Search results for: controlled balanced boolean function

Authors: Raphael M. Ritti-Dias, Marilia A. Correia, Wagner J. R. Domingues, Aline C. Palmeira, Paulo Longano, Nelson Wolosker, Lauro C. Vianna, Gabriel G. Cucato

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Patients with peripheral arterial disease (PAD) have a high prevalence of hypertension, which contributes to a high risk of acute cardiovascular events and cardiovascular mortality. Strategies to reduce cardiovascular risk of these patients are needed. Meta-analysis studies have shown that isometric handgrip training promotes reductions in clinical blood pressure in normotensive, pre-hypertensive and hypertensive individuals. However, the effect of this exercise training on other cardiovascular function indicators in PAD patients remains unknown. Thus, the aim of this study was to analyze the effects of isometric handgrip training on blood pressure in patients with PAD. In this clinical trial, 28 patients were randomly allocated into two groups: isometric handgrip training (HG) and control (CG). The HG conducted the unilateral handgrip training three days per week (four sets of two minutes, with 30% of maximum voluntary contraction with an interval of four minutes between sets). CG was encouraged to increase their physical activity levels. At baseline and after eight weeks blood pressure and heart rate were obtained. ANOVA two-way for repeated measures with the group (GH and GC) and time (pre- and post-intervention) as factors was performed. After 8 weeks of training there were no significant changes in systolic blood pressure (HG pre 141 ± 24.0 mmHg vs. HG post 142 ± 22.0 mmHg; CG pre 140 ± 22.1 mmHg vs. CG post 146 ± 16.2 mmHg; P=0.18), diastolic blood pressure (HG pre 74 ± 10.4 mmHg vs. HG post 74 ± 11.9 mmHg; CG pre 72 ± 6.9 mmHg vs. CG post 74 ± 8.0 mmHg; P=0.22) and heart rate (HG pre 61 ± 10.5 bpm vs. HG post 62 ± 8.0 bpm; CG pre 64 ± 11.8 bpm vs. CG post 65 ± 13.6 bpm; P=0.81). In conclusion, our preliminary data indicate that isometric handgrip training did not modify blood pressure and heart rate in patients with PAD.

Keywords: blood pressure, exercise, isometric, peripheral artery disease

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Authors: Abdul Azarrudin M. A., Pothiraj K., Kandasamy Satish

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In the current automobile scenario, there comes a demand on more sophistication and comfort drive feel on passenger segments. The clutch pedal effort is one such customer touch feels in manual transmission vehicles, where the driver continuous to operate the clutch pedal in his entire the driving maneuvers. Hence optimum pedal efforts at green condition and over mileage to be ensured for fatigue free the driving. As friction is one the predominant factor and its tendency to challenge the technicality by causing the function degradation. One such semi-hydraulic systems shows load efficiency of about 70-75% over lifetime only due to the increase in friction which leads to the increase in pedal effort and cause fatigue to the vehicle driver. This work deals with the study of friction with different interfaces and its influence in the fulcrum points over mileage, with the objective of understanding the trend over mileage and determining the alternative ways of resolving it. In that one way of methodology is the reduction of friction by experimental investigation of various friction reduction interfaces like metal-to-metal interface and it has been tried out and is detailed further. Also, the specific attention has been put up considering the fulcrum load and its contact interfaces to move on with this study. The main results of the experimental data with the influence of three different contact interfaces are being presented with an ultimate intention of ending up into less fatigue with longer consistent pedal effort, thus smoothens the operation of the end user. The Experimental validation also has been done through rig-level test setup to depict the performance at static condition and in-parallel vehicle level test has also been performed to record the additional influences if any.

Keywords: automobile, clutch, friction, fork

Procedia PDF Downloads 127

Authors: Yunjia Yang, Peng Li, Gordon Xu, Timothy Mahony, Bing Zhang, Neena Mitter, Karishma Mody

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Sheep flystrike is one of the most economically important diseases affecting the Australian sheep and wool industry (>356M/annually). Currently, control of Lucillia cuprina relies almost exclusively on chemicals controls, and the parasite has developed resistance to nearly all control chemicals used in the past. It is, therefore, critical to develop an alternative solution for the sustainable control and management of flystrike. RNA interference (RNAi) technologies have been successfully explored in multiple animal industries for developing parasites controls. This research project aims to develop a RNAi based biological control for sheep blowfly. Double-stranded RNA (dsRNA) has already proven successful against viruses, fungi, and insects. However, the environmental instability of dsRNA is a major bottleneck for successful RNAi. Bentonite polymer (BenPol) technology can overcome this problem, as it can be tuned for the controlled release of dsRNA in the gut challenging pH environment of the blowfly larvae, prolonging its exposure time to and uptake by target cells. To investigate the potential of BenPol technology for dsRNA delivery, four different BenPol carriers were tested for their dsRNA loading capabilities, and three of them were found to be capable of affording dsRNA stability under multiple temperatures (4°C, 22°C, 40°C, 55°C) in sheep serum. Based on stability results, dsRNA from potential targeted genes was loaded onto BenPol carriers and tested in larvae feeding assays, three genes resulting in knockdowns. Meanwhile, a primary blowfly embryo cell line (BFEC) derived from L. cuprina embryos was successfully established, aim for an effective insect cell model for testing RNAi efficacy for preliminary assessments and screening. The results of this study establish that the dsRNA is stable when loaded on BenPol particles, unlike naked dsRNA rapidly degraded in sheep serum. The stable nanoparticle delivery system offered by BenPol technology can protect and increase the inherent stability of dsRNA molecules at higher temperatures in a complex biological fluid like serum, providing promise for its future use in enhancing animal protection.

Keywords: lucilia cuprina, primary cell line establishment, RNA interference, insect cell transfection

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Authors: Vineeta Kaushik, Manisha Goel

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Chaperones are proteins that help other proteins fold correctly, and are found in all domains of life i.e., prokaryotes, eukaryotes and archaea. Various comparative genomic studies have suggested that the archaeal protein folding machinery appears to be highly similar to that found in eukaryotes. In case of protein folding; slow rotation of peptide prolyl-imide bond is often the rate limiting step. Formation of the prolyl-imide bond during the folding of a protein requires the assistance of other proteins, termed as peptide prolyl cis-trans isomerases (PPIases). Cyclophilins constitute the class of peptide prolyl isomerases with a wide range of biological function like protein folding, signaling and chaperoning. Most of the cyclophilins exhibit PPIase enzymatic activity and play active role in substrate protein folding which classifies them as a category of molecular chaperones. Till date, there is not very much data available in the literature on archaeal cyclophilins. We aim to compare the structural and biochemical features of the cyclophilin protein from within the three domains to elucidate the features affecting their stability and enzyme activity. In the present study, we carry out in-silico analysis of the cyclophilin proteins to predict their conserved residues, sites under positive selection and compare these proteins to their bacterial and eukaryotic counterparts to predict functional divergence. We also aim to clone and express these proteins in heterologous system and study their biophysical characteristics in detail using techniques like CD and fluorescence spectroscopy. Overall we aim to understand the features contributing to the folding, stability and dynamics of the archaeal cyclophilin proteins.

Keywords: biophysical characterization, x-ray crystallography, chaperone-like activity, cyclophilin, PPIase activity

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Authors: Nabaouia.Maktouf, Ali Ben Moussa, Saïd Turki

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This paper discusses the effect of an attached flexible membrane on the control of fluid around a circular cylinder. A parametric study has been investigated for different positions, sizes, modes as well as frequencies of oscillation of the flexible membrane. The numerical investigation was conducted for a Reynolds number equal to 150 using the commercial code Fluent 16.0 and parallel calculation into 4 processors. The motion of the flexible membrane was managed by the dynamic mesh and compiled into Fluent as a user-defined function. The first part of this paper discusses the effect of changing the position of a flexible membrane sized 8° as an angle of aperture on the aerodynamic coefficients. Results show that the flexible membrane placed at 110° from the stagnation point presents more non-linearity on the behavior of the drag coefficient compared to the drag behavior when placed at 180°, relative to the stagnation point. The effect of the size of the flexible surface was studied for the corresponding angles of aperture: 32° and 42°, respectively. The effect of modes (modes 1, 2, and 3) of vibrations has been investigated at a constant frequency of vibration f=2Hz for angles 32° and 42°. All the calculations have been done with a constant amplitude A =0.001m. A non-linearity of the drag coefficient was clearly observed for all the sizes, modes as well as frequencies of excitation. The Fast Fourier transformation shows the appearance of the natural shedding frequency and the multiples of the frequency of excitation. An increase in the modes of oscillation leads to a more linear behavior of the drag coefficient.

Keywords: fluid flow control, numerical simulation, dynamic mesh, aerodynamic forces, flexible membrane

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Authors: Gabriel Efomeh Omolaiye, Olatunji Seminu, Jimoh Ajadi, Yusuf Ayoola Jimoh

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The Nigerian part of the Chad Basin till date has been one of the few critically studied basins, with few published scholarly works, compared to other basins such as Niger Delta, Dahomey, etc. This work was undertaken by the integration of 3D seismic interpretations and the well data analysis of eight wells fairly distributed in block A, Baga/Lake sub-basin in Borno basin with the aim of determining the thickness of Chad, Kerri-Kerri, Fika, and Gongila Formations in the sub-basin. Da-1 well (type-well) used in this study was subdivided into stratigraphic units based on the regional stratigraphic subdivision of the Chad basin and was later correlated with other wells using similarity of observed log responses. The combined density and sonic logs were used to generate synthetic seismograms for seismic to well ties. Five horizons were mapped, representing the tops of the formations on the 3D seismic data covering the block; average velocity function with maximum error/residual of 0.48% was adopted in the time to depth conversion of all the generated maps. There is a general thickening of sediments from the west to the east, and the estimated thicknesses of the various formations in the Baga/Lake sub-basin are Chad Formation (400-750 m), Kerri-Kerri Formation (300-1200 m), Fika Formation (300-2200 m) and Gongila Formation (100-1300 m). The thickness of the Bima Formation could not be established because the deepest well (Da-1) terminates within the formation. This is a modification to the previous and widely referenced studies of over forty decades that based the estimation of formation thickness within the study area on the observed outcrops at different locations and the use of few well data.

Keywords: Baga/Lake sub-basin, Chad basin, formation thickness, seismic, velocity

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Authors: Falntina Ahmad Alata, Natheer Abu Obeid

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This paper revolves around the concept of affordance. It aims to discover and develop an architectural typology based on the ecological concept of affordance. In order to achieve this aim, an analytical study is conducted and two sources were taken into account: 1- Gibson's definition of the concept of affordance and 2- The researches that are concerned on the affordance categorisation. As a result, this paper concluded 16 typologies of affordances, including the possibilities of mixing them based on both sources. To clarify these typologies and provide further understanding, a wide range of architectural examples are presented and proposed in the paper. To prove this vocabulary’s capability to diagnose and evaluate the affordance of different environments, an experimental study with two processes have been adapted: 1. Diagnostic process: the interpretation of the environments with regards to its affordance by using the new vocabulary (the developed typologies). 2. Evaluating process: the evaluation of the environments that have been interpreted and classified with regards to their affordances. By using the measures of emotional experience (the positive affect ‘PA’ and the negative affect ‘NA’) and the architectural evaluation criteria (beauty, economy and function). The experimental study proves that the typologies are capable of reading the affordance within different environments. Additionally, it explains how these different typologies reflect different interactions based on the previous processes. The data which are concluded from the evaluation of measures explain how different typologies of affordance that have already reflected different environments had different evaluations. In fact, some of them are recommended while the others are not. In other words, the paper draws a roadmap for designers to diagnose, evaluate and analyse the affordance into different architectural environments. After that, it guides them through adapting the best interaction (affordance category), which they intend to adapt into their proposed designs.

Keywords: Affordance theory, Affordance categories, Architectural environments, Architectural Evaluation Criteria (AEC), emotional experience (PA, NA)

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Authors: Marzieh Moattari Mitra Abbasi, Masoud Mousavinasab, Poorahmad

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Background: Nurses in their daily practice need to communicate with patients and their families as well as health professional team members. Effective communication contributes to patients’ satisfaction which is a fundamental outcome of nursing practice. There are some evidences in support of patients' dissatisfaction with nurses’ performance in communication process. Therefore improving nurses’ communication skills is a necessity for nursing scholars and nursing administrators. Objective: The aim of the present study was to evaluate the effect of a 2-days workshop on nurses’ competencies and performances in communication in a central hospital located in the sought of Iran. Materials and Method: This is a randomized controlled trial which comprised of a convenient sample of 70 eligible nurses, working in a central hospital. They were randomly divided into 2 experimental and control groups. Nurses’ competencies was measured by an Objective Structured Clinical Examination (OSCE) and their performance was measured by asking eligible patients hospitalized in the nurses work setting during a one month period to evaluate nurses' communication skills before and 2 months after intervention. The experimental group participated in a 2 day workshop on communication skills. Content included in this workshop were: the importance of communication (verbal and non verbal), basic communication skills such as initiating the communication, active listening and questioning technique. Other subjects were patient teaching, problem solving, and decision making, cross cultural communication and breaking bad news. Appropriate teaching strategies such as brief didactic sessions, small group discussion and reflection were applied to enhance participants learning. The data was analyzed using SPSS 16. Result: A significant between group differences was found in nurses’ communication skills competencies and performances in the posttest. The mean scores of the experimental group was higher than that of the control group in the total score of OSCE as well as all stations of OSCE (p<0.003). Overall posttest mean scores of patient satisfaction with nurse's communication skills and all of its four dimensions significantly differed between the two groups of the study (p<0.001). Conclusion: This study shows that the education of nurses in communication skills, improves their competencies and performances. Measurement of Nurses’ communication skills as a central component of efficient nurse patient relationship by valid and reliable methods of evaluation is recommended. Also it is necessary to integrate teaching of communication skills in continuing nursing education programs. Trial Registration Number: IRCT201204042621N11

Keywords: communication skills, simulation, performance, competency, objective structure, clinical evaluation

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Authors: Mbida Yem, Alessandra Ribodetti, Joseph Quentin Yéné Atangana, Fabrice Jouffray, Dieudonné Bisso

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Central Cameroon is a mosaic complex of Proterozoïc litho-tectonic units, with structural deformations mainly inherited from Panafrican orogeny. It consists of a para-derived series with epicontinental affinity, structured as successive nappe thrusting southward on the Ntem complex, considered as the Congo Craton northern margin. A well-developed prograde metamorphic gradient is described from SE (Dja and Yokadouma meta-detritic series) to NW (gneiss and migmatites of the Yaounde series) with ages estimated at 600-620 Ma. Syn- to late phase of the Panafrican deformations crosscut the nappes structured with large mylonitic shear zones (Sanaga fault, Adamawa fault, Tcholiré-Banyo fault) coeval with intrusive granitoids. The scientific and industrial communities interested in exploring the groundwater resources of these litho-tectonic units using geophysics and geohydrology methods have grown steadily since the 1970s. In this paper, we present shallow and deep geophysical cross-sections that describe the most productive groundwater targets of the Central Cameroon litho-tectonic units. This study also discusses geological factors that control groundwater occurrences. The data analyzed were gathered from public and private groundwater surveys conducted in recent years and included 18 well-controlled resistivity sections and hydrogeological parameters of 150 drilling points. The depth of well records extends from 40 to 180m. Also, one of the challenges of geophysics investigations was to image groundwater reservoirs located above 120m depth. Therefore, the resistivity data were acquired using a 1200 m long digital streamer, with a 10 m electrode spacing in the selected sites. The modelled sections derived from these data show that the most productive groundwater targets of the study area include lithological contacts and dyke fault-zones. The average width of dyke fault-zones ranges between 40 and 380 m. These structures display a significant lateral extent, and their spatial distribution is often in correlation with mountain terranes and regional fault zones trending from SW-NE to NNW-SSE. Following these observations, transboundaries aquifers associated with fractured magmatic rocks can be found in the study area.

Keywords: Proterozoic, resistivity sections, dyke fault-zones, groundwater target

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Authors: Mathieu Audet, Monica Soliman, Emilie Eve Gravel, Rebecca Friesdorf

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Access to higher education is critical for reducing social inequalities. The Canada Learning Bond (CLB) is a government savings incentive aimed at increasing higher education access for children of low income families by providing money toward a Registered Education Savings Plan. To better understand the educational and financial decision-making of low income families, Employment Social Development Canada conducted qualitative fieldwork with eligible parents and children, teachers, and community organizations promoting the Bond. Insights from this fieldwork were then used to develop letters to better target the needs and experiences of eligible families. In the present study, we conducted a randomized controlled trial with children ages 12 to 13, the oldest cohort of eligible children, to test the effectiveness of the new letters. Parents or caregivers of 150,088 eligible children were assigned to one of five letter conditions promoting the Bond or to a control condition that did not receive a letter. The letter conditions were: (a) the standard letter from past outreach, (b) a letter presenting the exact amount the child was eligible to receive, enhancing the salience of benefits, (c) a letter with a social norm, (d) a letter with an image emphasizing the feasibility of higher education by presenting the diversity of options (i.e., college, trade schools, apprenticeships) – many participants interviewed viewed that university was unfeasible, and (e) a letter minimizing references to 'saving' (i.e., not framing the Bond explicitly as a savings incentive) – a concept that did not resonate with low income families who felt they could not afford to save. The exact amount was also presented in letters (c) through (e). The letter minimizing references to 'saving' and presenting the exact amount had the highest net take-up rate at 6.6%, compared to 3.5% for the standard letter group. Furthermore, this trial’s BI-informed letters showed the largest impact on take-up so far, with a net take-up of 5.7% compared to 3.0% and 3.9% in the first two trials. This research highlights the value of mixed-method approaches combining qualitative and behavioural insights methods for developing context-sensitive interventions for social programs. By gaining a deeper understanding of the needs and experiences of program users through qualitative fieldwork, and then integrating these insights into behaviourally informed communications, we were able to increase take-up of an education savings program, which may ultimately improve access to higher education in children of low income families.

Keywords: access to higher education, behavioral insights, government, innovation, mixed-methods, social programs

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Authors: Deepanjali Gurav, Kun Qian

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In-vitro metabolic diagnosis relies on designed materials-based analytical platforms for detection of selected metabolites in biological samples, which has a key role in disease detection and therapeutic evaluation in clinics. However, the basic challenge deals with developing a simple approach for metabolic analysis in bio-samples with high sample complexity and low molecular abundance. In this work, we report a designer plasmonic nanoshells based platform for direct detection of small metabolites in clinical samples for in-vitro metabolic diagnostics. We first synthesized a series of plasmonic core-shell particles with tunable nanoshell structures. The optimized plasmonic nanoshells as new matrices allowed fast, multiplex, sensitive, and selective LDI MS (Laser desorption/ionization mass spectrometry) detection of small metabolites in 0.5 μL of bio-fluids without enrichment or purification. Furthermore, coupling with isotopic quantification of selected metabolites, we demonstrated the use of these plasmonic nanoshells for disease detection and therapeutic evaluation in clinics. For disease detection, we identified patients with postoperative brain infection through glucose quantitation and daily monitoring by cerebrospinal fluid (CSF) analysis. For therapeutic evaluation, we investigated drug distribution in blood and CSF systems and validated the function and permeability of blood-brain/CSF-barriers, during therapeutic treatment of patients with cerebral edema for pharmacokinetic study. Our work sheds light on the design of materials for high-performance metabolic analysis and precision diagnostics in real cases.

Keywords: plasmonic nanoparticles, metabolites, fingerprinting, mass spectrometry, in-vitro diagnostics

Procedia PDF Downloads 142

Authors: Mimi My Tse

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The prevalence of chronic non-cancer pain is high among community-dwelling older adults. Pain affects physical and psychosocial abilities. Older adults tend to be less mobile and have a high tendency to fall risk. In addition, older adults with pain are depressed, anxious, and not too willing to join social activities. This will make them feel very lonely and social isolation. Instead of giving pain management education and programs to older adults/clients, both older adults and their caregivers, it is sad to find that the majority of existing services are given to older adults only. Given the importance of family members in increasing compliance with health-promoting programs, we proposed to offer pain management programs to both older adults with his/her caregiver as a “dyad.” We used the Health Promotion Model and implemented a dyadic pain management program (DPM). The DPM is an 8-week group-based program. The DPM comprises 4 weeks of center-based, face-to-face activities and 4 weeks of digital-based activities delivered via a WhatsApp group. There were 30 dyads (15 in the experimental group with DPM and 15 in the control group with pain education pamphlets). Upon the completion of DPM, pain intensity and pain interference were significantly lower in the intervention group as compared to the control group. At the same time, physical function showed significant improvement and lower depression scores in the intervention group. In conclusion, the study highlights the potential benefits of involving caregivers in the management of chronic pain for older adults. This approach should be widely promoted in managing chronic pain situations for community-dwelling older adults and their caregivers.

Keywords: pain, older adults, dyadic approach, education

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Authors: Tanit Daniel Jodar Vecina, Adriane Prisco Petry

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The shape of the wind velocity profile changes according to local features of terrain shape and roughness, which are parameters responsible for defining the Atmospheric Boundary Layer (ABL) profile. Air flow characteristics over and around landforms, such as hills, are of considerable importance for applications related to Wind Farm and Turbine Engineering. The air flow is accelerated on top of hills, which can represent a decisive factor for Wind Turbine placement choices. The present work focuses on the study of ABL behavior as a function of slope and surface roughness of hill-shaped landforms, using the Computational Fluid Dynamics (CFD) to build wind velocity and turbulent intensity profiles. Reynolds-Averaged Navier-Stokes (RANS) equations are closed using the SST k-ω turbulence model; numerical results are compared to experimental data measured in wind tunnel over scale models of the hills under consideration. Eight hill models with slopes varying from 25° to 68° were tested for two types of terrain categories in 2D and 3D, and two analytical codes are used to represent the inlet velocity profiles. Numerical results for the velocity profiles show differences under 4% when compared to their respective experimental data. Turbulent intensity profiles show maximum differences around 7% when compared to experimental data; this can be explained by not being possible to insert inlet turbulent intensity profiles in the simulations. Alternatively, constant values based on the averages of the turbulent intensity at the wind tunnel inlet were used.

Keywords: Atmospheric Boundary Layer, Computational Fluid Dynamic (CFD), Numerical Modeling, Wind Tunnel

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Authors: Amenawo I. Offiong, Hodo B. Riman

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Public debt profile of Nigeria has continuously been on the increase over the years. The drop in international crude oil prices has further worsened revenue position of the country, thus, necessitating further acquisition of public debt to bridge the gap in revenue deficit. Yet, when we look back at the increasing public sector spending, there are concerns that the government spending do not amount to increase in public goods provided for the country. Using data from 1980 to 2014 the study therefore seeks to investigate the factors responsible for the poor provision of public goods in the face of increasing public debt profile. Using the unrestricted VAR model Governance and Tax revenue were introduced into the model as structural variables. The result suggested that governance and tax revenue were structural determinants of the effectiveness of public goods provisioning in Nigeria. The study therefore identified weak governance as the major reason for the non-provision of public goods in Nigeria. While tax revenue exerted positive influence on the provisions of public goods, weak/poor governance was observed to crowd the benefits from increase tax revenue. The study therefore recommends reappraisal of the governance system in Nigeria. Elected officers in governance should be more transparent and accountable to the electorates they represent. Furthermore, the study advocates for an annual auditing of all government MDAs accounts by external auditors to ensure (a) accountability of public debts utilization, (b) transparent in implementation of program support funds, (c) integrity of agencies responsible for program management, and (d) measuring program effectiveness with amount of funds expended.

Keywords: impulse response function, public debt shocks, governance, public goods, tax revenue, vector auto-regression

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Authors: Jia Li, Huacong Li, Xiaobao Han

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Due to the more variable geometry parameters of VCE (variable cycle aircraft engine), presents an adaptive controller method based on the full-state linear model of VCE and has simulated to solve the multivariate controller design problem of the whole flight envelops. First, analyzes the static and dynamic performances of bypass ratio and other state parameters caused by variable geometric components, and develops nonlinear component model of VCE. Then based on the component model, through small deviation linearization of main fuel (Wf), the area of tail nozzle throat (A8) and the angle of rear bypass ejector (A163), setting up multiple linear model which variable geometric parameters can be inputs. Second, designs the adaptive controllers for VCE linear models of different nominal points. Among them, considering of modeling uncertainties and external disturbances, derives the adaptive law by lyapunov function. The simulation results showed that, the adaptive controller method based on full-state linear model used the angle of rear bypass ejector as input and effectively solved the multivariate control problems of VCE. The performance of all nominal points could track the desired closed-loop reference instructions. The adjust time was less than 1.2s, and the system overshoot was less than 1%, at the same time, the errors of steady states were less than 0.5% and the dynamic tracking errors were less than 1%. In addition, the designed controller could effectively suppress interference and reached the desired commands with different external random noise signals.

Keywords: variable cycle engine (VCE), full-state linear model, adaptive control, by-pass ratio

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Authors: T. Qasim, B. El Masoud, D. Ailabouni

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This in vitro study focused on investigating the fatigue resistance of veneered zirconia molar crowns with different veneering ceramic thicknesses, simulating the relative wear depths under simulated cyclic loading. A mandibular first molar was prepared and then scanned using computer-aided design/computer-aided manufacturing (CAD/CAM) technology to fabricate 32 zirconia copings of uniform 0.5 mm thickness. The manufactured copings then veneered with 1.5 mm, 1.0 mm, 0.5 mm, and 0.0 mm representing 0%, 33%, 66%, and 100% relative wear of a normal ceramic thickness of 1.5 mm. All samples were thermally aged to 6000 thermo-cycles for 2 minutes with distilled water between 5 ˚C and 55 ˚C. The samples subjected to cyclic fatigue and fracture testing using SD Mechatronik chewing simulator. These samples are loaded up to 1.25x10⁶ cycles or until they fail. During fatigue, testing, extensive cracks were observed in samples with 0.5 mm veneering layer thickness. Veneering layer thickness 1.5-mm group and 1.0-mm group were not different in terms of resisting loads necessary to cause an initial crack or final failure. All ceramic zirconia-based crown restorations with varying occlusal veneering layer thicknesses appeared to be fatigue resistant. Fracture load measurement for all tested groups before and after fatigue loading exceeded the clinical chewing forces in the posterior region. In general, the fracture loads increased after fatigue loading and with the increase in the thickness of the occlusal layering ceramic.

Keywords: all ceramic, cyclic loading, chewing simulator, dental crowns, relative wear, thermally ageing

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Authors: Ishani Majumdar, Jaishree Paul

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Introduction: Ulcerative Colitis (UC) is an inflammatory disease of the colon resulting from an autoimmune response towards individual’s own microbiota. Excessive inflammation is characterized by hyper-activation of NFkB, a transcription factor regulating expression of various pro-inflammatory genes. The ubiquitin editing complex consisting of TNFAIP3, ITCH, RNF11 and TAX1BP1 maintains homeostatic levels of active NFkB through feedback inhibition and assembles in response to various stimuli that activate NFkB. TNFAIP3 deubiquitinates key signaling molecules involved in NFkB activation pathway. ITCH, RNF11 and TAX1BP1 provide substrate specificity, acting as adaptors for TNFAIP3 function. Aim: This study aimed to find expression of members of the ubiquitin editing complex at the transcript level in inflamed colon tissues of UC patients. Materials and Methods: Colonic biopsy samples were collected from 30 UC patients recruited at Department of Gastroenterology, AIIMS (New Delhi). Control group (n= 10) consisted of individuals undergoing examination for functional disorders. Real Time PCR was used to determine relative expression with GAPDH as housekeeping gene. Results: Expression of members of the ubiquitin editing complex was significantly altered during active disease. Expression of TNFAIP3 was upregulated while concomitant decrease in expression of ITCH, RNF11, TAX1BP1 was seen in UC patients. Discussion: This study reveals that increase in expression of TNFAIP3 was unable to control inflammation during active UC. Further, insufficient upregulation of ITCH, RNF11, TAX1BP1 may limit the formation of the ubiquitin complex and contribute to pathogenesis of UC.

Keywords: altered expression, inflammation, ubiquitin editing complex, ulcerative colitis

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Authors: Sanjay Shukla

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Excessive use of antibiotics is a main problem in the treatment of wounds and other chronic infections and antibiotic treatment is frequently non-curative, thus alternative treatment is necessary. Phage therapy is considered one of the most effective approaches to treat multi-drug resistant bacterial pathogens. Infections caused by Staphylococcus aureus are very efficiently controlled with phage cocktails, containing a different individual phages lysate infecting a majority of known pathogenic S. aureus strains. The aim of current study was to investigate the efficiency of a purified phage cocktail for prophylactic as well as therapeutic application in mouse model and in large animals with chronic septic infection of wounds. A total of 150 sewage samples were collected from various livestock farms. These samples were subjected for the isolation of bacteriophage by double agar layer method. A total of 27 sewage samples showed plaque formation by producing lytic activity against S. aureus in double agar overlay method out of 150 sewage samples. In TEM recovered isolates of bacteriophages showed hexagonal structure with tail fiber. In the bacteriophage (ØVS) had an icosahedral symmetry with the head size 52.20 nm in diameter and long tail of 109 nm. Head and tail were held together by connector and can be classified as a member of the Myoviridae family under the order of Caudovirale. Recovered bacteriophage had shown the antibacterial activity against the S. aureus in vitro. Cocktail (ØVS1, ØVS5, ØVS9 and ØVS 27) of phage lysate were tested to know in vivo antibacterial activity as well as the safety profile. Result of mice experiment indicated that the bacteriophage lysate was very safe, did not show any appearance of abscess formation which indicates its safety in living system. The mice were also prophylactically protected against S. aureus when administered with cocktail of bacteriophage lysate just before the administration of S. aureus which indicates that they are good prophylactic agent. The S. aureus inoculated mice were completely recovered by bacteriophage administration with 100% recovery which was very good as compere to conventional therapy. In present study ten chronic cases of wound were treated with phage lysate and follow up of these cases was done regularly up to ten days (at 0, 5 and 10 d). Result indicated that the six cases out of ten showed complete recovery of wounds within 10 d. The efficacy of bacteriophage therapy was found to be 60% which was very good as compared to the conventional antibiotic therapy in chronic septic wounds infections. Thus, the application of lytic phage in single dose proved to be innovative and effective therapy for treatment of septic chronic wounds.

Keywords: phage therapy, phage lysate, antimicrobial resistance, S. aureus

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Authors: Samantha Meyr, Eman Mirdamadi, Martha Wang, Tao Lowe, Ryan Smith, Quinn Burke

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Critical-sized bone defects (CSD) treatment options remain a major clinical orthopedic challenge. They are uniquely contoured diseased or damaged bones and can be defined as those that will not heal spontaneously and require surgical intervention. Autografts are the current gold standard CSD treatment, which are histocompatible and provoke a minimal immunogenic response; however, they can cause donor site morbidity and will not suffice for the size required for replacement. As an alternative to traditional surgical methods, bone tissue engineering will be implemented via 3D printing methods. A freeze-dried bone matrix (FDBM) is a type of graft material available but will only function as desired when in the presence of bone growth factors. Polycaprolactone (PCL) is a known biodegradable material with good biocompatibility that has been proven manageable in 3D printing as a medical device. A 3D-extrusion printing strategy is introduced to print these materials into scaffolds for bone grafting purposes, which could be more accessible and rapid than the current standard. Mechanical, thermal, cytotoxic, and physical properties were investigated throughout a degradation period of 6 months using fibroblasts and dental pulp stem cells. PCL-FDBM scaffolds were successfully printed with high print fidelity in their respective pore sizes and allograft content. Additionally, we have created a method for evaluating PCL using differential scanning calorimetry (DSC) and have evaluated PCL degradation over roughly 6 months.

Keywords: 3D printing, bone tissue engineering, cytotoxicity, degradation, scaffolds

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Authors: Wenbo Wang, Yi-Fang Brook Wu

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The spread of misinformation and disinformation has become a major concern, particularly with the rise of social media as a primary source of information for many people. As a means to address this phenomenon, automated fact-checking has emerged as a safeguard against the spread of misinformation and disinformation. Existing fact-checking approaches aim to determine whether a news claim is true or false, and they have achieved decent veracity prediction accuracy. However, the state-of-the-art methods rely on manually verified external information to assist the checking model in making judgments, which requires significant human resources. This study introduces a framework, SAC, which focuses on 1) augmenting the representation of a claim by incorporating additional context using general-purpose, comprehensive, and authoritative data; 2) developing a search function to automatically select relevant, new, and credible references; 3) focusing on the important parts of the representations of a claim and its reference that are most relevant to the fact-checking task. The experimental results demonstrate that 1) Augmenting the representations of claims and references through the use of a knowledge base, combined with the multi-head attention technique, contributes to improved performance of fact-checking. 2) SAC with auto-selected references outperforms existing fact-checking approaches with manual selected references. Future directions of this study include I) exploring knowledge graphs in Wikidata to dynamically augment the representations of claims and references without introducing too much noise, II) exploring semantic relations in claims and references to further enhance fact-checking.

Keywords: fact checking, claim verification, deep learning, natural language processing

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Authors: M. Cabral, A. Verdin, G. Garçon, A. Touré, C. Diop, M. Fall, S. Bouhsina, D. Dewaele, F.Cazier, A. Tall Dia, P. Shirali, A. Diouf

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This case-control study dealt with the health adverse effects within the population neighboring the Mbeubeuss waste dump, which is located near the district of Malika (Diamalaye II) in Dakar (Senegal). All the household and industrial waste arising from Dakar are stored in this open landfill without being covered and are therefore possible sources of Pb and Cd contaminated air emissions and lixiviates. The objective of this study is part of improving the health of the population neighboring Mbeubeuss by determining Pb and Cd concentrations both in environment and humans, and studying possible renal function alterations within the adults. Soil and air samples were collected in the control site (Darou Salam) and the waste dump neighboring site (Diamalaye II). Control and exposed adults were recruited as living in Darou Salam (n = 52) and in Diamalaye II (n = 77). Pb and Cd concentrations in soil, air and biological samples were determined. Moreover, we were interested in analyzing some impregnation (zinc protoporphyrin, d-aminolevulinic acid dehydratase) and oxidative stress biomarkers (malonedialdehyde, gluthatione status), in addition to several nephrotoxicity parameters (creatinuria, proteinuria, lactate dehydrogenase, CC16 protein, glutathione S-transferase-alpha and retinol binding protein) in blood and/or urine. The results showed the significant Pb and Cd contamination of the soil and air samples derived from the landfill, and therefore of the neighboring population of adults. This critical exposure to environmental Pb and Cd had some harmful consequences for their health, as shown by the reported oxidative stress and nephrotoxicity signs.

Keywords: Pb and Cd environmental exposure, impregnation markers, landfill, nephrotoxicity markers

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Authors: Heba Khader, Victor Solodushko, Brian Fouty

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Hyperglycemia is a hallmark of uncontrolled diabetes and causes vascular endothelial dysfunction. An increase in glucose uptake and metabolism by vascular endothelial cells is the presumed trigger for this hyperglycemia-induced dysfunction. Glucose uptake into vascular endothelial cells is mediated largely by Glut-1. Glut-1 is an equilibrative glucose transporter with a Km value of 2 mM. At physiologic glucose concentrations, Glut-1 is almost saturated and, therefore, increasing glucose concentration does not increase glucose uptake unless Glut-1 is upregulated. However, hyperglycemia downregulates Glut-1 and decreases rather than increases glucose uptake in vascular endothelial cells. This apparent discrepancy necessitates further study on the effect of increasing glucose uptake on the oxidative state and function of vascular endothelial cells. To test this, a Tet-on system was generated to conditionally regulate Glut-1 expression in endothelial cells by the addition and removal of doxycycline. Glut-1 overexpression was confirmed by Western blot and radiolabeled glucose uptake measurements. Upregulation of Glut-1 resulted in a 4-fold increase in glucose uptake into endothelial cells as determined by 3H deoxy-D-glucose uptake. Increased glucose uptake through Glut-1 did not induce an oxidative stress nor did it cause endothelial dysfunction in rat pulmonary microvascular endothelial cells determined by monolayer resistance, cell proliferation or advanced glycation end product formation. Increased glucose uptake through Glut-1did not lead to an increase in glucose metabolism, due in part to inhibition of hexokinase in Glut-1 overexpressing cells. In summary, this study demonstrates that increasing glucose uptake and intracellular glucose by overexpression of Glut-1 does not alter the oxidative state of rat pulmonary microvascular endothelial cells or cause endothelial cell dysfunction. These results conflict with the current paradigm that hyperglycemia leads to oxidative stress and endothelial dysfunction in vascular endothelial cells through an increase in glucose uptake.

Keywords: endothelial cells, glucose uptake, Glut1, hyperglycemia

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Authors: Arkadiusz Gut, Robert Mirski

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The nativist-constructivist debate constitutes a considerable part of current research on mindreading. Peter Carruthers and his colleagues are known for their nativist position in the debate and take issue with constructivist views proposed by other researchers, with Henry Wellman, Alison Gopnik, and Ian Apperly at the forefront. More specifically, Carruthers together with Evan Westra propose a nativistic explanation of Theory of Mind Scale study results that Wellman et al. see as supporting constructivism. While allowing for development of the innate mindreading system, Westra and Carruthers base their argumentation essentially on a competence-performance gap, claiming that cross-cultural differences in Theory of Mind Scale progression as well as discrepancies between infants’ and toddlers’ results on verbal and non-verbal false-belief tasks are fully explainable in terms of acquisition of other, pragmatic, cognitive developments, which are said to allow for an expression of the innately present Theory of Mind understanding. The goal of the present paper is to bring together arguments against the view offered by Westra and Carruthers. It will be shown that even though Carruthers et al.’s interpretation has not been directly controlled for in Wellman et al.’s experiments, there are serious reasons to dismiss such nativistic views which Carruthers et al. advance. The present paper discusses the following issues that undermine Carruthers et al.’s nativistic conception: (1) The concept of innateness is argued to be developmentally inaccurate; it has been dropped in many biological sciences altogether and many developmental psychologists advocate for doing the same in cognitive psychology. Reality of development is a complex interaction of changing elements that is belied by the simplistic notion of ‘the innate.’ (2) The purported innate mindreading conceptual system posited by Carruthers ascribes adult-like understanding to infants, ignoring the difference between first- and second-order understanding, between what can be called ‘presentation’ and ‘representation.’ (3) Advances in neurobiology speak strongly against any inborn conceptual knowledge; neocortex, where conceptual knowledge finds its correlates, is said to be largely equipotential at birth. (4) Carruthers et al.’s interpretations are excessively charitable; they extend results of studies done with 15-month-olds to conclusions about innateness, whereas in reality at that age there has been plenty of time for construction of the skill. (5) Looking-time experiment paradigm used in non-verbal false belief tasks that provide the main support for Carruthers’ argumentation has been criticized on methodological grounds. In the light of the presented arguments, nativism in theory of mind research is concluded to be an untenable position.

Keywords: development, false belief, mindreading, nativism, theory of mind

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Authors: A. Katsman, L. Bloch, Y. Etinger, Y. Kauffmann, B. Pokroy

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Various nanosized amorphous alumina thin films in the range of (2.4 - 63.1) nm were deposited onto amorphous carbon and amorphous Si3N4 membrane grids. Transmission electron microscopy (TEM), electron energy loss spectroscopy (EELS), X-ray photoelectron spectroscopy (XPS) and differential scanning calorimetry (DSC) techniques were used to probe the size effect on the short range order and the amorphous to crystalline phase transition temperature. It was found that the short-range order changes as a function of size: the fraction of tetrahedral Al sites is greater in thinner amorphous films. This result correlates with the change of amorphous alumina density with the film thickness demonstrated by the reflectivity experiments: the thinner amorphous films have the less density. These effects are discussed in terms of surface reconstruction of the amorphous alumina films. The average atomic binding energy in the thin film layer decreases with decease of the thickness, while the average O-Al interatomic distance increases. The reconstruction of amorphous alumina is induced by the surface reconstruction, and the short range order changes being dependent on the density. Decrease of the surface energy during reconstruction is the driving force of the alumina reconstruction (density change) followed by relaxation process (short range order change). The amorphous to crystalline phase transition temperature measured by DSC rises with the decrease in thickness from 997.6°C for 13.9 nm to 1020.4 °C for 2.7 nm thick. This effect was attributed to the different film densities: formation of nanovoids preceding and accompanying crystallization process influences the crystallization rate, and by these means, the temperature of crystallization peak.

Keywords: amorphous alumina, density, short range order, size effect

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Authors: Mala Tankam Carine, Kekeunou Sévilor, Nukenine Elias

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Storage and preservation of agricultural products remain the only conditions ensuring the almost permanent availability of foodstuffs. However, infestations due to insects and microorganisms often occur. Callosobruchus maculatus is a pest that causes a lot of damage to cowpea stocks in the tropics. Several methods are adopted to limit their damage, but the use of synthetic chemical insecticides is the most widespread. Biopesticides in sustainable agriculture respond to several environmental, economic and social concerns while offering innovative opportunities that are ecologically and economically viable for producers, workers, consumers and ecosystems. Our main objective is to evaluate the insecticidal efficacy of binary combinations of Fossilshield with root-bark powder of Securidaca longepedunculata against Callosobruchus maculatus in stored cowpea Vigna unguiculata. Laboratory bioassays were conducted in stored grains to evaluate the toxicity of root-bark powder of Securidaca longepedunculata alone or combined with diatomaceous earth Fossil-Shield ® against C. maculatus. Twenty-hour-old adults of C. maculatus were exposed to 50g of cowpea seeds treated with four doses (10, 20, 30, and 40g/kg) of root-bark powder of S. longepedunculata, on the one hand, and (0.5, 1, 1.5, and 2 g/kg) on DE and binary combinations on the other hand. 0g/kg corresponded to untreated control. Adult mortality was recorded up to 7 days (d) post-treatment, whereas the number of F1 progeny was assessed after 30 d. Weight loss and germinative ability were conducted after 120 d. All treatments were arranged according to a completely randomized block with four replicates. The combined mixture of S. longepedunculata and DE controlled the beetle faster compared to the root-bark powder of S. longepedunculata alone. According to the Co-toxicity coefficient, additive effect of binary combinations was recorded at 3-day post-exposure time with the mixture 25% FossilShield + 75% S. longepedunculata. A synergistic action was observed after 3-d post-exposure at mixture 50% FossilShield + 50% S. longepedunculata and at 1-d and 3-d post-exposure periods at mixture 75% FossilShield + 25% S. longepedunculata. The mixture 25% FossilShield + 75% S. longepedunculata induced a decreased progeny of 6 times fewer individuals for 4.5 times less weight loss and 2, 9 times more sprouted grains than with root-bark powder of S. longepedunculata. The combination of FossilShield + S. longepedunculata was more potent than root-bark powder of S. longepedunculata alone, although the root-bark powder of S. longepedunculata caused significant reduction of F1 adults compared to the control. Combined action of botanical insecticides with FossilShield as a grain protectant in an integrated pest management approach is discussed.

Keywords: diatomaceous earth, cowpea, callosobruchus maculatus, securidaca longepedunculata, combined action, co-toxicity coefficient

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Authors: Christopher Dick

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While the translation of 'literal language' poses numerous challenges for the translator, the translation of 'figurative language' creates even more complicated issues. It has been only in the last several decades that scholars have attempted to propose theories of figurative language translation, including metaphor translation. Even less work has applied these theories to metaphoric translation in literary texts. And almost no work has linked an analysis of metaphors in translation with the recent scholarship on conceptual metaphors. A study of literature in translation must not only examine the inevitable shifts that occur as specific metaphors move from source language to target language but also analyze the ways in which these shifts impact conceptual metaphors and, ultimately, the text as a whole. Doing so contributes to on-going efforts to bridge the sometimes wide gulf between considerations of content and form in literary studies. This paper attempts to add to the body of scholarly literature on metaphor translation and the function of metaphor in a literary text. Specifically, the study examines the metaphoric expressions in Hemingway’s The Sun Also Rises. First, the issue of Hemingway and metaphor is addressed. Next, the study examines the specific metaphors in the original novel in English and the German translations, first in Annemarie Horschitz’s 1928 German version and then in the recent Werner Schmitz 2013 translation. Hemingway’s metaphors, far from being random occurrences of figurative language, are linguistic manifestations of deeper conceptual metaphors that are central to an interpretation of the text. By examining the modifications that are made to these original metaphoric expressions as they are translated into German, one can begin to appreciate the shifts involved with metaphor translation. The translation of Hemingway’s metaphors into German represents significant metaphoric loss and shifting that subsequently shakes the important conceptual metaphors in the novel.

Keywords: Hemingway, Conceptual Metaphor, Translation, Stylistics

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Authors: Thinakar Mani Balusamy, Venkateswaran A. R., Bharat Narasimhan, Ratnakar Kini S., Kani Sheikh M., Prem Kumar K., Pugazhendi Thangavelu, Arun Murugan, Sibi Thooran Karmegam, Radhakrishnan N., Mohammed Noufal, Amit Soni

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Background and Aims: The liver is integral to lipid metabolism, and a compromise in its function leads to perturbations in these pathways. In this study, we hope to determine the correlation between CLD severity and its effect on lipid parameters. We also look at the etiology-specific effects on lipid levels. Materials and Methods: This is a retrospective cross-sectional analysis of 250 patients with cirrhosis compared to 250 healthy age and sex-matched controls. Severity assessment of CLD using MELD and Child-Pugh scores was performed and etiological details collected. A questionnaire was used to obtain patient demographic details and lastly, a fasting lipid profile (Total, LDL, HDL cholesterol, Triglycerides and VLDL) was obtained. Results: All components of the lipid profile declined linearly with increasing severity of CLD as determined by MELD and Child-Pugh scores. Lipid levels were clearly lower in CLD patients as compared to healthy controls. Interestingly, preliminary analysis indicated that CLD of different etiologies had differential effects on Lipid profiles. This aspect is under further analysis. Conclusion: All components of the lipid profile were definitely lower in CLD patients as compared to controls and demonstrated an inverse correlation with increasing severity. The utilization of this parameter as a prognosticating aid requires further study. Additionally, preliminary analysis indicates that various CLD etiologies appear to have specific effects on the lipid profile – a finding under further analysis.

Keywords: CLD, cholesterol, HDL, LDL, lipid profile, triglycerides, VLDL

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Authors: Ankita Singh

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Sex trafficking and child pornography are those kinds of borderless crimes which can not be effectively prevented only through the laws and efforts of one country because it requires a proper and smooth collaboration among countries. Eradication of international human trafficking syndicates, criminalisation of international cyber offenders, and effective ban on child pornography is not possible without applying effective universal laws; hence, continuous collaboration of all countries is much needed to adopt and routinely update these universal laws. Congregation of countries on an international platform is very necessary from time to time, where they can simultaneously adopt international agendas and create powerful universal laws to prevent sex trafficking and child pornography in this modern digital era. In the past, some international steps have been taken through The Convention on the Rights of the Child (CRC) and through The Optional Protocol to the Convention on the Rights of the Child on the Sale of Children, Child Prostitution, and Child Pornography, but in reality, these measures are quite weak and are not capable in effectively protecting children from sexual abuse in this modern & highly advanced digital era. The uncontrolled growth of artificial intelligence (AI) and its misuse, lack of proper legal jurisdiction over foreign child abusers and difficulties in their extradition, improper control over international trade of digital child pornographic content, etc., are some prominent issues which can only be controlled through some new, effective and powerful universal laws. Due to a lack of effective international standards and a lack of improper collaboration among countries, Indian laws are also not capable of taking effective actions against child abusers. This research will be conducted through both doctrinal as well as empirical methods. Various literary sources will be examined, and a questionnaire survey will be conducted to analyse the effectiveness of international standards and Indian laws against child pornography. Participants in this survey will be Indian University students. In this work, the existing international norms made for protecting children from sexual abuse will be critically analysed. It will explore why effective and strong collaboration between countries is required in modern times. It will be analysed whether existing international steps are enough to protect children from getting trafficked or being subjected to pornography, and if these steps are not found to be sufficient enough, then suggestions will be given on how international standards and protections can be made more effective and powerful in this digital era. The approach of India towards the existing international standards, the Indian laws to protect children from being subjected to pornography, and the contributions & capabilities of India in strengthening the international standards will also be analysed.

Keywords: child pornography, prevention of children from sexual offences act, the optional protocol to the convention on the rights of the child on the sale of children, child prostitution and child pornography, the convention on the rights of the child

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Authors: Habib Alshuwaikhat, Nahid Hossain

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Residential sector consumes more than half of the produced electricity in Saudi Arabia, and fossil fuel is the main source of energy to meet growing household electricity demand in the Kingdom. Several studies forecasted and expressed concern that unless the domestic energy demand growth is controlled, it will reduce Saudi Arabia’s crude oil export capacity within a decade and the Kingdom is likely to be incapable of exporting crude oil within next three decades. Though the Saudi government has initiated to address the domestic energy demand growth issue, the demand side energy management policies and programs are focused on industrial and commercial sectors. It is apparent that there is an urgent need to develop a comprehensive energy efficiency strategy for addressing efficient energy use in residential sector in the Kingdom. Then again as Saudi Arabia is at its primary stage in addressing energy efficiency issues in its residential sector, there is a scope for the Kingdom to learn from global energy efficiency practices and design its own energy efficiency policies and programs. However, in order to do that sustainable, it is essential to address local contexts of energy efficiency. It is also necessary to find out the policies and programs that will fit to the local contexts. Thus the objective of this study was set to identify globally best practice energy efficiency policies and programs in residential sector that have replication potential in Saudi Arabia. In this regard two sets of multi-criteria decision analysis matrices were developed to evaluate the energy efficiency policies and programs. The first matrix was used to evaluate the global energy efficiency policies and programs, and the second matrix was used to evaluate the replication potential of global best practice energy efficiency policies and programs for Saudi Arabia. Wuppertal Institute’s guidelines for energy efficiency policy evaluation were used to develop the matrices, and the different attributes of the matrices were set through available literature review. The study reveals that the best practice energy efficiency policies and programs with good replication potential for Saudi Arabia are those which have multiple components to address energy efficiency and are diversified in their characteristics. The study also indicates the more diversified components are included in a policy and program, the more replication potential it has for the Kingdom. This finding is consistent with other studies, where it is observed that in order to be successful in energy efficiency practices, it is required to introduce multiple policy components in a cluster rather than concentrate on a single policy measure. The developed multi-criteria decision analysis matrices for energy efficiency policy and program evaluation could be utilized to assess the replication potential of other globally best practice energy efficiency policies and programs for the residential sector of the Kingdom. In addition it has potential to guide Saudi policy makers to adopt and formulate its own energy efficiency policies and programs for Saudi Arabia.

Keywords: Saudi Arabia, residential sector, energy efficiency, policy evaluation

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Authors: Zohar Manber, Ran Elkon

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Accumulation of somatic mutations (SMs) in the genome is a major driving force of cancer development. Most SMs in the tumor's genome are functionally neutral; however, some cause damage to critical processes and provide the tumor with a selective growth advantage (termed cancer driver mutations). Current research on functional significance of SMs is mainly focused on finding alterations in protein coding sequences. However, the exome comprises only 3% of the human genome, and thus, SMs in the noncoding genome significantly outnumber those that map to protein-coding regions. Although our understanding of noncoding driver SMs is very rudimentary, it is likely that disruption of regulatory elements in the genome is an important, yet largely underexplored mechanism by which somatic mutations contribute to cancer development. The expression of most human genes is controlled by multiple enhancers, and therefore, it is conceivable that regulatory SMs are distributed across different enhancers of the same target gene. Yet, to date, most statistical searches for regulatory SMs have considered each regulatory element individually, which may reduce statistical power. The first challenge in considering the cumulative activity of all the enhancers of a gene as a single unit is to map enhancers to their target promoters. Such mapping defines for each gene its set of regulating enhancers (termed "set of regulatory elements" (SRE)). Considering multiple enhancers of each gene as one unit holds great promise for enhancing the identification of driver regulatory SMs. However, the success of this approach is greatly dependent on the availability of comprehensive and accurate enhancer-promoter (E-P) maps. To date, the discovery of driver regulatory SMs has been hindered by insufficient sample sizes and statistical analyses that often considered each regulatory element separately. In this study, we analyzed more than 2,500 whole-genome sequence (WGS) samples provided by The Cancer Genome Atlas (TCGA) and The International Cancer Genome Consortium (ICGC) in order to identify such driver regulatory SMs. Our analyses took into account the combinatorial aspect of gene regulation by considering all the enhancers that control the same target gene as one unit, based on E-P maps from three genomics resources. The identification of candidate driver noncoding SMs is based on their recurrence. We searched for SREs of genes that are "hotspots" for SMs (that is, they accumulate SMs at a significantly elevated rate). To test the statistical significance of recurrence of SMs within a gene's SRE, we used both global and local background mutation rates. Using this approach, we detected - in seven different cancer types - numerous "hotspots" for SMs. To support the functional significance of these recurrent noncoding SMs, we further examined their association with the expression level of their target gene (using gene expression data provided by the ICGC and TCGA for samples that were also analyzed by WGS).

Keywords: cancer genomics, enhancers, noncoding genome, regulatory elements

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