Search results for: biophysical model

Authors: Iman Farasat, Howard M. Salis

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The CRISPR/Cas9 system has revolutionized genome engineering by enabling site-directed and high-throughput genome editing, genome insertion, and gene knockdowns in several species, including bacteria, yeast, flies, worms, and human cell lines. This technology has the potential to enable human gene therapy to treat genetic diseases and cancer at the molecular level; however, the current CRISPR/Cas9 system suffers from seemingly sporadic off-target genome mutagenesis that prevents its use in gene therapy. A comprehensive mechanistic model that explains how the CRISPR/Cas9 functions would enable the rational design of the guide-RNAs responsible for target site selection while minimizing unexpected genome mutagenesis. Here, we present the first quantitative model of the CRISPR/Cas9 genome mutagenesis system that predicts how guide-RNA sequences (crRNAs) control target site selection and cleavage activity. We used statistical thermodynamics and law of mass action to develop a five-step biophysical model of cas9 cleavage, and examined it in vivo and in vitro. To predict a crRNA's binding specificities and cleavage rates, we then compiled a nearest neighbor (NN) energy model that accounts for all possible base pairings and mismatches between the crRNA and the possible genomic DNA sites. These calculations correctly predicted crRNA specificity across 5518 sites. Our analysis reveals that cas9 activity and specificity are anti-correlated, and, the trade-off between them is the determining factor in performing an RNA-mediated cleavage with minimal off-targets. To find an optimal solution, we first created a scheme of safe-design criteria for Cas9 target selection by systematic analysis of available high throughput measurements. We then used our biophysical model to determine the optimal Cas9 expression levels and timing that maximizes on-target cleavage and minimizes off-target activity. We successfully applied this approach in bacterial and mammalian cell lines to reduce off-target activity to near background mutagenesis level while maintaining high on-target cleavage rate.

Keywords: biophysical model, CRISPR, Cas9, genome editing

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Authors: Abhimanyu Thakur, Youngjin Lee

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Glioma is a lethal brain cancer whose early diagnosis and prognosis are limited due to the dearth of a suitable technique for its early detection. Current approaches, including magnetic resonance imaging (MRI), computed tomography (CT), and invasive biopsy for the diagnosis of this lethal disease, hold several limitations, demanding an alternative method. Recently, extracellular vesicles (EVs) have been used in numerous biomarker studies, majorly exosomes and microvesicles (MVs), which are found in most of the cells and biofluids, including blood, cerebrospinal fluid (CSF), and urine. Remarkably, glioma cells (GMs) release a high number of EVs, which are found to cross the blood-brain-barrier (BBB) and impersonate the constituents of parent GMs including protein, and lncRNA; however, biophysical properties of EVs have not been explored yet as a biomarker for glioma. We isolated EVs from cell culture conditioned medium of GMs and regular primary culture, blood, and urine of wild-type (WT)- and glioma mouse models, and characterized by nano tracking analyzer, transmission electron microscopy, immunogold-EM, and differential light scanning. Next, we measured the biophysical parameters of GMs-EVs by using atomic force microscopy. Further, the functional constituents of EVs were examined by FTIR and Raman spectroscopy. Exosomes and MVs-derived from GMs, blood, and urine showed distinction biophysical parameters (roughness, adhesion force, and stiffness) and different from that of regular primary glial cells, WT-blood, and -urine, which can be attributed to the characteristic functional constituents. Therefore, biophysical features can be potential diagnostic biomarkers for glioma.

Keywords: glioma, extracellular vesicles, exosomes, microvesicles, biophysical properties

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Authors: Shreedevi Moharana, Subashisa Dutta

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The present study focuses on the estimation of crop biophysical parameters like crop chlorophyll, nitrogen and water stress at plot scale in the crop fields. To achieve these, we have used high-resolution satellite LISS IV imagery. A new methodology has proposed in this research work, the spectral shape function of paddy crop is employed to get the significant wavelengths sensitive to paddy crop parameters. From the shape functions, regression index models were established for the critical wavelength with minimum and maximum wavelengths of multi-spectrum high-resolution LISS IV data. Moreover, the functional relationships were utilized to develop the index models. From these index models crop, biophysical parameters were estimated and mapped from LISS IV imagery at plot scale in crop field level. The result showed that the nitrogen content of the paddy crop varied from 2-8%, chlorophyll from 1.5-9% and water content variation observed from 40-90% respectively. It was observed that the variability in rice agriculture system in India was purely a function of field topography.

Keywords: crop parameters, index model, LISS IV imagery, plot scale, shape function

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Authors: Catherine Felce, Lior Pachter

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Current methods for building phylogenetic trees from gene expression data consider mean expression levels. With single-cell technologies, we can leverage more information about cell dynamics by considering the entire distribution of gene expression across cells. Using biophysical modeling, we propose a method for constructing phylogenetic trees from scRNA-seq data, building on Felsenstein's method of continuous characters. This method can highlight genes whose level of expression may be unchanged between species, but whose rates of transcription/decay may have evolved over time.

Keywords: phylogenetics, single-cell, biophysical modeling, transcription

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Authors: Weiam Daear, Patrick Lai, Elmar Prenner

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The human body offers many avenues that could be used for drug delivery. The pulmonary route, which is delivered through the lungs, presents many advantages that have sparked interested in the field. These advantages include; 1) direct access to the lungs and the large surface area it provides, and 2) close proximity to the blood circulation. The air-blood barrier of the alveoli is about 500 nm thick. The air-blood barrier consist of a monolayer of lipids and few proteins called the lung surfactant and cells. This monolayer consists of ~90% lipids and ~10% proteins that are produced by the alveolar epithelial cells. The two major lipid classes constitutes of various saturation and chain length of phosphatidylcholine (PC) and phosphatidylglycerol (PG) representing 80% of total lipid component. The major role of the lung surfactant monolayer is to reduce surface tension experienced during breathing cycles in order to prevent lung collapse. In terms of the pulmonary drug delivery route, drugs pass through various parts of the respiratory system before reaching the alveoli. It is at this location that the lung surfactant functions as the air-blood barrier for drugs. As the field of nanomedicine advances, the use of nanoparticles (NPs) as drug delivery vehicles is becoming very important. This is due to the advantages NPs provide with their large surface area and potential specific targeting. Therefore, studying the interaction of NPs with lung surfactant and whether they affect its stability becomes very essential. The aim of this research is to develop a biomimetic model of the human lung surfactant followed by a biophysical analysis of the interaction of polymeric NPs. This biomimetic model will function as a fast initial mode of testing for whether NPs affect the stability of the human lung surfactant. The model developed thus far is an 8-component lipid system that contains major PC and PG lipids. Recently, a custom made 16:0/16:1 PC and PG lipids were added to the model system. In the human lung surfactant, these lipids constitute 16% of the total lipid component. According to the author’s knowledge, there is not much monolayer data on the biophysical analysis of the 16:0/16:1 lipids, therefore more analysis will be discussed here. Biophysical techniques such as the Langmuir Trough is used for stability measurements which monitors changes to a monolayer's surface pressure upon NP interaction. Furthermore, Brewster Angle Microscopy (BAM) employed to visualize changes to the lateral domain organization. Results show preferential interactions of NPs with different lipid groups that is also dependent on the monolayer fluidity. Furthermore, results show that the film stability upon compression is unaffected, but there are significant changes in the lateral domain organization of the lung surfactant upon NP addition. This research is significant in the field of pulmonary drug delivery. It is shown that NPs within a certain size range are safe for the pulmonary route, but little is known about the mode of interaction of those polymeric NPs. Moreover, this work will provide additional information about the nanotoxicology of NPs tested.

Keywords: Brewster angle microscopy, lipids, lung surfactant, nanoparticles

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Authors: Kakali Bhadra

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Harmalol administration caused remarkable reduction in proliferation of HepG₂ cells with GI₅₀ of 14.2 mM, without showing much cytotoxicity in embryonic liver cell line, WRL-68. Data from circular dichroism and differential scanning calorimetric analysis of harmalol-CT DNA complex shows conformational changes with prominent CD perturbation and stabilization of CT DNA by 8 ^oC. Binding constant and stoichiometry was also calculated using the above biophysical techniques. Further, dose dependent apoptotic induction ability of harmalol was studied in HepG₂ cells using different biochemical assays. Generation of ROS, DNA damage, changes in cellular external and ultramorphology, alteration of membrane, formation of comet tail, decreased mitochondrial membrane potential and a significant increase in Sub G_o/G₁ population made the cancer cell, HepG₂, prone to apoptosis. Up regulation of p53 and caspase 3 further indicated the apoptotic role of harmalol.

Keywords: apoptosis, beta carboline alkaloid, comet assay, cytotoxicity, ROS

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Authors: Bagher Bayat, Wouter Verhoef, Behnaz Arabi, Christiaan Van der Tol

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The aim of this study was to follow the canopy reflectance patterns in response to soil water deficit and to detect trends of changes in biophysical and biochemical parameters of grass (Poa pratensis species). We used visual interpretation, imaging spectroscopy and radiative transfer model inversion to monitor the gradual manifestation of water stress effects in a laboratory setting. Plots of 21 cm x 14.5 cm surface area with Poa pratensis plants that formed a closed canopy were subjected to water stress for 50 days. In a regular weekly schedule, canopy reflectance was measured. In addition, Leaf Area Index (LAI), Chlorophyll (a+b) content (Cab) and Leaf Water Content (Cw) were measured at regular time intervals. The 1-D bidirectional canopy reflectance model SAIL, coupled with the leaf optical properties model PROSPECT, was inverted using hyperspectral measurements by means of an iterative optimization method to retrieve vegetation biophysical and biochemical parameters. The relationships between retrieved LAI, Cab, Cw, and Cs (Senescent material) with soil moisture content were established in two separated groups; stress and non-stressed. To differentiate the water stress condition from the non-stressed condition, a threshold was defined that was based on the laboratory produced Soil Water Characteristic (SWC) curve. All parameters retrieved by model inversion using canopy spectral data showed good correlation with soil water content in the water stress condition. These parameters co-varied with soil moisture content under the stress condition (Chl: R2= 0.91, Cw: R2= 0.97, Cs: R2= 0.88 and LAI: R2=0.48) at the canopy level. To validate the results, the relationship between vegetation parameters that were measured in the laboratory and soil moisture content was established. The results were totally in agreement with the modeling outputs and confirmed the results produced by radiative transfer model inversion and spectroscopy. Since water stress changes all parts of the spectrum, we concluded that analysis of the reflectance spectrum in the VIS-NIR-MIR region is a promising tool for monitoring water stress impacts on vegetation.

Keywords: hyperspectral remote sensing, model inversion, vegetation responses, water stress

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Authors: Abdellatif Chebboub

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Agricultural production is sensitive to weather and thus directly affected by climate change. Plausible estimates of these climate change impacts require combined use of climate, crop, and economic models. Results from previous studies vary substantially due to differences in models, scenarios, and data. This paper is part of a collective effort to systematically integrate these three types of models. We focus on the economic component of the assessment, investigating how nine global economic models of agriculture represent endogenous responses to seven standardized climate change scenarios produced by two climate and five crop models. These responses include adjustments in yields, area, consumption, and international trade. We apply biophysical shocks derived from the Intergovernmental Panel on Climate Change’s representative concentration pathway with end-of-century radiative forcing of 8.5 W/m2. The mean biophysical yield effect with no incremental CO2 fertilization is a 17% reduction globally by 2050 relative to a scenario with unchanging climate. Endogenous economic responses reduce yield loss to 11%, increase area of major crops by 11%, and reduce consumption by 3%. Agricultural production, cropland area, trade, and prices show the greatest degree of variability in response to climate change, and consumption the lowest. The sources of these differences include model structure and specification; in particular, model assumptions about ease of land use conversion, intensification, and trade. This study identifies where models disagree on the relative responses to climate shocks and highlights research activities needed to improve the representation of agricultural adaptation responses to climate change.

Keywords: climate change, agriculture, weather change, danger of climate change

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Authors: Vineeta Kaushik, Manisha Goel

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Chaperones are proteins that help other proteins fold correctly, and are found in all domains of life i.e., prokaryotes, eukaryotes and archaea. Various comparative genomic studies have suggested that the archaeal protein folding machinery appears to be highly similar to that found in eukaryotes. In case of protein folding; slow rotation of peptide prolyl-imide bond is often the rate limiting step. Formation of the prolyl-imide bond during the folding of a protein requires the assistance of other proteins, termed as peptide prolyl cis-trans isomerases (PPIases). Cyclophilins constitute the class of peptide prolyl isomerases with a wide range of biological function like protein folding, signaling and chaperoning. Most of the cyclophilins exhibit PPIase enzymatic activity and play active role in substrate protein folding which classifies them as a category of molecular chaperones. Till date, there is not very much data available in the literature on archaeal cyclophilins. We aim to compare the structural and biochemical features of the cyclophilin protein from within the three domains to elucidate the features affecting their stability and enzyme activity. In the present study, we carry out in-silico analysis of the cyclophilin proteins to predict their conserved residues, sites under positive selection and compare these proteins to their bacterial and eukaryotic counterparts to predict functional divergence. We also aim to clone and express these proteins in heterologous system and study their biophysical characteristics in detail using techniques like CD and fluorescence spectroscopy. Overall we aim to understand the features contributing to the folding, stability and dynamics of the archaeal cyclophilin proteins.

Keywords: biophysical characterization, x-ray crystallography, chaperone-like activity, cyclophilin, PPIase activity

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Authors: Anna Cameron, Chunxia Zhao, Haofei Wang, Yun Liu, Guang Ze Yang

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Since the first publication in 1775, cancer research has built a comprehensive understanding of how cellular components of the tumor niche promote disease development. However, only within the last decade has research begun to establish the impact of non-cellular components of the niche, particularly the extracellular matrix (ECM). The ECM, a three-dimensional scaffold that sustains the tumor microenvironment, plays a crucial role in disease progression. Cancer cells actively deregulate and remodel the ECM to establish a tumor-promoting environment. Recent work has highlighted the need to further our understanding of the complexity of this cancer-ECM relationship. In vitro models use hydrogels to mimic the ECM, as hydrogel matrices offer biological compatibility and stability needed for long term cell culture. However, natural hydrogels are being used in these models verbatim, without tuning their biophysical characteristics to achieve pathophysiological relevance, thus limiting their broad use within cancer research. The biophysical attributes of these gels dictate cancer cell proliferation, invasion, metastasis, and therapeutic response. Evaluating the three most widely used natural hydrogels, Matrigel, collagen, and agarose gel, the permeability, stiffness, and pore-size of each gel were measured and compared to the in vivo environment. The pore size of all three gels fell between 0.5-6 µm, which coincides with the 0.1-5 µm in vivo pore size found in the literature. However, the stiffness for hydrogels able to support cell culture ranged between 0.05 and 0.3 kPa, which falls outside the range of 0.3-20,000 kPa reported in the literature for an in vivo ECM. Permeability was ~100x greater than in vivo measurements, due in large part to the lack of cellular components which impede permeation. Though, these measurements prove important when assessing therapeutic particle delivery, as the ECM permeability decreased with increasing particle size, with 100 nm particles exhibiting a fifth of the permeability of 10 nm particles. This work explores ways of adjusting the biophysical characteristics of hydrogels by changing protein concentration and the trade-off, which occurs due to the interdependence of these factors. The global aim of this work is to produce a more pathophysiologically relevant model for each tumor type.

Keywords: cancer, extracellular matrix, hydrogel, microfluidic

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Authors: Amritee Bora, B. S. Mipun

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Land degradation is often used to describe the land environmental phenomena that reduce land’s original productivity both qualitatively and quantitatively. The study of land degradation vulnerability primarily deals with “Environmentally Sensitive Areas” (ESA) and the amount of topsoil loss due to erosion. In many studies, it is observed that the assessment of the existing status of land degradation is used to represent the vulnerability. Moreover, it is also noticed that in most studies, the primary emphasis of land degradation vulnerability is to assess its sensitivity to soil erosion only. However, the concept of land degradation vulnerability can have different objectives depending upon the perspective of the study. It shows the extent to which changes in land use land cover can imprint their effect on the land. In other words, it represents the susceptibility of a piece of land to degrade its productive quality permanently or in the long run. It is also important to mention that the vulnerability of land degradation is not a single factor outcome. It is a probability assessment to evaluate the status of land degradation and needs to consider both biophysical and human induce parameters. To avoid the complexity of the previous models in this regard, the present study has emphasized on to generate a simplified model to assess the land degradation vulnerability in terms of its current human population pressure, land use practices, and existing biophysical conditions. It is a “Mixed-Method” termed as the land degradation vulnerability index (LDVi). It was originally inspired by the MEDALUS model (Mediterranean Desertification and Land Use), 1999, and Farazadeh’s 2007 revised version of it. It has followed the guidelines of Space Application Center, Ahmedabad / Indian Space Research Organization for land degradation vulnerability. The model integrates the climatic index (Ci), vegetation index (Vi), erosion index (Ei), land utilization index (Li), population pressure index (Pi), and cover management index (CMi) by giving equal weightage to each parameter. The final result shows that the very high vulnerable zone primarily indicates three (3) prominent circumstances; land under continuous population pressure, high concentration of human settlement, and high amount of topsoil loss due to surface runoff within the study sites. As all the parameters of the model are amalgamated with equal weightage further with the help of regression analysis, the LDVi model also provides a strong grasp of each parameter and how far they are competent to trigger the land degradation process.

Keywords: population pressure, land utilization, soil erosion, land degradation vulnerability

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Authors: Maria Christofi, George Plastiras, Rafaella Elia, Vaggelis Tsiourtis, Theocharis Theocharides, Miltiadis Katsaros

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The rapidly expanding urban areas of the world constitute a challenge of how we need to make the transition to "the next urbanization", which will be defined by new analytical tools and new sources of data. This paper is about the production of a spatial application, the ‘FUMapp’, where space and its initiative will be available literally, in meters, but also abstractly, at a sensed level. While existing spatial applications typically focus on illustrations of the urban infrastructure, the suggested application goes beyond the existing: It investigates how our environment's perception adapts to the alterations of the built environment through a dataset construction of biophysical measurements (eye-tracking, heart beating), and physical metrics (spatial characteristics, size of stimuli, rhythm of mobility). It explores the intersections between architecture, cognition, and computing where future design can be improved and identifies the flexibility and livability of the ‘available space’ of specific examined urban paths.

Keywords: biophysical data, flexibility of urban, livability, next urbanization, spatial application

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Authors: Dimitrios Triantakonstantis, Demetris Stathakis

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Urban areas have been expanded throughout the globe. Monitoring and modeling urban growth have become a necessity for a sustainable urban planning and decision making. Urban prediction models are important tools for analyzing the causes and consequences of urban land use dynamics. The objective of this research paper is to analyze and model the urban change, which has been occurred from 1990 to 2000 using CORINE land cover maps. The model was developed using drivers of urban changes (such as road distance, slope, etc.) under an Artificial Neural Network modeling approach. Validation was achieved using a prediction map for 2006 which was compared with a real map of Urban Atlas of 2006. The accuracy produced a Kappa index of agreement of 0,639 and a value of Cramer's V of 0,648. These encouraging results indicate the importance of the developed urban growth prediction model which using a set of available common biophysical drivers could serve as a management tool for the assessment of urban change.

Keywords: artificial neural networks, CORINE, urban atlas, urban growth prediction

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Authors: Juliana A. Knocikova, Yann Bouret, Médéric Argentina, Laurent Counillon

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Cell volume, together with membrane potential and intracellular hydrogen ion concentration, is an essential biophysical parameter for normal cellular activity. Cell volumes can be altered by osmotically active compounds and extracellular tonicity. In this study, a simple mathematical model of osmotically induced cell swelling and shrinking is presented. Emphasis is given to water diffusion across the membrane. The mathematical description of the cellular behavior consists in a system of coupled ordinary differential equations. We compare experimental data of cell volume alterations driven by differences in osmotic pressure with mathematical simulations under hypotonic and hypertonic conditions. Implications for a future model are also discussed.

Keywords: eukaryotic cell, mathematical modeling, osmosis, volume alterations

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Authors: Neelofar, Khursheed Alam, Jamal Ahmad

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Protein modification in diabetes mellitus may lead to early glycation products (EGPs) or amadori product as well as advanced glycation end products (AGEs). Early glycation involves the reaction of glucose with N-terminal and lysyl side chain amino groups to form Schiff’s base which undergoes rearrangements to form more stable early glycation product known as Amadori product. After Amadori, the reactions become more complicated leading to the formation of advanced glycation end products (AGEs) that interact with various AGE receptors, thereby playing an important role in the long-term complications of diabetes. Millard reaction or nonenzymatic glycation reaction accelerate in diabetes due to hyperglycation and alter serum protein’s structure, their normal functions that lead micro and macro vascular complications in diabetic patients. In this study, Human Serum Albumin (HSA) with a constant concentration was incubated with different concentrations of glucose at 370C for a week. At 4th day, Amadori product was formed that was confirmed by colorimetric method NBT assay and TBA assay which both are authenticate early glycation product. Conformational changes in native as well as all samples of Amadori albumin with different concentrations of glucose were investigated by various biophysical and biochemical techniques. Main biophysical techniques hyperchromacity, quenching of fluorescence intensity, FTIR, CD and SDS-PAGE were used. Further conformational changes were observed by biochemical assays mainly HMF formation, fructoseamine, reduction of fructoseamine with NaBH4, carbonyl content estimation, lysine and arginine residues estimation, ANS binding property and thiol group estimation. This study find structural and biochemical changes in Amadori modified HSA with normal to hyperchronic range of glucose with respect to native HSA. When glucose concentration was increased from normal to chronic range biochemical and structural changes also increased. Highest alteration in secondary and tertiary structure and conformation in glycated HSA was observed at the hyperchronic concentration (75mM) of glucose. Although it has been found that Amadori modified proteins is also involved in secondary complications of diabetes as AGEs but very few studies have been done to analyze the conformational changes in Amadori modified proteins due to early glycation. Most of the studies were found on the structural changes in Amadori protein at a particular glucose concentration but no study was found to compare the biophysical and biochemical changes in HSA due to early glycation with a range of glucose concentration at a constant incubation time. So this study provide the information about the biochemical and biophysical changes occur in Amadori modified albumin at a range of glucose normal to chronic in diabetes. Although many implicates currently in use i.e. glycaemic control, insulin treatment and other chemical therapies that can control many aspects of diabetes. However, even with intensive use of current antidiabetic agents more than 50 % of diabetic patient’s type 2 suffers poor glycaemic control and 18 % develop serious complications within six years of diagnosis. Experimental evidence related to diabetes suggests that preventing the nonenzymatic glycation of relevant proteins or blocking their biological effects might beneficially influence the evolution of vascular complications in diabetic patients or quantization of amadori adduct of HSA by authentic antibodies against HSA-EGPs can be used as marker for early detection of the initiation/progression of secondary complications of diabetes. So this research work may be helpful for the same.

Keywords: diabetes mellitus, glycation, albumin, amadori, biophysical and biochemical techniques

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Authors: Iman Farasat, Howard M. Salis

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Engineered genetic circuits reprogram cellular behavior to act as living computers with applications in detecting cancer, creating self-controlling artificial tissues, and dynamically regulating metabolic pathways. Phenemenological models are often used to simulate and design genetic circuit behavior towards a desired behavior. While such models assume that each circuit component’s function is modular and independent, even small changes in a circuit (e.g. a new promoter, a change in transcription factor expression level, or even a new media) can have significant effects on the circuit’s function. Here, we use statistical thermodynamics to account for the several factors that control transcriptional regulation in bacteria, and experimentally demonstrate the model’s accuracy across 825 measurements in several genetic contexts and hosts. We then employ our first principles model to design, experimentally construct, and characterize a family of signal amplifying genetic circuits (genetic OpAmps) that expand the dynamic range of cell sensors. To develop these models, we needed a new approach to measuring the in vivo binding free energies of transcription factors (TFs), a key ingredient of statistical thermodynamic models of gene regulation. We developed a new high-throughput assay to measure RNA polymerase and TF binding free energies, requiring the construction and characterization of only a few constructs and data analysis (Figure 1A). We experimentally verified the assay on 6 TetR-homolog repressors and a CRISPR/dCas9 guide RNA. We found that our binding free energy measurements quantitatively explains why changing TF expression levels alters circuit function. Altogether, by combining these measurements with our biophysical model of translation (the RBS Calculator) as well as other measurements (Figure 1B), our model can account for changes in TF binding sites, TF expression levels, circuit copy number, host genome size, and host growth rate (Figure 1C). Model predictions correctly accounted for how these 8 factors control a promoter’s transcription rate (Figure 1D). Using the model, we developed a design framework for engineering multi-promoter genetic circuits that greatly reduces the number of degrees of freedom (8 factors per promoter) to a single dimensionless unit. We propose the Ptashne (Pt) number to encapsulate the 8 co-dependent factors that control transcriptional regulation into a single number. Therefore, a single number controls a promoter’s output rather than these 8 co-dependent factors, and designing a genetic circuit with N promoters requires specification of only N Pt numbers. We demonstrate how to design genetic circuits in Pt number space by constructing and characterizing 15 2-repressor OpAmp circuits that act as signal amplifiers when within an optimal Pt region. We experimentally show that OpAmp circuits using different TFs and TF expression levels will only amplify the dynamic range of input signals when their corresponding Pt numbers are within the optimal region. Thus, the use of the Pt number greatly simplifies the genetic circuit design, particularly important as circuits employ more TFs to perform increasingly complex functions.

Keywords: transcription factor, synthetic biology, genetic circuit, biophysical model, binding energy measurement

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Authors: Marie-Claude Roy, David Locky, Ermias Azeria, Jim Schieck

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It is estimated that up to 70% of the wetlands in the Parkland and Grassland natural regions of Alberta have been lost due to various land-use activities. These losses include ecosystem function and services they once provided. Those wetlands remaining are often embedded in a matrix of human-modified habitats and despite efforts taken to protect them the effects of land-uses on wetland condition and function remain largely unknown. We used biophysical field data and remotely-sensed human footprint data collected at 322 open-water wetlands by the Alberta Biodiversity Monitoring Institute (ABMI) to evaluate the impact of surrounding land use on the physico-chemistry characteristics and plant functional traits of wetlands. Eight physio-chemistry parameters were assessed: wetland water depth, water temperature, pH, salinity, dissolved oxygen, total phosphorus, total nitrogen, and dissolved organic carbon. Three plant functional traits were evaluated: 1) origin (native and non-native), 2) life history (annual, biennial, and perennial), and 3) habitat requirements (obligate-wetland and obligate-upland). Intensity land-use was quantified within a 250-meter buffer around each wetland. Ninety-nine percent of wetlands in the Grassland and Parkland regions of Alberta have land-use activities in their surroundings, with most being agriculture-related. Total phosphorus in wetlands increased with the cover of surrounding agriculture, while salinity, total nitrogen, and dissolved organic carbon were positively associated with the degree of soft-linear (e.g. pipelines, trails) land-uses. The abundance of non-native and annual/biennial plants increased with the amount of agriculture, while urban-industrial land-use lowered abundance of natives, perennials, and obligate wetland plants. Our study suggests that land-use types surrounding wetlands affect the physicochemical and biological conditions of wetlands. This research suggests that reducing human disturbances through reclamation of wetland buffers may enhance the condition and function of wetlands in agricultural landscapes.

Keywords: wetlands, biophysical assessment, land use, grassland and parkland natural regions

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Authors: Mutaz Dwairy

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Solid tumors have high interstitial fluid pressure (IFP), high mechanical stress, and low oxygen levels. Solid stresses may induce apoptosis, stimulate the invasiveness and metastasis of cancer cells, and lower their proliferation rate, while oxygen concentration may affect the response of cancer cells to treatment. Although tumors grow in a nonhomogeneous environment, many existing theoretical models assume homogeneous growth and tissue has uniform mechanical properties. For example, the brain consists of three primary materials: white matter, gray matter, and cerebrospinal fluid (CSF). Therefore, tissue inhomogeneity should be considered in the analysis. This study established a physical model based on convection-diffusion equations and continuum mechanics principles. The model considers the geometrical inhomogeneity of the brain by including the three different matters in the analysis: white matter, gray matter, and CSF. The model also considers fluid-solid interaction and explicitly describes the effect of mechanical factors, e.g., solid stresses and IFP, chemical factors, e.g., oxygen concentration, and biological factors, e.g., cancer cell concentration, on growing tumors. In this article, we applied the model on a brain tumor positioned within the white matter, considering the brain inhomogeneity to estimate solid stresses, IFP, the cancer cell concentration, oxygen concentration, and the deformation of the tissues within the neoplasm and the surrounding. Tumor size was estimated at different time points. This model might be clinically crucial for cancer detection and treatment planning by measuring mechanical stresses, IFP, and oxygen levels in the tissue.

Keywords: biomechanical model, interstitial fluid pressure, solid stress, tumor microenvironment

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Authors: Kun Chen, Yan Wang, Yangyu Zhao, Shufang Li, Lian Chen, Xiaoyue Guo, Jue Zhang, Jing Fang

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The coupling strength between uterine electromyography (UEMG) and Fetal heart rate (FHR) signals during peripartum reflects the fetal biophysical activities. Therefore, UEMG-FHR coupling characterization is instructive in assessing placenta function. This study introduced a physiological marker named elevated frequency of UEMG-FHR coupling (E-UFC) and explored its predictive value for pregnancies complicated by pre-eclampsia and small for gestational age (SGA). Placental insufficiency patients (n=12) and healthy volunteers (n=24) were recruited and participated. UEMG and FHR were recorded non-invasively by a trans-abdominal device in women at term with singleton pregnancy (32-37 weeks) from 10:00 pm to 8:00 am. The product of the wavelet coherence and the wavelet cross-spectral power between UEMG and FHR was used to weight these two effects in order to quantify the degree of the UEMG-FHR coupling. E-UFC was exacted from the resultant spectrogram by calculating the mean value of the high-coherence (r > 0.5) frequency band. Results showed the high-coherence between UEMG and FHR was observed in the frequency band (1/512-1/16Hz). In addition, E-UFC in placental insufficiency patients was weaker compared to healthy controls (p < 0.001) at group level. These findings suggested the proposed approach could be used to quantitatively characterize the fetal biophysical activities, which is beneficial for early detection of placental insufficiency and reduces the occurrence of adverse pregnancy.

Keywords: uterine electromyography, fetal heart rate, coupling analysis, wavelet analysis

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Authors: Samaneh Farokhirad, Fatemeh Ahmadpoor

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Biological membranes are constantly in contact with various filamentous soft nanostructures that either reside on their surface or are being transported between the cell and its environment. In particular, viral infections are determined by the interaction of viruses (such as filovirus) with cell membranes, membrane protein organization (such as cytoskeletal proteins and actin filament bundles) has been proposed to influence the mechanical properties of lipid membranes, and the adhesion of filamentous nanoparticles influence their delivery yield into target cells or tissues. The goal of this research is to integrate the rapidly increasing but still fragmented experimental observations on the adhesion and self-assembly of nanofilaments (including filoviruses, actin filaments, as well as natural and synthetic nanofilaments) on cell membranes into a general, rigorous, and unified knowledge framework. The global outbreak of the coronavirus disease in 2020, which has persisted for over three years, highlights the crucial role that nanofilamentbased delivery systems play in human health. This work will unravel the role of a unique property of all cell membranes, namely flexoelectricity, and the significance of nanofilaments’ flexibility in the adhesion and self-assembly of nanofilaments on cell membranes. This will be achieved utilizing a set of continuum mechanics, statistical mechanics, and molecular dynamics and Monte Carlo simulations. The findings will help address the societal needs to understand biophysical principles that govern the attachment of filoviruses and flexible nanofilaments onto the living cells and provide guidance on the development of nanofilament-based vaccines for a range of diseases, including infectious diseases and cancer.

Keywords: virus nanofilaments, cell mechanics, computational biophysics, statistical mechanics

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Authors: Guadalupe Pérez, Jorge Islas, Mirna Guevara, Raúl Suárez

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Jatropha curcas is a perennial oleaginous plant that is currently considered an energy crop with high potential as an environmentally sustainable biofuel. During the last decades, research in biofuels has grown in tropical and subtropical regions in Latin America. However, as far we know, there are no reports on the growth and yield patterns of Jatropha curcas under the specific agro climatic scenarios of the State of Morelos, Mexico. This study presents the results of 52 months monitoring of 10 toxic and non-toxic ecotypes of Jatropha curcas (E1M, E2M, E3M, E4M, E5M, E6O, E7O, E8O, E9C, E10C) in an experimental plantation with minimum watering and fertilization resources. The main objective is to identify the ecotypes with the highest potential as biodiesel raw material in the select region, by developing experimental information. Specifically, we monitored biophysical and growth parameters, including plant survival and seed production (at the end of month 52), to study the performance of each ecotype and to establish differences among the variables of morphological growth, net seed oil content, and toxicity. To analyze the morphological growth, a statistical approach to the biophysical parameters was used; the net seed oil content -80 to 192 kg/ha- was estimated with the first harvest; and the toxicity was evaluated by examining the phorbol ester concentration (µg/L) in the oil extracted from the seeds. The comparison and selection of ecotypes was performed through a methodology developed based on the normalization of results. We identified four outstanding ecotypes (E1M, E2M, E3M, and E4M) that can be used to establish Jatropha curcas as energy crops in the state of Morelos for feasible agro-industrial production of biodiesel and other products related to the use of biomass.

Keywords: biodiesel production, Jatropha curcas, seed oil content, toxic and non-toxic ecotypes

Procedia PDF Downloads 133

Authors: Javed Mallick

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In metropolitan areas, rapid changes in land use and land cover (LULC) have ecological and environmental consequences. Saudi Arabia's cities have experienced tremendous urban growth since the 1990s, resulting in urban heat islands, groundwater depletion, air pollution, loss of ecosystem services, and so on. From 1990 to 2020, this study examines the variance and heterogeneity in land surface temperature (LST) caused by LULC changes in Abha-Khamis Mushyet, Saudi Arabia. LULC was mapped using the support vector machine (SVM). The mono-window algorithm was used to calculate the land surface temperature (LST). To identify LST clusters, the local indicator of spatial associations (LISA) model was applied to spatiotemporal LST maps. In addition, the parallel coordinate (PCP) method was used to investigate the relationship between LST clusters and urban biophysical variables as a proxy for LULC. According to LULC maps, urban areas increased by more than 330% between 1990 and 2018. Between 1990 and 2018, built-up areas had an 83.6% transitional probability. Furthermore, between 1990 and 2020, vegetation and agricultural land were converted into built-up areas at a rate of 17.9% and 21.8%, respectively. Uneven LULC changes in built-up areas result in more LST hotspots. LST hotspots were associated with high NDBI but not NDWI or NDVI. This study could assist policymakers in developing mitigation strategies for urban heat islands

Keywords: land use land cover mapping, land surface temperature, support vector machine, LISA model, parallel coordinate plot

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Authors: G. Carrero, C. Contreras, M. J. Hendzel

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Linker histones or histones H1 are highly mobile nuclear proteins that regulate the organization of chromatin and limit DNA accessibility by binding to the chromatin structure (DNA and associated proteins). It is known that this binding process is driven by both slow (strong binding) and rapid (weak binding) interactions. However, the exact binding mechanism has not been fully described. Moreover, the existing models only account for one type of bound population that does not distinguish explicitly between the weakly and strongly bound proteins. Thus, we propose different systems of reaction-diffusion equations to describe explicitly the rapid and slow interactions during a FRAP (Fluorescence Recovery After Photobleaching) experiment. We perform a model comparison analysis to characterize the binding mechanism of histone H1 and provide new meaningful biophysical information on the kinetics of histone H1.

Keywords: FRAP (Fluorescence Recovery After Photobleaching), histone H1, histone H1 binding kinetics, linker histone, reaction-diffusion equation

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Authors: Peter Palasti, Eva Kerepeczki

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Extensive fish farming is one of the most traditional forms of aquaculture in Europe, usually practiced in large pond systems with earthen beds, where the growth of fish is based on natural feed and supplementary foraging. These farms have semi-natural environmental conditions, sustaining diverse wildlife communities that have complex effects on fish production and also provide a livelihood for many wetland related taxa. Based on their characteristics, these communities could be sources of various ecosystem services (ESs), that could also enhance the value and enable the multifunctional use of these artificially constructed and maintained production zones. To identify and estimate the whole range of wildlife’s contribution we have conducted an integrated assessment in an extensively managed pond system in Biharugra, Hungary, where we studied 14 previously revealed ESs: fish and reed production, water storage, water and air quality regulation, CO2 absorption, groundwater recharge, aesthetics, recreational activities, inspiration, education, scientific research, presence of semi-natural habitats and useful/protected species. ESs were collected through structured interviews with the local experts of all major stakeholder groups, where we have also gathered information about the known forms, levels (none, low, high) and orientations (positive, negative) of the contributions of the wildlife community. After that, a quantitative analysis was carried out: we calculated the total mean value of the services being used between 2014-16, then we estimated the value and percentage of contributions. For the quantification, we mainly used biophysical indicators with the available data and empirical knowledge of the local experts. During the interviews, 12 of the previously listed services (85%) were mentioned to be related to wildlife community, consisting of 5 fully (e.g., recreation, reed production) and seven partially dependent ESs (e.g., inspiration, CO2 absorption) from our list. The orientation of the contributions was said to be positive almost every time; however, in the case of fish production, the feeding habit of some wild species (Phalacrocorax carbo, Lutra lutra) caused significant losses in fish stocks in the study period. During the biophysical assessment, we calculated the total mean value of the services and quantified the aid of wildlife community at the following services: fish and reed production, recreation, CO2 absorption, and the presence of semi-natural habitats and wild species. The combined results of our interviews and biophysical evaluations showed that the presence of wildlife community not just greatly increased the productivity of the fish farms in Biharugra (with ~53% of natural yield generated by planktonic and benthic communities) but also enhanced the multifunctionality of the system through expanding the quality and number of its services. With these abilities, extensively managed fishponds could play an important role in the future as refugia for wetland related services and species threatened by the effects of global warming.

Keywords: ecosystem services, fishpond systems, integrated assessment, wildlife community

Procedia PDF Downloads 115

Authors: Xiangtuo Chen, Paul-Henry Cournéde

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Crop yield prediction is a paramount issue in agriculture. The main idea of this paper is to find out efficient way to predict the yield of corn based meteorological records. The prediction models used in this paper can be classified into model-driven approaches and data-driven approaches, according to the different modeling methodologies. The model-driven approaches are based on crop mechanistic modeling. They describe crop growth in interaction with their environment as dynamical systems. But the calibration process of the dynamic system comes up with much difficulty, because it turns out to be a multidimensional non-convex optimization problem. An original contribution of this paper is to propose a statistical methodology, Multi-Scenarios Parameters Estimation (MSPE), for the parametrization of potentially complex mechanistic models from a new type of datasets (climatic data, final yield in many situations). It is tested with CORNFLO, a crop model for maize growth. On the other hand, the data-driven approach for yield prediction is free of the complex biophysical process. But it has some strict requirements about the dataset. A second contribution of the paper is the comparison of these model-driven methods with classical data-driven methods. For this purpose, we consider two classes of regression methods, methods derived from linear regression (Ridge and Lasso Regression, Principal Components Regression or Partial Least Squares Regression) and machine learning methods (Random Forest, k-Nearest Neighbor, Artificial Neural Network and SVM regression). The dataset consists of 720 records of corn yield at county scale provided by the United States Department of Agriculture (USDA) and the associated climatic data. A 5-folds cross-validation process and two accuracy metrics: root mean square error of prediction(RMSEP), mean absolute error of prediction(MAEP) were used to evaluate the crop prediction capacity. The results show that among the data-driven approaches, Random Forest is the most robust and generally achieves the best prediction error (MAEP 4.27%). It also outperforms our model-driven approach (MAEP 6.11%). However, the method to calibrate the mechanistic model from dataset easy to access offers several side-perspectives. The mechanistic model can potentially help to underline the stresses suffered by the crop or to identify the biological parameters of interest for breeding purposes. For this reason, an interesting perspective is to combine these two types of approaches.

Keywords: crop yield prediction, crop model, sensitivity analysis, paramater estimation, particle swarm optimization, random forest

Procedia PDF Downloads 231

Authors: Mark Joseph Quinto, Roan Beronilla, Guiller Damian, Eliza Camaso, Ronaldo Alberto

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Forest inventories are essential to assess the composition, structure and distribution of forest vegetation that can be used as baseline information for management decisions. Classical forest inventory is labor intensive and time-consuming and sometimes even dangerous. The use of Light Detection and Ranging (LiDAR) in forest inventory would improve and overcome these restrictions. This study was conducted to determine the possibility of using LiDAR derived data in extracting high accuracy forest biophysical parameters and as a non-destructive method for forest status analysis of San Manual, Pangasinan. Forest resources extraction was carried out using LAS tools, GIS, Envi and .bat scripts with the available LiDAR data. The process includes the generation of derivatives such as Digital Terrain Model (DTM), Canopy Height Model (CHM) and Canopy Cover Model (CCM) in .bat scripts followed by the generation of 17 composite bands to be used in the extraction of forest classification covers using ENVI 4.8 and GIS software. The Diameter in Breast Height (DBH), Above Ground Biomass (AGB) and Carbon Stock (CS) were estimated for each classified forest cover and Tree Count Extraction was carried out using GIS. Subsequently, field validation was conducted for accuracy assessment. Results showed that the forest of San Manuel has 73% Forest Cover, which is relatively much higher as compared to the 10% canopy cover requirement. On the extracted canopy height, 80% of the tree’s height ranges from 12 m to 17 m. CS of the three forest covers based on the AGB were: 20819.59 kg/20x20 m for closed broadleaf, 8609.82 kg/20x20 m for broadleaf plantation and 15545.57 kg/20x20m for open broadleaf. Average tree counts for the tree forest plantation was 413 trees/ha. As such, the forest of San Manuel has high percent forest cover and high CS.

Keywords: carbon stock, forest inventory, LiDAR, tree count

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Authors: Luca Indovina, Carmela Coppola, Carlo Altucci, Riccardo Barberi, Rocco Romano

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In this paper a real court case, held in Italy at the Court of Nola, in which a correct physical description, conducted with both a Monte Carlo and biophysical analysis, would have been sufficient to arrive at conclusions confirmed by documentary evidence, is considered. This will be an example of how forensic physics can be useful in confirming documentary evidence in order to reach hardly questionable conclusions. This was a libel trial in which the defendant, Mr. DS (Defendant for Slander), had falsely accused one of his neighbors, Mr. OP (Offended Person), of having caused him some damages. The damages would have been caused by an external plaster piece that would have detached from the neighbor’s property and would have hit Mr DS while he was in his garden, much more than a meter far away from the facade of the building from which the plaster piece would have detached. In the trial, Mr. DS claimed to have suffered a scratch on his forehead, but he never showed the plaster that had hit him, nor was able to tell from where the plaster would have arrived. Furthermore, Mr. DS presented a medical certificate with a diagnosis of contusion of the cerebral cortex. On the contrary, the images of Mr. OP’s security cameras do not show any movement in the garden of Mr. DS in a long interval of time (about 2 hours) around the time of the alleged accident, nor do they show any people entering or coming out from the house of Mr. DS in the same interval of time. Biophysical analysis shows that both the diagnosis of the medical certificate and the wound declared by the defendant, already in conflict with each other, are not compatible with the fall of external plaster pieces too small to be found. The wind was at a level 1 of the Beaufort scale, that is, unable to raise even dust (level 4 of the Beaufort scale). Therefore, the motion of the plaster pieces can be described as a projectile motion, whereas collisions with the building cornice can be treated using Newtons law of coefficients of restitution. Numerous numerical Monte Carlo simulations show that the pieces of plaster would not have been able to reach even the garden of Mr. DS, let alone a distance over 1.30 meters. Results agree with the documentary evidence (images of Mr. OP’s security cameras) that Mr. DS could not have been hit by plaster pieces coming from Mr. OP’s property.

Keywords: biophysics analysis, Monte Carlo simulations, Newton’s law of restitution, projectile motion

Procedia PDF Downloads 131

Authors: Abdullah Eqal Al Mazrooei

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In this work, a new nonlinear model will be introduced. The model is in the state-space form. The nonlinearity of this model is in the state equation where the state vector is multiplied by its self. This technique makes our model generalizes many famous models as Lotka-Volterra model and Lorenz model which have many applications in the real life. We will apply our new model to estimate the wind speed by using a new nonlinear estimator which suitable to work with our model.

Keywords: nonlinear systems, state-space model, Kronecker product, nonlinear estimator

Procedia PDF Downloads 691

Authors: Arafan Traore, Teiji Watanabe

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Conakry, the capital city of the Republic of Guinea, has experienced a rapid urban expansion and population increased in the last two decades, which has resulted in remarkable local weather and climate change, raise energy demand and pollution and treating social, economic and environmental development. In this study, the spatiotemporal variation of the land surface temperature (LST) is retrieved to characterize the effect of urban growth on the thermal environment and quantify its relationship with biophysical indices, a normalized difference vegetation index (NDVI) and a normalized difference built up Index (NDBI). Landsat data TM and OLI/TIRS acquired respectively in 1986, 2000 and 2016 were used for LST retrieval and Land use/cover change analysis. A quantitative analysis based on the integration of a remote sensing and a geography information system (GIS) has revealed an important increased in the LST pattern in the average from 25.21°C in 1986 to 27.06°C in 2000 and 29.34°C in 2016, which was quite eminent with an average gain in surface temperature of 4.13°C over 30 years study period. Additionally, an analysis using a Pearson correlation (r) between (LST) and the biophysical indices, normalized difference vegetation index (NDVI) and a normalized difference built-up Index (NDBI) has revealed a negative relationship between LST and NDVI and a strong positive relationship between LST and NDBI. Which implies that an increase in the NDVI value can reduce the LST intensity; conversely increase in NDBI value may strengthen LST intensity in the study area. Although Landsat data were found efficient in assessing the thermal environment in Conakry, however, the method needs to be refined with in situ measurements of LST in the future studies. The results of this study may assist urban planners, scientists and policies makers concerned about climate variability to make decisions that will enhance sustainable environmental practices in Conakry.

Keywords: Conakry, land surface temperature, urban heat island, geography information system, remote sensing, land use/cover change

Procedia PDF Downloads 247

Authors: Iris Vogeler, Rogerio Cichota, Armin Werner

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Dairy farms are under pressure to increase productivity while reducing environmental impacts. Effective fertiliser management practices are critical to achieve this. Determination of optimum nitrogen (N) fertilisation rates which maximise pasture growth and minimise N losses is challenging due to variability in plant requirements and likely near-future supply of N by the soil. Remote sensing can be used for mapping N nutrition status of plants and to rapidly assess the spatial variability within a field. An algorithm is, however, lacking which relates the N status of the plants to the expected yield response to additions of N. The aim of this simulation study was to develop a multi-variate model for determining N fertilisation rate for a target percentage of the maximum achievable yield based on the pasture N concentration (ii) use of an algorithm for guiding fertilisation rates, and (iii) evaluation of the model regarding pasture yield and N losses, including N leaching, denitrification and volatilisation. A simulation study was carried out using the Agricultural Production Systems Simulator (APSIM). The simulations were done for an irrigated ryegrass pasture in the Canterbury region of New Zealand. A multi-variate model was developed and used to determine monthly required N fertilisation rates based on pasture N content prior to fertilisation and targets of 50, 75, 90 and 100% of the potential monthly yield. These monthly optimised fertilisation rules were evaluated by running APSIM for a ten-year period to provide yield and N loss estimates from both nonurine and urine affected areas. Comparison with typical fertilisation rates of 150 and 400 kg N/ha/year was also done. Assessment of pasture yield and leaching from fertiliser and urine patches indicated a large reduction in N losses when N fertilisation rates were controlled by the multi-variate model. However, the reduction in leaching losses was much smaller when taking into account the effects of urine patches. The proposed approach based on biophysical modelling to develop a multi-variate model for determining optimum N fertilisation rates dependent on pasture N content is very promising. Further analysis, under different environmental conditions and validation is required before the approach can be used to help adjust fertiliser management practices to temporal and spatial N demand based on the nitrogen status of the pasture.

Keywords: APSIM modelling, optimum N fertilization rate, pasture N content, ryegrass pasture, three dimensional surface response function.

Procedia PDF Downloads 130