Search results for: progressive%20collapse

Authors: F. Boukli Hacene, W. Soufi, S. Ghalem

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Glaucoma disease is a progressive degenerative optic neuropathy, with irreversible visual field deficits and high eye pressure being one of the risk factors. Sulfonamides are carbonic anhydrase-II inhibitors that aim to decrease the secretion of aqueous humor by direct inhibition of this enzyme at the level of the ciliary processes. These drugs present undesirable effects that are difficult to accept by the patient. In our study, we are interested in the inhibition of carbonic anhydrase-II by different natural ligands (curcumin analogues) using molecular modeling methods using molecular operating environment (MOE) software to predict their interaction with this enzyme.

Keywords: carbonic anhydrase-II, curcumin analogues, drug research, molecular modeling

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Authors: Amit R. Bhende, G. K. Awari

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Remaining useful life (RUL) prediction is one of key technologies to realize prognostics and health management that is being widely applied in many industrial systems to ensure high system availability over their life cycles. The present work proposes a data-driven method of RUL prediction based on multiple health state assessment for rolling element bearings. Bearing degradation data at three different conditions from run to failure is used. A RUL prediction model is separately built in each condition. Feed forward back propagation neural network models are developed for prediction modeling.

Keywords: bearing degradation data, remaining useful life (RUL), back propagation, prognosis

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Authors: Yolanda Ramirez, Angel Tejada, Agustin Baidez

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In recent years, the intellectual capital reporting in higher education institutions has been acquiring progressive importance worldwide. Intellectual capital approaches becomes critical at universities, mainly due to the fact that knowledge is the main output as well as input in these institutions. Universities produce knowledge, either through scientific and technical research (the results of investigation, publications, etc.) or through teaching (students trained and productive relationships with their stakeholders). The purpose of the present paper is to identify the intangible elements about which university stakeholders demand most information. The results of a study done at Spanish universities are used to see which groups of universities have stakeholders who are more proactive to the disclosure of intellectual capital.

Keywords: intellectual capital, universities, Spain, cluster analysis

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Authors: Michal Duchek, Jan Palán, Tomas Kubina

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Bars made of titanium grade 2 and grade 4 were subjected to rotary forging with up to 2.2 true strain reduction in the cross-section from 10 to 3.81 mm. During progressive deformation, grain refinement in the transverse direction took place. In the longitudinal direction, ultrafine microstructure has not developed. It has been demonstrated that titanium grade 2 strengthens more than grade 4. The ultimate tensile strength increased from 650 MPa to 1040 MPa in titanium grade 4. Hardness profiles on the cross section in both materials show an increase in the centre of the wire.

Keywords: commercial-purity titanium, wire, rotary swaging, tensile test, hardness, modulus of elasticity, microstructure

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Authors: Josef Brychta, Jiri Kratochvil, Marek Pagac

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The group of progressive cutting materials can include non-traditional, emerging and less-used materials that can be an efficient use of cutting their lead to a quantum leap in the field of machining. This is essentially a “superhard” materials (STM) based on polycrystalline diamond (PCD) and polycrystalline cubic boron nitride (PCBN) cutting performance ceramics and development is constantly "perfecting" fine coated cemented carbides. The latter cutting materials are broken down by two parameters, toughness and hardness. A variation of alloying elements is always possible to improve only one of each parameter. Reducing the size of the core on the other hand doing achieves "contradictory" properties, namely to increase both hardness and toughness.

Keywords: grained cutting materials difficult to machine materials, optimum utilization, mechanic, manufacturing

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Authors: Abdullahi Mohammed Auwal

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Formation and change or decamping from one political party to another have now become a common trend in Nigeria. Many of the parties’ members who could not secure positions and or win elections in their parties or are not very much satisfied with the trends occurring in the party’s internal democratic principles and mechanisms, change their respective parties. This paper developed/presented and analyzed the used of non linear mathematical model for defections between two political parties using epidemiological approach. The whole population was assumed to be a constant and homogeneously mixed. Equilibria have been analytically obtained and their local and global stability discussed. Conditions for the co-existence of both the political parties have been determined, in the study of defections between People Democratic Party (PDP) and All Progressive Congress (APC) in Nigeria using numerical simulations to support the analytical results.

Keywords: model, political parties, deffection, stability, equilibrium, epidemiology

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Authors: Jawharah Alasmari

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In verb inflection, tense marks past/present/future action, and aspect marks progressive/continues perfect/completed actions. This usage and meaning of tense and aspect differ in Arabic and English. In this research, we applied data mining methods to test the predictive function of candidate features by using our dataset of Arabic verbs in-context, and their 7 translations. Weka machine learning classifiers is used in this experiment in order to examine the key features that can be used to provide guidance to enable a translator’s appropriate English translation of the Arabic verb tense and aspect.

Keywords: Arabic verb, English translations, mining methods, Weka software

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Authors: Somya Sharma

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Ahalya, the critically acclaimed short film, is known to demolish the gender constructs of the age old myth of Ahalya. The paper tries to crack the overt meaning of the short film by reading between the dialogues and deconstructing the idea of the pseudo feminism in the short film Ahalya by Sujoy Ghosh. The film, by subverting the role of male character by making it seem submissive as compared to the female character's role seems to be just a surface level reading of the text. It seems that Sujoy Ghosh has played not just with changing the paradigm, but also trying to alter the history by doing so. The age old myth of putting Ahalya as a part of the five virgins (panchkanya) of Hindu mythology is explored in the paper. God's manoeuvre cannot be questioned and the two male characters tend to again shape the deed and the life of the female character, Ahalya. It is of importance to note that even in the 21st century, progressive actors like Radhika Apte fail to acknowledge the politics of altering history, not in a progressive way. The film blinds the viewer in the first watch to fall for the female strength and ownership of her sexuality, which is reflected in the opening scene itself where she opens the gate for the police man Indra Sen (representing God Indra who seduced her) who is charmed by her white dress. White, in Hindu mythology, stands for mourning, and this can be a hint towards the prophecy of what is about to come. Ahalya, bold, strong, and confident in this scene seems to be in total ownership of her sexual identity. Further, as the film progresses, control of Ahalya over her acts becomes even more dominant. In the myth of Ahalya, Gautama Maharishi, her husband, who wins her by Brahma's courtesy, curses her for her infidelity. She is then turned into a stone because of the curse and is redeemed when Lord Rama's foot brushes the stone. In the film, it is with the help of Ahalya that Goutam Sadhu turns Indra Sen into a stone doll. Ahalya is seen as a seductress who bewitches Indra Sen, and because the latter falls for the trap laid by the husband wife duo, he is turned into a doll. The attempt made by the paper is to read Ahalya as a character of the stand in wife who is yet again a pawn in the play of Goutama's revenge from Indra (who in the myth is able to escape from any curse or punishment for the act). The paper, therefore, reverts the idea which has till now been signified by the film and attempts to study the feminism this film appropriates. It is essential to break down the structure formed by such overt transgressing films in order to provide a real outlook of how feminism is twisted and moulded according to a man’s wishes.

Keywords: deconstructing, Hindu mythology, Panchkanya, predominant feminism, seductress, stone doll

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Authors: Stephanie Newman

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Niemann-Pick Type C disease is a rare, usually fatal lysosomal storage disorder. Although clinically characterized by progressive neurodegeneration, there is also evidence of altered innate immune responses such as neuroinflammation that promote disease progression. We have initiated an investigation into whether phagocytosis, an important innate immune activity and the process by which particles are ingested is defective in NPC. Using an in vitro assay, we have shown that NPC macrophages have a deficiency in the phagocytosis of different particles. We plan to investigate the mechanistic basis for impaired phagocytosis, the contribution that this deficiency makes to disease pathology, and whether therapies that have shown in vivo benefit are able to restore phagocytic activity.

Keywords: Niemann Pick Disease C, phagocytosis, innate immunity, lysosomal storage disorder

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Authors: Abdul Basit Kiani

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Web development, the art of creating and maintaining websites, has witnessed remarkable advancements. The aim is to provide an overview of some of the cutting-edge developments in the field. Firstly, the rise of responsive web design has revolutionized user experiences across devices. With the increasing prevalence of smartphones and tablets, web developers have adapted to ensure seamless browsing experiences, regardless of screen size. This progress has greatly enhanced accessibility and usability, catering to the diverse needs of users worldwide. Additionally, the evolution of web frameworks and libraries has significantly streamlined the development process. Tools such as React, Angular, and Vue.js have empowered developers to build dynamic and interactive web applications with ease. These frameworks not only enhance efficiency but also bolster scalability, allowing for the creation of complex and feature-rich web solutions. Furthermore, the emergence of progressive web applications (PWAs) has bridged the gap between native mobile apps and web development. PWAs leverage modern web technologies to deliver app-like experiences, including offline functionality, push notifications, and seamless installation. This innovation has transformed the way users interact with websites, blurring the boundaries between traditional web and mobile applications. Moreover, the integration of artificial intelligence (AI) and machine learning (ML) has opened new horizons in web development. Chatbots, intelligent recommendation systems, and personalization algorithms have become integral components of modern websites. These AI-powered features enhance user engagement, provide personalized experiences, and streamline customer support processes, revolutionizing the way businesses interact with their audiences. Lastly, the emphasis on web security and privacy has been a pivotal area of progress. With the increasing incidents of cyber threats, web developers have implemented robust security measures to safeguard user data and ensure secure transactions. Innovations such as HTTPS protocol, two-factor authentication, and advanced encryption techniques have bolstered the overall security of web applications, fostering trust and confidence among users. Hence, recent progress in web development has propelled the industry forward, enabling developers to craft innovative and immersive digital experiences. From responsive design to AI integration and enhanced security, the landscape of web development continues to evolve, promising a future filled with endless possibilities.

Keywords: progressive web applications (PWAs), web security, machine learning (ML), web frameworks, advancement responsive web design

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Authors: Fatih Sonmez

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Alzheimer’s disease (AD) is a progressive neurodegenerative disease and it is the most common form of dementia that affects aged people. Acetylcholinesterase is a hydrolase involved in the termination of impulse transmission at cholinergic synapses by rapid hydrolysis of the neurotransmitter ACh in the central and peripheral nervous system. Carvacrol (5-iso-propyl-2-methyl-phenol) is a main bioactive monoterpene isolated from many medicinal herbs, such as Thymus vulgaris, Monarda punctate and Origanum vulgare spp. It is known that carvacrol has been widely used as an active anti-inflammatory ingredient, which can inhibit the isoproterenol induced inflammation in myocardial infarcted rats. In this paper, a series of 12 carvacrol substituted carbamate derivatives (2a-l) was synthesized and their inhibitory activities on AChE and BuChE were evaluated. Among them, 2d exhibited the strongest inhibition against AChE with an IC50 value of 2.22 µM, which was 130-fold more than that of carvacrol (IC50 = 288.26 µM).

Keywords: Acetylcholinesterase, Butyrylcholinesterase, Carbamate, Carvacrol

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Authors: Nikolaos Mavropoulos

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Imperialism and colonialism had and still have a predominantly negative nuisance. In many ways the two terms are synonyms of racist behavior, exploitation, and oppression, imposed by the supposedly civilized West at Africa’s and Asia’s expense. Paradoxically enough, imperialism was not thoroughly negative for some Marxist scholars. For them, in reality, it served a historical necessity as the only mean to liberate the backward societies from their millennial stagnation and to introduce them to industrialization and progress. To Marx as immoral and cruel the imposition of imperial rule and the eradication of traditional structures may have been, the process is still a progressive step towards the formation of class consciousness, global revolution and socialism in a world scale. Overlooking the fact that imperialism could actually delay and put an end to capitalist development, some Marxists proponents considered it as a positive development for the colonized peoples.

Keywords: Colonialism, , Marxist theory, Modern history, , 19th century Imperialism,

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Authors: Fahad A. Alotaibi

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An increase in salt dissolution rate with continuous water flow is expected to lead to the progressive collapse of the soil structure. Evaluation of the relationship between soil salt dissolution and the variation of sabkha soil permeability in terms of type, rate, and quantity in order to assure construction safety in these environments. The current study investigates the relationship of soil permeability with the rate of dissolution of calcium (Ca2+), sulfate (SO4-2), chloride (CL−1), magnesium (Mg2+), sodium (Na+), and potassium (K+1) ions. Results revealed an increase in sabkha soil permeability with the rate of ions dissolution. This makes the efficiency of using a waterproofing stabilization agent in the reduction of sabkha salts dissolution the main criterion is selecting suitable stabilizing method.

Keywords: sabkha, permeability, salts, dissolution

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Authors: A. Chellil, A. Nour, S. Lecheb , H. Mechakra, L. Addar, H. Kebir

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This paper present a mechanical characteristics on fatigue crack propagation in Aluminium Plate based on strain and stress distribution using the abaqus software. The changes in shear strain and stress distribution during the fatigue cycle with crack growth is identified. In progressive crack in the strain distribution and the stress is increase in the critical zone. Numerical Modal analysis of the model developed, prove that the Eigen frequencies of aluminium plate were decreased after cracking, and this reduce is nonlinear. These results can provide a reference for analysts and designers of aluminium alloys in aeronautical systems. Therefore, the modal analysis is an important factor for monitoring the aeronautic structures.

Keywords: aluminum alloys, plate, crack, failure

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Authors: Zaima Umar, Anas S. Qureshi, Adeel Sarfraz, Saqib Umar, Talha Umar, Muhammad Usman

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Ostrich has been a good source of food and income for people across the world. To get a better understanding of health and health-related problems, the knowledge of its digestive system is of utmost importance. The present study was conducted to determine the morphological and histometrical variations in the digestive system and associated glands of ostrich (Struthio camelus) as regard to the gender and progressive age. A total of 40 apparently healthy ostriches of both genders and two progressive age groups; young one (less than two year, group A); and adult (2-15 years, group B) in equal number were used in this study. Digestive organs including tongue, esophagus, proventriculus, gizzard, small and large intestines and associated glands like liver and pancreas were collected immediately after slaughtering the birds. The organs of the digestive system and associated glands of each group were studied grossly and histologically. Grossly colour, shape consistency, weight and various dimensions (length, width, and circumference) of organs of the digestive tract and associated glands were recorded. The mean (± SEM) of all gross anatomical parameters in group A were significantly (p ≤ 0.01) different from that of group B. For microscopic studies, 1-2 cm tissue samples of organs of the digestive system and associated glands were taken. The tissue was marked and fixed in the neutral buffer formaldehyde solution for histological studies. After fixation, the sections of 5-7 µm were cut and stained by haematoxylin and eosin stain. All the layers (epithelium, lamina propria, lamina muscularis, submucosa and tunica muscularis) were measured (µm) with the help of automated computer software Image J®. The results of this study provide valuable information on the gender and age-related histological and histometrical variations in the digestive organs of ostrich (Struthio camelus). The microscopic studies of different parts of the digestive system revealed highly significant differences (p ≤ 0.01) among the two groups. The esophagus was lined by non-keratinized stratified squamous epithelium. The duodenum, jejunum, and ileum showed similar histological structures. Statistical analysis revealed significant (p ≤ 0.05) increase in the thickness of different tunics of the gastrointestinal tract in adult birds (up to 15 years) as compared with young ones (less than two years). Therefore, it can be concluded that there is a gradual but consistent growth in the observed digestive organs mimicking that of other poultry species and may be helpful in determining the growth pattern in this bird. However, there is a need to record the changes at closer time intervals.

Keywords: ostrich, digestive system, histomorphometry, grossly

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Authors: Ahmed Rashed

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Sarcoptic mange is generally recognized as one of the most serious diseases in camels in Libya. It is an extremely pruritic and contagious skin condition caused by Sarcoptes scabiei var cameli. Thirteen camels (camelis dromedaries), showing progressive infection with S.scabiei mites in skin scrapings, were chosen randomly from different affected herds at AL-Assa camel project. Ten camels were treated with ivermectin (22,23-dihydroavermectin B1, Ivomec, Merck) at a dose rate of 0.2 mg./kg.body weight. Scratching and rubbing had completely disappeared in the treated camels one week after the second injection. Two weeks after the second injection motile mites were found on only one camel, and three weeks after the second injection, no motile mites were detected. Motile mites were observed in the three untreated camels up to the end of the trial.

Keywords: ivermecti, Sarcoptes scabiei, camels, scrapings

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Authors: Meriem Hamla, Mohamed Benaicha, Sabrine Derbal

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In the present work, several materials such as M/glass (M = Pt, Mo) were investigated to test their suitability for studying the early nucleation stages and growth of copper-tin clusters. It was found that most of these materials stand as good substrates to be used in the study of the nucleation and growth of electrodeposited Cu-Sn alloys from aqueous solution containing CuCl2, SnCl2 as electroactive species and Na3C6H5O7 as complexing agent. Among these substrates, Pt shows instantaneous models followed by 3D diffusion-limited growth. On the other hand, the electrodeposited copper-tin thin films onto Mo substrate followed progressive nucleation. The deposition mechanism of the Cu-Sn films has been studied using stationary electrochemical techniques (cyclic voltammetery (CV) and chronoamperometry (CA). The structural, morphological and compositional of characterization have been studied using X-ray diffraction (XRD), scanning electron microscopy (SEM) and EDAX techniques respectively.

Keywords: electrodeposition, CuSn, nucleation, mechanism

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Authors: Ľubomír Šooš, Peter Križan, Juraj Beniak, Miloš Matúš

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The success of introducing a new product on the market is the new principle of production, or progressive design, improved efficiency or high quality of manufactured products. Proportionally with the growth of interest in press-biofuels - pellets or briquettes, is also growing interest in the new design better, more efficiently machines produce pellets, briquettes or granules completely new shapes. Our department has for years dedicated to the development of new highly productive designs pressing machines and new optimized press-biofuels. In this field, we have more than 40 national and international patents. The aim of paper is description of the introduction of a new principle pelleting mill and the description of his process of research, development, manufacturing and testing to deployment into production.

Keywords: compacting process, pellets mill, design, new conception, press-biofuels, patent, waste

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Authors: Jagannath Mohanty, Shiv Nath Sinha

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India is the first country in the world, where spending on Corporate Social Responsibily (CSR) has been made mandatory. Predominantly Indian enterprises have been philanthrophic for hundreds of years, where giving back to the society is the religious duty of the rich. Therefore Indian businesses have been voluntarily spending on CSR activities, while several businesses kept spending on non business activities a significant number of entrepreneurs abstained from social spending, leading Government of India to take the lesgislative route by mandating 2% spend of net profit on CSR activities failing which companeis will be dealt legally. While the legislation on suface appers progressive and pro social, yet the consequences of making a rather volutary action a legally binding act is yet to be seen. This paper examines the possible social impact of the legislation and potential response of the corporate to a legislation of this kind.

Keywords: corporate social responsibility (CSR), companies act 2013, corporate citizenship, social spending

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Authors: J. O. Yeboah, K Aboraa, K. Kodom

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The chemical and physical characteristics of rainwater harvested from a typical rooftop were progressively studied. The samples of rainwater collected were analyzed for pH, major ion concentrations, TDS, turbidity, conductivity. All the physicochemical constituents fell within the WHO guideline limits at some points as rainfall progresses except the pH. All the components of rainwater quality measured during the study showed higher concentrations during the early stages of rainfall and reduce as time progresses. There was a downward trend in terms of pH as rain progressed, with 18% of the samples recording pH below the WHO limit of 6.5-8.0. It was observed that iron concentration was above the WHO threshold value of 0.3 mg/l on occasions of heavy rains. The results revealed that most of physicochemical characteristics of rainwater samples were generally below the WHO threshold, as such, the rainwater characteristics showed satisfactory conditions in terms of physicochemical constituents.

Keywords: conductivity, pH, physicochemical, rainwater quality, TDS

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Authors: Ammar Maziz, Mostapha Tarfaoui, Said Rechak

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The high mechanical performance of composite pipes can be adversely affected by their low resistance to impact loads. Loads in dynamic origin are dangerous and cause consequences on the operation of pipes because the damage is often not detected and can affect the structural integrity of composite pipes. In this work, an advanced 3-D finite element (FE) model, based on the use of intralaminar damage models was developed and used to predict damage under low-velocity impact. The performance of the numerical model is validated with the confrontation with the results of experimental tests. The results show that at low impact energy, the damage happens mainly by matrix cracking and delamination. The model capabilities to simulate the low-velocity impact events on the full-scale composite structures were proved.

Keywords: composite materials, low velocity impact, FEA, dynamic behavior, progressive damage modeling

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Authors: Kelsi Hagerty, Ami Rosen, Aaliyah Heyward, Nadia Ali, Emily Brown, Erin Demo, Yue Guan, Modele Ogunniyi, Brianna McDaniels, Alanna Morris, Kunal Bhatt

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Hereditary transthyretin amyloidosis (hATTR) is a progressive, multi-systemic, and life-threatening disease caused by a disruption in the TTR protein that delivers thyroxine and retinol to the liver. This disruption causes the protein to misfold into amyloid fibrils, leading to the accumulation of the amyloid fibrils in the heart, nerves, and GI tract. Over 130 variants in the TTR gene are known to cause hATTR. The Val122Ile variant is the most common in the United States and is seen almost exclusively in people of African descent. TTR variants are inherited in an autosomal dominant fashion and have incomplete penetrance and variable expressivity. Individuals with hATTR may exhibit symptoms from as early as 30 years to as late as 80 years of age. hATTR is characterized by a wide range of clinical symptoms such as cardiomyopathy, neuropathy, carpal tunnel syndrome, and GI complications. Without treatment, hATTR leads to progressive disease and can ultimately lead to heart failure. hATTR disproportionately affects individuals of African descent; the estimated prevalence of hATTR among Black individuals in the US is 3.4%. Unfortunately, hATTR is often underdiagnosed and misdiagnosed because many symptoms of the disease overlap with other cardiac conditions. Due to the progressive nature of the disease, multi-systemic manifestations that can lead to a shortened lifespan, and the availability of free genetic testing and promising FDA-approved therapies that enhance treatability, early identification of individuals with a pathogenic hATTR variant is important, as this can significantly impact medical management for patients and their relatives. Furthermore, recent literature suggests that TTR genetic testing should be performed in all patients with suspicion of TTR-related cardiomyopathy, regardless of age, and that follow-up with genetic counseling services is recommended. Relatives of patients with hATTR benefit from genetic testing because testing can identify carriers early and allow relatives to receive regular screening and management. Despite the striking prevalence of hATTR among Black individuals, hATTR remains underdiagnosed in this patient population, and germline genetic testing for hATTR in Black individuals seems to be underrepresented, though the reasons for this have not yet been brought to light. Historically, Black patients experience a number of barriers to seeking healthcare that has been hypothesized to perpetuate the underdiagnosis of hATTR, such as lack of access and mistrust of healthcare professionals. Prior research has described a myriad of factors that shape an individual’s decision about whether to pursue presymptomatic genetic testing for a familial pathogenic variant, such as family closeness and communication, family dynamics, and a desire to inform other family members about potential health risks. This study explores these factors through 10 in-depth interviews with patients with hATTR about what factors may be contributing to the underdiagnosis of hATTR in the Black population. Participants were selected from the Emory University Amyloidosis clinic based on having a molecular diagnosis of hATTR. Interviews were recorded and transcribed verbatim, then coded using MAXQDA software. Thematic analysis was completed to draw commonalities between participants. Upon preliminary analysis, several themes have emerged. Barriers identified include i) Misdiagnosis and a prolonged diagnostic odyssey, ii) Family communication and dynamics surrounding health issues, iii) Perceptions of healthcare and one’s own health risks, and iv) The need for more intimate provider-patient relationships and communication. Overall, this study gleaned valuable insight from members of the Black community about possible factors contributing to the underdiagnosis of hATTR, as well as potential solutions to go about resolving this issue.

Keywords: cardiac amyloidosis, heart failure, TTR, genetic testing

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Authors: Hadiseh Hosamirudsari, Farhad Afsarikordehmahin, Pooria Sekhavatfar

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Concomitant cortical blindness and deafness that follow varicella zoster virus (VZV) infection is rare. We describe a case of ophthalmic zoster that caused cortical blindness and deafness after central nervous system (CNS) involvement. A 42-year old, HIV infected woman has developed progressive blurry vision and deafness, 4 weeks after ophthalmic zoster. A physical examination and positive VZV polymerase chain reaction (PCR) of cerebrospinal fluid (CSF) suggested VZV encephalitis. Complication of VZV encephalitis is considered as the cause of blindness and deafness. In neurological deficit patient especially with a history of herpes zoster, VZV infection should be regarded as the responsible agent in inflammatory disorders of nervous system. The immunocompromised state of patient (including HIV) is as important an agent as VZV infection in developing the disease.

Keywords: blindness, deafness, hiv, VZV encephalitis

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Authors: Ghada Al-Kafaji, Mohamed Sabry

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Mitochondria are the site of cellular respiration and produce energy in the form of adenosine triphosphate (ATP) via oxidative phosphorylation. They are the major source of intracellular reactive oxygen species (ROS) and are also direct target to ROS attack. Oxidative stress and ROS-mediated disruptions of mitochondrial function are major components involved in the pathogenicity of diabetic complications. In this work, the changes in mitochondrial DNA (mtDNA) copy number, biogenesis, gene expression of mtDNA-encoded subunits of electron transport chain (ETC) complexes, and mitochondrial function in response to hyperglycemia-induced ROS and the effect of direct inhibition of ROS on mitochondria were investigated in an in vitro model of diabetic nephropathy using human renal mesangial cells. The cells were exposed to normoglycemic and hyperglycemic conditions in the presence and absence of Mn(III)tetrakis(4-benzoic acid) porphyrin chloride (MnTBAP) or catalase for 1, 4 and 7 days. ROS production was assessed by the confocal microscope and flow cytometry. mtDNA copy number and PGC-1a, NRF-1, and TFAM, as well as ND2, CYTB, COI, and ATPase 6 transcripts, were all analyzed by real-time PCR. PGC-1a, NRF-1, and TFAM, as well as ND2, CYTB, COI, and ATPase 6 proteins, were analyzed by Western blotting. Mitochondrial function was determined by assessing mitochondrial membrane potential and adenosine triphosphate (ATP) levels. Hyperglycemia-induced a significant increase in the production of mitochondrial superoxide and hydrogen peroxide at day 1 (P < 0.05), and this increase remained significantly elevated at days 4 and 7 (P < 0.05). The copy number of mtDNA and expression of PGC-1a, NRF-1, and TFAM as well as ND2, CYTB, CO1 and ATPase 6 increased after one day of hyperglycemia (P < 0.05), with a significant reduction in all those parameters at 4 and 7 days (P < 0.05). The mitochondrial membrane potential decreased progressively at 1 to 7 days of hyperglycemia with the parallel progressive reduction in ATP levels over time (P < 0.05). MnTBAP and catalase treatment of cells cultured under hyperglycemic conditions attenuated ROS production reversed renal mitochondrial oxidative stress and improved mtDNA, mitochondrial biogenesis, and function. These results show that hyperglycemia-induced ROS caused an early increase in mtDNA copy number, mitochondrial biogenesis and mtDNA-encoded gene expression of the ETC subunits in human mesangial cells as a compensatory response to the decline in mitochondrial function, which precede the mtDNA defect and mitochondrial dysfunction with a progressive oxidative response. Protection from ROS-mediated damage to renal mitochondria induced by hyperglycemia may be a novel therapeutic approach for the prevention/treatment of DN.

Keywords: diabetic nephropathy, hyperglycemia, reactive oxygen species, oxidative stress, mtDNA, mitochondrial dysfunction, manganese superoxide dismutase, catalase

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Authors: J. E. Appel, R. N. Bouwmeester, L. Crombach, K. Georgieva, N. O’Shea, T. I. van Rijssel, L. Wingens

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The Netherlands has a unique and progressive euthanasia law. Even people with advanced neurodegenerative diseases, like dementia, can request euthanasia when an Advanced Euthanasia Directive (AED) was written. Although the law sets some guidelines, in practice many complexities occur. Especially doctors experience difficult situations, as they have to decide whether euthanasia is justified. Research suggests that this leads to an emotional burden for them, due to feelings of isolation, fear of prosecution, as well as pressures from patient, family, or society. Existing literature, however, failed to address problems arising in dementia cases in particular, as well as possible sources of support. In order to investigate these issues, semi-structured in-depth interviews with 20 Dutch general practitioners and elderly care physicians will be conducted. Results are expected to be obtained by the end of December 2017.

Keywords: dementia, euthanasia, general practitioners, elderly care physicians, palliative care

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Authors: Spira A., Marabelle A., Kientop D., Moser E., Mumm J.

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Background: Both interleukin-2 (IL-2) and interleukin-10 (IL-10) have been extensively studied for their stimulatory function on T cells and their potential to obtain sustainable tumor control in RCC, melanoma, lung, and pancreatic cancer as monotherapy, as well as combination with PD-1 blockers, radiation, and chemotherapy. While approved, IL-2 retains significant toxicity, preventing its widespread use. The significant efforts undertaken to uncouple IL-2 toxicity from its anti-tumor function have been unsuccessful, and early phase clinical safety observed with PEGylated IL-10 was not met in a blinded Phase 3 trial. Deka Biosciences has engineered a novel molecule coupling wild-type IL-2 to a high affinity variant of Epstein Barr Viral (EBV) IL-10 via a scaffold (scFv) that binds to epidermal growth factor receptors (EGFR). This patented molecule, termed DK210 (EGFR), is retained at high levels within the tumor microenvironment for days after dosing. In addition to overlapping and non-redundant anti-tumor function, IL-10 reduces IL-2 mediated cytokine release syndrome risks and inhibits IL-2 mediated T regulatory cell proliferation. Methods: DK210 (EGFR) is being evaluated in an open-label, dose-escalation (Phase 1) study with 5 (0.025-0.3 mg/kg) monotherapy dose levels and (expansion cohorts) in combination with PD-1 blockers, or radiation or chemotherapy in patients with advanced solid tumors overexpressing EGFR. Key eligibility criteria include 1) confirmed progressive disease on at least one line of systemic treatment, 2) EGFR overexpression or amplification documented in histology reports, 3) at least a 4 week or 5 half-lives window since last treatment, and 4) excluding subjects with long QT syndrome, multiple myeloma, multiple sclerosis, myasthenia gravis or uncontrolled infectious, psychiatric, neurologic, or cancer disease. Plasma and tissue samples will be investigated for pharmacodynamic and predictive biomarkers and genetic signatures associated with IFN-gamma secretion, aiming to select subjects for treatment in Phase 2. Conclusion: Through successful coupling of wild-type IL-2 with a high affinity IL-10 and targeting directly to the tumor microenvironment, DK210 (EGFR) has the potential to harness IL-2 and IL-10’s known anti-cancer promise while reducing immunogenicity and toxicity risks enabling safe concomitant cytokine treatment with other anti-cancer modalities.

Keywords: cytokine, EGFR over expression, interleukine-2, interleukine-10, clinical trial

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Authors: Keigo Nishitani, Kohei Mizuta Mizuta, Kazuyoshi Kurita, Yukinori Taniguchi

Abstract:

To establish mass production process of Ti capsule which has Fe powder inside as magnetic hyperthermia implant, we assumed that Ti thin sheet can be drawn into a φ1.0 mm die hole through the medium of Fe Powder and becomes outer shell of capsule. This study discusses mechanism of powder assisted deep drawing process by both of numerical simulation and experiment. Ti thin sheet blank was placed on die, and was covered by Fe powder layer without pressurizing. Then upper punch was indented on the Fe powder layer, and the blank can be drawn into die cavity as pressurized powder particles were extruded into die cavity from behind of the drawn blank. Distinct Element Method (DEM) has been used to demonstrate the process. To identify bonding parameters on Fe particles which are cohesion, tensile bond stress and inter particle friction angle, axial and diametrical compression failure test of Fe powder compact was conducted. Several density ratios of powder compacts in range of 0.70 - 0.85 were investigated and relationship between mean stress and equivalent stress was calculated with consideration of critical state line which rules failure criterion in consolidation of Fe powder. Since variation of bonding parameters with density ratio has been experimentally identified, and good agreement has been recognized between several failure tests and its simulation, demonstration of powder assisted sheet forming by using DEM becomes applicable. Results of simulation indicated that indent/drawing length of Ti thin sheet is promoted by smaller Fe particle size, larger indent punch diameter, lower friction coefficient between die surface and Ti sheet and certain degrees of die inlet taper angle. In the deep drawing test, we have made die-set with φ2.4 mm punch and φ1.0 mm die bore diameter. Pure Ti sheet with 100 μm thickness, annealed at 650 deg. C has been tested. After indentation, indented/drawn capsule has been observed by microscope, and its length was measured to discuss the feasibility of this capsulation process. Longer drawing length exists on progressive loading pass comparing with the case of single stroke loading. It is expected that progressive loading has an advantage of which extrusion of powder particle into die cavity with Ti sheet is promoted since powder particle layer can be rebuilt while the punch is withdrawn from the layer in each loading steps. This capsulation phenomenon is qualitatively demonstrated by DEM simulation. Finally, we have fabricated Ti capsule which has Fe powder inside for magnetic hyperthermia cancer care treatment. It is concluded that suggested method is possible to use the manufacturing of Ti capsule implant for magnetic hyperthermia cancer care.

Keywords: metal powder compaction, metal forming, distinct element method, cancer care, magnetic hyperthermia

Procedia PDF Downloads 257

Authors: Kechikeche Nabil

Abstract:

The MENA region has undergone many mutations throughout history. The most significant one was, yet, to happen during the colonial era, where the Arab Muslim ‘cosmic’ clock was recalibrated to match a more or less modern perception of time. As for modern civic and political experiences of life, they were left in a state of inertia. This article considers the problematic amalgam of traditional Islam, modernity and democratization in the Arab world, as well as the effects on the configuration of recent progressive endeavours. It is argued that the assimilation of democratic ethos - as a requisite for modernity - depends on the assimilation of power, progress and time, by what is referred to as the Umma. Drawing on postmodern and political literature, it is suggested that because of a conceptualization which draws mainly on traditional Islam, the Umma and the state in the Arab world remain in conflict while, at times, they appear to act collaboratively, either to embrace modernity or to obstruct democratization.

Keywords: Islam, democracy, Arab world, modernity

Procedia PDF Downloads 11

Authors: Jin Huang

Abstract:

Research shows that asset-building policies have positive financial and non-financial impacts on children and families. To promote the development of asset-building policies for children in China, it is important to understand the current status of family savings for children. We use the data from the 2016 China Family Panel Studies and show only 16% of families have savings designated for children’s future education. Families with advantaged socioeconomic backgrounds are more likely to save and also save more for their children than their counterparts with disadvantaged backgrounds. Without large-scale and progressive policy interventions, families with disadvantaged backgrounds are less likely to build assets for children. Policy and practice implications for family social workers are discussed.

Keywords: assets, asset building, child, china, education, family, savings

Procedia PDF Downloads 60

Authors: Hong Dongchen, Chen Qiuxiao, Wu Shuang

Abstract:

Systematic science reveals the complex nonlinear mechanisms of behaviour in urban system. However, in China, when the current city planners face with the system, most of them are still taking simple linear thinking to consider the open complex giant system. This paper introduces the hyper-cycle theory, which is one of the basis theories of systematic science, based on the analysis of the reasons why the current urban planning failed, and proposals for optimization ideas that urban planning compilation should change, from controlling quantitative to the changes of relationship, from blueprint planning to progressive planning based on the nonlinear characteristics and from management control to dynamically monitor feedback.

Keywords: systematic science, hyper-cycle theory, urban planning, urban management

Procedia PDF Downloads 367