This study was aimed to develop doxorubicin loaded quaternary ammonium palmitoyl glycol chitosan (DOX-GCPQ) nanoformulation for DOX delivery and non-invasive monitoring of DOX accumulation and biodistribution at tumor site utilizing DOX’s self-florescent property. DOX-GCPQ amphiphilic polymeric nanoformulations were prepared and optimized using artificial neural network (ANN) and characterized for surface morphology by atomic force microscopy, particle size with polydispersity index (PDI) and zeta potential by dynamic light scattering. FTIR and XRD studies were performed to examine drug polymer interaction. The ANN-optimized nanoformulation was investigated for in-vitro release, cellular, tumor and tissue uptake. Since a nanoformulation, on accounts of the smaller size and higher surface to volume ratio alters its biological behavior and encapsulated therapeutic agent, the newly developed nanoformulation-based drug delivery system was also assessed for its toxicity and safety. The optimized DOX-GCPQ nanoformulation was anionic spherical micelles with hydrodynamic particle size of 97.8 ± 1.5 nm, PDI <0.3, zeta potential 28 ± 2mV and encapsulation efficiency of 81 ± 1.5%. Nanoformulation demonstrated a sustained release pattern over 48 h, assuming Weibull model. Fluorescence microscopy revealed higher uptake of DOX-GCPQ in Human Rhabdomyosarcoma (RD) cells as compared to free DOX. In-vitro cytotoxicity assay indicated a significant cytotoxicity of DOX-GCPQ against RD cells as compared to DOX and blank GCPQ (P < 0.05). DOX-GCPQ exhibited low IC50 (1.7 ± 0.404 µmol) when compared to that of DOX (3.0 ± 0.968 µmol). In skin tumor xenografts, optical imaging revealed significantly lower DOX II GCPQ in heart and liver (P < 0.05) and accumulated mainly in tumor (P < 0.05) as compared to other tissues. For toxicological studies, the optimized and characterized DOX-GCPQ was for size, charge, population dispersity, stability, encapsulation efficiency and in-vitro biocompatibility against rat’s whole blood. Apoptosis was studied in Human Rhabdomyosarcoma (RD) cells. DNA damage was investigated in rat bone marrow using in-vivo micronucleus assay. Hemo-, nephro-, hepato- and cardio- toxicities were studied after three dose cycles (6mg/kg each) in DOX vs DOX GCPQ treated mice keeping untreated group as healthy control. DOX-GCPQ demonstrated higher hemocompatibility, significant apoptotic potential as compared to DOX alone. Rat bone marrow examination depicted fewer micronucleus formation after 24 h of single oral dose of DOX-GCPQ (6mg/kg). Significant (P<0.001) decrease in whole body weight and weights of heart, liver and kidney was observed in DOX vs DOX-GCPQ. DOX induced nephron-, hepato- and cardio-toxicities were indicated by significantly (p<0.0001) high serum biomarkers (urea, uric acid, creatinine, ALT, AST, ALP, total bilirubin, CK, CK-MB, LDH); and low antioxidant enzyme (SOD, CAT, GSH, MDH) levels when compared with DOX-GCPQ. Mild vascular congestion in liver and kidney tissues was observed with DOX-GCPQ, while DOX induced vasculature changes coupled with marked vascular congestion, and distorted glomerulus. DOX raised cardiac risk ratio and atherogenic coefficient that modifies lipid metabolism. However, a mild vascular congestion in liver, kidney and heart tissues, nevertheless comparatively lesser than DOX was found with DOX-GCPQ. DOX significantly (p<0.005) reduced serum lipid markers and raised serum electrolytes (p<0.005) in contrast to control. DOX-GCPQ nanoformulation sustained (p>0.005) above parameters. The features of nanoformulation, i.e., small particle size, sustained drug release, enhanced cellular uptake, potential to target tumor passively coupled with the possibility of monitoring of tumor localization by optical imaging may make DOX-GCPQ an efficient nanotheranostic system which may also work as future safe drug carrier system with reduced DOX-induced organ toxicity.
یہودیت میں تاریخ کو بنیادی حیثیت حاصل ہے تاہم جس بے کسی کی زندگی یہودیوں کا مقدر رہی ہے اس سے ان کی تاریخ کا ہر گوشہ متاثر ہوا ہے۔ یہودی فرقوں کی تاریخ کو بھی اس ضمن میں استثنا حاصل نہیں ہے۔ نیز فرقوں کی تقسیم کے بیان کرنے میں بھی یہودی مؤرخین منفرد مزاج کے حامل ہیں، مثلاً پرانے وقتوں میں بارہ یہودی قبائلشمالی اور جنوبی ریاستوں میں بٹ گئے تھے۔ شمالی ریاست میں بتوں کی عبادت کو رواج دیا جانے لگا تھا۔ اول سلاطین میں اس حوالے سے آیا ہے:
۔۔۔ یُربعام نے سو نے کے دو بچھڑے بنوائے۔ بادشاہ یربعام نے لوگوں سے کہا، 'تمہیں یروشلم کو عبادت کے لئے نہیں جانا چاہیے اے اسرائیلیو! یہی سب دیوتا ہیں جو تمہیں مصر سے باہر لائے۔ بادشاہ یُر بعام نے ایک سونے کا بچھڑا بیت ایل میں رکھا۔ اس نے دوسرا سونے کا بچھڑا شہر دان میں رکھالیکن یہ گناہ عظیم تھا۔ بنی اسرائیلیوں نے بیت ایل اور دان کے شہروں میں بچھڑوں کی پرستش کر نے کے لئے سفر کیے لیکن یہ بہت بڑا گناہ تھا۔[1]
شمالی ریاست نے نہ صرف ایک خدا پر یقین کے عقیدے کو بدل ڈالا اور دو بچھڑوں کو معبود بنا لیا۔ ان واقعات کو ایک نئے فرقے کی شروعات کے طور پر دیکھا جا سکتا ہے اس کے برعکس یہودی محققین نہ صرف ان عوامل کو بلکہ موسیؑ، داؤدؑ...
Islam is the complete code of life. The Prophet (PBUH) and his companions made every effort to safeguard it. They handed it over in fully preserved form without any flaw to their true followers. However, adversaries of Islam have been trying to find faults with safety of Quran and the life of Prophet (PBUH). Orientalists are among them. Orientalists are those non-Muslim scholars, who do their research about Muslim’s beliefs, culture and values. Their purpose is to double edge. First to create doubts in the minds of Muslims regarding their religion. Secondly to marsh hated in the hearts and minds of non-believers. This is why these prejudiced scholars criticize Quran and the personal life of Prophet (PBUH). In the following discussion we have analyzed these objections in detail regarding the safeguard of the Holy Quran during the time of Muhammad (PBUH).
Despite significant investments in information technology in developing nations like Pakistan over recent decades, concern still exists over the extent to which such expenditures have produced the intended benefits. At least part of this concern is based around the issue of how information technology and information systems are accepted by the intended users. The Technology Acceptance Model (TAM) provides us with the fundamental frame work to analyse the acceptance of Information Systems from a behavioural perspective. In this study, we intend to enhance and classify the variables of the existing TAM to account for their importance so that organizations and institutions can rely on this classification to focus on the most important variables for quicker and smooth adoption of technology. Especially in the context of developing countries’ dynamics, the technology acceptance variables will be explored. A classification of the technology acceptance variables has been developed. This is the first of its kind classification based on the random Fuzzy (Burney, Ali, & Mahmood, 2012) Forest model, which in comparison with other fuzzy techniques has given better results for classification. To analyse the results, different statistical methods have been used. The study also involves extensive field study as well as data collection and data-mining techniques to analyse and identify multi-dimensional patterns in data. Measures of social influence on/of Information and Communication Technologies (ICT) will also be identified and a suitable Technology Implementation Model will also be developed. For this purpose, the case of smart watch dissemination in Pakistan will be used and appropriate model to enhance user acceptance of smart watch technology will be proposed. This thesis focuses on the acceptance and adoption of smartwatches, specifically in Pakistan. While there are several research studies on the subject of wearable technology, many do not emphasize a specific piece of wearable technology like the smartwatch. Either that or they are focused on the utilization of these wearable products where fitness tracking, healthcare, biometric sensors and other such applications are discussed. It is important that an innovation be understood from the user’s perspective, especially in its Page 3 of 155 early stages when knowledge of consumer requirements is insufficient. Smartwatch studies should be audience driven instead of technology driven which is the situation in most cases. Because the innovation is made for the user therefore should revolve around not what the technology is capable of but if it fulfils the needs and requirements of the users. Hence, this quantitative research aims to fill that gap and identify the factors that influence people’s intention to use a smartwatch along with the discussion of wearable and smart technology, its history, its advantages and disadvantages, different technology acceptance and adoption frameworks as well as their comparison. In addition to that, a model is proposed along with the respective hypotheses to examine the adoption and acceptance of smartwatches and for validation analyses conducted on the data gathered. A classification of the technology acceptance variables has been developed. This is the first of its kind classification based on the random Fuzzy Forest model, which in comparison with other fuzzy techniques has given better results for classification.