Search results for: small molecule inhibitors
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 5575

Search results for: small molecule inhibitors

4345 Application of Compressed Sensing and Different Sampling Trajectories for Data Reduction of Small Animal Magnetic Resonance Image

Authors: Matheus Madureira Matos, Alexandre Rodrigues Farias

Abstract:

Magnetic Resonance Imaging (MRI) is a vital imaging technique used in both clinical and pre-clinical areas to obtain detailed anatomical and functional information. However, MRI scans can be expensive, time-consuming, and often require the use of anesthetics to keep animals still during the imaging process. Anesthetics are commonly administered to animals undergoing MRI scans to ensure they remain still during the imaging process. However, prolonged or repeated exposure to anesthetics can have adverse effects on animals, including physiological alterations and potential toxicity. Minimizing the duration and frequency of anesthesia is, therefore, crucial for the well-being of research animals. In recent years, various sampling trajectories have been investigated to reduce the number of MRI measurements leading to shorter scanning time and minimizing the duration of animal exposure to the effects of anesthetics. Compressed sensing (CS) and sampling trajectories, such as cartesian, spiral, and radial, have emerged as powerful tools to reduce MRI data while preserving diagnostic quality. This work aims to apply CS and cartesian, spiral, and radial sampling trajectories for the reconstruction of MRI of the abdomen of mice sub-sampled at levels below that defined by the Nyquist theorem. The methodology of this work consists of using a fully sampled reference MRI of a female model C57B1/6 mouse acquired experimentally in a 4.7 Tesla MRI scanner for small animals using Spin Echo pulse sequences. The image is down-sampled by cartesian, radial, and spiral sampling paths and then reconstructed by CS. The quality of the reconstructed images is objectively assessed by three quality assessment techniques RMSE (Root mean square error), PSNR (Peak to Signal Noise Ratio), and SSIM (Structural similarity index measure). The utilization of optimized sampling trajectories and CS technique has demonstrated the potential for a significant reduction of up to 70% of image data acquisition. This result translates into shorter scan times, minimizing the duration and frequency of anesthesia administration and reducing the potential risks associated with it.

Keywords: compressed sensing, magnetic resonance, sampling trajectories, small animals

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4344 Comparing Double-Stranded RNA Uptake Mechanisms in Dipteran and Lepidopteran Cell Lines

Authors: Nazanin Amanat, Alison Tayler, Steve Whyard

Abstract:

While chemical insecticides effectively control many insect pests, they also harm many non-target species. Double-stranded RNA (dsRNA) pesticides, in contrast, can be designed to target unique gene sequences and thus act in a species-specific manner. DsRNA insecticides do not, however, work equally well for all insects, and for some species that are considered refractory to dsRNA, a primary factor affecting efficacy is the relative ease by which dsRNA can enter a target cell’s cytoplasm. In this study, we are examining how different structured dsRNAs (linear, hairpin, and paperclip) can enter mosquito and lepidopteran cells, as they represent dsRNA-sensitive and refractory species, respectively. To determine how the dsRNAs enter the cells, we are using chemical inhibitors and RNA interference (RNAi)-mediated knockdown of key proteins associated with different endocytosis processes. Understanding how different dsRNAs enter cells will ultimately help in the design of molecules that overcome refractoriness to RNAi or develop resistance to dsRNA-based insecticides. To date, we have conducted chemical inhibitor experiments on both cell lines and have evidence that linear dsRNAs enter the cells using clathrin-mediated endocytosis, while the paperclip dsRNAs (pcRNAs) can enter both species’ cells in a clathrin-independent manner to induce RNAi. An alternative uptake mechanism for the pcRNAs has been tentatively identified, and the outcomes of our RNAi-mediated knockdown experiments, which should provide corroborative evidence of our initial findings, will be discussed.

Keywords: dsRNA, RNAi, uptake, insecticides, dipteran, lepidopteran

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4343 Pathological and Molecular Diagnosis of Caseous Lymphadenitis in Chinkara Deer (Gazella Bennettii), in Pakistan

Authors: Mudassar Iqbal, Riaz Hussain, Khalid Mehmood, Farah Ali, Fazal Mahmood, Abdul Ghaffar

Abstract:

Corynebacterium pseudotuberculosis is an important cause of caseous lymphadenitis (CL), a complex, chronic devastating and destructive disease of small ruminants. In present study, postmortem examination of Chinkara deer (n=25) was conducted in year 2014. Pus samples suggestive of CL were collected from the superficial lymph nodes, liver, spleen and lungs during necropsy and subjected to standard microbiological procedures for isolation and molecular analysis of bacterial pathogens. Pus samples collected from carcasses (25) presenting clinical lesions of C. pseudotuberculosis infection was identified in 19 (76%) carcasses on the basis of culture characteristics. The frequency of C. pseudotuberculosis bacterium was higher in older animals as compared to young animals. Grossly, multiple tubercles of variable size having caseous material were observed in liver, lungs, spleen and lymph nodes. Histopathologically, tissue sections from all the visceral organs were extensively plugged with abscess. In present study specific prolineiminopeptidase (PIP) gene of the C. pseudotuberculosis was amplified by the Polymerase chain reaction technique (PCR) in 17(25) cases. The efficient and reliable molecular analysis along with necropsy findings in present study can be used as valuable approach for diagnosis of caseous lymphadenitis in small ruminants.

Keywords: Chinkara deer, Corynebacterium pseudotuberculosis, Caseous lymphadenitis, PCR

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4342 A Study of Different Retail Models That Penetrates South African Townships

Authors: Beaula, M. Kruger, Silindisipho, T. Belot

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Small informal retailers are considered one of the most important features of developing countries around the world. Those small informal retailers form part of the local communities in South African townships and are estimated to be more than 100,000 across the country. The township economic landscape has changed over time in South Africa. The traditional small informal retailers in South African Townships have been faced with numerous challenges of increasing competition; an increase in the number of local retail shops and foreign-owned shops. There is evidence that the South African personal and disposable income has increased amongst black African consumers. Historically, people residing in townships were restricted to informal retail shops; however, this has changed due to the growing number of formal large retail chains entering into the township market. The larger retail chains are aware of the improved income levels of the middle-income townships residence and as a result, larger retailers have followed certain strategies such as; (1) retail format development; (2) diversification growth strategy; (3) market penetration growth strategy and (4) market expansion. This research did a comparative analysis between the different retail models developed by Pick n Pay, Spar and Shoprite. The research methodology employed for this study was of a qualitative nature and made use of a case study to conduct a comparative analysis between larger retailers. A questionnaire was also designed to obtain data from existing smaller retailers. The study found that larger retailers have developed smaller retail formats to compete with the traditional smaller retailers operating in South African townships. Only one out of the two large retailers offers entrepreneurs a franchise model. One of the big retailers offers the opportunity to employ between 15 to 20 employees while the others are subject to the outcome of a feasibility study. The response obtained from the entrepreneurs in the townships were mixed, while some found their presence as having a “negative impact,” which has increased competition; others saw them as a means to obtain a variety of products. This research found that the most beneficial retail model for both bigger retail and existing and new entrepreneurs are from Pick n Pay. The other retail format models are more beneficial for the bigger retailers and not to new and existing entrepreneurs.

Keywords: Pick n Pay, retailers, shoprite, spar, townships

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4341 Embodied Communication - Examining Multimodal Actions in a Digital Primary School Project

Authors: Anne Öman

Abstract:

Today in Sweden and in other countries, a variety of digital artefacts, such as laptops, tablets, interactive whiteboards, are being used at all school levels. From an educational perspective, digital artefacts challenge traditional teaching because they provide a range of modes for expression and communication and are not limited to the traditional medium of paper. Digital technologies offer new opportunities for representations and physical interactions with objects, which put forward the role of the body in interaction and learning. From a multimodal perspective the emphasis is on the use of multiple semiotic resources for meaning- making and the study presented here has examined the differential use of semiotic resources by pupils interacting in a digitally designed task in a primary school context. The instances analyzed in this paper come from a case study where the learning task was to create an advertising film in a film-software. The study in focus involves the analysis of a single case with the emphasis on the examination of the classroom setting. The research design used in this paper was based on a micro ethnographic perspective and the empirical material was collected through video recordings of small-group work in order to explore pupils’ communication within the group activity. The designed task described here allowed students to build, share, collaborate upon and publish the redesigned products. The analysis illustrates the variety of communicative modes such as body position, gestures, visualizations, speech and the interaction between these modes and the representations made by the pupils. The findings pointed out the importance of embodied communication during the small- group processes from a learning perspective as well as a pedagogical understanding of pupils’ representations, which were similar from a cultural literacy perspective. These findings open up for discussions with further implications for the school practice concerning the small- group processes as well as the redesigned products. Wider, the findings could point out how multimodal interactions shape the learning experience in the meaning-making processes taking into account that language in a globalized society is more than reading and writing skills.

Keywords: communicative learning, interactive learning environments, pedagogical issues, primary school education

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4340 Measuring the Economic Empowerment of Women Using an Index: An Application to Small-Scale Fisheries and Agriculture in Sebaste, Antique

Authors: Ritchie Ann Dionela, Jorilyn Tabuena

Abstract:

This study measured the economic empowerment of women from small-scale fisheries and agriculture sector of Sebaste, Antique. There were a total of 199 respondents selected using stratified random sampling. The Five Domains of Empowerment (5DE) Index was used in measuring the economic empowerment of study participants. Through this composite index, it was determined how women scored in the five domains of empowerment, namely production, resources, income, leadership, and time. The result of the study shows that women fishers are more economically empowered than women farmers. The two sectors showed high disparity in their scores on input in productive decision; autonomy in production; ownership of assets; control over use of income; group member; speaking in public; workload; and leisure. Group member indicator contributed largely to the disempowered population in both sectors. Although income of women farmers is higher than that of women fishers, the latter are still economically empowered which suggests that economic empowerment is not dependent on income alone. The study recommends that fisheries and agriculture organization for women should be established so that their needs and concerns will be heard and addressed. It is further recommended that government projects focused on enhancing women empowerment should also give importance on other factors such as organization and leisure and not just income to totally promote of women empowerment. Further studies on measuring women’s empowerment using other methods should be pursued to provide more information on women’s well-being.

Keywords: agriculture, composite index, fisheries, women economic empowerment

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4339 Collision Tumor of Plasmacytoma with Hematological and Non-Hematological Malignancies

Authors: Arati Inamdar, Siddharth Bhattacharyya, Kester Haye

Abstract:

Collision tumors are rare entities characterized by neoplasms of two different cell populations with distinct separating boundaries. Such tumors could be benign, malignant, or a combination of both. The exact mechanism of origin for collision tumors is predicted to be tumor heterogeneity or concurrent occurrence of neoplasm in the same organ. We present two cases of plasmacytoma presenting as a collision tumor, one with a tumor of hematological origin and another with a non-hematological origin, namely Chronic Lymphocytic Leukemia and Adenocarcinoma of the colon, respectively. The immunohistochemical stains and flowcytometry analysis performed on the specimens aided incorrect diagnosis. Interestingly, neoplastic cells of plasmacytoma in the first case demonstrated strong cytokeratin along with weak Epithelial Specific Antigen/ Epithelial cell adhesion molecule Monoclonal Antibody (MOC31) positivity, indicating that the tumor may influence the microenvironment of the tumor in the vicinity. Furthermore, the next-generation sequencing studies performed on the specimen with plasmacytoma and chronic lymphocytic lymphoma demonstrated BReast CAncer gene (BRCA2) and Tumor Necrosis Factor Alpha Induced Protein 3 (TNFAIP3) as a disease associated variants suggestive of risk for multiple tumors including collision tumors. Our reports highlight the unique collision tumors involving plasmacytoma, which have never been reported previously, as well as provide necessary insights about the underline genetic aberrations and tumor heterogeneity through sequencing studies and allow clonality assessment for subsequent tumors.

Keywords: BRCA2, collision tumor, chronic lymphocytic leukemia, plasmacytoma

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4338 Mitigating the Aggregation of Human Islet Amyloid Polypeptide with Nanomaterials

Authors: Ava Faridi, Pouya Faridi, Aleksandr Kakinen, Ibrahim Javed, Thomas P. Davis, Pu Chun Ke

Abstract:

Human islet amyloid polypeptide (IAPP) is a hormone associated with glycemic control and type 2 diabetes. Biophysically, the chirality of IAPP fibrils has been little explored with respect to the aggregation and toxicity of the peptide. Biochemically, it remains unclear as for how protein expression in pancreatic beta cells may be altered by cell exposure to the peptide, and how such changes may be mitigated by nanoparticle inhibitors for IAPP aggregation. In this study, we first demonstrated the elimination of the IAPP nucleation phase and shortening of its elongation phase by silica nanoribbons. This accelerated IAPP fibrillization translated to reduced toxicity, especially for the right-handed silica nanoribbons, as revealed by cell viability, helium ion microscopy, as well as zebrafish embryo survival, developmental and behavioral assays. We then examined the proteomes of βTC6 pancreatic beta cells exposed to the three main aggregation states of monomeric, oligomeric and amyloid fibrillar IAPP, and compared that with cellular protein expression modulated by graphene quantum dots (GQDs). A total of 29 proteins were significantly regulated by different forms of IAPP, and the majority of these proteins were nucleotide-binding proteins. A regulatory capacity of GQDs against aberrant protein expression was confirmed. These studies have demonstrated the great potential of employing nanomaterials targeting the mesoscopic enantioselectivity and protein expression dysregulation in pancreatic beta cells.

Keywords: graphene quantum dots, IAPP, silica nanoribbons, protein expression, toxicity

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4337 Combined Treatment of PARP-1 Inhibitor and Carbon Ion or Gamma Exposure Reduces the Metastatic Potential in Cultured Human Cells

Authors: Priyanka Chowdhury, Asitikantha Sarma, Utpal Ghosh

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Hadron therapy using high Linear Energy Transfer (LET) ion beam is producing promising clinical results worldwide. The major advantages are its ability to kill radio-resistant tumor and its anti-metastatic activity. Poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors have been widely used as radiosensitizer, but its role in metastasis is unknown. The purpose of our study was to investigate the effect of PARP-1 depletion in combination with either Carbon Ion Beam (CIB) or gamma irradiation on metastatic potential of cultured cancerous cells. A549 cells were irradiated with CIB (0-4Gy) or gamma (0, 2, 4, 6 and 10 Gy) with and without PARP-1 inhibition. The metastatic potential of the cells was determined by cell migratory assay, expression, and activity of MMP-2 and MMP-9, expression of Cadherin, Fibronectin, and Vimentin. CIB exposure reduced migratory property and activity of MMP-2 and MMP-9 significantly. CIB with PARP-1 inhibition reduced cell migration and Matrix Metalloproteinase (MMPs) activity in a synergistic manner. Expression of MMPs was also down-regulated in CIB and combined treatment. On the contrary, MMP- 2 and MMP-9 activity was significantly increased in gamma irradiated cells but decreased upon combined treatment of gamma and PARP-1 inhibitor. MMPs expression and migration was reduced when gamma irradiation was combined with PARP-1 inhibition. Thus, our study clearly demonstrates that PARP-1 inhibition in combination with either high or low LET can significantly suppress metastatic potential in cancer cells and thereby can be a promising tool in controlling metastatic cancers.

Keywords: high LET, low LET, matrix metalloproteinase (MMP), PARP-1

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4336 Management of ASD with Co-morbid OCD: A Literature Review to Compare the Pharmacological and Psychological Treatment Options in Individuals Under the Age of 18

Authors: Gursimran Jandu, Melissa Nelson, Mia Ingram, Hana Jalal

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There is a significant overlap between autism spectrum disorder (ASD) and obsessive-compulsive disorder (OCD), with up to 90% of young people diagnosed with ASD having this co-morbidity. Distinguishing between the symptoms of the two leads to issues with accurate treatment, yet this is paramount in benefiting the young person. There are two distinct methods of treatment, psychological or pharmacological, with clinicians tending to choose one or the other, potentially due to the lack of research available. This report reviews the efficacy of psychological and pharmacological treatments for young people diagnosed with ASD and co-morbid OCD. A literature review was performed on papers from the last fifteen years including ‘ASD’, ‘OCD’ and individuals under the age of 18. Eleven papers were selected as relevant. The report looks at the comparison between more traditional methods, such as selective-serotonin-reuptake-inhibitors (SSRI) and Cognitive behaviour therapy (CBT), and newer therapies, such as modified or intensive ASD focused psychotherapies, and the use of other medication classes. On reviewing the data, it was identified that there was a distinct lack of information on this important topic. The most widely used treatment was medication such as Fluoxetine, an SSRI, which rarely showed improvement in symptoms or outcomes. This is in contrast to modified forms of CBT which often reduces symptoms or even results in OCD remission. With increased research into non-traditional management of these co-morbid conditions, it is clear there is scope that modified CBT may become the future treatment of choice for OCD in young people with ASD.

Keywords: autism spectrum disorder, intensive or adapted cognitive behavioural therapy, obsessive compulsive disorder, pharmacological management

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4335 The Influence of Knowledge Spillovers on High-Impact Firm Growth: A Comparison of Indigenous and Foreign Firms

Authors: Yazid Abdullahi Abubakar, Jay Mitra

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This paper is concerned with entrepreneurial high-impact firms, which are firms that generate ‘both’ disproportionate levels of employment and sales growth, and have high levels of innovative activity. It investigates differences in factors influencing high-impact growth between indigenous and foreign firms. The study is based on an analysis of data from United Kingdom (UK) Innovation Scoreboard on 865 firms, which were divided into high-impact firms (those achieving positive growth in both sales and employment) and low-impact firms (negative or no growth in sales or employment); in order to identifying the critical differences in regional, sectorial and size related factors that facilitate knowledge spillovers and high-impact growth between indigenous and foreign firms. The findings suggest that: 1) Firms’ access to regional knowledge spillovers (from businesses and higher education institutions) is more significantly associated with high-impact growth of UK firms in comparison to foreign firms, 2) Because high-tech sectors have greater use of knowledge spillovers (compared to low-tech sectors), high-tech sectors are more associated with high-impact growth, but the relationship is stronger for UK firms compared to foreign firms, 3) Because small firms have greater need for knowledge spillovers (relative to large firms), there is a negative relationship between firm size and high-impact growth, but the negative relationship is greater for UK firms in comparison to foreign firms.

Keywords: entrepreneurship, high-growth, indigenous firms, foreign firms, small firms, large firms

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4334 Low Carbon Tourism Management: Strategies for Climate-Friendly Tourism of Koh Mak, Thailand

Authors: Panwad Wongthong, Thanan Apivantanaporn, Sutthiwan Amattayakul

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Nature-based tourism is one of the fastest growing industries that can bring in economic benefits, improve quality of life and promote conservation of biodiversity and habitats. As tourism develops, substantial socio-economic and environmental costs become more explicit. Particularly in island destinations, the dynamic system and geographical limitations makes the intensity of tourism development and severity of the negative environmental impacts greater. The current contribution of the tourism sector to global climate change is established at approximately 5% of global anthropogenic CO2 emissions. In all scenarios, tourism is anticipated to grow substantially and to account for an increasingly large share of global greenhouse gas emissions. This has prompted an urgent call for more sustainable alternatives. This study selected a small island of Koh Mak in Thailand as a case study because of its reputation of being laid back, family oriented and rich in biodiversity. Importantly, it is a test platform for low carbon tourism development project supported by the Designated Areas for Sustainable Tourism Administration (DASTA) in collaboration with the Institute for Small and Medium Enterprises Development (ISMED). The study explores strategies for low carbon tourism management and assesses challenges and opportunities for Koh Mak to become a low carbon tourism destination. The goal is to identify suitable management approaches applicable for Koh Mak which may then be adapted to other small islands in Thailand and the region. Interventions/initiatives to increase energy efficiency in hotels and resorts; cut carbon emissions; reduce impacts on the environment; and promote conservation will be analyzed. Ways toward long-term sustainability of climate-friendly tourism will be recommended. Recognizing the importance of multi-stakeholder involvement in the tourism sector, findings from this study can reward Koh Mak tourism industry with a triple-win: cost savings and compliance with higher standards/markets; less waste, air emissions and effluents; and better capabilities of change, motivation of business owners, staff, tourists as well as residents. The consideration of climate change issues in the planning and implementation of tourism development is of great significance to protect the tourism sector from negative impacts.

Keywords: climate change, CO2 emissions, low carbon tourism, sustainable tourism management

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4333 Crude Extracts of Medicinal Plants Can Inhibit Some Bacteria of Clinical Importance in Minced Meat

Authors: Chika C. Ogueke, Ijeoma M. Agunwah

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The antimicrobial activities and preservative potentials of crude extracts of Alstonia boonei stem bark and Euphorbia hirta leaves were studied. Soxhlet extraction and cold ethanol extraction methods were used for the extraction of the dried and ground plant samples. Well in agar diffusion method was used for the antimicrobial screening at different concentrations of 25mg/ml, 50mg/ml, 100mg/ml and 200mg/ml on E.coli and B.subtilis. The preservative effects of the extracts at 0.1%, 0.2% and 0.3% singly and in combination were determined in minced meat using E. coli and B. subtilis as test isolates. Phytochemical analysis was also conducted on the extracts using standard analytical methods. E.hirta cold and A.boonei cold extracts gave the highest zone of growth inhibition on E. coli and B.substilis with 20mm zone diameter at 200mg/ml concentration. Phytochemical analysis revealed the presence of alkaloids, flavonoids, tannins, saponins and cardiac glycosides. A.boonei at 0.1, 0.2 and 0.3% produced a log cycle reduction on the growth of E.coli. Mixture of A. boonei and E. hirta extracts (1:1) at 0.1% and 0.2% also produced a log cycle reduction on the growth of E.coli and B. subtilis, however the A. boonei extracts had more significant effect on the isolates. The observed antimicrobial activities are attributed to the phytochemicals identified in the extracts. The results reveal the potentials of plant extracts as natural antimicrobial preservatives in minced meat. Thus the crude extracts can act as inhibitors of bacteria in a food system. Upon further purification better results may be obtained.

Keywords: antimicrobial preservative, crude extracts, minced meat, test isolates

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4332 Measuring the Lean Readiness of Kuwaiti Manufacturing Industries

Authors: Mohamad Alnajem

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Purpose: To measure the readiness of the Kuwaiti small and medium sized manufacturing industries (K-SMMIs) to implement the lean system (LS) through an evaluation of their existing quality practices, and compare such readiness among different product sectors and ownership types. Design/methodology/approach: This study adopts the measurement framework developed by Al-Najem et al. (2013), which establishes six constructs related to lean quality practices, namely: process, planning and control, customer relations, suppliers relations, HR, and top management and leadership. Data were collected from a survey of 50 K-SMMIs operating in different industrial sectors. One research question and two hypotheses were developed and tested using t-test and Levene’s test, descriptive analysis, and one-way ANOVA. Findings: The results demonstrate that the K-SMMIs are far from being ready to implement lean. In addition, the study found that product sector and ownership type have no significant impact on the lean readiness in the K-SMMIs. Practical implications: This research provides insight into preparing Kuwaiti, and other SMMIs, to implement the LS by creating an assessment of their existing lean practices and readiness. Originality/value: This research is among a limited number of studies that have addressed lean within the Arab region, and only the second to examine the level of lean readiness of the K-SMMIs. It expands the literature on lean in developing countries, particularly in the Arab region, and can provide guidance to research within other countries in the region.

Keywords: Kuwaiti small and medium sized industries, lean system, lean readiness, manufacturing industries

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4331 External Noise Distillation in Quantum Holography with Undetected Light

Authors: Sebastian Töpfer, Jorge Fuenzalida, Marta Gilaberte Basset, Juan P. Torres, Markus Gräfe

Abstract:

This work presents an experimental and theoretical study about the noise resilience of quantum holography with undetected photons. Quantum imaging has become an important research topic in the recent years after its first publication in 2014. Following this research, advances towards different spectral ranges in detection and different optical geometries have been made. Especially an interest in the field of near infrared to mid infrared measurements has developed, because of the unique characteristic, that allows to sample a probe with photons in a different wavelength than the photons arriving at the detector. This promising effect can be used for medical applications, to measure in the so-called molecule fingerprint region, while using broadly available detectors for the visible spectral range. Further advance the development of quantum imaging methods have been made by new measurement and detection schemes. One of which is quantum holography with undetected light. It combines digital phase shifting holography with quantum imaging to extent the obtainable sample information, by measuring not only the object transmission, but also its influence on the phase shift experienced by the transmitted light. This work will present extended research for the quantum holography with undetected light scheme regarding the influence of external noise. It is shown experimentally and theoretically that the samples information can still be at noise levels of 250 times higher than the signal level, because of its information being transmitted by the interferometric pattern. A detailed theoretic explanation is also provided.

Keywords: distillation, quantum holography, quantum imaging, quantum metrology

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4330 Structure-Based Virtual Screening and in Silico Toxicity Test of Compounds against Mycobacterium tuberculosis 7,8-Diaminopelargonic Acid Aminotransferase (MtbBioA)

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

Abstract:

One of the major interferences in the Philippines’ tuberculosis control program is the widespread prevalence of Mtb strains that are resistant to known drugs, such as the MDR-TB (Multi Drug Resistant Tuberculosis) and XDR-TB (Extensively Drug Resistant Tuberculosis). Therefore, there is a pressing need to search for novel Mtb drug targets in order to be able to combat these drug resistant strains. The enzyme 7,8-diaminopelargonic acid aminotransferase enzyme, or more commonly known as BioA, is one such ideal target, as it is known that humans do not possess this enzyme. BioA primarily plays a key role in Mtb’s lipid biosynthesis pathway; more specifically in the synthesis of the enzyme cofactor biotin. In this study, structure-based pharmacophore screening, docking, and ADMET evaluation of compounds obtained from the DrugBank chemical database were performed against the MtbBioA enzyme. Results of the screening, docking, ADMET, and TOPKAT calculations revealed that out of the 6,516 compounds in the library, only 7 compounds indicated more favorable binding energies as compared to the enzyme’s known inhibitor, amiclenomycin (ACM), as well as good solubility and toxicity properties. Moreover, out of these 7 compounds, Molecule 6 exhibited the best solubility and toxicity properties. In the future, these lead compounds may then be subjected to bioactivity assays in vitro or in vivo for further evaluation of its therapeutic efficacy.

Keywords: 7, 8-diaminopelargonic acid aminotransferase, BioA, pharmacophore, molecular docking, ADMET, TOPKAT

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4329 Experimental Work to Estimate the Strength of Ferrocement Slabs Incorporating Silica Fume and Steel Fibre

Authors: Mohammed Mashrei

Abstract:

Ferrocement is a type of thin reinforced concrete made of cement-sand matrix with closely spaced relatively small diameter wire meshes, with or without steel bars of small diameter called skeletal steel. This work concerns on the behavior of square ferrocement slabs of dimensions (500) mm x (500) mm and 30 mm subjected to a central load. This study includes testing thirteen ferrocement slabs. The main variables considered in the experimental work are the number of wire mesh layers, percentage of silica fume and the presence of steel fiber. The effects of these variables on the behavior and load carrying capacity of tested slabs under central load were investigated. From the experimental results, it is found that by increasing the percentage of silica fume from (0 to 1.5, 3, 4.5 and 6) of weight of cement the ultimate loads are affected. Also From this study, it is observed that the load carrying capacity increases with the presence of steel fiber reinforcement, the ductility is high in the case of steel fibers. The increasing wire mesh layer from six to ten layers increased the load capacity by 76%. Also, a reduction in width of crack with increasing in number of cracks in the samples that content on steel fibers comparing with samples without steel fibers was observed from the results.

Keywords: ferrocement, fibre, silica fume, slab, strength

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4328 Programmable Microfluidic Device Based on Stimuli Responsive Hydrogels

Authors: Martin Elstner

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Processing of information by means of handling chemicals is a ubiquitous phenomenon in nature. Technical implementations of chemical information processing lack of low integration densities compared to electronic devices. Stimuli responsive hydrogels are promising candidates for materials with information processing capabilities. These hydrogels are sensitive toward chemical stimuli like metal ions or amino acids. The binding of an analyte molecule induces conformational changes inside the polymer network and subsequently the water content and volume of the hydrogel varies. This volume change can control material flows, and concurrently information flows, in microfluidic devices. The combination of this technology with powerful chemical logic gates yields in a platform for highly integrated chemical circuits. The manufacturing process of such devices is very challenging and rapid prototyping is a key technology used in the study. 3D printing allows generating three-dimensional defined structures of high complexity in a single and fast process step. This thermoplastic master is molded into PDMS and the master is removed by dissolution in an organic solvent. A variety of hydrogel materials is prepared by dispenser printing of pre-polymer solutions. By a variation of functional groups or cross-linking units, the functionality of the hole circuit can be programmed. Finally, applications in the field of bio-molecular analytics were demonstrated with an autonomously operating microfluidic chip.

Keywords: bioanalytics, hydrogels, information processing, microvalve

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4327 Functional Profiling of a Circular RNA from the Huntingtin (HTT) Gene

Authors: Laura Gantley, Vanessa M. Conn, Stuart Webb, Kirsty Kirk, Marta Gabryelska, Duncan Holds, Brett W. Stringer, Simon J. Conn

Abstract:

Trinucleotide repeat disorders comprise ~20 severe, inherited human neuromuscular and neurodegenerative disorders, which are a result of an abnormal expansion of repetitive sequences in the DNA. The most common of these, Huntington’s disease, results from the expansion of the CAG repeat region in exon 1 of the HTT gene via an unknown mechanism. Non-coding RNAs have been implicated in the initiation and progression of many diseases; thus, we focus on one circular RNA (circRNA) molecule arising from non-canonical splicing (back splicing) of HTT pre-mRNA. This circRNA and its mouse orthologue were transgenically overexpressed in human cells (SHSY-5Y and HEK293T) and mouse cells (Mb1), respectively. High-content imaging and flow cytometry demonstrated the overexpression of this circRNA reduces cell proliferation, reduces nuclear size independent of cellular size, and alters cell cycle progression. Analysis of protein by western blot and immunofluorescence demonstrated no change to HTT protein levels but altered nuclear-cytoplasmic distribution without impacting the expansion of the HTT repeat region. As these phenotypic and genotypic changes are found in Huntington’s disease patients, these results may suggest that this circRNA may play a functional role in the progression of Huntington’s disease.

Keywords: cell biology, circular RNAs, Huntington’s disease, molecular biology, neurodegenerative disorders

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4326 Production Value, Constraints, and Opportunities in East African Freshwater Fisheries: Systematic Review

Authors: Alamrew Eyayu, Abebe Getahun, James Last Keyombe

Abstract:

Demand for fish continued to grow worldwide while production from capture fisheries has decreased. In the Eastern African Region (EAR), the open-access nature of capture fisheries has resulted in illegal fishing. Within communities engaged in fishing, small-scale fisheries support food security strategies and sustain livelihoods. Despite the role of fisheries in EAR, inland fisheries are vulnerable to loss, and management solutions authorized for inland fisheries are inadequate. This review investigates production potential, challenges, opportunities, and management of inland fisheries in the EAR. It is therefore expected that in aquaculture promising areas, the EAR will turn to depend more on aquaculture to meet the extended needs and supply gaps created as a result of capture fisheries shortfalls. However, aquaculture is still in its infant stage in the region, and there exists no adequate aquaculture policy framework and funds in some EAR (e.g., Ethiopia, Somalia). Stakeholders at all levels should entertain the importance of fishery-based activities for food security in EAR. As a result, easily implemented and community-oriented fisheries legislative documents need to be prepared for advancing sustainable fisheries management. Legislative documents might consider techniques of continual catch statistics (consider small water bodies as much as possible) of inland fisheries and enforcing existing laws to manage illegal fishing activities to accustom sustainable development of inland capture fisheries.

Keywords: aquaculture, capture fisheries, East Africa, fisheries management

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4325 Non-Coplanar Nuclei in Heavy-Ion Reactions

Authors: Sahila Chopra, Hemdeep, Arshdeep Kaur, Raj K. Gupta

Abstract:

In recent times, we noticed an interesting and important role of non-coplanar degree-of-freedom (Φ = 00) in heavy ion reactions. Using the dynamical cluster-decay model (DCM) with Φ degree-of-freedom included, we have studied three compound systems 246Bk∗, 164Yb∗ and 105Ag∗. Here, within the DCM with pocket formula for nuclear proximity potential, we look for the effects of including compact, non-coplanar configurations (Φc = 00) on the non-compound nucleus (nCN) contribution in total fusion cross section σfus. For 246Bk∗, formed in 11B+235U and 14N+232Th reaction channels, the DCM with coplanar nuclei (Φc = 00) shows an nCN contribution for 11B+235U channel, but none for 14N+232Th channel, which on including Φ gives both reaction channels as pure compound nucleus decays. In the case of 164Yb∗, formed in 64Ni+100Mo, the small nCN effects for Φ=00 are reduced to almost zero for Φ = 00. Interestingly, however, 105Ag∗ for Φ = 00 shows a small nCN contribution, which gets strongly enhanced for Φ = 00, such that the characteristic property of PCN presents a change of behaviour, like that of a strongly fissioning superheavy element to a weakly fissioning nucleus; note that 105Ag∗ is a weakly fissioning nucleus and Psurv behaves like one for a weakly fissioning nucleus for both Φ = 00 and Φ = 00. Apparently, Φ is presenting itself like a good degree-of-freedom in the DCM.

Keywords: dynamical cluster-decay model, fusion cross sections, non-compound nucleus effects, non-coplanarity

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4324 Induced Chemistry for Dissociative Electron Attachment to Focused Electron Beam Induced Deposition Precursors Based on Ti, Si and Fe Metal Elements

Authors: Maria Pintea, Nigel Mason

Abstract:

Induced chemistry is one of the newest pathways in the nanotechnology field with applications in the focused electron beam induced processes for deposition of nm scale structures. Si(OPr)₄ and Ti(OEt)₄ are two of the precursors that have not been so extensively researched, though highly sought for semiconductor and medical applications fields, the two compounds make good candidates for FEBIP and are the subject of velocity slice map imaging analysis for deposition purposes, offering information on kinetic energies, fragmentation channels, and angular distributions. The velocity slice map imaging technique is a method used for the characterization of molecular dynamics of the molecule and the fragmentation channels as a result of induced chemistry. To support the gas-phase analysis, Meso-Bio-Nano simulations of irradiation dynamics studies are employed with final results on Fe(CO)₅ deposited on various substrates. The software is capable of running large scale simulations for complex biomolecular, nano- and mesoscopic systems with applications to thermos-mechanical DNA damage, complex materials, gases, nanoparticles for cancer research and deposition applications for nanotechnology, using a large library of classical potentials, many-body force fields, molecular force fields involved in the classical molecular dynamics.

Keywords: focused electron beam induced deposition, FEBID, induced chemistry, molecular dynamics, velocity map slice imaging

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4323 Liver Histopathological Findings after Treatment with Anastrazole and Letrozole in Ovariectomized Rats

Authors: Ioannis Boutas, Vasilios Pergialiotis, Nicolaos Salakos, George Agrogiannis, Panagiotis Konstantopoulos, Laskarina-Maria Korou, Theodoros Kalampokas, Odysseas Gregoriou, George Creatsas, Despina Perrea

Abstract:

Introduction: The effect of third generation aromatase inhibitors in the lipid profile among women with breast cancer, present diversities. It has been also shown that low levels of estrogens affect liver metabolism in mice in numerous ways, such as lipid accumulation and hepatic steatosis. Materials and Methods: Forty-five female Wistar rats underwent surgical ovariectomy. The animals were anesthetized with a combination of ketamine (75 mg/kg) and xylazine (10 mg/kg) which were administered intraperitoneally. After the ovariectomy, the operated animals were randomized in three groups. The first group did not receive any drug regimen (ovariectomized control group). The second group received Anastrazole and the third group received Letrozole. Four months after the initiation of the study, the animals were euthanized and livers were dissected immediately for further histopathological analysis. The histological features were grouped into 4 broad categories: steatosis, ballooning, portal inflammation and lobular activity. A score from 0 (absence) to 3 (severe) was assigned to each parameter. Results: The liver pathology analysis revealed significant differences among groups with favored mild steatosis and ballooning among animals that received Anastrazole or Letrozole. Conclusion: The effect of Anastrazole and Letrozole on liver function have not yet been clarified. In our study mild histological liver alterations seem also to occur and these alterations should be taken in mind in future clinical studies

Keywords: anastrazole, letrozole, liver, rats

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4322 Information Retrieval from Internet Using Hand Gestures

Authors: Aniket S. Joshi, Aditya R. Mane, Arjun Tukaram

Abstract:

In the 21st century, in the era of e-world, people are continuously getting updated by daily information such as weather conditions, news, stock exchange market updates, new projects, cricket updates, sports and other such applications. In the busy situation, they want this information on the little use of keyboard, time. Today in order to get such information user have to repeat same mouse and keyboard actions which includes time and inconvenience. In India due to rural background many people are not much familiar about the use of computer and internet also. Also in small clinics, small offices, and hotels and in the airport there should be a system which retrieves daily information with the minimum use of keyboard and mouse actions. We plan to design application based project that can easily retrieve information with minimum use of keyboard and mouse actions and make our task more convenient and easier. This can be possible with an image processing application which takes real time hand gestures which will get matched by system and retrieve information. Once selected the functions with hand gestures, the system will report action information to user. In this project we use real time hand gesture movements to select required option which is stored on the screen in the form of RSS Feeds. Gesture will select the required option and the information will be popped and we got the information. A real time hand gesture makes the application handier and easier to use.

Keywords: hand detection, hand tracking, hand gesture recognition, HSV color model, Blob detection

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4321 Anticancer Activity of Calyx of Diospyros kaki Thunb. through Downregulation of Cyclin D1 Protein Level in Human Colorectal Cancer Cells

Authors: Jin Boo Jeong

Abstract:

In this study, we elucidated anti-cancer activity and potential molecular mechanism of DKC against human colorectal cancer cells. DKC-E70 suppressed the proliferation of human colorectal cancer cell lines such as HCT116, SW480, LoVo and HT-29. Although DKC-E70 decreased cyclin D1 expression in protein and mRNA level, decreased level of cyclin D1 protein by DKC-E70 occurred at the earlier time than that of cyclin D1 mRNA, which indicates that DKC-E70-mediated downregulation of cyclin D1 protein may be a consequence of the induction of degradation and transcriptional inhibition of cyclin D1. In cyclin D1 degradation, we found that cyclin D1 downregulation by DKC-E70 was attenuated in presence of MG132. In addition, DKC-E70 phosphorylated threonine-286 (T286) of cyclin D1 and T286A abolished cyclin D1 downregulation by DKC-E70. We also observed that DKC-E70-mediated T286 phosphorylation and subsequent cyclin D1 degradation was blocked in presence of the inhibitors of ERK1/2, p38 or GSK3β. In cyclin D1 transcriptional inhibition, DKC-E70 inhibited the expression of β-catenin and TCF4, and β–catenin/TCF-dependent luciferase activity. Our results suggest that DKC-E70 may downregulate cyclin D1 as one of the potential anti-cancer targets through cyclin D1 degradation by T286 phosphorylation dependent on ERK1/2, p38 or GSK3β, and cyclin D1 transcriptional inhibition through Wnt signaling. From these findings, DKC-E70 has potential to be a candidate for the development of chemoprevention or therapeutic agents for human colorectal cancer. This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2016R1D1A3B03931713).

Keywords: anticancer, calyx of persimmon, cyclin D1, Diospyros kaki Thunb., human colorectal cancer

Procedia PDF Downloads 315
4320 Small Scale Solar-Photovoltaic and Wind Pump-Storage Hydroelectric System for Remote Residential Applications

Authors: Seshi Reddy Kasu, Florian Misoc

Abstract:

The use of hydroelectric pump-storage system at large scale, MW-size systems, is already widespread around the world. Designed for large scale applications, pump-storage station can be scaled-down for small, remote residential applications. Given the cost and complexity associated with installing a substation further than 100 miles from the main transmission lines, a remote, independent and self-sufficient system is by far the most feasible solution. This article is aiming at the design of wind and solar power generating system, by means of pumped-storage to replace the wind and/or solar power systems with a battery bank energy storage. Wind and solar pumped-storage power generating system can reduce the cost of power generation system, according to the user's electricity load and resource condition and also can ensure system reliability of power supply. Wind and solar pumped-storage power generation system is well suited for remote residential applications with intermittent wind and/or solar energy. This type of power systems, installed in these locations, could be a very good alternative, with economic benefits and positive social effects. The advantage of pumped storage power system, where wind power regulation is calculated, shows that a significant smoothing of the produced power is obtained, resulting in a power-on-demand system’s capability, concomitant to extra economic benefits.

Keywords: battery bank, photo-voltaic, pump-storage, wind energy

Procedia PDF Downloads 597
4319 Structural, Electrochemical and Electrocatalysis Studies of a New 2D Metal-Organic Coordination Polymer of Ni (II) Constructed by Naphthalene-1,4-Dicarboxylic Acid; Oxidation and Determination of Fructose

Authors: Zohreh Derikvand

Abstract:

One new 2D metal-organic coordination polymer of Ni(II) namely [Ni2(ndc)2(DMSO)4(H2O)]n, where ndc = naphthalene-1,4-dicarboxylic acid and DMSO= dimethyl sulfoxide has been synthesized and characterized by elemental analysis, spectral (IR, UV-Vis), thermal (TG/DTG) analysis and single crystal X-ray diffraction. Compound 1 possesses a 2D layer structure constructed from dinuclear nickel(II) building blocks in which two crystallographically independent Ni2+ ions are bridged by ndc2– ligands and water molecule. The ndc2– ligands adopt μ3 bridging modes, linking the metal centers into a two-dimensional coordination framework. The two independent NiII cations are surrounded by dimethyl sulfoxide and naphthalene-1,4-dicarboxylate molecules in distorted octahedron geometry. In the crystal structures of 1 there are non-classical hydrogen bonding arrangements and C-H–π stacking interactions. Electrochemical behavior of [Ni2(ndc)2(DMSO)4(H2O)]n, (Ni-NDA) on the surface of carbon nanotube (CNTs) glassy carbon electrode (GCE) was described. The surface structure and composition of the sensor were characterized by scanning electron microscopy (SEM). Oxidation of fructose on the surface of modified electrode was investigated with cyclic voltammetry and electrochemical impedance spectroscopy (EIS) and the results showed that the Ni-NDA/CNTs film displays excellent electrochemical catalytic activities towards fructose oxidation.

Keywords: naphthalene-1, 4-dicarboxylic acid, crystal structure, coordination polymer, electrocatalysis, impedance spectroscopy

Procedia PDF Downloads 333
4318 Sensitivity Based Robust Optimization Using 9 Level Orthogonal Array and Stepwise Regression

Authors: K. K. Lee, H. W. Han, H. L. Kang, T. A. Kim, S. H. Han

Abstract:

For the robust optimization of the manufacturing product design, there are design objectives that must be achieved, such as a minimization of the mean and standard deviation in objective functions within the required sensitivity constraints. The authors utilized the sensitivity of objective functions and constraints with respect to the effective design variables to reduce the computational burden associated with the evaluation of the probabilities. The individual mean and sensitivity values could be estimated easily by using the 9 level orthogonal array based response surface models optimized by the stepwise regression. The present study evaluates a proposed procedure from the robust optimization of rubber domes that are commonly used for keyboard switching, by using the 9 level orthogonal array and stepwise regression along with a desirability function. In addition, a new robust optimization process, i.e., the I2GEO (Identify, Integrate, Generate, Explore and Optimize), was proposed on the basis of the robust optimization in rubber domes. The optimized results from the response surface models and the estimated results by using the finite element analysis were consistent within a small margin of error. The standard deviation of objective function is decreasing 54.17% with suggested sensitivity based robust optimization. (Business for Cooperative R&D between Industry, Academy, and Research Institute funded Korea Small and Medium Business Administration in 2017, S2455569)

Keywords: objective function, orthogonal array, response surface model, robust optimization, stepwise regression

Procedia PDF Downloads 291
4317 Management of ASD with Co-Morbid OCD: A Literature Review to Compare the Pharmacological and Psychological Treatment Options in Individuals Under the Age of 18

Authors: Melissa Nelson, Simran Jandu, Hana Jalal, Mia Ingram, Chrysi Stefanidou

Abstract:

There is a significant overlap between autism spectrum disorder (ASD) and obsessive compulsive disorder (OCD), with up to 90% of young people diagnosed with ASD having this co-morbidity. Distinguishing between the symptoms of the two leads to issues with accurate treatment, yet this is paramount in benefitting the young person. There are two distinct methods of treatment, psychological or pharmacological, with clinicians tending to choose one or the other, potentially due to the lack of research available. This report reviews the efficacy of psychological and pharmacological treatments for young people diagnosed with ASD and co-morbid OCD. A literature review was performed on papers from the last fifteen years, including “ASD,” “OCD,” and individuals under the age of 18. Eleven papers were selected as relevant. The report looks at the comparison between more traditional methods, such as selective serotonin reuptake inhibitors (SSRI) and cognitive behavior therapy (CBT), and newer therapies, such as modified or intensive ASD-focused psychotherapies and the use of other medication classes. On reviewing the data, it was identified that there was a distinct lack of information on this important topic. The most widely used treatment was medication such as Fluoxetine, an SSRI, which rarely showed an improvement in symptoms or outcomes. This is in contrast to modified forms of CBT, which often reduces symptoms or even results in OCD remission. With increased research into the non-traditional management of these co-morbid conditions, it is clear there is scope that modified CBT may become the future treatment of choice for OCD in young people with ASD.

Keywords: autism spectrum disorder, intensive or adapted cognitive behavioral therapy, obsessive compulsive disorder, pharmacological management

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4316 Compression and Air Storage Systems for Small Size CAES Plants: Design and Off-Design Analysis

Authors: Coriolano Salvini, Ambra Giovannelli

Abstract:

The use of renewable energy sources for electric power production leads to reduced CO2 emissions and contributes to improving the domestic energy security. On the other hand, the intermittency and unpredictability of their availability poses relevant problems in fulfilling safely and in a cost efficient way the load demand along the time. Significant benefits in terms of “grid system applications”, “end-use applications” and “renewable applications” can be achieved by introducing energy storage systems. Among the currently available solutions, CAES (Compressed Air Energy Storage) shows favorable features. Small-medium size plants equipped with artificial air reservoirs can constitute an interesting option to get efficient and cost-effective distributed energy storage systems. The present paper is addressed to the design and off-design analysis of the compression system of small size CAES plants suited to absorb electric power in the range of hundreds of kilowatt. The system of interest is constituted by an intercooled (in case aftercooled) multi-stage reciprocating compressor and a man-made reservoir obtained by connecting large diameter steel pipe sections. A specific methodology for the system preliminary sizing and off-design modeling has been developed. Since during the charging phase the electric power absorbed along the time has to change according to the peculiar CAES requirements and the pressure ratio increases continuously during the filling of the reservoir, the compressor has to work at variable mass flow rate. In order to ensure an appropriately wide range of operations, particular attention has been paid to the selection of the most suitable compressor capacity control device. Given the capacity regulation margin of the compressor and the actual level of charge of the reservoir, the proposed approach allows the instant-by-instant evaluation of minimum and maximum electric power absorbable from the grid. The developed tool gives useful information to appropriately size the compression system and to manage it in the most effective way. Various cases characterized by different system requirements are analysed. Results are given and widely discussed.

Keywords: artificial air storage reservoir, compressed air energy storage (CAES), compressor design, compression system management.

Procedia PDF Downloads 233