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سلطان کھاروی دی گیت نگاری

سلطان کھاروی دی گیت نگاری

’’گیت ہندی زبان دالفظ اے جیدے معنی نیں راگ، سنگیت، بھجن ، سرور وغیرہ۔‘‘(۱)

ایس لئی گیت تے سنگیت دا آپو وچ گوہڑا سمندھ اے جتھے گیت اے اوتھے سنگیت اے تے جتھے سنگیت ہووے گا اوتھے گیت وی ہووے گا۔ گیت دراصل من دیاں ڈوھنگایاں چ جنم لین والے جذبیاں تے احساساں دے آپ مہارے پر گھٹاوے داناں اے ۔ جیہدے وچ سادگی، سلاست تے روانی مکمل درجے تک موجود ہوندی اے۔ ایسے پاروں آکھیا جاندا اے کہ گیت کوتا دا اک اجہیا روپ اے جو دلاں دیاں اتھا ڈوھنگایاں وچ پیدا ہوندی اے، تے دلاں دیاں اتھاہ ڈوھنگایاں تیک اثر کردی اے ۔ گیت کیول جذبیاں دے اظہار دا ناں ہی نہیں بلکہ ایہدے سرنانویاں وچ بڑی وسعت تے ون سونتا پائی جاندی اے۔نظم وانگوں گیت نوں وی خاص موضوع تیک محدود نہیں رکھیا گیاسگوں نظم جذبہ تے احساس دیاں نکی توں نکی کیفیتاں گیت دا موضوع بن سکدیاں نیں۔ ایس لئی عشق تے محبت ، کوشش تے محنت ، قومیت ، حریت رزم تے بزم ، کرم تے ظلم ، ہجر تے وصال ، جذبہ تے خیال، حسن تے جمال، عشق بے مثال ،ہراوہ شے جیڑی انسانی احساس دا حصہ اے گیت دا موضوع بن سکدی اے۔گیت بارے ڈاکٹر وزیر آغا لکھدے نیں:

’’گیت کا امتیازی وصف یہ ہے کہ ماں ، زمین یا معاشرے کے باطن میں پیدا ہونے والی کروٹ کا علم بردار ہے۔ اسی لیے گیت میں زمین سے وابستگی بہت توانا ہے۔ مثلاًگیت کی آواز میں دھرتی کی بہت سی دوسرے آوازیں شامل ہوجاتی ہیں۔ جسے کوئل کی کوک،مینا کا ترنم، بھنورے کی گھن گھن وغیرہ۔(۲)

سلطان کھاوری پنجابی زبان دے اچ کوٹی دے کوی نیں...

Digital Marketing and Creative Economy Theory in Economic Development During the Pandemic

Changes in the world require a company to make innovations that are necessary in order to survive the onslaught of other companies' innovations, especially similar companies. A new economic concept that focuses on information and creativity that relies on creative ideas and knowledge from human resources for the main production factors. Creative economynowadays it is increasingly being carried out by the people, especially the younger generation in country because they feel this is a profession that is suitable to be done. Information technology is also needed in the distribution, promotion and sales transaction processes so that the process runs more effectively and efficiently. The potential for the development of this industry is due to several factors, namely the development of information technology as the main factor develops rapidly, access to information centers via the internet is much easier, the social innovation process runs smoothly, each region has a unique local cultural potential and the openness of society to modern culture, there are sources of knowledge such as many campuses that are a source of quality human resources, have high creativity and innovation.

Combined Ligand and Structure Based Studies on Modulators of Akt Kinases

Protein kinase B (PKB/Akt) belongs to the AGC superfamily of related serine/threonine kinases with three structurally homologous mammalian isoforms, Akt1 (PKBα), Akt2 (PKBβ), and Akt3 (PKBγ). Akt isoforms emerged as anti-cancer drug targets because of their constitutive hyperactivation in various oncological disorders. However, due to high intra-family similarity within ATP binding region, the development of isoform-selective modulators of Akt represent a challenging endeavor and thus, until now only a handful of compounds were selected for the clinical investigation. Yet none of them could reach the market for routine clinical use due to their off-target toxicity and poor pharmacokinetic properties. Recent reports on achieving isoform selectivity by designing inhibitors against less conserved pleckstrin homology (PH) domain offer the opportunity to reduce the major off-target toxic effects of Akt antagonists. Therefore, in this thesis, combined ligand- and structure-based in silico strategies have been utilized to probe the key structural features for the inhibition of the PH domain of Akt2 which is more commonly overexpressed in solid tumors. Toward this end, various predictive 2DQSAR (two-dimensional quantitative structure-activity relationship) and GridIndependent Molecular Descriptor (GRIND) and pharmacophore models using structurally diverse data set of 111 quinoline analogs have been developed. Our key findings demonstrate that the presence of three hydrogen bond donors (D1-D3) at a molecular distance of ~8.4, 21.6, 16.8 Å between D1–D2, D1–D3 and D2–D3, respectively is important for selective inhibition of PH domain of Akt2. In addition, our docking results indicated a crucial role of Lys30 for the optimal fit of quinoline-type inhibitors within the binding cavity of the Akt2 PH domain. Moreover, the structurebased pharmacophore model exhibited three hydrogen bond acceptors (A1-A3) at a distance of 4.05 Å (A1-A2), 11.58 Å (A2-A3) and 15.33 Å (A1-A3) that are complementary to the molecular distances identified by GRIND which further validate the reliability of our developed models. Additionally, identified hits through pharmacophoric-based virtual screening provided a new arsenal of potentially selective chemical scaffolds which have a broad structural diversity and less chemical similarity to any of the other known Akt2-PH domain inhibitors. Subsequently, selectivity profiling with the help of proteochemometric modeling revealed essential substructures such as Nmethylpent-3-en-2-amine for selective inhibition of Akt1, methylene amine, isoproenylterazol and 2H-tetrazole for Akt2, and formaldehyde hydrazine for the Akt3 selective inhibition. The present work also illustrates the substructure based similarity search of ChemBridge database to identify Akt2-selective hit compounds. In the present study, one of the selected carboxamide-type hit showed 1.2 and 2.1 fold selectivity against Akt2 as compared to Akt1 and Akt3, respectively. Overall, the work described in this thesis could pave the way towards the identification of potential modulators of Akt2 against cell proliferation in cancer with high isoform-selectivity and limited side effects.
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