Role of Jagged1 in the Enrichment of Cancer Stem Cells in HER2+ Breast Cancer

Purpose: Breast cancer is the second leading cause of cancer-related deaths among women worldwide. Human Epidermal Growth Factor Receptor 2 (HER2) positive subtype of breast cancer is driven by a subpopulation of cells possessing stem cell properties of self-renewal and differentiation, known as Cancer Stem Cells (CSCs). CSCs are implicated in tumor growth as well as radiotherapy and chemotherapy associated resistance. Notch receptors promote breast CSCs survival and self-renewal, and overexpression of Notch ligand Jagged1 predicts poor prognosis. We showed previously that Notch could be an important target in trastuzumab/lapatinib resistant HER2+ breast cancer. Experimental Design: Here, we sought to determine whether anti-HER2 therapy selects for Jagged-1/Notch-dependent CSCs that are responsible for tumor recurrence. Results: The current study describes a novel role of surface expression of Jagged1 in the enrichment of CSCs. HER2 inhibition selects out a subpopulation of cells that i. express higher Jagged1 on the membrane, ii. interact with Notch-1 and Notch-3 and have higher Notch activation, iii. are enriched for CSCs and iv. predict poor overall cumulative survival in women with HER2+ breast cancer. Conclusions: The results demonstrate that HER2 blockade in breast cancer cells enriches a Jagged1 high subpopulation that has higher CSC potential and is resistant to HER2 inhibitors. The implications of this work are that dual blockade of Jagged-1 and HER2 could be more effective than either therapy alone to eliminate both HER2 and Jagged-1 dependent cancer cells

Design and Analysis of a Lift Assist Walker

Walkers provided stability to the elderly but cannot assist a person from sitting to standing. The objective of this project is to present the design and analysis of a lift assist walker. This report discusses the design and analysis of a collapsible lift assist walker capable of lifting a patient up to 250 lbs. from seated to standing in under 10 seconds. The designed walker utilized a two stage scissor mechanism with a gas spring assisted embedded linear actuator

Investigation of Si(1-x)Ge(x) (x ≥ 0.85) Solar Cells for Affordable High Efficiency Solar Energy Conversion

Increasing global demand on energy mixed with climate change is demanding a cleaner, more robust energy source. Moreover, access to low cost energy sources in much of the developing world is essential to sustain human vitality and growth. Thus, solar photovoltaics has come to the forefront of the clean energy realm as one of the most promising energy generation devices. The novel semiconductor material known as Si0.05Ge0.95 has been proposed as an ideal bottom cell (infrared sensitive) as part of a multijunction stack that has the potential to exceed 45% energy conversion efficiency in a low cost format. However, these devices have not been studied experimentally; therefore the devices must be experimentally investigated and the cells’ dependence on material properties and processing must be determined and an optimized process flow must be developed. This has been done via various processing techniques and electrical characterization tools such as lighted current-voltage, quantum efficiency (QE), and energy-dispersive X-ray spectroscopy (EDX), as part of a Department of Energy supported effort. A working device has been produced using a Ni/Ge/Au front contact, which have made ohmic contact to the material without spiking through the junction. An internal quantum efficiency (IQE) measurement greater than 50% within the 1000 – 1600 nm wavelength range has also been measured on the cell. The information obtained thus far has created a pathway forward to substantially increase the IQE within the cell, making it amenable for future integration into a final multijunction solar cell architecture that has a practically achievable efficiency limit of 45%-50%.DoE - FPACEOSU - College of EngineeringNo embargoAcademic Major: Chemical Engineerin

Cytokine release syndrome and cancer immunotherapies - historical challenges and promising futures.

Cancer is the leading cause of death worldwide. Cancer immunotherapy involves reinvigorating the patient\u27s own immune system to fight against cancer. While novel approaches like Chimeric Antigen Receptor (CAR) T cells, bispecific T cell engagers, and immune checkpoint inhibitors have shown promising efficacy, Cytokine Release Syndrome (CRS) is a serious adverse effect and remains a major concern. CRS is a phenomenon of immune hyperactivation that results in excessive cytokine secretion, and if left unchecked, it may lead to multi-organ failure and death. Here we review the pathophysiology of CRS, its occurrence and management in the context of cancer immunotherapy, and the screening approaches that can be used to assess CRS and de-risk drug discovery earlier in the clinical setting with more predictive pre-clinical data. Furthermore, the review also sheds light on the potential immunotherapeutic approaches that can be used to overcome CRS associated with T cell activation

Performance of deep oxidation ditch

Performance of deep oxidation ditc

SHORT REVIEW ON PAIN (VEDANA) BY SUSHRUTA

Pain is an unpleasing sensation and emotional experience that links to tissue damage. It allows the body to react and prevent further tissue damage. It is an unpleasant feeling which only the individual himself can experiences because of that it cannot be objectively defined satisfactorily. However, International Association for the Study of Pain (IASP) defines pain as, “An unpleasant sensory and emotional experience associated with actual or potential tissue damage. It is not just a physical sensation, it is an influenced by attitudes, beliefs, personality and social factors, and can affect emotional and mental wellbeing” which somehow help to define pain. The present study reviewed all the literature related with pain in Ayurvedic literature as mentioned in Sushruta Samhita. The basic aim of this study was to explore briefly and review the concept of pain as per Sushruta Samhita. And for the same various books especially Sushruta Samhita and related supportive books and other web-based articles were reviewed for the better understanding of the concept. Only secondary data were used for writing this article

MUTRASHMARI (UROLITHIASIS): A CASE SUCCESSFULLY TREATED WITH GOKSHURADI GUGGULU

Urolithiasis is a process of resembling stone in urinary tract (In Kidney/Ureter/ Bladder). It is also known as Kidney stone disease. In Ayurvedic literature Urolithiasis is refereed as Mutrashmari. Urolithiasis is very common disease in India, men are more affected than woman and its recurrent rates are very high. The common symptoms of Urolithiasis are Intermittent dull or colicky flank Pain, Painful or Burning urination, Cloudy or foul-smelling urine, blood in the urine and Nausea/Vomiting. In modern system, extracorporeal shock wave lithotripsy, Percutaneous Nephrolithotomy, Retrograde Intrarenal Surgery and Laparoscopic Ureterolithotomy are the surgical option available for big size kidney stone. However, there is no proper internal medication available for small size Urolithiasis but causative factors, clinical features, type and prognosis of Mutrashmari are elaborately described in classical text of Ayurveda. Gokshuradi Guggulu is commonly used herbal medicine in Ayurveda for urinary disorders. Small kidney stones with a diameter of less than 5 millimeters are often flushed out in the urine. But here in this case 4mm kidney stone was creating pain and not flushing out even after more than a week. After medication it was found that the stone easily flushed out in the urine with the help of Gokshuradi Guggulu