Anita Goel

7,8-Dihydroxy-4-methylcoumarin induces apoptosis of human lung adenocarcinoma cells by ROS-independent mitochondrial pathway through partial inhibition of ERK/MAPK signaling

Coumarins have attracted intense interest in recent years because they have been identified from natural sources, especially green plants and have diverse pharmacological properties. In this study, we investigated whether 7,8‐dihydroxy‐4‐methylcoumarin (DHMC) caused apoptosis in A549 human non‐small cell lung carcinoma cells (NSCLC) and, if so, by what mechanisms. Here, we show that, in A549 human NSCLC cells, DHMC induces apoptosis through mitochondria‐mediated caspase‐dependent pathway. Although an increase in the levels of reactive oxygen species (ROS) was observed, pre‐treatment with antioxidant showed no protective effect against DHMC‐induced apoptosis. In addition, our immunoblot data revealed that DHMC treatment led to down‐regulation of Bcl‐xl, Bax, p21, Cox‐2, p53 and upregulation of c‐Myc. Results in the present study for the first time suggest that DHMC induces apoptosis in human lung A549 cells through partial inhibition of ERK/MAPK signaling.

Apoptogenic effect of 7,8-diacetoxy-4-methylcoumarin and 7,8-diacetoxy-4-methylthiocoumarin in human lung adenocarcinoma cell line : Role of NF-κB, Akt, ROS and MAP kinase pathway

Coumarin (1,2-benzopyrone) is a naturally occurring fragrant compound found in a variety of plants and spices. Coumarins have attracted intense interest in recent years because of their diverse pharmacological activities. This study examines the antioxidant coumarin 7,8-diacetoxy-4-methylcoumarin (DAMC) and its thiocoumarin derivative 7,8-diacetoxy-4-methylthiocoumarin (DAMTC) for their effect on human non-small cell lung cancer A549 cells. Here we show that both DAMC and DAMTC not only inhibited cell proliferation, but also induced apoptosis with an IC(50) of 160 microg/ml as confirmed by morphological examination, annexin-V assay and flow cytometric analysis. Interestingly, it was observed that these two coumarin compounds exhibited little cytotoxicity towards peripheral blood mononuclear cells but induced apoptosis in malignant cells. DAMC/DAMTC treatment also resulted in pronounced release of apoptogenic cytochrome c from mitochondria to cytosol, alteration of mitochondrial membrane potential (DeltaPsi(m)), and activation of caspase-9 and caspase-3. Although an increase in the levels of reactive oxygen species (ROS) was observed, pre-treatment with antioxidant showed no protective effect against DAMC/DAMTC-induced apoptosis. Results of present study suggest that downregulation of Bcl-xl, Cox-2 and mitogen activated protein kinase pathway and upregulation of p53, Akt and NF-kappaB pathway are involved in the underlying molecular mechanism of apoptosis induction by DAMC and DAMTC in A549 cells.

DAMTC regulates cytoskeletal reorganization and cell motility in human lung adenocarcinoma cell line: an integrated proteomics and transcriptomics approach

DAMTC (7,8-diacetoxy-4-methylcoumarin) is a thioderivative of 4-methyl coumarin, and previously we have shown that DAMTC is a potent inhibitor of cell growth and an inducer of apoptosis in non-small cell lung cancer (A549) cells. It induces apoptosis through mitochondrial pathway by modulating NF-κB, mitogen-activated protein kinase (MAPK) and p53 pathways. Herein, we explored the genome-wide effects of DAMTC in A549 cells using the concerted approach of transcriptomics and proteomics. In addition to apoptotic pathways, which have been validated earlier, the bioinformatic analysis of microarray data identified small GTPase-mediated signal transduction among the significantly altered biological processes. Interestingly, we observed significant downregulation of some members of the Rho family GTPases in the proteomics data too. Downregulation of Rho GTPases (RhoGDIα (Rho GDP dissociation inhibitor-α, also known as ARHGDIA), Ras homolog family member A, Ras-related C3 botulinum toxin substrate 1 and cell division cycle 42) was validated by western blotting. The Rho protein family is implicated in maintaining the actin filament assembly and cell motility, and we also observed that DAMTC treatment causes actin cytoskeletal reorganization, promotes filopodia formation and inhibits cell motility in A549 cells. The effect of DAMTC treatment on cytoskeleton was reversed after the overexpression of RhoGDIα. In addition, DAMTC augmented the apoptotic effect of etoposide, a proapoptotic chemotherapeutic drug. This elucidation of the mechanism behind DAMTC-induced apoptosis and inhibition of cell motility in A549 cells may make it a potential therapeutic for lung cancer.

Probe mechanism for object-oriented software testing

This paper presents a probe-based testing technique that facilitates observing internal details of execution at different levels of abstraction-unit, integration and system levels, during testing of object-oriented software. Our technique adapts probe, an observability measure, to suit the testing needs of object-oriented software. It uses source-code instrumentation, which requires probes to be pre-determined and pre-built in the software during the development phase. Test coverage reports are generated from the information gathered by the executed probes. It includes coverage of probes at probe, method, class, inheritance, regression and dynamic binding levels. During regression testing, our technique helps in the selection of test cases that must be re-executed. Furthermore, the log generated by active probes can be used for post-analysis.

Enhancing MOOC with Augmented Reality, Adaptive Learning and Gamification

Massive Open Online Course (MOOC) is an innovative way of disseminating knowledge to millions of students around the world. Despite being an excellent learning tool with global reach, MOOC has its own set of limitations which results in incredibly low rate of course completion. Conservative techniques of content presentation (fixed video, audio, scripts) lack personalization and interaction. There is a need for MOOC to embrace advanced learning techniques to provide more engaging experience to its learners. This paper delves into three such techniques namely, Augmented Reality, Adaptive Learning and Gamification. It illustrates the positive impact of these techniques in present learning scenario and studies how these techniques are being adopted by MOOC to generate interactive and more engaging content.

Tagging requirements for web application

Tagging systems exist that support tagging of resources, like, web pages, web links, videos, images and blogs. In web applications, use of tag facilitates categorization of related content and improves search within a resource, like, searching a blog or a page. During the development of web application, there is a need for eliciting the requirements for the tagging functionality in the web application. In this paper, we present a requirement checklist for tagging, from the viewpoint of incorporating the tagging functionality in a web application. A use-case based approach has been followed to identify the requirements for tagging. We see that the requirements for tagging vary, depending on the kind of permission provided to the user for the purposes of tagging. Also, there is a need to include resource-specific features. Accordingly, we categorize user requirements based on user-permissions for tagging, and also list the resource-specific features. Our checklist is beneficial both for the web application and the developer during the requirement specification process. During testing, the requirement checklist for tagging is useful for the validation and verification purposes.

Controllability mechanism for object-oriented software testing

We present a controllability mechanism that facilitates creation of difficult-to-achieve states, for execution of state specific tests, during object-oriented software testing. Provisions are made in the software during the design phase and coded during the coding phase of software development. The mechanism requires creating the control environment and incorporating control commands in the software during software development. We illustrate the control mechanism using three examples, each requiring a unique control environment to attain the difficult-to-create states.

Requirement checklist for blog in web application

Blog is a communication tool that plays a key role in a web application. Integration of blog in a web application has resulted in a paradigm shift in the way a web application interacts with the customer. During development of web application, there is a need to elicit and specify requirements for the blogging functionality. In this paper, a requirements checklist for the blog is presented, from the perspective of integrating blog in a web application. The use-case based approach has been used for identifying software requirement for the blog. The requirement checklist helps both the web application and the developer during requirement elicitation of the blog software. The checklist is also useful during the testing phase for validation and verification of the blog functionality.

Towards Adapting Sakai for e-Learning Provider

Massive Open Online Course (MOOC) is an emerging method in online education. Sakai is a popular open source platform widely used by e-learning providers to offer MOOC. Sakai provides a set of collaborative tools for teachers, learners and researchers to support teaching, learning and research. For using Sakai, the e-learning provider needs to customize and adapt the interface of Sakai, like, banner, logo, background color etc. to suit their requirement. This paper presents the development of a tool named SkinChanger that facilitates customizing of Sakai interface, based on need of the e-learning provider. SkinChanger customizes the appearance of Sakai body, header and footer. It facilitates skin changing by providing a user friendly interface. SkinChanger is component-based tool and can be plug-in. This paper illustrates the use of tool to customize the Sakai interface for University of Delhi.

Comparing Infrastructure Monitoring with CloudStack Compute Services for Cloud Computing Systems

CloudStack is an open source IaaS cloud that provides compute, network and storage services to the users. Efficient management of available resources in the cloud is required in order to improve resource utilization and offer predictable performance to the customers. To facilitate providing of better quality of service, high availability and good performance; a comprehensive, reliable, centralized and accurate monitoring system is required. For this, the data needs to be collected from the components of CloudStack and analyzed in an efficient manner. In this paper, we present a detailed list of attributes required for monitoring the infrastructure associated with CloudStack. We identify the processes related with the compute services and its associated parameters that need to be monitored. We categorize the infrastructure monitoring, and list the parameters for monitoring parameters. Further, the proposed list is applied to three monitoring software that are commonly used for monitoring resources and processes associated with CloudStack. Developers and system administrators can benefit from this list while selecting the monitoring software for their system. The list is useful during the development of new monitoring software for CloudStack, as the functionality to be monitored can be selected from the list.