Search results for: the spiral of silence

Authors: Raza Abdulla Saeed

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In this study, the three-dimensional cavitating turbulent flow in a complete Francis turbine is simulated using mixture model for cavity/liquid two-phase flows. Numerical analysis is carried out using ANSYS CFX software release 12, and standard k-ε turbulence model is adopted for this analysis. The computational fluid domain consist of spiral casing, stay vanes, guide vanes, runner and draft tube. The computational domain is discretized with a three-dimensional mesh system of unstructured tetrahedron mesh. The finite volume method (FVM) is used to solve the governing equations of the mixture model. Results of cavitation on the runner’s blades under three different boundary conditions are presented and discussed. From the numerical results it has been found that the numerical method was successfully applied to simulate the cavitating two-phase turbulent flow through a Francis turbine, and also cavitation is clearly predicted in the form of water vapor formation inside the turbine. By comparison the numerical prediction results with a real runner; it’s shown that the region of higher volume fraction obtained by simulation is consistent with the region of runner cavitation damage.

Keywords: computational fluid dynamics, hydraulic francis turbine, numerical simulation, two-phase mixture cavitation model

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Authors: Ashwin Bala, K. Panthalaraja Kumaran, S. Prithviraj, R. Pradeep, J. Udhayakumar, S. Ajith

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In this paper, studies have been carried out for an in-house design of a waste heat recovery system for effectively utilizing the domestic air conditioner heat energy for producing hot water. Theoretical studies have been carried to optimizing the flow rate for getting maximum output with a minimum size of the heater. Critical diameter, wall thickness, and total length of the water pipeline have been estimated from the conventional heat transfer model. Several combinations of pipeline shapes viz., spiral, coil, zigzag wound through the radiator has been attempted and accordingly shape has been optimized using heat transfer analyses. The initial condition is declared based on the water flow rate and temperature. Through the parametric analytical studies we have conjectured that water flow rate, temperature difference between incoming water and radiator skin temperature, pipe material, radiator material, geometry of the water pipe viz., length, diameter, and wall thickness are having bearing on the lucrative design of a waste heat recovery system for air conditioners. Results generated through the numerical studies have been validated using an in-house waste heat recovery system for air conditioners.

Keywords: air conditioner design, energy conversion system, radiator design for energy recovery systems, waste heat recovery system

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Authors: Sherly Ferro Lensun, Donal Matheos Ratu, Elni Jeini Usoh, Helena M. L. Pandi, Mayske Rinny Liando

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This study aims to gain a deep understanding of the process and the increase resulting in mastery of Kanji with a Language Learning Strategies through multimedia. This research aims to gain scientific data on process and the result of improving kanji mastery by using Chokusetsu strategy in Kanji learning. The method used in this research is Action Research developed by Kemmis and Mc. Taggart is known as Spiral Model. This model consists of following stages: planning, implementation, observation, and reflection. The research results in following findings: (1) Kanji mastery comprises 4 major aspects, those are reading, writing, the use in sentence, and memorizing, and those aspects show gradual improvement from time to time. (2) Students have more participation in learning activities which can be identified from some positive behaviours such giving respond in finishing exercise in class. (3) Students’ better attention to the lesson shown by active behaviour in giving more questions or asking for more explanation to the lecturers, memorizing Kanji card, finishing the task of making Kanji card/house, doing the exercises more seriously, and finishing homework assignment punctually. (4) More attractive learning activities and tasks in the forms of more engaging colour and pictures enables students to conduct self-evaluation on their learning process.

Keywords: Kanji, action research, language learning strategies, multimedia

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Authors: Narendra Nath Patra

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Several recent studies reinforce the existence of a thick molecular disc in galaxies along with the dynamically cold thin disc. Assuming a two-component molecular disc, we model the disc of NGC 6946 as a four-component system consists of stars, HI, thin disc molecular gas, and thick disc molecular gas in vertical hydrostatic equilibrium. Following, we set up the joint Poisson-Boltzmann equation of hydrostatic equilibrium and solve it numerically to obtain a three-dimensional density distribution of different baryonic components. Using the density solutions and the observed rotation curve, we further build a three-dimensional dynamical model of the molecular disc and consecutively produce simulated CO spectral cube and spectral width profile. We find that the simulated spectral width profiles distinguishably differs for different assumed thick disc molecular gas fraction. Several CO spectral width profiles are then produced for different assumed thick disc molecular gas fractions and compared with the observed one to obtain the best fit thick disc molecular gas fraction profile. We find that the thick disc molecular gas fraction in NGC 6946 largely remains constant across its molecular disc with a mean value of 0.70 +/- 0.09. We also estimate the amount of extra-planar molecular gas in NGC 6946. We find 60% of the total molecular gas is extra-planar at the central region, whereas this fraction reduces to ~ 35% at the edge of the molecular disc. With our method, for the first time, we estimate the thick disc molecular gas fraction as a function of radius in an external galaxy with sub-kpc resolution.

Keywords: galaxies: kinematics and dynamic, galaxies: spiral, galaxies: structure , ISM: molecules, molecular data

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Authors: Shafag Dadashova

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The study discusses relativity of perception and interpretation of power, its interdependence with conformity level of an individual. It describes an autobiography as a form of epiphany. It is suggested that life-writing helps the author analyze the past and define the borders of his personal power and sources of empowerment. As all life-writings deal with behaviors, values, attitudes, relationships and emotions, their investigation requires qualitative methods to understand social norms, gender roles, religion, and their role in empowerment and disempowerment of the author. The study consists of two parts. The first part is theoretical and interrogates the notion of personal power and how writing the own life can bring to conscious empowerment. The second part presents two autobiographies by female authors from two different Muslim cultures who negotiate between the larger nationalist agenda and their own personal concerns. These autobiographies (Tehmina Durrani, Pakistani author ‘My Feudal Lord’, Banine, Azerbaijani writer 'Caucasian days' and 'Parisian days') are the end of their authors’ long silence, their revolt against the conventional norms, their decision to have an agency to confess and protest. These autobiographies are the authors’ attempts to break the established matrix of perceptions, imposed norms, and gain power to build the real picture of their identity. The study sums up with the conclusion that in spite of very similar motifs of female authors to get empowered through self-analysis, different cultures and time create specific subjectivities associated with particular historical events and geographical location.

Keywords: conformity level, empowerment, female autobiography, self-identity

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Authors: Saira Hossain

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Well-being commonly refers to the concept that equates to a good life. Similarly, student well-being can be understood as a notion of a good life at school. What constitutes a good life at school for students? – is an emerging question that poses huge interest in this area of research. Student well-being is not only associated with a student’s socio-emotional and academic development at school but also success in life after school as an adult. Today, student well-being is a popular agenda for educators, policymakers, teachers, parents, and most importantly, for students. With the emergence of student well-being, student's voice in matters important to them at school is increasingly getting priority. However, the coin has another side too. Despite the growing importance of understanding student well-being, it is still an alien concept in countries like Bangladesh. The education system of Bangladesh is highly rigid, centralized, and exam-focused. Student's academic achievement has been given the utmost priority at school, whereas their voice, as well as their well-being, is grossly neglected in practice. In this regard, the study set out to explore students' conceptualization of well-being at school in Bangladesh. The study was qualitative. It employed a participatory research approach to elicit the views of 25 secondary school students of aged 14-16 in Bangladesh to explore the concept of well-being. Data analysis was conducted following the thematic analysis technique. The results suggested that student conceptualized well-being as a multidimensional concept with multiple domains, including having, being, relating, feeling, thinking, functioning, and striving. The future implication of the study findings is discussed. Additionally, the study also underscores the implication of the participatory approach as a research technique to explore students' opinion in Bangladesh, where there exists a culture of silence regarding the student's voice.

Keywords: Bangladesh, participatory research, secondary school, student well-being

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Authors: C. Castro-Egler, A. Durán-Escalante, A. García-González

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This paper presents a method to generate a finite element model of the human auditory inner ear system. The geometric model has been realized using 2D images from a virtual model of temporal bones. A point cloud has been gotten manually from those images to construct a whole mesh with hexahedral elements. The main difference with the predecessor models is the spiral shape of the cochlea with its three scales completely defined: scala tympani, scala media and scala vestibuli; which are separate by basilar membrane and Reissner membrane. To validate this model, numerical simulations have been realised with two models: an isolated inner ear and a whole model of human auditory system. Ideal conditions of displacement are applied over the oval window in the isolated Inner Ear model. The whole model is made up of the outer auditory channel, the tympani, the ossicular chain, and the inner ear. The boundary condition for the whole model is 1Pa over the auditory channel entrance. The numerical simulations by FEM have been done using a harmonic analysis with a frequency range between 100-10.000 Hz with an interval of 100Hz. The following results have been carried out: basilar membrane displacement; the scala media pressure according to the cochlea length and the transfer function of the middle ear normalized with the pressure in the tympanic membrane. The basilar membrane displacements and the pressure in the scala media make it possible to validate the response in frequency of the basilar membrane.

Keywords: finite elements method, human auditory system model, numerical analysis, 3D modelling cochlea

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Authors: Usman Abubakar, Xiaoyuan Wang, Sayyed Haleem Shah, Sadiq Ur Rahman, Rabiu Saleh Zakariyya

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High-speed Permanent magnet synchronous machine (HSPMSM) uses in different industrial applications like blowers, compressors as a result of its superb performance. Nevertheless, the over-temperature rise of both winding and PM is one of their substantial problem for a high-power HSPMSM, which affects its lifespan and performance. According to the literature, HSPMSM with a Hybrid cooling configuration has a much lower temperature rise than non-hybrid cooling. This paper presents the design 185kW, 26K rpm with two different cooling configurations, i.e., hybrid cooling configuration (forced air and housing spiral water jacket) and non-hybrid (forced air cooling assisted with winding’s potting material and sleeve’s material) to enhance the heat dissipation of winding and PM respectively. Firstly, the machine’s electromagnetic design is conducted by the finite element method to accurately account for machine losses. Then machine’s cooling configurations are introduced, and their effectiveness is validated by lumped parameter thermal network (LPTN). Investigation shows that using potting, sleeve materials to assist non-hybrid cooling configuration makes the machine’s winding and PM temperature closer to hybrid cooling configuration. Therefore, the machine with non-hybrid cooling is prototyped and tested due to its simplicity, lower energy consumption and can still maintain the lifespan and performance of the HSPMSM.

Keywords: airflow network, axial ventilation, high-speed PMSM, thermal network

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Authors: Yan Lyu

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Japanese degree adverbs can be explained in different ways, which is hard for Japanese learners to comprehend. For instance, when ‘tyotto’ is used as a degree word, it can be interpreted literally or not. In the sentence ‘Ano mise, tyotto oishi yo. zehi iku to ii yo.’, ‘tyotto’ can be interpreted as a high degree contextually. Despite pragmatic factors, phonetics factors can also affect the interpretation of such ‘tyotto’. Concentrating on the pattern of ‘tyotto +adjective’, the paper aims to investigate the correlation between the interpretation of ‘tyotto’ and the phonetic factors in some specific contexts based on a listening experiment via PRAAT. It is also investigated that how the phonetic factors affect the interpretation of high degree adverbs, including ‘soutou’ , ‘totemo’ , ‘kanari’ and ‘sugoku’. In the experiment, Japanese speakers listened to sentences which were composed of degree adverbs and adjectives in different intonations and judged which degree the sentences expressed. Two conclusions can be drawn from the experiment results. Firstly, for adverbs expressing a high degree, in the pattern of ‘degree adverb + adjective’, either degree adverb or adjective is pronounced in a higher pitch, or both are highly pronounced, a higher degree can be expressed. Besides, with the insertion of geminate consonant and the extension of the vowel, the longer the duration of the degree adverb becomes, the higher degree can be expressed. Secondly, for ‘tyotto’, which expresses a low degree, the interpretation will be influenced by both phonetic and contextual factors. Phonetically, there are three factors causing ‘tyotto’ to be interpreted as a common degree or a high degree. The three factors are the high pitch of the modified adjective, the extended silence period of the geminate consonant and the change in the intonations of ‘tyotto’. In some contexts just like the comparison sentences, no matter how ‘tyotto + adjective’ is pronounced, ‘tyotto’ tends to be interpreted as a low degree literally.

Keywords: contextual interpretation, Japanese degree adverbs, phonetic interpretation, PRAAT

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Authors: Dutica Luminita

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For the music composer Myriam Marbe the musical time and memory represent 2 (complementary) phenomena with conclusive impact on the settlement of new musical ontologies. Summarizing the most important achievements of the contemporary techniques of composition, her vision on the microform presented in The Concert for Daniel Kientzy, saxophone and orchestra transcends the linear and unidirectional time in favour of a flexible, multi-vectorial speech with spiral developments, where the sound substance is auto(re)generated by analogy with the fundamental processes of the memory. The conceptual model is of an archetypal essence, the music composer being concerned with identifying the mechanisms of the creation process, especially of those specific to the collective creation (of oral tradition). Hence the spontaneity of expression, improvisation tint, free rhythm, micro-interval intonation, coloristic-timbral universe dominated by multiphonics and unique sound effects. Hence the atmosphere of ritual, however purged by the primary connotations and reprojected into a wonderful spectacular space. The Concert is a work of artistic maturity and enforces respect, among others, by the timbral diversity of the three species of saxophone required by the music composer (baritone, sopranino and alt), in Part III Daniel Kientzy shows the performance of playing two saxophones concomitantly. The score of the music composer Myriam Marbe contains a deeply spiritualized music, full or archetypal symbols, a music whose drama suggests a real cinematographic movement.

Keywords: archetype, chronogenesis, concert, multiphonics

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Authors: Alex Soares Castro, Matheus Manoel Teles de Menezes, Larissa Silva de Azevedo, Ana Carolina Caleffi Patelli, Osmair Vital de Oliveira, Aline Thais Bruni, Marcelo Firmino de Oliveira

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Considering the problem of the seizure of illicit drugs, as well as the development of electrochemical sensors using chemically modified electrodes, this work shows the study of the electrochemical activity of cocaine in carbon paste electrode chemically modified with Cu (II) trans 3-MeO salcn complex. In this context, cyclic voltammetry was performed on 0.1 mol.L⁻¹ KCl supporting electrolyte at a scan speed of 100 mV s⁻¹, using an electrochemical cell composed of three electrodes: Ag /AgCl electrode (filled KCl 3 mol.L⁻¹) from Metrohm® (reference electrode); a platinum spiral electrode, as an auxiliary electrode, and a carbon paste electrode chemically modified with Cu (II) trans 3-MeO complex (as working electrode). Two forms of cocaine were analyzed: cocaine hydrochloride (pH 3) and cocaine free base form (pH 8). The PM7 computational method predicted that the hydrochloride form is more stable than the free base form of cocaine, so with cyclic voltammetry, we found electrochemical signal only for cocaine in the form of hydrochloride, with an anodic peak at 1.10 V, with a linearity range between 2 and 20 μmol L⁻¹ had LD and LQ of 2.39 and 7.26x10-5 mol L⁻¹, respectively. The study also proved that cocaine is adsorbed on the surface of the working electrode, where through an irreversible process, where only anode peaks are observed, we have the oxidation of cocaine, which occurs in the hydrophilic region due to the loss of two electrons. The mechanism of this reaction was confirmed by the ab-inito quantum method.

Keywords: ab-initio computational method, analytical method, cocaine, Schiff base complex, voltammetry

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Authors: Ihab Al-Mokrani

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The Arabic heritage has two types of spoken rhetoric: the first type which al-Jaahiz calls “the rhetoric of the sign,” which means body language, and the rhetoric of silence which is of no less importance than the rhetoric of the sign, the speaker’s appearance and movements, etc. The second type is the spoken performance of utterances which bears written rhetoric arts like metaphor, simile, metonymy, etc. Rationale of the study: First: in spite of the factual existence of rhetorical phenomena in the Arabic heritage, there has been no contemporary study handling the spoken rhetoric in the Arabic heritage. Second: Arabic Civilization is originally a spoken one. Comparing the Arabic culture and civilization, from one side, to the Greek, roman or Pharaonic cultures and civilizations, from the other side, shows that the latter cultures and civilizations started and flourished written while the former started among illiterate people who had no interest in writing until recently. That sort of difference on the part of the Arabic culture and civilization created a rhetoric different from rhetoric in the other cultures and civilizations. Third: the spoken nature of the Arabic civilization influenced the Arabic rhetoric in the sense that specific rhetorical arts have been introduced matching that spoken nature. One of these arts is the art of concision which compensates for the absence of writing’s means of preserving the text. In addition, this interprets why many of the definitions of the Arabic rhetoric were defining rhetoric as the art of concision. Also, this interprets the fact that the literary genres known in the Arabic culture were limited by the available narrow space like poetry, anecdotes, and stories, while the literary genres in the Greek culture were of wide space as epics and drama. This is not of any contrast to the fact that some Arabic poetry would exceed 100 lines of poetry as Arabic poetry was based on the line organic unity, which means that every line could stand alone with a full meaning that is not dependent on the rest of the poem; and that last aspect has never happened in any culture other than the Arabic culture.

Keywords: Arabic rhetoric, spoken rhetoric, Arabic heritage, culture

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Authors: Tahira Hussain, Ilhom Rahamkulov, Muhammad Aasim, Ugur Pirlak, Emre Aksoy, Mehmet Emin Caliskan, Allah Bakhsh

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RNA interference (RNAi) has proved its usefulness in functional genomic research on insects recently and is considered potential strategy in crop improvement for the control of insect pests. The different insect pests incur significant losses to potato yield worldwide, Colorado Potato Beetle (CPB) being most notorious one. The present study focuses to knock down highly specific 20-hydroxyecdysone hormone-receptor complex interaction by using RNAi approach to silence Ecdysone receptor (EcR) gene of CPB in transgenic potato plants expressing dsRNA of EcR gene. The partial cDNA of Ecdysone receptor gene of CPB was amplified using specific primers in sense and anti-sense orientation and cloned in pRNAi-GG vector flanked by an intronic sequence (pdk). Leaf and internodal explants of Lady Olympia, Agria and Granola cultivars of potato were infected with Agrobacterium strain LBA4404 harboring plasmid pRNAi-CPB, pRNAi-GFP (used as control). Neomycin phosphotransferase (nptII) gene was used as a plant selectable marker at a concentration of 100 mg L⁻¹. The primary transformants obtained have shown proper integration of T-DNA in plant genome by standard molecular analysis like polymerase chain reaction (PCR), real-time PCR, Sothern blot. The transgenic plants developed out of these cultivars are being evaluated for their efficacy against larvae as well adults of CPB. The transgenic lines are expected to inhibit expression of EcR protein gene, hindering their molting process, hence leading to increased potato yield.

Keywords: plant mediated RNAi, molecular strategy, ecdysone receptor, insect metamorphosis

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Authors: Matthias Feiner, Francisco Javier Fernández García, Michael Arneman, Martin Kipfmüller

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To ensure reliability in miniaturized devices or processes with increased heat fluxes, very efficient cooling methods have to be employed in order to cope with small available cooling surfaces. To address this problem, a certain type of evaporator/heat exchanger was developed: It is called a swirl evaporator due to its flow characteristic. The swirl evaporator consists of a concentrically eroded screw geometry in which a capillary tube is guided, which is inserted into a pocket hole in components with high heat load. The liquid refrigerant R32 is sprayed through the capillary tube to the end face of the blind hole and is sucked off against the injection direction in the screw geometry. Its inner diameter is between one and three millimeters. The refrigerant is sprayed into the pocket hole via a small tube aligned in the center of the bore hole and is sucked off on the front side of the hole against the direction of injection. The refrigerant is sucked off in a helical geometry (twisted flow) so that it is accelerated against the hot wall (centrifugal acceleration). This results in an increase in the critical heat flux of up to 40%. In this way, more heat can be dissipated on the same surface/available installation space. This enables a wide range of technical applications. To optimize the design for the needs in various fields of industry, like the internal tool cooling when machining nickel base alloys like Inconel 718, a correlation-based model of the swirl-evaporator was developed. The model is separated into 3 subgroups with overall 5 regimes. The pressure drop and heat transfer are calculated separately. An approach to determine the locality of phase change in the capillary and the swirl was implemented. A test stand has been developed to verify the simulation.

Keywords: helically-shaped, oil-free, R-32, swirl-evaporator, twist-flow

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Authors: Zeinab Gharibi, B. Stoevesandt, J. Peinke

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Long term surface erosion of wind turbine blades, especially at the leading edge, impairs aerodynamic performance; therefore, lowers efficiency of the blades mostly in the high-speed rotor tip regions. Blade protection provides significant improvements in annual energy production, reduces costly downtime, and protects the integrity of the blades. However, this protection still influences the aerodynamic behavior, and broadband noise caused by interaction between the impinging turbulence and blade’s leading edge. This paper presents an extensive numerical aeroacoustics approach by investigating the sound power spectra of the eroded and coated NACA 64-618 wind turbine airfoil and evaluates aeroacoustics improvements after the protection procedure. Using computational fluid dynamics (CFD), different quasi 2D numerical grids were implemented and special attention was paid to the refinement of the boundary layers. The noise sources were captured and decoupled with acoustic propagation via the derived formulation of Curle’s analogy implemented in OpenFOAM. Therefore, the noise spectra were compared for clean, coated and eroded profiles in the range of chord-based Reynolds number (1.6e6 ≤ Re ≤ 11.5e6). Angle of attack was zero in all cases. Verifications were conducted for the clean profile using available experimental data. Sensitivity studies for the far-field were done on different observational positions. Furthermore, beamforming studies were done simulating an Archimedean spiral microphone array for far-field noise directivity patterns. Comparing the noise spectra of the coated and eroded geometries, results show that, coating clearly improves aerodynamic and acoustic performance of the eroded airfoil.

Keywords: computational fluid dynamics, computational aeroacoustics, leading edge, OpenFOAM

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Authors: Balaji Devanathan, Gokul G., Abilash S., Abhishek Yadav, Sudhir K. Gupta

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Background: As an alternative to the traditional autopsy, a virtual autopsy is carried out using scanning and imaging technologies, mainly post-mortem computed tomography (PMCT). This facility aims to supplement traditional autopsy results and reduce or eliminate internal dissection in subsequent autopsies. For emotional and religious reasons, the deceased's relatives have historically disapproved such interior dissection. The non-invasive, objective, and preservative PMCT is what friends and family would rather have than a traditional autopsy. Additionally, it aids in the examination of the technologies and the benefits and drawbacks of each, demonstrating the significance of contemporary imaging in the field of forensic medicine. Results: One hundred falls resulting in fatalities was analysed by the writers. Before the autopsy, each case underwent a PMCT examination using a 16-slice Multi-Slice CT spiral scanner. By using specialised software, MPR and VR reconstructions were carried out following the capture of the raw images. The accurate detection of fractures in the skull, face bones, clavicle, scapula, and vertebra was better observed in comparison to a routine autopsy. The interpretation of pneumothorax, Pneumoperitoneum, pneumocephalus, and hemosiuns are much enhanced by PMCT than traditional autopsy. Conclusion. It is useful to visualise the skeletal damage in fall from height cases using a virtual autopsy based on PMCT. So, the ideal tool in traumatising patients is a virtual autopsy based on PMCT scans. When assessing trauma victims, PMCT should be viewed as an additional helpful tool to traditional autopsy. This is because it can identify additional bone fractures in body parts that are challenging to examine during autopsy, such as posterior regions, which helps the pathologist reconstruct the victim's life and determine the cause of death.

Keywords: PMCT, fall from height, autopsy, fracture

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Authors: Silvia Alaimo

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This lecture brings to our attention the theme of spirituality within Gestalt therapy’s theoretical and clinical perspectives and which is closely connected to the fertile emptiness and creative indifference’ experiences. First of all, the premise that must be done is the overcoming traditional western culture’s philosophical and religious misunderstandings, such as the dicotomy between spirituality and pratical/material daily life, as well as the widespread secular perspective of classic psychology. Even fullness and emptiness have traditionally been associated with the concepts of being and not being. "There is only one way through which we can contact the deepest layers of our existence, rejuvenate our thinking and reach intuition (the harmony of thought and being): inner silence" (Perls) *. Therefore, "fertile void" doesn't mean empty in itself, but rather an useful condition of every creative and responsible act, making room for a deeper dimension close to spirituality. Spirituality concerns questions about the meaning of existence, which lays beyond the concrete and literal dimension, looking for the essence of things, and looking at the value of personal experience. Looking at fundamentals of Gestalt epistemology, phenomenology, aesthetics, and the relationship, we can reach the heart of a therapeutic work that takes spiritual contours and which are based on an embodied (incarnate size), through the relational aesthetic knowledge (Spagnuolo Lobb ), the deep contact with each other, the role of compassion and responsibility, as the patient's recognition criteria (Orange, 2013) rooted in the body. The aesthetic dimension, like the spiritual dimension to which it is often associated, is a subtle dimension: it is the dimension of the essence of things, of their "soul." In clinical practice, it implies that the relationship between therapist and patient is "in the absence of judgment," also called "zero point of creative indifference," expressed by ‘therapeutic mentality’. It consists in following with interest and authentic curiosity where the patient wants to go and support him in his intentionality of contact. It’s a condition of pure and simple awareness, of the full acceptance of "what is," a moment of detachment from one's own life in which one does not take oneself too seriously, a starting point for finding a center of balance and integration that brings to the creative act, to growth, and, as Perls would say, to the excitement and adventure of living.

Keywords: spirituality, bodily, embodied aesthetics, phenomenology, relationship

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Authors: Ahmad Ali Shahid, Mukhtar Ahmed

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The demand for long staple fiber having better strength and length is increasing with the introduction of modern spinning and weaving industry in Pakistan. Work on gene discovery from developing cotton fibers has helped to identify dozens of genes that take part in cotton fiber development and several genes have been characterized for their role in fiber development. Sucrose synthase (SuS) is a key enzyme in the metabolism of sucrose in a plant cell, in cotton fiber it catalyzes a reversible reaction, but preferentially converts sucrose and UDP into fructose and UDP-glucose. UDP-glucose (UDPG) is a nucleotide sugar act as a donor for glucose residue in many glycosylation reactions and is essential for the cytosolic formation of sucrose and involved in the synthesis of cell wall cellulose. The study was focused on successful Agrobacterium-mediated stable transformation of SuS gene in pCAMBIA 1301 into cotton under a CaMV35S promoter. Integration and expression of the gene were confirmed by PCR, GUS assay, and real-time PCR. Young leaves of SuS overexpressing lines showed increased total soluble sugars and plant biomass as compared to non-transgenic control plants. Cellulose contents from fiber were significantly increased. SEM analysis revealed that fibers from transgenic cotton were highly spiral and fiber twist number increased per unit length when compared with control. Morphological data from field plants showed that transgenic plants performed better in field conditions. Incorporation of genes related to cotton fiber length and quality can provide new avenues for fiber improvement. The utilization of this technology would provide an efficient import substitution and sustained production of long-staple fiber in Pakistan to fulfill the industrial requirements.

Keywords: agrobacterium-mediated transformation, cotton fiber, sucrose synthase gene, staple length

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Authors: Rajasekar Elangopandian, Anand Shanmugam

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In order to reduce the cost of launching satellite and payloads to the orbit this project envisages some immense combined technology. This new technology in space odyssey contains literally four concepts. The first mode in this innovation is flight mission characteristics which, says how the mission will induct. The conventional technique of magnetic levitation will help us to produce the initial thrust. The name states reusable launch vehicle shows its viability of reuseness. The flight consists miniature rocket which produces the required thrust and the two JATO (jet assisted takeoff) boosters which gives the initial boost for the vehicle. The vehicle ostensibly looks like an airplane design and will be located on the super conducting rail track. When the high power electric current given to the rail track, the vehicle starts floating as per the principle of magnetic levitation. If the flight reaches the particular takeoff distance the two boosters gets starts and will give the 48KN thrust each. Obviously it`ll follow the vertical path up to the atmosphere end/start to space. As soon as it gets its speed the two boosters will cutoff. Once it reaches the space the inbuilt spacecraft keep the satellite in the desired orbit. When the work finishes, the apogee motors gives the initial kick to the vehicle to come in to the earth’s atmosphere with 22N thrust and automatically comes to the ground by following the free fall, the help of gravitational force. After the flying region it makes the spiral flight mode then gets landing where the super conducting levitated rail track located. It will catch up the vehicle and keep it by changing the poles of magnets and varying the current. Initial cost for making this vehicle might be high but for the frequent usage this will reduce the launch cost exactly half than the now-a-days technology. The incorporation of such a mechanism gives `hybrid` and the reusability gives `reusable launch vehicle` and ultimately Hybrid reusable launch vehicle.

Keywords: the two JATO (jet assisted takeoff) boosters, magnetic levitation, 48KN thrust each, 22N thrust and automatically comes to the ground

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Authors: Cindy Woods

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After years of implacable neoliberal globalization, multinational corporations have moved from the periphery to the center of the international legal agenda. Human rights advocates have long called for greater corporate accountability in the international arena. The creation of the Global Compact in 2000, while aimed at fostering greater corporate respect for human rights, did not silence these calls. After multiple unsuccessful attempts to adopt a set of norms relating to the human rights responsibilities of transnational corporations, the United Nations succeeded in 2008 with the Guiding Principles on Business and Human Rights (Guiding Principles). The Guiding Principles, praised by some within the international human rights community for their recognition of an individual corporate responsibility to respect human rights, have not escaped their share of criticism. Many view the Guiding Principles to be toothless, failing to directly impose obligations upon corporations, and call for binding international obligations on corporate entities. After decades of attempting to promulgate human rights obligations for multinational corporations, the existing legal frameworks in place fall short of protecting individuals from the human rights abuses of multinational corporations. The Global Compact and Guiding Principles are proof of the United Nations’ unwillingness to impose international legal obligations on corporate actors. In June 2014, the Human Rights Council adopted a resolution to draft international legally binding human rights norms for business entities; however, key players in the international arena have already announced they will not cooperate with such efforts. This Note, through an overview of the existing corporate accountability frameworks and a study of Newmont Mining’s Minas Conga project in Peru, argues that binding international human rights obligations on corporations are necessary to fully protect human rights. Where states refuse to or simply cannot uphold their duty to protect individuals from transnational businesses’ human rights transgressions, there must exist mechanisms to pursue justice directly against the multinational corporation.

Keywords: business and human rights, Latin America, international treaty on business and human rights, mining, human rights

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Authors: John Ibanga

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Since May 1999, when Nigeria returned to uninterrupted democratic rule, there have been various attempts by successive governments at committing themselves to democratic ideals. Such efforts include a revision of communication policies after repeated calls by civil society organisations, development partners, researchers, and academics to allow not only the commencement of campus radio broadcasting but also the takeoff of community radio broadcasting. Thus, in 2015, operating licenses were granted to several communities spread across the six geopolitical zones in the country for the establishment of community radio stations culminating in the establishment of the first community radio in Nigeria on July 17, 2015. And, since citizens’ involvement in policy matters and governance is one of the tenets of participatory democracy, it becomes imperative to investigate how the emerging community radio sector in Nigeria is facilitating participatory democracy among Nigerians, even in the face of attempts by the present government to silence all dissenting voices. This study, therefore, examines how residents in Ondo State, Southwest Nigeria, are utilising programmes on Ejule Nen and Kakaaki community radio stations in Ondo State, Nigeria, to deepen participatory democracy. Much of the existing studies on the role of community radio in participatory democracy and citizens' engagement efforts miss out on Nigeria because of the delayed implementation of community radio policy in Nigeria being Africa’s most populous nation as well as a major player in the affairs of the African continent. While the participatory communication and communication infrastructure theories were used as framework, data were collected from in-depth interviews with staff of the community radio station and community leaders, focus group discussions with the community residents, and qualitative content analysis of programmes on the station. The residents used the community radio stations as platforms for demanding accountability from government, mobilising resources for the execution of a number of community projects, promoting credible electoral practices, and influencing the implementation of free education policy in their communities. Hence the community radio stations became the reliable and authoritative voices of residents for participating in the public sphere and, generally, the democratic process.

Keywords: community, community radio, democracy, participatory democracy

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Authors: Ravan Samadov

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Mentally disabled people are the most discriminated against among other disabled people and face much stronger negative attitudes across many cultures. The most complex and severe form of exclusion of these people is deprivation of liberty on the grounds of their disability. This problem was for many years overlooked to a great extent by the core human rights instruments. However, the United Nations (UN) Convention on the Rights of Persons with Disabilities (CRPD), adopted in 2006, is considered a potential tool to successfully fill the gap. It is especially vital for the developing countries with the vast majority of disabled people of the world and the CRPD is presumed to be able to trigger drastic positive changes. Article 14 of the mentioned human rights treaty has brought into the international forum a new notion, as prohibits deprivation of liberty on the grounds of disability. It is to be understood as an absolute prohibition of deprivation of liberty on the grounds of disability, including mental disability, which manifests in the form of non-consensual psychiatric hospitalisation. The interpretation by the CRPD Committee indicates that this prohibition well embraces all types of non-consensual psychiatric hospitalisation – whether it is based on illness, impairment or disability. This prohibition also extends to such justifications as ‘dangerousness’, ‘need for treatment’ and ‘diminished capacity’. Moreover, providing due substantive and/or procedural safeguards does not render any legitimacy to application of deprivation of liberty on the grounds of mental disability. Logically, this new prohibition form was to be duly considered by different UN human rights bodies, and was subsequently to bring changes to their practices. However, the analyses of post-CRPD work of those bodies allows for asserting the contrary, as they have continued displaying the position which recognises deprivation of liberty on the grounds of disability to be legitimate. While such a position could be justified in the pre-CRPD time as stemming from the silence of human rights documents about it, the continuation of this course after the CRPD entered into force may call the integrity and coherence of the UN human rights treaty system into question. The non-coherent approaches of different UN bodies to this novelty give grounds for misinterpretation thereof, and hinder its due implementation by the States Parties. The paper will discuss the nature of the mentioned new prohibition and the controversial approaches to that notion by different UN human rights bodies.

Keywords: CRPD, deprivation of liberty, mental disability, non-consensual psychiatric hospitalisation, UN bodies

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Authors: Daniel J. Patricio Jiménez

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Digital reality demands new ways of thinking, flexibility in learning, acquisition of new competencies, visualizing reality under new approaches, generating open spaces, understanding dimensions in continuous change, etc. We need inclusive growth, where colors are not lacking, where lights do not give a distorted reality, where science is not half-truth. In carrying out this study, the documentary or bibliographic collection has been taken into account, providing a reflective and analytical analysis of current reality. In this context, deductive and inductive methods have been used on different multidisciplinary information sources. Women today and tomorrow are a strategic element in science and arts, which, under the umbrella of sustainability, implies ‘meeting current needs without detriment to future generations’. We must build new scenarios, which qualify ‘the feminine and the masculine’ as an inseparable whole, encouraging cooperative behavior; nothing is exclusive or excluding, and that is where true respect for diversity must be based. We are all part of an ecosystem, which we will make better as long as there is a real balance in terms of gender. It is the time of ‘the lifting of the veil’, in other words, it is the time to discover the pseudonyms, the women who painted, wrote, investigated, recorded advances, etc. However, the current reality demands much more; we must remove doors where they are not needed. Mass processing of data, big data, needs to incorporate algorithms under the perspective of ‘the feminine’. However, most STEM students (science, technology, engineering, and math) are men. Our way of doing science is biased, focused on honors and short-term results to the detriment of sustainability. Historically, the canons of beauty, the way of looking, of perceiving, of feeling, depended on the circumstances and interests of each moment, and women had no voice in this. Parallel to science, there is an under-representation of women in the arts, but not so much in the universities, but when we look at galleries, museums, art dealers, etc., colours impoverish the gaze and once again highlight the gender gap and the silence of the feminine. Art registers sensations by divining the future, science will turn them into reality. The uniqueness of the so-called new normality requires women to be protagonists both in new forms of emotion and thought, and in the experimentation and development of new models. This will result in women playing a decisive role in the so-called "5.0 society" or, in other words, in a more sustainable, more humane world.

Keywords: art, digitalization, gender, science

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Authors: Suraj Mehrotra

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The stock market is a volatile, bustling marketplace that is a cornerstone of economics. It defines whether companies are successful or in spiral. A thorough understanding of it is important - many companies have whole divisions dedicated to analysis of both their stock and of rivaling companies. Linking the world of finance and artificial intelligence (AI), especially the stock market, has been a relatively recent development. Predicting how stocks will do considering all external factors and previous data has always been a human task. With the help of AI, however, machine learning models can help us make more complete predictions in financial trends. Taking a look at the stock market specifically, predicting the open, closing, high, and low prices for the next day is very hard to do. Machine learning makes this task a lot easier. A model that builds upon itself that takes in external factors as weights can predict trends far into the future. When used effectively, new doors can be opened up in the business and finance world, and companies can make better and more complete decisions. This paper explores the various techniques used in the prediction of stock prices, from traditional statistical methods to deep learning and neural networks based approaches, among other methods. It provides a detailed analysis of the techniques and also explores the challenges in predictive analysis. For the accuracy of the testing set, taking a look at four different models - linear regression, neural network, decision tree, and naïve Bayes - on the different stocks, Apple, Google, Tesla, Amazon, United Healthcare, Exxon Mobil, J.P. Morgan & Chase, and Johnson & Johnson, the naïve Bayes model and linear regression models worked best. For the testing set, the naïve Bayes model had the highest accuracy along with the linear regression model, followed by the neural network model and then the decision tree model. The training set had similar results except for the fact that the decision tree model was perfect with complete accuracy in its predictions, which makes sense. This means that the decision tree model likely overfitted the training set when used for the testing set.

Keywords: machine learning, testing set, artificial intelligence, stock analysis

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Authors: Chiara Magliacane

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This project aims to analyse the relationship between the post-conflict Northern Irish environment and youth trauma in deprived areas. Using an anthropological perspective and methodology, the study investigates the possible contribution that a socio-cultural perspective can give to the current research on the field, with a special focus on the role of transgenerational trauma. The recognition of the role that socio-economic determinants have on health is usually a challenge for social researchers. In post-conflict Northern Ireland, the overall lack of research about connections between the social context and youth trauma opens the way to the present project. Anthropological studies on social implications of mental disorders have achieved impressive results in many societies; they show how conditions of sufferance and poverty are not intrinsically given, but are the products of historical processes and events. The continuum of violence and the politics of victimhood sustains a culture of silence and fear in deprived areas; this implies the need of investigating the structural and symbolic violence that lies behind the diffusion of mental suffering. The project refers to these concepts from Medical Anthropology and looks at connections between trauma and social, political and economic structures. Accordingly, the study considers factors such as poverty, unemployment, social inequality and gender and class perspectives. At the same time, the project problematises categories such as youth and trauma. 'Trauma' is currently debated within the social sciences since the 'invention' of the Post-Traumatic Stress Disorder (PTSD) in 1980. Current critics made to its clinical conception show how trauma has been mainly analysed as a memory of the past. On the contrary, medical anthropological research focuses on wider perspectives on society and its structures; this is a new and original approach to the study of youth trauma considering that, to author’s best knowledge, there is no research of this kind regarding Northern Ireland. Methods: Qualitative interviews, participant observation. Expected Impact: Local Northern Ireland organizations, i.e. specific charities that provide mental health support. Ongoing and present connections will ensure they will hear about this research.

Keywords: health and social inequalities, Northern Ireland, structural violence, youth

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Authors: Stacy Jarvis

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A silent culmination is a musical technique that creates or increases tension in a piece of music. It is a type of cadence in which the music gradually builds to a climax but suddenly stops without any resolution. This technique can create suspense and anticipation in the listener as they wait to find out what will happen next. It can also draw attention to a particular element of the music, such as a particular instrument or vocal line. Silent culminations can evoke a sense of mystery or ambiguity by not resolving the tension created. This technique has been used by composers of all musical genres, from classical to jazz, as well as in film scores. Silent culminations can also make a piece of music more dynamic and exciting. Verdi’s Aida is a classic example of the use of silent culminations to create tension and suspense. Throughout the opera, Verdi uses a technique of gradually building to a climax, only to abruptly stop without any resolution. This technique brings out the story's drama and intensity and creates anticipation for the climactic moments. For example, at the end of the second act, Verdi reaches a crescendo of tension as Aida and Radamès swear their undying love for one another, only to stop with a moment of silence. This technique also helps to draw attention to the important moments in the story, such as the duets between Aida and Radamès. By stopping the music just before it resolves, Verdi can create an atmosphere of anticipation and suspense that carries through to the opera's end. Silent culminations are used greatly in Aida and are integral to Verdi’s dramatic style. In his symphonic poem Mazeppa, Tchaikovsky uses silent culminations to emphasize the piece's drama and powerful emotions. The piece begins with a gentle introduction but quickly builds to a powerful climax. Throughout the piece, Tchaikovsky uses silent culminations to create tension and suspense, drawing the listener in and heightening the intensity of the music 2. The most dramatic moment of the piece comes when the music builds to a frantic climax and then suddenly cuts out, leaving the listener hanging in anticipation of what will happen next. This technique creates an intense atmosphere and leaves the listener eager to hear what comes next. In addition, the use of silent culminations helps to emphasize the strong emotions of the piece, such as fear, horror, and despair. By not resolving the tension with a resolution, the listener is left with a feeling of uneasiness and uncertainty that helps to convey the story of Mazeppa’s tragic fate.

Keywords: Verdi, Tchaikovsky, opera, culmination

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Authors: Jiri Kysucan, Dusan Klos, Katherine Vomackova, Pavel Koranda, Martin Lovecek, Cestmir Neoral, Roman Havlik

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Aim: The prognosis of patients with pancreatic cancer is poor. The median of survival after establishing diagnosis is 3-11 months without surgical treatment, 13-20 months with surgical treatment depending on the disease stage, 5-year survival is less than 5%. Radical surgical resection remains the only hope of curing the disease. Early diagnosis with valid establishment of tumor resectability is, therefore, the most important aim for patients with pancreatic cancer. The aim of the work is to evaluate the contribution and define the role of 18F-FDG PET/CT in preoperative staging. Material and Methods: In 195 patients (103 males, 92 females, median age 66,7 years, 32-88 years) with a suspect pancreatic lesion, as part of the standard preoperative staging, in addition to standard examination methods (ultrasonography, contrast spiral CT, endoscopic ultrasonography, endoscopic ultrasonographic biopsy), a hybrid 18F-FDG PET/CT was performed. All PET/CT findings were subsequently compared with standard staging (CT, EUS, EUS FNA), with peroperative findings and definitive histology in the operated patients as reference standards. Interpretation defined the extent of the tumor according to TNM classification. Limitations of resectability were local advancement (T4) and presence of distant metastases (M1). Results: PET/CT was performed in a total of 195 patients with a suspect pancreatic lesion. In 153 patients, pancreatic carcinoma was confirmed and of these patients, 72 were not indicated for radical surgical procedure due to local inoperability or generalization of the disease. The sensitivity of PET/CT in detecting the primary lesion was 92.2%, specificity was 90.5%. A false negative finding in 12 patients, a false positive finding was seen in 4 cases, positive predictive value (PPV) 97.2%, negative predictive value (NPV) 76,0%. In evaluating regional lymph nodes, sensitivity was 51.9%, specificity 58.3%, PPV 58,3%, NPV 51.9%. In detecting distant metastases, PET/CT reached a sensitivity of 82.8%, specificity was 97.8%, PPV 96.9%, NPV 87.0%. PET/CT found distant metastases in 12 patients, which were not detected by standard methods. In 15 patients (15.6%) with potentially radically resectable findings, the procedure was contraindicated based on PET/CT findings and the treatment strategy was changed. Conclusion: PET/CT is a highly sensitive and specific method useful in preoperative staging of pancreatic cancer. It improves the selection of patients for radical surgical procedures, who can benefit from it and decreases the number of incorrectly indicated operations.

Keywords: cancer, PET/CT, staging, surgery

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Authors: Daniel J. Patricio Jiménez

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The term 'total compensation’ refers to salary, training, innovation, and development, and of course, motivation; total compensation is an open and flexible system which must facilitate personal and family conciliation and therefore cannot be isolated from social reality. Today, the challenge for any company that wants to have a future is to be sustainable, and women play a ‘special’ role in this. Spain, in its statutory and conventional development, has not given sufficient response to new phenomena such as ‘bonuses’, ‘stock options’ or ‘fringe benefits’ (constructed dogmatically and by court decisions), the new digital reality, where cryptocurrency, new collaborative models and service provision -such as remote work-, are always ahead of the law. To talk about compensation is to talk about the gender gap, and with the entry into force of RD.902 /2020 on 14 April 2021, certain measures are necessary under the principle of salary transparency; the valuation of jobs, the pay register (Rd. 6/2019) and the pay audit, are an example of this. Analyzing the methodologies, and in particular the determination and weight of the factors -so that the system itself is not discriminatory- is essential. The wage gap in Spain is smaller than in Europe, but the sources do not reflect the reality, and since the beginning of the pandemic, there has been a clear stagnation. A living wage is not the minimum wage; it is identified with rights and needs; it is that which, based on internal equity, reflects the competitiveness of the company in terms of human capital. Spain has lost and has not recovered the relative weight of its wages; this is having a direct impact on our competitiveness, consequently on the precariousness of employment and undoubtedly on the levels of extreme poverty. Training is becoming more than ever a strategic factor; the new digital reality requires that each component of the system is connected, the transversality is imposed on us, this forces us to redefine content, to give answers to the new demands that the new normality requires because technology and robotization are changing the concept of employability. The presence of women in this context is necessary, and there is a long way to go. The so-called emotional compensation becomes particularly relevant at a time when pandemics, silence, and disruption, are leaving after-effects; technostress (in all its manifestations) is just one of them. Talking about motivation today makes no sense without first being aware that mental health is a priority, that it must be treated and communicated in an inclusive way because it increases satisfaction, productivity, and engagement. There is a clear conclusion to all this: compensation systems do not respond to the ‘new normality’: diversity, and in particular women, cannot be invisible in human resources policies if the company wants to be sustainable.

Keywords: diversity, gender gap, human resources, sustainability.

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Authors: Denise Ben-Porath, Tracy Masterson

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In the past, individuals who struggled with and sought treatment for mental health difficulties were stigmatized. However, the current generation holds more open attitudes around mental health issues. Indeed, public figures such as Demi Lovato, Naomi Osaka, and Simone Biles have taken to social media to break the silence around mental health, discussing their own struggles and the benefits of treatment. Thus, there is considerable reason to believe that this generation would hold fewer stigmatizing attitudes toward mental health difficulties and treatment compared to previous ones. In this study, we explored possible changes in stigma on mental health diagnosis and treatment seeking behavior between two generations: Gen Z, the current generation, and Gen X, those born between 1965-1980. It was hypothesized that Gen Z would hold less stigmatizing views on mental illness than Gen X. To examine possible changes in stigma attitudes between these two generations, we conducted a cross-generational cohort design by using the same methodology employed 20 years ago from the Ben-Porath (2002) study. Thus, participants were randomly assigned to read one of the following four case vignettes employed in the Ben-Porath (2002) study: (a) “Tom” who has received psychotherapy due to depression (b) “Tom” who has been depressed but received no psychological help, (c) “Tom” who has received medical treatment due to a back pain, or (d) “Tom” who had a back pain but did not receive medical attention. After reading the vignette, participants rated “Tom” on various personality dimensions using the IFQ Questionnaire and answered questions about their frequency of social media use and willingness to seek mental health treatment on a scale from 1-10. Identical to the results 20 years prior, a significant main effect was found for diagnosis with “Tom” being viewed in more negative terms when he was described as having depression vs. a medical condition (back pain) [F (1, 376) = 126.53, p < .001]. However, in the study conducted 20 years earlier, a significant interaction was found between diagnosis and help-seeking behavior [F (1, 376) = 8.28, p < .005]. Specifically, “Tom” was viewed in the most negative terms when described as depressed and seeking treatment. Alternatively, the current study failed to find a significant interaction between depression and help seeking behavior. These findings suggest that while individuals who hold a mental health diagnosis may still be stigmatized as they were 20 years prior, seeking treatment for mental health issues may be less so. Findings are discussed in the context of social media use and its impact on destigmatization.

Keywords: stigma, mental illness, help-seeking, social media

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Authors: Xi Chen, King-Yip Cheng

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Hypercholesterolemia, characterized by high low-density lipoprotein cholesterol (LDL-C), raises cardiovascular events in patients with type 2 diabetes (T2D). Although several drugs, such as statin and PCSK9 inhibitors, are available for the treatment of hypercholesterolemia, they exert detrimental effects on glucose metabolism and hence increase the risk of T2D. On the other hand, the drugs used to treat T2D have minimal effect on improving the lipid profile. Therefore, there is an urgent need to develop treatments that can simultaneously improve glucose and lipid homeostasis. Adaptor protein phosphotyrosine interacting with PH domain and leucine zipper 2 (APPL2) causes insulin resistance in the liver and skeletal muscle via inhibiting insulin and adiponectin actions in animal models. Single-nucleotide polymorphisms in the APPL2 gene were associated with LDL-C, non-alcoholic fatty liver disease, and coronary artery disease in humans. The aim of this project is to investigate whether APPL2 antisense oligonucleotide (ASO) can alleviate dietary-induced T2D and hypercholesterolemia. High-fat diet (HFD) was used to induce obesity and insulin resistance in mice. GalNAc-conjugated APPL2 ASO (GalNAc-APPL2-ASO) was used to silence hepatic APPL2 expression in C57/BL6J mice selectively. Glucose, lipid, and energy metabolism were monitored. Immunoblotting and quantitative PCR analysis showed that GalNAc-APPL2-ASO treatment selectively reduced APPL2 expression in the liver instead of other tissues, like adipose tissues, kidneys, muscle, and heart. The glucose tolerance test and insulin sensitivity test revealed that GalNAc-APPL2-ASO improved glucose tolerance and insulin sensitivity progressively. Blood chemistry analysis revealed that the mice treated with GalNAc-APPL2-ASO had significantly lower circulating levels of total cholesterol and LDL cholesterol. However, there was no difference in circulating levels of high-density lipoprotein (HDL) cholesterol, triglyceride, and free fatty acid between the mice treated with GalNac-APPL2-ASO and GalNAc-Control-ASO. No obvious effect on food intake, body weight, and liver injury markers after GalNAc-APPL2-ASO treatment was found, supporting its tolerability and safety. We showed that selectively silencing hepatic APPL2 alleviated insulin resistance and hypercholesterolemia and improved energy metabolism in the dietary-induced obese mouse model, indicating APPL2 as a therapeutic target for metabolic diseases.

Keywords: APPL2, antisense oligonucleotide, hypercholesterolemia, type 2 diabetes

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