Search results for: genetic algorithm optimization

Authors: Meiling Yu, Nadia Rouatbi, Khuloud T. Al-Jamal

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Background: Treatment of neurological disorders with modern medical and surgical approaches remains difficult. Gene therapy, allowing the delivery of genetic materials that encodes potential therapeutic molecules, represents an attractive option. The treatment of brain diseases with gene therapy requires the gene-editing tool to be delivered efficiently to the central nervous system. In this study, we explored the efficiency of different delivery routes, namely intravenous (i.v.), intra-cranial (i.c.), and intra-nasal (i.n.), to deliver stable nucleic acid-lipid particles (SNALPs) containing gene-editing tools namely Cas9 mRNA and sgRNA encoding for GFP as a reporter protein. We hypothesise that SNALPs can reach the brain and perform gene-editing to different extents depending on the administration route. Intranasal administration (i.n.) offers an attractive and non-invasive way to access the brain circumventing the blood–brain barrier. Successful delivery of gene-editing tools to the brain offers a great opportunity for therapeutic target validation and nucleic acids therapeutics delivery to improve treatment options for a range of neurodegenerative diseases. In this study, we utilised Rosa26-Cas9 knock-in mice, expressing GFP, to study brain distribution and gene-editing efficiency of SNALPs after i.v.; i.c. and i.n. routes of administration. Methods: Single guide RNA (sgRNA) against GFP has been designed and validated by in vitro nuclease assay. SNALPs were formulated and characterised using dynamic light scattering. The encapsulation efficiency of nucleic acids (NA) was measured by RiboGreen™ assay. SNALPs were incubated in serum to assess their ability to protect NA from degradation. Rosa26-Cas9 knock-in mice were i.v., i.n., or i.c. administered with SNALPs to test in vivo gene-editing (GFP knockout) efficiency. SNALPs were given as three doses of 0.64 mg/kg sgGFP following i.v. and i.n. or a single dose of 0.25 mg/kg sgGFP following i.c.. knockout efficiency was assessed after seven days using Sanger Sequencing and Inference of CRISPR Edits (ICE) analysis. In vivo, the biodistribution of DiR labelled SNALPs (SNALPs-DiR) was assessed at 24h post-administration using IVIS Lumina Series III. Results: Serum-stable SNALPs produced were 130-140 nm in diameter with ~90% nucleic acid loading efficiency. SNALPs could reach and stay in the brain for up to 24h following i.v.; i.n. and i.c. administration. Decreasing GFP expression (around 50% after i.v. and i.c. and 20% following i.n.) was confirmed by optical imaging. Despite the small number of mice used, ICE analysis confirmed GFP knockout in mice brains. Additional studies are currently taking place to increase mice numbers. Conclusion: Results confirmed efficient gene knockout achieved by SNALPs in Rosa26-Cas9 knock-in mice expressing GFP following different routes of administrations in the following order i.v.= i.c.> i.n. Each of the administration routes has its pros and cons. The next stages of the project involve assessing gene-editing efficiency in wild-type mice and replacing GFP as a model target with therapeutic target genes implicated in Motor Neuron Disease pathology.

Keywords: CRISPR, nanoparticles, brain diseases, administration routes

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Authors: Temesgen Sidamo, Prakruti S. Rao, Eleni Akllilu, Workineh Shibeshi, Yumi Park, Yong-Soon Cho, Jae-Gook Shin, Scott K. Heysell, Stellah G. Mpagama, Ephrem Engidawork

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The fluoroquinolones (FQs) are used off-label for the treatment of multidrug-resistant tuberculosis (MDR-TB), and for evaluation in shortening the duration of drug-susceptible TB in recently prioritized regimens. Within the class, levofloxacin (LFX) and moxifloxacin (MXF) play a substantial role in ensuring success in treatment outcomes. However, sub-therapeutic plasma concentrations of either LFX or MXF may drive unfavorable treatment outcomes. To the best of our knowledge, the pharmacokinetics of LFX and MXF in Ethiopian patients with MDR-TB have not yet been investigated. Therefore, the aim of this study was to develop a population pharmacokinetic (PopPK) model of levofloxacin (LFX) and moxifloxacin (MXF) and assess the percent probability of target attainment (PTA) as defined by the ratio of the area under the plasma concentration-time curve over 24-h (AUC0-24) and the in vitro minimum inhibitory concentration (MIC) (AUC0-24/MIC) in Ethiopian MDR-TB patients. Steady-state plasma was collected from 39 MDR-TB patients enrolled in the programmatic treatment course and the drug concentrations were determined using optimized liquid chromatography-tandem mass spectrometry. In addition, the in vitro MIC of the patients' pretreatment clinical isolates was determined. PopPK and simulations were run at various doses, and PK parameters were estimated. The effect of covariates on the PK parameters and the PTA for maximum mycobacterial kill and resistance prevention was also investigated. LFX and MXF both fit in a one-compartment model with adjustments. The apparent volume of distribution (V) and clearance (CL) of LFX were influenced by serum creatinine (Scr), whereas the absorption constant (Ka) and V of MXF were influenced by Scr and BMI, respectively. The PTA for LFX maximal mycobacterial kill at the critical MIC of 0.5 mg/L was 29%, 62%, and 95% with the simulated 750 mg, 1000 mg, and 1500 mg doses, respectively, whereas the PTA for resistance prevention at 1500 mg was only 4.8%, with none of the lower doses achieving this target. At the critical MIC of 0.25 mg/L, there was no difference in the PTA (94.4%) for maximum bacterial kill among the simulated doses of MXF (600 mg, 800 mg, and 1000 mg), but the PTA for resistance prevention improved proportionately with dose. Standard LFX and MXF doses may not provide adequate drug exposure. LFX PopPK is more predictable for maximum mycobacterial kill, whereas MXF's resistance prevention target increases with dose. Scr and BMI are likely to be important covariates in dose optimization or therapeutic drug monitoring (TDM) studies in Ethiopian patients.

Keywords: population PK, PTA, moxifloxacin, levofloxacin, MDR-TB patients, ethiopia

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Authors: Anu S. Nair, V. Anantha Subramanian

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This paper presents a surface development and fairing technique combining the features of a modern computer-aided design tool namely the Non-Uniform Rational Basis Spline (NURBS) with an algorithm to obtain a rapidly faired hull form. Some of the older series based designs give sectional area distribution such as in the Wageningen-Lap Series. Others such as the FORMDATA give more comprehensive offset data points. Nevertheless, this basic data still requires fairing to obtain an acceptable faired hull form. This method uses the input of sectional area distribution as an example and arrives at the faired form. Characteristic section shapes define any general ship hull form in the entrance, parallel mid-body and run regions. The method defines a minimum of control points at each section and using the Golden search method or the bisection method; the section shape converges to the one with the prescribed sectional area with a minimized error in the area fit. The section shapes combine into evolving the faired surface by NURBS and typically takes 20 iterations. The advantage of the method is that it is fast, robust and evolves the faired hull form through minimal iterations. The curvature criterion check for the hull lines shows the evolution of the smooth faired surface. The method is applicable to hull form from any parent series and the evolved form can be evaluated for hydrodynamic performance as is done in more modern design practice. The method can handle complex shape such as that of the bulbous bow. Surface patches developed fit together at their common boundaries with curvature continuity and fairness check. The development is coded in MATLAB and the example illustrates the development of the method. The most important advantage is quick time, the rapid iterative fairing of the hull form.

Keywords: computer-aided design, methodical series, NURBS, ship design

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Authors: Wajeeha Zahid, Shafquat Rozi, Farhan Raza, Masood Kadir

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Background: Dental caries affects the overall health and well-being of children. Findings from various international studies regarding the association of dental caries with asthma are inconsistent. With the increasing burden of caries and childhood asthma, it becomes imperative for an underdeveloped country like Pakistan where resources are limited to identify whether there is a relationship between the two. This study aims to identify an association between dental caries and asthma. Methods: A cross-sectional study was conducted on 544 children aged 12-15 years recruited from five private schools in Karachi. Information on asthma was collected through the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire. The questionnaire addressed questions regarding child’s demographics, physician diagnoses of asthma, type of medication administered, family history of asthma and allergies, dietary habits and oral hygiene behavior. Dental caries was assessed using DMFT Index (Decayed, Missing, Filled teeth) index The data was analyzed using Cox proportional Hazard algorithm and crude and adjusted prevalence ratios with 95% CI were reported. Results: This study comprises of 306 (56.3%) boys and 238 (43.8%) girls. The mean age of children was 13.2 ± (0.05) years. The total number of children with carious teeth (DMFT > 0) were 166/544 (30.5%), and the decayed component contributed largely (22.8%) to the DMFT score. The prevalence of physician’s diagnosed asthma was 13%. This study identified almost 7% asthmatic children using the internationally validated International Study of Asthma and Allergies in Childhood (ISAAC) tool and 8 children with childhood asthma were identified by parent interviews. Overall prevalence of asthma was 109/544 (20%). The prevalence of caries in asthmatic children was 28.4% as compared to 31% among non-asthmatic children. The adjusted prevalence ratio of dental caries in asthmatic children was 0.8 (95% CI 0.59-1.29). After adjusting for carious food intake, age, oral hygiene index and dentist visit, the association between asthma and dental caries turned out to be non-significant. Conclusion: There was no association between asthma and dental caries among children who participated in this study.

Keywords: asthma, caries, children, school-based

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Authors: Ibrahim Khan, Waqas Khalid

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The Healthcare sector is known to consume a higher proportion of total energy consumption in the HVAC market owing to an excessive cooling and heating requirement in maintaining human thermal comfort in indoor conditions, catering to patients undergoing treatment in hospital wards, rooms, and intensive care units. The indoor thermal comfort conditions in selected hospitals of Islamabad, Pakistan, were measured on a real-time basis with the collection of first-hand experimental data using calibrated sensors measuring Ambient Temperature, Wet Bulb Globe Temperature, Relative Humidity, Air Velocity, Light Intensity and CO2 levels. The Experimental data recorded was analyzed in conjunction with the Thermal Comfort Questionnaire Surveys, where the participants, including patients, doctors, nurses, and hospital staff, were assessed based on their thermal sensation, acceptability, preference, and comfort responses. The Recorded Dataset, including experimental and survey-based responses, was further analyzed in the development of a correlation between operative temperature, operative relative humidity, and other measured operative parameters with the predicted mean vote and adaptive predicted mean vote, with the adaptive temperature and adaptive relative humidity estimated using the seasonal data set gathered for both summer – hot and dry, and hot and humid as well as winter – cold and dry, and cold and humid climate conditions. The Machine Learning Logistic Regression Algorithm was incorporated to train the operative experimental data parameters and develop a correlation between patient sensations and the thermal environmental parameters for which a new ML-based adaptive thermal comfort model was proposed and developed in our study. Finally, the accuracy of our model was determined using the K-fold cross-validation.

Keywords: predicted mean vote, thermal comfort, energy management, logistic regression, machine learning

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Authors: Fernando M. Soto, Gaetano Di Mino

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The design of an unmodified bituminous mixture and three rubber-aggregate mixtures containing rubber-aggregate by a dry process (RUMAC) was evaluated, using an empirical-analytical approach based on experimental findings obtained in the laboratory with the volumetric mix design by gyratory compaction. A reference dense-graded bituminous sub-ballast mixture (3% of air voids and a bitumen 4% over the total weight of the mix), and three rubberized mixtures by dry process (1,5 to 3% of rubber by total weight and 5-7% of binder) were used applying the Superpave mix-design for a level 3 (high-traffic) design rail lines. The railway trackbed section analyzed was a granular layer of 19 cm compacted, while for the sub-ballast a thickness of 12 cm has been used. In order to evaluate the effect of increasing the specimen density (as a percent of its theoretical maximum specific gravity), in this article, are illustrated the results obtained after different comparative analysis into the influence of varying the binder-rubber percentages under the sub-ballast layer mix-design. This work demonstrates that rubberized blends containing crumb and ground rubber in bituminous asphalt mixtures behave at least similar or better than conventional asphalt materials. By using the same methodology of volumetric compaction, the densification curves resulting from each mixture have been studied. The purpose is to obtain an optimum empirical parameter multiplier of the number of gyrations necessary to reach the same compaction energy as in conventional mixtures. It has provided some experimental parameters adopting an empirical-analytical method, evaluating the results obtained from the gyratory-compaction of bituminous mixtures with an HMA and rubber-aggregate blends. An extensive integrated research has been carried out to assess the suitability of rubber-modified hot mix asphalt mixtures as a sub-ballast layer in railway underlayment trackbed. Design optimization of the mixture was conducted for each mixture and the volumetric properties analyzed. Also, an improved and complete manufacturing process, compaction and curing of these blends are provided. By adopting this increase-parameters of compaction, called 'beta' factor, mixtures modified with rubber with uniform densification and workability are obtained that in the conventional mixtures. It is found that considering the usual bearing capacity requirements in rail track, the optimal rubber content is 2% (by weight) or 3.95% (by volumetric substitution) and a binder content of 6%.

Keywords: empirical approach, rubber-asphalt, sub-ballast, superpave mix-design

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Authors: Deborah Eric, Abbas Ahmad Khan

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Lead halide perovskites quantum dots have attracted immense scientific and technological interest for successful photovoltaic applications because of their remarkable optoelectronic properties. In this paper, we have simulated CsMAPbI3-xBrx based quantum dots to implement their use in intermediate band solar cells (IBSC). These types of materials exhibit optical and electrical properties distinct from their bulk counterparts due to quantum confinement. The conceptual framework provides a route to analyze the electronic properties of quantum dots. This layer of quantum dots optimizes the position and bandwidth of IB that lies in the forbidden region of the conventional bandgap. A three-dimensional MAPbI3 quantum dot (QD) with geometries including spherical, cubic, and conical has been embedded in the CsPbBr3 matrix. Bound energy wavefunction gives rise to miniband, which results in the formation of IB. If there is more than one miniband, then there is a possibility of having more than one IB. The optimization of QD size results in more IBs in the forbidden region. One band time-independent Schrödinger equation using the effective mass approximation with step potential barrier is solved to compute the electronic states. Envelope function approximation with BenDaniel-Duke boundary condition is used in combination with the Schrödinger equation for the calculation of eigen energies and Eigen energies are solved for the quasi-bound states using an eigenvalue study. The transfer matrix method is used to study the quantum tunneling of MAPbI3 QD through neighbor barriers of CsPbI3. Electronic states are computed using Schrödinger equation with effective mass approximation by considering quantum dot and wetting layer assembly. Results have shown the varying the quantum dot size affects the energy pinning of QD. Changes in the ground, first, second state energies have been observed. The QD is non-zero at the center and decays exponentially to zero at boundaries. Quasi-bound states are characterized by envelope functions. It has been observed that conical quantum dots have maximum ground state energy at a small radius. Increasing the wetting layer thickness exhibits energy signatures similar to bulk material for each QD size.

Keywords: perovskite, intermediate bandgap, quantum dots, miniband formation

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Authors: Yaolin Tian, Shanxiong Chen, Fujia Zhao, Xiaoyu Lin, Hailing Xiong

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Ancient books are significant culture inheritors and their background textures convey the potential history information. However, multi-style texture recovery of ancient books has received little attention. Restricted by insufficient ancient textures and complex handling process, the generation of ancient textures confronts with new challenges. For instance, training without sufficient data usually brings about overfitting or mode collapse, so some of the outputs are prone to be fake. Recently, image generation and style transfer based on deep learning are widely applied in computer vision. Breakthroughs within the field make it possible to conduct research upon multi-style texture recovery of ancient books. Under the circumstances, we proposed a network of layout analysis and image fusion system. Firstly, we trained models by using Deep Convolution Generative against Networks (DCGAN) to synthesize multi-style ancient textures; then, we analyzed layouts based on the Position Rearrangement (PR) algorithm that we proposed to adjust the layout structure of foreground content; at last, we realized our goal by fusing rearranged foreground texts and generated background. In experiments, diversified samples such as ancient Yi, Jurchen, Seal were selected as our training sets. Then, the performances of different fine-turning models were gradually improved by adjusting DCGAN model in parameters as well as structures. In order to evaluate the results scientifically, cross entropy loss function and Fréchet Inception Distance (FID) are selected to be our assessment criteria. Eventually, we got model M8 with lowest FID score. Compared with DCGAN model proposed by Radford at el., the FID score of M8 improved by 19.26%, enhancing the quality of the synthetic images profoundly.

Keywords: deep learning, image fusion, image generation, layout analysis

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Authors: O. Antypenko, I. Vasilieva, S. Kovalenko

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Investigations for new effective and less toxic antimicrobials agents are always up-to-date. The tetrazole derivatives are quite interesting objects as for synthesis as well as for pharmacological screening. Thus, some derivatives of tetrazole demonstrated antimicrobial activity, namely 5-phenyl-tetrazolo[1,5-c]quinazoline was effective one against Staphylococcus aureus and Esherichia faecalis (MIC = 250 mg/L). Besides, investigation of the 9-bromo(chloro)-5-morpholin(piperidine)-4-yl-tetrazolo[1,5-c]quinazoline’s antimicrobial activity against Esherichia coli and Enterococcus faecalis, Pseudomonas aeruginosa and Staphylococcus aureus revealed that sensitivity of Gram-positive bacteria to the compounds was higher than that of Gram-negative bacteria. So, our previously synthesized, 31 derivatives of 1-(2-(1H-tetrazol-5-yl)-R1-phenyl)-3-R2-phenyl(ethyl)ureas were decided to test for their in vitro antibacterial activity against Gram-positive bacteria (Staphylococcus aureus ATCC 25923, Enterobacter aerogenes, Enterococcus faecalis ATCC 29212), Gram-negative bacteria (Pseudomonas aeruginosa ATCC 9027, Escherichia coli ATCC 25922, Klebsiella pneumoniae 68) and antifungal properties against Candida albicans ATCC 885653. Agar-diffusion method was used for determination of the preliminary activity compared to well-known reference antimicrobials. All the compounds were dissolved in DMSO at a concentration of 100 μg/disk, using inhibition zone diameter (IZD, mm) as a measure for the antimicrobial activity. The most active turned to be 3 structures, that inhibited several bacterial strains: 1-ethyl-3-(5-fluoro-2-(1H-tetrazol-5-yl)phenyl)urea (1), 1-(4-bromo-2-(1H-tetrazol-5-yl)-phenyl)-3-(4-(trifluoromethyl)phenyl)urea (2) and 1-(4-chloro-2-(1H-tetrazol-5-yl)phenyl)-3-(3-(trifluoromethyl)phenyl)urea (3). IZM (mm) was 40 (Escherichia coli), 25 (Klebsiella pneumonia) for compound 1; 12 (Pseudomonas aeruginosa), 15 (Staphylococcus aureus), 10 (Enterococcus faecalis) for compound 2; 25 (Staphylococcus aureus), 15 (Enterococcus faecalis) for compound 3. The most sensitive to the activity of the substances were Gram-negative bacteria Pseudomonas aeruginosa. While none of compound effected on Candida albicans. Speaking about, reference drugs: Amikacin (30 µg/disk) showed 27 and Ceftazide (30 µg/disk) 25 against Pseudomonas aeruginosa. That is, unfortunately, higher than studied 1-(2-(1H-tetrazol-5-yl)-R1-phenyl)-3-R2-phenyl(ethyl)ureas. Obtained results will be used for further purposeful optimization of the leading compounds in the more effective antimicrobials because of the ever-mounting problem of microorganism’s resistance.

Keywords: antimicrobial, antifungal, compounds, 1-(2-(1H-tetrazol-5-yl)-R1-phenyl)-3-R2-phenyl(ethyl)ureas

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Authors: Milton Ixquiac, Erick Montenegro, Francisco Reynoso, Matthew Schmidt, Thomas Mazur, Tianyu Zhao, Hiram Gay, Geoffrey Hugo, Lauren Henke, Jeff Michael Michalski, Angel Velarde, Vicky de Falla, Franky Reyes, Osmar Hernandez, Edgar Aparicio Ruiz, Baozhou Sun

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Purpose: Radiotherapy departments in low- and middle-income countries (LMICs) like Guatemala have recently introduced intensity-modulated radiotherapy (IMRT). IMRT has become the standard of care in high-income countries (HIC) due to reduced toxicity and improved outcomes in some cancers. The purpose of this work is to show the agreement between the dosimetric results shown in the Dose Volume Histograms (DVH) to the objectives proposed in the adopted protocol. This is the initial experience with an O-ring Linac. Methods and Materials: An O-Linac Linac was installed at our clinic in Guatemala in 2019 and has been used to treat approximately 90 patients daily with IMRT. This Linac is a completely Image Guided Device since to deliver each radiotherapy session must take a Mega Voltage Cone Beam Computerized Tomography (MVCBCT). In each MVCBCT, the Linac deliver 9 UM, and they are taken into account while performing the planning. To start the standardization, the TG263 was employed in the nomenclature and adopted a hypofractionated protocol to treat ChestWall, including supraclavicular nodes achieving 40.05Gy in 15 fractions. The planning was developed using 4 semiarcs from 179-305 degrees. The planner must create optimization volumes for targets and Organs at Risk (OARs); the difficulty for the planner was the dose base due to the MVCBCT. To evaluate the planning modality, we used 30 chestwall cases. Results: The plans created manually achieve the protocol objectives. The protocol objectives are the same as the RTOG1005, and the DHV curves look clinically acceptable. Conclusions: Despite the O-ring Linac doesn´t have the capacity to obtain kv images, the cone beam CT was created using MV energy, the dose delivered by the daily image setup process still without affect the dosimetric quality of the plans, and the dose distribution is acceptable achieving the protocol objectives.

Keywords: hypofrationation, VMAT, chestwall, radiotherapy planning

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Authors: Antonios Paraskevas, Michael Madas

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For a university to maintain its international competitiveness in education, it is essential to recruit qualitative academic staff as it constitutes its most valuable asset. This selection demonstrates a significant role in achieving strategic objectives, particularly by emphasizing a firm commitment to exceptional student experience and innovative teaching and learning practices of high quality. In this vein, the appropriate selection of academic staff establishes a very important factor of competitiveness, efficiency and reputation of an academic institute. Within this framework, our work demonstrates a comprehensive methodological concept that emphasizes on the multi-criteria nature of the problem and on how decision makers could utilize our approach in order to proceed to the appropriate judgment. The conceptual framework introduced in this paper is built upon a hybrid neutrosophic method based on the Neutrosophic Analytical Hierarchy Process (N-AHP), which uses the theory of neutrosophy sets and is considered suitable in terms of significant degree of ambiguity and indeterminacy observed in decision-making process. To this end, our framework extends the N-AHP by incorporating the Neutrosophic Delphi Method (N-DM). By applying the N-DM, we can take into consideration the importance of each decision-maker and their preferences per evaluation criterion. To the best of our knowledge, the proposed model is the first which applies Neutrosophic Delphi Method in the selection of academic staff. As a case study, it was decided to use our method to a real problem of academic personnel selection, having as main goal to enhance the algorithm proposed in previous scholars’ work, and thus taking care of the inherit ineffectiveness which becomes apparent in traditional multi-criteria decision-making methods when dealing with situations alike. As a further result, we prove that our method demonstrates greater applicability and reliability when compared to other decision models.

Keywords: analytical hierarchy process, delphi method, multi-criteria decision maiking method, neutrosophic set theory, personnel recruitment

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Authors: Faheema Khan

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To investigate the ability of sensitive and tolerant genotype of Glycine max to adapt to a saline environment in a field, we examined the growth performance, water relation and activities of antioxidant enzymes in relation to photosynthetic rate, chlorophyll a fluorescence, photosynthetic pigment concentration, protein and proline in plants exposed to salt stress. Ten soybean genotypes (Pusa-20, Pusa-40, Pusa-37, Pusa-16, Pusa-24, Pusa-22, BRAGG, PK-416, PK-1042, and DS-9712) were selected and grown hydroponically. After 3 days of proper germination, the seedlings were transferred to Hoagland’s solution (Hoagland and Arnon 1950). The growth chamber was maintained at a photosynthetic photon flux density of 430 μmol m−2 s−1, 14 h of light, 10 h of dark and a relative humidity of 60%. The nutrient solution was bubbled with sterile air and changed on alternate days. Ten-day-old seedlings were given seven levels of salt in the form of NaCl viz., T1 = 0 mM NaCl, T2=25 mM NaCl, T3=50 mM NaCl, T4=75 mM NaCl, T5=100 mM NaCl, T6=125 mM NaCl, T7=150 mM NaCl. The investigation showed that genotype Pusa-24, PK-416 and Pusa-20 appeared to be the most salt-sensitive. genotypes as inferred from their significantly reduced length, fresh weight and dry weight in response to the NaCl exposure. Pusa-37 appeared to be the most tolerant genotype since no significant effect of NaCl treatment on growth was found. We observed a greater decline in the photosynthetic variables like photosynthetic rate, chlorophyll fluorescence and chlorophyll content, in salt-sensitive (Pusa-24) genotype than in salt-tolerant Pusa-37 under high salinity. Numerous primers were verified on ten soybean genotypes obtained from Operon technologies among which 30 RAPD primers shown high polymorphism and genetic variation. The Jaccard’s similarity coefficient values for each pairwise comparison between cultivars were calculated and similarity coefficient matrix was constructed. The closer varieties in the cluster behaved similar in their response to salinity tolerance. Intra-clustering within the two clusters precisely grouped the 10 genotypes in sub-cluster as expected from their physiological findings.Salt tolerant genotype Pusa-37, was further analysed by 2-Dimensional gel electrophoresis to analyse the differential expression of proteins at high salt stress. In the Present study, 173 protein spots were identified. Of these, 40 proteins responsive to salinity were either up- or down-regulated in Pusa-37. Proteomic analysis in salt-tolerant genotype (Pusa-37) led to the detection of proteins involved in a variety of biological processes, such as protein synthesis (12 %), redox regulation (19 %), primary and secondary metabolism (25 %), or disease- and defence-related processes (32 %). In conclusion, the soybean plants in our study responded to salt stress by changing their protein expression pattern. The photosynthetic, biochemical and molecular study showed that there is variability in salt tolerance behaviour in soybean genotypes. Pusa-24 is the salt-sensitive and Pusa-37 is the salt-tolerant genotype. Moreover this study gives new insights into the salt-stress response in soybean and demonstrates the power of genomic and proteomic approach in plant biology studies which finally could help us in identifying the possible regulatory switches (gene/s) controlling the salt tolerant genotype of the crop plants and their possible role in defence mechanism.

Keywords: glycine max, salt stress, RAPD, genomic and proteomic variability

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Authors: Massimiliano Biagini, Marco Spinsanti, Gabriella De Angelis, Sara Tomei, Ilaria Ferlenghi, Maria Scarselli, Alessia Biolchi, Alessandro Muzzi, Brunella Brunelli, Silvana Savino, Marzia M. Giuliani, Isabel Delany, Paolo Costantino, Rino Rappuoli, Vega Masignani, Nathalie Norais

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The gram-negative bacterium Neisseria meningitidis serogroup B (MenB) is an exclusively human pathogen representing the major cause of meningitides and severe sepsis in infants and children but also in young adults. This pathogen is usually present in the 30% of healthy population that act as a reservoir, spreading it through saliva and respiratory fluids during coughing, sneezing, kissing. Among surface-exposed protein components of this diplococcus, factor H binding protein is a lipoprotein proved to be a protective antigen used as a component of the recently licensed Bexsero vaccine. fHbp is a highly variable meningococcal protein: to reflect its remarkable sequence variability, it has been classified in three variants (or two subfamilies), and with poor cross-protection among the different variants. Furthermore, the level of fHbp expression varies significantly among strains, and this has also been considered an important factor for predicting MenB strain susceptibility to anti-fHbp antisera. Different methods have been used to assess fHbp expression on meningococcal strains, however, all these methods use anti-fHbp antibodies, and for this reason, the results are affected by the different affinity that antibodies can have to different antigenic variants. To overcome the limitations of an antibody-based quantification, we developed a quantitative Mass Spectrometry (MS) approach. Selected Reaction Monitoring (SRM) recently emerged as a powerful MS tool for detecting and quantifying proteins in complex mixtures. SRM is based on the targeted detection of ProteoTypicPeptides (PTPs), which are unique signatures of a protein that can be easily detected and quantified by MS. This approach, proven to be highly sensitive, quantitatively accurate and highly reproducible, was used to quantify the absolute amount of fHbp antigen in total extracts derived from 105 clinical isolates, evenly distributed among the three main variant groups and selected to be representative of the fHbp circulating subvariants around the world. We extended the study at the genetic level investigating the correlation between the differential level of expression and polymorphisms present within the genes and their promoter sequences. The implications of fHbp expression on the susceptibility of the strain to killing by anti-fHbp antisera are also presented. To date this is the first comprehensive fHbp expression profiling in a large panel of Neisseria meningitidis clinical isolates driven by an antibody-independent MS-based methodology, opening the door to new applications in vaccine coverage prediction and reinforcing the molecular understanding of released vaccines.

Keywords: quantitative mass spectrometry, Neisseria meningitidis, vaccines, bexsero, molecular epidemiology

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Authors: Mst Shapna Akter, Hossain Shahriar

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One of the most important challenges in the field of software code audit is the presence of vulnerabilities in software source code. Every year, more and more software flaws are found, either internally in proprietary code or revealed publicly. These flaws are highly likely exploited and lead to system compromise, data leakage, or denial of service. C and C++ open-source code are now available in order to create a largescale, machine-learning system for function-level vulnerability identification. We assembled a sizable dataset of millions of opensource functions that point to potential exploits. We developed an efficient and scalable vulnerability detection method based on deep neural network models that learn features extracted from the source codes. The source code is first converted into a minimal intermediate representation to remove the pointless components and shorten the dependency. Moreover, we keep the semantic and syntactic information using state-of-the-art word embedding algorithms such as glove and fastText. The embedded vectors are subsequently fed into deep learning networks such as LSTM, BilSTM, LSTM-Autoencoder, word2vec, BERT, and GPT-2 to classify the possible vulnerabilities. Furthermore, we proposed a neural network model which can overcome issues associated with traditional neural networks. Evaluation metrics such as f1 score, precision, recall, accuracy, and total execution time have been used to measure the performance. We made a comparative analysis between results derived from features containing a minimal text representation and semantic and syntactic information. We found that all of the deep learning models provide comparatively higher accuracy when we use semantic and syntactic information as the features but require higher execution time as the word embedding the algorithm puts on a bit of complexity to the overall system.

Keywords: cyber security, vulnerability detection, neural networks, feature extraction

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Authors: Changhan Ouyang, Zhonglin Xie

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In response to proatherosclerotic factors such as oxidized lipids, or to therapeutic interventions such as angioplasty, stents, or bypass surgery, vascular smooth muscle cells (VSMCs) migrate from the media to the intima, resulting in intimal hyperplasia, restenosis, graft failure, or atherosclerosis. These proatherosclerotic factors also activate autophagy in VSMCs. However, the functional role of autophagy in vascular health and disease remains poorly understood. In the present study, we determined the role of autophagy in the regulation of VSMC migration. Autophagy activity in cultured human aortic smooth muscle cells (HASMCs) and mouse carotid arteries was measured by Western blot analysis of microtubule-associated protein 1 light chain 3 B (LC3B) and P62. The VSMC migration was determined by scratch wound assay and transwell migration assay. Ex vivo smooth muscle cell migration was determined using aortic ring assay. The in vivo SMC migration was examined by staining the carotid artery sections with smooth muscle alpha actin (alpha SMA) after carotid artery ligation. To examine the relationship between autophagy and neointimal hyperplasia, C57BL/6J mice were subjected to carotid artery ligation. Seven days after injury, protein levels of Atg5, Atg7, Beclin1, and LC3B drastically increased and remained higher in the injured arteries three weeks after the injury. In parallel with the activation of autophagy, vascular injury-induced neointimal hyperplasia as estimated by increased intima/media ratio. The en face staining of carotid artery showed that vascular injury enhanced alpha SMA staining in the intimal cells as compared with the sham operation. Treatment of HASMCs with platelet-derived growth factor (PDGF), one of the major factors for vascular remodeling in response to vascular injury, increased Atg7 and LC3 II protein levels and enhanced autophagosome formation. In addition, aortic ring assay demonstrated that PDGF treated aortic rings displayed an increase in neovessel formation compared with control rings. Whole mount staining for CD31 and alpha SMA in PDGF treated neovessels revealed that the neovessel structures were stained by alpha SMA but not CD31. In contrast, pharmacological and genetic suppression of autophagy inhibits VSMC migration. Especially, gene silencing of Atg7 inhibited VSMC migration induced by PDGF. Furthermore, three weeks after ligation, markedly decreased neointimal formation was found in mice treated with chloroquine, an inhibitor of autophagy. Quantitative morphometric analysis of the injured vessels revealed a marked reduction in the intima/media ratio in the mice treated with chloroquine. Conclusion: Autophagy activation increases VSMC migration while autophagy suppression inhibits VSMC migration. These findings suggest that autophagy suppression may be an important therapeutic strategy for atherosclerosis and intimal hyperplasia.

Keywords: autophagy, vascular smooth muscle cell, migration, neointimal formation

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Authors: Nikoloz Jalabadze, Roin Chedia, Lili Nadaraia, Levan Khundadze

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Nanocrystalline materials in powder condition can be manufactured by a number of different methods, however manufacture of composite materials product in the same nanocrystalline state is still a problem because the processes of compaction and synthesis of nanocrystalline powders go with intensive growth of particles – the process which promotes formation of pieces in an ordinary crystalline state instead of being crystallized in the desirable nanocrystalline state. To date spark plasma sintering (SPS) has been considered as the most promising and energy efficient method for producing dense bodies of composite materials. An advantage of the SPS method in comparison with other methods is mainly low temperature and short time of the sintering procedure. That finally gives an opportunity to obtain dense material with nanocrystalline structure. Graphene has recently garnered significant interest as a reinforcing phase in composite materials because of its excellent electrical, thermal and mechanical properties. Graphene nanoplatelets (GNPs) in particular have attracted much interest as reinforcements for ceramic matrix composites (mostly in Al2O3, Si3N4, TiO2, ZrB2 a. c.). SPS has been shown to fully densify a variety of ceramic systems effectively including Al2O3 and often with improvements in mechanical and functional behavior. Alumina consolidated by SPS has been shown to have superior hardness, fracture toughness, plasticity and optical translucency compared to conventionally processed alumina. Knowledge of how GNPs influence sintering behavior is important to effectively process and manufacture process. In this study, the effects of GNPs on the SPS processing of Al2O3 are investigated by systematically varying sintering temperature, holding time and pressure. Our experiments showed that SPS process is also appropriate for the synthesis of nanocrystalline powders of alumina-graphene composites. Depending on the size of the molds, it is possible to obtain different amount of nanopowders. Investigation of the structure, physical-chemical, mechanical and performance properties of the elaborated composite materials was performed. The results of this study provide a fundamental understanding of the effects of GNP on sintering behavior, thereby providing a foundation for future optimization of the processing of these promising nanocomposite systems.

Keywords: alumina oxide, ceramic matrix composites, graphene nanoplatelets, spark-plasma sintering

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Authors: Abiodun Amusan, Olugbenga Akinola, Kazeem Akano, María Hernández-Castañeda, Jenna Dick, Akintunde Sowunmi, Geoffrey Hart, Grace Gbotosho

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Introduction: Artemisinin-based Combination Therapy (ACTs) is the cornerstone malaria treatment option in most malaria-endemic countries. Unfortunately, the malaria control effort is constantly being threatened by resistance of Plasmodium falciparum to ACTs. The recent evidence of artemisinin resistance in East Africa and its possibility of spreading to other African regions portends an imminent health catastrophe. This study aimed at evaluating the occurrence, prevalence, and influence of artemisinin-resistance markers on treatment outcomes in Ibadan before and after post-adoption of artemisinin combination therapy (ACTs) in Nigeria in 2005. Method: The study involved day zero dry blood spot (DBS) obtained from malaria patients during retrospective (2000-2005) and prospective (2021) studies. A cohort in the prospective study received oral dihydroartemisinin-piperaquine and underwent a 42-day follow-up to observe treatment outcomes. Genomic DNA was extracted from the DBS samples using a QIAamp blood extraction kit. Fragments of P. falciparum kelch13 (Pfkelch13), P. falciparum coronin (Pfcoronin), P. falciparum multidrug resistance 2 (PfMDR2), and P. falciparum chloroquine resistance transporter (PfCRT) genes were amplified and sequenced on a sanger sequencing platform to identify artemisinin resistance-associated mutations. Mutations were identified by aligning sequenced data with reference sequences obtained from the National Center for Biotechnology Information. Data were analyzed using descriptive statistics and student t-tests. Results: Mean parasite clearance time (PCT) and fever clearance time (FCT) were 2.1 ± 0.6 days (95% CI: 1.97-2.24) and 1.3 ± 0.7 days (95% CI: 1.1-1.6) respectively. Four mutations, K189T [34/53(64.2%)], R255K [2/53(3.8%)], K189N [1/53(1.9%)] and N217H [1/53(1.9%)] were identified within the N-terminal (Coiled-coil containing) domain of Pfkelch13. No artemisinin resistance-associated mutation usually found within the β-propeller domain of the Pfkelch13 gene was found in these analyzed samples. However, K189T and R255K mutations showed a significant correlation with longer parasite clearance time in the patients (P<0.002). The observed Pfkelch13 gene changes did not influence the baseline mean parasitemia (P = 0.44). P76S [17/100 (17%)] and V62M [1/100 (1%)] changes were identified in the Pfcoronin gene fragment without any influence on the parasitological parameters. No change was observed in the PfMDR2 gene, while no artemisinin resistance-associated mutation was found in the PfCRT gene. Furthermore, a sample each in the retrospective study contained the Pfkelch13 K189T and Pfcoronin P76S mutations. Conclusion: The study revealed absence of genetic-based evidence of artemisinin resistance in the study population at the time of study. The high frequency of K189T Pfkelch13 mutation and its correlation with increased parasite clearance time in this study may depict geographical variation of resistance mediators and imminent artemisinin resistance, respectively. The study also revealed an inherent potential of parasites to harbour drug-resistant genotypes before the introduction of ACTs in Nigeria.

Keywords: artemisinin resistance, plasmodium falciparum, Pfkelch13 mutations, Pfcoronin

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Authors: Pia Kastl

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Potentials of blended learning are the flexibility of learning and the possibility to get in touch with lecturers and fellow students on site. By combining face-to-face sessions with digital self-learning units, the learning process can be optimized, and learning success increased. To examine wether blended learning outperforms online and face-to-face teaching, a theory-based questionnaire survey was conducted. The results show that the interaction and cooperation among students is poorly provided in blended learning, and face-to-face teaching performs better in this respect. The aim of this article is to identify concrete suggestions students have for improving cooperation and interaction in blended learning courses. For this purpose, interviews were conducted with students from various academic disciplines in face-to-face, online, or blended learning courses (N= 60). The questions referred to opinions and suggestions for improvement regarding the course design of the respective learning environment. The analysis was carried out by qualitative content analysis. The results show that students perceive the interaction as beneficial to their learning. They verbalize their knowledge and are exposed to different perspectives. In addition, emotional support is particularly important in exam phases. Interaction and cooperation were primarily enabled in the face-to-face component of the courses studied, while there was very limited contact with fellow students in the asynchronous component. Forums offered were hardly used or not used at all because the barrier to asking a question publicly is too high, and students prefer private channels for communication. This is accompanied by the disadvantage that the interaction occurs only among people who already know each other. Creating contacts is not fostered in the blended learning courses. Students consider optimization possibilities as a task of the lecturers in the face-to-face sessions: Here, interaction and cooperation should be encouraged through get-to-know-you rounds or group work. It is important here to group the participants randomly to establish contact with new people. In addition, sufficient time for interaction is desired in the lecture, e.g., in the context of discussions or partner work. In the digital component, students prefer synchronous exchange at a fixed time, for example, in breakout rooms or an MS Teams channel. The results provide an overview of how interaction and cooperation can be implemented in blended learning courses. Positive design possibilities are partly dependent on subject area and course. Future studies could tie in here with a course-specific analysis.

Keywords: blended learning, higher education, hybrid teaching, qualitative research, student learning

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Authors: M. Uysal, M. Yilmaz, I. Tiryakioğlu

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Digital Terrain Model (DTM) is a digital numerical representation of the Earth's surface. DTMs have been applied to a diverse field of tasks, such as urban planning, military, glacier mapping, disaster management. In the expression of the Earth' surface as a mathematical model, an infinite number of point measurements are needed. Because of the impossibility of this case, the points at regular intervals are measured to characterize the Earth's surface and DTM of the Earth is generated. Hitherto, the classical measurement techniques and photogrammetry method have widespread use in the construction of DTM. At present, RADAR, LiDAR, and stereo satellite images are also used for the construction of DTM. In recent years, especially because of its superiorities, Airborne Light Detection and Ranging (LiDAR) has an increased use in DTM applications. A 3D point cloud is created with LiDAR technology by obtaining numerous point data. However recently, by the development in image mapping methods, the use of unmanned aerial vehicles (UAV) for photogrammetric data acquisition has increased DTM generation from image-based point cloud. The accuracy of the DTM depends on various factors such as data collection method, the distribution of elevation points, the point density, properties of the surface and interpolation methods. In this study, the random data reduction method is compared for DTMs generated from image based point cloud data. The original image based point cloud data set (100%) is reduced to a series of subsets by using random algorithm, representing the 75, 50, 25 and 5% of the original image based point cloud data set. Over the ANS campus of Afyon Kocatepe University as the test area, DTM constructed from the original image based point cloud data set is compared with DTMs interpolated from reduced data sets by Kriging interpolation method. The results show that the random data reduction method can be used to reduce the image based point cloud datasets to 50% density level while still maintaining the quality of DTM.

Keywords: DTM, Unmanned Aerial Vehicle (UAV), uniform, random, kriging

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Authors: Paola Causin, Andrea Aspri, Alessandro Benfenati

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Diffuse Optical Tomography (DOT) is an emergent medical imaging technique which employs NIR light to estimate the spatial distribution of optical coefficients in biological tissues for diagnostic purposes, in a noninvasive and non-ionizing manner. DOT reconstruction is a severely ill-conditioned problem due to prevalent scattering of light in the tissue. In this contribution, we present our research in adopting hybrid knowledgedriven/data-driven approaches which exploit the existence of well assessed physical models and build upon them neural networks integrating the availability of data. Namely, since in this context regularization procedures are mandatory to obtain a reasonable reconstruction [1], we explore the use of neural networks as tools to include prior information on the solution. 2. Materials and Methods The idea underlying our approach is to leverage neural networks to solve PDE-constrained inverse problems of the form 𝒒 ∗ = 𝒂𝒓𝒈 𝒎𝒊𝒏𝒒 𝐃(𝒚, 𝒚̃), (1) where D is a loss function which typically contains a discrepancy measure (or data fidelity) term plus other possible ad-hoc designed terms enforcing specific constraints. In the context of inverse problems like (1), one seeks the optimal set of physical parameters q, given the set of observations y. Moreover, 𝑦̃ is the computable approximation of y, which may be as well obtained from a neural network but also in a classic way via the resolution of a PDE with given input coefficients (forward problem, Fig.1 box ). Due to the severe ill conditioning of the reconstruction problem, we adopt a two-fold approach: i) we restrict the solutions (optical coefficients) to lie in a lower-dimensional subspace generated by auto-decoder type networks. This procedure forms priors of the solution (Fig.1 box ); ii) we use regularization procedures of type 𝒒̂ ∗ = 𝒂𝒓𝒈𝒎𝒊𝒏𝒒 𝐃(𝒚, 𝒚̃)+ 𝑹(𝒒), where 𝑹(𝒒) is a regularization functional depending on regularization parameters which can be fixed a-priori or learned via a neural network in a data-driven modality. To further improve the generalizability of the proposed framework, we also infuse physics knowledge via soft penalty constraints (Fig.1 box ) in the overall optimization procedure (Fig.1 box ). 3. Discussion and Conclusion DOT reconstruction is severely hindered by ill-conditioning. The combined use of data-driven and knowledgedriven elements is beneficial and allows to obtain improved results, especially with a restricted dataset and in presence of variable sources of noise.

Keywords: inverse problem in tomography, deep learning, diffuse optical tomography, regularization

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Authors: Shweh Fern Loo, Jun Yin Ong, Than Zaw Oo

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Acute respiratory distress syndrome (ARDS) is a common serious condition of bilateral lung infiltrates that develops secondary to various underlying conditions such as diseases or injuries. ARDS with severe hypercapnia is associated with higher ICU mortality and morbidity. Venovenous Extracorporeal membrane oxygenation (VV-ECMO) support has been established to avert life-threatening hypoxemia and hypercapnic respiratory failure despite optimal conventional mechanical ventilation. However, VV-ECMO is relatively not advisable in particular groups of patients, especially in multi-organ failure, advanced age, hemorrhagic complications and irreversible central nervous system pathology. We presented a case of a 79-year-old Chinese lady without any pre-existing lung disease admitted to our hospital intensive care unit (ICU) after acute presentation of breathlessness and chest pain. After extensive workup, she was diagnosed with rapidly progressing acute interstitial pneumonia with ARDS and hypercapnia respiratory failure. The patient received lung protective strategies of mechanical ventilation and neuromuscular blockage therapy as per clinical guidelines. However, hypercapnia respiratory failure was refractory, and she was deemed not a good candidate for VV-ECMO support given her advanced age and high vasopressor requirements from shock. Alternative therapy with extracorporeal CO2 removal (ECCO2R) was considered and implemented. The patient received 12 days of ECCO2R paired with muscle paralysis, optimization of lung-protective mechanical ventilation and dialysis. Unfortunately, the patient still had refractory hypercapnic respiratory failure with dual vasopressor support despite prolonged therapy. Given failed and futile medical treatment, the family opted for withdrawal of care, a conservative approach, and comfort care, which led to her demise. The effectivity of extracorporeal CO2 removal may depend on disease burden, involvement and severity of the disease. There is insufficient data to make strong recommendations about its benefit-risk ratio for ECCO2R devices, and further studies and data would be required. Nonetheless, ECCO2R can be considered an alternative treatment for refractory hypercapnic respiratory failure patients who are unsuitable for initiating venovenous ECMO.

Keywords: extracorporeal CO2 removal (ECCO2R), acute respiratory distress syndrome (ARDS), acute interstitial pneumonia (AIP), hypercapnic respiratory failure

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Authors: Gherbi Khadidja

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In the Mediterranean region, water resources are limited and very unevenly distributed in space and time. The main objective of this project is the development of a wireless network for the management of water resources in northern Algeria, the Mitidja plain, which helps farmers to irrigate in the most optimized way and solve the problem of water shortage in the region. Therefore, we will develop an aid tool that can modernize and replace some traditional techniques, according to the real needs of the crops and according to the soil conditions as well as the climatic conditions (soil moisture, precipitation, characteristics of the unsaturated zone), These data are collected in real-time by sensors and analyzed by an algorithm and displayed on a mobile application and the website. The results are essential information and alerts with recommendations for action to farmers to ensure the sustainability of the agricultural sector under water shortage conditions. In the first part: We want to set up a wireless sensor network, for precise management of water resources, by presenting another type of equipment that allows us to measure the water content of the soil, such as the Watermark probe connected to the sensor via the acquisition card and an Arduino Uno, which allows collecting the captured data and then program them transmitted via a GSM module that will send these data to a web site and store them in a database for a later study. In a second part: We want to display the results on a website or a mobile application using the database to remotely manage our smart irrigation system, which allows the farmer to use this technology and offers the possibility to the growers to access remotely via wireless communication to see the field conditions and the irrigation operation, at home or at the office. The tool to be developed will be based on satellite imagery as regards land use and soil moisture. These tools will make it possible to follow the evolution of the needs of the cultures in time, but also to time, and also to predict the impact on water resources. According to the references consulted, if such a tool is used, it can reduce irrigation volumes by up to up to 40%, which represents more than 100 million m3 of savings per year for the Mitidja. This volume is equivalent to a medium-size dam.

Keywords: optimal irrigation, soil moisture, smart irrigation, water management

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Authors: Chor Yi Ng, Christine Kong, Loretta Teo, Stephen Yau, FC Cheung, TL Poon, Francis Lee

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Purpose: Dynamic conformal arc (DCA) and intensity modulated radiotherapy (IMRT) are two treatment techniques commonly used for stereotactic radiosurgery/radiotherapy of cranial lesions. IMRT plans usually give better dose conformity while DCA plans have better dose fall off. Rapid dose fall off is preferred for radiotherapy of cranial lesions, but dose conformity is also important. For certain lesions, DCA plans have good conformity, while for some lesions, the conformity is just unacceptable with DCA plans, and IMRT has to be used. The choice between the two may not be apparent until each plan is prepared and dose indices compared. We described a deviation index (DI) which is a measurement of the deviation of the target shape from a sphere, and test its functionality to choose between the two techniques. Method and Materials: From May 2015 to May 2017, our institute has performed stereotactic radiotherapy for 105 patients treating a total of 115 lesions (64 DCA plans and 51 IMRT plans). Patients were treated with the Varian Clinac iX with HDMLC. Brainlab Exactrac system was used for patient setup. Treatment planning was done with Brainlab iPlan RT Dose (Version 4.5.4). DCA plans were found to give better dose fall off in terms of R50% (R50% (DCA) = 4.75 Vs R50% (IMRT) = 5.242) while IMRT plans have better conformity in terms of treatment volume ratio (TVR) (TVR(DCA) = 1.273 Vs TVR(IMRT) = 1.222). Deviation Index (DI) is proposed to better facilitate the choice between the two techniques. DI is the ratio of the volume of a 1 mm shell of the PTV and the volume of a 1 mm shell of a sphere of identical volume. DI will be close to 1 for a near spherical PTV while a large DI will imply a more irregular PTV. To study the functionality of DI, 23 cases were chosen with PTV volume ranged from 1.149 cc to 29.83 cc, and DI ranged from 1.059 to 3.202. For each case, we did a nine field IMRT plan with one pass optimization and a five arc DCA plan. Then the TVR and R50% of each case were compared and correlated with the DI. Results: For the 23 cases, TVRs and R50% of the DCA and IMRT plans were examined. The conformity for IMRT plans are better than DCA plans, with majority of the TVR(DCA)/TVR(IMRT) ratios > 1, values ranging from 0.877 to1.538. While the dose fall off is better for DCA plans, with majority of the R50%(DCA)/ R50%(IMRT) ratios < 1. Their correlations with DI were also studied. A strong positive correlation was found between the ratio of TVRs and DI (correlation coefficient = 0.839), while the correlation between the ratio of R50%s and DI was insignificant (correlation coefficient = -0.190). Conclusion: The results suggest DI can be used as a guide for choosing the planning technique. For DI greater than a certain value, we can expect the conformity for DCA plans to become unacceptably great, and IMRT will be the technique of choice.

Keywords: cranial lesions, dynamic conformal arc, IMRT, image guided radiotherapy, stereotactic radiotherapy

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Authors: Esra Zengin, Sinan Akkar

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Reliable and accurate prediction of nonlinear structural response requires specification of appropriate earthquake ground motions to be used in nonlinear time history analysis. The current research has mainly focused on selection and manipulation of real earthquake records that can be seen as the most critical step in the performance based seismic design and assessment of the structures. Utilizing amplitude scaled ground motions that matches with the target spectra is commonly used technique for the estimation of nonlinear structural response. Representative ground motion ensembles are selected to match target spectrum such as scenario-based spectrum derived from ground motion prediction equations, Uniform Hazard Spectrum (UHS), Conditional Mean Spectrum (CMS) or Conditional Spectrum (CS). Different sets of criteria exist among those developed methodologies to select and scale ground motions with the objective of obtaining robust estimation of the structural performance. This study presents ground motion selection and scaling procedure that considers the spectral variability at target demand with the level of ground motion dispersion. The proposed methodology provides a set of ground motions whose response spectra match target median and corresponding variance within a specified period interval. The efficient and simple algorithm is used to assemble the ground motion sets. The scaling stage is based on the minimization of the error between scaled median and the target spectra where the dispersion of the earthquake shaking is preserved along the period interval. The impact of the spectral variability on nonlinear response distribution is investigated at the level of inelastic single degree of freedom systems. In order to see the effect of different selection and scaling methodologies on fragility curve estimations, results are compared with those obtained by CMS-based scaling methodology. The variability in fragility curves due to the consideration of dispersion in ground motion selection process is also examined.

Keywords: ground motion selection, scaling, uncertainty, fragility curve

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Authors: Oscar E. Cariceo, Claudia V. Casal

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Machine learning offers a set of techniques to promote social work interventions and can lead to support decisions of practitioners in order to predict new behaviors based on data produced by the organizations, services agencies, users, clients or individuals. Machine learning techniques include a set of generalizable algorithms that are data-driven, which means that rules and solutions are derived by examining data, based on the patterns that are present within any data set. In other words, the goal of machine learning is teaching computers through 'examples', by training data to test specifics hypothesis and predict what would be a certain outcome, based on a current scenario and improve that experience. Machine learning can be classified into two general categories depending on the nature of the problem that this technique needs to tackle. First, supervised learning involves a dataset that is already known in terms of their output. Supervising learning problems are categorized, into regression problems, which involve a prediction from quantitative variables, using a continuous function; and classification problems, which seek predict results from discrete qualitative variables. For social work research, machine learning generates predictions as a key element to improving social interventions on complex social issues by providing better inference from data and establishing more precise estimated effects, for example in services that seek to improve their outcomes. This paper exposes the results of a classification algorithm to predict cyberbullying among adolescents. Data were retrieved from the National Polyvictimization Survey conducted by the government of Chile in 2017. A logistic regression model was created to predict if an adolescent would experience cyberbullying based on the interaction and behavior of gender, age, grade, type of school, and self-esteem sentiments. The model can predict with an accuracy of 59.8% if an adolescent will suffer cyberbullying. These results can help to promote programs to avoid cyberbullying at schools and improve evidence based practice.

Keywords: cyberbullying, evidence based practice, machine learning, social work research

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Authors: Javed Mohammed

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Right now, bio-medical infrastructure lags well behind the curve. Our healthcare system is dispersed and disjointed; medical records are a bit of a mess; and we do not yet have the capacity to store and process the crazy amounts of data coming our way from widespread whole-genome sequencing. And then there are privacy issues. Despite these infrastructure challenges, some researchers are plunging into bio medical Big Data now, in hopes of extracting new and actionable knowledge. They are doing delving into molecular-level data to discover bio markers that help classify patients based on their response to existing treatments; and pushing their results out to physicians in novel and creative ways. Computer scientists and bio medical researchers are able to transform data into models and simulations that will enable scientists for the first time to gain a profound under-standing of the deepest biological functions. Solving biological problems may require High-Performance Computing HPC due either to the massive parallel computation required to solve a particular problem or to algorithmic complexity that may range from difficult to intractable. Many problems involve seemingly well-behaved polynomial time algorithms (such as all-to-all comparisons) but have massive computational requirements due to the large data sets that must be analyzed. High-throughput techniques for DNA sequencing and analysis of gene expression have led to exponential growth in the amount of publicly available genomic data. With the increased availability of genomic data traditional database approaches are no longer sufficient for rapidly performing life science queries involving the fusion of data types. Computing systems are now so powerful it is possible for researchers to consider modeling the folding of a protein or even the simulation of an entire human body. This research paper emphasizes the computational biology's growing need for high-performance computing and Big Data. It illustrates this article’s indispensability in meeting the scientific and engineering challenges of the twenty-first century, and how Protein Folding (the structure and function of proteins) and Phylogeny Reconstruction (evolutionary history of a group of genes) can use HPC that provides sufficient capability for evaluating or solving more limited but meaningful instances. This article also indicates solutions to optimization problems, and benefits Big Data and Computational Biology. The article illustrates the Current State-of-the-Art and Future-Generation Biology of HPC Computing with Big Data.

Keywords: high performance, big data, parallel computation, molecular data, computational biology

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Authors: Vijay Kumar, Jaspreet Singh, Manoj Wadhwa

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Piezo-resistive pressure sensors were one of the first developed micromechanical system (MEMS) devices and still display a significant growth prompted by the advancements in micromachining techniques and material technology. In MEMS based piezo-resistive pressure sensors, temperature can be considered as the main environmental condition which affects the system performance. The study of the thermal behavior of these sensors is essential to define the parameters that cause the output characteristics to drift. In this work, a study on the effects of temperature and doping concentration in a boron implanted piezoresistor for a silicon-based pressure sensor is discussed. We have optimized the temperature coefficient of resistance (TCR) and temperature coefficient of sensitivity (TCS) values to determine the effect of temperature drift on the sensor performance. To be more precise, in order to reduce the temperature drift, a high doping concentration is needed. And it is well known that the Wheatstone bridge in a pressure sensor is supplied with a constant voltage or a constant current input supply. With a constant voltage supply, the thermal drift can be compensated along with an external compensation circuit, whereas the thermal drift in the constant current supply can be directly compensated by the bridge itself. But it would be beneficial to also compensate the temperature coefficient of piezoresistors so as to further reduce the temperature drift. So, with a current supply, the TCS is dependent on both the TCπ and TCR. As TCπ is a negative quantity and TCR is a positive quantity, it is possible to choose an appropriate doping concentration at which both of them cancel each other. An exact cancellation of TCR and TCπ values is not readily attainable; therefore, an adjustable approach is generally used in practical applications. Thus, one goal of this work has been to better understand the origin of temperature drift in pressure sensor devices so that the temperature effects can be minimized or eliminated. This paper describes the optimum doping levels for the piezoresistors where the TCS of the pressure transducers will be zero due to the cancellation of TCR and TCπ values. Also, the fabrication and characterization of the pressure sensor are carried out. The optimized TCR value obtained for the fabricated die is 2300 ± 100ppm/ᵒC, for which the piezoresistors are implanted at a doping concentration of 5E13 ions/cm³ and the TCS value of -2100ppm/ᵒC is achieved. Therefore, the desired TCR and TCS value is achieved, which are approximately equal to each other, so the thermal effects are considerably reduced. Finally, we have calculated the effect of temperature and doping concentration on the output characteristics of the sensor. This study allows us to predict the sensor behavior against temperature and to minimize this effect by optimizing the doping concentration.

Keywords: piezo-resistive, pressure sensor, doping concentration, TCR, TCS

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Authors: Kathryn Rooney, Kaitlyn Eddy, Evan Landers, Weihui Li

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The international mortality rate for neonates and infants has been declining at a disproportionally low rate when compared to the overall decline in child mortality in recent decades. A significant portion of infant deaths could be prevented with the implementation of low-cost and easy to use physiological monitoring devices, by enabling early identification of symptoms before they progress into life-threatening illnesses. The oral diagnostic device discussed in this paper serves to continuously monitor the key vital signs of body temperature, respiratory rate, heart rate, and oxygen saturation. The device mimics an infant pacifier, designed to be easily tolerated by infants as well as orthodontically inert. The fundamental measurements are gathered via thermistors and a pulse oximeter, each encapsulated in medical-grade silicone and wired internally to a microcontroller chip. The chip then translates the raw measurements into physiological values via an internal algorithm, before outputting the data to a liquid crystal display screen and an Android application. Additionally, a biological sample collection chamber is incorporated into the internal portion of the device. The movement within the oral chamber created by sucking on the pacifier-like device pushes saliva through a small check valve in the distal end, where it is accumulated and stored. The collection chamber can be easily removed, making the sample readily available to be tested for various diseases and analytes. With the vital sign monitoring and sample collection offered by this device, abnormal fluctuations in physiological parameters can be identified and appropriate medical care can be sought. This device enables preventative diagnosis for infants who may otherwise have gone undiagnosed, due to the inaccessibility of healthcare that plagues vast numbers of underprivileged populations.

Keywords: neonate mortality, infant mortality, low-cost diagnostics, vital signs, saliva testing, preventative care

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Authors: Kana Matsuyanagi

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Anorexia Nervosa (AN) is a psychiatric disorder characterized by a relentless pursuit of thinness and strict restriction of food. The current therapeutic approaches for AN predominantly revolve around outpatient psychotherapies, which create significant financial barriers for the majority of affected patients, hindering their access to treatment. Nonetheless, AN exhibit one of the highest mortality and relapse rates among psychological disorders, underscoring the urgent need to provide patients with an affordable self-treatment tool, enabling those unable to access conventional medical intervention to address their condition autonomously. To this end, a neurofeedback software, termed RelaxNeuron, was developed with the objective of providing an economical and portable means to aid individuals in self-managing AN. Electroencephalography (EEG) was chosen as the preferred modality for RelaxNeuron, as it aligns with the study's goal of supplying a cost-effective and convenient solution for addressing AN. The primary aim of the software is to ameliorate the negative emotional responses towards food stimuli and the accompanying aberrant eye-tracking patterns observed in AN patient, ultimately alleviating the profound fear towards food an elemental symptom and, conceivably, the fundamental etiology of AN. The core functionality of RelaxNeuron hinges on the acquisition and analysis of EEG signals, alongside an electrocardiogram (ECG) signal, to infer the user's emotional state while viewing dynamic food-related imagery on the screen. Moreover, the software quantifies the user's performance in accurately tracking the moving food image. Subsequently, these two parameters undergo further processing in the subsequent algorithm, informing the delivery of either negative or positive feedback to the user. Preliminary test results have exhibited promising outcomes, suggesting the potential advantages of employing RelaxNeuron in the treatment of AN, as evidenced by its capacity to enhance emotional regulation and attentional processing through repetitive and persistent therapeutic interventions.

Keywords: Anorexia Nervosa, fear conditioning, neurofeedback, BCI

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Authors: A. Kachmazova, A. Shadiev, Y. Teterin, P. Yartcev

Abstract:

Introduction: Biliary calculi disease (LCS) still occupies the leading position among urgent diseases of the abdominal cavity, manifesting itself from asymptomatic course to life-threatening states. Nowadays arsenal of diagnostic methods for choledocholithiasis is quite wide: ultrasound, hepatobiliscintigraphy (HBSG), magnetic resonance imaging (MRI), endoscopic retrograde cholangiography (ERCP). Among them, transabdominal ultrasound (TA ultrasound) is the most accessible and routine diagnostic method. Nowadays ERCG is the "gold" standard in diagnosis and one-stage treatment of biliary tract obstruction. However, transpapillary techniques are accompanied by serious postoperative complications (postmanipulative pancreatitis (3-5%), endoscopic papillosphincterotomy bleeding (2%), cholangitis (1%)), the lethality being 0.4%. GBSG and MRI are also quite informative methods in the diagnosis of choledocholithiasis. Small size of concrements, their localization in intrapancreatic and retroduodenal part of common bile duct significantly reduces informativity of all diagnostic methods described above, that demands additional studying of this problem. Materials and Methods: 890 patients with the diagnosis of cholelithiasis (calculous cholecystitis) were admitted to the Sklifosovsky Scientific Research Institute of Hospital Medicine in the period from August, 2020 to June, 2021. Of them 115 people with mechanical jaundice caused by concrements in bile ducts. Results: Final EUS diagnosis was made in all patients (100,0%). In all patients in whom choledocholithiasis diagnosis was revealed or confirmed after EUS, ERCP was performed urgently (within two days from the moment of its detection) as the X-ray operation room was provided; it confirmed the presence of concrements. All stones were removed by lithoextraction using Dormia basket. The postoperative period in these patients had no complications. Conclusions: EUS is the most informative and safe diagnostic method, which allows to detect choledocholithiasis in patients with discrepancies between clinical-laboratory and instrumental methods of diagnosis in shortest time, that in its turn will help to decide promptly on the further tactics of patient treatment. We consider it reasonable to include EUS in the diagnostic algorithm for choledocholithiasis. Disclosure: Nothing to disclose.

Keywords: endoscopic ultrasonography, choledocholithiasis, common bile duct, concrement, ERCP

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