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Prediction of Mirna Target Genes in Renal Cell Carcinoma by Using Machine Learning Algorithms

Thesis Info

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Author

Saddam Hussain

Institute

Virtual University of Pakistan

Institute Type

Public

City

Lahore

Province

Punjab

Country

Pakistan

Thesis Completing Year

2019

Thesis Completion Status

Completed

Subject

Software Engineering

Language

English

Link

http://vspace.vu.edu.pk/detail.aspx?id=274

Added

2021-02-17 19:49:13

Modified

2024-03-24 20:25:49

ARI ID

1676721012284

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Renal cell cancer (RCC) is most prevalent type of renal carcinoma found in adults.The association of miRNAs with cancers is confirmed by identifying crucial role in many physiological processes like development, proliferation and death of cells. miRNAs enable the early cancer diagnosis and prognosis by classifying the miRNAs required for cancer diagnosis. Early stage cancer identification is soothing to deal and miRNAs are potentially incredible markers. Researchers looked at expressed miRNAs in the RCC and Scrabbled to create miRNA profiles to submit early detection and successful intervention. The prediction of miRNAs target genes can better understand personalized medicine and the application of machine learning (ML) methods are used to cope with big problems. So, we used Microsoft Azure ML (Platform as a Service) services to design a predictive experiment model with classification algorithms (Naive Bayes and Support vector machine), predictive models are trained and tested by putative datasets downloaded from miRTar.human and consume as web services and office add-ins in MS Excel. These models retrieved predicted information from 11460 results about 620 different miRNAs targeting 164 transcripts with 1695 different position on 20 genes of 14 Chromosome. The results showed that hsa-miR-1273d transcript ABCC2 and MAPK1 (with BC099905 and NM_002745 transcripts respectively), hsa-miR-744* transcript BRAF and BCL2 (with M14745 and NM_000633 transcripts) and hsa-miR-143* transcript PIK3CA, ALOX5, HIF1A, MAPK and TP53.
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آپ ؐ بحیثیت معلم

آپ ؐ بحیثیت مُعلّم
نحمدہ ونصلی علی رسولہ الکریم امّا بعد فاعوذ بااللہ من الشیطن الرجیم
بسم اللہ الرحمن الرحیم
لقد کان لکم فی رسول اللہ اسوۃ حسنہ
صدر ِذی وقار اور میرے ہم مکتب ساتھیو!
آج مجھے جس موضوع پر لب کشائی کی سعادت حاصل ہور ہی ہے وہ ہے:’’آپؐ بحیثیت معلم ‘‘
جنابِ صدر!
’’وہ ہے اسوۂ حسنہ‘‘ اس مختصر وقت میں آپ ؐ کی زندگی کے تمام گوشوں پر روشنی ڈالنانا ممکن ہے میں صرف آپؐ بحیثیت معلم پراظہار خیال کروں گا۔
صاحبِ صدر!
حضورؐ کی سیرت طیبہ پر اگر سرسری نظر ڈالی جائے تو ہمیں وہاں زندگی کی بوقلمونیوں کا ایک حسین و جمیل مرقعّ نظر آتا ہے، وہاں جنگ کی شعلہ بیانیاں بھی ہیں اورصلح کی راحت و رحمت بھی، دشمن نفرت کے انگارے بھی برساتے ہیں اور عقیدت مند اپنی محبت و مودت کے رنگین پھول بھی نچھاور کر رہے ہوتے ہیں۔ ہم نے محبوبِ خداؐ کو حلقہ یاراں میں بھی دیکھا ہے اور حملہ آوروں کے نرغہ میں بھی۔ ہم نے ان کی کاروباری مصروفیتوں کا بھی مطالعہ کیا ہے، اور غارِ حرا میں خلوتوں میں ان کے سوز و گداز کا بھی جائزہ لیا ہے ،ہم نے انہیں اپنے وطن سے بظاہر انتہائی بے بسی اور بے کسی میں ہجرت کرتے بھی دیکھا ہے اور چند سال بعد اس شہر میں فاتحانہ انداز میں داخل ہونے کا منظر بھی ملاحظہ کیا ہے۔ اپنے اہل وعیال کے ساتھ ان کے برتاؤ کا ریکارڈ بھی ہمارے سامنے ہے اور اپنے جاں نثار اور وفا شعار ساتھیوں کے ساتھ حسن سلوک کی تفصیلات بھی ہمارے پیش نظر ہیں۔
جنابِ صدر!
زندگی کے وسیع وعریض میدان کا کوئی کونہ ایسانہیں ہے جہاں حبیب کبریا ؐنے اپنے اسوۂ حسنہ کے حسین و جمیل نقوش نہ چھوڑے ہوں۔ یہ جامعیت، یہ...

الأخلاق الإسلامية في شعر عبد الله بن الـمبارك

‘Abdullah bin al-Mubark was born in Marw’ one of the prime cities in Khurasan, (nowadays in the surroundings of Afghanistan and Central Asia), in the year 118 AH. In addition to his many talents, achievements and abilities, ‘Abdullah bin al-Mubarak was also gifted in literacy, particularly in the art of poetry. He held an eloquent tongue which was recognized by all who conversed with him and his language displayed the nature of someone who had been taught well. Most of the poetry which has been recorded from him is actually his advice to others, whether they were close friends or high-ranking Caliphs and Rulers. The topics spoken of concerned the common issues which had arisen in his time (e.g. Matters pertaining to theology, politics, the worldview, the community etc) and as always, they contained much wisdom and hence the books of history have sealed them and recorded them. This research article discussed    Biography of Abdullah ibn Al Mubarak, The Islamic Ethics in his poetry,    Impact of Rhetoric on his poetry with special concentration on the four kinds i.e. Citation, impact of Quranic words, Quranic pictorial and Quranic style on his poetry.

Linguistic Competence and Self Actualization of Pakistani Postgraduate Research Schoalrs in Psychosocial Perspectives.

The aim of any pharmaceutical dosage form designing is to formulate a product that not only provide the desired therapeutic responses but improve patient satisfaction too. For this purpose, modification in the existing dosage forms has been continued through alteration of additives and the optimization of manufacturing technique to achieve targets. Controlled release (CR) formulations have ability to maintain plasma drug concentration within the therapeutic range for longer duration of time resulting in reduced dosing. The goal of the present study was to prepare once daily valsartan CR 160 mg tablets using swellable hydrophilic and hydrophobic polymers to reduce the fluctuation in plasma level and to sustain steady state over an extended time. Being angiotensin-II receptor blocker, commonly prescribed to manage hypertension. It can also be used in patients of heart failures who cannot tolerate ACE inhibitors or others. Valsartan is commonly prescribed for treatments of left ventricular hypertrophy, isolated systolic hypertension and diabetic nephropathy. Moreover, it is considered an alternative drug to treat myocardial infarction, heart failure, coronary artery disease and systolic dysfunction. In this study different hydrophobic and hydrophilic polymers were utilized to develop valsartan controlled release formulations. They included Methocel® K4M (K4M1- K4M9), K15M (K15M1-K15M9) & K100M (K100M1-K100M9), Ethocel® Standard 7 FP (E7FP1-E7FP9), Kollidon® SR (KSR1- KSR9) and blend of Methocel® K4M & Kollidon® SR (K4M : KSR1-K4M : KSR20). These polymers were used in different concentrations to observe their influence on drug release. Each formulation contained valsartan, rate controlling polymer, Avicel PH 101 and magnesium stearate. Total sixty-five valsartan SR formulations were prepared by CCRD using software Design Expert® (ver. 7.0.). Drug-excipient compatibilities were determined using Fourier transformed-infrared spectroscopy (FT-IR) and no interactions were found between valsartan and various formulation excipients. Powder blend properties (Hausner ratio, compressibility index and angle of repose) and compressed tablets evaluation (weight variation, thickness, hardness and friability) were carried out and found to be satisfactory for formulations of Methocel® K4M (K4M2, K4M3, K4M9), Methocel® K15M (K15M3, K15M6, K15M9), Methocel® K100M (K100M2, K100M3, K100M5, K100M9), Ethocel® Standard 7 FP Premium (E7FP2, E7FP3, E7FP9), Kollidon® SR (KSR2, KSR3, KSR9) and blend of Methocel® K4M & Kollidon® SR formulations (K4M : KSR1, K4M : KSR2, K4M : KSR5, K4M : KSR11, K4M : KSR12, K4M : KSR18 and K4M : KSR20). All trial valsartan formulations were assayed using a validated spectrophotometric and HPLC methods at wavelength of 250 and 264 nm respectively. Assay results of all formulations were found within the official range of 95-105 %. In vitro dissolution of developed formulations were performed in different dissolution media including HCl pH 1.2, phosphate buffer pH 4.5 and 6.8. Desirable drug release profile was achieved by K4M9 formulation (25 % Methocel® K4M) which showed 23 %, 82 % and 100.16 % drug release in 4, 16 and 24 hrs respectively. Higher viscosity grades of Methocel® K15M (K15M3, K15M6 & K15M9) and K100M (K100M2, K100M3, K100M5 & K100M9) excessively sustained the release of valsartan. Excessive control on drug release was exhibited by hydrophobic Ethocel® based formulations (E7FP3 & E7FP9) at various concentrations not showing compliance with the criteria of CR formulation. Although KSR2 and KSR9 formulations of Kollidon® SR (25 % & 32 %) exhibited acceptable drug release (94 to 99 %) profile but having comparatively shorter shelf life in comparison to optimized K4M9 formulation. Excessive retardation in drug release was observed in valsartan CR formulations containing blend of Methocel® K4M & Kollidon® SR at various concentrations. Drug release kinetics of valsartan controlled release tablets were analyzed in various dissolution media using different mathematical models like first order, zero order, Hixon-Crowell, Higuchi, Weibull, Bakers-Lonsdale and Korsmeyer designs. DDSolver® Microsoft Excel based software was used to calculate the regression coefficients and release constants. Among all Methocel® valsartan controlled release formulations, K4M9 indicated higher linearity values for zero order, Korsmeyer-Peppas and Weibull kinetics at pH 1.2, 4.5 & 6.8. Non Fickian or anomalous diffusion release (n > 0.45) was observed showing erosion and diffusion of drug in controlled manner. β value of Weibull model was greater than 1, presenting sigmoid curve which indicated initial slower release followed by a rapid drug liberation. K4M2, K4M3 & KSR2 trial formulations exhibited higher similarity factor (f2) against K4M9 formulation, which was taken as reference due to the best physicochemical characteristics and controlled release profile. Response surface methodology was utilized to demonstrate the effect of independent variables (Polymer and Avicel PH 101 concentrations) on the responses (release of drug at 2, 8 and 16 h). Quadratic model analysis and P-value of coefficients showed strong influence of polymer on responses as compared to Avicel PH 101. Stability of controlled release formulations (K4M2, K4M3, K4M9, E7FP3, E7FP9, KSR2, KSR9 and K4M : KSR11) with desired drug release profiles were evaluated as per ICH guidelines. Samples were analyzed at long term (25±2 oC / 60±5 % RH) and accelerated (40±2 °C / 75±5 % RH) conditions. Swelling behavior of formulations containing Kollidon® SR and Methocel® K4M was also assessed. Results showed Methocel® polymer had the highest hydration ability as compared to Kollidon® SR. Methocel® and Kollidon® SR based valsartan formulations presented variable buoyancy times (< 15 h) without using any gas generating ingredients. With reference to buoyancy values, HPMC (K4M) polymers containing formulations displayed good floating lag time. Formulation K4M9 was selected as the most optimized formulation on the basis of physicochemical characteristics, desired drug release profile and zero order release kinetics among all the other formulations. Reproducibility of the complete adopted methodology was analyzed by preparing three separate lots of the optimized formulation K4M9. In vitro testing was repeated in all dissolution media and the f2 values confirmed the robustness and reproducibility of the developed formulation. A modified and validated HPLC technique was employed for the assessment of valsartan in human plasma. HPLC (LC-20A, Shimadzu, Kyoto, Japan) consisting of auto-sampler SIL-20A, column oven CTO-20A and PDA detector SPDM-20A equipped with Zorbax SB-C18 column (5 μm, 4.6 mm × 15 cm) adjusted at 40 °C was used to obtain chromatographic separation. LC solution software was used for chromatogram generation and data analysis. Mobile phase containing acetonitrile, water and glacial acetic acid in the ratio of 40 : 59 : 1 (pH 2.9) was pumped to the column with a flow rate of 1 mL/min. Each sample of valsartan was eluted at 4.1±0.2 min with a total run time of 8 min. Assay of valsartan was performed after extraction of drug with acetonitrile from plasma using precipitation method. In vivo pharmacokinetics and bioavailability studies of optimized (K4M9) controlled release valsartan tablet (160 mg) against reference immediate release (IR) brand (Diovan®) of same dose were carried out in local healthy subjects. Comparative bioavailability study of valsartan controlled release tablet with immediate release tablets was performed due to unavailability of controlled release brand in commercial market. Following FDA guidelines a single dose, open label, two treatments, two period, cross over pharmacokinetic study was conducted, comprising of twelve healthy young male Compartmental and non-compartmental parameters of valsartan controlled release formulations were computed by Kinetica® (version 5.1) software. Significant difference (P < 0.05) was observed between pharmacokinetics of test and reference tablets. The Cmax and Tmax of the commercial brand and the trial product (K4M9) were found to be 3.062±0.008 μg/mL, 2.396±0.016 μg/mL and 2.597±0.013 h, 5.844±0.027 h respectively. Considerable change in AUC0-t was also observed between reference (23.668±0.330 μg/mL.h) and K4M9 (50.723±0.414 μg/mL.h). The mean residence time of the currently developed formulation was found to be two folds greater than the reference IR tablets. Similarly, the T1/2Kel values of reference immediate release (Diovan®) vs. test controlled release (K4M9) were estimated as 6.023±0.473 h and 11.188±0.720 h respectively. This work focused on the designing of a quality pharmaceutical product with simple, cost effective methodology that could be beneficial for pharmaceutical industries. The findings of the current study will be helpful in the development of the controlled release valsartan tablets by direct compression method using different polymers. The pharmacokinetic evaluation of the newly designed formulation in healthy human subjects assured the steady drug plasma profile in biological system. Therefore, valsartan CR tablets will overcome the drawbacks associated with the conventional immediate release therapy resulting in better patient compliance and drug adherence." xml:lang="en_US