SPHINGOSINE KINASE 1 REGULATES FASCIN EXPRESSION TO PROMOTE METASTASIS IN TRIPLE NEGATIVE BREAST CANCER

Distant metastasis is the primary cause of breast cancer–related mortality. To date, effective therapeutic drugs that target metastasis are still lacking. Triple negative breast cancer (TNBC) occurs in high frequency in young women and are more likely to recur and metastasize than are other breast cancer subtypes. Also, TNBC patients cannot benefit from currently available hormonal or targeted therapies, as they lack estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2. Thus, understanding the signaling pathways that promote TNBC metastasis and developing novel therapeutic approaches to target them are critical, in order to prolong the survival and improve the quality of life for these patients. Aiming for fast clinical-translation, I performed bioinformatic analysis of patient-derived TCGA dataset to identify gene targets whose expressions are elevated in TNBC and which also have FDA-approved or in-pipeline pharmaceutical agents for repurposed intervention. Here, I found that sphingosine kinase 1 (SPHK1) was expressed at higher levels in TNBCs patients samples than in other breast cancer subtypes and high SPHK1 expression is associated with poor survival in TNBC patients. Also, TNBC cell lines have relatively higher expression of SPHK1 at both protein and mRNA levels compared to cell lines of other subtypes of breast cancer. In this dissertation, I studied a role of SPHK1 in promoting TNBC progression and metastasis and identified a molecular mechanism by which SPHK1 promotes TNBC metastasis. Overall, this study identifies a targetable molecular axis which plays an important role in TNBC metastasis and provide an opportunity for fast repositioning of available therapeutics for treatment of TNBC metastasis

Importance of Ghrita as Abhyantara Sneha in Vruddhavastha

The prevalence of illness increases as we age; at the same time, life expectancy decreases. Ayurveda, as ancient science has potential for prevention of diseases by health promotion and management of geriatric. Management needs not only curative but also preventive, rehabilitative and terminal care. In Ayurveda, Ghrita is indicated Nityasevaniya Rasayana and also in old age being best among all the Snehas and Vayasthapana. Ghrita plays an important role in controlling Vata Dosha, which is the main causative factor of old age. The presence of Mahabhutas and Gunas in Ghrita helps to maintain the health of old age persons from deterioration. Being best among all the Snehas and Vayasthapana, maintains the normal functions of Doshas, Dhatus, Malas and adds to the essence of Ojas. Therefore Ghrita is considered as par excellence and drug of choice in old age. It is the need of the time to develop an effective holistic aproach for geriatric care by combining Rasayana, Panchkarma and Dietetics, Ayurvedic medicines, lifestyle and Yoga

Efficacy of ProTaper Retreatment System in Root Canals Obturated with Gutta-Percha Using Two Different Sealers and GuttaFlow

Objective. To compare the efficacy of ProTaper retreatment files in removing three different obturating materials. Study Design. Forty-five human, single-rooted premolars were divided into three experimental groups. Group 1 was obturated with gutta-percha and AH Plus sealer, Group 2 was obturated with gutta-percha and zinc oxide eugenol sealer, and Group 3 was obturated with GuttaFlow. Retreatment was done using the ProTaper universal rotary retreatment files. Root halves were visualized using magnifying loops at 3X magnification and optical stereomicroscope at 10X magnification. Images were analyzed using AutoCAD 2004 software to calculate area of the remaining debris in the canal. For statistical analysis were used variance test and ANOVA. Results. Total debris/canal area ratio between the three groups showed a statistically significant difference (P < 0.001). Conclusion. ProTaper retreatment system did not produce completely clean canals in any of the groups. However, it had the best efficacy towards removing silicon based obturating material GuttaFlow

First Principles Study on Structural, Electronic, Elastic and Thermal Properties of Equiatomic MTi (M = Fe, Co, Ni)

We have investigated the structural, electronic, elastic and thermal properties of MTi (M = Fe, Co and Ni) using ab-initio full potential linearized augmented plane wave (FP-LAPW) method within generalized gradient approximation (GGA) and local spin density approximation (LSDA). We have calculated the ground state and electronic properties such as lattice constant (a0), bulk modulus (B), pressure derivative of bulk modulus (B') and density of states at Fermi level N(EF) which are in good agreement with experimental and available other theoretical results. The elastic constants (C11, C12 and C44) and mechanical properties such as Poisson’s ratio (? ), Young’s modulus (E), shear modulus (GH), anisotropic factor (A) are also calculated which are agree well with the experimental and other theoretical results. Ductility for these compounds have been analyzed by Pugh’s rule (B/GH ratio) and Cauchy pressure (C12 - C44). Our calculated results reveals that NiTi is most ductile amongst the MTi (M = Fe, Co and Ni) compounds.Keywords: Ab-initio, electronic properties, elastic properties, thermal properties

Structural, Electronic and Elastic Properties of TMAl (TM=Co, Ni and Ru) Intermetallics: An ab-initio Study

The structural, electronic, elastic, mechanical and thermal properties of transition metal aluminides (CoAl, NiAl and RuAl) have been investigated systematically using first principle density functional theory (DFT). Ground state properties such as lattice constant (a0), bulk modulus (B) and its pressure derivative (B?) are calculated which show well agreement with the experimental and other theoretical results. The electronic properties have been analyzed quantitatively. The values of elastic constants are also reported. The ductility of these compounds has been analyzed using the Pugh’s rule, Cauchy’s pressure (C12-C44) and electronic structure.  Our calculated results indicate that NiAl is ductile while CoAl and RuAl are brittle. The elastic properties such as Young's modulus (E), Poisson's ratio (?) and anisotropic ratio (A) are also reported. We have also correlated the ductility and bonding behaviour of these compounds. Keywords: Density functional theory; intermetallic compounds; electronic properties; ductility; thermal properties

Political Economy of International Climate Finance: Navigating Decisions in PPCR and SREP

This working paper explores how countries can build their own 'climate finance readiness' by understanding their internal political economy and use that understanding to steer consensus-based decisions on climate finance investments. For climate finance to be effective, national leaders must build shared commitments. This involves considering the arguments, incentives and power dynamics at play to ensure priorities are more equitable and representative of a broader group of stakeholders. Doing so will also help to reduce the risk of implementation delays. This paper uses case studies from Bangladesh, Ethiopia and Nepal to explore how narratives and incentives within the political economy drive climate investment outcomes under the Pilot Programme for Climate Resilience (PPCR) and the Scaling up Renewable Energy Programme (SREP). It draws from broader analysis of the discourses around these investments, including 80 interviews with government; multilateral development banks (MDBs) and other stakeholders

A study on the protective effects of calcium channel blockers against anoxic brain damage

Introduction It is now widely accepted that a rapid neuronal influx of Ca2+ following cerebral ischaemia! hypoxia is intimately connected with the cascade of events- including activation of enzymes which give rise to the production of reactive oxygen species and nitric oxide, thereby leading to free-radical induced damage -which reseult in neuronal injury and death. It is also known that a burst of free radical generation I occurs during re-oxygenation of the tissues following a period,ofischaernialhypoxia as also a prolonged purturbation of the membrane functions continues after the perfusion/oxygenation has been restored, which leads to continued accumulnnon of calcium intracellularly ; resulting ultimately in delayed damage and death of the neurone. Estimation of lipid peroxidation products proviqes a reliable estimate of free radical induced damage to tissues, and has been widely used for this purpose

Concept of Shukra Dhatu with special reference to Dhatu Sarata

As roots of tree are very important for maintenance, stability and growth similarly Dosha, Dhatu and Mala (Three bio energies + seven body tissues + three wastes) are very important for maintaining human body. Shukra Dhatu is one of the seven Dhatus in the body. According to them Garbhotpadana (reproduction) is chief function of Shukra Dhatu. Shukra Dhatu is one of Pranayatanas of Sharira. Shukra Pramana (Quantity) of Shukra in human body is half anjali. Well nourished Dhatus give strength to maintain health and immunity. The strength of body and mind can be evaluated by Dhatusarata. Dhatu Sarata is qualitative, quantitative and functional assessment of Dhatus. Shukra Sara person is known to possess unctuous (Snigdha), compact (Samhat) and white (Shweta) bones (Asthi), teeth (Danta), nails (Nakha), and has excessive sexual desire and children (Bahula Kamapraja)

Pharmacotherapy in idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis or cryptogenic fibrosing alveolitis is a form of chronic, progressive interstitial lung disease causing scarring of lung tissue and usually affect adults. Treatment is usually aimed at controlling inflammation and thus slowing the process of fibrosis. With only few patients responding to treatment and the disease being ultimately fatal with poor progression, the underlying lesion was considered to be fibrotic rather than inflammatory. Fibrotic foci, deposition of collagen, and lack of inflammatory cells are a predominant finding. Pirfenidone and N-acetyl cysteine are the only effective pharmacotherapy available till date. Interim results of PANTHER Trial clearly indicate more risk with triple therapy. However, in Indian patients, trial of steroid therapy may be tried when there is doubt of chronic hypersensitivity pneumonitis. BIBF 1120 has also shown positive results in Phase II clinical trial and shows a positive response in deteriorating lung function. Supplemental oxygen, education of patient, pulmonary rehabilitation, and Streptococcus pneumoniae and influenza vaccine are the most important supportive care. Pulmonary rehabilitation should be used as a treatment in the majority of patients

Perceptions of climate change: Applying assessments to policy and practice

The National Climate Change Impact Survey 2016 (NCCIS) asked households across Nepal to recall their individual experiences of short-term weather variations, impacts and their adaptation responses. This paper uses examples from Nepal and elsewhere to explore how survey data based on people’s perceptions can inform understanding and policy-making on climate change impacts, vulnerability and adaptation. We are able to distinguish four areas of policy and practice where such data has made particularly valuable contributions