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Home > Identification and Modeling of Regulatory Networks and Development of Anti-Cancer Drug-Conjugated Nanoparticles for Breast Cancer Therapy

Identification and Modeling of Regulatory Networks and Development of Anti-Cancer Drug-Conjugated Nanoparticles for Breast Cancer Therapy

Thesis Info

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Author

Khalid, Sumara

Program

PhD

Institute

National University of Sciences & Technology

City

Islamabad

Province

Islamabad

Country

Pakistan

Thesis Completing Year

2018

Thesis Completion Status

Completed

Subject

Bio sciences

Language

English

Link

http://prr.hec.gov.pk/jspui/bitstream/123456789/12958/1/Samra_khalid_Applied_Biosciences_HSR_2018_NUST_10.08.2018.pdf

Added

2021-02-17 19:49:13

Modified

2024-03-24 20:25:49

ARI ID

1676726389994

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Breast cancer is the second leading cause of cancer-related mortalities among females worldwide. It is genetically heterogeneous disease caused by various environmental and genetic factors. Abnormal expression of various genes/proteins such as chemokine C-X-C motif (receptor 4), insulin like growth factor-1 receptor and estrogen growth factor receptor and their associated biological regulatory networks are linked with breast cancer. In this study, the crosstalk interaction between these genes/proteins and their associated signaling networks involved in breast cancer metastasis were studied by using both in-silico (qualitative modeling, hybrid PetriNet modeling, pharmacophore modeling and virtual screening) and in-vitro approaches (genotyping, cell viability assay, quantitative real time polymerase chain reaction and western blotting). The association of rs1801157 single nucleotide polymorphism, located within the C-X-C motif ligand 12 (CXCL12) gene, with the development of breast cancer was assessed. The results of genotyping showed the significant prevalence of genotype GG (p<0.05) with a number of variables including patient’s age, weight, lymph nodes status, hormonal imbalances (ER and PR) and family history using multivariable logistic regression among Pakistani breast cancer patients as compared to AA genotype. Our in-silico results suggested that rs1801157 single nucleotide polymorphism identified in CXCL12 gene has crosstalk link with insulin like growth factor-1 receptor (IGF-1R) and epidermal growth factor receptor (EGFR) signaling and is an important factor in predicting the outcomes of breast cancer therapy, which can also result in multidrug resistance due to induction of insulin like growth factor-1. Furthermore, to address the problem of multidrug resistance in breast cancer cells, an effective and non-toxic biologically synthesized silver nanoparticles (drug delivery vehicles) were conjugated with anti-cancer inhibitors such as fulvestrant and gefitinib to inhibit the activity of multiple genes and proteins such as estrogen growth factor receptor, C-X-C motif (ligand 12), phosphoinositide 3 kinase, insulin receptor substrate-1, insulin like growth factor-1 receptor, PDZ domain containing 1 and estrogen receptor-α to treat breast cancer cells. In conclusion, for a multifactorial disease like breast cancer, more than one therapeutic targets should be inhibited with an effective drug delivery vehicle to induce apoptosis in cancer cells.
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شیخ احمد علی شوقؔ

جناب شیخ احمد علی شوقؔ

نہایت افسوس ہے کہ کہنہ ادیب و شاعر شیخ احمد علی صاحب متخلص بہ شوق نے ۲۷؍ اپریل کو گونڈہ میں انتقال کیا، مرحوم ۱۸۸۲؁ء اور ۱۸۹۰؁ء کے درمیان لکھنؤ سے ’’آزاد‘‘ نام کا اخبارنکالتے تھے، جو اس عہد کے معزز و مشہور اخباروں میں تھا اور اس زمانہ کے ادباء کا مظہر خیال تھا اور سرسید کی تحریکات سے کافی ہمدردی رکھتا تھا، کئی چھوٹی چھوٹی مثنویوں کے بھی وہ مصنف تھے، اسیرؔ مرحوم کے وہ شاگرد تھے اور غالباً وہ اس خانوادۂ تربیت کی آخری یادگار باقی تھے، انہیں کے عہد میں اردو کی نئی شاعری کا آغاز ہوا، مرحوم ان قدیم شعراء میں تھے، جنہوں نے اس نئے رنگ کے قبول کرنے میں جھجک نہیں کی۔
ترانۂ شوق کے علاوہ ان کی غالباً آخری مطبوعہ مثنوی عالم خیال کے چار رخ اردو شاعری میں ایک نئی چیز ہے، کاش ان کے احباب و اعزہ ان کے کلام کا مجموعہ شائع کرکے انکی روحانی یادگاروں کو زندہ رکھ سکیں۔ (سید سليمان ندوی، اپریل ۱۹۲۵ء)

Development Discourse and Womens Empowerment in Sindh

This research paper investigates and introduces the idea of development discourse and women empowerment question in Sindh. Based on the investigation and analysis of the writings by Sindhi intelligentsia in the Sindhi print media and book publications that present the discourse of development, progress, prosperity, and social change in Sindh, in this paper we engage with and call attention to the question of women empowerment. By integrating women empowerment and rights in this paper, we aim to set the research agenda and draw attention to gender and development theory and practice. In a way, this paper takes up and supports the gender-sensitive research approach to development discourse, public policy, and planning in Pakistan. It prioritizes gender and women's empowerment framework in research, teaching, and development practice.

Theoretical Analysis of the Effective Parameters of Rod Metamaterials

This thesis is dedicated to theoretical characterizing of two component metamaterials as arrays of metal rods/wires periodically immersed in a dielectric isotropic matrix. The rods material is supposed to be non-magnetic. Only a circular cross section case of the rods is considered in the thesis while the rods do not touch each other. At the same time, there is no restriction to the radius of cross section of the rods. The microwave frequency range (from 0 to 5 GHz) has only been considered in this study. The metamaterial media/structures are being considered in the thesis as artificial semiconductors with their own effective complex dielectric and magnetic constants. So, the presented metamaterial media/structures in the thesis are considered as perfect crystals with their own dispersive properties studied in the microwave frequency range. The lattice constant of the crystal is equal to the constant of unit cell of metamaterial under consideration. The characterizations of considered metamaterial structures in the thesis are identified with the study of properties of the effective dielectric and magnetic constants as functions of the frequency (in the GHz frequencies) of incident electromagnetic wave and the volume fraction of metal rods in the unit cell. The above characterizing is the key for defining unusual material properties unavailable in real nature: enhancement of the effective parameters; a possibility to get negative values of the effective parameters; ultra-low values of the refractive index. Throughout the thesis, we consider the initial plane electromagnetic wave that is normally incident to the flat boundaries of the chain. The wave has the magnetic induction vector parallel to the axes of rods while the electric intensity vector is perpendicular to the ones. The above effective complex dielectric and magnetic constants have been obtained for the first time by author of the thesis on base of extension of the case of 2-D infinite metamaterial medium to a slab metamaterial scatterer under consideration through the implementation of the Effective Medium Theory (EMT) in appropriate frequency range. The expressions of the appropriate effective constants for the infinite medium are obtained by other authors. These expressions of the effective constants obtained in this thesis takes in account multipole effects for the case of composite with a very small value of the rods volume fraction while dipole effects are taken in account for the case of large volume fraction values. The accuracy of obtained mathematical models was always benchmarked through a comparison with numerical calculations obtained via the implementations of Finite-Domain Time-Difference (FDTD) method for calculating S-parameters of a metamaterial structure under considerations. S-parameters were used to calculate the effective constants by means of the using Nicolson-Ross approach. All of the numerical experiments presented in the thesis have been carried out with the help of the free Meep FDTD software package while analytical modeling has been done using MatLab software. In this thesis, an improved broadband method for determining complex effective refractive index, dielectric and magnetic constants of an arbitrary passive metamaterial has been proposed. Evaluation of the effective parameters is realized using the reflection-transmission S-parameters obtained by simulation or experimental measurements and analytically evaluated interface reflection coefficient of the slab. In consideration of practical party of this thesis, the obtained qualitative and quantitative results in this thesis have allowed to formulating some properties of two component slab metamaterial structures as arrays of metal rods/wires periodically immersed in a dielectric isotropic matrix: 1. The effective electromagnetic properties of infinite 2-D array of copper cylinders immersed in metal-dielectric matrix in the GHz frequencies shows the existence of the enhancement of effective dielectric constant and low absorption in the microwave frequencies. 2. The obtained analytical models of the composite in the thesis gives a good qualitative but a weak quantitative correlation with results of numerical simulations in the case if cylinders touch each other. 3. The above analytical models of infinite metamaterial medium quantitatively describes well the slabs embedded with the above metamaterial medium if there is some relation between the width of slabs and the dimension of unit cell of the metamaterial medium for appropriate frequency range. 4. The considered artificial material medium can be used to increase the directivity of patch antenna and to obtain ULI structures in the GHz frequency range and to design a new type of waveguides. 5. The obtained mathematical models cannot reveal negative values of the effective dielectric and/or magnetic constants (their real parts) in the GHz frequency range. The main theoretical results of this thesis can be presented by two theoretical methods of characterizing of any 2-D slab metamaterial structures in the microwave frequencies via EMT approach: 1. Non-destructive broadband method for the evaluation of the effective complex dielectric and magnetic parameters of 2-D slab metamaterials. 2. The analytical and numerical optimization method for separating a slab metamaterial into its elementary sub-slabs of the order of the unit cell dimension of the slab. It is important to mention that the above methods have been designed irrespective to the shape of inclusion in the unit cell. Moreover these methods allow to easy evaluating the optical and transport properties of slab metamaterial structures including magnetic ones trough using the relation for the total reflection and transmit ion coefficients and the above constants of single layer. The obtained results in this thesis are in a good quantitative and qualitative agreement with the results of experimental research carried out earlier by one of the supervisors. Moreover these results can be used for creating the course of laboratory works with the using of personal computers for students of Engineer and Sciences directions (Industrial Mathematics, Theoretical Physics, Electrical & Electronic Engineering, Material Science) to study the optical and transport properties of slab metamaterial structures in the microwave frequency range.