Search results for: target of rapamycin

Authors: Kristine Kalnica-Dorosenko, Aiga Svede

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Amblyopia or 'lazy eye' is impaired or dim vision without obvious defect or change in the eye. It is often associated with abnormal visual experience, most commonly strabismus, anisometropia or both, and form deprivation. The main task of amblyopia treatment is to ameliorate etiological factors to create a clear retinal image and, to ensure the participation of the amblyopic eye in the visual process. The treatment of amblyopia and eccentric fixation is usually associated with problems in the therapy. Eccentric fixation is present in around 44% of all patients with amblyopia and in 30% of patients with strabismic amblyopia. In Latvia, amblyopia is carefully treated in various clinics, but eccentricity diagnosis is relatively rare. Conflict which has developed relating to the relationship between the visual disorder and the degree of eccentric fixation in amblyopia should to be rethoughted, because it has an important bearing on the cause and treatment of amblyopia, and the role of the eccentric fixation in this case. Visuoscopy is the most frequently used method for determination of eccentric fixation. With traditional visuoscopy, a fixation target is projected onto the patient retina, and the examiner asks to look straight directly at the center of the target. An optometrist then observes the point on the macula used for fixation. This objective test provides clinicians with direct observation of the fixation point of the eye. It requires patients to voluntarily fixate the target and assumes the foveal reflex accurately demarcates the center of the foveal pit. In the end, by having a very simple method to evaluate fixation, it is possible to indirectly evaluate treatment improvement, as eccentric fixation is always associated with reduced visual acuity. So, one may expect that if eccentric fixation in amlyopic eye is found with visuoscopy, then visual acuity should be less than 1.0 (in decimal units). With occlusion or another amblyopia therapy, one would expect both visual acuity and fixation to improve simultaneously, that is fixation would become more central. Consequently, improvement in fixation pattern by treatment is an indirect measurement of improvement of visual acuity. Evaluation of eccentric fixation in the child may be helpful in identifying amblyopia in children prior to measurement of visual acuity. This is very important because the earlier amblyopia is diagnosed – the better the chance of improving visual acuity.

Keywords: amblyopia, eccentric fixation, visual acuity, visuoscopy

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Authors: Scott A. Ochsner, Christopher M. Watkins, Apollo McOwiti, David L. Steffen Lauren B. Becnel, Neil J. McKenna

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Understanding signaling by nuclear receptors (NRs) requires an appreciation of their cognate ligand- and tissue-specific transcriptomes. While target gene regulation data are abundant in this field, they reside in hundreds of discrete publications in formats refractory to routine query and analysis and, accordingly, their full value to the NR signaling community has not been realized. One of the mandates of the Nuclear Receptor Signaling Atlas (NURSA) is to facilitate access of the community to existing public datasets. Pursuant to this mandate we are developing a freely-accessible community web resource, Transcriptomine, to bring together the sum total of available expression array and RNA-Seq data points generated by the field in a single location. Transcriptomine currently contains over 25,000,000 gene fold change datapoints from over 1200 contrasts relevant to over 100 NRs, ligands and coregulators in over 200 tissues and cell lines. Transcriptomine is designed to accommodate a spectrum of end users ranging from the bench researcher to those with advanced bioinformatic training. Visualization tools allow users to build custom charts to compare and contrast patterns of gene regulation across different tissues and in response to different ligands. Our resource affords an entirely new paradigm for leveraging gene expression data in the NR signaling field, empowering users to query gene fold changes across diverse regulatory molecules, tissues and cell lines, target genes, biological functions and disease associations, and that would otherwise be prohibitive in terms of time and effort. Transcriptomine will be regularly updated with gene lists from future genome-wide expression array and expression-sequencing datasets in the NR signaling field.

Keywords: target gene database, informatics, gene expression, transcriptomics

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Authors: Nichole Haag, Kimberly Velk, Tyler McCune, Chun Wu

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Methicillin/multiple-resistant Staphylococcus aureus (MRSA) are infectious bacteria that are resistant to common antibiotics. A previous in silico study in our group has identified a hypothetical protein SAV1226 as one of the potential drug targets. In this study, we reported the bioinformatics characterization, as well as cloning, expression, purification and kinetic assays of hypothetical protein SAV1226 from methicillin/vancomycin-resistant Staphylococcus aureus Mu50 strain. MALDI-TOF/MS analysis revealed a low degree of structural similarity with known proteins. Kinetic assays demonstrated that hypothetical protein SAV1226 is neither a domain of an ATP dependent dihydroxyacetone kinase nor of a phosphotransferase system (PTS) dihydroxyacetone kinase, suggesting that the function of hypothetical protein SAV1226 might be misannotated on public databases such as UniProt and InterProScan 5.

Keywords: Methicillin-resistant Staphylococcus aureus, dihydroxyacetone kinase, essential genes, drug target, phosphoryl group donor

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Authors: Sema Şenoğlu, Sevgi Karakuş

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Hydrazone scaffold is important to design new drug groups and is found to possess numerous uses in pharmaceutical chemistry. Besides, hydrazone derivatives are also known for biological activities such as anticancer, antimicrobial, antiviral, and antifungal. Hydrazone derivatives are promising anticancer agents because they inhibit cancer proliferation and induce apoptosis. Human carbonic anhydrase IX has a high potential to be an antiproliferative drug target, and targeting this protein is also important for obtaining potential anticancer inhibitors. The protein construct was retrieved as a PDB file from the RCSB protein database. This binding interaction of proteins and ligands was performed using Discovery Studio Visualizer. In vitro inhibitory activity of hydrazone derivatives was tested against enzyme carbonic anhydrase IX on the PyRx programme. Most of these molecules showed remarkable human carbonic anhydrase IX inhibitory activity compared to the acetazolamide. As a result, these compounds appear to be a potential target in drug design against human carbonic anhydrase IX.

Keywords: cancer, carbonic anhydrase IX enzyme, docking, hydrazone

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Authors: Ziyue Zeng

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Bacteriophages are viruses which infect bacteria specifically. Over the past decades, phage λ has been extensively studied, especially its interaction with the Escherichia coli LamB (EcLamB) protein receptor. Nonetheless, despite the enormous numbers and near-ubiquity of environmental phages, aside from phage λ, there is a paucity of information on other phages which target EcLamB as a receptor. In this study, to answer the question of whether there are other EcLamB-targeting phages in the natural environment, a simple and convenient method was developed and used for isolating environmental phages which target a particular surface structure of a particular bacterium; in this case, the EcLamB outer membrane protein. From the enrichments with the engineered bacterial hosts, a collection of EcLamB-targeting phages (ΦZZ phages) were easily isolated. Intriguingly, unlike phage λ, an obligate EcLamB-dependent phage in the Siphoviridae family, the newly isolated ΦZZ phages alternatively recognised EcLamB or E. coli OmpC (EcOmpC) as a receptor when infecting E. coli. Furthermore, ΦZZ phages were suggested to represent new species in the Tequatrovirus genus in the Myoviridae family, based on phage morphology and genomic sequences. Most phages are thought to have a narrow host range due to their exquisite specificity in receptor recognition. With the ability to optionally recognise two receptors, ΦZZ phages were considered relatively promiscuous. Via the heterologous expression of EcLamB on the bacterial cell surface, the host range of ΦZZ phages was further extended to three different enterobacterial genera. Besides, an interesting selection of evolved phage mutants with a broader host range was isolated, and the key mutations involved in their evolution to adapt to new hosts were investigated by genomic analysis. Finally, and importantly, two ΦZZ phages were found to be putative generalised transducers, which could be exploited as tools for DNA manipulations.

Keywords: environmental microbiology, phage, microbe-host interactions, microbial ecology

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Authors: Siddhant Sethi, Yasuharu Takashima, Shigetaka Nakamura, Kenzo Fujimoto

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Site-directed mutagenesis is a renowned technique to introduce specific mutations in the genome. To achieve site-directed mutagenesis, many chemical and enzymatic approaches have been reported in the past like disulphite induced genome editing, CRISPR-Cas9, TALEN etc. The chemical methods are invasive whereas the enzymatic approaches are time-consuming and expensive. Most of these techniques are unusable in the cellular application due to their toxicity and other limitations. Photo-chemical cytosine deamination, introduced in 2010, is one of the major technique for enzyme-free single-point mutation of cytosine to uracil in DNA and RNA, wherein, 3-cyanovinylcarbazole nucleoside (CNVK) containing oligodeoxyribonucleotide (ODN) having CNVK at -1 position to that of target cytosine is reversibly crosslinked to target DNA strand using 366 nm and then incubated at 90ºC to accommodate deamination. This technique is superior to enzymatic methods of site-directed mutagenesis but has a disadvantage that it requires the use of high temperature for the deamination step which restricts its applicability in the in vivo applications. This study has been focused on improving the technique by reducing the temperature required for deamination. Firstly, the photo-cross-linker, CNVK has been modified by replacing cyano group attached to vinyl group with methyl ester (OMeVK), amide (NH2VK), and carboxylic acid (OHVK) to observe the acceleration in the deamination of target cytosine cross-linked to vinylcarbazole derivative. Among the derivatives, OHVK has shown 2 times acceleration in deamination reaction as compared to CNVK, while the other two derivatives have shown deceleration towards deamination reaction. The trend of rate of deamination reaction follows the same order as that of hydrophilicity of the vinylcarbazole derivatives. OHVK being most hydrophilic has shown highest acceleration while OMeVK is least hydrophilic has proven to be least active for deamination. Secondly, in the related study, the counter-base of the target cytosine, guanine has been replaced by inosine, 2-aminopurine, nebularine, and 5-nitroindole having distinct hydrogen bonding patterns with target cytosine. Among the ODNs with these counter bases, ODN with inosine has shown 12 fold acceleration towards deamination of cytosine cross-linked to CNVK at physiological conditions as compared to guanosine. Whereas, when 2-aminopurine, nebularine, and 5-nitroindole were used, no deamination reaction took place. It can be concluded that inosine has potential to be used as the counter base of target cytosine for the CNVK mediated photo-cross-linking induced deamination of cytosine. The increase in rate of deamination reaction has been attributed to pattern and number of hydrogen bonding between the cytosine and counter base. One of the important factor is presence of hydrogen bond between exo-cyclic amino group of cytosine and the counter base. These results will be useful for development of more efficient technique for site-directed mutagenesis for C → U transformations in the DNA/RNA which might be used in the living system for treatment of various genetic disorders and genome engineering for making designer and non-native proteins.

Keywords: C to U transformation, DNA editing, genome engineering, ultra-fast photo-cross-linking

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Authors: Temesgen Sidamo, Prakruti S. Rao, Eleni Akllilu, Workineh Shibeshi, Yumi Park, Yong-Soon Cho, Jae-Gook Shin, Scott K. Heysell, Stellah G. Mpagama, Ephrem Engidawork

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The fluoroquinolones (FQs) are used off-label for the treatment of multidrug-resistant tuberculosis (MDR-TB), and for evaluation in shortening the duration of drug-susceptible TB in recently prioritized regimens. Within the class, levofloxacin (LFX) and moxifloxacin (MXF) play a substantial role in ensuring success in treatment outcomes. However, sub-therapeutic plasma concentrations of either LFX or MXF may drive unfavorable treatment outcomes. To the best of our knowledge, the pharmacokinetics of LFX and MXF in Ethiopian patients with MDR-TB have not yet been investigated. Therefore, the aim of this study was to develop a population pharmacokinetic (PopPK) model of levofloxacin (LFX) and moxifloxacin (MXF) and assess the percent probability of target attainment (PTA) as defined by the ratio of the area under the plasma concentration-time curve over 24-h (AUC0-24) and the in vitro minimum inhibitory concentration (MIC) (AUC0-24/MIC) in Ethiopian MDR-TB patients. Steady-state plasma was collected from 39 MDR-TB patients enrolled in the programmatic treatment course and the drug concentrations were determined using optimized liquid chromatography-tandem mass spectrometry. In addition, the in vitro MIC of the patients' pretreatment clinical isolates was determined. PopPK and simulations were run at various doses, and PK parameters were estimated. The effect of covariates on the PK parameters and the PTA for maximum mycobacterial kill and resistance prevention was also investigated. LFX and MXF both fit in a one-compartment model with adjustments. The apparent volume of distribution (V) and clearance (CL) of LFX were influenced by serum creatinine (Scr), whereas the absorption constant (Ka) and V of MXF were influenced by Scr and BMI, respectively. The PTA for LFX maximal mycobacterial kill at the critical MIC of 0.5 mg/L was 29%, 62%, and 95% with the simulated 750 mg, 1000 mg, and 1500 mg doses, respectively, whereas the PTA for resistance prevention at 1500 mg was only 4.8%, with none of the lower doses achieving this target. At the critical MIC of 0.25 mg/L, there was no difference in the PTA (94.4%) for maximum bacterial kill among the simulated doses of MXF (600 mg, 800 mg, and 1000 mg), but the PTA for resistance prevention improved proportionately with dose. Standard LFX and MXF doses may not provide adequate drug exposure. LFX PopPK is more predictable for maximum mycobacterial kill, whereas MXF's resistance prevention target increases with dose. Scr and BMI are likely to be important covariates in dose optimization or therapeutic drug monitoring (TDM) studies in Ethiopian patients.

Keywords: population PK, PTA, moxifloxacin, levofloxacin, MDR-TB patients, ethiopia

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Authors: A. Ishag, E. Witruk, C. Altmayer

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Motivation and attitudes are considered as hypothetical psychological constructs in explaining the process of second language learning. Gardner (1985) – who first systematically investigated the motivational factors in second language acquisition – found that L2 achievement is related not only to the individual learner’s linguistic aptitude or general intelligence but also to the learner’s motivation and interest in learning the target language. Traditionally language learning motivation can be divided into two types: integrative motivation – the desire to integrate oneself with the target culture; and instrumental motivation – the desire to learn a language in order to meet a specific language requirement such as for employment. One of the Gardner’s main ideas is that the integrative motivation plays an important role in second language acquisition. It is directly and positively related to second language achievement more than instrumental motivation. However, the significance of integrative motivation reflects a rather controversial set of findings. On the other hand, Students’ attitudes towards the target language, its speakers and the learning context may all play some part in explaining their success in learning a language. Accordingly, the present study aims at exploring the significance of motivational and attitudinal factors in learning foreign languages, namely English and German among Sudanese undergraduate students from a psycholinguistic and interdisciplinary perspective. The sample composed of 221 students from the English and German language departments respectively at the University of Khartoum in Sudan. The results indicate that English language’s learners are instrumentally motivated and that German language’s learners have positive attitudes towards the German language community and culture. Furthermore, there are statistical significant differences in the attitudes toward the two languages due to gender; where female students have more positive attitudes than their male counterparts. However, there are no differences along the variables of academic grade and study level. Finally, the reasons of studying the English or German language have also been indicated.

Keywords: motivation and attitudes, foreign language learning, english language, german language

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Authors: Giorgio Bertolazzi, Panayiotis Benos, Michele Tumminello, Claudia Coronnello

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MicroRNAs are small non-coding RNAs that post-transcriptionally regulate the expression levels of messenger RNAs. MicroRNA regulation activity depends on the recognition of binding sites located on mRNA molecules. ComiR (Combinatorial miRNA targeting) is a user friendly web tool realized to predict the targets of a set of microRNAs, starting from their expression profile. ComiR incorporates miRNA expression in a thermodynamic binding model, and it associates each gene with the probability of being a target of a set of miRNAs. ComiR algorithms were trained with the information regarding binding sites in the 3’UTR region, by using a reliable dataset containing the targets of endogenously expressed microRNA in D. melanogaster S2 cells. This dataset was obtained by comparing the results from two different experimental approaches, i.e., inhibition, and immunoprecipitation of the AGO1 protein; this protein is a component of the microRNA induced silencing complex. In this work, we tested whether including coding region binding sites in the ComiR algorithm improves the performance of the tool in predicting microRNA targets. We focused the analysis on the D. melanogaster species and updated the ComiR underlying database with the currently available releases of mRNA and microRNA sequences. As a result, we find that the ComiR algorithm trained with the information related to the coding regions is more efficient in predicting the microRNA targets, with respect to the algorithm trained with 3’utr information. On the other hand, we show that 3’utr based predictions can be seen as complementary to the coding region based predictions, which suggests that both predictions, from 3'UTR and coding regions, should be considered in a comprehensive analysis. Furthermore, we observed that the lists of targets obtained by analyzing data from one experimental approach only, that is, inhibition or immunoprecipitation of AGO1, are not reliable enough to test the performance of our microRNA target prediction algorithm. Further analysis will be conducted to investigate the effectiveness of the tool with data from other species, provided that validated datasets, as obtained from the comparison of RISC proteins inhibition and immunoprecipitation experiments, will be available for the same samples. Finally, we propose to upgrade the existing ComiR web-tool by including the coding region based trained model, available together with the 3’UTR based one.

Keywords: AGO1, coding region, Drosophila melanogaster, microRNA target prediction

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Authors: Sabin Aslam, Sultan Habibullah Khan, James G. Thomson, Abhaya M. Dandekar

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Losses due to viral diseases are posing a serious threat to crop production. A quick breakdown of resistance to viruses like Cotton Leaf Curl Virus (CLCuV) demands the application of a proficient technology to engineer durable resistance. Gene stacking has recently emerged as a potential approach for integrating multiple genes in crop plants. In the present study, recombinase technology has been used for site-specific gene stacking. A target vector (pG-Rec) was designed for engineering a predetermined specific site in the plant genome whereby genes can be stacked repeatedly. Using Agrobacterium-mediated transformation, the pG-Rec was transformed into Coker-312 along with Nicotiana tabacum L. cv. Xanthi and Nicotiana benthamiana. The transgene analysis of target lines was conducted through junction PCR. The transgene positive target lines were used for further transformations to site-specifically stack two genes of interest using Bxb1 and PhiC31 recombinases. In the first instance, Cas9 driven by multiplex gRNAs (for Rep gene of CLCuV) was site-specifically integrated into the target lines and determined by the junction PCR and real-time PCR. The resulting plants were subsequently used to stack the second gene of interest (AVP3 gene from Arabidopsis for enhancing cotton plant growth). The addition of the genes is simultaneously achieved with the removal of marker genes for recycling with the next round of gene stacking. Consequently, transgenic marker-free plants were produced with two genes stacked at the specific site. These transgenic plants can be potential germplasm to introduce resistance against various strains of cotton leaf curl virus (CLCuV) and abiotic stresses. The results of the research demonstrate gene stacking in crop plants, a technology that can be used to introduce multiple genes sequentially at predefined genomic sites. The current climate change scenario highlights the use of such technologies so that gigantic environmental issues can be tackled by several traits in a single step. After evaluating virus resistance in the resulting plants, the lines can be a primer to initiate stacking of further genes in Cotton for other traits as well as molecular breeding with elite cotton lines.

Keywords: cotton, CRISPR/Cas9, gene stacking, genome editing, recombinases

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Authors: Junie B. Billones, Maria Constancia O. Carrillo, Voltaire G. Organo, Stephani Joy Y. Macalino, Inno A. Emnacen, Jamie Bernadette A. Sy

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The drug discovery and development process is generally known to be a very lengthy and labor-intensive process. Therefore, in order to be able to deliver prompt and effective responses to cure certain diseases, there is an urgent need to reduce the time and resources needed to design, develop, and optimize potential drugs. Computer-aided drug design (CADD) is able to alleviate this issue by applying computational power in order to streamline the whole drug discovery process, starting from target identification to lead optimization. This drug design approach can be predominantly applied to diseases that cause major public health concerns, such as tuberculosis. Hitherto, there has been no concrete cure for this disease, especially with the continuing emergence of drug resistant strains. In this study, CADD is employed for tuberculosis by first identifying a key enzyme in the mycobacterium’s metabolic pathway that would make a good drug target. One such potential target is the lipoate protein ligase B enzyme (LipB), which is a key enzyme in the M. tuberculosis metabolic pathway involved in the biosynthesis of the lipoic acid cofactor. Its expression is considerably up-regulated in patients with multi-drug resistant tuberculosis (MDR-TB) and it has no known back-up mechanism that can take over its function when inhibited, making it an extremely attractive target. Using cutting-edge computational methods, compounds from AnalytiCon Discovery Natural Derivatives database were screened and docked against the LipB enzyme in order to rank them based on their binding affinities. Compounds which have better binding affinities than LipB’s known inhibitor, decanoic acid, were subjected to in silico toxicity evaluation using the ADMET and TOPKAT protocols. Out of the 31,692 compounds in the database, 112 of these showed better binding energies than decanoic acid. Furthermore, 12 out of the 112 compounds showed highly promising ADMET and TOPKAT properties. Future studies involving in vitro or in vivo bioassays may be done to further confirm the therapeutic efficacy of these 12 compounds, which eventually may then lead to a novel class of anti-tuberculosis drugs.

Keywords: pharmacophore, molecular docking, lipoate protein ligase B (LipB), ADMET, TOPKAT

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Authors: Rahul Agarwal, Ashutosh Singh

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Colorectal cancer (CRC) also refers as bowel cancer or colon cancer. It involves the development of abnormal growth of cells in colon or rectum part of the body. This work leads to the development of a miRNA database in colorectal cancer. We named this database- miCoRe. This database comprises of all validated colon-rectal cancer miRNAs information from various published literature with an effectual knowledge based information retrieval system. miRNAs have been collected from various published literature reports. MySQL is used for main-framework of miCoRe while the front-end was developed in PHP script. The aim of developing miCoRe is to create a comprehensive central repository of colorectal carcinoma miRNAs with all germane information of miRNAs and their target genes. The current version of miCoRe consists of 238 miRNAs which are known to be implicated in malignancy of CRC. Alongside with miRNA information, miCoRe also contains the information related to the target genes of these miRNA. miCoRe furnishes the information about the mechanism of incidence and progression of the disease, which would further help the researchers to look for colorectal specific miRNAs therapies and CRC specific targeted drug designing. Moreover, it will also help in development of biomarkers for the better and early detection of CRC and will help in better clinical management of the disease.

Keywords: colorectal cancer, database, miCoRe, miRNAs

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Authors: Sweta Sinha

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Rapid evolution of technology has changed language pedagogy as well as perspectives on language use, leading to strategic changes in discourse studies. We are now firmly embedded in a time when digital technologies have become an integral part of our daily lives. This has led to generalized approaches to English Language Teaching (ELT) which has raised two-pronged concerns in linguistically diverse settings: a) the diverse linguistic background of the learner might interfere/ intervene with the learning process and b) the differential level of already acquired knowledge of target language might make the classroom practices too easy or too difficult for the target group of learners. ELT needs a more systematic and differential pedagogical approach for greater efficiency and accuracy. The present research analyses the need of identifying learner groups based on different levels of target language proficiency based on a longitudinal study done on 150 undergraduate students. The learners were divided into five groups based on their performance on a twenty point scale in Listening Speaking Reading and Writing (LSRW). The groups were then subjected to varying durations of technology aided language learning sessions and their performance was recorded again on the same scale. Identifying groups and introducing differential teaching and learning strategies led to better results compared to generalized teaching strategies. Language teaching includes different aspects: the organizational, the technological, the sociological, the psychological, the pedagogical and the linguistic. And a facilitator must account for all these aspects in a carefully devised differential approach meeting the challenge of learner diversity. Apart from the justification of the formation of differential groups the paper attempts to devise framework to account for all these aspects in order to make ELT in multilingual setting much more effective.

Keywords: differential groups, English language teaching, language pedagogy, multilingualism, technology aided language learning

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Authors: Hanna Schübel, Ivo Wallimann-Helmer

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In order to reach the goal of the Paris Agreement to not overshoot 1.5°C of warming above pre-industrial levels, various countries including the UK and Switzerland have committed themselves to net zero emissions by 2050. The employment of negative emission technologies (NETs) is very likely going to be necessary for meeting these national objectives as well as other internationally agreed climate targets. NETs are methods of removing carbon from the atmosphere and are thus a means for addressing climate change. They range from afforestation to technological measures such as direct air capture and carbon storage (DACCS), where CO2 is captured from the air and stored underground. As all so-called geoengineering technologies, the development and deployment of NETs are often subject to moral hazard arguments. As these technologies could be perceived as an alternative to mitigation efforts, so the argument goes, they are potentially a dangerous distraction from the main target of mitigating emissions. We think that this is a dangerous argument to make as it may hinder the development of NETs which are an essential element of net zero emission targets. In this paper we argue that the moral hazard argument is only problematic if we do not reflect upon which levels of emissions are at stake in order to meet net zero emissions. In response to the moral hazard argument we develop an account of which levels of emissions in given societies should be mitigated and not be the target of NETs and which levels of emissions can legitimately be a target of NETs. For this purpose, we define four different levels of emissions: the current level of individual emissions, the level individuals emit in order to appear in public without shame, the level of a fair share of individual emissions in the global budget, and finally the baseline of net zero emissions. At each level of emissions there are different subjects to be assigned responsibilities if societies and/or individuals are committed to the target of net zero emissions. We argue that all emissions within one’s fair share do not demand individual mitigation efforts. The same holds with regard to individuals and the baseline level of emissions necessary to appear in public in their societies without shame. Individuals are only under duty to reduce their emissions if they exceed this baseline level. This is different for whole societies. Societies demanding more emissions to appear in public without shame than the individual fair share are under duty to foster emission reductions and are not legitimate to reduce by introducing NETs. NETs are legitimate for reducing emissions only below the level of fair shares and for reaching net zero emissions. Since access to NETs to achieve net zero emissions demands technology not affordable to individuals there are also no full individual responsibilities to achieve net zero emissions. This is mainly a responsibility of societies as a whole.

Keywords: climate change, mitigation, moral hazard, negative emission technologies, responsibility

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Authors: Lynndee Kemmet

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The U.S. military plays an increasing role in supporting political stability efforts, and this includes efforts to prevent the food insecurity that can trigger political and social instability. This paper presents a model that assists military commanders in identifying variables that impact food production and distribution in their areas of operation (AO), in identifying connections between variables and in assessing the impacts of those variables on food production and distribution. Through use of the model, military units can better target their data collection efforts and can categorize and analyze data within the data categorization framework most widely-used by military forces—PMESII-PT (Political, Military, Economic, Infrastructure, Information, Physical Environment and Time). The model provides flexibility of analysis in that commanders can target analysis to be highly focused on a specific PMESII-PT domain or variable or conduct analysis across multiple PMESII-PT domains. The model is also designed to assist commanders in mapping food systems in their AOs and then identifying components of those systems that must be strengthened or protected.

Keywords: food security, food system model, political stability, US Military

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Authors: Rui Yin, Haojie Wang, Xun Li

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Recently, mainstream dense retrieval methods have obtained state-of-the-art results on some datasets and tasks. However, they require large amounts of training data, which is not available in most domains. The severe performance degradation of dense retrievers on new data domains has limited the use of dense retrieval methods to only a few domains with large training datasets. In this paper, we propose an unsupervised domain-adaptive approach based on query generation. First, a generative model is used to generate relevant queries for each passage in the target corpus, and then, the generated queries are used for mining negative passages. Finally, the query-passage pairs are labeled with a cross-encoder and used to train a domain-adapted dense retriever. We also explore contrastive learning as a method for training domain-adapted dense retrievers and show that it leads to strong performance in various retrieval settings. Experiments show that our approach is more robust than previous methods in target domains that require less unlabeled data.

Keywords: dense retrieval, query generation, contrastive learning, unsupervised training

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Authors: Alok Madan, Arshad K. Hashmi

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The paper presents a plastic analysis procedure based on the energy balance concept for performance based seismic retrofit of multi-story multi-bay masonry infilled reinforced concrete (R/C) frames with a ‘soft’ ground story using passive energy dissipation (PED) devices with the objective of achieving a target performance level of the retrofitted R/C frame for a given seismic hazard level at the building site. The proposed energy based plastic analysis procedure was employed for developing performance based design (PBD) formulations for PED devices for a simulated application in seismic retrofit of existing frame structures designed in compliance with the prevalent standard codes of practice. The PBD formulations developed for PED devices were implemented for simulated seismic retrofit of a representative code-compliant masonry infilled R/C frame with a ‘soft’ ground story using friction dampers as the PED device. Non-linear dynamic analyses of the retrofitted masonry infilled R/C frames is performed to investigate the efficacy and accuracy of the proposed energy based plastic analysis procedure in achieving the target performance level under design level earthquakes. Results of non-linear dynamic analyses demonstrate that the maximum inter-story drifts in the masonry infilled R/C frames with a ‘soft’ ground story that is retrofitted with the friction dampers designed using the proposed PBD formulations are controlled within the target drifts under near-field as well far-field earthquakes.

Keywords: energy methods, masonry infilled frame, near-field earthquakes, seismic protection, supplemental damping devices

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Authors: Riky Tri Hartagung, Mohammad Syamsu Rosid

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The lithology prediction process, as well as the fluid content is the most important part in the reservoir characterization. One of the methods used in this process is the simultaneous seismic inversion method. In the Posseidon field, Browse Basin, Australia, the parameters generated through simultaneous seismic inversion are not able to characterize the reservoir accurately because of the overlapping impedance values between hydrocarbon sand, water sand, and shale, which causes a high level of ambiguity in the interpretation. The Poisson Impedance inversion provides a solution to this problem by rotating the impedance a few degrees, which is obtained through the coefficient c. Coefficient c is obtained through the Target Correlation Coefficient Analysis (TCCA) by finding the optimum correlation coefficient between Poisson Impedance and the target log, namely gamma ray, effective porosity, and resistivity. Correlation of each of these target logs will produce Lithology Impedance (LI) which is sensitive to lithology sand, Porosity Impedance (ϕI) which is sensitive to porous sand, and Fluid Impedance (FI) which is sensitive to fluid content. The results show that PI gives better results in separating hydrocarbon saturated reservoir zones. Based on the results of the LI-GR crossplot, the ϕI-effective porosity crossplot, and the FI-Sw crossplot with optimum correlations of 0.74, 0.91, and 0.82 respectively, it shows that the lithology of hidrocarbon-saturated porous sand is at the value of LI ≤ 2800 (m/s)(g *cc), ϕI ≤ 5500 (m/s)(g*cc), and FI ≤ 4000 (m/s)(g*cc). The presence of low values of LI, ϕI, and FI correlates accurately with the presence of hydrocarbons in the well. Each value of c is then applied to the seismic data. The results show that the PI inversion gives a good distribution of Hydrocarbon-saturated porous sand lithology. The distribution of hydrocarbon saturated porous sand on the seismic inversion section is seen in the northeast – southwest direction, which is estimated as the direction of gas distribution.

Keywords: reservoir characterization, poisson impedance, browse basin, poseidon field

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Authors: R. Pillai Aparna, S. R. Gandhi

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Soft clay deposits having low strength and high compressibility are found all over the world. Preloading with vertical drains is a widely used method for improving such type of soils. The coefficient of consolidation, irrespective of the drainage type, plays an important role in the design of vertical drains and it controls accurate prediction of the rate of consolidation of soil. Also, the increase in shear strength of soil with consolidation is another important factor considered in preloading or staged construction. To our best knowledge no clear guidelines are available to estimate the increase in shear strength for a particular degree of consolidation (U) at various stages during the construction. Various methods are available for finding out the consolidation coefficient. This study mainly focuses on the variation of, consolidation coefficient which was found out using different methods and shear strength with pressure intensity. The variation of shear strength with the degree of consolidation was also studied. The consolidation test was done using two types of highly compressible clays with vertical, radial and a few with combined drainage. The test was carried out at different pressures intensities and for each pressure intensity, once the target degree of consolidation is achieved, vane shear test was done at different locations in the sample, in order to determine the shear strength. The shear strength of clayey soils under the application of vertical stress with vertical and radial drainage with target U value of 70% and 90% was studied. It was found that there is not much variation in cv or cr value beyond 80kPa pressure intensity. Correlations were developed between shear strength ratio and consolidation pressure based on laboratory testing under controlled condition. It was observed that the shear strength of sample with target U value of 90% is about 1.4 to 2 times than that of 70% consolidated sample. Settlement analysis was done using Asaoka’s and hyperbolic method. The variation of strength with respect to the depth of sample was also studied, using large-scale consolidation test. It was found, based on the present study that the gain in strength is more on the top half of the clay layer, and also the shear strength of the sample ensuring radial drainage is slightly higher than that of the vertical drainage.

Keywords: consolidation coefficient, degree of consolidation, PVDs, shear strength

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Authors: Feixiang Zhao, Shuangcheng Jia, Qian Li

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High-precision measurement of the target’s position and size is one of the hotspots in the field of vision inspection. This paper proposes a three-dimensional object positioning and measurement method using a monocular camera and GPS, namely the Distance Area Number-New Minimize Projection Error (DAN-NMPE). Our algorithm contains two parts: DAN and NMPE; specifically, DAN is a picture sequence algorithm, NMPE is a relatively positive optimization algorithm, which greatly improves the measurement accuracy of the target’s position and size. Comprehensive experiments validate the effectiveness of our proposed method on a self-made traffic sign dataset. The results show that with the laser point cloud as the ground truth, the size and position errors of the traffic sign measured by this method are ± 5% and 0.48 ± 0.3m, respectively. In addition, we also compared it with the current mainstream method, which uses a monocular camera to locate and measure traffic signs. DAN-NMPE attains significant improvements compared to existing state-of-the-art methods, which improves the measurement accuracy of size and position by 50% and 15.8%, respectively.

Keywords: monocular camera, GPS, positioning, measurement

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Authors: Frank Papworth, Inam Khan

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Fib’s model code 2020 has four approaches for design life verification. Historically ‘deemed to satisfy provisions have been the principal approach, but this has limited options for materials and covers. The use of an equation in fib’s model code for service life design to predict time to corrosion initiation has become increasingly popular to justify further options, but in some cases, the analysis approaches are incorrect. Even when the equations are computed using full probabilistic analysis, there are common mistakes. This paper reviews the work of recent fib commissions on implementing the service life model to assess the reliability of durability designs, including initiation and propagation periods. The paper goes on to consider the assessment of deemed to satisfy requirements in national codes and considers the influence of various options, including different steel types, various cement systems, quality of concrete and cover, on reliability achieved. As modelling is based on achieving agreed target reliability, consideration is given to how a project might determine appropriate target reliability.

Keywords: chlorides, marine, exposure, design life, reliability, modelling

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Authors: Xing Lyu

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Multimodal metaphor promotes the further development and refinement of multimodal discourse study. Cultural aspects matter a lot not only in creating but also in comprehending multimodal metaphor. By analyzing the target domain and the source domain in 10 public service advertisements of China and Germany about environmental protection, this paper compares the source when the target is alike in each multimodal metaphor in order to seek similarities and differences across cultures. The findings are as follows: first, the multimodal metaphors center around three major topics: the earth crisis, consequences of environmental damage, and appeal for environmental protection; second, the multimodal metaphors mainly grounded in three universal conceptual metaphors which focused on high level is up; earth is mother and all lives are precious. However, there are five Chinese culture-specific multimodal metaphors which are not discovered in Germany ads: east is high leve; a purposeful life is a journey; a nation is a person; good is clean, and water is mother. Since metaphors are excellent instruments on studying ideology, this study can be helpful on intercultural/cross-cultural communication.

Keywords: multimodal metaphor, cultural aspects, public service advertising, cross-cultural communication

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Authors: Bahar Urhan Torun, Havva Nur Tarakcı

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At the present time, online marketing has become the common target of small and full-scale organizations. Today’s humanbeing who has to spend most of their time in front of the computer because of his job, prefers to socialize by internet due to the easy access to technology. So online marketing area expands day by day. All business organizations from the smallest to the biggest are in a race in order to get a cut from the virtual market share in an extreme competitive environment. However these organizations which use the internet to reach more consumers cannot determine their target group accurately, so this is the biggest handicap of online marketing sales nowadays. The aim of this study is to determine some significant elements about need for communicating efficiently with the consumer on the internet on online marketing. The strategies that can be used in order to increase sales and the limitations of virtual environment where cannot be communicated with the consumer face to face are argued in this study’s scope. As a consequence it is thought that to study on this subject because of lacking and also being limited efficiency of researches and outputs. Within this scope suggesting some proposals about how to communicate efficiently with the consumer and also offering the consumers’ demands efficiently is the essential objective of this study.

Keywords: online marketing, competition, consumer, communication

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Authors: Pedro Gómez-del-Hoyo, Jose-Luis Bárcena-Humanes, Nerea del-Rey-Maestre, María-Pilar Jarabo-Amores, David Mata-Moya

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A study of achievable coverages using passive radar systems in terrestrial traffic monitoring applications is presented. The study includes the estimation of the bistatic radar cross section of different commercial vehicle models that provide challenging low values which make detection really difficult. A semi-urban scenario is selected to evaluate the impact of excess propagation losses generated by an irregular relief. A bistatic passive radar exploiting UHF frequencies radiated by digital video broadcasting transmitters is assumed. A general method of coverage estimation using electromagnetic simulators in combination with estimated car average bistatic radar cross section is applied. In order to reduce the computational cost, hybrid solution is implemented, assuming free space for the target-receiver path but estimating the excess propagation losses for the transmitter-target one.

Keywords: bistatic radar cross section, passive radar, propagation losses, radar coverage

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Authors: Ghazwan Al-Haji

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Traffic safety has become a major concern in Southeast Asia due to the increasing number of road accidents resulting in fatalities and injuries. Southeast Asia has one of the highest road traffic fatality rates in the world, in terms of both population and number of cars, nearly six times higher than the EU region. One of the reasons for this concerning trend is the increasing share of motorcycles as a form of transportation throughout Southeast Asia. The purpose of this study is to benchmark traffic safety situations and statistics in six countries in Asia and the EU, which Indonesia, Malaysia, Vietnam, Italy, Portugal and Sweden. The research will assess the priorities and causes of road accidents in the target nations. Further, the study will analyze the existing practices and promote best practices that can be implemented toward safer roads in Asian target countries. In order to achieve this goal, the study categorizes various factors contributing to traffic accidents and best practices into 4 pillars (Safer Behavior, Safer Roads, Safer Vehicles and Road Safety Management). The result of the study consists of a list of recommendations that can be applied by policymakers to promote safer roads in Asia towards 2030. The study is co-financed by the EU project ASIASAFE.

Keywords: traffic safety, ASIASAFE, Southeast Asia, EU project

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Authors: R. Furutani, K. Ishii

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Laser interferometers are now widely used for length and displacement measurement. In conventional methods, the optical path difference between two mirrors, one of which is a reference mirror and the other is a target mirror, is measured, as in Michelson interferometry, or two target mirrors are set up and the optical path difference between the two targets is measured, as in differential interferometry. In these interferometers, the two laser beams pass through different optical elements so that the measurement result is affected by the vibration and other effects in the optical paths. In addition, it is difficult to measure the roll angle around the optical axis. The proposed interferometer simultaneously measures both the translational motion along the optical axis and the roll motion around it by combining the retroreflective principle of the ball lens (BL) and the polarization. This interferometer detects the interferogram by the two beams traveling along the identical optical path from the beam source to BL. This principle is expected to reduce external influences by using the interferogram between the two lasers in an identical optical path. The proposed interferometer uses a BL so that the reflected light from the lens travels on the identical optical path as the incident light. After reaching the aperture of the He-Ne laser oscillator, the reflected light is reflected by a mirror with a very high reflectivity installed in the aperture and is irradiated back toward the BL. Both the first laser beam that enters the BL and the second laser beam that enters the BL after the round trip interferes with each other, enabling the measurement of displacement along the optical axis. In addition, for the measurement of the roll motion, a quarter-wave plate is installed on the optical path to change the polarization state of the laser. The polarization states of the first laser beam and second laser beam are different by the roll angle of the target. As a result, this system can measure the displacement and the roll angle of BL simultaneously. It was verified by the simulation and the experiment that the proposed optical system could measure the displacement and the roll angle simultaneously.

Keywords: common path interferometer, displacement measurement, laser interferometer, simultaneous measurement, roll angle measurement

Procedia PDF Downloads 53

Authors: A. Kumar, D. Himanshu, Ak Vaish, K. Usman , A. Singh, R. Misra, V. Atam, S. P. Verma, S. Singhal

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Introduction: Resistant and uncontrolled hypertension offer great challenge, in terms of higher risk of morbidity, mortality and not the least, difficulty in diagnosis and management. Our study tries to identify the importance of two crucial aspects of hypertension management, i.e. drug compliance and optimum dosing and also the effect of spironolactone on blood pressure in cases of resistant hypertension. Methodology: A prospective study was carried out among patients, who were referred as case of resistant hypertension to Hypertension Clinic at Gandhi memorial and associated hospital, Lucknow, India from August, 2013 to July 2014. A total of 122 Subjects having uncontrolled BP with ≥3 antihypertensives were selected. After ruling out secondary resistance and with appropriate lifestyle modifications, effect of adherence and optimum doses was seen with monitoring of BP. Only those having blood pressure still uncontrolled were true resistant. These patients were given spironolactone to see its effect on BP over next 12 weeks. Results: Mean baseline BP of all (n=122) patients was 150.4±7.2 mmHg systolic and 92.1±5.7 mmHg diastolic. After promoting adherence to the regimen, there was reduction of 4.20±3.65 mmHg systolic and 2.08±4.74 mmHg Diastolic blood pressure, with 26 patients achieving target blood pressure goal. Further reduction of 6.66±5.99 mmHg in systolic and 2.59±3.67 mmHg in diastolic BP was observed after optimizing the drug doses with another 66 patients achieving target blood pressure goal. Only 30 patients were true resistant hypertensive and prescribed spironolactone. Over 12 weeks, mean reduction of 20.62±3.65 mmHg in systolic and 10.08 ± 6.46 mmHg in diastolic BP was observed. Out of these 30, BP was controlled in 24 patients. Side effects observed were hyperkalemia in 2 patients and breast tenderness in 2 patients. Conclusion: Improper adherence and suboptimal regimen appear to be the important reasons for uncontrolled hypertension. By virtue of maintaining proper adherence to an optimum regimen, target BP goal can be reached in many without adding much to the regimen. Spironolactone is effective in patients with resistant hypertension, in terms of blood pressure reduction with minimal side effects.

Keywords: resistant, hypertension, spironolactone, blood pressure

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Authors: Sarah A. Goodchild, Rachel Gao, Philip N. Bartlett

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A novel detection approach using immobilized DNA probes labeled with Anthraquinone (AQ) as an electrochemically active reporter moiety has been successfully developed as a new, simple, reliable method for the detection of DNA. This method represents a step forward in DNA detection as it can discriminate between multiple nucleotide polymorphisms within target DNA strands without the need for any additional reagents, reporters or processes such as melting of DNA strands. The detection approach utilizes single-stranded DNA probes immobilized on gold surfaces labeled at the distal terminus with AQ. The effective immobilization has been monitored using techniques such as AC impedance and Raman spectroscopy. Simple voltammetry techniques (Differential Pulse Voltammetry, Cyclic Voltammetry) are then used to monitor the reduction potential of the AQ before and after the addition of complementary strand of target DNA. A reliable relationship between the shift in reduction potential and the number of base pair mismatch has been established and can be used to discriminate between DNA from highly related pathogenic organisms of clinical importance. This indicates that this approach may have great potential to be exploited within biosensor kits for detection and diagnosis of pathogenic organisms in Point of Care devices.

Keywords: Anthraquinone, discrimination, DNA detection, electrochemical biosensor

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Authors: Sara Fallahi

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This paper reviews the importance of content familiarity of receptive skills and offers solutions to the issue of content unfamiliarity in language learning materials. Presently, language learning materials are mainly comprised of global issues and target language speakers’ culture(s) in receptive skills. This might leadlearners to focus on content rather than the language. As a solution, materials on receptive skills can be developed with a focus on learners’culture and social concerns, especially in the beginner levels of learning. Language learners often learn their target language through the receptive skills of listening and reading before language production ensues through speaking and writing. Students’ journey from receptive skills to productive skills is mainly concentrated on by teachers. There are barriers to language learning, such as time and energy, that can hinder learners’ understanding and ability to build the required background knowledge of the content. This is generated due to learners’ unfamiliarity with the skill’s content. Therefore, materials that improve content familiarity will help learners improve their language comprehension, learning, and usage. This presentation will conclude with practical solutions to help teachers and learners more authentically integrate language and culture to elevate language learning.

Keywords: language learning, listening content, reading content, content familiarity, ESL books, language learning books, cultural familiarity

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Authors: Onur Özdemir, M.Erhan ORHAN

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Knowledge Development (KD) is just one of the important phases of Knowledge Management (KM). KD is the phase in which intelligence is used to see the big picture. In order to understand whether information is important or not, we have to use the intelligence cycle that includes four main steps: aiming, collecting data, processing and utilizing. KD also needs these steps. To make a precise decision, the decision maker has to be aware of his subordinates’ ideas. If the decision maker ignores the ideas of his subordinates or participants of the organization, it is not possible for him to get the target. KD is a way of using wisdom to accumulate the puzzle. If the decision maker does not bring together the puzzle pieces, he cannot get the big picture, and this shows its effects on the battlefield. In order to understand the battlefield, the decision maker has to use the intelligence cycle. To convert information to knowledge, KD is the main means for the intelligence cycle. On the other hand, the “Z Generation” born after the millennium are really the game changers. They have different attitudes from their elders. Their understanding of life is different - the definition of freedom and independence have different meanings to them than others. Decision makers have to consider these factors and rethink their decisions accordingly. This article tries to explain the relation between KD and Generation Z. KD is the main method of target managing. But if leaders neglect their people, the world will be seeing much more movements like the Arab Spring and other insurgencies.

Keywords: knowledge development, knowledge management, generation Z, intelligence cycle

Procedia PDF Downloads 486