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Home > Development of Novel Radiolabeled Polydentate Ligands As Potential Diagnostic Probes

Development of Novel Radiolabeled Polydentate Ligands As Potential Diagnostic Probes

Thesis Info

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Author

Nadeem, Qaisar

Program

PhD

Institute

University of the Punjab

City

Lahore

Province

Punjab

Country

Pakistan

Thesis Completing Year

2014

Thesis Completion Status

Completed

Subject

Chemistry

Language

English

Link

http://prr.hec.gov.pk/jspui/handle/123456789/1341

Added

2021-02-17 19:49:13

Modified

2024-03-24 20:25:49

ARI ID

1676725883419

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The technetium ( 99m Tc) radiopharmaceuticals have been used for diagnosis of many diseases especially cancer in nuclear medicine for many years ago. Currently, target specific radiopharmaceuticals containing peptides have become more interesting due to increasing the knowledge of receptor binding affinity of specific peptides as well as ease of chemical modification of peptide sequences. Many chelators have been developed as bifunctional chelators for 99m conjugation to peptides as well as for chelation with Tc. Small size chelators are desireable for labeling the small peptides. One of the most important requirements of radiopharmaceuticals is an aqueous phase labeling the biomolecules to 99m Tc. These requirements must meet in order to use for nuclear medicine. In this context, cyclopentadiene (Cp - ) is obviously as a good choice of chelator due to its small size and low molecular weight. The 99m Tc radiolabeled peptide comprising Cp - core have not been synthesized in an aqueous phase. Instead, they have been synthesized by double ligand transfer approach in an organic solvent using harsh reaction conditions which are still not suitable for routing use. In this study we describe the syntheses of half-sandwich complexes of the type [h 5 -Cp(CONH-R)M(CO) 3 ] with M=Re or 99m Tc. The R group represents different tri-peptides which display high binding affinities for oligopeptide transporters PEPT2 and cyclic RGD peptides which have high binding affinity with integrin family receptor. The 99m Tc complexes [(h 5 - CpCONH-R) 99m Tc(CO) 3 ] were prepared directly from [ 99m Tc(OH 2 ) 3 (CO) 3 ] + and Diels-Alder dimerized, cyclopentadienyl derivatized peptides in an aqueous phase. This approach corroborates the feasibility of metal-mediated retro- Diels-Alder reactions for the preparation of not only small molecules but also of peptides for carrying a [(h 5 -Cp) 99m Tc(CO) 3 ] tag. The Diel-Alder products [(HCpCONH-R) 2 ] containing selected peptides were synthesized from Thiele’s acid [(HCp-COOH) 2 ] via double peptide coupling. The peptides of different sequences in this study were prepared through solid phase peptide synthesisxiv (SPPS). The Re-complexes [(h 5 -CpCONH-R)Re(CO) 3 ] were synthesized by attaching [(Cp-COOH)Re(CO) 3 ] directly to the N-terminus amino group of peptides as prepared from SPPS. The authenticity of the 99m Tc-complexes is confirmed by HPLC retention time comparison with the corresponding rhenium complexes, fully characterized by spectroscopic techniques.
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اعلانِ نبوت سے پہلے حضوؐر کا عقیدہ اور ایمان

اعلان نبوت سے پہلے حضورؐ کا عقیدہ اور ایمان
اعتراض نمبر۹۳
ما رگولیس کہتا ہے حضرت خدیجہ ؓ اور آنحضرت ﷺ قبل از نبوت ‘ دونوں سونے سے پہلے ایک بت کی پرستش کر لیا کرتے تھے جس کا نام عزیٰ تھا ۔ ( مارگولیس ۔امہات المو منین ۔۵۹)
۲ ۔انسائیکلو پیڈیا آف اسلام واقعہ غرانیق کے تحت متعدد الزامات تحریر کیے ، اس کے بعد کہا ’’ابتدائی اعتقادات کی جھلک اس طرح بھی نظر آتی ہے کہ عربوں کی طرح انہیں ( محمد ﷺ) بھی جن و شیطان پر عقیدہ تھا ۔ مکہ اپنے حرم کے ساتھ ان کے نزدیک بھی مقدس تھا جن کے تقدس اور رسوم کو انہوں نے اپنے مذہب میں باقی رکھا پھر ایک مرتبہ کفر کی طرف لوٹ جانے کی خواہش نے زور کیا جس پر جلد قابو پا لیا ‘‘۔
جواب: انبیاء اور رسل اعلان نبوت و رسالت سے قبل بھی صفات خداوندی سے آشنا ہوتے ہیں اور ذرا برابر انہیں ان صفات میں شک و شبہ نہیں ہوتا ارشاد ربانی ہے ’’ و لقد الھنا ابراہیم۔۔۔۔۔ عالمین‘‘۔ ’’ترجمہ ‘‘ بے شک ہم نے ابراہیم ؑ کو پہلے ہی سے ان کی شان کے مطابق رشد عطا کیا اور ہم ان کی استعداد کو پہلے سے خوب جانتے تھے ۔‘‘ یہ رشد کیا ہے ؟ سورہ الحجرات میں ہے کہ ’’ رشد قلب میں ایمان و اطاعت خدا وندی کی محبت اور کفر و فسق اور معصیت کی نفرت راسخ ہو جائے اس کا نام رشد ہے ۔ اس سے ظاہر ہے کہ سید نا ابراہیم ؑ ابتدا ہی سے رشد و ہدایت پر تھے یہی حال تمام انبیاء و رسل کا ہے ۔ آپ کا ارشاد ہے ’’ جب میرا نشوو نما شروع ہوا ‘ اس وقت سے بتوں کی شدید نفرت اور عداوت اور اشعار سے سخت...

Pengaruh Ekspektasi Kinerja Dan Risiko Yang Diterima Terhadap Niat Perilaku Menggunakan Mobile Banking Pada Nasabah Bank Syariah Indonesia Cabang Rantauprapat

Penelitian ini bertujuan untuk menganalisis tentang niat konsumen menggunakan teknologi baru, dengan menguji aplikasi mobile banking. Penelitian ini mengukur hubungan antara ekpektasi kinerja dan resiko yang dirasakan terhadap niat prilaku untuk menggunakan mobile banking. Sampel dalam penelitian ini yaitu nasabah Bank Syariah Indonesia (BSI) cabang Rantauprapat. Penelitian ini merupakan penelitian surve dengan pendekatan kuantitatif. Analisis data dalam penelitian ini menggunakan beberapa langkah, meliputi: uji validitas, uji reliabilitas, uji statistik deskriptif, uji confirmatory, uji outlier, uji struktural equation model, serta pengujian hipotesis. Hasil penelitian ini menemukan bahwa ekspektasi kinerja berpengaruh secara positif terhadap niat prilaku nasabah untuk menggunakan mobile banking. Hasil penelitian juga menemukan bahwa resiko yang diterima juga berpengaruh secara positif terhadap niat nasabah untuk menggunakan mobile banking, yang artinya semakin tinggi resiko yang dirasakan oleh nasabah semakin rendah niat nasabah untuk menggunakan mobile banking, penelitian juga menemukan bahwa niat yang tinggi akan berpengaruh terhadap penggunaan mobile banking

Biochemical Characterization of in Vitro Salt Tolerant Cell Lines and Regenerated Plants of Potato Solanum Tuberosum L.

The present investigation deals with the establishment of an efficient in vitro selection strategy to produce salt-tolerant cell lines and subsequent regeneration protocols in potato (cvs. Cardinal and Desiree). The activities of antioxidant enzymes (peroxidase, catalase and superoxide dismutase) and total soluble protein contents of various tissues under stress were evaluated to understand their possible role in salinity tolerance. Exogenous application of ascorbic acid and salicylic acid were also tested for salt stress alleviation. In order to proceed with these objectives, the initial focus was to establish protocols for micropropagation, callus induction and maintenance, plant regeneration, establishment of cell suspension cultures and ex vitro acclimatization of regenerated plants. Three different concentrations of TDZ (10-8, 10-9, or 10-10 M) in MS medium were tested for the purpose of in vitro clonal propagation. MS basal medium fairly supported micropropagation of both the tested potato cultivars followed closely by MS medium supplemented with TDZ (10-10 M). For callus induction and proliferation in dark, internodal segments proved to be a good explant source whereas MS medium fortified with 2, 4-D (18.09 μM) was the best medium composition equally effective for both the potato cultivars. A combination of NAA (2.64 μM) and TDZ (1.00 μM) supplemented to MS medium was the best choice for shoot initiation from callus cultures after 20 and 21 days in Cardinal and Desiree, respectively. Rooting of regenerated shoots was achieved on MS medium supplemented with 8.87 μM BAP, 2.64 μM NAA and 0.123 μM IBA. Cell suspension cultures using friable calluses were developed successfully using MS2 medium for the two cultivars. The best supporting medium for ex-vitro transplantation of potato plants was vermiculite. It was observed in this study that different in vitro growth parameters, i.e., shoot/root length and numbers of roots decreased while number of shoots increased with an increase in NaCl (20-140 mM) concentration in the medium. In Desiree, rosette-type of shoot development initiated at 100 mM whereas in Cardinal it was evident at 120 mM NaCl level. During this investigation, a direct recurrent selection procedure was employed to select salt- tolerant cell lines in potato (Cvs. Cardinal and Desiree) on the basis of sub-lethal concentration of salt. Results have shown more than 50% reduction in relative fresh weight in both the cultivars above 100 mM NaCl. Callus morphology correspondingly changed from off-white to blackish-brown above 100 mM to acutely-necrotic at 140 mM NaCl. Regeneration potential of recurrently-selected callus cultures (100 mM NaCl-treated) on salt- free medium was more pronounced in Desiree as compared to Cardinal. When well- acclimatized recurrently-selected plants were treated with 100 mM NaCl and compared with control plants to check their acquired salinity tolerance, it was observed that recurrently- selected plants showed higher fresh/dry weight and number of tubers in both the cultivars. A slight decrease in protein contents of in vitro Cardinal cultures was observed as the concentration of NaCl (20-140 mM) gradually increased in the media. However, there was an increase in protein contents in Desiree plants when subjected to increasing salt concentrations. In case of in vitro recurrently-selected plants, protein contents were higher as compared to control (non-selected ones) in both the cultivars. The peroxidase activity exhibited a slightly decreasing trend in Cardinal though an increasing one was observed in Desiree with an increasing NaCl level in the medium. In the present investigation, recurrently-selected plants had higher POD, CAT and SOD activities as compared to the control ones in both the cultivars.