Search results for: target organs
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 3036

Search results for: target organs

2946 Influence of Improved Roughage Quality and Period of Meal Termination on Digesta Load in the Digestive Organs of Goats

Authors: Rasheed A. Adebayo, Mehluli M. Moyo, Ignatius V. Nsahlai

Abstract:

Ruminants are known to relish roughage for productivity but the effect of its quality on digesta load in rumen, omasum, abomasum and other distal organs of the digestive tract is yet unknown. Reticulorumen fill is a strong indicator for long-term control of intake in ruminants. As such, the measurement and prediction of digesta load in these compartments may be crucial to productivity in the ruminant industry. The current study aimed at determining the effect of (a) diet quality on digesta load in digestive organs of goats, and (b) period of meal termination on the reticulorumen fill and digesta load in other distal compartments of the digestive tract of goats. Goats were fed with urea-treated hay (UTH), urea-sprayed hay (USH) and non-treated hay (NTH). At the end of eight weeks of a feeding trial period, upon termination of a meal in the morning, afternoon or evening, all goats were slaughtered in random groups of three per day to measure reticulorumen fill and digesta loads in other distal compartments of the digestive tract. Both diet quality and period affected (P < 0.05) the measure of reticulorumen fill. However, reticulorumen fill in the evening was larger (P < 0.05) than afternoon, while afternoon was similar (P > 0.05) to morning. Also, diet quality affected (P < 0.05) the wet omasal digesta load, wet abomasum, dry abomasum and dry caecum digesta loads but did not affect (P > 0.05) both wet and dry digesta loads in other compartments of the digestive tract. Period of measurement did not affect (P > 0.05) the wet omasal digesta load, and both wet and dry digesta loads in other compartments of the digestive tract except wet abomasum digesta load (P < 0.05) and dry caecum digesta load (P < 0.05). Both wet and dry reticulorumen fill were correlated (P < 0.05) with omasum (r = 0.623) and (r = 0.723), respectively. In conclusion, reticulorumen fill of goats decreased by improving the roughage quality; and the period of meal termination and measurement of the fill is a key factor to the quantity of digesta load.

Keywords: digesta, goats, meal termination, reticulo-rumen fill

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2945 Determine of Design Variables and Target Reliability Indexes of Underground Structure

Authors: Yo-Seph Byun, Gyu-Phil Lee, Young-Bin Park, Gye-Chun Cho, Seong-Won Lee

Abstract:

In Korea, a study on Limit State Design (LSD) for underground structures is being conducted in order to perform more effective design. In this study, as a result of MCS (Monte-Carlo Simulation) technique, failure probabilities of the structure during normal and earthquake are estimated in reliability analysis. Target reliability indexes are determined depending on load combinations for underground structure, and then, design variables such as load and material factors in LSD are decided. As a result, through the research in order to determine more reliable design variables, a specification of LSD for underground structures is able to be developed.

Keywords: design variable, limit state design, target reliability index, underground structure

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2944 Quality Assurances for an On-Board Imaging System of a Linear Accelerator: Five Months Data Analysis

Authors: Liyun Chang, Cheng-Hsiang Tsai

Abstract:

To ensure the radiation precisely delivering to the target of cancer patients, the linear accelerator equipped with the pretreatment on-board imaging system is introduced and through it the patient setup is verified before the daily treatment. New generation radiotherapy using beam-intensity modulation, usually associated the treatment with steep dose gradients, claimed to have achieved both a higher degree of dose conformation in the targets and a further reduction of toxicity in normal tissues. However, this benefit is counterproductive if the beam is delivered imprecisely. To avoid shooting critical organs or normal tissues rather than the target, it is very important to carry out the quality assurance (QA) of this on-board imaging system. The QA of the On-Board Imager® (OBI) system of one Varian Clinac-iX linear accelerator was performed through our procedures modified from a relevant report and AAPM TG142. Two image modalities, 2D radiography and 3D cone-beam computed tomography (CBCT), of the OBI system were examined. The daily and monthly QA was executed for five months in the categories of safety, geometrical accuracy and image quality. A marker phantom and a blade calibration plate were used for the QA of geometrical accuracy, while the Leeds phantom and Catphan 504 phantom were used in the QA of radiographic and CBCT image quality, respectively. The reference images were generated through a GE LightSpeed CT simulator with an ADAC Pinnacle treatment planning system. Finally, the image quality was analyzed via an OsiriX medical imaging system. For the geometrical accuracy test, the average deviations of the OBI isocenter in each direction are less than 0.6 mm with uncertainties less than 0.2 mm, while all the other items have the displacements less than 1 mm. For radiographic image quality, the spatial resolution is 1.6 lp/cm with contrasts less than 2.2%. The spatial resolution, low contrast, and HU homogenous of CBCT are larger than 6 lp/cm, less than 1% and within 20 HU, respectively. All tests are within the criteria, except the HU value of Teflon measured with the full fan mode exceeding the suggested value that could be due to itself high HU value and needed to be rechecked. The OBI system in our facility was then demonstrated to be reliable with stable image quality. The QA of OBI system is really necessary to achieve the best treatment for a patient.

Keywords: CBCT, image quality, quality assurance, OBI

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2943 Vision Based People Tracking System

Authors: Boukerch Haroun, Luo Qing Sheng, Li Hua Shi, Boukraa Sebti

Abstract:

In this paper we present the design and the implementation of a target tracking system where the target is set to be a moving person in a video sequence. The system can be applied easily as a vision system for mobile robot. The system is composed of two major parts the first is the detection of the person in the video frame using the SVM learning machine based on the “HOG” descriptors. The second part is the tracking of a moving person it’s done by using a combination of the Kalman filter and a modified version of the Camshift tracking algorithm by adding the target motion feature to the color feature, the experimental results had shown that the new algorithm had overcame the traditional Camshift algorithm in robustness and in case of occlusion.

Keywords: camshift algorithm, computer vision, Kalman filter, object tracking

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2942 Spectrophotometric Determination of L-Dopa in Germinated and Non-Germinated Broad Beans (Vicia faba L.) and Chickpea (Cicer aritinum L.)

Authors: Wissame Gouigah, Amina Medellel, Mahmoud Trachi, Djedjiga Benamara, Salem Benamara

Abstract:

The purpose of this work is to investigate, by UV/VIS spectrophotometry, the distribution of L-dopa, known as precursor of dopamine which is used in the treatment of Parkinson's disease, in broad beans (Vicia faba) (Vf) and chickpea (Cicer aritinum L.) (CA). In the case of Vf, the different organs were analyzed separately: 1) First, in the fresh state: pod (GF), cotyledons (CF), green shell (EF) and placenta (PF) which is the organ through which the seed is attached to the pod, 2) in the dry state (S): peel of the dry seed (ES) and cotyledons (CS), and 3) in the germinated state: peel (EGe), cotyledons (CGe) and germ (GeVf). Results showed that the content of L-dopa is unevenly distributed between different parts of fresh Vf. But the most important result concerns the predominance of L-dopa in placenta with an L-dopa content (~ 60 mg/g of wet weight, ww) sometimes 7-fold higher (p≤0.05) than those of other considered parts of fresh Vf. In the case of CA, the L-dopa concentration in germinated gains was higher than those found in all analyzed Vf organs, excepted PF.

Keywords: broad bean (Vicia faba L.), chickpea (Cicer aritinum L.), L-dopa, Parkinson disease, placenta

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2941 Intra-miR-ExploreR, a Novel Bioinformatics Platform for Integrated Discovery of MiRNA:mRNA Gene Regulatory Networks

Authors: Surajit Bhattacharya, Daniel Veltri, Atit A. Patel, Daniel N. Cox

Abstract:

miRNAs have emerged as key post-transcriptional regulators of gene expression, however identification of biologically-relevant target genes for this epigenetic regulatory mechanism remains a significant challenge. To address this knowledge gap, we have developed a novel tool in R, Intra-miR-ExploreR, that facilitates integrated discovery of miRNA targets by incorporating target databases and novel target prediction algorithms, using statistical methods including Pearson and Distance Correlation on microarray data, to arrive at high confidence intragenic miRNA target predictions. We have explored the efficacy of this tool using Drosophila melanogaster as a model organism for bioinformatics analyses and functional validation. A number of putative targets were obtained which were also validated using qRT-PCR analysis. Additional features of the tool include downloadable text files containing GO analysis from DAVID and Pubmed links of literature related to gene sets. Moreover, we are constructing interaction maps of intragenic miRNAs, using both micro array and RNA-seq data, focusing on neural tissues to uncover regulatory codes via which these molecules regulate gene expression to direct cellular development.

Keywords: miRNA, miRNA:mRNA target prediction, statistical methods, miRNA:mRNA interaction network

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2940 An Image Segmentation Algorithm for Gradient Target Based on Mean-Shift and Dictionary Learning

Authors: Yanwen Li, Shuguo Xie

Abstract:

In electromagnetic imaging, because of the diffraction limited system, the pixel values could change slowly near the edge of the image targets and they also change with the location in the same target. Using traditional digital image segmentation methods to segment electromagnetic gradient images could result in lots of errors because of this change in pixel values. To address this issue, this paper proposes a novel image segmentation and extraction algorithm based on Mean-Shift and dictionary learning. Firstly, the preliminary segmentation results from adaptive bandwidth Mean-Shift algorithm are expanded, merged and extracted. Then the overlap rate of the extracted image block is detected before determining a segmentation region with a single complete target. Last, the gradient edge of the extracted targets is recovered and reconstructed by using a dictionary-learning algorithm, while the final segmentation results are obtained which are very close to the gradient target in the original image. Both the experimental results and the simulated results show that the segmentation results are very accurate. The Dice coefficients are improved by 70% to 80% compared with the Mean-Shift only method.

Keywords: gradient image, segmentation and extract, mean-shift algorithm, dictionary iearning

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2939 An Improved Tracking Approach Using Particle Filter and Background Subtraction

Authors: Amir Mukhtar, Dr. Likun Xia

Abstract:

An improved, robust and efficient visual target tracking algorithm using particle filtering is proposed. Particle filtering has been proven very successful in estimating non-Gaussian and non-linear problems. In this paper, the particle filter is used with color feature to estimate the target state with time. Color distributions are applied as this feature is scale and rotational invariant, shows robustness to partial occlusion and computationally efficient. The performance is made more robust by choosing the different (YIQ) color scheme. Tracking is performed by comparison of chrominance histograms of target and candidate positions (particles). Color based particle filter tracking often leads to inaccurate results when light intensity changes during a video stream. Furthermore, background subtraction technique is used for size estimation of the target. The qualitative evaluation of proposed algorithm is performed on several real-world videos. The experimental results demonstrate that the improved algorithm can track the moving objects very well under illumination changes, occlusion and moving background.

Keywords: tracking, particle filter, histogram, corner points, occlusion, illumination

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2938 Prospects of Low Immune Response Transplants Based on Acellular Organ Scaffolds

Authors: Inna Kornienko, Svetlana Guryeva, Anatoly Shekhter, Elena Petersen

Abstract:

Transplantation is an effective treatment option for patients suffering from different end-stage diseases. However, it is plagued by a constant shortage of donor organs and the subsequent need of a lifelong immunosuppressive therapy for the patient. Currently some researchers look towards using of pig organs to replace human organs for transplantation since the matrix derived from porcine organs is a convenient substitute for the human matrix. As an initial step to create a new ex vivo tissue engineered model, optimized protocols have been created to obtain organ-specific acellular matrices and evaluated their potential as tissue engineered scaffolds for culture of normal cells and tumor cell lines. These protocols include decellularization by perfusion in a bioreactor system and immersion-agitation on an orbital shaker with use of various detergents (SDS, Triton X-100) and freezing. Complete decellularization – in terms of residual DNA amount – is an important predictor of probability of immune rejection of materials of natural origin. However, the signs of cellular material may still remain within the matrix even after harsh decellularization protocols. In this regard, the matrices obtained from tissues of low-immunogenic pigs with α3Galactosyl-tranferase gene knock out (GalT-KO) may be a promising alternative to native animal sources. The research included a study of induced effect of frozen and fresh fragments of GalT-KO skin on healing of full-thickness plane wounds in 80 rats. Commercially available wound dressings (Ksenoderm, Hyamatrix and Alloderm) as well as allogenic skin were used as a positive control and untreated wounds were analyzed as a negative control. The results were evaluated on the 4th day after grafting, which corresponds to the time of start of normal wound epithelization. It has been shown that a non-specific immune response in models treated with GalT-Ko pig skin was milder than in all the control groups. Research has been performed to measure technical skin characteristics: stiffness and elasticity properties, corneometry, tevametry, and cutometry. These metrics enabled the evaluation of hydratation level, corneous layer husking level, as well as skin elasticity and micro- and macro-landscape. These preliminary data may contribute to development of personalized transplantable organs from GalT-Ko pigs with significantly limited potential of immune rejection. By applying growth factors to a decellularized skin sample it is possible to achieve various regenerative effects based on the particular situation. In this particular research BMP2 and Heparin-binding EGF-like growth factor have been used. Ideally, a bioengineered organ must be biocompatible, non-immunogenic and support cell growth. Porcine organs are attractive for xenotransplantation if severe immunologic concerns can be bypassed. The results indicate that genetically modified pig tissues with knock-outed α3Galactosyl-tranferase gene may be used for production of low-immunogenic matrix suitable for transplantation.

Keywords: decellularization, low-immunogenic, matrix, scaffolds, transplants

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2937 Prediction of Solanum Lycopersicum Genome Encoded microRNAs Targeting Tomato Spotted Wilt Virus

Authors: Muhammad Shahzad Iqbal, Zobia Sarwar, Salah-ud-Din

Abstract:

Tomato spotted wilt virus (TSWV) belongs to the genus Tospoviruses (family Bunyaviridae). It is one of the most devastating pathogens of tomato (Solanum Lycopersicum) and heavily damages the crop yield each year around the globe. In this study, we retrieved 329 mature miRNA sequences from two microRNA databases (miRBase and miRSoldb) and checked the putative target sites in the downloaded-genome sequence of TSWV. A consensus of three miRNA target prediction tools (RNA22, miRanda and psRNATarget) was used to screen the false-positive microRNAs targeting sites in the TSWV genome. These tools calculated different target sites by calculating minimum free energy (mfe), site-complementarity, minimum folding energy and other microRNA-mRNA binding factors. R language was used to plot the predicted target-site data. All the genes having possible target sites for different miRNAs were screened by building a consensus table. Out of these 329 mature miRNAs predicted by three algorithms, only eight miRNAs met all the criteria/threshold specifications. MC-Fold and MC-Sym were used to predict three-dimensional structures of miRNAs and further analyzed in USCF chimera to visualize the structural and conformational changes before and after microRNA-mRNA interactions. The results of the current study show that the predicted eight miRNAs could further be evaluated by in vitro experiments to develop TSWV-resistant transgenic tomato plants in the future.

Keywords: tomato spotted wild virus (TSWV), Solanum lycopersicum, plant virus, miRNAs, microRNA target prediction, mRNA

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2936 The Pharmacology and Physiology of Steroid Oral Contraceptives

Authors: Ragy Raafat Gaber Attaalla

Abstract:

PIP: This review, based on 2 large-scale studies, discusses the pharmacology and physiology of oral steroid contraceptives (OCs). The pharmacological distinction between synthetic and naturally occurring steroids centers on changes in biological activity dependent on compound formulation and an individual's metabolism. OC mechanism of action is explained as the main prevention of ovulation by interference with gonadotropin-releasing hormone. Since some 52 metabolic alterations have been reported in OC users, these phenomena are dealt with in 3 categories: 1) effects on the primary target organs of the female reproductive tract (ovary, myometrium, endometrium, cervix, vagina, breasts, and hypothalamus), 2) general metabolic effects (serum proteins, carbohydrate metabolism, lipid metabolism, water and electrolyte metabolism, body weight, tryptophan metabolism, and vitamins and minerals), and 3) effects on other organ systems (liver, central nervous system, skin, genitourinary, gastrointestinal tract, eye, immune phenomena, and effect on subsequent fertility). The choice of the proper OC formulation and use of OCs by adolescents are discussed. Assessment of OC safety, contraindications, and patient monitoring are provided.

Keywords: steroid oral contraceptives, ovulation, female reproductive tract, metabolic effects

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2935 The Twelfth Rib as a Landmark for Surgery

Authors: Jake Tempo, Georgina Williams, Iain Robertson, Claire Pascoe, Darren Rama, Richard Cetti

Abstract:

Introduction: The twelfth rib is commonly used as a landmark for surgery; however, its variability in length has not been formally studied. The highly variable rib length provides a challenge for urologists seeking a consistent landmark for percutaneous nephrolithotomy and retroperitoneoscopic surgery. Methods and materials: We analysed CT scans of 100 adults who had imaging between 23rd March and twelfth April 2020 at an Australian Hospital. We measured the distance from the mid-sagittal line to the twelfth rib tip in the axial plane as a surrogate for true rib length. We also measured the distance from the twelfth rib tip to the kidney, spleen, and liver. Results: Length from the mid-sagittal line to the right twelfth rib tip varied from 46 (percentile 95%CI 40 to 57) to 136mm (percentile 95%CI 133 to 138). On the left, the distances varied from 55 (percentile 95%CI 50 to 64) to 134mm (percentile 95%CI 131 to 135). Twenty-three percent of people had an organ lying between the tip of the twelfth rib and the kidney on the right, and 11% of people had the same finding on the left. Conclusion: The twelfth rib is highly variable in its length. Similar variability was recorded in the distance from the tip to intra-abdominal organs. Due to the frequency of organs lying between the tip of the rib and the kidney, it should not be used as a landmark for accessing the kidney without prior knowledge of an individual patient’s anatomy, as seen on imaging.

Keywords: PCNL, rib, anatomy, nephrolithotomy

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2934 Sounds of Power: An Ethnoorganological Approach to Understanding Colonial Music Culture in the Peruvian Andes

Authors: Natascha Reich

Abstract:

In colonial Peru, the Spanish crown relied on religious orders, most notably Dominicans, Franciscans, and Jesuits, for accelerating processes of colonization. The dissemination of Christian art, architecture, and music, and most of all, the agency of indigenous people in their production played a key role in facilitating the acceptance of the new religious and political system. Current research on Peruvian colonial music culture and its role as a vehicle for colonization focus on practices in urban centers. The lack of (written) primary sources seems to turn rural areas into a less attractive research territory for musicologists. This paper advocates for a more inclusive approach. By investigating seventeenth-century pipe organs as material remains of Franciscan missionary music culture, it shows how reactions to colonial forces and Christianization in rural Andean locations could follow tendencies different from those in urban areas. Indigenous musicians in cities tried to 'fit' into the European system in order to be accepted by the ruling Spanish elite. By contrast, the indigenous-built pipe organs in the rural Peruvian Colca-Valley show distinctly native-Andean influences. This paper argues that this syncretism can be interpreted as hybridity in Homi K. Bhabha’s sense, as a means of the colonized to undermine the power of the colonizer and to advance reactionary politics. Not only will it show the necessity of considering rural Peruvian music history in modern scholarship for arriving at a more complete picture of colonial culture, but it will also evidence the advantages of a mixed-methodology approach. Historical organology, combined with concepts from ethnomusicology and post-colonial studies, proves as a useful tool in the absence or scarcity of written primary sources.

Keywords: cultural hybridity, music as reactionary politics, Latin American pipe organs, Peruvian colonial music

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2933 Tuning of Kalman Filter Using Genetic Algorithm

Authors: Hesham Abdin, Mohamed Zakaria, Talaat Abd-Elmonaem, Alaa El-Din Sayed Hafez

Abstract:

Kalman filter algorithm is an estimator known as the workhorse of estimation. It has an important application in missile guidance, especially in lack of accurate data of the target due to noise or uncertainty. In this paper, a Kalman filter is used as a tracking filter in a simulated target-interceptor scenario with noise. It estimates the position, velocity, and acceleration of the target in the presence of noise. These estimations are needed for both proportional navigation and differential geometry guidance laws. A Kalman filter has a good performance at low noise, but a large noise causes considerable errors leads to performance degradation. Therefore, a new technique is required to overcome this defect using tuning factors to tune a Kalman filter to adapt increasing of noise. The values of the tuning factors are between 0.8 and 1.2, they have a specific value for the first half of range and a different value for the second half. they are multiplied by the estimated values. These factors have its optimum values and are altered with the change of the target heading. A genetic algorithm updates these selections to increase the maximum effective range which was previously reduced by noise. The results show that the selected factors have other benefits such as decreasing the minimum effective range that was increased earlier due to noise. In addition to, the selected factors decrease the miss distance for all ranges of this direction of the target, and expand the effective range which leads to increase probability of kill.

Keywords: proportional navigation, differential geometry, Kalman filter, genetic algorithm

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2932 Designing State Feedback Multi-Target Controllers by the Use of Particle Swarm Optimization Algorithm

Authors: Seyedmahdi Mousavihashemi

Abstract:

One of the most important subjects of interest in researches is 'improving' which result in various algorithms. In so many geometrical problems we are faced with target functions which should be optimized. In group practices, all the functions’ cooperation lead to convergence. In the study, the optimization algorithm of dense particles is used. Usage of the algorithm improves the given performance norms. The results reveal that usage of swarm algorithm for reinforced particles in designing state feedback improves the given performance norm and in optimized designing of multi-target state feedback controlling, the network will maintain its bearing structure. The results also show that PSO is usable for optimization of state feedback controllers.

Keywords: multi-objective, enhanced, feedback, optimization, algorithm, particle, design

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2931 Evidences for Better Recall with Compatible Items in Episodic Memory

Authors: X. Laurent, M. A. Estevez, P. Mari-Beffa

Abstract:

A focus of recent research is to understand the role of our own response goals in the selection of information that will be encoded in episodic memory. For example, if we respond to a target in the presence of distractors, an important aspect under study is whether the distractor and the target share a common response (compatible) or not (incompatible). Some studies have found that compatible objects tend to be groups together and stored in episodic memory, whereas others found that targets in the presence of incompatible distractors are remembered better. Our current research seems to support both views. We used a Tulving-based definition of episodic memory to differentiate memory from episodic and non-episodic traces. In this task, participants first had to classify a blue object as human or animal (target) which appeared in the presence of a green one (distractor) that could belong to the same category of the target (compatible), to the opposite (incompatible) or to an irrelevant one (neutral). Later they had to report the identity (What), location (Where) and time (When) of both target objects (which had been previously responded to) and distractors (which had been ignored). Episodic memory was inferred when the three scene properties (identity, location and time) were correct. The measure of non-episodic memory consisted of those trials in which the identity was correctly remembered, but not the location or time. Our results showed that episodic memory for compatible stimuli is significantly superior to incompatible ones. In sharp contrast, non-episodic measures found superior memory for targets in the presence of incompatible distractors. Our results demonstrate that response compatibility affects the encoding of episodic and non-episodic memory traces in different ways.

Keywords: episodic memory, action systems, compatible response, what-where-when task

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2930 Effect of Diazepam on Internal Organs of Chrysomya megacephala Using Micro-Computed Tomograph

Authors: Sangkhao M., Butcher B. A.

Abstract:

Diazepam (known as valium) is a medication for calming effect. Many reports on committed suicide cases shown that diazepam is frequently used for this purpose. This research aims to study effect of diazepam on the development of forensically important blowflies, Chrysomya megacephala (Diptera: Calliphoridae) using micro-computed tomography (micro CT). In this study, four rabbits were treated with three different lethal doses of diazepam and one control (LD₀, LD₅₀, LD₁₀₀ and LC). The rabbit’s livers were removed for rearing the blowflies. Pupae were sampled for two series (ages; S1: 24h and S2: 120h) of development. After preparing the specimens, all samples were performed Micro CT using Skyscan 1172. The results shown the effect of diazepam on internal organs and tissues such as brain, cavity of the body, gas bubble, meconium and especially fat body. In the control group, in series 1 (LCS1), fat body was equally dispersed in the head, thorax, and abdomen, development of internal organs were not completed, however, brain, thoracic muscle, wings, legs and rectum were able to observe at 24h after developing into the pupal stage. Development of each organ in the control group in the series two was completed. In the treatment groups, LD₀, LD₅₀, LD₁₀₀ (Series 1 and Series 2), tissues are different, such as gas bubble in LD₀S1, was observed due to rapidity morphological changes during the metamorphosis of blowfly’s pupa in this treatment. Meconium was observed in LD₅₀S2 group because excretion of metabolic waste was not completed. All of the samples in the treatment groups had differentiation of fat bodies because metabolic activities were not completed and these changes affected on functions of every internal system. Discovering of differentiated fat bodies are important results because fat bodies of insect functions as liver in human, therefore it is shown that toxin eliminates from blowfly’s body and homeostatic maintenance of the hemolymph proteins, lipid and carbohydrates in each treatment group are abnormal.

Keywords: forensic toxicology, forensic entomology, diptera, diazepam

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2929 A Biophysical Model of CRISPR/Cas9 on- and off-Target Binding for Rational Design of Guide RNAs

Authors: Iman Farasat, Howard M. Salis

Abstract:

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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2928 Towards a Systematic Evaluation of Web Design

Authors: Ivayla Trifonova, Naoum Jamous, Holger Schrödl

Abstract:

A good web design is a prerequisite for a successful business nowadays, especially since the internet is the most common way for people to inform themselves. Web design includes the optical composition, the structure, and the user guidance of websites. The importance of each website leads to the question if there is a way to measure its usefulness. The aim of this paper is to suggest a methodology for the evaluation of web design. The desired outcome is to have an evaluation that is concentrated on a specific website and its target group.

Keywords: evaluation methodology, factor analysis, target group, web design

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2927 Histological Characteristics of the Organs of Adult Zebrafish as a Biomarker for the Study of New Drugs with Effect on the Snake Venom of Bothrops alternatus

Authors: Jose Carlos Tavares Carvalho, Hady Keita, Giovanna Rocha Santana, Igor Victor Ferreira Dos Santos, Jesus Rafael Rodriguez Amado, Ariadna Lafourcade Prada, Adriana Maciel Ferreira, Helison Oliveira

Abstract:

Summary: As animal model, zebrafish can be a good opportunity to establish a profile of tissue alteration caused by Bothrops alternatus venom and to screen new anti-venom drugs. Objective: To establish tissue biomarkers from zebrafish injected by snake venom and elucidate the use of glucocorticoids in ophidic accidents. Materials and Methods: The Danio rerio fish were randomly divided into four groups: control group, venom group, Dexamethasone1h before venom injected group and Dexamethasone 1 h after venom injected group. The concentration of Bothrops alternatus venom was 0.13 mg/ml and the fish received 20µl/Fish. The Body weight measurement and histological characteristics of gills, kidneys, liver, and intestine were determinate. Results: Physical analysis shows necrosis accompanied by inflammation in animals receiving the Bothrops alternatus venom. Significant difference was observed in the variation of weight between the control group, and the groups received the venom (t student test, p < 0.05). The average histological alterations index of gill, liver, kidney or intestine was statistically higher in animals received the venom (t Student test, p < 0.05). The alterations were lower in the groups that received Dexamethasone 1h before and after venom injected compared to the group that received only the venom. Dexamethasone 1h before venom injected group had minor histopathological alterations. Conclusion: The organs of zebrafish may be a tissue biomarker of alterations from Bothrops alternatus venom and dexamethasone reduced the damage caused by this venom in the organs studied, which may suggest the use of zebrafish as animal model for research related to screening new drug against snake venom.

Keywords: zebrafish, snake venom, biomarker, drugs

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2926 Improving Decision Support for Organ Transplant

Authors: Ian McCulloh, Andrew Placona, Darren Stewart, Daniel Gause, Kevin Kiernan, Morgan Stuart, Christopher Zinner, Laura Cartwright

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An estimated 22-25% of viable deceased donor kidneys are discarded every year in the US, while waitlisted candidates are dying every day. As many as 85% of transplanted organs are refused at least once for a patient that scored higher on the match list. There are hundreds of clinical variables involved in making a clinical transplant decision and there is rarely an ideal match. Decision makers exhibit an optimism bias where they may refuse an organ offer assuming a better match is imminent. We propose a semi-parametric Cox proportional hazard model, augmented by an accelerated failure time model based on patient specific suitable organ supply and demand to estimate a time-to-next-offer. Performance is assessed with Cox-Snell residuals and decision curve analysis, demonstrating improved decision support for up to a 5-year outlook. Providing clinical decision makers with quantitative evidence of likely patient outcomes (e.g., time to next offer and the mortality associated with waiting) may improve decisions and reduce optimism bias, thus reducing discarded organs and matching more patients on the waitlist.

Keywords: decision science, KDPI, optimism bias, organ transplant

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2925 Auction Theory In Competitive Takeovers: Ideas For Regulators

Authors: Emanuele Peggi

Abstract:

The regulation of competitive takeover bids is one of the most problematic issues of any legislation on takeovers since it concerns a particular type of market, that of corporate control, whose peculiar characteristic is that companies represent "assets" unique of their kind, for each of which there will be a relevant market characterized by the presence of different subjects interested in acquiring control. Firstly, this work aims to analyze, from a comparative point of view, the regulation of takeover bids in competitive scenarios, characterized by the presence of multiple takeover bids for the same target company, and contribute to the debate on the impact that various solutions adopted in some legal systems examined (Italy, UK, and USA) have had on the efficiency of the market for corporate control. Secondly, the different auction models identified by the economic literature and their possible applications to corporate acquisitions in competitive scenarios will be examined, as well as the consequences that the application of each of them causes on the efficiency of the market for corporate control and the interests of the target shareholders. The scope is to study the possibility of attributing to the management of the target company the power to design the auction in order to better protect the interests of shareholders through the adoption of ad hoc models according to the specific context. and in particular on the ground of their assessment of the buyer's risk profile.

Keywords: takeovers, auction theory, shareholders, target company

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2924 Event Related Potentials in Terms of Visual and Auditory Stimuli

Authors: Seokbeen Lim, KyeongSeok Sim, DaKyeong Shin, Gilwon Yoon

Abstract:

Event-related potential (ERP) is one of the useful tools for investigating cognitive reactions. In this study, the potential of ERP components detected after auditory and visual stimuli was examined. Subjects were asked to respond upon stimuli that were of three categories; Target, Non-Target and Standard stimuli. The ERP after stimulus was measured. In the experiment of visual evoked potentials (VEPs), the subjects were asked to gaze at a center point on the monitor screen where the stimuli were provided by the reversal pattern of the checkerboard. In consequence of the VEP experiments, we observed consistent reactions. Each peak voltage could be measured when the ensemble average was applied. Visual stimuli had smaller amplitude and a longer latency compared to that of auditory stimuli. The amplitude was the highest with Target and the smallest with Standard in both stimuli.

Keywords: auditory stimulus, EEG, event related potential, oddball task, visual stimulus

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2923 Hsa-miR-326 Functions as a Tumor Suppressor in Non-Small Cell Lung Cancer through Targeting CCND1

Authors: Cheng-Cao Sun, Shu-Jun Li, Cuili Yang, Yongyong Xi, Liang Wang, Feng Zhang, De-Jia Li

Abstract:

Hsa-miRNA-326 (miR-326) has recently been discovered having anticancer efficacy in different organs. However, the role of miR-326 on non-small cell lung cancer (NSCLC) is still ambiguous. In this study, we investigated the role of miR-326 on the development of NSCLC. The results indicated that miR-326 was significantly down-regulated in primary tumor tissues and very low levels were found in NSCLC cell lines. Ectopic expression of miR-326 in NSCLC cell lines significantly suppressed cell growth as evidenced by cell viability assay, colony formation assay and BrdU staining, through inhibition of cyclin D1, cyclin D2, CDK4, and up-regulation of p57(Kip2) and p21(Waf1/Cip1). In addition, miR-326 induced apoptosis, as indicated by concomitantly with up-regulation of key apoptosis protein cleaved caspase-3, and down-regulation of anti-apoptosis protein Bcl2. Moreover, miR-326 inhibited cellular migration and invasiveness through inhibition of matrix metalloproteinases (MMP)-7 and MMP-9. Further, oncogene CCND1 was revealed to be a putative target of miR-326, which was inversely correlated with miR-326 expression in NSCLC. Taken together, our results demonstrated that miR-326 played a pivotal role on NSCLC through inhibiting cell proliferation, migration, invasion, and promoting apoptosis by targeting oncogenic CCND1.

Keywords: hsa-miRNA-326 (miR-326), cyclin D1, non-small cell lung cancer (NSCLC), proliferation, apoptosis

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2922 Strategy and Mechanism for Intercepting Unpredictable Moving Targets in the Blue-Tailed Damselfly (Ischnura elegans)

Authors: Ziv Kassner, Gal Ribak

Abstract:

Members of the Odonata order (dragonflies and damselflies) stand out for their maneuverability and superb flight control, which allow them to catch flying prey in the air. These outstanding aerial abilities were fine-tuned during millions of years of an evolutionary arms race between Odonata and their prey, providing an attractive research model for studying the relationship between sensory input – and aerodynamic output in a flying insect. The ability to catch a maneuvering target in air is interesting not just for insect behavioral ecology and neuroethology but also for designing small and efficient robotic air vehicles. While the aerial prey interception of dragonflies (suborder: Anisoptera) have been studied before, little is known about how damselflies (suborder: Zygoptera) intercept prey. Here, high-speed cameras (filming at 1000 frames per second) were used to explore how damselflies catch unpredictable targets that move through air. Blue-tailed damselflies - Ischnura elegans (family: Coenagrionidae) were introduced to a flight arena and filmed while landing on moving targets that were oscillated harmonically. The insects succeeded in capturing targets that were moved with an amplitude of 6 cm and frequencies of 0-2.5 Hz (fastest mean target speed of 0.3 m s⁻¹) and targets that were moved in 1 Hz (an average speed of 0.3 m s⁻¹) but with an amplitude of 15 cm. To land on stationary or slow targets, damselflies either flew directly to the target, or flew sideways, up to a point in which the target was fixed in the center of the field of view, followed by direct flight path towards the target. As the target moved in increased frequency, damselflies demonstrated an ability to track the targets while flying sideways and minimizing the changes of their body direction on the yaw axis. This was likely an attempt to keep the targets at the center of the visual field while minimizing rotational optic flow of the surrounding visual panorama. Stabilizing rotational optic flow helps in estimation of the velocity and distance of the target. These results illustrate how dynamic visual information is used by damselflies to guide them towards a maneuvering target, enabling the superb aerial hunting abilities of these insects. They also exemplifies the plasticity of the damselfly flight apparatus which enables flight in any direction, irrespective of the direction of the body.

Keywords: bio-mechanics, insect flight, target fixation, tracking and interception

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2921 The Effect of Different Levels of Seed and Extract of Harmal (Peganum harmala L.) on Immune Responses of Broiler Chicks

Authors: M. Toghyani, A. Ghasemi, S. A. Tabeidian

Abstract:

The present study was carried out to evaluate the effect of different levels of dietary seed and extract of Harmal (Peganum harmala L.) on immunity of broiler chicks. A total of 350 one-day old broiler chicks (Ross 308) were randomly allocated to five dietary treatments with four replicates pen of 14 birds each. Dietary treatments consisted of control, 1 and 2 g/kg Harmal seed in diet, 100 and 200 mg/L Harmal seed extract in water. Broilers received dietary treatments from 1 to 42 d. Two birds from each pen were randomly weighed and sacrificed at 42 d of age, the relative weight of lymphoid organs (bursa of Fabercius and spleen) to live weight were calculated. Antibody titers against Newcastle and influenza viruses and sheep red blood cell were measured at 30 d of age. Results showed that the relative weights of lymphoid organs were not affected by dietary treatments. Furthermore, antibody titer against Newcastle and influenza viruses as well as sheep red blood cell antigen were significantly (P<0.05) enhanced by feeding Harmal seed and extract. In conclusion, the results indicated that dietary inclusion of Harmal seed and extract enhanced immunological responses in broiler chicks.

Keywords: broiler chicks, Harmal, immunity, Peganum harmala

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2920 Changes of Mitochondrial Potential in the Midgut Epithelium of Lithobius forficatus (Myriapoda, Chilopoda) Exposed to Cadmium Concentrated in Soil

Authors: Magdalena Rost-Roszkowska, Izabela Poprawa, Alina Chachulska-Zymelka, Lukasz Chajec, Grazyna Wilczek, Piotr Wilczek, Malgorzata Lesniewska

Abstract:

Lithobius forficatus, commonly known as the brown centipede, is a widespread European species, which lives in the upper layers of soil, under stones, litter, rocks, and leaves. As the soil organism, it is exposed to numerous stressors such as xenobiotics, including heavy metals, temperature, starvation, pathogens, etc. Heavy metals are treated as the environmental pollutants of the soil because of their toxic effects on plants, animals and human being. One of the heavy metals which is xenobiotic and can be taken up by plants or animals from the soil is cadmium. The digestive system of centipedes is composed of three distinct regions: fore-, mid- and hindgut. The salivary glands of centipedes are the organs which belong to the anterior region of the digestive system and take part in the synthesis, accumulation, and secretion of many substances. The middle region having contact with the food masses is treated as one of the barriers which protect the organism against any stressors which originate from the external environment, e.g., toxic metals. As the material for our studies, we chose two organs of the digestive system in brown centipede, the organs which take part in homeostasis maintenance: the salivary glands and the midgut. The main purpose of the project was to investigate the relationship between the percentage of depolarized mitochondria, mitophagy and ATP level in cells of mentioned above organs. The animals were divided into experimental groups: K – the control group, the animals cultured in a laboratory conditions in a horticultural soil and fed with Acheta domesticus larvae; Cd1 – the animals cultured in a horticultural soil supplemented with 80 mg/kg (dry weight) of CdCl2, fed with A. domesticus larvae maintained in tap water, 12 days – short-term exposure; Cd2 – the animals cultured in a horticultural soil supplemented with 80 mg/kg (dry weight) of CdCl2, fed with A. domesticus larvae maintained in tap water, 45 days – long-term exposure. The studies were conducted using transmission electron microscopy (TEM), flow cytometry and confocal microscopy. Quantitative analysis revealed that regardless of the organ, a progressive increase in the percentage of cells with depolarized mitochondria was registered, but only in the salivary glands. These were statistically significant changes from the control. In both organs, there were no differences in the level of the analyzed parameter depending on the duration of exposure of individuals to cadmium. Changes in the ultrastructure of mitochondria have been observed. With the extension of the body's exposure time to metal, an increase in the ADP/ATP index was recorded. However, changes statistically significant to the control were demonstrated in the intestine and salivary glands. The size of this intestinal index and salivary glands in the Cd2 group was about thirty and twenty times higher, respectively than in control. Acknowledgment: The study has been financed by the National Science Centre, Poland, grant no 2017/25/B/NZ4/00420.

Keywords: cadmium, digestive system, ultrastructure, centipede

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2919 Design and Test a Robust Bearing-Only Target Motion Analysis Algorithm Based on Modified Gain Extended Kalman Filter

Authors: Mohammad Tarek Al Muallim, Ozhan Duzenli, Ceyhun Ilguy

Abstract:

Passive sonar is a method for detecting acoustic signals in the ocean. It detects the acoustic signals emanating from external sources. With passive sonar, we can determine the bearing of the target only, no information about the range of the target. Target Motion Analysis (TMA) is a process to estimate the position and speed of a target using passive sonar information. Since bearing is the only available information, the TMA technique called Bearing-only TMA. Many TMA techniques have been developed. However, until now, there is not a very effective method that could be used to always track an unknown target and extract its moving trace. In this work, a design of effective Bearing-only TMA Algorithm is done. The measured bearing angles are very noisy. Moreover, for multi-beam sonar, the measurements is quantized due to the sonar beam width. To deal with this, modified gain extended Kalman filter algorithm is used. The algorithm is fine-tuned, and many modules are added to improve the performance. A special validation gate module is used to insure stability of the algorithm. Many indicators of the performance and confidence level measurement are designed and tested. A new method to detect if the target is maneuvering is proposed. Moreover, a reactive optimal observer maneuver based on bearing measurements is proposed, which insure converging to the right solution all of the times. To test the performance of the proposed TMA algorithm a simulation is done with a MATLAB program. The simulator program tries to model a discrete scenario for an observer and a target. The simulator takes into consideration all the practical aspects of the problem such as a smooth transition in the speed, a circular turn of the ship, noisy measurements, and a quantized bearing measurement come for multi-beam sonar. The tests are done for a lot of given test scenarios. For all the tests, full tracking is achieved within 10 minutes with very little error. The range estimation error was less than 5%, speed error less than 5% and heading error less than 2 degree. For the online performance estimator, it is mostly aligned with the real performance. The range estimation confidence level gives a value equal to 90% when the range error less than 10%. The experiments show that the proposed TMA algorithm is very robust and has low estimation error. However, the converging time of the algorithm is needed to be improved.

Keywords: target motion analysis, Kalman filter, passive sonar, bearing-only tracking

Procedia PDF Downloads 367
2918 Target-Triggered DNA Motors and their Applications to Biosensing

Authors: Hongquan Zhang

Abstract:

Inspired by endogenous protein motors, researchers have constructed various synthetic DNA motors based on the specificity and predictability of Watson-Crick base pairing. However, the application of DNA motors to signal amplification and biosensing is limited because of low mobility and difficulty in real-time monitoring of the walking process. The objective of our work was to construct a new type of DNA motor termed target-triggered DNA motors that can walk for hundreds of steps in response to a single target binding event. To improve the mobility and processivity of DNA motors, we used gold nanoparticles (AuNPs) as scaffolds to build high-density, three-dimensional tracks. Hundreds of track strands are conjugated to a single AuNP. To enable DNA motors to respond to specific protein and nucleic acid targets, we adapted the binding-induced DNA assembly into the design of the target-triggered DNA motors. In response to the binding of specific target molecules, DNA motors are activated to autonomously walk along AuNP, which is powered by a nicking endonuclease or DNAzyme-catalyzed cleavage of track strands. Each moving step restores the fluorescence of a dye molecule, enabling monitoring of the operation of DNA motors in real time. The motors can translate a single binding event into the generation of hundreds of oligonucleotides from a single nanoparticle. The motors have been applied to amplify the detection of proteins and nucleic acids in test tubes and live cells. The motors were able to detect low pM concentrations of specific protein and nucleic acid targets in homogeneous solutions without the need for separation. Target-triggered DNA motors are significant for broadening applications of DNA motors to molecular sensing, cell imagining, molecular interaction monitoring, and controlled delivery and release of therapeutics.

Keywords: biosensing, DNA motors, gold nanoparticles, signal amplification

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2917 Detection of Elephant Endotheliotropic Herpes Virus in a Wild Asian Elephant Calf in Thailand by Using Real-Time PCR

Authors: Bopit Puyati, Anchittha Kaewchana, Nuntita Ruksachat

Abstract:

In January 2018, a male wild elephant, approximately 2 years old, was found dead in Phu Luang Wildlife Sanctuary, Loei province. The elephant was likely to die around 2 weeks earlier. The carcass was decayed without any signs of attack or bullet. No organs were removed. A deadly viral disease was suspected. Different organs including lung, liver, intestine and tongue were collected and submitted to the veterinary research and development center, Surin province for viral detection. The samples were then examined with real-time PCR for detecting U41 Major DNA binding protein (MDBP) gene and with conventional PCR for the presence of specific polymerase gene. We used tumor necrosis factor (TNF) gene as the internal control. In our real-time PCR, elephant endotheliotropic herpesvirus (EEHV) was recovered from lung, liver, and tongue whereas only tongue provided a positive result in the conventional PCR. All samples were positive with TNF gene detection. To our knowledge, this is the first report of EEHV detection in wild elephant in Thailand. EEHV surveillance in this wild population is strongly suggested. Linkage between EEHV in wild and domestic elephants should be further explored.

Keywords: elephant endotheliotropic herpes virus, PCR, Thailand, wild Asian elephant

Procedia PDF Downloads 112