Natural Analogues Research Articles

A Spark-Based Parallel Implementation of Arithmetic Optimization Algorithm

Arithmetic optimization algorithm (AOA) is a recent population-based metaheuristic widely used for solving optimization problems. However, the emerging large-scale optimization problems pose a great challenge for AOA due to its prohibitive computational cost to traverse the huge solution space effectively. This article proposes a parallel Spark-AOA using Scala on Apache Spark computing platform. Spark-AOA leverages the intrinsic parallel nature of the population-based AOA and the native iterative in-memory computation support of Spark through resilient distributed datasets (RDD) to accelerate the optimization process. Spark-AOA divides the solutions population into several subpopulations that are distributed into multiple RDD partitions and manipulated concurrently. Simulation experiments on different benchmark functions with up to 1,000-dimension and three engineering design problems demonstrate that Spark-AOA outperforms considerably standard AOA and Spark-based implementations of two recent metaheuristics both in terms of run-time and solution quality.

Continuous-variable neural network quantum states and the quantum rotor model

We initiate the study of neural network quantum state algorithms for analyzing continuous-variable quantum systems in which the quantum degrees of freedom correspond to coordinates on a smooth manifold. A simple family of continuous-variable trial wavefunctions is introduced which naturally generalizes the restricted Boltzmann machine (RBM) wavefunction introduced for analyzing quantum spin systems. By virtue of its simplicity, the same variational Monte Carlo training algorithms that have been developed for ground state determination and time evolution of spin systems have natural analogues in the continuum. We offer a proof of principle demonstration in the context of ground state determination of a stoquastic quantum rotor Hamiltonian. Results are compared against those obtained from partial differential equation (PDE) based scalable eigensolvers. This study serves as a benchmark against which future investigation of continuous-variable neural quantum states can be compared, and points to the need to consider deep network architectures and more sophisticated training algorithms.

Ocean acidification stunts molluscan growth at CO2 seeps

Ocean acidification can severely affect bivalve molluscs, especially their shell calcification. Assessing the fate of this vulnerable group in a rapidly acidifying ocean is therefore a pressing challenge. Volcanic CO2 seeps are natural analogues of future ocean conditions that offer unique insights into the scope of marine bivalves to cope with acidification. Here, we used a 2-month reciprocal transplantation of the coastal mussel Septifer bilocularis collected from reference and elevated pCO2 habitats to explore how they calcify and grow at CO2 seeps on the Pacific coast of Japan. We found significant decreases in condition index (an indication of tissue energy reserves) and shell growth of mussels living under elevated pCO2 conditions. These negative responses in their physiological performance under acidified conditions were closely associated with changes in their food sources (shown by changes to the soft tissue δ13C and δ15N ratios) and changes in their calcifying fluid carbonate chemistry (based on shell carbonate isotopic and elemental signatures). The reduced shell growth rate during the transplantation experiment was further supported by shell δ13C records along their incremental growth layers, as well as their smaller shell size despite being of comparable ontogenetic ages (5–7 years old, based on shell δ18O records). Taken together, these findings demonstrate how ocean acidification at CO2 seeps affects mussel growth and reveal that lowered shell growth helps them survive stressful conditions.

Effect of Walnut-Shell Additive on the Structure and Characteristics of Concrete.

The partial replacement of the mineral components of concrete with natural renewable analogues in full possession of the performance characteristics of the final material, allows not only the concrete-production process to be made more environmentally friendly and inexpensive, but also to solve an important task for the agricultural industry, which is that associated with waste disposal. The scientific novelty of the work is in the obtaining of new concrete compositions by the partial replacement of coarse aggregate with a natural analogue in the form of a walnut shell, which has the maximum ratio of the strength of the composite to its density, as well as in identifying new dependencies of strength and density and their ratio on the amount of replacement of mineral coarse-aggregate walnut shell. The main goal of this article was to analyze the effect of composition factors on characteristics of concrete with partial replacement of large aggregates with walnut shells and to search for the optimal compound that would make it possible to obtain concrete with a minimum decrease in strength characteristics with a maximum decrease in concrete density. Cubes and prism laboratory samples were made from concrete of normal density with the replacement of coarse aggregate by 5, 10, 15, 20, 25 and 30%, by volume. The main mechanical properties, such as density, strength (compressive, tensile, tensile strength in bending) of the concrete samples were studied. The investigation used standard methods and scanning electron microscopy. An increase into strength characteristics up to 3.5%, as well as the maximum ratio of strength to density of concrete, was observed at a walnut-shell dosage of 5%. Effective partial replacement of coarse aggregate with walnut shells leads to a reduction in the consumption of crushed stone by up to 10% and a decrease in the mass of concrete by up to 6%.

Imaging of Escherichia coli K5 and glycosaminoglycan precursors via targeted metabolic labeling of capsular polysaccharides in bacteria.

The introduction of unnatural chemical moieties into glycosaminoglycans (GAGs) has enormous potential to facilitate studies of the mechanism and application of these critical, widespread molecules. Unnatural N-acetylhexosamine analogs were metabolically incorporated into the capsule polysaccharides of Escherichia coli and Bacillus subtilis via bacterial metabolism. Targeted metabolic labeled hyaluronan and the precursors of heparin and chondroitin sulfate were obtained. The azido-labeled polysaccharides (purified or in capsules) were reacted with dyes, via bioorthogonal chemistry, to enable detection and imaging. Site-specific introduction of fluorophores directly onto cell surfaces affords another choice for observing and quantifying bacteria in vivo and in vitro. Furthermore, azido-polysaccharides retain similar biological properties to their natural analogs, and reliable and predictable introduction of functionalities, such as fluorophores, onto azido-N-hexosamines in the disaccharide repeat units provides chemical tools for imaging and metabolic analysis of GAGs in vivo and in vitro.

A Bioinspired Skin UV Filter with Broadband UV Protection, Photostability, and Resistance to Oxidative Damage.

In recent years, sunscreens' adverse impacts on the environment and biology have gained wide attention. The improvement of sunscreen safety has become one of the major priorities in skin photoprotection research. It is an effective strategy to develop bionic photoprotective materials by simulating the photoprotective mechanism existing in nature. Inspired by the photoprotective mechanisms of skin and plant leaves, the bionic photoprotective material CS-SA-PDA nanosheet was developed using the free radical grafting method and Michael addition, with natural melanin analogue polydopamine (PDA) nanoparticles and plant sunscreen molecular sinapic acid (SA) as sun protection factors and natural polymer chitosan (CS) as the connecting arm. The results show that CS-SA-PDA can effectively shield UVB and UVA due to the possible synergistic effect between PDA and SA. The introduction of polymer CS significantly improved the photostability of SA and reduced the skin permeability of PDA nanoparticles. The CS-SA-PDA nanosheet can also effectively scavenge photoinduced free radicals. Furthermore, in vivo toxicity and anti-UV evaluations confirm that CS-SA-PDA has no skin irritation and is excellent against skin photodamage, which makes it an ideal skin photoprotective material.

Ugi Four-Component Reactions Using Alternative Reactants.

The Ugi four-component reaction (Ugi-4CR) undoubtedly is the most prominent multicomponent reaction (MCRs) that has sparked organic chemists' interest in the field. It has been widely used in the synthesis of diverse heterocycle molecules such as potential drugs, natural product analogs, pseudo peptides, macrocycles, and functional materials. The Ugi-4CRs involve the use of an amine, an aldehyde or ketone, an isocyanide, and a carboxylic acid to produce an α-acetamido carboxamide derivative, which has significantly advanced the field of isocyanide-based MCRs. The so-called intermediate nitrilium ion could be trapped by a nucleophile such as azide, N-hydroxyphthalimide, thiol, saccharin, phenol, water, and hydrogen sulfide instead of the original carboxylic acid to allow for a wide variety of Ugi-type reactions to occur.β In addition to isocyanide, there are alternative reagents for the other three components: amine, isocyanide, and aldehyde or ketone. All these alternative components render the Ugi reaction an aptly diversity-oriented synthesis of a myriad of biologically active molecules and complex scaffolds. Consequently, this review will delve deeper into alternative components used in the Ugi MCRs, particularly over the past ten years.

Molecular Insights into Bifunctional Ambruticin DH3 for Substrate Specificity and Catalytic Mechanism.

Dehydratase (DH), a domain located at polyketide synthase (PKS) modules, commonly catalyzes the dehydration of β-hydroxy to an α,β-unsaturated acyl intermediate. As a unique bifunctional dehydratase, AmbDH3 (the DH domain of module 3 of the ambruticin PKS) is verified to be responsible for both dehydration and the following pyran-forming cyclization. Besides, in vitro studies showed that its catalytic efficiency varies with different chiral substrates. However, the detailed molecular mechanism of AmbDH3 remains unclear. In this work, the structural rationale for the substrate specificity (2R/2S- and 6R/6S-substrates) in AmbDH3 was elucidated and the complete reaction pathways including dehydration and cyclization were presented. Both MD simulations and binding free energy calculations indicated AmbDH3 had a stronger preference for 2R-substrates (2R6R-2, 2R6S-3) than 2S-substrates (2S6R-1), and residue H51 and G61 around the catalytic pocket were emphasized by forming stable hydrogen bonds with 2R-substrates. In addition, AmbDH3's mild tolerance at C6 was explained by comparison of substrate conformation and hydrogen bond network in 6S- and 6R-substrate systems. The QM/MM results supported a consecutive one-base dehydration and cyclization mechanism for 2R6S-3 substrate with the energy barrier of 25.2 kcal mol-1 and 24.5 kcal mol-1 , respectively. Our computational results uncover the substrate recognition and catalytic process of the first bifunctional dehydratase-cyclase AmbDH3, which will shed light on the application of multifunctional DH domains in PKSs for diverse natural product analogs and benefit the chemoenzymatic synthesis of stereoselective pyran-containing products.

DURABILITY IN WATER OF MATRICES FOR RARE-EARTH – ACTINIDE FRACTION OF HIGH-LEVEL RADIOACTIVE WASTE

The durability in waters of matrices for rare-earth – actinide fraction HLW has been studied at 25 (1 atm.), 200 or 240°C (pressure of saturated vapor). The samples composed of Nd2ZrTiO7 (cubic pyrochlore-type structure) or Nd4(Ti,Zr)9O24 (orthorhombic symmetry, no natural analogue), phases were obtained by induction melting in a “cold” crucible. Leaching rate of Nd (imitator of REE-MA fraction) on the 28th day of experiment was lower than 5 × 10–8 g/(cm2 day). These results confirmed a very high durability of the ceramic waste forms in hot underground waters.

Modeling and simulating human mitochondrial RNA polymerase nucleotide addition cycle using computational microscope.

Human mitochondrial RNA polymerase (POLRMT) is essential to the transcription of mitochondrial DNA and cell metabolism. This work contributes to an all-atom structural dynamics model for individual steps of the nucleotide addition cycle of POLRMT. We aim to establish a computational model using all-atom molecular dynamics to reveal Watson-Crick base pair regulation of natural nucleotide and nucleotide analog binding and insertion in POLRMT, and a model for the post-catalytic mechanochemical coupling between product release and POLRMT translocation. The models are currently constructed combining the available high-resolution structures of POLRMT in the open and closed conformations with the bound NTP and Mg2+ ions detected in structurally similar T7 bacteriophage RNA polymerase, and by additionally using curve interpolation to place a missing non-template DNA segment. The models have been evaluated for protein subdomain stability and the presence of the appropriate protein conformation, open or closed, via subdomain motion regulation on the active site. Ongoing work will establish a model for the post-translocation mechanochemical regulations that reset for a new nucleotide addition cycle. Since POLRMT is structurally similar to viral RNA polymerases, the studies are particularly important for antiviral drug design, where nucleotide analog drug candidates are expected to be well screened for POLRMT toxicity.

Low-density parity-check codes: Highway to channel capacity

Low-density parity-check (LDPC) codes are not only capacity-approaching, but also greatly suitable for high-throughput implementation. Thus, they are the most popular codes for high-speed data transmission in the past two decades. Thanks to the low-density property of their parity-check matrices, the optimal maximum a posteriori probability decoding of LDPC codes can be approximated by message-passing decoding with linear complexity and highly parallel nature. Then, it reveals that the approximation has to carry on Tanner graphs without short cycles and small trapping sets. Last, it demonstrates that well-designed LDPC codes with the aid of computer simulation and asymptotic analysis tools are able to approach the channel capacity. Moreover, quasi-cyclic (QC) structure is introduced to significantly facilitate their high-throughput implementation. In fact, compared to the other capacity-approaching codes, QC-LDPC codes can provide better area-efficiency and energy-efficiency. As a result, they are widely applied in numerous communication systems, e.g., Landsat satellites, Chang'e Chinese Lunar mission, 5G mobile communications and so on. What's more, its extension to non-binary Galois fields has been adopted as the channel coding scheme for BeiDou navigation satellite system.

Explicit molecular dynamics simulation studies to discover novel natural compound analogues as Mycobacterium tuberculosis inhibitors

Tuberculosis (TB) in one of the dreadful diseases present globally. This is caused by Mycobacterium tuberculosis. Mycobacterium tuberculosis dethiobiotin synthetase (MtDTBS) is an essential enzyme in biotin biosynthesis and is an ideal target to design and develop novel inhibitors. In order to effectively combat this disease six natural compound (butein) analogues were subjected to molecular docking to determine their binding mode and the binding affinities. The resultant complex structures were subjected to 500 ns simulation run to estimate their binding stabilities using GROMACS. The molecular dynamics simulation studies provided essential evidence that the systems were stable during the progression of 500 ns simulation run. The root mean square deviation (RMSD) of all the systems was found to be below 0.3 nm stating that the systems are well converged. The radius of gyration (Rg) profiles indicated that the systems were highly compact without any major fluctuations. The principle component analysis (PCA) and Gibbs energy landscape studies have revealed that the comp3, comp5 and comp11 systems navigated marginally through the PC2. The intermolecular interactions have further demonstrated that all the compounds have displayed key residue interactions, firmly holding the ligands at the binding pocket. The residue Lys37 was found consistently to interact with all the ligands highlighting its potential role in inhibiting the MtDTBS. Our investigation further put forth two novel compounds (comp10 and comp11) as putative antituberculosis agents. Collectively, we propose six compounds has plausible inhibitors to curtail TB and further can act as scaffolds in designing new compounds.

Computer-aided drug design approaches applied to screen natural product’s structural analogs targeting arginase in Leishmania spp

Introduction: Leishmaniasis is a disease with high mortality rates and approximately 1.5 million new cases each year. Despite the new approaches and advances to fight the disease, there are no effective therapies. Methods: Hence, this study aims to screen for natural products' structural analogs as new drug candidates against leishmaniasis. We applied Computer-aided drug design (CADD) approaches, such as virtual screening, molecular docking, molecular dynamics simulation, molecular mechanics–generalized Born surface area (MM–GBSA) binding free estimation, and free energy perturbation (FEP) aiming to select structural analogs from natural products that have shown anti-leishmanial and anti-arginase activities and that could bind selectively against the Leishmania arginase enzyme. Results: The compounds 2H-1-benzopyran, 3,4-dihydro-2-(2-methylphenyl)-(9CI), echioidinin, and malvidin showed good results against arginase targets from three parasite species and negative results for potential toxicities. The echioidinin and malvidin ligands generated interactions in the active center at pH 2.0 conditions and hydrogen bonds enhancing enzyme–ligand coupling. Conclusions: This work suggests the potential anti-leishmanial activity of the compounds and thus can be further in vitro and in vivo experimentally validated.

Immobilize Nd2O3 as simulated nuclear waste in silicate-apatite glass-ceramics

The solidification of nuclear waste has far-reaching developmental implications. Nuclear waste management is not only essential for the earth’s ecological balance but also can address the increasing depletion of human exploitable resources in the future. Scientists are dedicated to finding a better solidification matrix and ensuring the sustainable development of the nuclear industry in search of alternative energy sources. The present work has fabricated a simulated nuclear waste form using a sintering process of diopside. The results have shown that the Fe element in diopside granite porphyry shows an impact on the amorphization process and mechanical properties of the final waste form. Moreover, the study finds a natural analog in the glassy bulk, i.e. (Ca2Nd8(SiO4)6O2 or (K, Na)Nd9(SiO4)6O2), which can solidify the simulated trivalent actinide of Nd3+. The FT-IR results suggested that the polymerization degree of glass components in waste form decreased initially and then increased with Nd2O3 doping. Q3 unit is considered to be a key component in the waste forms. Finally, the loading capacity of Nd2O3 in waste form reached 19 wt.%. The waste form has the characteristics of glass-ceramics containing a silicate-apatite structure that is evenly distributed and has a quite considerable prospect for mechanical properties.

Garcinol and its analogues: Synthesis, cytotoxic activity and mechanistic investigation

Garcinol is a polyisoprenylated benzophenone isolated from Garcinia. It has been reported to have a variety of intriguing biological effects, including anticancer, anti-inflammatory, and antioxidant capabilities. The purpose of this research is to thoroughly evaluate garcinol and a series of its analogues in terms of synthesis, structural diversity, biosynthesis, and potential for preventing carcinoma cell proliferation. Garcinopicrobenzophenone and eugeniaphenone, which contain a unique cyclobutyl unit at C-5, were initially synthesized using the procedures utilized in the synthesis of garcinol. All the natural analogs of garcinol were produced at completion of the synthesis, and their structures and absolute configurations were clarified. Based on the synthesis, a possible biogenetic synthesis pathway towards cambogin, 13,14-didehydroxyisogarcinol via O-cyclization, and garcinopicrobenzophenone or eugeniaphenone via C-cyclization was proposed. The cytotoxicity of polyisoprenylated benzophenones produced in our group was tested, and the structure–activity relationship was summarized. The mechanism by which garcinol, cambogin, and 21′ induce apoptosis was studied. Cambogin and 21′ were shown to have a greater capacity to cause apoptosis in pancreatic cancer BXPC3 cells, and the suppression of BXPC3 cells by 21′ might be attributed to the target of STAT3 signaling. Garcinol could cause pyroptosis and apoptosis in pancreatic cancer cells at the same time, which was the first time that garcinol was identified as a possible chemotherapeutic agent that could significantly promote pyroptosis in cancer cells.

Penerapan Internet Of Things (IoT) Pada Sistem Monitoring Penggunaan Air PDAM Rumah Tangga

Water is a source of life that is needed by living things. Many people have switched to using PDAM water to fulfill their daily water needs so in the distribution process the PDAM requires a process of checking or recording by officials the amount of water used that is distributed to each customer. This raises a problem, namely that there is often a discrepancy between the amount of water used and the fees that must be paid and the water meters used by the PDAM are still analog in nature so the water usage data is difficult for customers to know. This is one of the factors causing the soaring bills of fees that must be paid for water needs to the PDAM every month which often results in several possibilities, namely non-payment, leaks, or fraud. So we need a tool to facilitate the PDAM and PDAM water customers in monitoring water use as well as the amount of payment. The tool is in the form of a PDAM Water Usage Monitoring System Design using Internet of Things technology using a water flow sensor that will detect the use of water used, RTC to determine a date and time in the BLYNK application display, processed via the ESP32 Node MCU and displayed on the LCD as the output of current usage and bills to be paid. The processed data results will be sent to the BLYNK web server and can be viewed through the BLYNK application on an Android smartphone. The error value from the reading of the water flow sensor is 1%, which means the accuracy level is 99%. Meanwhile, the data from the reading of the system for calculating the cost of using PDAM water does not contain errors so the accuracy of the data reaches 100%.

Marine-Derived Natural Product HDYL-GQQ-495 Targets P62 to Inhibit Autophagy.

Autophagy is widely implicated in pathophysiological processes such as tumors and metabolic and neurodegenerative disorders, making it an attractive target for drug discovery. Several chemical screening approaches have been developed to uncover autophagy-modulating compounds. However, the modulation capacity of marine compounds with significant pharmacological activities is largely unknown. We constructed an EGFPKI-LC3B cell line using the CRISPR/Cas9 knock-in strategy in which green fluorescence indicated endogenous autophagy regulation. Using this cell line, we screened a compound library of approximately 500 marine natural products and analogues to investigate molecules that altered the EGFP fluorescence. We identified eight potential candidates that enhanced EGFP fluorescence, and HDYL-GQQ-495 was the leading one. Further validation with immunoblotting demonstrated that cleaved LC3 was increased in dose- and time-dependent manners, and the autophagy adaptor P62 showed oligomerization after HDYL-GQQ-495 treatment. We also demonstrated that HDYL-GQQ-495 treatment caused autophagy substrate aggregation, which indicated that HDYL-GQQ-495 serves as an autophagy inhibitor. Furthermore, HDYL-GQQ-495 induced Gasdermin E (GSDME) cleavage and promoted pyroptosis. Moreover, HDYL-GQQ-495 directly combined with P62 to induce P62 polymerization. In P62 knockout cells, the cleavage of LC3 or GSDME was blocked after HDYL-GQQ-495 treatment. The EGFPKI-LC3B cell line was an effective tool for autophagy modulator screening. Using this tool, we found a novel marine-derived compound, HDYL-GQQ-495, targeting P62 to inhibit autophagy and promote pyroptosis.

Discovery of Natural Bisbenzylisoquinoline Analogs from the Library of Thai Traditional Plants as SARS-CoV-2 3CLPro Inhibitors: In Silico Molecular Docking, Molecular Dynamics, and In Vitro Enzymatic Activity.

The emergence of SARS-CoV-2 in December 2019 has become a global issue due to the continuous upsurge in patients and the lack of drug efficacy for treatment. SARS-CoV-2 3CLPro is one of the most intriguing biomolecular targets among scientists worldwide for developing antiviral drugs due to its relevance in viral replication and transcription. Herein, we utilized computer-assisted drug screening to investigate 326 natural products from Thai traditional plants using structure-based virtual screening against SARS-CoV-2 3CLPro. Following the virtual screening, the top 15 compounds based on binding energy and their interactions with key amino acid Cys145 were obtained. Subsequently, they were further evaluated for protein-ligand complex stability via molecular dynamics simulation and binding free energy calculation using molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) approaches. Following drug-likeness and ADME/Tox assessments, seven bisbenzylisoquinolines were obtained, including neferine (3), liensinine (4), isoliensinine (5), dinklacorine (8), tiliacorinine (13), 2'-nortiliacorinine (14), and yanangcorinine (15). These compounds computationally showed a higher binding affinity than native N3 and GC-373 inhibitors and attained stable interactions on the active site of 3CLpro during 100 ns in molecular dynamics (MD) simulation. Moreover, the in vitro enzymatic assay showed that most bisbenzylisoquinolines could experimentally inhibit SARS-CoV-2 3CLPro. To our delight, isoliensinine (5) isolated from Nelumbo nucifera demonstrated the highest inhibition of protease activity with the IC50 value of 29.93 μM with low toxicity on Vero cells. Our findings suggested that bisbenzylisoquinoline scaffolds could be potentially used as an in vivo model for the development of effective anti-SARS-CoV-2 drugs.

Antibiotic-sterol interactions provide insight into the selectivity of natural aromatic analogues of amphotericin B and their photoisomers

Aromatic heptaene macrolides (AHMs) belong to the group of polyene macrolide antifungal antibiotics. Members of this group were the first to be used in the treatment of systemic fungal infections. Amphotericin B (AmB), a non-aromatic representative of heptaene macrolides, is of significant clinical importance in the treatment of internal mycoses. It includes the all-trans heptaene chromophore, whereas the native AHMs contain two cis-type (Z) double bonds within the chromophore system. Lately we have proven that it is possible to obtain AHMs’ stable derivatives in the form of all-trans (AmB-type) isomers by photochemical isomerization. Our further studies have shown that such alteration leads to the improvement of their selective toxicity in vitro. Computational experiments carried out so far were only an initial contribution in the investigation of the molecular basis of the mechanism of action of AHMs and did not provide explanation to observed differences in biological activity between the native (cis-trans) and isomeric (all-trans) AHMs. Herein, we presented the results of two-dimensional metadynamics studies upon AmB and its aromatic analogues (AHMs), regarding preferable binary antibiotic/sterol complexes orientation, as well as more detailed research on the behaviour of AHMs’ alkyl-aromatic side chain in cholesterol- or ergosterol-enriched lipid bilayers.

Photogrammetry and GIS in Human-Occupied Digital Landscapes

ABSTRACTIn the last decade, archaeologists have been using human-occupied interactive digital built environments to investigate human agency, settlement, and behavior. To document this evidence, we provide here one method of conducting drone-based photogrammetry and GIS mapping from within these digital spaces based on well-established methods conducted in physical landscapes. Mapping is an integral part of archaeology in the natural world, but it has largely eluded researchers in these new, populated digital landscapes. We hope that our proposed method helps to resolve this issue. We argue that employing archaeological methods in digital environments provides a successful methodological framework to investigate human agency in digital spaces for anthropological purposes and has the potential for extrapolating data from human-digital landscape interactions and applying them to their natural analogues.