to establish the main agronomic traits of crops (e.g., yield potential and input requirements). A Geographical Information System (GIS)-based procedure with remotely sensed data is also used to evaluate the land suitability and the actual land use/cover, considering a future scenario of expansion of energy crops on these marginal areas avoiding potential conflicts with food production. The re... [more]

The characteristics of biochar vary with pyrolysis temperature. Chloropicrin (CP) is an effective fumigant for controlling soil-borne pests. This study investigated the characteristics of biochars prepared at 300, 500, and 700 °C by michelia alba (Magnolia denudata) wood and evaluated their capacity to adsorb CP. The study also determined the potential influence of biochar, which was added to sterilized and unsterilized soils at rates of 0%, 1%, 5%, and 100%, on CP degradation. The specific surface area, pore volume, and micropores increased considerably with an increase in the pyrolytic temperature. The adsorption rate of biochar for CP increased with increasing pyrolytic temperature. The maximum adsorption amounts of CP were similar for the three biochars. Next, the study examined the degradation ability of the biochar for CP. The degradation rate constant (k) of CP increased when biochar was added to the soil, and k increased with increased amendment rate and pyrolysis temperature.... [more]

This paper builds upon a research project funded by the Italian Ministry of Environment, and aims to recover stranded driftwood residues (SDRs), in order to transform a potential pollution and safety issue into valuable bio-resources. In particular, one of the experiments consisted of bioethanol production from lignocellulosic residues. The SDRs were gathered from the Italian coast (Abruzzo Region, Italy) after an intense storm. The biomass recalcitrance, due to its lignocellulosic structure, was reduced by a steam explosion (SE) pretreatment process. Four different pretreatment severity factors (R₀) were tested (LogR₀ 3.65, 4.05, 4.24 and 4.64) in order to evaluate the pretreated material’s accessibility to enzymatic attack and the holocellulose (cellulose plus hemicellulose) recovery. A first enzymatic hydrolysis was performed on the pretreated materials by employing a solid/liquid (S/L) ratio of 1% (w/w) and an enzyme dosage of 30% (w enzyme/w cellulose), in order to estimate the ma... [more]

Concerns about climate change and food productivity have spurred interest in biochar, a form of charred organic material typically used in agriculture to improve soil productivity and as a means of carbon sequestration. An innovative approach in agriculture is the use of agro-forestry waste for the production of soil fertilisers for agricultural purposes and as a source of energy. A common agricultural practice is to burn crop residues in the field to produce ashes that can be used as soil fertilisers. This approach is able to supply plants with certain nutrients, such as Ca, K, Mg, Na, B, S, and Mo. However, the low concentration of N and P in the ashes, together with the occasional presence of heavy metals (Ni, Pb, Cd, Se, Al, etc.), has a negative effect on soil and, therefore, crop productivity. This work describes the opportunity to create an innovative supply chain from agricultural waste biomass. Olive (Olea europaea) and hazelnut (Corylus avellana) pruning residues represent a... [more]