Investigating the Impact of Different Acrylamide (Electrophilic Warhead) on Osimertinib’s Pharmacological Spectrum by Molecular Mechanic and Quantum Mechanic Approach

Background: Lung cancer has become the prominent cause of the cancer-related deaths globally. More than 80 % of all lung cancers have been diagnosed with Non- Small Cell Lung Cancer (NSCLC). The USFDA approved osimertinib to treat patients with metastatic T790M EGFR NSCLC on a regular basis in March 2017. Recently, C797S mutation to osimertinib has been reported, which indicates the need for structural modification to overcome the problem of mutation. Objective: In this bioinformatics study, we have evaluated the impact of various acrylamide as an electrophilic warhead on the activity and selectivity of osimertinib. Result: Osimertinib analouge 48, 50, 60, 61, 67, 75, 80, 86, 89, 92, 93, 116 and 124 were the most active and selective compounds against T790M EGFR mutants compared to Osimertinib. Conclusion: These compounds also showed less inclination towards WT-EGFR.

Mood Mechanic

Depression is a major problem being faced by a lot of people. It is the extremely low mood faced by an individual. Some cope up with this mood change very quickly but some drastically fall into it. Those who fall into it suffer from depression. Prediction of a person’s mood plays a major role in treatment of depression. But predicting a person’s mood from previously collected data is challenging. Mood of a person can depend on various factors such body language, facial expressions and current mind state .But mood prediction is not enough, instead the proposed system involves ways in which we can use the predicted data to provide assistance in case of any deviation from a healthy mental condition. Past approaches being used, predict mood considering only a few parameters .This can lead to results being less accurate making it less reliable. A lot of these issues can be handled by the ‘Mood Mechanic’ approach. This paper mainly emphasizes on the existing approaches related to mood prediction and their limitations so as to propose a system that would not only help in efficient prediction but also help in assisting the user of the system on the further actions to be taken based on the predicted results. This approach considers many parameters such as facial expressions, social media usage and self-evaluation results. On collecting all these data and performing analysis on them, the system will suggest the actions or solutions, which will help the person in deciding on tasks which are generally suggested and are necessary for getting better.

Influence of static strength on the fatigue resistance of welds

The present paper deals with a fracture mechanic approach that employs the Resistance-Curve concept, in order to predict fatigue endurances of welded components, with different tensile strengths of the base metal. The Resistance-Curve method compares the total driving force applied to a crack with its threshold for propagation, both defined as a function of crack length. The former depends on load scheme and weld geometry and it can be obtained from finite element analyses, while the second is inherently related to weld resistance. Results obtained herein showed that threshold curve shape is changed when static strength of the base material is modified. Consequently, its interaction with the driving force differed, giving raise to different fatigue endurances for various values of the tensile strength. However, this effect is only likely to be leveraged, provided that the initial crack length is small enough. In real welded structures, the presence of defects demands longer initial crack lengths to be used in calculations, at which the benefit of enhanced strength is minimised or even inverted. Moreover, at these lengths, the growing process is mainly controlled by weld geometry and long crack propagation threshold, whereas local properties become less important in fatigue limit prediction.

Undercut tolerances in industry from a fracture mechanic perspective

Fatigue is an important damage mechanism that particularly affects welded components, since they are likely to present residual stresses, inhomogeneities and stress raisers. Assessment of cyclic load effects on welds has concerned both industries and scientist for decades; unexpected failure must be prevented and at the same time, structures must withstand design loads with minimum requirements of material. All these facts together with economic issues have lead to the creation of normative that rule designing and construction of welded components. Particularly, toe undercuts are generally found in large structures, and large scatter and disagreement exists towards their significance and effects. Documents usually limit only their depth without considering radius, width or length, and there is currently no explanation to that fact. Understanding the damaging process will also help to set less conservative tolerances, with consequent cost reduction due to less demanding inspection. The present paper deals with a fracture mechanic approach that uses the Resistance Curve concept to predict fatigue limit of welded components with undercuts. Results revealed that depth is the most influencing variable, and it can be used as the limiting parameter in design regulations. Moreover, good correlation was obtained with FAT values normally assigned to this kind of defect.

Fatigue Capacity of Steel Cylindrical Bodies and Conduits Subjected to Cyclic Pressure

This paper presents a code review (API 17G, ASME VIII Div 2 and ASME VIII Div 3) for addressing the fatigue capacity of steel cylindrical bodies and conduits subjected to cyclic pressure only. The fatigue capacity for pipes with a yield strength of 75ksi and 90ksi and with rated working pressures (RWP) ranging from 5ksi to 30ksi have been considered using both the S-N approach and the fracture mechanic approach. The S-N based fatigue lives from API 17G are found to be much longer than the corresponding S-N based fatigue lives from ASME VIII Div 2 and Div 3 and by the fracture mechanic (FM) approach as required in ASME VIII Div 3 for vessels where a leak-before-break condition can not be demonstrated. The S-N predicted fatigue lives are found to decrease with increasing RWP while the FM based fatigue lives are found to be rather independent of the RWP. The S-N based fatigue lives from ASME VIII Div 2 and Div 3 for free corrosion conditions are found to be shorter than the corresponding FM based fatigue lives for RWPs ≥ 25ksi and ≥ 20ksi, respectively. Based on this work, it is recommended to establish the fatigue capacity of steel cylindrical bodies and conduits subjected to cyclic pressure using either ASME VIII Div 2 or Div 3. The FM approach is considered to give a lower bound fatigue life as the number of cycles to initiate a crack is disregarded. Guidance on when it is considered applicable to use the API 17G criterion is given in the conclusion section of this paper.