Targeting P53 Gene in Breast Cancer

Infectious diseases and breast cancer rely heavily on p53, a tumor suppressor that protects genetic integrity. It is present on chromosome 17p13 and controls angiogenesis, programmed cell death, and cell proliferation. The expression of p53 and its isoforms is more predictive of treatment outcomes and responses to chemotherapy for breast cancer patients than the presence or absence of TP53 mutations. Subtype-dependent mutations of p53's negative regulator MDM2 can both be signs of p53 deactivation in breast cancer. Targeting both wild-type and p53 mutant across various subtypes of breast cancer is one possible treatment strategy. Notably, through paracrine signaling, mutant p53 in stromal fibroblasts speeds up the formation of breast tumors. In the progression and trajectory of breast cancer, the pivotal involvement of the p53 gene, alongside the bcl-2 proto-oncogene, is noteworthy. Addressing the role of p53 is crucial in the context of breast cancer development and its course

Flow of shale gas in tight rocks using a non-Linear transport model with pressure dependent model parameters

A new source of energy has recently been discovered from unconventional hydrocarbon reservoirs, such as shale gas deposits. Shale gas is found in tight porous rocks which are characterised by nano-scale size porous networks with ultra-low permeability [1,2]. The modelling of transport through such tight porous media is very challenging because it is a relatively new discipline and not much is known but transport processes in them, and little data is available; but it is a growing sector and must be addressed. Here, we apply a recently developed non-linear gas transport model [3], to reservoir simulations of single-phase gas through homogeneous tight rocks. Please download the full abstract below

Time scheduling and optimization of industrial robotized tasks based on genetic algorithms

Today's industrial manipulators are more and more demanding in terms of productivity. This goal could be achieved by increasing speed of the robot manipulator and/or by optimizing the trajectories followed by manipulators while performing manufacturing, assembling, welding or similar tasks. Focusing on the second aspect, this research proposes a method based on genetic algorithms by exploiting CAD (computer aided design) capabilities to optimize and simulate cycle time in performing classical manufacturing tasks. The goal is to determine the shortest distance traveled by the robot manipulator in the coordinate space for every pair of successive points. In addition, our optimization procedure considers supplementary factors such as inverse kinematic model (IKM) and relative position/orientation of the manipulator w.r.t task points. All these factors were statistically assessed to determine both individual and cross influences in finding the optimal solution. The proposed approach has been validated on a real life setup, involving a 6-DOFs (degrees of freedom) industrial robot manipulator when performing a spot welding task on a car body. The obtained results are promising and show the effectiveness of the proposed strategy

Robotized task time scheduling and optimization based on Genetic Algorithms for non redundant industrial manipulators

Industrial robot manipulators must work as fast as possible in order to increase the productivity. This goal could be achieved by increasing robots speed or/and optimizing the trajectories followed by robots while performing assembly, welding or similar tasks. In our contribution, we focus on the second aspect and we target the shortening of paths between task-points. In other words, the goal is to find the shorter traveled distance between different configurations in the coordinate space. In addition to the short distance goal, we aim as well to impose both IKM (Inverse Kinematic Model) and the relative position and orientation of the manipulator regarding the task-points. To this end, we propose an optimization method based on Genetics Algorithms. The method is validated via numerical and graphical simulation, where, results show that the total cycle time required to perform a spot-welding task of an industrial car-body by a 6-DOFs (Degree Of Freedoms) industrial manipulator was drastically reduced

Family preference for the presence of cortical yellow

The population density of the insect on Alorat and fruits located in the lower part of the tree more than the middle part of the plant and insect in one place and demonstrates that there is a nest there were conducted laboratory and field studies on citrus Hsasahanwaa and the Alvdaúaa distribution of cortical insect yellow ...

IRoSim: Industrial Robotics Simulation Design Planning and Optimization platform based on CAD and knowledgeware technologies

This paper presents Industrial Robotics Simulation Design Planning and Optimization platform named IRoSim, which is based on SolidWorks Application Programming Interface (API) to offer an intuitive and convertible environment for designing and simulating robotized tasks. The core idea is to integrate features of mechanical CAD and robotics CAD into the same platform to facilitate the development process through the designed Graphical User Interface (GUI) which permits user friendly interaction. The platform includes various 3D models that are essential for developing any robotized task and offers possibility to integrate new models in simulation. Robotic manipulator library is one such example which contains several types of serial arms with different combinations of revolute and prismatic joints. The platform provides most important steps such as defining the task, CAD learning of the end-effector's trajectory, checking the manipulator's reachability to perform a task, simulating the motion and finally validating the manipulator's trajectory to avoid possible collisions. To demonstrate the efficiency of the proposed approach, two frequent and important tasks (spot welding and painting) using a 6-Degree Of Freedom (DOF) industrial robotic manipulator have been considered. The output of the proposed strategy provides collision-free trajectory of the manipulator's motion which can be directly mapped to a real site. Moreover, the approach permits addressing the problems related with the real implementation of robotized tasks

Assessment of Weight Management Practices among Adults in the United Arab Emirates

With a rise in global incidence of overweight and obesity, the number of patients seeking weight management (WM) advice is likely to increase. Our aim was to explore the prevalence of WM practices and investigate association of WM goals with sociodemographic variables and practices among United Arab Emirates (UAE) adults. An exploratory, cross-sectional research was conducted on 1275 adult males and females, residing in UAE. A structured questionnaire was administered. WM goals to lose/maintain/gain weight were reported in 88.3% participants. WM goals were significantly associated with age, sex, marital status, education, current body weight perception, and medical condition. Out of 21 selected WM practices, popular strategies included increasing physical activity (52.9%), eating less fat (51.1%), consuming fewer calories (43.3%), joining gym (27.5%), skipping meals (26.1%), and consuming natural herbs and teas (20.7%). Visiting dietitian (12.3%) ranked ninth in the order of preference. Males focused on physical activity, gyms, and wellness centers and females on calories counting, dietitian visits, meals replacement, skipping meals, and natural herbs/teas. Married adults reported eating less fat (54.3% versus 47.3%, p=0.020); singles opted calories counting, gyms, and meals replacement. Frequent referral sources were friends (37.8%) and Internet (32.1%). Most UAE adults had WM goals that were associated with sociodemographic variables and WM practices. Awareness about the ill-effects of unhealthy WM practices and importance of dietitian’s consultation are imperative

Design, synthesis, anti-inflammatory evaluation, and molecular modelling of new coumarin-based analogs combined curcumin and other heterocycles as potential TNF-α production inhibitors via upregulating Nrf2/HO-1, downregulating AKT/mTOR signalling pathways and downregulating NF-κB in LPS induced macrophages

AbstractPersistent inflammation contributes to various inflammatory conditions. Inflammation-related diseases may be treated by inhibiting pro-inflammatory mediators and cytokines. Curcumin and coumarin derivatives can target signalling pathways and cellular factors to address immune-related and inflammatory ailments. This study involved designing and synthesising three series of coumarin-based analogs that incorporated curcumin and other heterocycles. These analogs were evaluated for their potential as anti-inflammatory agents in LPS-induced macrophages. Among the fourteen synthesised coumarin derivatives, compound 14b, which contained 3,4-dimethoxybenzylidene hydrazinyl, demonstrated the highest anti-inflammatory activity with an EC50 value of 5.32 μM. The anti-inflammatory effects of 14b were achieved by modulating signalling pathways like AKT/mTOR and Nrf2/HO-1, and downregulating NF-kβ, resulting in reduced production of pro-inflammatory cytokines such as IL-6, IL-1β, and TNF-α. The modelling studies revealed that 14b and dexamethasone bind to the same TNF-α pocket, suggesting that 14b has potential as a therapeutic agent superior to dexamethasone for TNF-α

Obesity, Inflammation, and Mortality in COVID-19: An Observational Study from the Public Health Care System of New York City

Severe obesity increases the risk for negative outcomes in patients with coronavirus disease 2019 (COVID-19). Our objectives were to investigate the effect of BMI on in-hospital outcomes in our New York City Health and Hospitals’ ethnically diverse population, further explore this effect by age, sex, race/ethnicity, and timing of admission, and, given the relationship between COVID-19 and hyperinflammation, assess the concentrations of markers of systemic inflammation in different BMI groups. A retrospective study was conducted in hospitalized patients with COVID-19 in the public health care system of New York City from 1 March 2020 to 31 October 2020. A total of 8833 patients were included in this analysis (women: 3593, median age: 62 years). The median body mass index (BMI) was 27.9 kg/m2. Both overweight and obesity were independently associated with in-hospital death. The association of overweight and obesity with death appeared to be stronger in men, younger patients, and individuals of Hispanic ethnicity. We did not observe higher concentrations of inflammatory markers in patients with obesity as compared to those without obesity. In conclusion, overweight and obesity were independently associated with in-hospital death. Obesity was not associated with higher concentrations of inflammatory markers