The catastrophe Zika virus infused in South America including Brazil and other Caribbean countries obliterated the lives and health of the inhabitants. The neonatal health was badly infected as microcephaly come out the distinctive character of this grave viral attack. The need of the hour is to dive deep in the melancholy and find out robust scientific and advanced techniques both horizontally and vertically which ward off the next generations interim of antiviral drugs and preemptive measures. Due to congenital microcephaly and Guillain-Barre syndrome in human, Zika virus has been gaining attention from scientists. The Zika virus is amongst Flaviviruses like Dengue virus, Japanese encephalitis, Yellow Fever virus, Thick Warm virus and West Nile virus. These are mosquitoes borne human pathogens specially species Aedes aegypti. There are numerous proteins responsible for the pathogenesis of virus including seven of the NS proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B and NS5) which are integral part of replication complex, located at the cytoplasmic side of the endoplasmic reticulum membrane. Among these proteins three were selected as drug targets to halt virus infections. Availability of the X- ray crystal structures of Zika virus proteins enabled structure based drug design efforts. First drug target was lipid containing glycosylated NS1 that makes a homodimer inside the cells while its secretion take place inside the extracellular space as hexameric lipoprotein. This leads to the evasion of immune system and causes pathogenesis through establishment of interaction with components from both innate and adaptive immune system as well as other host factors. The second drug target was NS3 helicase protein triggered pathogenesis through replication of RNA and it depends upon ATP. NS3 is one of the most thoroughly studied antiviral drug targets. The enzymatic activity is coupled with the C-terminal region of the nonstructural protein NS3 in Flaviviruses, namely an RNA helicase (NS3-Hel) concerned in genome replication and RNA synthesis. The third target was NS5 protein which is distinctive among other RNA viruses because it contains a fused domain composed of two terminals an Nterminal RNA methyltransferase (MTase) domain and a C-terminal RNA-dependent RNA polymerase (RdRp) domain. The N-terminal MTase domain is responsible for 5′capping and thereby stabilizes the viral RNA genome, while the C-terminal RdRp domain is critical for viral RNA replication and beleaguered for inhibition. The above mentioned non-structural proteins were selected for molecular docking study while following various classes of compounds comprising flavonoids, 1,4-benzothiazene analogues and non-nucleoside inhibitors were selected for molecular docking. The docking results obtained would be exploration in the development of novel potent inhibitors because of the predicted adequate theoretical binding affinities. The molecular docking results were further corroborated with molecular dynamics simulation study including RMSD, RMSF, Rg, HB, P.E, MM/PBSA and PCA results which abetted in the finding of binding modes of inhibitor into the pocket and consequently used to incorporate flexibility in both components of complex which sturdily confirmed and supported the docking study. Besides, Zika virus another deadly virus is Ebola virus (EBOV) and it is a filamentous, enveloped, non-segmented, negative–strand ribonucleic acid (RNA) virus which belongs to family Filoviridae. Ebola virus includes different glycoproteins each of which plays their roles in different aspects of viral life cycle. The secreted glycoprotein (sGP) is a nonstructural protein with a single frame and has total 364–372 residues. Towards the N-terminal 295 residues which also include the signal sequence are similar with full length GP. It differs in the length of C-terminal sequences. The secreted glycoprotein is essential for virology therefore, it can be a decent drug target for the development of novel inhibitors. The lack 3D crystal structure of secreted glycoprotein is big hurdle in designing of drugs against Ebola virus. Therefore, In silico techniques were used to build model including homology modeling and built model was refined through simulation. Furthermore, docking was done through known classes of antiviral drugs and results were found satisfactory.
دس بارہ گھنٹے کی طویل مسافت کے بعد شرم الشیخ سے قاہرہ پہنچے ۔کانفرس کے مندوبین مختلف مقامات پر بس سے اترتے گئے ۔دکتورمجید،دکتورہ رعشہ،دکتورہ شائمہ، دکتوریحی ٰ ایک ساتھ اترے ۔دکتورہ مونا جو الازہر یونیورسٹی میں اردو کی استاد ہیں جنھوں نے ڈاکٹر مبارک علی کی کتاب پاکستانی معاشرے میں گھٹن اور خواتین کے استحصال پر اپنا مقالہ پڑھا تھا ،جس پر سوال و جواب کے سیشن میں میری طرف سے شدید تنقیدی گفتگو ہوئی تھی اور کانفرس کے باقی ایام میں و ہ مجھ سے کنی کتراتی تھیں، نے بھی آج بس سے اترتے ہوئے چہرے پر خفیف سی مسکراہٹ لا کر آواز دی ’’اﷲ حافظ یا دکتورالطاف‘‘ دکتورہ بسنت کا گھر بھی ہماری رہائش سے پہلے آیا ،انھوں نے مجھے دکتورمحمود کے حوالے کیا اور خود اگلے دن شام کو ملنے کا وعدہ کر کے بس سے اتر گئیں ۔دکتورہ ایمان کو لینے ان کے بھائی وقت پر نہ پہنچ سکے تو ہمارے ساتھ ٹیکسی میں سوار ہو گئیں ۔ایمان کا گھر عسکری فلیٹس میں تھا جہاں قدرے خوشحال لوگ رہتے تھے ،میں نے پوچھا کہ آپ کے شوہر فوج میں ہیں ؟اس نے کہا نہیں وہ سعودی عرب میں ملازمت کر رہے ہیں ۔باقی عربوں کی نسبت مصری زیادہ ہنر مند اور جفا کش ہوتے ہیں ۔ان کا المیہ یہ ہے کہ دورِ فراعنہ سے لے کر عصرِحاضر تک مطلق العنانی اور مارشل لائی طرز حکمرانی نے حاکموں کو مالدار اور عام مصریوں کو غریب تر بنا دیا ہے ۔
One of the main arguments that Allah has made in the Quran about the authenticity of this last book is that the Quran is free from all kinds of contradictions and differences. Whoever interprets the Quran, the authenticity of the Quran has become clearer on it. Different forms of language and literature are adopted in the Quran. If one is not familiar with the Quranic verses or does not have access to the truth of the words or is unfamiliar with the reality of the ayah, it may be possible to feel the contradiction in some places, when in reality it is not.
In structures or machine components, fatigue failure is very common. It is initiated by a small defect which leads it to a catastrophic failure. The material defects, inclusion, impurities and machine operation can always be vulnerable to crack initiation and hence fatigue cannot be avoided. In metallic structures, the thermal loads can also alter the material properties such as young’s modulus, tangent modulus, yield stress, and ultimate tensile strength, etc. Consequently, in the presence of increasing temperature, it can be inferred that the material might become soft near the vicinity of the crack tip, which can lead to increase the size of the plastic zone under the same mechanical loads. Therefore, it is very complicated to estimate the retardation or acceleration of fatigue crack propagation under thermo-mechanical loads. This research investigates the interdependencies of crack depth and crack location on the dynamic response of a non-prismatic cantilever beam under thermo-mechanical loads. Temperature can influence the stiffness of the structure, thus, the change in stiffness can lead to variation in frequency, damping and amplitude response. These variations are used as key parameters to quantify damage of Aluminum 2024 specimen under thermo-mechanical loads. Experiments are performed on non-prismatic cantilever beams at non-heating (room temperature) and elevated temperature, i.e., 50°C, 100°C, 150°C and 200°C. This study considers a non-prismatic cantilever beam having various initially seeded crack depth (0.5 mm to 2.5 mm) and crack of 0.5 mm with natural propagation under load located at various locations, i.e., 5%, 10% and 15% of the total length from fixed end, respectively. The analytical, numerical and experimental results for all configurations are found in good agreement. Using available experimental data, a novel tool is formulated for in-situ damage assessment in the metallic structures for the first time under thermo-mechanical loads. This tool can quantify and locate damage using the dynamic response and temperature including the diagnosis of subsurface cracking. It fits around 82% of available data for validation within 10% of prediction error against a small change in the response parameter. The obtained results demonstrate the possibility to diagnose the crack growth at any instant within the operational condition under thermo-mechanical loads.