Search results for: single and multi-objective function
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 9194

Search results for: single and multi-objective function

7424 Estimation of Natural Pozzolan Reserves in the Volcanic Province of the Moroccan Middle Atlas Using a Geographic Information System in Order to Valorize Them

Authors: Brahim Balizi, Ayoub Aziz, Abdelilah Bellil, Abdellali El Khadiri, Jamal Mabrouki

Abstract:

Mio-polio-quaternary volcanism of the Tabular Middle Atlas, which corresponds to prospective levels of exploitable usable raw minerals, is a feature of Morocco's Middle Atlas, especially the Azrou-Timahdite region. Given their importance in national policy in terms of human development by supporting the sociological and economic component, this area has consequently been the focus of various research and prospecting of these levels in order to develop these reserves. The outcome of this labor is a massive amount of data that needs to be managed appropriately because it comes from multiple sources and formats, including side points, contour lines, geology, hydrogeology, hydrology, geological and topographical maps, satellite photos, and more. In this regard, putting in place a Geographic Information System (GIS) is essential to be able to offer a side plan that makes it possible to see the most recent topography of the area being exploited, to compute the volume of exploitation that occurs every day, and to make decisions with the fewest possible restrictions in order to use the reserves for the realization of ecological light mortars The three sites' mining will follow the contour lines in five steps that are six meters high and decline. It is anticipated that each quarry produces about 90,000 m3/year. For a single quarry, this translates to a daily production of about 450 m3 (200 days/year). About 3,540,240 m3 and 10,620,720 m3, respectively, represent the possible net exploitable volume in place for a single quarry and the three exploitable zones.

Keywords: GIS, topography, exploitation, quarrying, lightweight mortar

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7423 Opacity Synthesis with Orwellian Observers

Authors: Moez Yeddes

Abstract:

The property of opacity is widely used in the formal verification of security in computer systems and protocols. Opacity is a general language-theoretic scheme of many security properties of systems. Opacity is parametrized with framework in which several security properties of a system can be expressed. A secret behaviour of a system is opaque if a passive attacker can never deduce its occurrence from the system observation. Instead of considering the case of static observability where the set of observable events is fixed off-line or dynamic observability where the set of observable events changes over time depending on the history of the trace, we introduce Orwellian partial observability where unobservable events are not revealed provided that downgrading events never occurs in the future of the trace. Orwellian partial observability is needed to model intransitive information flow. This Orwellian observability is knwon as ipurge function. We show in previous work how to verify opacity for regular secret is opaque for a regular language L w.r.t. an Orwellian projection is PSPACE-complete while it has been proved undecidable even for a regular language L w.r.t. a general Orwellian observation function. In this paper, we address two problems of opacification of a regular secret ϕ for a regular language L w.r.t. an Orwellian projection: Given L and a secret ϕ ∈ L, the first problem consist to compute some minimal regular super-language M of L, if it exists, such that ϕ is opaque for M and the second consists to compute the supremal sub-language M′ of L such that ϕ is opaque for M′. We derive both language-theoretic characterizations and algorithms to solve these two dual problems.

Keywords: security policies, opacity, formal verification, orwellian observation

Procedia PDF Downloads 226
7422 Comparison of Microleakage of Composite Restorations Using Fifth and Seventh Generation of Bonding Agents

Authors: Karina Nabilla, Dedi Sumantri, Nurul T. Rizal, Siti H. Yavitha

Abstract:

Background: Composite resin is the most frequently used material for restoring teeth, but still failure cases are seen which leading to microleakage. Microleakage might be attributed to various factors, one of them is bonding agent. Various generations of bonding agents have been introduced to overcome the microleakage. The aim of this study was to evaluate the microleakage of composite restorations using the fifth and seventh bonding agent. Methods: Class I cavities (3X2X2 mm) were prepared on the occlusal surfaces of 32 human upper premolars. Teeth were classified into two groups according to the type of bonding agent used (n =16). Group I: Fifth Generation of Bonding Agent-Adper Single Bond2. Group II: Seventh Generation of Bonding Agent-Single Bond Universal. All cavities were restored with Filtek Z250 XT composite resin, stored in sterile aquades water at 370C for 24 h. The root apices were sealed with sticky wax, and all the surfaces, except for 2 mm from the margins, were coated with nail varnish. The teeth were immersed in a 1% methylene blue dye solution for 24 h, and then rinsed in running water, blot-dried and sectioned longitudinally through the center of restorations from the buccal to palatal surface. The sections were blindly assessed for microleakage of dye penetration by using a stereomicroscope. Dye penetration along margin was measured in µm then calculated into the percentage and classified into scoring system 1 to 3. Data were collected and statistically analyzed by Chi-Square test. Result: There was no significant difference (p > 0,05) between two groups. Conclusion: Fifth generation of bonding agent revealed less leakage compared to the seventh generation even statistically there was no significant difference.

Keywords: composite restoration, fifth generation of bonding agent, microleakage, seventh generation of bonding agent

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7421 Selective Solvent Extraction of Co from Ni and Mn through Outer-Sphere Interactions

Authors: Korban Oosthuizen, Robert C. Luckay

Abstract:

Due to the growing popularity of electric vehicles and the importance of cobalt as part of the cathode material for lithium-ion batteries, demand for this metal is on the rise. Recycling of the cathode materials by means of solvent extraction is an attractive means of recovering cobalt and easing the pressure on limited natural resources. In this study, a series of straight chain and macrocyclic diamine ligands were developed for the selective recovery of cobalt from the solution containing nickel and manganese by means of solvent extraction. This combination of metals is the major cathode material used in electric vehicle batteries. The ligands can be protonated and function as ion-pairing ligands targeting the anionic [CoCl₄]²⁻, a species which is not observed for Ni or Mn. Selectivity for Co was found to be good at very high chloride concentrations and low pH. Longer chains or larger macrocycles were found to enhance selectivity, and linear chains on the amide side groups also resulted in greater selectivity over the branched groups. The cation of the chloride salt used for adjusting chloride concentrations seems to play a major role in extraction through salting-out effects. The ligands developed in this study show good selectivity for Co over Ni and Mn but require very high chloride concentrations to function. This research does, however, open the door for further investigations into using diamines as solvent extraction ligands for the recovery of cobalt from spent lithium-ion batteries.

Keywords: hydrometallurgy, solvent extraction, cobalt, lithium-ion batteries

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7420 Human Immune Response to Surgery: The Surrogate Prediction of Postoperative Outcomes

Authors: Husham Bayazed

Abstract:

Immune responses following surgical trauma play a pivotal role in predicting postoperative outcomes from healing and recovery to postoperative complications. Postoperative complications, including infections and protracted recovery, occur in a significant number of about 300 million surgeries performed annually worldwide. Complications cause personal suffering along with a significant economic burden on the healthcare system in any community. The accurate prediction of postoperative complications and patient-targeted interventions for their prevention remain major clinical provocations. Recent Findings: Recent studies are focusing on immune dysregulation mechanisms that occur in response to surgical trauma as a key determinant of postoperative complications. Antecedent studies mainly were plunging into the detection of inflammatory plasma markers, which facilitate in providing important clues regarding their pathogenesis. However, recent Single-cell technologies, such as mass cytometry or single-cell RNA sequencing, have markedly enhanced our ability to understand the immunological basis of postoperative immunological trauma complications and to identify their prognostic biological signatures. Summary: The advent of proteomic technologies has significantly advanced our ability to predict the risk of postoperative complications. Multiomic modeling of patients' immune states holds promise for the discovery of preoperative predictive biomarkers and providing patients and surgeons with information to improve surgical outcomes. However, more studies are required to accurately predict the risk of postoperative complications in individual patients.

Keywords: immune dysregulation, postoperative complications, surgical trauma, flow cytometry

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7419 Maryland Restoration of Anterior Tooth Loss as a Minimal Invasive Dentistry: An Alternative Treatment

Authors: B. Oral, C. Bal, M. S. Kar, A. Akgürbüz

Abstract:

Loss of maxillary central incisors occurs in many patients, and the treatment of young adults with this problem is a challenge for both prosthodontists and orthodontists. Common treatment alternatives are distalization of adjacent teeth and fabrication of a conventional 3-unit fixed partial denture, a single implant supported crown restoration or a resin-bonded fixed partial denture. This case report describes the indication of a resin-bonded fixed partial denture, preparation of the abutment teeth and the prosthetic procedures. The technique described here represents a conservative, esthetically pleasing and rapid solution for the missing maxillary central incisor when implant placement and/or guided bone regeneration techniques are not feasible because of financial, social or time restrictions. In this case a 16 year-old female patient who lost her maxillary left central incisor six years ago in a bicycle accident applied to our clinic with a major complaint of her unaesthetic appearance associated with the loss of her maxillary left central incisor. Although there was an indication for orthodontic treatment because of the limited space at the traumatized area, the patient did not accept to receive any orthodontic procedure. That is why an implant supported restoration could not be an option for the narrow area. Therefore maryland bridge as a minimal invasive dental therapy was preferred as a retention appliance so the patient's aesthetic appearance was restored.

Keywords: Maryland bridge, single tooth restoration, aesthetics, maxillary central incisors

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7418 A Comparative Study of Single- and Multi-Walled Carbon Nanotube Incorporation to Indium Tin Oxide Electrodes for Solar Cells

Authors: G. Gokceli, O. Eksik, E. Ozkan Zayim, N. Karatepe

Abstract:

Alternative electrode materials for optoelectronic devices have been widely investigated in recent years. Since indium tin oxide (ITO) is the most preferred transparent conductive electrode, producing ITO films by simple and cost-effective solution-based techniques with enhanced optical and electrical properties has great importance. In this study, single- and multi-walled carbon nanotubes (SWCNT and MWCNT) incorporated into the ITO structure to increase electrical conductivity, mechanical strength, and chemical stability. Carbon nanotubes (CNTs) were firstly functionalized by acid treatment (HNO3:H2SO4), and the thermal resistance of CNTs after functionalization was determined by thermogravimetric analysis (TGA). Thin films were then prepared by spin coating technique and characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), four-point probe measurement system and UV-Vis spectrophotometer. The effects of process parameters were compared for ITO, MWCNT-ITO, and SWCNT-ITO films. Two factors including CNT concentration and annealing temperature were considered. The UV-Vis measurements demonstrated that the transmittance of ITO films was 83.58% at 550 nm, which was decreased depending on the concentration of CNT dopant. On the other hand, both CNT dopants provided an enhancement in the crystalline structure and electrical conductivity. Due to compatible diameter and better dispersibility of SWCNTs in the ITO solution, the best result in terms of electrical conductivity was obtained by SWCNT-ITO films with the 0.1 g/L SWCNT dopant concentration and heat-treatment at 550 °C for 1 hour.

Keywords: CNT incorporation, ITO electrode, spin coating, thin film

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7417 Arginase Activity and Nitric Oxide Levels in Patients Undergoing Open Heart Surgery with Cardiopulmonary Bypass

Authors: Mehmet Ali Kisaçam, P. Sema Temizer Ozan, Ayşe Doğan, Gonca Ozan, F. Sarper Türker

Abstract:

Cardiovascular disease which is one of the most common health problems worldwide has crucial importance because of its’ morbidity and mortality rates. Nitric oxide synthase and arginase use L-arginine as a substrate and produce nitric oxide (NO), citrulline and urea, ornithine respectively. Endothelial dysfunction is characterized by reduced bioavailability of vasodilator and anti-inflammatory molecule NO. The purpose of the study to assess endothelial function via arginase activity and NO levels in patients undergoing coronary artery bypass grafting (CABG) surgery. The study was conducted on 26 patients (14 male, 12 female) undergoing CABG surgery. Blood samples were collected from the subjects before surgery, after the termination and after 24 hours of the surgery. Arginase activity and NO levels measured in collected samples spectrophotometrically. Arginase activity decreased significantly in subjects after the termination of the surgery compared to before surgery data. 24 hours after the surgery there wasn’t any significance in arginase activity as it compared to before surgery and after the termination of the surgery. On the other hand, NO levels increased significantly in the subject after the termination of the surgery. However there was no significant increase in NO levels after 24 hours of the surgery, but there was an insignificant increase compared to before surgery data. The results indicate that after the termination of the surgery vascular and endothelial function improved and after 24 hours of the surgery arginase activity and NO levels returned to normal.

Keywords: arginase, bypass, cordiopulmonary, nitric oxide

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7416 An Analysis of the Impact of Immunosuppression upon the Prevalence and Risk of Cancer

Authors: Aruha Khan, Brynn E. Kankel, Paraskevi Papadopoulou

Abstract:

In recent years, extensive research upon ‘stress’ has provided insight into its two distinct guises, namely the short–term (fight–or–flight) response versus the long–term (chronic) response. Specifically, the long–term or chronic response is associated with the suppression or dysregulation of immune function. It is also widely noted that the occurrence of cancer is greatly correlated to the suppression of the immune system. It is thus necessary to explore the impact of long–term or chronic stress upon the prevalence and risk of cancer. To what extent can the dysregulation of immune function caused by long–term exposure to stress be controlled or minimized? This study focuses explicitly upon immunosuppression due to its ability to increase disease susceptibility, including cancer itself. Based upon an analysis of the literature relating to the fundamental structure of the immune system alongside the prospective linkage of chronic stress and the development of cancer, immunosuppression may not necessarily correlate directly to the acquisition of cancer—although it remains a contributing factor. A cross-sectional analysis of the survey data from the University of Tennessee Medical Center (UTMC) and Harvard Medical School (HMS) will provide additional supporting evidence (or otherwise) for the hypothesis of the study about whether immunosuppression (caused by the chronic stress response) notably impacts the prevalence of cancer. Finally, a multidimensional framework related to education on chronic stress and its effects is proposed.

Keywords: immune system, immunosuppression, long–term (chronic) stress, risk of cancer

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7415 Retrofitting Residential Buildings for Energy Efficiency: An Experimental Investigation

Authors: Naseer M. A.

Abstract:

Buildings are major consumers of energy in both their construction and operation. They account for 40% of World’s energy use. It is estimated that 40-60% of this goes for conditioning the indoor environment. In India, like many other countries, the residential buildings have a major share (more than 50%) in the building sector. Of these, single-family units take a mammoth share. The single-family dwelling units in the urban and fringe areas are built in two stories to minimize the building foot print on small land parcels. And quite often, the bedrooms are located in the first floors. The modern buildings are provided with reinforced concrete (RC) roofs that absorb heat throughout the day and radiate the heat into the interiors during the night. The rooms that are occupied in the night, like bedrooms, are having their indoors uncomfortable. This has resulted in the use of active systems like air-conditioners and air coolers, thereby increasing the energy use. An investigation conducted by monitoring the thermal comfort condition in the residential building with RC roofs have proved that the indoors are really uncomfortable in the night hours. A sustainable solution to improve the thermal performance of the RC roofs was developed by an experimental study by continuously monitoring the thermal comfort parameters during summer (the period that is most uncomfortable in temperate climate). The study conducted in the southern peninsular India, prove that retrofitting of existing residential building can give a sustainable solution in abating the ever increasing energy demand especially when it is a fact that these residential buildings that are built for a normal life span of 40 years would continue to consume the energy for the rest of its useful life.

Keywords: energy efficiency, thermal comfort, retrofitting, residential buildings

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7414 Numerical Simulation of Two-Dimensional Flow over a Stationary Circular Cylinder Using Feedback Forcing Scheme Based Immersed Boundary Finite Volume Method

Authors: Ranjith Maniyeri, Ahamed C. Saleel

Abstract:

Two-dimensional fluid flow over a stationary circular cylinder is one of the bench mark problem in the field of fluid-structure interaction in computational fluid dynamics (CFD). Motivated by this, in the present work, a two-dimensional computational model is developed using an improved version of immersed boundary method which combines the feedback forcing scheme of the virtual boundary method with Peskin’s regularized delta function approach. Lagrangian coordinates are used to represent the cylinder and Eulerian coordinates are used to describe the fluid flow. A two-dimensional Dirac delta function is used to transfer the quantities between the sold to fluid domain. Further, continuity and momentum equations governing the fluid flow are solved using fractional step based finite volume method on a staggered Cartesian grid system. The developed code is validated by comparing the values of drag coefficient obtained for different Reynolds numbers with that of other researcher’s results. Also, through numerical simulations for different Reynolds numbers flow behavior is well captured. The stability analysis of the improved version of immersed boundary method is tested for different values of feedback forcing coefficients.

Keywords: Feedback Forcing Scheme, Finite Volume Method, Immersed Boundary Method, Navier-Stokes Equations

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7413 Nanoparaquat Effects on Oxidative Stress Status and Liver Function in Male Rats

Authors: Zahra Azizi, Ashkan Karbasi, Farzin Firouzian, Sara Soleimani Asl, Akram Ranjbar

Abstract:

Background: One of the most often used herbicides in agriculture is paraquat (PQ), which is very harmful to both people and animals. Chitosan is a well-known, non-toxic polymer commonly used in preparing particles via ionotropic gelation facilitated by negatively charged agents such as sodium alginate. This study aimed to compare the effects of PQ and nanoparaquat (PQNPs) on liver function in male rats. Materials & Methods: Rats were exposed to PQ & PQNPs (4 mg/kg/day, intraperitoneally) for seven days. Then, rats were anesthetized, and serum and liver samples were collected. Later, enzymatic activities such as alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP) in serum and oxidative stress biomarkers such as lipid peroxidation (LPO), total antioxidant capacity (TAC) and total thiol groups (TTG) levels in liver tissue were measured by colorimetric methods. Also, histological changes in the liver were evaluated. Results: PQ altered the levels of ALT, AST, and ALP while inducing oxidative stress in the liver. Additionally, liver homogenates with PQ exposure had challenged LPO, TAC, and TTG levels. The severe liver damage is indicated by a significant increase in the enzyme activity of AST, ALT, and ALP in serum. According to the results of the current study, PQNPs, as compared to PQ and the control group, lowered ALT, AST, ALP, and LPO levels while increasing TAC and TTG levels. Conclusion: According to biochemical and histological investigations, PQ loaded in chitosan-alginate particles is more efficient than free PQ at reducing liver toxicity.

Keywords: paraquat, paraquat nanoparticles, liver, oxidative stress

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7412 Behavioral Response of Dogs to Interior Environment: An Exploratory Study on Design Parameters for Designing Dog Boarding Centers in Indian Context

Authors: M. R. Akshaya, Veena Rao

Abstract:

Pet population in India is increasing phenomenally owing to the changes in urban lifestyle with increasing number of single professionals, single parents, delayed parenthood etc. The animal companionship as a means of reducing stress levels, deriving emotional support, and unconditional love provided by dogs are a few reasons attributed for increasing pet ownership. The consequence is the booming of the pet care products and dog care centers catering to the different requirements of rearing the pets. Dog care centers quite popular in tier 1 metros of India cater to the requirement of the dog owners providing space for the dogs in absence of the owner. However, it is often reported that the absence of the owner leads to destructive and exploratory behavior issues; the main being the anxiety disorders. In the above context, it becomes imperative for a designer to design dog boarding centers that help in reducing the separation anxiety in dogs keeping in mind the different interior design parameters. An exploratory research with focus group discussion is employed involving a group of dog owners, behaviorists, proprietors of day care as well as boarding centers, and veterinarians to understand their perception on the significance of different interior parameters of color, texture, ventilation, aroma therapy and acoustics as a means of reducing the stress levels in dogs sent to the boarding centers. The data collected is organized as thematic networks thus enabling the listing of the interior design parameters that needs to be considered in designing dog boarding centers. 

Keywords: behavioral response, design parameters, dog boarding centers, interior environment

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7411 U.S. Trade and Trade Balance with China: Testing for Marshall-Lerner Condition and the J-Curve Hypothesis

Authors: Anisul Islam

Abstract:

The U.S. has a very strong trade relationship with China but with a large and persistent trade deficit. Some has argued that the undervalued Chinese Yuan is to be blamed for the persistent trade deficit. The empirical results are mixed at best. This paper empirically estimates the U.S. export function along with the U.S. import function with its trade with China with the purpose of testing for the existence of the Marshall-Lerner (ML) condition as well for the possible existence of the J-curve hypothesis. Annual export and import data will be utilized for as long as the time series data exists. The export and import functions will be estimated using advanced econometric techniques, along with appropriate diagnostic tests performed to examine the validity and reliability of the estimated results. The annual time-series data covers from 1975 to 2022 with a sample size of 48 years, the longest period ever utilized before in any previous study. The data is collected from several sources, such as the World Bank’s World Development Indicators, IMF Financial Statistics, IMF Direction of Trade Statistics, and several other sources. The paper is expected to shed important light on the ongoing debate regarding the persistent U.S. trade deficit with China and the policies that may be useful to reduce such deficits over time. As such, the paper will be of great interest for the academics, researchers, think tanks, global organizations, and policy makers in both China and the U.S.

Keywords: exports, imports, marshall-lerner condition, j-curve hypothesis, united states, china

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7410 Rayleigh-Bénard-Taylor Convection of Newtonian Nanoliquid

Authors: P. G. Siddheshwar, T. N. Sakshath

Abstract:

In the paper we make linear and non-linear stability analyses of Rayleigh-Bénard convection of a Newtonian nanoliquid in a rotating medium (called as Rayleigh-Bénard-Taylor convection). Rigid-rigid isothermal boundaries are considered for investigation. Khanafer-Vafai-Lightstone single phase model is used for studying instabilities in nanoliquids. Various thermophysical properties of nanoliquid are obtained using phenomenological laws and mixture theory. The eigen boundary value problem is solved for the Rayleigh number using an analytical method by considering trigonometric eigen functions. We observe that the critical nanoliquid Rayleigh number is less than that of the base liquid. Thus the onset of convection is advanced due to the addition of nanoparticles. So, increase in volume fraction leads to advanced onset and thereby increase in heat transport. The amplitudes of convective modes required for estimating the heat transport are determined analytically. The tri-modal standard Lorenz model is derived for the steady state assuming small scale convective motions. The effect of rotation on the onset of convection and on heat transport is investigated and depicted graphically. It is observed that the onset of convection is delayed due to rotation and hence leads to decrease in heat transport. Hence, rotation has a stabilizing effect on the system. This is due to the fact that the energy of the system is used to create the component V. We observe that the amount of heat transport is less in the case of rigid-rigid isothermal boundaries compared to free-free isothermal boundaries.

Keywords: nanoliquid, rigid-rigid, rotation, single phase

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7409 Hybrid Wind Solar Gas Reliability Optimization Using Harmony Search under Performance and Budget Constraints

Authors: Meziane Rachid, Boufala Seddik, Hamzi Amar, Amara Mohamed

Abstract:

Today’s energy industry seeks maximum benefit with maximum reliability. In order to achieve this goal, design engineers depend on reliability optimization techniques. This work uses a harmony search algorithm (HS) meta-heuristic optimization method to solve the problem of wind-Solar-Gas power systems design optimization. We consider the case where redundant electrical components are chosen to achieve a desirable level of reliability. The electrical power components of the system are characterized by their cost, capacity and reliability. The reliability is considered in this work as the ability to satisfy the consumer demand which is represented as a piecewise cumulative load curve. This definition of the reliability index is widely used for power systems. The proposed meta-heuristic seeks for the optimal design of series-parallel power systems in which a multiple choice of wind generators, transformers and lines are allowed from a list of product available in the market. Our approach has the advantage to allow electrical power components with different parameters to be allocated in electrical power systems. To allow fast reliability estimation, a universal moment generating function (UMGF) method is applied. A computer program has been developed to implement the UMGF and the HS algorithm. An illustrative example is presented.

Keywords: reliability optimization, harmony search optimization (HSA), universal generating function (UMGF)

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7408 Plethora of Drivers Transforming Colonial Cities: The Case of Allahabad

Authors: Akanksha Gupta, Vishal Dubey

Abstract:

In the Neoliberal era, there has been a much-talked discourse about urban issues that arise from a narrow approach of the single rationality of market-driven planning in Indian cities. More to this, India's urban planning is already jeopardized by the captious shortage of infrastructure, a cluster of incoherent governing bodies and implementation mechanism, leading cities to lie in the plethora of urban challenges. In this context, Allahabad (now known as Prayagraj) a city in North India is not an exception. Once known as the most planned splendid Colonial city of the British regime in India collapsed phenomenally because of the incompetent approach of planning machinery, straightforward market-driven accession and lack of attention on urban equity and sustainability. Particularly Civil Lines a Colonial neighbourhood, reached to the zenith of the glorified legacy of the Colonial era, transformed into filthy and congested urban form. Contextually this study contemplates and assesses the chronological episodes of major changes in land management reforms and policies under the ad hoc approach of political economy and land use planning which radically degraded the living environment in the present context. This study would empirically showcase the selected sample area detailing some of the major consequences in terms of gradual change in urban morphology, land use, and function. Here the method of study is primarily a qualitative study implying oral history and other historical methods to exhibit the idiom of planning conundrum. This subsequently reflects the repercussions translated into major issues like unclear land titles, encroachment, and unauthorized development and mushrooming of informal and squatter settlements. In nutshell, the study seeks to distinct out the limitations of the land reform and land management policies, which impacted the general degradation to the beautiful setting of Colonial neighbourhood. The Colonial legacy of Civil Lines now exists in the traces of history- memories of people, who once took pride in its serenity have now witnessed the transformation bit by bit till neo-liberal market forces completely swallow it.

Keywords: civil lines, land reforms, policies, urban challenges

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7407 A Combination of Mesenchymal Stem Cells and Low-Intensity Ultrasound for Knee Meniscus Regeneration: A Preliminary Study

Authors: Mohammad Nasb, Muhammad Rehan, Chen Hong

Abstract:

Background Meniscus defects critically alter knee function and lead to degenerative changes. Regenerative medicine applications including stem cell transplantation have showed a promising efficacy in finding alternatives to overcome traditional treatment limitations. However, stem cell therapy remains limited due to the substantially reduced viability and inhibitory microenvironment. Since tissue growth and repair are under the control of biochemical and mechanical signals, several approaches have recently been investigated (e.g., low intensity pulsed ultrasound [LIPUS]) to promote the regeneration process. This study employed LIPUS to improve growth and osteogenic differentiation of mesenchymal stem cells derived from human embryonic stem cells to improve the regeneration of meniscus tissue. Methodology: The Mesenchymal stromal cells (MSCs) were transplanted into the epicenter of the injured meniscus in rabbits, which were randomized into two main groups: a treatment group (n=32 New Zealand rabbits) including 4 subgroups of 8 rabbits in each subgroup (LIPUS treatment, MSC treatment, LIPUS with MSC and control), and a second group (n=9) to track implanted cells and their progeny using green fluorescence protein (GFP). GFP consists of the MSC and LIPUS-MSC combination subgroups. Rabbits were then subjected to histological, immunohistochemistry, and MRI assessment. Results: The quantity of the newly regenerated tissue in the combination treatment group that had Ultrasound irradiation after mesenchymal stem cells were better at all end points. Likewise, Tissue quality scores were also greater in knees treated with both approaches compared with controls and single treatment at all end points, achieving significance at twelve and twenty-four weeks [p < 0.05], and [p = 0.008] at twelve weeks. Differentiation into type-I and II collagen-expressing cells were higher in the combination group at up to twenty-four weeks. Conclusions: the combination of mesenchymal stem cells and LIPUS showed greater adhering to the sites of meniscus injury, differentiate into cells resembling meniscal fibrochondrocytes, and improve both quality and quantity of meniscal regeneration.

Keywords: stem cells, regenerative medicine, osteoarthritis, knee

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7406 Legal Implications of a Single African Air Transport Market on Airlines and Passengers in Nigeria

Authors: Adejoke Omowumi Adediran

Abstract:

The commitment of African states to liberalise civil aviation in Africa through the implementation of the Yamoussoukro Decision of 1999 was reiterated in 2015 at the African Union Assembly meeting. A declaration was made by African Heads of government at the meeting to ensure the immediate implementation of the decision towards the establishment of a Single African Air Transport Market (SAATM) by 2017. A SAATM will imply among others, a removal of all commercial restrictions for African airlines in Africa; access to any route in Africa by African airlines without any required permit or authorisation; and a common set of regulations for airlines in African member states. As the envisioned 2017 date for launching the SAATM could not be met, a new date of January 2018 has been set. The lack of political will by African States, however, remains a prominent challenge to the realisation of the SAATM. As at June 2017, only twenty-one states had signed the commitment to actualise the decision creating the SAATM. In actualisation of the SAATM, a regulatory framework has been established to efficiently manage the new African airline industry, and regulatory texts have been adopted as part of the legal regime. This legal regime is to regulate both interstate and domestic operations. Airlines in Nigeria are currently faced with certain challenges which ultimately affect their effectiveness and passengers as well do not enjoy utmost customer satisfaction with services rendered by the airlines. Although Nigeria has demonstrated support for the SAATM since 2015, as Nigeria alongside ten other states, signed the initial commitment, whether or not SAATM will eventually be beneficial to airlines and passengers has become an issue in the light of the challenges of the Nigerian airline industry. Remarkably, the benefit of the SAATM is to a large extent ultimately determined by its legal framework. Using doctrinal research, this paper examines the legal implications of the SAATM on airlines and passengers in Nigeria. This paper analyses the legal framework of SAATM and juxtaposes this with the particular issues affecting airlines and passengers in Nigeria such as financial difficulties on the part of airlines and consumer protection as regards passengers. Among others, it can be asserted that the legal regime affords an opportunity for business expansion and creates a fair environment for competition. This is beneficial not only to the airlines but to passengers as well. In addition, in the interest of passengers, consumer rights are prescribed, and the regulations also cater for situations where airlines interrupt their services, as losses arising from these situations will be mitigated. There is indeed no doubt that the SAATM will be of great utility to both airlines and passengers in Nigeria.

Keywords: airlines, civil aviation, competition, consumer protection, passengers, single African air transport market, yamoussoukro decision

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7405 An Efficient Tool for Mitigating Voltage Unbalance with Reactive Power Control of Distributed Grid-Connected Photovoltaic Systems

Authors: Malinwo Estone Ayikpa

Abstract:

With the rapid increase of grid-connected PV systems over the last decades, genuine challenges have arisen for engineers and professionals of energy field in the planning and operation of existing distribution networks with the integration of new generation sources. However, the conventional distribution network, in its design was not expected to receive other generation outside the main power supply. The tools generally used to analyze the networks become inefficient and cannot take into account all the constraints related to the operation of grid-connected PV systems. Some of these constraints are voltage control difficulty, reverse power flow, and especially voltage unbalance which could be due to the poor distribution of single-phase PV systems in the network. In order to analyze the impact of the connection of small and large number of PV systems to the distribution networks, this paper presents an efficient optimization tool that minimizes voltage unbalance in three-phase distribution networks with active and reactive power injections from the allocation of single-phase and three-phase PV plants. Reactive power can be generated or absorbed using the available capacity and the adjustable power factor of the inverter. Good reduction of voltage unbalance can be achieved by reactive power control of the PV systems. The presented tool is based on the three-phase current injection method and the PV systems are modeled via an equivalent circuit. The primal-dual interior point method is used to obtain the optimal operating points for the systems.

Keywords: Photovoltaic system, Primal-dual interior point method, Three-phase optimal power flow, Voltage unbalance

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7404 The Ongoing Impact of Secondary Stressors on Businesses in Northern Ireland Affected by Flood Events

Authors: Jill Stephenson, Marie Vaganay, Robert Cameron, Caoimhe McGurk, Neil Hewitt

Abstract:

Purpose: The key aim of the research was to identify the secondary stressors experienced by businesses affected by single or repeated flooding and to determine to what extent businesses were affected by these stressors, along with any resulting impact on health. Additionally, the research aimed to establish the likelihood of businesses being re-exposed to the secondary stressors through assessing awareness of flood risk, implementation of property protection measures and level of community resilience. Design/methodology/approach: The chosen research method involved the distribution of a questionnaire survey to businesses affected by either single or repeated flood events. The questionnaire included the Impact of Event Scale (a 15-item self-report measure which assesses subjective distress caused by traumatic events). Findings: 55 completed questionnaires were returned by flood impacted businesses. 89% of the businesses had sustained internal flooding while 11% had experienced external flooding. The results established that the key secondary stressors experienced by businesses, in order of priority, were: flood damage, fear of reoccurring flooding, prevention of access to the premise/closure, loss of income, repair works, length of closure and insurance issues. There was a lack of preparedness for potential future floods and consequent vulnerability to the emergence of secondary stressors among flood affected businesses, as flood resistance or flood resilience measures had only been implemented by 11% and 13% respectively. In relation to the psychological repercussions, the Impact of Event scores suggested that potential prevalence of post-traumatic stress disorder (PTSD) was noted among 8 out of 55 respondents (l5%). Originality/value: The results improve understanding of the enduring repercussions of flood events on businesses, indicating that not only residents may be susceptible to the detrimental health impacts of flood events and single flood events may be just as likely as reoccurring flooding to contribute to ongoing stress. Lack of financial resources is a possible explanation for the lack of implementation of property protection measures among businesses, despite 49% experiencing flooding on multiple occasions. Therefore it is recommended that policymakers should consider potential sources of financial support or grants towards flood defences for flood impacted businesses. Any form of assistance should be made available to businesses at the earliest opportunity as there was no significant association between the time of the last flood event and the likelihood of experiencing PTSD symptoms.

Keywords: flood event, flood resilience, flood resistance, PTSD, secondary stressors

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7403 The Effect of the Structural Arrangement of Binary Bisamide Organogelators on their Self-Assembly Behavior

Authors: Elmira Ghanbari, Jan Van Esch, Stephen J. Picken, Sahil Aggarwal

Abstract:

Low-molecular-weight organogelators form gels by self-assembly into the crystalline network which immobilizes the organic solvent. For single bisamide organogelator systems, the effect of the molecular structure on the molecular interaction and their self-assembly behavior has been explored. The spatial arrangement of bisamide molecules in the gel-state is driven by a combination of hydrogen bonding and Van der Waals interactions. The hydrogen-bonding pattern between the amide groups of bisamide molecules is regulated by the number of methylene spacers; the even number of methylene spacers between two amide groups, in even-spaced bisamides, leads to the antiparallel position of amide groups within a molecule. An even-spaced bisamide molecule with antiparallel amide groups can make two pairs of hydrogen bonding with the molecules on the same plane. The odd-spaced bisamide with a parallel directionality of amide groups can form four independent hydrogen bonds with four other bisamide molecules on different planes. The arrangement of bisamide molecules in the crystalline state and the interaction of these molecules depends on the molecular structure, particularly the parity of the spacer length between the amide groups in the bisamide molecule. In this study, the directionality of amide groups has been exploited as a structural characteristic to affect the arrangement of molecules in the crystalline state and produce different binary bisamide gelators with different degrees of crystallinities. Single odd- and even-spaced single bisamides were synthesized and blended to produce binary bisamide organogelators to be characterized in order to understand the effect of the different directionality of amide groups on the molecular interaction in the crystalline state. The pattern of molecular interactions between these blended molecules, mixing or phase separation, has been monitored via differential scanning calorimetry (DSC) and crystallography techniques; X-ray powder diffraction (XRD) and Small-angle X-ray scattering (SAXS). The formation of lamellar structures for odd- and even-spaced bisamide gelators was confirmed by using SAXS and XRD techniques. DSC results have shown that binary bisamide organogelators with different parity of methylene spacers (odd-even binary blends) have a higher tendency for phase separation compared to the binary bisamides with the same parity (odd-odd or even-even binary blends). Phase separation in binary odd-even bisamides was confirmed by the presence of individual (100) reflections of odd and even lamellar structures. The structural characteristic of bisamide organogelators, the parity of spacer length in binary systems, is a promising tool to control the arrangement of molecules and their crystalline structure.

Keywords: binary bisamide organogelators, crystalline structure, phase separation, self-assembly behavior

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7402 Incorporating Spatial Transcriptome Data into Ligand-Receptor Analyses to Discover Regional Activation in Cells

Authors: Eric Bang

Abstract:

Interactions between receptors and ligands are crucial for many essential biological processes, including neurotransmission and metabolism. Ligand-receptor analyses that examine cell behavior and interactions often utilize cell type-specific RNA expressions from single-cell RNA sequencing (scRNA-seq) data. Using CellPhoneDB, a public repository consisting of ligands, receptors, and ligand-receptor interactions, the cell-cell interactions were explored in a specific scRNA-seq dataset from kidney tissue and portrayed the results with dot plots and heat maps. Depending on the type of cell, each ligand-receptor pair was aligned with the interacting cell type and calculated the positori probabilities of these associations, with corresponding P values reflecting average expression values between the triads and their significance. Using single-cell data (sample kidney cell references), genes in the dataset were cross-referenced with ones in the existing CellPhoneDB dataset. For example, a gene such as Pleiotrophin (PTN) present in the single-cell data also needed to be present in the CellPhoneDB dataset. Using the single-cell transcriptomics data via slide-seq and reference data, the CellPhoneDB program defines cell types and plots them in different formats, with the two main ones being dot plots and heat map plots. The dot plot displays derived measures of the cell to cell interaction scores and p values. For the dot plot, each row shows a ligand-receptor pair, and each column shows the two interacting cell types. CellPhoneDB defines interactions and interaction levels from the gene expression level, so since the p-value is on a -log10 scale, the larger dots represent more significant interactions. By performing an interaction analysis, a significant interaction was discovered for myeloid and T-cell ligand-receptor pairs, including those between Secreted Phosphoprotein 1 (SPP1) and Fibronectin 1 (FN1), which is consistent with previous findings. It was proposed that an effective protocol would involve a filtration step where cell types would be filtered out, depending on which ligand-receptor pair is activated in that part of the tissue, as well as the incorporation of the CellPhoneDB data in a streamlined workflow pipeline. The filtration step would be in the form of a Python script that expedites the manual process necessary for dataset filtration. Being in Python allows it to be integrated with the CellPhoneDB dataset for future workflow analysis. The manual process involves filtering cell types based on what ligand/receptor pair is activated in kidney cells. One limitation of this would be the fact that some pairings are activated in multiple cells at a time, so the manual manipulation of the data is reflected prior to analysis. Using the filtration script, accurate sorting is incorporated into the CellPhoneDB database rather than waiting until the output is produced and then subsequently applying spatial data. It was envisioned that this would reveal wherein the cell various ligands and receptors are interacting with different cell types, allowing for easier identification of which cells are being impacted and why, for the purpose of disease treatment. The hope is this new computational method utilizing spatially explicit ligand-receptor association data can be used to uncover previously unknown specific interactions within kidney tissue.

Keywords: bioinformatics, Ligands, kidney tissue, receptors, spatial transcriptome

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7401 Frequent Pattern Mining for Digenic Human Traits

Authors: Atsuko Okazaki, Jurg Ott

Abstract:

Some genetic diseases (‘digenic traits’) are due to the interaction between two DNA variants. For example, certain forms of Retinitis Pigmentosa (a genetic form of blindness) occur in the presence of two mutant variants, one in the ROM1 gene and one in the RDS gene, while the occurrence of only one of these mutant variants leads to a completely normal phenotype. Detecting such digenic traits by genetic methods is difficult. A common approach to finding disease-causing variants is to compare 100,000s of variants between individuals with a trait (cases) and those without the trait (controls). Such genome-wide association studies (GWASs) have been very successful but hinge on genetic effects of single variants, that is, there should be a difference in allele or genotype frequencies between cases and controls at a disease-causing variant. Frequent pattern mining (FPM) methods offer an avenue at detecting digenic traits even in the absence of single-variant effects. The idea is to enumerate pairs of genotypes (genotype patterns) with each of the two genotypes originating from different variants that may be located at very different genomic positions. What is needed is for genotype patterns to be significantly more common in cases than in controls. Let Y = 2 refer to cases and Y = 1 to controls, with X denoting a specific genotype pattern. We are seeking association rules, ‘X → Y’, with high confidence, P(Y = 2|X), significantly higher than the proportion of cases, P(Y = 2) in the study. Clearly, generally available FPM methods are very suitable for detecting disease-associated genotype patterns. We use fpgrowth as the basic FPM algorithm and built a framework around it to enumerate high-frequency digenic genotype patterns and to evaluate their statistical significance by permutation analysis. Application to a published dataset on opioid dependence furnished results that could not be found with classical GWAS methodology. There were 143 cases and 153 healthy controls, each genotyped for 82 variants in eight genes of the opioid system. The aim was to find out whether any of these variants were disease-associated. The single-variant analysis did not lead to significant results. Application of our FPM implementation resulted in one significant (p < 0.01) genotype pattern with both genotypes in the pattern being heterozygous and originating from two variants on different chromosomes. This pattern occurred in 14 cases and none of the controls. Thus, the pattern seems quite specific to this form of substance abuse and is also rather predictive of disease. An algorithm called Multifactor Dimension Reduction (MDR) was developed some 20 years ago and has been in use in human genetics ever since. This and our algorithms share some similar properties, but they are also very different in other respects. The main difference seems to be that our algorithm focuses on patterns of genotypes while the main object of inference in MDR is the 3 × 3 table of genotypes at two variants.

Keywords: digenic traits, DNA variants, epistasis, statistical genetics

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7400 The Impact of Passive Design Factors on House Energy Efficiency for New Cities in Egypt

Authors: Mahmoud Mourad, Ahmad Hamza H. Ali, S.Ookawara, Ali Kamel Abdel-Rahman, Nady M. Abdelkariem

Abstract:

The energy consumption of a house can be affected simultaneously by many building design factors related to its main architectural features, building elements and materials. This study focuses on the impact of passive design factors on the annual energy consumption of a suggested prototype house for single-family detached houses of 240 m2 in two floors, each floor of 120 m2 in new Egyptian cities located in (Alexandria - Cairo - Siwa - Assuit – Aswan) which resemble five different climatic zones (Northern coast – Northern upper Egypt - dessert region- Southern upper Egypt – South Egypt) respectively. This study present the effect of the passive design factors affecting the building energy consumption as building orientation, building material (walls, roof and slabs), building type (residential, educational, commercial), building occupancy (type of occupant, no. of occupant, age), building landscape and site selection, building envelope and fenestration (glazing material, shading), and building plan form. This information can be used to estimate the approximate saving in energy consumption, which would result on a change in the design datum for the future houses development, and to identify the major design problems for energy efficiency. To achieve the above objective, this paper presents a study for the factors affecting on the building energy consumption in the hot arid area in new Egyptian cities in five different climatic zones , followed by defining the energy needs for different utilization in this suggested prototype house. Consequently, a detailed analysis of the available Renewable Energy utilizations technologies used in the suggested home, and a calculation of the energy as a function of yearly distribution that required for this home will presented. The results obtained from building annual energy analyses show that architecture passive design factors saves about 35% of the annual energy consumption. It shows also passive cooling techniques saves about 45%, and renewable energy systems saves about 40% of the annual energy needs for this proposed home depending on the cities location on the climatic zones.

Keywords: architecture passive design factors, energy efficient homes, Egypt new cites, renewable energy technologies

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7399 Possible Number of Dwelling Units Using Waste Plastic Bottle for Construction

Authors: Dibya Jivan Pati, Kazuhisa Iki, Riken Homma

Abstract:

Unlike other metro cities of India, Bhubaneswar–the capital city of Odisha, is expected to reach 1-million-mark population by now. The demands of dwelling unit requirement mostly among urban poor belonging to Economically Weaker section (EWS) and Low Income groups (LIG) is becoming a challenge due to high housing cost and rents. As a matter of fact, it’s also noted that, with increase in population, the solid waste generation also increases subsequently affecting the environment due to inefficiency in collection of waste by local government bodies. Methods of utilizing Solid Waste - especially in form of Plastic bottles, Glass bottles and Metal cans (PGM) are now widely used as an alternative material for construction of low-cost building by Non-Government Organizations (NGOs) in developing countries like India to help the urban poor afford a shelter. The application of disposed plastic bottle used in construction of single dwelling significantly reduces the overall cost of construction to as much as 14% compared to traditional construction material. Therefore, considering its cost-benefit result, it’s possible to provide housing to EWS and LIGs at an affordable price. In this paper, we estimated the quantity of plastic bottles generated in Bhubaneswar which further helped to estimate the possible number of single dwelling unit that can be constructed on yearly basis so as to refrain from further housing shortage. The estimation results will be practically used for planning and managing low-cost housing business by local government and NGOs.

Keywords: construction, dwelling unit, plastic bottle, solid waste generation, groups

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7398 A 30 Year Audit of the Vascular Complications of Ports: Permanent Intravascular Access Devices

Authors: S. Kershaw, P. J. Barry, K. Webb

Abstract:

Background: Cystic Fibrosis (CF) is a chronic lung disease where patients have chronic lung infection punctuated by acute exacerbations that require intermittent intravenous (IV) antibiotics during their lives. With time, peripheral venous access can become difficult and limited. Accessing these veins can become arduous, traumatic, painful and unworkable. A permanent intravascular access device or Port is a small device that is inserted into the central venous system that allows the delivery of medicine eliminating the need for peripheral venous access. Ports represent a convenient and efficient method when venous access is required on a permanent basis however they are also associated with significant vascular complications. Superior Vena Cava Obstruction (SVCO) is a rare but significant vascular complication of ports in this setting. Objective: We aimed to look at a single CF centre’s experience of port-related SVCO over a thirty year period. Methods: Retrospective data was extracted using patient’s notes, electronic radiological reports and local databases over a period in excess of 30 years from 1982 to 2014. Results: 13 patients were identified with SVCO as a result of their port. 11 patients had CF (9 female, 2 male), one male patient had Primary Ciliary Dyskinesia and one female patient had severe Asthma. The mean port function was 1532 days (range 110 – 4049) and the mean age at SVCO was 24 years (range 11.1 to 36.5 years). The most common symptoms were facial oedema (n=8, 61.5%) and dilated veins (n=6, 46.2%). 7 patients had their Ports removed after SVCO. 6 patients underwent attempted stenting (46.2%) and 6 did not. 4 out of the 6 who underwent stenting required/had re-intervention. 3 of the 6 patients who underwent stenting had symptom resolution, however, 4 of the 6 patients who were not stented had symptom resolution also. Symptom resolution was not guaranteed with stenting and required re-intervention in two-thirds. Conclusion: This case series represents the experience of one of the longest established CF units in the UK and represents the largest cohort ever reported in the literature.

Keywords: ports, Superior Vena Cava Obstruction, cystic fibrosis, access devices

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7397 The Reenactment of Historic Memory and the Ways to Read past Traces through Contemporary Architecture in European Urban Contexts: The Case Study of the Medieval Walls of Naples

Authors: Francesco Scarpati

Abstract:

Because of their long history, ranging from ancient times to the present day, European cities feature many historical layers, whose single identities are represented by traces surviving in the urban design. However, urban transformations, in particular, the ones that have been produced by the property speculation phenomena of the 20th century, often compromised the readability of these traces, resulting in a loss of the historical identities of the single layers. The purpose of this research is, therefore, a reflection on the theme of the reenactment of the historical memory in the stratified European contexts and on how contemporary architecture can help to reveal past signs of the cities. The research work starts from an analysis of a series of emblematic examples that have already provided an original solution to the described problem, going from the architectural detail scale to the urban and landscape scale. The results of these analyses are then applied to the case study of the city of Naples, as an emblematic example of a stratified city, with an ancient Greek origin; a city where it is possible to read most of the traces of its transformations. Particular consideration is given to the trace of the medieval walls of the city, which a long time ago clearly divided the city itself from the outer fields, and that is no longer readable at the current time. Finally, solutions and methods of intervention are proposed to ensure that the trace of the walls, read as a boundary, can be revealed through the contemporary project.

Keywords: contemporary project, historic memory, historic urban contexts, medieval walls, naples, stratified cities, urban traces

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7396 Rational Bureaucracy and E-Government: A Philosophical Study of Universality of E-Government

Authors: Akbar Jamali

Abstract:

Hegel is the first great political philosopher who specifically contemplates on bureaucracy. For Hegel bureaucracy is the function of the state. Since state, essentially is a rational organization, its function; namely, bureaucracy must be rational. Since, what is rational is universal; Hegel had to explain how the bureaucracy could be understood as universal. Hegel discusses bureaucracy in his treatment of ‘executive power’. He analyses modern bureaucracy as a form of political organization, its constituent members, and its relation to the social environment. Therefore, the essence of bureaucracy in Hegel’s philosophy is the implementation of law and rules. Hegel argues that unlike the other social classes that are particular because they look for their own private interest, bureaucracy as a class is a ‘universal’ because their orientation is the interest of the state. State for Hegel is essentially rational and universal. It is the actualization of ‘objective Spirit’. Marx criticizes Hegel’s argument on the universality of state and bureaucracy. For Marx state is equal to bureaucracy, it constitutes a social class that based on the interest of bourgeois class that dominates the society and exploits proletarian class. Therefore, the main disagreement between these political philosophers is: whether the state (bureaucracy) is universal or particular. Growing e-government in modern state as an important aspect of development leads us to contemplate on the particularity and universality of e-government. In this article, we will argue that e-government essentially is universal. E-government, in itself, is impartial; therefore, it cannot be particular. The development of e-government eliminates many side effects of the private, personal or particular interest of the individuals who work as bureaucracy. Finally, we will argue that more a state is developed more it is universal. Therefore, development of e-government makes the state a more universal and affects the modern philosophical debate on the particularity or universality of bureaucracy and state.

Keywords: particularity, universality, rational bureaucracy, impartiality

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7395 Molecular Insights into the 5α-Reductase Inhibitors: Quantitative Structure Activity Relationship, Pre-Absorption, Distribution, Metabolism, and Excretion and Docking Studies

Authors: Richa Dhingra, Monika, Manav Malhotra, Tilak Raj Bhardwaj, Neelima Dhingra

Abstract:

5-Alpha-reductases (5AR), a membrane bound, NADPH dependent enzyme and convert male hormone testosterone (T) into more potent androgen dihydrotestosterone (DHT). DHT is the required for the development and function of male sex organs, but its overproduction has been found to be associated with physiological conditions like Benign Prostatic Hyperplasia (BPH). Thus the inhibition of 5ARs could be a key target for the treatment of BPH. In present study, 2D and 3D Quantitative Structure Activity Relationship (QSAR) pharmacophore models have been generated for 5AR based on known inhibitory concentration (IC₅₀) values with extensive validations. The four featured 2D pharmacophore based PLS model correlated the topological interactions (–OH group connected with one single bond) (SsOHE-index); semi-empirical (Quadrupole2) and physicochemical descriptors (Mol. wt, Bromines Count, Chlorines Count) with 5AR inhibitory activity, and has the highest correlation coefficient (r² = 0.98, q² =0.84; F = 57.87, pred r² = 0.88). Internal and external validation was carried out using test and proposed set of compounds. The contribution plot of electrostatic field effects and steric interactions generated by 3D-QSAR showed interesting results in terms of internal and external predictability. The well validated 2D Partial Least Squares (PLS) and 3D k-nearest neighbour (kNN) models were used to search novel 5AR inhibitors with different chemical scaffold. To gain more insights into the molecular mechanism of action of these steroidal derivatives, molecular docking and in silico absorption, distribution, metabolism, and excretion (ADME) studies were also performed. Studies have revealed the hydrophobic and hydrogen bonding of the ligand with residues Alanine (ALA) 63A, Threonine (THR) 60A, and Arginine (ARG) 456A of 4AT0 protein at the hinge region. The results of QSAR, molecular docking, in silico ADME studies provide guideline and mechanistic scope for the identification of more potent 5-Alpha-reductase inhibitors (5ARI).

Keywords: 5α-reductase inhibitor, benign prostatic hyperplasia, ligands, molecular docking, QSAR

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