Search results for: target of rapamycin
Commenced in January 2007
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Edition: International
Paper Count: 2736

Search results for: target of rapamycin

1926 Research on Internet Attention of Tourism and Marketing Strategy in Northeast Sichuan Economic Zone in China Based on Baidu Index

Authors: Chuanqiao Zheng, Wei Zeng, Haozhen Lin

Abstract:

As of March 2020, the number of Chinese netizens has reached 904 million. The proportion of Internet users accessing the Internet through mobile phones is as high as 99.3%. Under the background of 'Internet +', tourists have a stronger sense of independence in the choice of tourism destinations and tourism products. Tourists are more inclined to learn about the relevant information on tourism destinations and other tourists' evaluations of tourist products through the Internet. The search engine, as an integrated platform that contains a wealth of information, is highly valuable to the analysis of the characteristics of the Internet attention given to various tourism destinations, through big data mining and analysis. This article uses the Baidu Index as the data source, which is one of the products of Baidu Search. The Baidu Index is based on big data, which collects and shares the search results of a large number of Internet users on the Baidu search engine. The big data used in this article includes search index, demand map, population profile, etc. The main research methods used are: (1) based on the search index, analyzing the Internet attention given to the tourism in five cities in Northeast Sichuan at different times, so as to obtain the overall trend and individual characteristics of tourism development in the region; (2) based on the demand map and the population profile, analyzing the demographic characteristics and market positioning of the tourist groups in these cities to understand the characteristics and needs of the target groups; (3) correlating the Internet attention data with the permanent population of each province in China in the corresponding to construct the Boston matrix of the Internet attention rate of the Northeast Sichuan tourism, obtain the tourism target markets, and then propose development strategies for different markets. The study has found that: a) the Internet attention given to the tourism in the region can be categorized into tourist off-season and peak season; the Internet attention given to tourism in different cities is quite different. b) tourists look for information including tour guide information, ticket information, traffic information, weather information, and information on the competing tourism cities; with regard to the population profile, the main group of potential tourists searching for the keywords of tourism in the five prefecture-level cities in Northeast Sichuan are youth. The male to female ratio is about 6 to 4, with males being predominant. c) through the construction of the Boston matrix, it is concluded that the star market for tourism in the Northeast Sichuan Economic Zone includes Sichuan and Shaanxi; the cash cows market includes Hainan and Ningxia; the question market includes Jiangsu and Shanghai; the dog market includes Hubei and Jiangxi. The study concludes with the following planning strategies and recommendations: i) creating a diversified business format that integrates cultural and tourism; ii) creating a brand image of niche tourism; iii) focusing on the development of tourism products; iv) innovating composite three-dimensional marketing channels.

Keywords: Baidu Index, big data, internet attention, tourism

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1925 Synthesis and in-vitro Evaluation of Quinozolines as Potent EGFR Inhibitor

Authors: Vinaya Kambappa, Chinnadurai Mani, Komaraiah Palle

Abstract:

Non-small cell-lung cancer (NSCLC) cells have increased expression of EGFR, which makes them a potential target for cancer therapy. Based on molecular docking and previous reports, we designed and synthesized quinazoline derivatives as potent EGFR inhibitors. Among the derivatives, three compounds showed good antiproliferative activity against A-549 and H-1299 cells. Furthermore, these compounds inhibited EGFR signaling exhibiting diminishing p-EGFR and its downstream proteins like p-Akt, p-Erk1/2, and p-mTOR; however, it did not alter the levels of EGFR, Akt, Erk1/2 and mTOR proteins. Flow cytometric analysis indicated the accumulation of cells at G1 phase suggesting induction of apoptosis, which was further confirmed by annexin V/propidium iodide staining. Our study suggested that quinazoline scaffold can be developed as novel EGFR kinase inhibitors for cancer therapy.

Keywords: apoptosis, non-small cell-lung cancer cells, EGFR, quinazoline

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1924 Slurry Erosion Behaviour of Cryotreated SS316L Impeller Steel Used for Irrigation Pumps

Authors: Jagtar Singh, Kulwinder Singh

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Slurry erosion is a type of erosion wherein material is removed from the target surface due to impingement of solid particles entrained in liquid medium. Slurry erosion performance of deep cryogenic treatment on impeller steel SS 316 L has been investigated. Slurry collected from an actual irrigation pump used as the abrasive media in an erosion test rig. An attempt has been made to study the effect of velocity of fluid and impingement angle by constant concentration (ppm) on the slurry erosion behavior of these cryotreated steels under different experimental conditions. The slurry erosion wear analysis of cryotreated and untreated steels was done. The slurry erosion performance of cryotreated SS 316L impeller steel has been found to superior to that of untreated steel. Metallurgical investigation, hardness as well as %age of carbide in both types of steel was also investigated.

Keywords: deep cryogenic treatment, impeller, Irrigation pumps SS316L, slurry erosion

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1923 Community Pharmacist's Perceptions Towards Generic Drugs in Algeria

Authors: M. Y. Achouri, O. A. Alleg, M. C. L. Moulai, M. A. Selka

Abstract:

This study aims to assess the perception and attitudes of community pharmacists in Sidi-Bel-Abbes (Algeria) towards generic drugs. This is a descriptive cross-sectional prospective survey and quantitative, conducted over a period of two months from April to May 2014. The target population consisted of 118 pharmacists practicing in pharmacies in Sidi-Bel-Abbes. Data collection was conducted through a questionnaire consisting of thirteen (13) items. Fifty six (67%) of community pharmacists in the town of Sidi-Bel-Abbes in the survey believe that generics have a lower quality compared to brand name medicines Only 42% of respondents viewed locally manufactured generic medicines as equal in quality compared to the imported generic medicines, and 63% believe that the generics substitution has led to change the relationship between a pharmacist and patient. In order to promote the practice of generic medicines in Algeria, an educational program should be implemented.

Keywords: generic drugs, perception, attitudes, community pharmacists

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1922 Impact of Pharmacist-Led Care on Glycaemic Control in Patients with Type 2 Diabetes: A Randomised-Controlled Trial

Authors: Emmanuel A. David, Rebecca O. Soremekun, Roseline I. Aderemi-Williams

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Background: The complexities involved in the management of diabetes mellitus require a multi-dimensional, multi-professional collaborative and continuous care by health care providers and a substantial self-care by the patients in order to achieve desired treatment outcomes. The effect of pharmacists’ care in the management of diabetes in resource-endowed nations is well documented in literature, but randomised-controlled assessment of the impact of pharmacist-led care among patients with diabetes in resource-limited settings like Nigeria and sub-Saharan Africa countries is scarce. Objective: To evaluate the impact of Pharmacist-led care on glycaemic control in patients with uncontrolled type 2 diabetes, using a randomised-controlled study design Methods: This study employed a prospective randomised controlled design, to assess the impact of pharmacist-led care on glycaemic control of 108 poorly controlled type 2 diabetic patients. A total of 200 clinically diagnosed type 2 diabetes patients were purposively selected using fasting blood glucose ≥ 7mmol/L and tested for long term glucose control using Glycated haemoglobin measure. One hundred and eight (108) patients with ≥ 7% Glycated haemoglobin were recruited for the study and assigned unique identification numbers. They were further randomly allocated to intervention and usual care groups using computer generated random numbers, with each group containing 54 subjects. Patients in the intervention group received pharmacist-structured intervention, including education, periodic phone calls, adherence counselling, referral and 6 months follow-up, while patients in usual care group only kept clinic appointments with their physicians. Data collected at baseline and six months included socio-demographic characteristics, fasting blood glucose, Glycated haemoglobin, blood pressure, lipid profile. With an intention to treat analysis, Mann-Whitney U test was used to compared median change from baseline in the primary outcome (Glycated haemoglobin) and secondary outcomes measure, effect size was computed and proportion of patients that reached target laboratory parameter were compared in both arms. Results: All enrolled participants (108) completed the study, 54 in each study. Mean age was 51±11.75 and majority were female (68.5%). Intervention patients had significant reduction in Glycated haemoglobin (-0.75%; P<0.001; η2 = 0.144), with greater proportion attaining target laboratory parameter after 6 months of care compared to usual care group (Glycated haemoglobin: 42.6% vs 20.8%; P=0.02). Furthermore, patients who received pharmacist-led care were about 3 times more likely to have better glucose control (AOR 2.718, 95%CI: 1.143-6.461) compared to usual care group. Conclusion: Pharmacist-led care significantly improved glucose control in patients with uncontrolled type 2 diabetes mellitus and should be integrated in the routine management of diabetes patients, especially in resource-limited settings.

Keywords: glycaemic control , pharmacist-led care, randomised-controlled trial , type 2 diabetes mellitus

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1921 Self-Compacting White Concrete Mix Design Using the Particle Matrix Model

Authors: Samindi Samarakoon, Ørjan Sletbakk Vie, Remi Kleiven Fjelldal

Abstract:

White concrete facade elements are widely used in construction industry. It is challenging to achieve the desired workability in casting of white concrete elements. Particle Matrix model was used for proportioning the self-compacting white concrete (SCWC) to control segregation and bleeding and to improve workability. The paper presents how to reach the target slump flow while controlling bleeding and segregation in SCWC. The amount of aggregates, binders and mixing water, as well as type and dosage of superplasticizer (SP) to be used are the major factors influencing the properties of SCWC. Slump flow and compressive strength tests were carried out to examine the performance of SCWC, and the results indicate that the particle matrix model could produce successfully SCWC controlling segregation and bleeding.

Keywords: white concrete, particle matrix model, mix design, construction industry

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1920 Alwadei Syndrome - A Genetic Cause Of Intellectual Disability

Authors: Mafalda Moreira, Diana Alba, Inês Paiva Ferreira, Rita Calejo, Ana Rita Soares, Leonilde Machado

Abstract:

Intellectual disability (ID) is characterized by deficits in intellectualfunctioningassociatedwithalterations in the adaptive behaviour, whose onset is inthedevelopmentalperiod. Itaffects 3% of the population, ofwhich 10% have a geneticaetiology. One of those causes isAlwadeiSyndrome, with 3 cases describedworldwide. It results from a homozygous nonsense mutation in theRUSC2 gene andisassociatedwithintellectualdisabilityanddysmorphic facialfeatures. Theauthorsreportthe case of a 5-year-old-boy, born to a healthymotherafter a full-termuneventfulpregnancy, thatwasreferred to Neurodevelopmentalconsultationdue toglobal developmentaldelay. Familyhistoryrevealedlearningdifficulties in the paternal brotherhood. Milddismorphicfeatureswereevidentsuch as darkinfraorbitalregion, low-set ears, beakednose, retrognathism, high-archedpalateandjointhyperlaxity. WechslerIntelligenceScale for Children III fullscaleIQ quoted 61. Karyotypeandchromosomalmicroarrayanalysiswerenormal, as well as the fragile X molecular study. DNA sequencingwasthenperformedandallowedtheidentificationof amutation in the RUSC2 gene. Theetiologicaldiagnosisof ID remains unknown in up to 80% of cases, creatinguncertainty in children’sfamilies. Theadvances in DNA sequencingtechnologieshaveincreasedourknowledgeofthegeneticdiseasesinvolved, as theAlwadeisyndromewasonlydescribedsince 2016. Thegeneticdiagnosisof ID allowsfamilygeneticcounselingandenablesthedevelopmentof target therapeutic approaches.

Keywords: intellectual disability, genetic aetiology, alwadei syndrome, RUSC2

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1919 In Silico Study of the Biological and Pharmacological Activity of Nigella sativa

Authors: Ammar Ouahab, Meriem Houichi , Sanna Mihoubi

Abstract:

Background: Nigella sativa is an annual flowering plant, belongs to the Ranunculaceae family. It has many pharmacological activities such as anti-inflammatory; anti-bacterial; anti-hepatotoxic activities etc. Materials: In order to predict the pharmacological activity of Nigella Sativa’s compounds, some web based servers were used, namely, PubChem, Molinspiration, ADMET-SAR, PASS online and PharMapper. In addition to that, AutoDOCK was used to investigate the different molecular interactions between the selected compounds and their target proteins. Results: All compounds displayed a stable interaction with their targets and satisfactory binding energies, which means that they are active on their targets. Conclusion: Nigella sativa is an effective medicinal plant that has several ethno-medical uses; the latter uses are proven herein via an in-silico study of their pharmacological activities.

Keywords: Nigella sativa, AutoDOCK, PubChem, Molinspiration, ADMET-SAR, PharMapper, PASS online server, docking

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1918 Specialized Translation Teaching Strategies: A Corpus-Based Approach

Authors: Yingying Ding

Abstract:

This study presents a methodology of specialized translation with the objective of helping teachers to improve the strategies in teaching translation. In order to allow students to acquire skills to translate specialized texts, they need to become familiar with the semantic and syntactic features of source texts and target texts. The aim of our study is to use a corpus-based approach in the teaching of specialized translation between Chinese and Italian. This study proposes to construct a specialized Chinese - Italian comparable corpus that consists of 50 economic contracts from the domain of food. With the help of AntConc, we propose to compile a comparable corpus in for translation teaching purposes. This paper attempts to provide insight into how teachers could benefit from comparable corpus in the teaching of specialized translation from Italian into Chinese and through some examples of passive sentences how students could learn to apply different strategies for translating appropriately the voice.

Keywords: contrastive studies, specialised translation, corpus-based approach, teaching

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1917 Development of DNDC Modelling Method for Evaluation of Carbon Dioxide Emission from Arable Soils in European Russia

Authors: Olga Sukhoveeva

Abstract:

Carbon dioxide (CO2) is the main component of carbon biogeochemical cycle and one of the most important greenhouse gases (GHG). Agriculture, particularly arable soils, are one the largest sources of GHG emission for the atmosphere including CO2.Models may be used for estimation of GHG emission from agriculture if they can be adapted for different countries conditions. The only model used in officially at national level in United Kingdom and China for this purpose is DNDC (DeNitrification-DeComposition). In our research, the model DNDC is offered for estimation of GHG emission from arable soils in Russia. The aim of our research was to create the method of DNDC using for evaluation of CO2 emission in Russia based on official statistical information. The target territory was European part of Russia where many field experiments are located. At the first step of research the database on climate, soil and cropping characteristics for the target region from governmental, statistical, and literature sources were created. All-Russia Research Institute of Hydrometeorological Information – World Data Centre provides open daily data about average meteorological and climatic conditions. It must be calculated spatial average values of maximum and minimum air temperature and precipitation over the region. Spatial average values of soil characteristics (soil texture, bulk density, pH, soil organic carbon content) can be determined on the base of Union state register of soil recourses of Russia. Cropping technologies are published by agricultural research institutes and departments. We offer to define cropping system parameters (annual information about crop yields, amount and types of fertilizers and manure) on the base of the Federal State Statistics Service data. Content of carbon in plant biomass may be calculated via formulas developed and published by Ministry of Natural Resources and Environment of the Russian Federation. At the second step CO2 emission from soil in this region were calculated by DNDC. Modelling data were compared with empirical and literature data and good results were obtained, modelled values were equivalent to the measured ones. It was revealed that the DNDC model may be used to evaluate and forecast the CO2 emission from arable soils in Russia based on the official statistical information. Also, it can be used for creation of the program for decreasing GHG emission from arable soils to the atmosphere. Financial Support: fundamental scientific researching theme 0148-2014-0005 No 01201352499 ‘Solution of fundamental problems of analysis and forecast of Earth climatic system condition’ for 2014-2020; fundamental research program of Presidium of RAS No 51 ‘Climate change: causes, risks, consequences, problems of adaptation and regulation’ for 2018-2020.

Keywords: arable soils, carbon dioxide emission, DNDC model, European Russia

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1916 Reconfigurable Efficient IIR Filter Design Using MAC Algorithm

Authors: Rajesh Mehra

Abstract:

In this paper an IIR filter has been designed and simulated on an FPGA. The implementation is based on MAC algorithm which uses multiply-and-accumulate operations IIR filter design implementation. Parallel Pipelined structure is used to implement the proposed IIR Filter taking optimal advantage of the look up table of the FPGA device. The designed filter has been synthesized on DSP slice based FPGA to perform multiplier function of MAC unit. The DSP slices are useful to enhance the speed performance. The developed IIR filter is designed and simulated with MATLAB and synthesized with Xilinx Synthesis Tool (XST), and implemented on Virtex 5 and Spartan 3 ADSP FPGA devices. The IIR filter implemented on Virtex 5 FPGA can operate at an estimated frequency of 81.5 MHz as compared to 40.5 MHz in case of Spartan 3 ADSP FPGA. The Virtex 5 based implementation also consumes less slices and slice flip flops of target FPGA in comparison to Spartan 3 ADSP based implementation to provide cost effective solution for signal processing applications.

Keywords: butterworth, DSP, IIR, MAC, FPGA

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1915 Prosodic Transfer in Foreign Language Learning: A Phonetic Crosscheck of Intonation and F₀ Range between Italian and German Native and Non-Native Speakers

Authors: Violetta Cataldo, Renata Savy, Simona Sbranna

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Background: Foreign Language Learning (FLL) is characterised by prosodic transfer phenomena regarding pitch accents placement, intonation patterns, and pitch range excursion from the learners’ mother tongue to their Foreign Language (FL) which suggests that the gradual development of general linguistic competence in FL does not imply an equally correspondent improvement of the prosodic competence. Topic: The present study aims to monitor the development of prosodic competence of learners of Italian and German throughout the FLL process. The primary object of this study is to investigate the intonational features and the f₀ range excursion of Italian and German from a cross-linguistic perspective; analyses of native speakers’ productions point out the differences between this pair of languages and provide models for the Target Language (TL). A following crosscheck compares the L2 productions in Italian and German by non-native speakers to the Target Language models, in order to verify the occurrence of prosodic interference phenomena, i.e., type, degree, and modalities. Methodology: The subjects of the research are university students belonging to two groups: Italian native speakers learning German as FL and German native speakers learning Italian as FL. Both of them have been divided into three subgroups according to the FL proficiency level (beginners, intermediate, advanced). The dataset consists of wh-questions placed in situational contexts uttered in both speakers’ L1 and FL. Using a phonetic approach, analyses have considered three domains of intonational contours (Initial Profile, Nuclear Accent, and Terminal Contour) and two dimensions of the f₀ range parameter (span and level), which provide a basis for comparison between L1 and L2 productions. Findings: Results highlight a strong presence of prosodic transfer phenomena affecting L2 productions in the majority of both Italian and German learners, irrespective of their FL proficiency level; the transfer concerns all the three domains of the contour taken into account, although with different modalities and characteristics. Currently, L2 productions of German learners show a pitch span compression on the domain of the Terminal Contour compared to their L1 towards the TL; furthermore, German learners tend to use lower pitch range values in deviation from their L1 when improving their general linguistic competence in Italian FL proficiency level. Results regarding pitch range span and level in L2 productions by Italian learners are still in progress. At present, they show a similar tendency to expand the pitch span and to raise the pitch level, which also reveals a deviation from the L1 possibly in the direction of German TL. Conclusion: Intonational features seem to be 'resistant' parameters to which learners appear not to be particularly sensitive. By contrast, they show a certain sensitiveness to FL pitch range dimensions. Making clear which the most resistant and the most sensitive parameters are when learning FL prosody could lay groundwork for the development of prosodic trainings thanks to which learners could finally acquire a clear and natural pronunciation and intonation.

Keywords: foreign language learning, German, Italian, L2 prosody, pitch range, transfer

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1914 Fabrication and Evaluation of Particleboards from Oil Palm Fronds Blend with Empty Fruit Bunch Fibre

Authors: Ghazi Faisal Najmuldeen, Wahida Amat Fadzila

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The aim of this study is to investigate physical and mechanical properties of experimental particleboards manufactured from mixing the oil palm fronds particles with empty fruit bunch fibers. Variables were two blending ratios (100:0 and 70:30), press temperature (160°C and 180°C) and press time (180 and 300 s). Experimental boards with a target density of 750 kg m-3 were manufactured from these two particles and fibers blended with urea formaldehyde resin and compressed into targeted thickness. The effect of these manufacturing conditions on bending strength, internal bonding, water absorption and thickness swelling were determined. From this research, it can be concluded that hybridization of fibers with fronds particles improved some properties of particleboard. Empty fruit bunch fibers and fronds particleboard showed better modulus of rupture and internal bonding than fronds particleboards.

Keywords: oil palm fronds, empty fruit bunch, particleboards, chemistry, environment

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1913 Exploring the Importance of Different Product Cues on the Selection for Chocolate from the Consumer Perspective

Authors: Ezeni Brzovska, Durdana Ozretic-Dosen

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The purpose of this paper is to deepen the understanding of the product cues that influence purchase decision for a specific product category – chocolate, and to identify demographic differences in the buying behavior. ANOVA was employed for analyzing the significance level for nine product cues, and the survey showed statistically significant differences among different age and gender groups, and between respondents with different levels of education. From the theoretical perspective, the study adds to the existing knowledge by contributing with the research results from the new environment (Southeast Europe, Macedonia), which has been neglected so far. Establishing the level of significance for the product cues that affect buying behavior in the chocolate consumption context might help managers to improve marketing decision-making, and better meet consumer needs through identifying opportunities for packaging innovations and/or personalization toward different target groups.

Keywords: chocolate consumption context, chocolate selection, demographic characteristics, product cues

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1912 Smart Multifunctionalized and Responsive Polymersomes as Targeted and Selective Recognition Systems

Authors: Silvia Moreno, Banu Iyisan, Hannes Gumz, Brigitte Voit, Dietmar Appelhans

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Polymersomes are materials which are considered as artificial counterparts of natural vesicles. The nanotechnology of such smart nanovesicles is very useful to enhance the efficiency of many therapeutic and diagnostic drugs. Those compounds show a higher stability, flexibility, and mechanical strength to the membrane compared to natural liposomes. In addition, they can be designed in detail, the permeability of the membrane can be controlled by different stimuli, and the surface can be functionalized with different biological molecules to facilitate monitoring and target. For this purpose, this study demonstrates the formation of multifunctional and pH sensitive polymersomes and their functionalization with different reactive groups or biomolecules inside and outside of polymersomes´ membrane providing by crossing the membrane and docking/undocking processes for biomedical applications. Overall, they are highly versatile and thus present new opportunities for the design of targeted and selective recognition systems, for example, in mimicking cell functions and in synthetic biology.

Keywords: multifunctionalized, pH stimulus, controllable release, cellular uptake

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1911 Enhancing Precision in Abdominal External Beam Radiation Therapy: Exhale Breath Hold Technique for Respiratory Motion Management

Authors: Stephanie P. Nigro

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The Exhale Breath Hold (EBH) technique presents a promising approach to enhance the precision and efficacy of External Beam Radiation Therapy (EBRT) for abdominal tumours, which include liver, pancreas, kidney, and adrenal glands. These tumours are challenging to treat due to their proximity to organs at risk (OARs) and the significant motion induced by respiration and physiological variations, such as stomach filling. Respiratory motion can cause up to 40mm of displacement in abdominal organs, complicating accurate targeting. While current practices like limiting fasting help reduce motion related to digestive processes, they do not address respiratory motion. 4DCT scans are used to assess this motion, but they require extensive workflow time and expose patients to higher doses of radiation. The EBH technique, which involves holding the breath in an exhale with no air in the lungs, stabilizes internal organ motion, thereby reducing respiratory-induced motion. The primary benefit of EBH is the reduction in treatment volume sizes, specifically the Internal Target Volume (ITV) and Planning Target Volume (PTV), as demonstrated by smaller ITVs when gated in EBH. This reduction also improves the quality of 3D Cone Beam CT (CBCT) images by minimizing respiratory artifacts, facilitating soft tissue matching akin to stereotactic treatments. Patients suitable for EBH must meet criteria including the ability to hold their breath for at least 15 seconds and maintain a consistent breathing pattern. For those who do not qualify, the traditional 4DCT protocol will be used. The implementation involves an EBH planning scan and additional short EBH scans to ensure reproducibility and assist in contouring and volume expansions, with a Free Breathing (FB) scan used for setup purposes. Treatment planning on EBH scans leads to smaller PTVs, though intrafractional and interfractional breath hold variations must be accounted for in margins. The treatment decision process includes performing CBCT in EBH intervals, with careful matching and adjustment based on soft tissue and fiducial markers. Initial studies at two sites will evaluate the necessity of multiple CBCTs, assessing shifts and the benefits of initial versus mid-treatment CBCT. Considerations for successful implementation include thorough patient coaching, staff training, and verification of breath holds, despite potential disadvantages such as longer treatment times and patient exhaustion. Overall, the EBH technique offers significant improvements in the accuracy and quality of abdominal EBRT, paving the way for more effective and safer treatments for patients.

Keywords: abdominal cancers, exhale breath hold, radiation therapy, respiratory motion

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1910 Safety and Efficacy of RM-001, Autologous HBG1/2 Promoter-Modified CD34+Hematopoietic Stem and Progenitor Cells, in Transfusion-Dependent β-Thalassemia

Authors: Rongrong Liu, Li Wang, Hui Xu, Jianpei Fang, Sixi Liu, Xiaolin Yin, Junbin Liang, Gaohui Yan, Yaoyun Li, Yali Zhou, Xinyu Li, Yue Li, Lei Shi, Yongrong Lai, Junjiu Huang, Xinhua Zhang

Abstract:

Background: Beta-Thalassemia is caused by reduced (β+) or absent (β0) synthesis of the β-globin chains of hemoglobin. Transfusions and oral iron chelation therapy have improved the quality of life for patients with Transfusion-Dependent thalassemia (TDT). Recent advances in genome editing platforms of CRISPR-Cas9 have paved the way for induction of HbF by reactivating expression of γ-chain.Aims: We performed CRISPR-Cas9-mediated genome editing of hematopoietic stem cells to mutate HBG1/HBG2 promoter sequence, thereby representing a naturally occurring HPFH-liked mutation, producing RM-001. Here, we present an initial assessment of safety and efficacy of RM-001 in patients with TDT. Methods: Patients (6–35 y of age) with TDT receiving packed red blood cell (pRBC) transfusions of ≥100 mL/kg/y or ≥10 units/y in the previous 2 y were eligible. CD34+ cells were edited with CRISPR-Cas9 using a guide RNA specific for the binding site of BCL11A on the HBG1/2 promoter. Prior to RM-001 product infusion (day 0), patients received myeloablative conditioning with Busulfan from day-7 to day-4. Patients were monitored for AEs Hb expression.Results: Data cut as of 28 Feb 2024, 16 TDT patients have been treated with RM-001 and followed ≥3 months. 5 of these 16 patients had finished their 24 months follow up. Eleven patients have β0/β0 genotype and five patients have β0/β+ genotype. In addition to β-thalassemia, two patients had α- deletion with the genotype of --/αα. Efficacy:All patients received a single dose intravenous infusion of RM-001 cells. 5 of them had been followed 24 months or longer. All patients achieved transfusion-independent (TI, total Hb continued ≥ 9g/dL) (Figure1). Patients demonstrated sustained and clinically meaningful increases in HbF levels since 4 month post-RM-001 infusion (Figure.2). Total hemoglobin in all patients was stable at 10-12g/dL during the follow-up period. Safety:The adverse events observed after RM-001 infusion were consistent with those that are typical of Busulfan-based myeloablation. The allelic editing analysis at 6-month visit showed that the on-target allelic editing frequency in bone marrow cells was 73.44% (64.65% to 84.6%, n=13).Summary/Conclusion: This interim analysis, in which all the 19 patients age from 7.9 to 25yo met the success criteria for the trial with respect to transfusion independence, showed that autologous HBG1/2 promoter-modified CD34+ HSPCs gene therapy resulted in an adequate amount of HbF as early as 2 months after infusion led to near-normal hemoglobin levels, remained transfusion-free through the reported period without product related SAE. After RM-001 infusion, high levels of HbF proportion and on-target editing in bone marrow cells were maintained. Submitted on behalf of the RM-001 Investigators.

Keywords: thalassemian, genetherapy, CRISPR/Cas9, HbF

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1909 Improving Binding Selectivity in Molecularly Imprinted Polymers from Templates of Higher Biomolecular Weight: An Application in Cancer Targeting and Drug Delivery

Authors: Ben Otange, Wolfgang Parak, Florian Schulz, Michael Alexander Rubhausen

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The feasibility of extending the usage of molecular imprinting technique in complex biomolecules is demonstrated in this research. This technique is promising in diverse applications in areas such as drug delivery, diagnosis of diseases, catalysts, and impurities detection as well as treatment of various complications. While molecularly imprinted polymers MIP remain robust in the synthesis of molecules with remarkable binding sites that have high affinities to specific molecules of interest, extending the usage to complex biomolecules remains futile. This work reports on the successful synthesis of MIP from complex proteins: BSA, Transferrin, and MUC1. We show in this research that despite the heterogeneous binding sites and higher conformational flexibility of the chosen proteins, relying on their respective epitopes and motifs rather than the whole template produces highly sensitive and selective MIPs for specific molecular binding. Introduction: Proteins are vital in most biological processes, ranging from cell structure and structural integrity to complex functions such as transport and immunity in biological systems. Unlike other imprinting templates, proteins have heterogeneous binding sites in their complex long-chain structure, which makes their imprinting to be marred by challenges. In addressing this challenge, our attention is inclined toward the targeted delivery, which will use molecular imprinting on the particle surface so that these particles may recognize overexpressed proteins on the target cells. Our goal is thus to make surfaces of nanoparticles that specifically bind to the target cells. Results and Discussions: Using epitopes of BSA and MUC1 proteins and motifs with conserved receptors of transferrin as the respective templates for MIPs, significant improvement in the MIP sensitivity to the binding of complex protein templates was noted. Through the Fluorescence Correlation Spectroscopy FCS measurements on the size of protein corona after incubation of the synthesized nanoparticles with proteins, we noted a high affinity of MIPs to the binding of their respective complex proteins. In addition, quantitative analysis of hard corona using SDS-PAGE showed that only a specific protein was strongly bound on the respective MIPs when incubated with similar concentrations of the protein mixture. Conclusion: Our findings have shown that the merits of MIPs can be extended to complex molecules of higher biomolecular mass. As such, the unique merits of the technique, including high sensitivity and selectivity, relative ease of synthesis, production of materials with higher physical robustness, and higher stability, can be extended to more templates that were previously not suitable candidates despite their abundance and usage within the body.

Keywords: molecularly imprinted polymers, specific binding, drug delivery, high biomolecular mass-templates

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1908 Neuro-Connectivity Analysis Using Abide Data in Autism Study

Authors: Dulal Bhaumik, Fei Jie, Runa Bhaumik, Bikas Sinha

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Human brain is an amazingly complex network. Aberrant activities in this network can lead to various neurological disorders such as multiple sclerosis, Parkinson’s disease, Alzheimer’s disease and autism. fMRI has emerged as an important tool to delineate the neural networks affected by such diseases, particularly autism. In this paper, we propose mixed-effects models together with an appropriate procedure for controlling false discoveries to detect disrupted connectivities in whole brain studies. Results are illustrated with a large data set known as Autism Brain Imaging Data Exchange or ABIDE which includes 361 subjects from 8 medical centers. We believe that our findings have addressed adequately the small sample inference problem, and thus are more reliable for therapeutic target for intervention. In addition, our result can be used for early detection of subjects who are at high risk of developing neurological disorders.

Keywords: ABIDE, autism spectrum disorder, fMRI, mixed-effects model

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1907 Best Perform of Rights and Justice in the Brothel Based Female Sex Worker's Community

Authors: Md. Kabir Azaharul Islam

Abstract:

Background: The purpose of this interventions was to describe the source and extent to increase health seeking rights and uptake of quality integrated maternal health, family planning and HIV information, clinical-non clinical services, and commodities amongst young people age 10-24 among brothel based Female Sex Worker’s in Bangladesh. Such Knowledge will equip with information to develop more appropriate and effective interventions that address the problem of HIV/AIDS and SRHR within the brothel based female sex worker’s community. Methods: Before start the intervention we observed situation in brothel and identify lack of knowledge about health issues, modern health facility, sexual harassment and violence & health rights. To enable access to the intervention obtained permission from a series of stakeholders within the brothel system. This intervention to the most vulnerable young key people during January 2014 to December, 2015, it designed an intervention that focuses on using peer education and sensitization meeting with self help group leader’s, pimbs, swardarni, house owner, local leaders, law enforcement agencies and target young key people (YKPs) through peer educator’s distributed BCC materials and conducted one to one and group session issues of HIV/AIDS, life skill education, maternal health, sexual reproductive health & rights, gender based violence, STD/STI and drug users in the community. Set up community based satellite clinic to provided clinical-non clinical services and commodities for SRH, FP and HIV including general health among brothel based FSWs. Peer educator frequently move and informed target beneficiaries’ age 10-24 YKPs about satellite clinic as well as time & date in the community. Results: This intervention highly promotes of brothel based FSW utilization of local facility based health providers private and public health facilities.2400 FSWs age 10-24 received information on SRHR, FP and HIV as well as existing health facilities, most of FSWs to received service from traditional healer before intervention. More than 1080 FSWs received clinical-non clinical services and commodities from satellite clinic including 12 ANC, 12 PNC and 25 MR. Most of young FSW age 10-24 are treated bonded girls under swardarni, house owner and pimbs, they have no rights to free movement as per need. As a result, they have no rights for free movement. However the brothel self help group (SHG) has become sensitized flowing this intervention. Conclusions: The majority of female sex workers well being regarding information on SRHR, FP and HIV as well as local health facilities now they feel free to go outside facilities for better health service. not only increased FSWs’ vulnerability to HIV infection and sexual reproductive health rights but also had huge implications for their human rights. This means that even when some clients impinged FSW’s rights (for example avoiding payment for services under the pretext of dissatisfaction), they might not be able to seek redress for fear of being ejected from the brothel. They raise voice national & local level different forum.

Keywords: ANC, HIV, PNC, SRHR

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1906 Prevention of Student Radicalism in School through Civic Education

Authors: Triyanto

Abstract:

Radicalism poses a real threat to Indonesia's future. The target of radicalism is the youth of Indonesia. This is proven by the majority of terrorists are young people. Radicalization is not only a repressive act but also requires educational action. One of the educational efforts is civic education. This study discusses the prevention of radicalism for students through civic education and its constraints. This is qualitative research. Data were collected through literature studies, observations and in-depth interviews. Data were validated by triangulation. The sample of this research is 30 high school students in Surakarta. Data were analyzed by the interactive model of analysis from Miles & Huberman. The results show that (1) civic education can be a way of preventing student radicalism in schools in the form of cultivating the values of education through learning in the classroom and outside the classroom; (2) The obstacles encountered include the lack of learning facilities, the limited ability of teachers and the low attention of students to the civic education.

Keywords: prevention, radicalism, senior high school student, civic education

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1905 Nonlinear Model Predictive Control for Biodiesel Production via Transesterification

Authors: Juliette Harper, Yu Yang

Abstract:

Biofuels have gained significant attention recently due to the new regulations and agreements regarding fossil fuels and greenhouse gases being made by countries around the globe. One of the most common types of biofuels is biodiesel, primarily made via the transesterification reaction. We model this nonlinear process in MATLAB using the standard kinetic equations. Then, a nonlinear Model predictive control (NMPC) was developed to regulate this process due to its capability to handle process constraints. The feeding flow uncertainty and kinetic disturbances are further incorporated in the model to capture the real-world operating conditions. The simulation results will show that the proposed NMPC can guarantee the final composition of fatty acid methyl esters (FAME) above the target threshold with a high chance by adjusting the process temperature and flowrate. This research will allow further understanding of NMPC under uncertainties and how to design the computational strategy for larger process with more variables.

Keywords: NMPC, biodiesel, uncertainties, nonlinear, MATLAB

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1904 Telomerase, a Biomarker in Oral Cancer Cell Proliferation and Tool for Its Prevention at Initial Stage

Authors: Shaista Suhail

Abstract:

As cancer populations is increasing sharply, the incidence of oral squamous cell carcinoma (OSCC) has also been expected to increase. Oral carcinogenesis is a highly complex, multistep process which involves accumulation of genetic alterations that lead to the induction of proteins promoting cell growth (encoded by oncogenes), increased enzymatic (telomerase) activity promoting cancer cell proliferation. The global increase in frequency and mortality, as well as the poor prognosis of oral squamous cell carcinoma, has intensified current research efforts in the field of prevention and early detection of this disease. The advances in the understanding of the molecular basis of oral cancer should help in the identification of new markers. The study of the carcinogenic process of the oral cancer, including continued analysis of new genetic alterations, along with their temporal sequencing during initiation, promotion and progression, will allow us to identify new diagnostic and prognostic factors, which will provide a promising basis for the application of more rational and efficient treatments. Telomerase activity has been readily found in most cancer biopsies, in premalignant lesions or germ cells. Activity of telomerase is generally absent in normal tissues. It is known to be induced upon immortalization or malignant transformation of human cells such as in oral cancer cells. Maintenance of telomeres plays an essential role during transformation of precancer to malignant stage. Mammalian telomeres, a specialized nucleoprotein structures are composed of large conctamers of the guanine-rich sequence 5_-TTAGGG-3_. The roles of telomeres in regulating both stability of genome and replicative immortality seem to contribute in essential ways in cancer initiation and progression. It is concluded that activity of telomerase can be used as a biomarker for diagnosis of malignant oral cancer and a target for inactivation in chemotherapy or gene therapy. Its expression will also prove to be an important diagnostic tool as well as a novel target for cancer therapy. The activation of telomerase may be an important step in tumorgenesis which can be controlled by inactivating its activity during chemotherapy. The expression and activity of telomerase are indispensable for cancer development. There are no drugs which can effect extremely to treat oral cancers. There is a general call for new emerging drugs or methods that are highly effective towards cancer treatment, possess low toxicity, and have a minor environment impact. Some novel natural products also offer opportunities for innovation in drug discovery. Natural compounds isolated from medicinal plants, as rich sources of novel anticancer drugs, have been of increasing interest with some enzyme (telomerase) blockage property. The alarming reports of cancer cases increase the awareness amongst the clinicians and researchers pertaining to investigate newer drug with low toxicity.

Keywords: oral carcinoma, telomere, telomerase, blockage

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1903 A Study on Websites of Public and Private Hospitals in Konya

Authors: H. Nur Görkemli, Mehmet Fidan

Abstract:

After the first acquaintance with internet in April 1993, number of internet users increased rapidly in Turkey. According to Turkish Statistical Institute’s 2013 data, internet usage in Turkey between 16-74 age group is 48,9%. Hospitals are one of the areas where internet is being intensively used like many other businesses. As a part of public relations application, websites are important tools for hospitals to reach a wide range of target audience within and outside the organization. With their websites, hospitals have opportunities to give information about their organization, strengthen their image, compete with their rivals, interact with shareholders, reflect their transparency and meet with new audiences. This study examines web sites of totally 31 hospitals which are located in Konya. Institutions are categorized as public and private hospitals and then three main research categories are determined: content, visual and technical. Main and sub categories are examined by using content analysis method. Results are interpreted in terms of public and private institutions.

Keywords: websites, hospital, health communication, internet, webpages

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1902 Research on Transmission Parameters Determination Method Based on Dynamic Characteristic Analysis

Authors: Baoshan Huang, Fanbiao Bao, Bing Li, Lianghua Zeng, Yi Zheng

Abstract:

Parameter control strategy based on statistical characteristics can analyze the choice of the transmission ratio of an automobile transmission. According to the difference of the transmission gear, the number and spacing of the gear can be determined. Transmission ratio distribution of transmission needs to satisfy certain distribution law. According to the statistic characteristics of driving parameters, the shift control strategy of the vehicle is analyzed. CVT shift schedule adjustment algorithm based on statistical characteristic parameters can be seen from the above analysis, if according to the certain algorithm to adjust the size of, can adjust the target point are in the best efficiency curve and dynamic curve between the location, to alter the vehicle characteristics. Based on the dynamic characteristics and the practical application of the vehicle, this paper presents the setting scheme of the transmission ratio.

Keywords: vehicle dynamics, transmission ratio, transmission parameters, statistical characteristics

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1901 Activation of Caspase 3 by Terpenoids and Flavonoids in Cancer Cell Lines

Authors: Nusrat Masood, Vijaya Dubey, Suaib Luqman

Abstract:

Caspase 3, a member of cysteine-aspartic acid protease family, is an imperative indicator for cell death particularly when substantiating apoptosis. Thus, caspase 3 is an interesting target for the discovery and development of anticancer agent. We adopted a four level assessment of both terpenoids and flavonoids and thus experimentally performed the enzymatic assay in cell free system as well as in cancer cell line which was validated through real time expression and molecular interaction studies. A significant difference was observed with both the class of natural products indicating terpenoids as better activators of caspase 3 compared to flavonoids both in the cell free system as well as in cell lines. The expression analysis, activation constant and binding energy also correlate well with the enzyme activity. Overall, terpenoids had an unswerving effect on caspase 3 in all the tested system while flavonoids indirectly affect enzyme activity.

Keywords: Caspase 3, terpenoids, flavonoids, activation constant, binding energy

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1900 The Current Status of Middle Class Internet Use in China: An Analysis Based on the Chinese General Social Survey 2015 Data and Semi-Structured Investigation

Authors: Abigail Qian Zhou

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In today's China, the well-educated middle class, with stable jobs and above-average income, are the driving force behind its Internet society. Through the analysis of data from the 2015 Chinese General Social Survey and 50 interviewees, this study investigates the current situation of this group’s specific internet usage. The findings of this study demonstrate that daily life among the members of this socioeconomic group is closely tied to the Internet. For Chinese middle class, the Internet is used to socialize and entertain self and others. It is also used to search for and share information as well as to build their identities. The empirical results of this study will provide a reference, supported by factual data, for enterprises seeking to target the Chinese middle class through online marketing efforts.

Keywords: middle class, Internet use, network behaviour, online marketing, China

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1899 FPGA Based IIR Filter Design Using MAC Algorithm

Authors: Rajesh Mehra, Bharti Thakur

Abstract:

In this paper, an IIR filter has been designed and simulated on an FPGA. The implementation is based on MAC algorithm which uses multiply-and-accumulate operations IIR filter design implementation. Parallel Pipelined structure is used to implement the proposed IIR Filter taking optimal advantage of the look up table of the FPGA device. The designed filter has been synthesized on DSP slice based FPGA to perform multiplier function of MAC unit. The DSP slices are useful to enhance the speed performance. The developed IIR filter is designed and simulated with Matlab and synthesized with Xilinx Synthesis Tool (XST), and implemented on Virtex 5 and Spartan 3 ADSP FPGA devices. The IIR filter implemented on Virtex 5 FPGA can operate at an estimated frequency of 81.5 MHz as compared to 40.5 MHz in case of Spartan 3 ADSP FPGA. The Virtex 5 based implementation also consumes less slices and slice flip flops of target FPGA in comparison to Spartan 3 ADSP based implementation to provide cost effective solution for signal processing applications.

Keywords: Butterworth filter, DSP, IIR, MAC, FPGA

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1898 The Roles of Mandarin and Local Dialect in the Acquisition of L2 English Consonants Among Chinese Learners of English: Evidence From Suzhou Dialect Areas

Authors: Weijing Zhou, Yuting Lei, Francis Nolan

Abstract:

In the domain of second language acquisition, whenever pronunciation errors or acquisition difficulties are found, researchers habitually attribute them to the negative transfer of the native language or local dialect. To what extent do Mandarin and local dialects affect English phonological acquisition for Chinese learners of English as a foreign language (EFL)? Little evidence, however, has been found via empirical research in China. To address this core issue, the present study conducted phonetic experiments to explore the roles of local dialects and Mandarin in Chinese EFL learners’ acquisition of L2 English consonants. Besides Mandarin, the sole national language in China, Suzhou dialect was selected as the target local dialect because of its distinct phonology from Mandarin. The experimental group consisted of 30 junior English majors at Yangzhou University, who were born and lived in Suzhou, acquired Suzhou Dialect since their early childhood, and were able to communicate freely and fluently with each other in Suzhou Dialect, Mandarin as well as English. The consonantal target segments were all the consonants of English, Mandarin and Suzhou Dialect in typical carrier words embedded in the carrier sentence Say again. The control group consisted of two Suzhou Dialect experts, two Mandarin radio broadcasters, and two British RP phoneticians, who served as the standard speakers of the three languages. The reading corpus was recorded and sampled in the phonetic laboratories at Yangzhou University, Soochow University and Cambridge University, respectively, then transcribed, segmented and analyzed acoustically via Praat software, and finally analyzed statistically via EXCEL and SPSS software. The main findings are as follows: First, in terms of correct acquisition rates (CARs) of all the consonants, Mandarin ranked top (92.83%), English second (74.81%) and Suzhou Dialect last (70.35%), and significant differences were found only between the CARs of Mandarin and English and between the CARs of Mandarin and Suzhou Dialect, demonstrating Mandarin was overwhelmingly more robust than English or Suzhou Dialect in subjects’ multilingual phonological ecology. Second, in terms of typical acoustic features, the average duration of all the consonants plus the voice onset time (VOT) of plosives, fricatives, and affricatives in 3 languages were much longer than those of standard speakers; the intensities of English fricatives and affricatives were higher than RP speakers but lower than Mandarin and Suzhou Dialect standard speakers; the formants of English nasals and approximants were significantly different from those of Mandarin and Suzhou Dialects, illustrating the inconsistent acoustic variations between the 3 languages. Thirdly, in terms of typical pronunciation variations or errors, there were significant interlingual interactions between the 3 consonant systems, in which Mandarin consonants were absolutely dominant, accounting for the strong transfer from L1 Mandarin to L2 English instead of from earlier-acquired L1 local dialect to L2 English. This is largely because the subjects were knowingly exposed to Mandarin since their nursery and were strictly required to speak in Mandarin through all the formal education periods from primary school to university.

Keywords: acquisition of L2 English consonants, role of Mandarin, role of local dialect, Chinese EFL learners from Suzhou Dialect areas

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1897 Challenge of Net-Zero Carbon Construction and Measurement of Energy Consumption and Carbon Emission Reduction to Climate Change, Economy and Job Growths in Hong Kong and Australia

Authors: Kwok Tak Kit

Abstract:

Under the Paris Agreement 2015, the countries committed to address and combat the climate change and its negative impacts and agree to the target of reducing the global greenhouse gas (GHG) emission substantially by limiting the global temperature to 20C above the pre-industrial level in this century. A internationally Submit named “ 26th United Nations Climate Conference” (COP26) was held in Glasgow in 2021 with all committed countries agreed to the finalize the outstanding element in Paris Agreement and Glasgow Climate Pact to keep 1.50C. In this paper, we will focus on the basic approach of waste strategy, recycling policy, circular economy strategy, net-zero strategy and sustainability strategy and the importance of the elements which affect the carbon emission, waste generation and energy conservation will be further reviewed with recommendation for future study.

Keywords: net-zero carbon, climate change, carbon emission, energy consumption

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