Antimalarial secondary metabolites from Morinda lucida
- Authors: Chithambo, Bertha
- Date: 2017
- Subjects: Botanical chemistry , Anthraquinones , Antimalarials , Rubiaceae -- Therapeutic use , Malaria -- Treatment
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/45730 , vital:25535
- Description: Antimalarial activities of secondary metabolites from Morinda lucida (Rubiaceae), were investigated. Even though M. lucida is traditionally used to treat malaria, diabetes, jaundice, hypertension, dysentery and many other diseases, the compounds in this plant have not yet been fully investigated and characterised. Most of the studies that have been done on this plant focused on the medicinal properties of the crude extracts but have not gone further to isolate and characterise the compounds. In this study, the methanol - dichloromethane crude extract from the bark of M. lucida was fractionated into fractions 1-8. Fractions 2-5 were purified in order to isolate active secondary metabolites. The isolated pure compounds were characterised and identified. An in vitro antimalarial assay was carried out on the crude extract, fractions, pure compounds and solutions made from different combinations of pure compounds using the parasite lactate dehydrogenase (pLDH) assay. An IC50 done on the methanolic crude extract gave a value of 25 µg/mL. The % cell viability for the crude extract in cell toxicity assay remained at 100%. Each of the pure compounds tested had very little activity. Their activities were increased when samples from the different compounds were mixed. One of these mixtures reduced malaria viability to about 22 % at 20 µM and gave an IC50 value of 17 µM. Antibacterial assays were also carried out on the crude extract and fractions. Fractions 2 and 3 were relatively active (MIC values ranging between 125-1000 µg/mL) against M. cattarhalis and E. faecalis. Fraction 2 was also the most active on S. typhimurium and S. aureus (MIC value of 1000 µg/mL) compared with the other fractions. This same fraction also showed some activity against M. tuberculosis with MIC90 and MIC99 values of 40.9 and 46.3 µg/mL respectively in an anti-tuberculosis assay.The following compounds, comprising of iridoids (asperuloside and asperulosidic acid), terpenoids (stigmasterol, P-sitosterol, campesterol, lanosterol and cycloartenol) and anthraquinones [5,15-O-dimethylmorindol, 1,7-dihydroxy-2-methoxy-5-(methoxymethyl) anthraquinone and 1,6-dihydroxy-2-methoxy-5-(methoxymethyl)anthraquinone], were isolated. All these compounds have been isolated from different plants before with the exception of 1,7-dihydroxy-2-methoxy-5-(methoxymethyl)anthraquinone and 1,6-dihydroxy-2-methoxy-5-(methoxymethyl)anthraquinone which were tentatively assigned the structures due to insufficient data. To the best of our knowledge, this is the first report on the identification of all of the mentioned compounds, with the exception of ß-sitosterol and stigmasterol, from M. lucida. Molecular docking was performed on one of the isolated anthraquinones (5,15-O- dimethylmorindol) to check if it can bind to cytochrome bci, a known target for atovaquone. This compound interacted with the same amino acids that atovaquone, a well known antimalarial agent, interacted with on cytochrome bc1 indicating a possible similar mode of action.
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- Date Issued: 2017
Characterisation, antimalarial and biological activities of secondary metabolites from leaves of anonidium mannii
- Authors: Makoni, Pfungwa Gervase
- Date: 2017
- Subjects: Anonidium mannii -- Therapeutic use , Botanical chemistry , Annonaceae -- Therapeutic use , Apocynaceae -- Therapeutic use , Malaria -- Chemotherapy , Tuberculosis -- Chemotherapy , Bacterial diseases -- Chemotherapy , Cancer -- Chemotherapy
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/4797 , vital:20725
- Description: Anonidium mannii is a plant of the Annonaceae genus which is used traditionally in Africa for the treatment of gonorrhoea, malaria, cancer, skin inflammation and dysentery. In this study we will evaluate antimalarial, antifungal, anti - tuberculosis, antibacterial activities and cytotoxicity of different fractions in order to provide a scientific rationale for the traditional use of Anonidium mannii as well as provide possible novel drugs in the treatment of multi drug resistant strains of parasites and bacteria. Extracts from dried leaves were obtained by using solvent extraction and different fractions obtained using column chromatography eluted with solvents of varying polarities to obtain a wide range of metabolites. The antimalarial activity of the various fractions and some pure compounds was evaluated using plasmodium lactate dehydrogenase (pLDH) assay. Cytotoxicity was evaluated using HeLa cells while anti – tuberculosis assay was evaluated using the green fluorescent protein. Antibacterial activity of the extracts was evaluated using micro-dilution assay against Gram-positive (Staphylococcus aureus and Enterococcus faecalis) bacteria and Gram-negative (Escherichia coli and Salmonella typhi) bacteria. Antifungal activity was evaluated against Candida albicans. The antimalarial assays yielded some fractions with promising IC50 values. The selected fractions yielded activities ranging between 0.73 μg/mL and 20.23 μg/mL. The fraction with the best activity was obtained from a hexane/ethyl acetate fraction. AM1C, a cholestane, showed the best activity from the pure metabolites that were screened. AM3C, stigmasterol, a pure compound gave the best antifungal activity with an MIC of 0.063 μg/mL. AM9C another pure compound (sterol) showed the best activity against S. typhi with a value of 0.031 μg/mL. AM2C a pure compound showed an activity of 0.063 μg/mL against E. faecalis. The best cytotoxicity was demonstrated by the fraction C2AM3P with a cell viability of 7.1 ± 0.2 % while AM1C had a viability of 20.2 ± 1.2 %. Several pure metabolites were isolated and four of these were positively identified as steroids. Of these steroids the structure of three novel metabolites from A. mannii was deduced. The study showed promising antibacterial, antifungal, anti – tuberculosis, antimalarial and anticancer activity of A. mannii. These results validate the use of A. manni against cancer, skin inflammation which is caused by fungus, malaria and bacterial diseases.
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- Date Issued: 2017
Inhalable particulate systems for anti-tubercular drug delivery
- Authors: Nkanga, Christian Isalomboto
- Date: 2017
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/37966 , vital:24720
- Description: Tuberculosis (TB) is a deadly infectious microbial disease that is currently dominating public health concerns. Among the pharmacological issues in the management of TB are the poor bioavailability of some anti-TB drugs, mostly due to the fast first-pass metabolism, and high drug load needed for combination therapy. These result in a lengthy treatment with several adverse effects causing decreased patient compliance. These factors often lead to the therapeutic failure and promote the development of drug resistant strains, justifying the urgent need for new therapeutic strategies. Liposomes are lipid-based particulate vehicles known to be the most clinically appointed drug carriers currently. Liposomal systems are reported to be rapidly engulfed by macrophages - where the mycobacterium often resides. This makes liposomes appropriate vehicles for targeted anti-TB drug delivery. Many research groups have reported the potential of liposomes systems to deliver anti-TB drugs. However, the costly formulation status of liposomes, due the use of expensive synthetic or highly purified natural phospholipids, is a limitation to the treatment of a poverty related infectious disease like TB. The aim of this study was to design and develop liposomes for pulmonary delivery of anti-TB drugs using crude soybean lecithin (CL) and its purirified version. CL is an FDA- approved naturally occurring phospholipid mixture that is quite cheap and readily available. Various liposome batches were prepared using a film hydration method and characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM). Liposomes composed of CL and cholesterol (Chol) in a 3:1 mass ratio were selected for drug encapsulation based on the following characteristics: polydispersity index (PDI, 0.28), mean particles sizes (PS, 502 nm) and zeta potential (ZP, -56 mV). Isoniazid (INH) was encapsulated as a model drug using a freeze-thaw loading technique and an HPLC method was validated for quantitative analysis. The physicochemical properties of INH-loaded liposomes were comprehensively investigated using thermal, microscopy and spectroscopic techniques. This formulation showed a high encapsulation efficiency (%EE) of 78%, much better than the liposomes made from purified lecithin, 20%. Other characteristics of INH- loaded liposomes, which make them attractive for pulmonary TB therapy, are presented in this dissertation. These include a controlled release of 50% of the encapsulated INH over 12 hours. Finally, rifampicin (RIF) was added as a hydrophobic model drug and several evaluations were conducted on these dual drug-loaded liposomes. Of particular interest, it was noted that the dual drug-loaded liposomes made of CL alone showed the highest %EE (59% for INH and 90% for RIF) compared to those containing Chol or those made of purified lecithin. Surprisingly, the average PS of the dual CL-based liposomes (1114 nm) was in the size range reported for optimum deep lung deposition and macrophage uptake. In addition, the mean ZP of these liposomes (-63 mV) seems to be favourable for their shelf stability and internalization by macrophages. Overall, these findings show that the dual CL-based liposomes developed would be promising for macrophage-targeting pulmonary delivery of anti-TB drugs.
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- Date Issued: 2017
Nonlinear optical properties of Sn(IV) phthalocyanines: experimental and theoretical approach
- Authors: Louzada, Marcel Severiano
- Date: 2017
- Subjects: Phthalocyanines , Nonlinear optics
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/57852 , vital:26996
- Description: This work presents the nonlinear properties of six Sn(IV) Phthalocyanines. Three of the phthalocyanines are linked by an alkylthiol substituent and the rest are linked with a phenoxy substituent. For all six compounds non-linear optic analysis was carried out in four solvents: chloroform, toluene, dichloromethane, and tetrahydrofuran, and their differences were recorded. Calculation of the linear, singlet excited, triplet excited and two photon absorption cross-sections were also carried out and the results compared. To form a comparison the first order hyperpolarizabilities, DFT calculations were also performed and the results compared to see if the behaviour between the two properties can be predicted using DFT.
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- Date Issued: 2017
Phenomenology: preconceptions and experiences of non-chemists at Rhodes University using milk paint
- Authors: Kelly, Kelvin Leigh
- Date: 2017
- Subjects: Phenomenology , Art and science , Casein , Paint , Chemistry -- Study and teaching , Science -- Study and teaching -- Philosophy
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/37942 , vital:24711
- Description: There exists an ever-increasing crisis in science education where students experience disinterest because of an inability to grasp true understanding of scientific subjects, and therefore there should be a call to increase the research of phenomenology in combination with science education. A rebalance and paradigm shift in the focus of the modes of teaching could result in a great improvement in the learning, comprehension, and intellectual self-confidence of students interested in the sciences. To study this, three research questions were established: How is chemistry perceived by non-chemists; what is the experience of the participants’ during the chemistry practical in a laboratory and; do the participants’ perspectives about chemistry change during the experience. The performed study consisted of a chemistry practical, two art works and, in some cases, an interview. Nine participants were asked to create the art under specific instructions of points of focus, namely their preconceptions prior to the practical (Artwork 1) and their lived experience during the practical (Artwork 2). Participants’ artworks were examined using methods of visual semiotics and classical art analysis techniques, looking at line, shape, and colour choice. The iterative analysis of the interviews from participants 1, 2, 7, and 9 coded with ATLAS.ti 7 software, led to the emergence of themes that constitute the core of the participants’ experience. This phenomenological study presents a path to engage the non-chemist with processes taking place in the laboratory by using ‘Kitchen Chemistry’ and illustrates how a phenomenological engagement with chemistry can make the subject more applicable to the general population of non-chemists.
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- Date Issued: 2017
Photophysical studies of conjugates of upconversion nanoparticles with aluminium phthalocyanines
- Authors: Watkins, Zane
- Date: 2017
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/4964 , vital:20747
- Description: NaYF4 :Yb/Er/Gd upconversion nanoparticles (UCNP) were synthesised and their photoemission stabilised by embedding these nanoparticles in electrospun fibres. The photophysical behaviour of chloro aluminium tetrasulfo-phthalocyanine chloride (ClAlTSPc) was studied in the presence of UCNPs on mixing the two species in solution. The fluorescence lifetimes for UCNPs were shortened at 658 nm in the presence of ClAlTSPc when the former was embedded in fibre and suspended in a dimethyl sulfoxide solution of the latter. A clear singlet oxygen generation by ClAlTSPc through Forster resonance energy transfer (FRET) was demonstrated using a singlet oxygen quencher, 1,3-diphenylisobenzofuran. UCNP capped with amino groups were then covalently attached to chloro aluminium tetrasulphonated phthalocyanine (ClAlTSPc) and chloro aluminium tetracarboxy phthalocyanine (ClAlTCPc). The conjugates were characterized using different techniques such as infrared spectroscopy (IR), X-ray photoelectron spectroscopy (XPS) and Transmission electron microscopy (TEM). There was a decrease in fluorescence emission spectra of the UCNPs at 658 nm in the presence of the phthalocyanines. This decrease indicates an energy transfer between the donor UCNP and conjugated accepting phthalocyanine (Pc), due to FRET. Low FRET efficiencies of 18 and 21 % for ClAlTSPc and ClAlTCPc, respectively, were obtained.
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- Date Issued: 2017
Spectroscopic and electrochemical characterization of thio binuclear phthalocyanine complexes
- Authors: Makinde, Zainab Olusola
- Date: 2017
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/59287 , vital:27541
- Description: Expected release date-April 2019
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- Date Issued: 2017
Spectroscopic and nonlinear optical characterisation of alpha substituted binuclear phthalocyanines
- Authors: Ngubeni, Grace Nomthandazo
- Date: 2017
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/5038 , vital:20757
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- Date Issued: 2017
Synthesis and bioassay of rationally designed DXR inhibitors as potential antimalarial lead compounds
- Authors: Nokalipa, Iviwe Cwaita
- Date: 2017
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/4888 , vital:20740
- Description: Globally, the eradication of malaria has been challenging due to the problem of resistance that past and currently available drugs exhibit. This is exacerbated by the inherent need for anti-malarial drugs to be affordable to the poverty-stricken majority that is primarily affected by this burden. This research has focused on the development of potential inhibitors of 1-deoxy-D- xylulose-5 phosphate reductoisomerase (DXR), an essential enzyme in the mevalonate- independent pathway for the biosynthesis of isoprenoids in Plasmodium falciparum. DXR mediates the isomerisation and reduction of 1-deoxy-D-xylulose-5-phosphate into 2-C- methyl-D-erithrytol 4-phosphate. This enzyme has been determined to be a target for the development of novel antimalarial agents and extensive molecular modelling has been undertaken to develop inhibitors that fit into the DXR active site. The in silico docking data have been used to inform the design and synthesis of various N-benzyl-substituted phosphoramidate ligands that were determined to have potential as novel substrate mimics of fosmidomycin, a known DXR inhibitor. Synthesis of the N-benzyl-substituted phosphoramidate ligands involved a nine-step sequence commencing from diethyl phosphoramidate. In all, some 40 compounds have been prepared, some of them new, and were fully characterized using NMR. Attention has also been given to the mass spectrometric fragmentation patterns exhibited by selected intermediates. Four of the final products were evaluated for in vitro antimalarial activity using a PLDH assay and exhibited IC50 values < 100 µM.
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- Date Issued: 2017
Synthesis and evaluation of arylpyrrole-chalcone hybrids as antiplasmodial and antitrypanosomal agents
- Authors: Zulu, Ayanda Ignatia
- Date: 2017
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/65268 , vital:28716
- Description: Expected release date-May 2019
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- Date Issued: 2017
Synthesis and photophysical studies of crown ether-bodipy dyes and the fabrication of bodipy embedded fluorescent nanofibers
- Authors: Stone, Justin
- Date: 2017
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/4953 , vital:20746
- Description: This study has three major objectives: 1) to synthesize a series of structurally related BODIPY dyes, 2) to fabricate BODIPY embedded electrospun nanofibers, and 3) to investigate and characterize the photophysical properties of all synthesized BODIPY dyes with a special focus on their ability to generate singlet oxygen. This thesis first explores the acid catalysed condensation reaction to produce two structurally analogous meso-substituted BODIPY dyes based on cuminaldehyde and 4-dimethylaminobenzaldehdye. In order to enhance the rate of ISC and promote the generation of reactive oxygen species bromine atoms were then attached to the BODIPY 2,6-positions. These BODIPY dyes were then embedded in a polystyrene solution and electrospun into nanofibers. The resulting nanofibers were found to be highly fluorescent, but were no longer able to generate singlet oxygen. Ion-sensitive BODIPYs were prepared from the dibrominated BODIPY dyes by employing a modified Knoevenagel condensation reaction to form a styryl bond with 4’-formylbenzo-15-crown-5 at the 3,5-position of the BODIPY core. Changes in the morphology and position of the absorption and emission spectra of these crown ether-styryl BODIPY dyes were observed in the presence of sodium ions. These results imply that crown ether-substituted BODIPY dyes could function as ion sensors.
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- Date Issued: 2017
Synthesis and physicochemical evaluation of a series of boron dipyrromethene dye derivatives for potential utility in antimicrobial photodynamic therapy and nonlinear optics
- Authors: Kubheka, Gugu Patience
- Date: 2017
- Subjects: Dyes and dyeing -- Chemistry , Photochemotherapy , Cancer -- Photochemotherapy , Anti-infective agents , Nonlinear optics , BODIPY
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/4776 , vital:20723
- Description: A series of new BODIPY dye derivatives have been synthesized and characterized using various characterization tools such as 1H-NMR, MALDI-TOF mass spectrometry, FT-IR, UV-visible spectrophotometry and elemental analysis. The aniline-substituted BODIPY derivative was further coordinated with gold nanorods and the characterization was achieved by transmission electron microscopy (TEM), X-ray diffractometry (XRD) and X-ray photoelectron spectroscopy (XPS).In addition to this dye, quaternized BODIPY dyes were also synthesized and investigated for their potential utility as photosentitizers in antimicrobial photodynamic therapy (APDT).BODIPY dyes with pyrene substituted styryl groups were embedded in polymer thin film using poly(bisphenol A carbonate) (PBC) to study their optical limiting properties. The optical limiting values of these BODIPY dyes once embedded in thin films were found to be greatly improved and the limiting intensityof each film was well below the maximum threshold which is set to be 0.95 J.cm-². The physicochemical properties and NLO parameters of all of the synthesized dyes were investigated.
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- Date Issued: 2017
Synthesis, characterisation and evaluation of novel ferrocene-thiazole derivatives as antiplasmodial agents
- Authors: Hakizimana, Emmanuel Victor
- Date: 2017
- Subjects: Plasmodium , Malaria -- Chemotherapy , Plasmodium falciparum , Plasmodium -- Inhibitors , Drug resistance in microorganisms , Thiaszoles
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/5304 , vital:20807
- Description: Malaria is mosquito-transmitted disease which continues to pose threat to humanity, despite the efforts undertaken by the scientific community, government entities and international organizations. The major problem is that Plasmodium species have developed resistance against available drugs. In order to counter this problem, antimalarial drugs that are efficacious and with novel mode of action are of great necessity. Thiazole derivatives, in particular aminomethylthiazole analogues, have been shown to exhibit promising antimalarial activity against Plasmodium falciparum strains. Previous studies reported the hit compound MMV010539, which showed good antimalarial activity against both K1 (CQ and multidrug resistant strains) and NF54 (CQ sensitive strain). In this study, MMV010539 was deemed to be as an attractive compound to generate novel analogues by addition of ferrocenyl organometallic unit. The ferrocene based compounds have shown biological activity; and with ferroquine currently in clinical trials there has been increasing research into identifying new ferrocenyl-containing molecules as potential antimalarial agents. Herein, thiazole ferrocene based molecules 3.22a-e were synthesised in low to good yields. Their structural identities were confirmed using conventional spectroscopic techniques (¹H and ¹³C NMR, FT-IR spectroscopy and mass spectrometry). The cell cytotoxicity assay of all final compounds confirmed that all ferrocene-thiazole blends 3.22a-e were non-toxic against HeLa cell lines. However, the in vitro biological assay revealed that despite the absence of cell cytotoxicity these compounds poorly inhibited the growth of Plasmodium falciparum parasite. As the aim was to expand further the structure-activity relationship (SAR) of MMV010539, this study confirmed the previous findings that there is a limited structural modification that could be accommodated as indicated in Figure 3.3 (Panel C). Moreover, the combination of ferrocenyl moiety and various alkylamines resulted in compounds with poor antiplasmodial potency, further suggesting that the free amine (Panel A, Figure 3.3) is important for activity.
- Full Text:
- Date Issued: 2017
Synthesis, characterisation and evaluation of novel ferrocene-thiazole derivatives as antiplasmodial agents
- Authors: Hakizimana, Emmanuel Victor
- Date: 2017
- Subjects: Plasmodium , Malaria -- Chemotherapy , Plasmodium falciparum , Plasmodium -- Inhibitors , Drug resistance in microorganisms , Thiaszoles
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/96068 , vital:31232
- Description: Malaria is mosquito-transmitted disease which continues to pose threat to humanity, despite the efforts undertaken by the scientific community, government entities and international organizations. The major problem is that Plasmodium species have developed resistance against available drugs. In order to counter this problem, antimalarial drugs that are efficacious and with novel mode of action are of great necessity. Thiazole derivatives, in particular aminomethylthiazole analogues, have been shown to exhibit promising antimalarial activity against Plasmodium falciparum strains. Previous studies reported the hit compound MMV010539, which showed good antimalarial activity against both K1 (CQ and multidrug resistant strains) and NF54 (CQ sensitive strain). In this study, MMV010539 was deemed to be as an attractive compound to generate novel analogues by addition of ferrocenyl organometallic unit. The ferrocene based compounds have shown biological activity; and with ferroquine currently in clinical trials there has been increasing research into identifying new ferrocenyl-containing molecules as potential antimalarial agents. Herein, thiazole ferrocene based molecules 3.22a-e were synthesised in low to good yields. Their structural identities were confirmed using conventional spectroscopic techniques (¹H and ¹³C NMR, FT-IR spectroscopy and mass spectrometry). The cell cytotoxicity assay of all final compounds confirmed that all ferrocene-thiazole blends 3.22a-e were non-toxic against HeLa cell lines. However, the in vitro biological assay revealed that despite the absence of cell cytotoxicity these compounds poorly inhibited the growth of Plasmodium falciparum parasite. As the aim was to expand further the structure-activity relationship (SAR) of MMV010539, this study confirmed the previous findings that there is a limited structural modification that could be accommodated as indicated in Figure 3.3 (Panel C). Moreover, the combination of ferrocenyl moiety and various alkylamines resulted in compounds with poor antiplasmodial potency, further suggesting that the free amine (Panel A, Figure 3.3) is important for activity.
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- Date Issued: 2017