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Ion Energy Spectrum by Velocity Selector Method Using Ssntds

Thesis Info

Author

Naeem Ahmad.

Department

Department of Physics, UET

Institute

University of Engineering and Technology

Institute Type

Public

Campus Location

UET Main Campus

City

Lahore

Province

Punjab

Country

Pakistan

Thesis Completing Year

2005

Thesis Completion Status

Completed

Page

69 . : illus.; diagrs.; tabs. ; 28 cm.

Subject

Physics

Language

English

Other

Hardcover; Includes references

Added

2021-02-17 19:49:13

Modified

2023-01-06 19:20:37

ARI ID

1676712727807

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دل کھول کے اگے رکھ

دل کھول کے اگے رکھ
جانے بھانویں یار نہ ککھ
جے عشق انگاری ہووے
اوہ جاندی اک دن بھکھ
’’اَلعشقُ نار‘‘ آیا
ہن مزہ ہجر دا چکھ
جد حسن انوکھا ہووے
دل ایویں جاندا بھکھ
وچ پانی سوٹا ماریے
اوہ کدی نہ ہوندا وکھ
جیہڑے ہیسن عاشق سچے
اوہو ہو گئے ساتھوں وکھ
نت جادو پئی جگاوے
تیری ہیریاں ورگی اکھ

Cytotoxic Assessment of Quinoline Based Derivatives on Liver Cancer Cell Line Quinoline compounds and their Cytotoxicity

Current scenario of newer diseases with multiple causes has drawn the attention of the researchers in the field of therapeutics and they are now inclined to identify molecules effective for targeted therapy. Objective: Quinoline (1-azanaphthalene); belongs to heterocyclic aromatic nitrogen compound. Some quinoline-based derivatives are also known for their anti-tumor activity. The study was planned to evaluate the cytotoxic potential of quinoline derivatives. Methods: Berberine; a quinoline compound was made part of study to make structural analogs which were docked against potential target proteins. Cytotoxic profiling of all derivatives was done using MTT cytotoxicity assay. Results: The pharmacoinformatic and structure activity relationship studies of analogs were done. The cytotoxic profiles were elucidated by comparing viability rates of analogs treated hepatic cancerous cell line with untreated hepatic cells and untreated mesenchymal stem cells as standards.  Marked cytotoxicity was seen in all molecules at low doses than reported in past studies with relevance to parent compound. Conclusions: The results will be further confirmed through various other cell culture assays targeting different marker proteins, pharmacoinformatics tools and structure activity relationship studies

Study of the Apoptotic Role of Granzyme H Before and After Chemotherapy of Breast Cancer

Breast cancer is the most common type of cancer—related mortality among women world-wide. Physiological changes of the patients were noted. Comparative study of analytical assay of GzmH was carried out in two different methods using serum samples of normal subjects with breast cancer patients of same age, socio—economic background and environmental conditions. One method is by using the substrate PARP and isocoumarin inhibitor. Other one is electrophoresis. It is found that the electrophoretic technique as compared to using substrate can be used for the detection of granzyme H is simple, accurate, and quick and may give better results than enzyme substrate assay. Identification by electrophoresis shows GzmH having a mass of appearance 32 KDa. 3D structure of GzmH was constructed by Modeller 9.0 in order to find out the different sites of granzyme. It showed highest homology with GzmB. The predicted 3D homology models show a conserved two similar domain structure, i.e., an N—terminal domain and a C—terminal domain comprising predominantly of beta—sheet structure with a little alpha—helical content. The basic mechanism of the role of GzmH like other granzymes especially GzmB, showed that the Gzm having two cationic sites; cs1and cs2. These binding sites participate in the binding of Gzm to cell surface thereby Ipromoting its uptake and release from the cytotoxic lymphocytes to the cell cytoplasm of virus or tumor or cell undergo autolysis. In the cell it causes the cleavage of proteins at its specific site like tyrosine or phenylalanine shows chymotrypsin-like activity. This cleavage stimulate the process of proteolysis which may cause the mitochondrial disruption (caspase independent pathway), it is predicted that cystiene residues present near the catalytic residues Ser202 and Cys49 may help in triggering the cell death in a caspase dependent manner. Besides this pathway GzmH may stimulate the conversion of procaspase to caspase which acts on the nuclear protein like Poly-amino ribose polymerase and causes DNA fragmentation that leads to cell death (caspase dependent pathway). However, significant differences between GzmH and GzmB in the X- ray structure and the protein model lie at the important functional sites. In the crystal structure of GzmB the catalytic triad is His57, Ser195 and Asp102, while in GzmH the catalytic triad is His64, Ser202 and Asp108. An ideal peptide present as cs1 site of GzmH. The peptide may promote the conversion of pro-caspase to caspase which successively cause cell death. A segment of Gly214 to Asn220 is present near the catalytic triad of GzmH. This segment may provide a template for substrate binding bulges out of the active site. On the other hand, a hydrophobic patch of Trp238, Ileu239, Lys240 and Arg241 present in the helical form that provides a site for enzyme substrate interaction. IIEnzyme inhibitor study showed that the inhibitor CMK (MAI-Pro-DPN) act as competitive inhibitor for GzmH which totally inhibit the enzyme activity by forming number of H-bonds with catalytic triad. The enzyme inhibitor study may be useful to probe and discuss the disease state with which they are associated. Present study tried to mutate amino acids of granzyme H but only few showed significant effect of mutation e.g., mutation of Lys222→Ala222 & Pro225®Arg225 causes to change their distance with the cs2 which may affect on the stability of cs2. The mutation of Lys222 to Ala markedly decreased the surface accessibility. It is stated that this mutation in turn may affect the uptake of GzmH into target cells; cytoplasmic distribution with reduced accumulation in target cell; and slightly impaired cytotoxicity of GzmH. Arg55 forms number of H—bonds with other amino acids and thereby showed apoptotic promoting activity, present near the peptide of cationic site cs1. It is observed that the mutation of Arg55®Gly55 causes the loss of H- bonds between mutated Gly to Asp57. It is therefore possible that mutation of Arg may affect the cytotoxic activity of GzmH. Mutational effect of Arg116 to Glu also observed. Present study observed that mutation of Arg116 to Glu may lose its H—bonds and salt bridges with Glu115. This shows that the mutation of both Arg55 and Arg116 affects the cytotoxic activity of GzmH. Asp210 is near to the cs2 binding site of GzmH. This mutation from Asp210—Gly210 may affect the H—bonding pattern of cs2 which may reduce IIIbinding to heparin; slightly reduced uptake into target cells; cytoplasmic distribution with reduced accumulation in cell; and in turn may impaired cytotoxicity. It is therefore concluded that GzmH due to its important functional effects may have diagnostic importance and it may be used as a tumor marker in breast cancer.