SMGen: A Generator of Synthetic Models of Biochemical Reaction Networks

Several software tools for the simulation and analysis of biochemical reaction networks have been developed in the last decades; however, assessing and comparing their computational performance in executing the typical tasks of computational systems biology can be limited by the lack of a standardized benchmarking approach. To overcome these limitations, we propose here a novel tool, named SMGen, designed to automatically generate synthetic models of reaction networks that, by construction, are characterized by relevant features (e.g., system connectivity and reaction discreteness) and non-trivial emergent dynamics of real biochemical networks. The generation of synthetic models in SMGen is based on the definition of an undirected graph consisting of a single connected component that, generally, results in a computationally demanding task; to speed up the overall process, SMGen exploits a main–worker paradigm. SMGen is also provided with a user-friendly graphical user interface, which allows the user to easily set up all the parameters required to generate a set of synthetic models with any number of reactions and species. We analysed the computational performance of SMGen by generating batches of symmetric and asymmetric reaction-based models (RBMs) of increasing size, showing how a different number of reactions and/or species affects the generation time. Our results show that when the number of reactions is higher than the number of species, SMGen has to identify and correct a large number of errors during the creation process of the RBMs, a circumstance that increases the running time. Still, SMGen can generate synthetic models with hundreds of species and reactions in less than 7 s.

Production of Synthetic Models for Neuro-Oncology Training by Additive Manufacturing

Neurosurgery is one of the medical specialties in which the practical training of students is more limiting since it requires a high degree of preparation for the interventions to be satisfactory. That is why the manufacture of synthetic models through additive manufacturing (AM) arises to develop the skills that the neurosurgeon requires. The present work is aimed at validating the use of AM for the neurosurgery training. To this regard, a meningioma case study was considered, and suitable materials and more appropriate AM technology were identified for a low-cost production of synthetic models of both skulls and brains with tumors. The skull was manufactured by material extrusion AM with two materials, a commercial composite filament composed of polylactic acid (PLA) with calcium carbonate (used in the area to be treated during the cutting process, due to its mechanical properties more comparable to those of the native bone, with 30% infill density) and standard PLA without additives (used in the rest of the model, with 20% infill density). On the other hand, different casting silicones in different proportions were tested under compression molding to find the best combination to mimic the brain and tumor. Ten synthetic models of a real-case meningioma were manufactured and used as training material by students in the neurosurgery sector, who rated the proposed training approach very highly, considering the employment of printed models as a key resource for improving their surgical skills.

Partial synthetic models of FeMoco with sulfide and carbyne ligands: Effect of interstitial atom in nitrogenase active site

Nitrogen-fixing organisms perform dinitrogen reduction to ammonia at an Fe-M (M = Mo, Fe, or V) cofactor (FeMco) of nitrogenase. FeMco displays eight metal centers bridged by sulfides and a carbide having the MFe7S8C cluster composition. The role of the carbide ligand, a unique motif in protein active sites, remains poorly understood. Toward addressing how the carbon bridge affects the physical and chemical properties of the cluster, we isolated synthetic models of subsite MFe3S3C displaying sulfides and a chelating carbyne ligand. We developed synthetic protocols for structurally related clusters, [Tp*M’Fe3S3X]n−, where M’ = Mo or W, the bridging ligand X = CR, N, NR, S, and Tp* = Tris(3,5-dimethyl-1-pyrazolyl)hydroborate, to study the effects of the identity of the heterometal and the bridging X group on structure and electrochemistry. While the nature of M’ results in minor changes, the chelating, μ3-bridging carbyne has a large impact on reduction potentials, being up to 1 V more reducing compared to nonchelating N and S analogs.

Correlating biological activity to thermo-structural analysis of the interaction of CTX with synthetic models of macrophage membranes

The important pharmacological actions of Crotoxin (CTX) on macrophages, the main toxin in the venom of Crotalus durissus terrificus, and its important participation in the control of different pathophysiological processes, have been demonstrated. The biological activities performed by macrophages are related to signaling mediated by receptors expressed on the membrane surface of these cells or opening and closing of ion channels, generation of membrane curvature and pore formation. In the present work, the interaction of the CTX complex with the cell membrane of macrophages is studied, both using biological cells and synthetic lipid membranes to monitor structural alterations induced by the protein. Here we show that CTX can penetrate THP-1 cells and induce pores only in anionic lipid model membranes, suggesting that a possible access pathway for CTX to the cell is via lipids with anionic polar heads. Considering that the selectivity of the lipid composition varies in different tissues and organs of the human body, the thermostructural studies presented here are extremely important to open new investigations on the biological activities of CTX in different biological systems.

Comparative Analysis of Tracers Against Pressure Pulse Code Interference Testing based on the Numerical Simulations of the Synthetic Oilfields with Complicated Geology

The main objective of the study is to compare the results of the cross-well tracers survey against the pulse code pressure interference testing (PCT) for the complicated geological structures. The study was based on the numerical simulations on the synthetic 3D models with popular geological complications, such as faults, vertical and horizontal reservoir anisotropy and pinch-outs. The study has set a special focus on quantitative analysis of the reservoir properties estimated by tracers and PCT as against the known values. This provides a text-book examples of advantages and disadvantages of both surveillance methods in different geological environment. Pulse code testing is specific implementation of pressure interference testing by creating a series of injection/production rate changes accordingly to a preset schedule to create a "pressure code" and monitoring the pressure response in the offset wells. The use of high-resolution quarts gauges is highly beneficial in case of large cross-well intervals scanning or poor reservoir quality in case of regular inter-well spacing. The tracer survey is based on injecting a liquid with chemical markers and subsequent capturing the markers at surface samples in the offset wells. The modern markers are relatively cheap and can be captured at very low concentrations thus making the cross-well scanning available even for high inter-well spacing. For synthetic models with vertical inhomogeneity the PCT provides a close estimate for compound dynamic reservoir properties (transmissibility and pressure diffusivity). For synthetic models with lateral inhomogeneity the PCT provides an accurate estimation for effective reservoir thickness and permeability. Tracers survey is not able to assess the reservoir thickness. The popular methods to assess reservoir permeability from tracers survey show a substantial deviation from the true reservoir permeability for synthetic models with vertical and lateral heterogeneity. This leads to conclusion that the most reliable application of racers survey is a qualitative assessment of cross-well connectivity and quantitative estimate of permeability in homogenous reservoirs. The first study of quantitative comparison of tracer survey against pressure pulse-code interference survey. Tracer survey and PCT efficiency was compared on 3D numerical models. Presence of synthetic models, describing geological complications, which may be seen very often on real reservoirs, provides a reliable basis for comparison.

River sedimentation modeling using ground-penetrating radar

In recent years, siltation has become quite a problem. It has been the main cause of flooding and a rapid decline in water quality. It is usually caused by a high river sedimentation rate and/or uncontrolled waste disposal. The increased rate of erosion also means that river sedimentation occurs faster than normal and could lead to environmental hazards, wildlife deaths, and the disruption of food and drinking water supply among other things. The question is how to monitor the sedimentation process of rivers without damaging the river itself. The suitable geophysical method is GPR. GPR is an active, non-intrusive geophysical method in which electromagnetic radiation and the reflected signals in the form of radar pulses are used for subsurface imaging. The objective is to investigate river sedimentation using GPR, we created the synthetic models based on geological models of rivers with different depths to create their 2-D radargrams to predict the actual model. We set up the first model RSM-I as control which consists of a layer of freshwater with ρ = 16 Ωm, k = 81 and μ r = 1 of depth 5 m, two layers of sandstone with ρ = 850 Ωm, k = 2.5 and μ r = 1 of total depth 4 m, and a layer of claystone with ρ = 120 Ωm, k = 11 and μ r = 1 of depth 1 m. RSM-II and III are added with a buildup of saturated sediment with ρ = 30 Ωm, k = 15, and μ r = 1 of depth 2.5 and 4 m, respectively. The radargrams’ reflector for each model shows a two-way travel time of 300-350, 150-200, and 60-90 ns in their respective order. GPR models can differentiate between the saturated sediment and freshwater, it shows good results regarding sediment investigation in rivers.

NeLF: Neural Light-transport Field for Portrait View Synthesis and Relighting

Human portraits exhibit various appearances when observed from different views under different lighting conditions. We can easily imagine how the face will look like in another setup, but computer algorithms still fail on this problem given limited observations. To this end, we present a system for portrait view synthesis and relighting: given multiple portraits, we use a neural network to predict the light-transport field in 3D space, and from the predicted Neural Light-transport Field (NeLF)produce a portrait from a new camera view under a new environmental lighting. Our system is trained on a large number of synthetic models, and can generalize to different synthetic and real portraits under various lighting conditions. Our method achieves simultaneous view synthesis and relighting given multi-view portraits as the input, and achieves state-of-the-art results.

A quantitative method for deriving salinity of subglacial water using ground-based transient electromagnetics

Liquid water can exist at temperatures well below freezing beneath glaciers and ice sheets, where subglacial water systems, fresh and saline, have been shown to host unique microbial ecosystems. Geophysical techniques sensitive to fluid-content contrasts, e.g. electromagnetics, can characterize subglacial water and its salinity. Here, we assess the ground-based transient electromagnetic (TEM) method for deriving the resistivity and salinity of subglacial water. We adapt an existing open-source Bayesian inversion algorithm, which uses independent depth constraints, to output posterior distributions of resistivity and pore fluid salinity with depth. A variety of synthetic models, including a thin (5 m), conductive (0.16 Ωm), hypersaline (147 psu) subglacial lake, are used to evaluate the TEM method for imaging under 800 m-thick ice. The study demonstrates that TEM methods can resolve conductive, saline bodies accurately using external depth constraints, for example, from radar or seismic data. The depth resolution of TEM can be limited beneath deep (>800 m), thick (>50 m) conductive, water bodies and additional constraints from passive electromagnetic (EM) methods could be used to reduce ambiguities in the TEM results. Subsequently, non-invasive active and passive EM methods could provide profound insights into remote aqueous systems under glaciers and ice sheets.

A Statistical Assessment of Blending Hydrogen into Gas Networks

The deployment of low-carbon hydrogen in gas grids comes with strategic benefits in terms of energy system integration and decarbonization. However, hydrogen thermophysical properties substantially differ from natural gas and pose concerns of technical and regulatory nature. The present study investigates the blending of hydrogen into distribution gas networks, focusing on the steady-state fluid dynamic response of the grids and gas quality compliance issues at increasing hydrogen admixture levels. Two blending strategies are analyzed, the first of which involves the supply of NG–H2 blends at the city gate, while the latter addresses the injection of pure hydrogen in internal grid locations. In contrast with traditional case-specific analyses, results are derived from simulations executed over a large number (i.e., one thousand) of synthetic models of gas networks. The responses of the grids are therefore analyzed in a statistical fashion. The results highlight that lower probabilities of violating fluid dynamic and quality restrictions are obtained when hydrogen injection occurs close to or in correspondence with the system city gate. When pure hydrogen is injected in internal grid locations, even very low volumes (1% vol of the total) may determine gas quality violations, while fluid dynamic issues arise only in rare cases of significant hydrogen injection volumes (30% vol of the total).

Practical application of synthetic head models in real ballistic cases

In shooting crimes, ballistics tests are often recommended in order to reproduce the wound characteristics of the involved persons. For this purpose, several “simulants” can be used. However, despite the efforts in the research of “surrogates” in the field of forensic ballistic, the development of synthetic models needs still to be improved through a validation process based on specific real caseworks. This study has been triggered by the findings observed during the autopsy performed on two victims killed in the same shooting incident, with similar wounding characteristics; namely two retained head shots with ricochet against the interior wall of the skull; both projectiles have been recovered during the autopsies after migration in the brain parenchyma. The thickness of the different tissues and structures along the bullets trajectories as well as the incident angles between the bullets paths and the skull walls have been measured and reproduced during the assemblage of the synthetic head models. Two different types of models (“open shape” and “spherical”) have been assembled using leather, polyurethane and gelatine to simulate respectively skin, bone and soft tissues. Six shots have been performed in total. The results of the models have been compared to the findings of post-mortem computed tomography (PMCT) and the autopsy findings.Out of the six shots, two perforated the models and four were retained. When the projectile was retained, the use of both models allowed reproducing the wounds characteristics observed on both victims in terms of penetration and ricochet behaviour. However, the projectiles recovered from the models showed less deformation than the bullets collected during the autopsies. The “open shape” model allowed a better controlling on the shooting parameters than the “spherical” model. Finally, the difference in bullet deformation could be caused by the choice of the bone simulant, which might under-represent either the strength or the density of the human bone. In our opinion, it would be worth to develop a new, more representative material for ballistic which simulates the human bone.