Search results for: breast motion

Authors: Nadine Ayasha

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Hail happened in Sukabumi (August 23, 2020), Sekadau (August 22, 2020), and Bogor (September 23, 2020), where this extreme weather phenomenon occurred in the dry season. This study uses the ERA5 reanalysis model data, it aims to examine the vertical velocity impact on the hail occurrence in the dry season, as well as its relation to other weather parameters such as relative humidity, streamline, and wind velocity. Moreover, HCAI product satellite data is used as supporting data for the convective cloud development analysis. Based on the results of graphs, contours, and Hovmoller vertical cut from ERA5 modeling, the vertical velocity values in the 925 Mb-300 Mb layer in Sukabumi, Sekadau, and Bogor before the hail event ranged between -1.2-(-0.2), -1.5-(-0.2), -1-0 Pa/s. A negative value indicates that there is an upward motion from the air mass that trigger the convective cloud growth, which produces hail. It is evidenced by the presence of Cumulonimbus cloud on HCAI product when the hail falls. Therefore, the vertical velocity has significant effect on the hail event. In addition, the relative humidity in the 850-700 Mb layer is quite wet, which ranges from 80-90%. Meanwhile, the streamline and wind velocity in the three regions show the convergence with slowing wind velocity ranging from 2-4 knots. These results show that the upward motion of the vertical velocity is enough to form the wet atmospheric humidity and form a convergence for the growth of the convective cloud, which produce hail in the dry season.

Keywords: hail, extreme weather, vertical velocity, relative humidity, streamline

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Authors: Ali Naghshineh, Ashutosh Bagchi

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Performance-based seismic design concepts are increasingly being adopted in various jurisdictions. While the National Building Code of Canada (NBCC) is not fully performance-based, it provides some features of a performance-based code, such as displacement control and objective-based solutions. Performance evaluation is an important part of a performance-based design. In this paper, the seismic performance of a set of code-designed 4, 8 and 12 story moment resisting concrete frames located in Victoria, BC, in the western part of Canada at different hazard levels namely, SLE (Service Level Event), DLE (Design Level Event) and MCE (Maximum Considered Event) has been studied. The seismic performance of these buildings has been evaluated based on FEMA 356 and ATC 72 procedures, and the nonlinear time history analysis. Pushover analysis has been used to investigate the different performance levels of these buildings and adjust their design based on the corresponding target displacements. Since pushover analysis ignores the higher mode effects, nonlinear dynamic time history using a set of ground motion records has been performed. Different types of ground motion records, such as crustal and subduction earthquake records have been used for the dynamic analysis to determine their effects. Results obtained from push over analysis on inter-story drift, displacement, shear and overturning moment are compared to those from the dynamic analysis.

Keywords: seismic performance., performance-based design, concrete moment resisting frame, crustal earthquakes, subduction earthquakes

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Authors: Pedro Ferraz-Gameiro

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Introduction: The Pellegrini-Stieda lesion is the result of post-traumatic calcification and/or ossification on the medial collateral ligament (MCL) of the knee. When this calcification is accompanied by gonalgia and limitation of knee flexion, it is called Pellegrini-Stieda syndrome. The pathogenesis is probably the calcification of a post-traumatic hematoma at least three weeks after the initial trauma or secondary to repetitive microtrauma. On anteroposterior radiographs, a Pellegrini-Stieda lesion is a linear vertical ossification or calcification of the proximal portion of the MCL and usually near the medial femoral condyle. Patients with Pellegrini-Stieda syndrome present knee pain associated with loss of range of motion. The treatment is usually conservative with analgesic and anti-inflammatory drugs, either systemic or intra-articular. Physical medicine and rehabilitation techniques associated with shock wave therapy can be a way of reduction of pain/inflammation. Patients who maintain instability with significant limitation of knee mobility may require surgical excision. Methods: Research was done using PubMed central using the terms Pellegrini-Stieda syndrome. Discussion/conclusion: Medical treatment is the rule, with initial rest, anti-inflammatory, and physiotherapy. If left untreated, this ossification can potentially form a significant bone mass, which can compromise the range of motion of the knee. Physical medicine and rehabilitation techniques associated with shock wave therapy are a way of reduction of pain/inflammation.

Keywords: knee, Pellegrini-Stieda syndrome, rehabilitation, shock waves therapy

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Authors: B. Vadiraj, S. N. Omkar, B. Kapil Bharadwaj, Yash Vardhan Gupta

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During manned exploration of space, missions will require astronaut crewmembers to perform Extra Vehicular Activities (EVAs) for a variety of tasks. These EVAs take place after long periods of operations in space, and in and around unique vehicles, space structures and systems. Considering the remoteness and time spans in which these vehicles will operate, EVA system operations should utilize common worksites, tools and procedures as much as possible to increase the efficiency of training and proficiency in operations. All of the preparations need to be carried out based on studies of astronaut motions. Until now, development and training activities associated with the planned EVAs in Russian and U.S. space programs have relied almost exclusively on physical simulators. These experimental tests are expensive and time consuming. During the past few years a strong increase has been observed in the use of computer simulations due to the fast developments in computer hardware and simulation software. Based on this idea, an effort to develop a computational simulation system to model human dynamic motion for EVA is initiated. This study focuses on the simulation of an astronaut moving the orbital replaceable units into the worksites or removing them from the worksites. Our physics-based methodology helps fill the gap in quantitative analysis of astronaut EVA by providing a multisegment human arm model. Simulation work described in the study improves on the realism of previous efforts, incorporating joint stops to account for the physiological limits of range of motion. To demonstrate the utility of this approach human arm model is simulated virtually using ADAMS/LifeMOD® software. Kinematic mechanism for the astronaut’s task is studied from joint angles and torques. Simulation results obtained is validated with numerical simulation based on the principles of Newton-Euler method. Torques determined using mathematical model are compared among the subjects to know the grace and consistency of the task performed. We conclude that due to uncertain nature of exploration-class EVA, a virtual model developed using multibody dynamics approach offers significant advantages over traditional human modeling approaches.

Keywords: extra vehicular activity, biomechanics, inverse kinematics, human body modeling

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Authors: Vemula Amalakrishna, S. Pushpavanam

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Change and motion characterize and persistently reshape the world around us, on scales from molecular to global. The subtle interplay between change (Reaction) and motion (Diffusion) gives rise to an astonishing intricate spatial or temporal pattern. These pattern formation in nature has been intellectually appealing for many scientists since antiquity. Periodic precipitation patterns, also known as Liesegang patterns (LP), are one of the stimulating examples of such self-assembling reaction-diffusion (RD) systems. LP formation has a great potential in micro and nanotechnology. So far, the research on LPs has been concentrated mostly on how these patterns are forming, retrieving information to build a universal mathematical model for them. Researchers have developed various theoretical models to comprehensively construct the geometrical diversity of LPs. To the best of our knowledge, simulation studies of LPs assume an arbitrary value of RD parameters to explain experimental observation qualitatively. In this work, existing models were studied to understand the mechanism behind this phenomenon and challenges pertaining to models were understood and explained. These models are not computationally effective due to the presence of discontinuous precipitation rate in RD equations. To overcome the computational challenges, smoothened Heaviside functions have been introduced, which downsizes the computational time as well. Experiments were performed using a conventional LP system (AgNO₃-K₂Cr₂O₇) to understand the effects of different gels and temperatures on formed LPs. The model is extended for real parameter values to compare the simulated results with experimental data for both 1-D (Cartesian test tubes) and 2-D(cylindrical and Petri dish).

Keywords: reaction-diffusion, spatio-temporal patterns, nucleation and growth, supersaturation

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Authors: Johns Paul, Santhosh J. Nalluveettil, P. Purushothaman, M. Premdas

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Lunar landing is one of the most critical phases of lunar mission. The lander is provided with a soft landing system to prevent structural damage of lunar module by absorbing the landing shock and also assure stability during landing. Presently available software are not capable to simulate the rigid body dynamics coupled with contact simulation and elastic/plastic deformation analysis. Hence a separate mathematical model has been generated for studying the dynamics of a typical lunar soft lander. Parameters used in the analysis includes lunar surface slope, coefficient of friction, initial touchdown velocity (vertical and horizontal), mass and moment of inertia of lander, crushing force due to energy absorbing material in the legs, number of legs and geometry of lander. The mathematical model is capable to simulate plastic and elastic deformation of honey comb, frictional force between landing leg and lunar soil, surface contact simulation, lunar gravitational force, rigid body dynamics and linkage dynamics of inverted tripod landing gear. The non linear differential equations generated for studying the dynamics of lunar lander is solved by numerical method. Matlab programme has been used as a computer tool for solving the numerical equations. The position of each kinematic joint is defined by mathematical equations for the generation of equation of motion. All hinged locations are defined by position vectors with respect to body fixed coordinate. The vehicle rigid body rotations and motions about body coordinate are only due to the external forces and moments arise from footpad reaction force due to impact, footpad frictional force and weight of vehicle. All these force are mathematically simulated for the generation of equation of motion. The validation of mathematical model is done by two different phases. First phase is the validation of plastic deformation of crushable elements by employing conservation of energy principle. The second phase is the validation of rigid body dynamics of model by simulating a lander model in ADAMS software after replacing the crushable elements to elastic spring element. Simulation of plastic deformation along with rigid body dynamics and contact force cannot be modeled in ADAMS. Hence plastic element of primary strut is replaced with a spring element and analysis is carried out in ADAMS software. The same analysis is also carried out using the mathematical model where the simulation of honeycomb crushing is replaced by elastic spring deformation and compared the results with ADAMS analysis. The rotational motion of linkages and 6 degree of freedom motion of lunar Lander about its CG can be validated by ADAMS software by replacing crushing element to spring element. The model is also validated by the drop test results of 4 leg lunar lander. This paper presents the details of mathematical model generated and its validation.

Keywords: honeycomb, landing leg tripod, lunar lander, primary link, secondary link

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Authors: Nuralam Sam, Irawan Yusuf, Irfan Idris, Endi Adnan

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The most case in the shoulder in the the adult is the frozen shoulder. It make an uncomfortable sensation which disturbance daily activity. The studies of frozen shoulder are still limited. This study used a true experimental pre and post test design with a group design. The participant underwent dextrose prolotherapy injection in the rotator cuff, intraarticular glenohumeral joint, long head tendon biceps, and acromioclavicular joint injections with 15% dextrose, respectively, at week 2, week 4, and week 6. Participants were followed for 12 weeks. The specific biomarker MMP and TIMP, ROM, DASH score were measured at baseline, at week 6, and week 12. The data were analyzed by multivariate analysis (repeated measurement ANOVA, Paired T-Test, and Wilcoxon) to determine the effect of the intervention. The result showed a significant decrease in The Disability of the Arm, Shoulder, and Hand (DASH) score in prolo injection patients in each measurement week (p < 0.05). While the measurement of Range of Motion (ROM), each direction of shoulder motion showed a significant difference in average each week, from week 0 to week 6 (p <0.05).Dextrose prolotherapy injection results give a significant improvement in functional outcome of the shoulder joint, and ROMand did not show significant results in assessing the specific biomarker, MMP-1, and TIMP-1 in tissue repair. This study suggestion an alternative to the use of injection prolotherapy in Frozen shoulder patients, which has fewer side effects and better effectiveness than the use of corticosteroid injections.

Keywords: frozen shoulder, ROM, DASH score, prolotherapy, MMP-1, TIMP-1

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Authors: Francys Souza, Alberto Ohashi, Dorival Leao

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We present a general solution for finding the ε-optimal controls for non-Markovian stochastic systems as stochastic differential equations driven by Brownian motion, which is a problem recognized as a difficult solution. The contribution appears in the development of mathematical tools to deal with modeling and control of non-Markovian systems, whose applicability in different areas is well known. The methodology used consists to discretize the problem through a random discretization. In this way, we transform an infinite dimensional problem in a finite dimensional, thereafter we use measurable selection arguments, to find a control on an explicit form for the discretized problem. Then, we prove the control found for the discretized problem is a ε-optimal control for the original problem. Our theory provides a concrete description of a rather general class, among the principals, we can highlight financial problems such as portfolio control, hedging, super-hedging, pairs-trading and others. Therefore, our main contribution is the development of a tool to explicitly the ε-optimal control for non-Markovian stochastic systems. The pathwise analysis was made through a random discretization jointly with measurable selection arguments, has provided us with a structure to transform an infinite dimensional problem into a finite dimensional. The theory is applied to stochastic control problems based on path-dependent stochastic differential equations, where both drift and diffusion components are controlled. We are able to explicitly show optimal control with our method.

Keywords: dynamic programming equation, optimal control, stochastic control, stochastic differential equation

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Authors: Shreya Sara Ittycheria, K. C. Sivakumar, Shijulal Nelson Sathi, Priya Srinivas

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hCG, a heterodimer composed of α and β subunits, is a peptide hormone having numerous biological functions. Although hCG is expressed by placenta during pregnancy, ectopic β-hCG secretion is observed in many non-trophoblastic tumors including that of breast. In-vitro and in-vivo studies done in the lab, have proved that BRCA1 defective cancers express β-hCG and when β-hCG is expressed or supplemented, it promotes tumor progression and exhibits resistance to carboplatin and ABT888, in such cancers but not in BRCA1 wild type cancers. In cancer cells, instead of binding to its regular receptor, LH-CGR, β-hCG binds with Transforming Growth Factor Receptor 2 (TGFβRII) and phosphorylates it resulting in faster tumor progression through the Smad signaling pathway. Targeting β-hCG could be a potential therapeutic strategy for managing BRCA1 defective cancers. Here, molecular docking and dynamic simulation studies were done to identify potential small molecule inhibitors against β-hCG as there are currently no such inhibitors reported. The binding sites of TGFβRII on β-hCG were identified from the top 10 predicted complexes from Z Dock. Virtual screening of selected commercially available small molecules from various libraries such as ZINC, NCI and Life Chemicals amounting to a total of 50,025 molecules were done. Four potential small molecule inhibitors were identified, RgcbPs-1, RgcbPs-2, RgcbPs-3 and RgcbPs-4 with binding affinities -60.778 kcal/mol, -45.447 kcal/mol, -65.2268 kcal/mol and -82.040 kcal/mol respectively. Further, 100ns Molecular Dynamics (MD) simulation showed that these molecules form stable complexes with β-hCG. RgcbPs-1 maintains hydrogen bonds with Q54, L52, Q46, C100, G36, C57, C38 residues, RgcbPs-2 maintains hydrogen bonds with A83 residue, RgcbPs-3 maintains hydrogen bonds with C57, Y58, R94, G101 residues and RgcbPs-4 maintains hydrogen bonds with G36, C38, T40, C57, D99, C100, G101 and L104 residues of β-hCG all of which coincide with the TGFβRII binding site on β-hCG. These results show that these two inhibitors could be used either singly or in combination for inhibiting β-hCG from binding to TGFβRII and thereby directly inhibiting the tumorigenesis pathway.

Keywords: β-hCG, breast cancer, dynamic simulations, molecular docking, small molecule inhibitors, virtual screening.

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Authors: Saule Balmagambetova, Zhenisgul Tlegenova, Saule Madinova

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Cardiotoxicity associated with anticancer treatment, now defined as cancer therapy-related cardiac dysfunction (CTRCD), accompanies cancer patients and negatively impacts their survivorship. Currently, a cardio-oncological service is being created in Kazakhstan based on the provisions of the European Society of Cardio-oncology (ESC) Guidelines. In the frames of a pilot project, a cohort study on CTRCD conditions was initiated at the Aktobe Cancer center. One hundred twenty-eight newly diagnosed breast cancer patients started on doxorubicin and/or trastuzumab were recruited. Echocardiography with global longitudinal strain (GLS) assessment, biomarkers panel (cardiac troponin (cTnI), brain natriuretic peptide (BNP), myeloperoxidase (MPO), galectin-3 (Gal-3), D-dimers, C-reactive protein (CRP)), and other tests were performed at baseline and every three months. Patients were stratified by the cardiovascular risks according to the ESC recommendations and allocated into the risk groups during the pre-treatment visit. Of them, 10 (7.8%) patients were assigned to the high-risk group, 48 (37.5%) to the medium-risk group, and 70 (54.7%) to the low-risk group, respectively. High-risk patients have been receiving their cardioprotective treatment from the outset. Patients were also divided by treatment - in the anthracycline-based 83 (64.8%), in trastuzumab- only 13 (10.2%), and in the mixed anthracycline/trastuzumab group 32 individuals (25%), respectively. Mild symptomatic CTRCD was revealed and treated in 2 (1.6%) participants, and a mild asymptomatic variant in 26 (20.5%). Mild asymptomatic conditions are defined as left ventricular ejection fraction (LVEF) ≥50% and further relative reduction in GLS by >15% from baseline and/or a further rise in cardiac biomarkers. The listed biomarkers were assessed longitudinally in repeated-measures linear regression models during 12 months of observation. The associations between changes in biomarkers and CTRCD and between changes in biomarkers and LVEF were evaluated. Analysis by risk groups revealed statistically significant differences in baseline LVEF scores (p 0.001), BNP (p 0.0075), and Gal-3 (p 0.0073). Treatment groups found no statistically significant differences at baseline. After 12 months of follow-up, only LVEF values showed a statistically significant difference by risk groups (p 0.0011). When assessing the temporal changes in the studied parameters for all treatment groups, there were statistically significant changes from visit to visit for LVEF (p 0.003); GLS (p 0.0001); BNP (p<0.00001); MPO (p<0.0001); and Gal-3 (p<0.0001). No moderate or strong correlations were found between the biomarkers values and LVEF, between biomarkers and GLS. Between the biomarkers themselves, a moderate, close to strong correlation was established between cTnI and D-dimer (r 0.65, p<0.05). The dose-dependent effect of anthracyclines has been confirmed: the summary dose has a moderate negative impact on GLS values: -r 0.31 for all treatment groups (p<0.05). The present study found myeloperoxidase as a promising biomarker of cardiac dysfunction in the mixed anthracycline/trastuzumab treatment group. The hazard of CTRCD increased by 24% (HR 1.21; 95% CI 1.01;1.73) per doubling in baseline MPO value (p 0.041). Increases in BNP were also associated with CTRCD (HR per doubling, 1.22; 95% CI 1.12;1.69). No cases of chemotherapy discontinuation due to cardiotoxic complications have been recorded. Further observations are needed to gain insight into the ability of biomarkers to predict CTRCD onset.

Keywords: breast cancer, chemotherapy, cardiotoxicity, Kazakhstan

Procedia PDF Downloads 86

Authors: Grzegorz Swiderski, Agata Jablonska-Trypuc, Natalia Popow, Renata Swislocka, Wlodzimierz Lewandowski

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Doxorubicin belongs to the group of anthracycline antitumor antibiotics. Because of the wide spectrum of actions, it is one of the most widely used anthracycline antibiotics, including the treatment of breast, ovary, bladder, lung cancers as well as neuroblastoma, lymphoma, leukemia and myeloid leukemia. Antitumor activity of doxorubicin is based on the same mechanisms as for most anthracyclines. Like the metal ions affect the nucleic acids on many biological processes, so the environment of the metal chelates of antibiotics can have a significant effect on the pharmacological properties of drugs. Complexation of anthracyclines with metal ions may contribute to the production of less toxic compounds. In the framework of this study, the composition of complexes obtained in aqueous solutions of doxorubicin with metal ions (Cu2+ and Zn2+). Complexation was analyzed by spectrophotometric titration in aqueous solution at pH 7.0. The pH was adjusted with 0.02M Tris-HCl buffer. The composition of the complexes found was Cu: doxorubicin (1: 2) and a Zn: doxorubicin (1: 1). The effect of Dox, Dox-Cu and Dox-Zn was examined in MCF-7 breast cancer cell line, which were obtained from American Type Culture Collection (ATCC). The compounds were added to the cultured cells for a final concentration in the range of 0,01µM to 0,5µM. The number of MCF-7 cells with division into living and dead, was determined by direct counts of cells with the use of trypan blue dye using LUNA Logos Biosystems cell counter. ApoTox-Glo Triplex Assay (Promega, Madison, Wisconsin, USA) was used according to the manufacturer’s instructions to measure the MCF-7 cells’ viability, cytotoxicity and apoptosis. We observed a decrease in cells proliferation in a dose-dependent manner. An increase in cytotoxicity and decrease in viability in the ApoTox Triplex assay was also showed for all tested compounds. Apoptosis, showed as caspase 3/7 activation, was observed only in Dox treatment. In Dox-Zn and Dox-Cu caspase 3/7 activation was not observed. This work was financially supported by National Science Centre, Poland, under the research project number 2014/13/B/NZ7/02 352.

Keywords: anticancer properties, anthracycline antibiotic, doxorubicine, metal complexes

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Authors: M. V. Belubekyan, S. R. Martirosyan

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On the example of an elastic rectangular plate streamlined by a supersonic gas flow, we have investigated the phenomenon of divergence and of panel flatter of the overrunning of the gas flow at a free edge under assumption of the presence of concentrated inertial masses and moments at the free edge. We applied a new approach of finding of solution of these problems, which was developed based on the algorithm for an analytical solution finding. This algorithm is easy to use for theoretical studies for the wides circle of nonconservative problems of linear elastic stability. We have established the relation between the characteristics of natural vibrations of the plate and velocity of the streamlining gas flow, which enables one to draw some conclusions on the stability of disturbed motion of the plate depending on the parameters of the system plate-flow. Its solution shows that either the divergence or the localized divergence and the flutter instability are possible. The regions of the stability and instability in space of parameters of the problem are identified. We have investigated the dynamic behavior of the disturbed motion of the panel near the boundaries of region of the stability. The safe and dangerous boundaries of region of the stability are found. The transition through safe boundary of the region of the stability leads to the divergence or localized divergence arising in the vicinity of free edge of the rectangular plate. The transition through dangerous boundary of the region of the stability leads to the panel flutter. The deformations arising at the flutter are more dangerous to the skin of the modern aircrafts and rockets resulting to the loss of the strength and appearance of the fatigue cracks.

Keywords: stability, elastic plate, divergence, localized divergence, supersonic panels flutter

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Authors: Barenten Suciu

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Classical matrix calculus and Routh-Hurwitz stability conditions, applied to the snake-like motion of the conical wheel axle, lead to the conclusion that the hunting mode is inherently unstable, and its natural frequency is a complex number. In order to analytically solve such a complicated vibration model, either the inertia terms were neglected, in the model designated as geometrical, or restrictions on the creep coefficients and yawing diameter were imposed, in the so-called dynamical model. Here, an alternative solution is proposed to solve the hunting mode, based on the observation that the bullet train wheel axle is equipped with cylindrical wheels. One argues that for such wheel treads, the geometrical hunting is irrelevant, since its natural frequency becomes nil, but the dynamical hunting is significant since its natural frequency reduces to a real number. Moreover, one illustrates that the geometrical simplification of the wheel causes the stabilization of the hunting mode, since the characteristic quartic equation, derived for conical wheels, reduces to a quadratic equation of positive coefficients, for cylindrical wheels. Quite simple analytical expressions for the damping ratio and natural frequency are obtained, without applying restrictions into the model of contact. Graphs of the time-depending hunting lateral perturbation, including the maximal and inflexion points, are presented both for the critically-damped and the over-damped wheel axles.

Keywords: bullet train, creep, cylindrical wheels, damping, dynamical hunting, stability, vibration analysis

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Authors: Engi E. I. Sarhan, Usama M. Rashad, Ibrahim M. I. Hamoda, Mohammed K. Mohamed

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Background: This study aimed to know the effect of nitrogen-based cryotherapy on the spasticity of calf muscle in stroke patients. Patients were selected from the outpatient clinic of Neurology, Al-Mansoura general hospital, Al-Mansoura University. Subjects and methods: Thirty Stroke Patients of both sexes ranged from 45 to 60 years old were divided randomly into two equal groups, a study group (A) received a nitrogen-based cryotherapy, a selective physical therapy program and ankle foot orthosis (AFO), while as patients in control group (B) received the same program and AFO only. The treatment duration was three times per week for four weeks for both groups. We assessed spasticity of calf muscle before and after treatment subjectively using modified Ashworth scale (MAS) and objectively via measuring H / M ratio on electromyography machine. We also assessed ankle dorsiflexion ROM objectively using two dimensions motion analysis (2D). Results: After treatment, there was a highly significant improvement in the study group compared to the control group regarding the score of MAS, no significant difference in the study group compared to the control group regarding the readings of H / M ratio, highly significant improvement in the study group compared to the control group regarding the 2D motion analysis findings. Conclusion: This modality considers effective in reducing spasticity in the calf muscle and improving ankle dorsiflexion of the affected limb.

Keywords: ankle foot orthosis, nitrogen-based cryotherapy, stroke, spasticity

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Authors: Khaled Hamdan, Abid Amorri, Fatima Hamdan

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Involving students in English language learning process and achieving an adequate English language proficiency in the target language can be a great challenge for both teachers and students. This can prove even a far greater challenge to engage students with special needs (Dyslexia) if they have physical impairment and inadequate mastery of basic communicative language competence/proficiency in the target language. From this perspective, technology like robots can probably be used to enhance learning process for the special needs students who have extensive communication needs, who face continuous struggle to interact with their peers and teachers and meet academic requirements. Robots, precisely NAO, can probably provide them with the perfect opportunity to practice social and communication skills, and meet their English academic requirements. This research paper aims to identify to what extent robots can be used to improve students’ social interaction and communication skills and to understand the potential for robotics-based education in motivating and engaging UAEU dyslexic students to meet university requirements. To reach this end, the paper will explore several factors that come into play – Motion Level-involving cognitive activities, Interaction Level-involving language processing, Behavior Level -establishing a close relationship with the robot and Appraisal Level- focusing on dyslexia students’ achievement in the target language.

Keywords: dyslexia, robot technology, motion, interaction, behavior and appraisal levels, social and communication skills

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Authors: Mohammad R. Jalali

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Movement of liquid with a free surface in a container is known as slosh. For instance, slosh occurs when water in a closed tank is set in motion by a free surface displacement, or when liquid natural gas in a container is vibrated by an external driving force, such as an earthquake or movement induced by transport. Slosh is also derived from resonant switching of a natural basin. During sloshing, different types of motion are produced by energy exchange between the liquid and its container. In present study, a numerical model is developed to simulate the nonlinear even harmonic oscillations of free surface sloshing of an initial disturbance to the free surface of a liquid in a closed square basin. The response of the liquid free surface is affected by amplitude and motion frequencies of its container; therefore, sloshing involves complex fluid-structure interactions. In the present study, nonlinear interaction of free surface sloshing of an initial Gaussian hump with its uneven container is predicted numerically. For this purpose, Green-Naghdi (GN) equations are applied as governing equation of fluid field to produce nonlinear second-order and higher-order wave interactions. These equations reduce the dimensions from three to two, yielding equations that can be solved efficiently. The GN approach assumes a particular flow kinematic structure in the vertical direction for shallow and deep-water problems. The fluid velocity profile is finite sum of coefficients depending on space and time multiplied by a weighting function. It should be noted that in GN theory, the flow is rotational. In this study, GN numerical simulations of initial Gaussian hump are compared with Fourier series semi-analytical solutions of the linearized shallow water equations. The comparison reveals that satisfactory agreement exists between the numerical simulation and the analytical solution of the overall free surface sloshing patterns. The resonant free surface motions driven by an initial Gaussian disturbance are obtained by Fast Fourier Transform (FFT) of the free surface elevation time history components. Numerically predicted velocity vectors and magnitude contours for the free surface patterns indicate that interaction of Gaussian hump with its container has localized effect. The result of this sloshing is applicable to the design of stable liquefied oil containers in tankers and offshore platforms.

Keywords: fluid-structure interactions, free surface sloshing, Gaussian hump, Green-Naghdi equations, numerical predictions

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Authors: J. Chamorro-Servent, S. Tassani, M. A. Gonzalez-Ballester, L. J. Roca, J. Romeu, O. Camara

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Electromagnetic and microwave imaging (MWI) have been used in medical imaging in the last years, being the most common applications of breast cancer and stroke detection or monitoring. In those applications, the subject or zone to observe is surrounded by a number of antennas, and the Nyquist criterium can be satisfied. Additionally, the space between the antennas (transmitting and receiving the electromagnetic fields) and the zone to study can be prepared in a homogeneous scenario. However, this may differ in other cases as could be intracardiac catheters, stomach monitoring devices, pelvic organ systems, liver ablation monitoring devices, or uterine fibroids’ ablation systems. In this work, we analyzed different MWI algorithms to find the most suitable method for dealing with an intrabody scenario. Due to the space limitations usually confronted on those applications, the device would have a cylindrical configuration of a maximum of eight transmitters and eight receiver antennas. This together with the positioning of the supposed device inside a body tract impose additional constraints in order to choose a reconstruction method; for instance, it inhabitants the use of well-known algorithms such as filtered backpropagation for diffraction tomography (due to the unusual configuration with probes enclosed by the imaging region). Finally, the difficulty of simulating a realistic non-homogeneous background inside the body (due to the incomplete knowledge of the dielectric properties of other tissues between the antennas’ position and the zone to observe), also prevents the use of Born and Rytov algorithms due to their limitations with a heterogeneous background. Instead, we decided to use a time-reversed algorithm (mostly used in geophysics) due to its characteristics of ignoring heterogeneities in the background medium, and of focusing its generated field onto the scatters. Therefore, a 2D time-reversed finite difference time domain was developed based on the time-reversed approach for microwave breast cancer detection. Simultaneously an in-silico testbed was also developed to compare ground-truth dielectric properties with corresponding microwave imaging reconstruction. Forward and inverse problems were computed varying: the frequency used related to a small zone to observe (7, 7.5 and 8 GHz); a small polyp diameter (5, 7 and 10 mm); two polyp positions with respect to the closest antenna (aligned or disaligned); and the (transmitters-to-receivers) antenna combination used for the reconstruction (1-1, 8-1, 8-8 or 8-3). Results indicate that when using the existent time-reversed method for breast cancer here for the different combinations of transmitters and receivers, we found false positives due to the high degrees of freedom and unusual configuration (and the possible violation of Nyquist criterium). Those false positives founded in 8-1 and 8-8 combinations, highly reduced with the 1-1 and 8-3 combination, being the 8-3 configuration de most suitable (three neighboring receivers at each time). The 8-3 configuration creates a region-of-interest reduced problem, decreasing the ill-posedness of the inverse problem. To conclude, the proposed algorithm solves the main limitations of the described intrabody application, successfully detecting the angular position of targets inside the body tract.

Keywords: FDTD, time-reversed, medical imaging, microwave imaging

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Authors: Jason R. King, Hugh H. T. Liu

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This research presents simulation and experimental work in the visual servoing of a quadrotor Unmanned Aerial Vehicle (UAV) to stabilize overtop of a moving target. Most previous work in the field assumes static or slow-moving, unpredictable targets. In this experiment, the target is assumed to be a friendly ground robot moving freely on a horizontal plane, which shares information with the UAV. This information includes velocity and acceleration information of the ground target to aid the quadrotor in its tracking task. The quadrotor is assumed to have a downward-facing camera which is fixed to the frame of the quadrotor. Only onboard sensing for the quadrotor is utilized for the experiment, with a VICON motion capture system in place used only to measure ground truth and evaluate the performance of the controller. The experimental platform consists of an ArDrone 2.0 and a Create Roomba, communicating using Robot Operating System (ROS). The addition of the target’s information is demonstrated to help the quadrotor in its tracking task using simulations of the dynamic model of a quadrotor in Matlab Simulink. A nested PID control loop is utilized for inner-loop control the quadrotor, similar to previous works at the Flight Systems and Controls Laboratory (FSC) at the University of Toronto Institute for Aerospace Studies (UTIAS). Experiments are performed with ground truth provided by an indoor motion capture system, and the results are analyzed. It is demonstrated that a velocity controller which incorporates the additional information is able to perform better than the controllers which do not have access to the target’s information.

Keywords: quadrotor, target tracking, unmanned aerial vehicle, UAV, UAS, visual servoing

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Authors: Supriya Manikrao Ovhal

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In India, the summer monsoon rainfall occurs owing to large scale convection with reference to continental ITCZ. It was found that convection over tropical ocean increases with SST from 26 to 28 degree C, and when SST is above 29 degree C, it sharply decreases for warm pool areas of Indian and for monsoon areas of West Pacific Ocean. The reduction in convection can be influenced by large scale subsidence forced by nearby or remotely generated deep convection, thus it was observed that under the influence of strong large scale rising motion, convection does not decreases but increases monotonically with SST even if SST value is higher than 29.5 degree C. Since convection is related to SST gradient, that helps to generate low level moisture convergence and upward vertical motion in the atmosphere. Strong wind fields like cross equatorial low level jet stream on equator ward side of the warm pool are produced due to convection initiated by SST gradient. Areas having maximum SST have low SST gradient, and that result in feeble convection. Hence it is imperative to mention that the oceanic role (other than SST) could be prominent in influencing large Scale Atmospheric convection. Since warm oceanic surface somewhere or the other contributes to penetrate the heat radiation to the subsurface of the ocean, and as there is no studies seen related to oceanic subsurface role in large Scale Atmospheric convection, in the present study, we are concentrating on the oceanic subsurface contribution in large Scale Atmospheric convection by considering the SST gradient, mixed layer depth (MLD), thermocline, barrier layer. The present study examines the probable role of subsurface ocean parameters in influencing convection.

Keywords: sst, d20, olr, wind

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Authors: Muhammad Asif Syed, Mirza Amir Baig

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Background: Pakistan is one of the two remaining polio-endemic countries, posing a significant public health challenge for global polio eradication due to failure to interrupt polio transmission. Country specific seroprevalence studies help in the evaluation of immunization program performance, the susceptibility of population against polio virus and identification of existing level of immunity with factors that affect seroconversion of the oral polio vaccine (OPV). The objective of the study was to find out factors associated with seroconversion of the OPV among children 6-59 months in Pakistan. Methods: A Hospital based cross-sectional serosurvey was undertaken in May-June 2015 at District Mirpurkhas, Sindh-Pakistan. Total 180 children aged 6–59 months were selected by using systematic random sampling from Muhammad Medical College Hospital, Mirpurkhas. Demographic, vaccination history and risk factors information were collected from the parents/guardian. Blood sample was collected and tested for the detection of poliovirus IgG antibodies by using ELISA Kit. The IgG titer <10 IU/ml, 50 to <150 IU/ml and >150 IU/ml was defined as negative, weak positive and positive immunity respectively. Pearson Chi-square test was used to determine the difference in seroprevalence in univariate analysis. Results: A total of 180 subjects were enrolled mean age was 23 months (7 -59 months). Off these 160 (89%) children were well and 18 (10%) partially protected against polio virus. Two (1.1%) children had no protection against polio virus as they had <10 IU/ml poliovirus IgG antibodies titer. Both negative cases belong from the female gender, age group 12-23 months, urban area and BMI <50 percentile. There was a difference between normal and the wasting children; it did attain statistical significance (χ2= 35.5, p=0.00). The difference in seroconversion was also observed in relation to the gender (χ2=6.23, p=0.04), duration of breast feeding (χ2=18.6, p=0.04), history of diarrheal disease before polio vaccine administration (χ2=7.7, p=0.02), and stunting (χ2= 114, p=0.00). Conclusion: This study demonstrated that near 90% children achieve seroconversion of OPV and well protected against polio virus. There is an urgent need to focus on factors like duration of breast feeding, diarrheal diseases and malnutrition (acute and chronic) among the children as an immunization strategy.

Keywords: seroconversion, oral polio vaccine, Polio, Pakistan

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Authors: Mark-Adam Kellerman

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Proteins are capable of exploring vast mutational spaces. This makes it difficult for protein engineers to devise rational methods to improve stability and function via mutagenesis. Deciding which residues to mutate requires knowledge of the characteristics they elicit. We probed the characteristics of residues in granulocyte-colony stimulating factor (G-CSF) using a thermal melt (from 295K to 323K) to denature it in a 700 MHz Bruker spectrometer. These characteristics included dynamics, micro-environmental changes experienced/ induced during denaturing and structure-function relationships. 15N-1H HSQC experiments were performed at 2K increments along with this thermal melt. We observed that dynamic residues that also undergo a lot of change in their microenvironment were predominantly in unstructured regions. Moreover, we were able to identify four residues (G4, A6, T133 and Q134) that we class as high priority targets for mutagenesis, given that they all appear in both the top 10% of measures for environmental changes and dynamics (∑Δ and ∆PI). We were also able to probe these NMR observables and combine them with molecular dynamics (MD) to elucidate what appears to be an opening motion of G-CSFs binding site III. V48 appears to be pivotal to this opening motion, which also seemingly distorts the loop region between helices A and B. This observation is in agreement with previous findings that the conformation of this loop region becomes altered in an aggregation-prone state of G-CSF. Hence, we present here an approach to profile the characteristics of residues in order to highlight their potential as rational mutagenesis targets and their roles in important conformational changes. These findings present not only an opportunity to effectively make biobetters, but also open up the possibility to further understand epistasis and machine learn residue behaviours.

Keywords: protein engineering, rational mutagenesis, NMR, molecular dynamics

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Authors: Ikram Hussain, Fuzail Ahmad, Tawseef Ahmad Bhat

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Tennis serve is characterized as one of the most prominent techniques pertaining to the success of winning a point. The study was aimed to explore the contributions of the upper body kinematics on the tennis performance during Davis Cup (Oceania Group). Four Indian International tennis players who participated in the Davis Cup held at Indore, India were inducted as the subjects for this study, with mean age 27 ± 4.79 Years, mean weight 186 ± 6.03 cm, mean weight 81.25 ± 7.41kg, respectively. The tennis serve was bifurcated into three phases viz, preparatory phase, force generation phase and follow through phase. The kinematic data for the study was recorded through the high speed canon camcorder having a shuttle speed of 1/2000, at a frame rate of 50 Hz. The data was analysed with the motion analysis software. The descriptive statistics and F-test was employed through SPSS version 17.0 for the determination of the undertaken kinematic parameters of the study, and was computed at a 0.05 level of significance with 46 degrees of freedom. Mean, standard deviation and correlation coefficient also employed to find out the relationship among the upper body kinematic parameter and performance. In the preparatory phase, the analysis revealed that no significant difference exists among the kinematic parameters of the players on the performance. However, in force generation phase, wrist velocity (r= 0.47), torso velocity (r= -0.53), racket velocity r= 0.60), and in follow through phase, torso acceleration r= 0.43), elbow angle (r= -0.48) play a significant role on the performance of the tennis serve. Therefore, players should ponder upon the velocities of the above segments at the time of preparation for the competitions.

Keywords: Davis Cup, kinematics, motion analysis, tennis serve

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Authors: Md. S. Ansari, S. S. Motsa

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In this paper, an analysis has been made on the flow of non-Newtonian viscoelastic nanofluid over a linearly stretching sheet under the influence of uniform magnetic field. Heat transfer characteristics is analyzed taking into the effect of nonlinear radiation and non-uniform heat source/sink. Transport equations contain the simultaneous effects of Brownian motion and thermophoretic diffusion of nanoparticles. The relevant partial differential equations are non-dimensionalized and transformed into ordinary differential equations by using appropriate similarity transformations. The transformed, highly nonlinear, ordinary differential equations are solved by spectral local linearisation method. The numerical convergence, error and stability analysis of iteration schemes are presented. The effects of different controlling parameters, namely, radiation, space and temperature-dependent heat source/sink, Brownian motion, thermophoresis, viscoelastic, Lewis number and the magnetic force parameter on the flow field, heat transfer characteristics and nanoparticles concentration are examined. The present investigation has many industrial and engineering applications in the fields of coatings and suspensions, cooling of metallic plates, oils and grease, paper production, coal water or coal–oil slurries, heat exchangers’ technology, and materials’ processing and exploiting.

Keywords: magnetic field, nonlinear radiation, non-uniform heat source/sink, similar solution, spectral local linearisation method, Rosseland diffusion approximation

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Authors: Kamyar Kildashti, Rasoul Mirghaderi

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This paper describes the three-dimensional seismic performance assessment of a high-rise steel moment-frame setback tower, designed and detailed per the 2010 ASCE7, under multiple support excitations. The vulnerability analyses are conducted based on nonlinear history analyses under a set of multi-directional strong ground motion records which are scaled to design-based site-specific spectrum in accordance with ASCE41-13. Spatial variation of input motions between far distant supports of each part of the tower is considered by defining time lag. Plastic hinge monotonic and cyclic behavior for prequalified steel connections, panel zones, as well as steel columns is obtained from predefined values presented in TBI Guidelines, PEER/ATC72 and FEMA P440A to include stiffness and strength degradation. Inter-story drift ratios, residual drift ratios, as well as plastic hinge rotation demands under multiple support excitations, are compared to those obtained from uniform support excitations. Performance objectives based on acceptance criteria declared by TBI Guidelines are compared between uniform and multiple support excitations. The results demonstrate that input motion discrepancy results in detrimental effects on the local and global response of the tower.

Keywords: high-rise building, nonlinear time history analysis, multiple support excitation, performance-based design

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Authors: Navah Z. Ratzon, Shlomit Cohen, Sigal Portnoy

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This work focuses on posture and risk factors for the musculoskeletal disorder in guitarists, which constitutes the largest group of musicians today. The source of the problems experienced by these musicians is linked to physical, psychosocial and personal risk factors. These muscular problems are referred to as Playing Related Musculoskeletal Disorder (PRMD). There is not enough research that specifically studies guitar players, and to the extent of our knowledge, there is almost no reference to the characteristics of their movement patterns while they play. This is in spite of the high prevalence of PRMD in this population. Kinematic research may provide a basis for the development of a prevention plan for this population and their unique characteristics of playing patterns. The aim of the study was to investigate the correlation between risk factors for PRMD among guitar players and self-reporting of pain in the skeletal muscles, and specifically to test whether there are differences in the kinematics of the upper body while playing in a sitting or standing posture. Twenty-five guitarists, aged 18-35, participated in the study. The methods included a motion analysis using a motion capture system, anthropometric measurements and questionnaires relating to risk factors. The questionnaires used were the Standardized Nordic Questionnaire for the Analysis of Musculoskeletal Symptoms and the Demand Control Support Questionnaire, as well as a questionnaire of personal details. All of the study participants complained of musculoskeletal pain in the past year; the most frequent complaints being in the left wrist. Statistically significant correlations were found between biodemographic indices and reports of pain in the past year and the previous week. No significant correlations were found between the physical posture while playing and reports of pain among professional guitarists. However, a difference was found in several kinematic parameters between seated and standing playing postures. In a majority of the joints, the joint angles while playing in a seated position were more extreme than those during standing. This finding may suggest a higher risk for musculoskeletal disorder while playing in a seated position. In conclusion, the results of the present research highlight the prevalence of musculoskeletal problems in guitar players and its correlation with various risk factors. The finding supports the need for intervention in the form of prevention through identifying the risk factors and addressing them. Relating to the person, to their occupation and environment, which are the basis of proper occupational therapy, can help meet this need.

Keywords: body posture, motion tracking, PRMD, guitarists

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Authors: Shabadini Sampath, Jinglang Feng

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With huge kinetic energy, space debris poses a major threat to astronauts’ space activities and spacecraft in orbit if a collision happens. The active removal of space debris is required in order to avoid frequent collisions that would occur. In addition, the amount of space debris will increase uncontrollably, posing a threat to the safety of the entire space system. But the safe and reliable removal of large-scale space debris has been a huge challenge to date. While capturing and deorbiting space debris, the space manipulator has to achieve high control precision. However, due to uncertainties and unknown disturbances, there is difficulty in coordinating the control of the space manipulator. To address this challenge, this paper focuses on developing a robust and intelligent control algorithm that controls joint movement and restricts it on the sliding manifold by reducing uncertainties. A neural network adaptive sliding mode controller (NNASMC) is applied with the objective of finding the control law such that the joint motions of the space manipulator follow the given trajectory. A computed torque control (CTC) is an effective motion control strategy that is used in this paper for computing space manipulator arm torque to generate the required motion. Based on the Lyapunov stability theorem, the proposed intelligent controller NNASMC and CTC guarantees the robustness and global asymptotic stability of the closed-loop control system. Finally, the controllers used in the paper are modeled and simulated using MATLAB Simulink. The results are presented to prove the effectiveness of the proposed controller approach.

Keywords: GNC, active removal of space debris, AI controllers, MatLabSimulink

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Authors: Rakesh Kumar, A. K. Ghosh

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The paper presents the modeling of linear and nonlinear longitudinal aerodynamics using real flight data of Hansa-3 aircraft gathered at low and high angles of attack. The Neural-Gauss-Newton (NGN) method has been applied to model the linear and nonlinear longitudinal dynamics and estimate parameters from flight data. Unsteady aerodynamics due to flow separation at high angles of attack near stall has been included in the aerodynamic model using Kirchhoff’s quasi-steady stall model. NGN method is an algorithm that utilizes Feed Forward Neural Network (FFNN) and Gauss-Newton optimization to estimate the parameters and it does not require any a priori postulation of mathematical model or solving of equations of motion. NGN method was validated on real flight data generated at moderate angles of attack before application to the data at high angles of attack. The estimates obtained from compatible flight data using NGN method were validated by comparing with wind tunnel values and the maximum likelihood estimates. Validation was also carried out by comparing the response of measured motion variables with the response generated by using estimates a different control input. Next, NGN method was applied to real flight data generated by executing a well-designed quasi-steady stall maneuver. The results obtained in terms of stall characteristics and aerodynamic parameters were encouraging and reasonably accurate to establish NGN as a method for modeling nonlinear aerodynamics from real flight data at high angles of attack.

Keywords: parameter estimation, NGN method, linear and nonlinear, aerodynamic modeling

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Authors: Malsawmtluanga, J. Malsawma, R. P. Tiwari, V. K. Gahalaut

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North East India is seismically one of the six most active regions of the world. It is placed in Zone V, the highest zone in the seismic zonation of India. It lies at the junction of Himalayan arc to the north and the Burmese arc to the east. The region has witnessed at least 18 large earthquakes including two great earthquakes Shillong (1987, M=8.7) and the Assam Tibet border (1950, M=8.7).The prominent Chite fault lies at the heart of Aizawl, the capital of Mizoram state and this hilly city is the home to about 2 million people. Geologically the area is a part of the Indo-Burmese Wedge and is prone to natural and man-made disasters. Unplanned constructions and urban dwellings on a rapid scale have lead to numerous unsafe structures adversely affecting the ongoing development and welfare projects of the government and they pose a huge threat for earthquakes. Crustal deformation measurements using campaign mode GPS were undertaken across this fault. Campaign mode GPS data were acquired and were processed with GAMIT-GLOBK software. The study presents the current velocity estimates at all the sites in ITRF 2008 and also in the fixed Indian reference frame. The site motion showed that there appears to be no differential motion anywhere across the fault area, thus confirming presently the fault is neither accumulating strain nor slipping aseismically. From the geological and geomorphological evidence, supported by geodetic measurements, lack of historic earthquakes, the Chite fault favours aseismic behaviour in this part of the Indo Burmese Arc (IBA).

Keywords: Chite fault, crustal deformation, geodesy, GPS, IBA

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Authors: E. G. Karvelas, C. Liosis, A. Theodorakakos, T. E. Karakasidis

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Magnetic navigation of the drug inside the human vessels is a very important concept since the drug is delivered to the desired area. Consequently, the quantity of the drug required to reach therapeutic levels is being reduced while the drug concentration at targeted sites is increased. Magnetic navigation of drug agents can be achieved with the use of magnetic nanoparticles where anti-tumor agents are loaded on the surface of the nanoparticles. The magnetic field that is required to navigate the particles inside the human arteries is produced by a magnetic resonance imaging (MRI) device. The main factors which influence the efficiency of the usage of magnetic nanoparticles for biomedical applications in magnetic driving are the size and the magnetization of the biocompatible nanoparticles. In this study, a computational platform for the simulation of the optimal gradient magnetic fields for the navigation of magnetic nanoparticles inside a carotid artery is presented. For the propulsion model of the particles, seven major forces are considered, i.e., the magnetic force from MRIs main magnet static field as well as the magnetic field gradient force from the special propulsion gradient coils. The static field is responsible for the aggregation of nanoparticles, while the magnetic gradient contributes to the navigation of the agglomerates that are formed. Moreover, the contact forces among the aggregated nanoparticles and the wall and the Stokes drag force for each particle are considered, while only spherical particles are used in this study. In addition, gravitational forces due to gravity and the force due to buoyancy are included. Finally, Van der Walls force and Brownian motion are taken into account in the simulation. The OpenFoam platform is used for the calculation of the flow field and the uncoupled equations of particles' motion. To verify the optimal gradient magnetic fields, a covariance matrix adaptation evolution strategy (CMAES) is used in order to navigate the particles into the desired area. A desired trajectory is inserted into the computational geometry, which the particles are going to be navigated in. Initially, the CMAES optimization strategy provides the OpenFOAM program with random values of the gradient magnetic field. At the end of each simulation, the computational platform evaluates the distance between the particles and the desired trajectory. The present model can simulate the motion of particles when they are navigated by the magnetic field that is produced by the MRI device. Under the influence of fluid flow, the model investigates the effect of different gradient magnetic fields in order to minimize the distance of particles from the desired trajectory. In addition, the platform can navigate the particles into the desired trajectory with an efficiency between 80-90%. On the other hand, a small number of particles are stuck to the walls and remains there for the rest of the simulation.

Keywords: artery, drug, nanoparticles, navigation

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Authors: Jaco Oosthuizen, Nerina C. Van Der Merwe

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The National Health Laboratory Services in Bloemfontien has been the diagnostic testing facility for 1830 patients for familial breast cancer since 1997. From the cohort, 540 were comprehensively screened using High-Resolution Melting Analysis or Next Generation Sequencing for the presence of point mutations and/or indels. Approximately 90% of these patients stil remain undiagnosed as they are BRCA1/2 negative. Multiplex ligation-dependent probe amplification was initially added to screen for copy number variation detection, but with the introduction of next generation sequencing in 2017, was substituted and is currently used as a confirmation assay. The aim was to investigate the viability of utilizing internationally designed copy number variation detection assays based on mostly European/Caucasian genomic data for use within a South African context. The multiplex ligation-dependent probe amplification technique is based on the hybridization and subsequent ligation of multiple probes to a targeted exon. The ligated probes are amplified using conventional polymerase chain reaction, followed by fragment analysis by means of capillary electrophoresis. The experimental design of the assay was performed according to the guidelines of MRC-Holland. For BRCA1 (P002-D1) and BRCA2 (P045-B3), both multiplex assays were validated, and results were confirmed using a secondary probe set for each gene. The next generation sequencing technique is based on target amplification via multiplex polymerase chain reaction, where after the amplicons are sequenced parallel on a semiconductor chip. Amplified read counts are visualized as relative copy numbers to determine the median of the absolute values of all pairwise differences. Various experimental parameters such as DNA quality, quantity, and signal intensity or read depth were verified using positive and negative patients previously tested internationally. DNA quality and quantity proved to be the critical factors during the verification of both assays. The quantity influenced the relative copy number frequency directly whereas the quality of the DNA and its salt concentration influenced denaturation consistency in both assays. Multiplex ligation-dependent probe amplification produced false positives due to ligation failure when ligation was inhibited due to a variant present within the ligation site. Next generation sequencing produced false positives due to read dropout when primer sequences did not meet optimal multiplex binding kinetics due to population variants in the primer binding site. The analytical sensitivity and specificity for the South African population have been proven. Verification resulted in repeatable reactions with regards to the detection of relative copy number differences. Both multiplex ligation-dependent probe amplification and next generation sequencing multiplex panels need to be optimized to accommodate South African polymorphisms present within the genetically diverse ethnic groups to reduce the false copy number variation positive rate and increase performance efficiency.

Keywords: familial breast cancer, multiplex ligation-dependent probe amplification, next generation sequencing, South Africa

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