Molecular Mechanisms of Oncogenesis & Precision Medicine Approaches for Pediatric Low-Grade Gliomas

Pediatric low-grade gliomas (PLGGs) are a heterogeneous group of tumors that collectively represent the most common childhood brain cancer. Despite favorable outcomes with surgical and adjuvant therapies, majority of patients suffer from long-term treatment-related morbidities and recurrent/inoperable disease. This necessitates a deeper understanding of PLGG biology to aid development of molecular diagnostics and low-toxicity targeted therapeutics. Hitherto, PLGGs have been defined by activating mutations that dysregulate the MAPK signaling pathway, leading to clinical testing of RAF/MAPK inhibitors for PLGGs. Interestingly, recent large-scale sequencing efforts discovered novel gene fusions in PLGGs and we identified the unique recurrent association of tumor suppressor Quaking (QKI) with distinct proto-oncogenes, MYB and RAF1, in different PLGG sub-types. We hypothesized that MYB-QKI and QKI-RAF1 function via novel oncogenic mechanisms invoking a two-hit mechanism of gain-of-function in the MYB/RAF1 oncoproteins collaborating with QKI loss of putative tumor suppressor function, describing for the first time a unique gene fusion setting involving both fusion partners with implications for therapeutic targeting. Utilizing heterologous cell model systems and in vivo mouse models, we found MYB-QKI and QKI-RAF1 are capable of driving oncogenesis. Furthermore, MYB-QKI is a specific driver mutation defining angiocentric gliomas and mediates tumorigenesis via a tri-partite mechanism: (1)MYB oncogenic activation via truncation, (2)rearrangement led enhancer translocation that drives MYB-QKI expression and (3)LOH of QKI tumor suppressor. In contrast, QKI-RAF1 drives some pilocytic astrocytomas via aberrant activation of the MAPK pathway in a QKI-dimerization dependent manner. We also found differential response to RAF targeted therapy in QKI-RAF1, compared to BRAF fusions in PLGGs, due to QKI-mediated dimerization. Hence, our study highlights distinct roles for the same gene, QKI in supporting the oncogenic functions of MYB and RAF1 in different PLGG-gene fusions. Overall, our study has uncovered distinct molecular mechanisms associated with different QKI gene fusions in PLGGs. We show that MYB-QKI is specific to angiocentric gliomas and mediates a unique oncogenic program, and with QKI-RAF1 we demonstrate how mutational context guides differential response to targeted therapy. Therefore, our study has important clinical implications on molecular diagnostics and targeted therapy for these rather understudied class of childhood brain tumors

Study

Wireless sensor networks are successfully used in the conditions of war as well as natural calamities like earthquake, flood, volcanoes etc. Rapid technological advances in the area of micro electro-mechanical systems have spurred the development of small inexpensive sensors capable of intelligent sensing. A significant amount of research has been done in the area of connecting large numbers of these sensors to create robust and scalable Wireless Sensor Networks (WSNs). Proposed applications for WSNs include habitat monitoring, battlefield surveillance, and security systems. WSNs aim to be energy efficient, self-organizing, scalable, and robust. Relatively little work has been done on security issues related to sensor networks. The resource scarcity, ad-hoc deployment, and immense scale of WSNs make secure communication a particularly challenging problem. The primary consideration for sensor networks is energy efficiency, security schemes must balance their security features against the communication and computational overhead required to implement them. This paper will describe the fundamental challenges in the emergent field of sensor network security and the initial approaches to solving them

Design of a Multidimensional Model Using Object Oriented Features in UML

A data warehouse is a single repository of data which includes data generated from various operational systems. Conceptual modeling is an important concept in the successful design of a data warehouse. The Unified Modeling Language (UML) has become a standard for object modeling during analysis and design steps of software system development. The paper proposes an object oriented approach to model the process of data warehouse design. The hierarchies of each data element can be explicitly defined, thus highlighting the data granularity. We propose a UML multidimensional model using various data sources based on UML schemas. We present a conceptual-level integration framework on diverse UML data sources on which OLAP operations can be performed. Our integration framework takes into account the benefits of UML (its concepts, relationships and extended features) which is more close to the real world and can model even the complex problems easily and accurately. Two steps are involved in our integration framework. The first one is to convert UML schemas into UML class diagrams. The second is to build a multidimensional model from the UML class diagrams. The white-paper focuses on the transformations used in the second step. We describe how to represent a multidimensional model using a UML star or snowflake diagram with the help of a case study. To the best of our knowledge, we are the first people to represent a UML snowflake diagram that integrates heterogeneous UML data sources

Photoinduced Synthesis of New Diisochromenochromen-4-ones and Their Antimicrobial Activities

The diisochromenochromen-4-one 3a-3b, 4a-4c, 5a-6a  & 7 have been prepared from the photocyclization reaction of bischromen-4-one 2a-2e. The later compounds are obtained from the O-alkylation of the suitable 3-hydroxy-2-aryl-4H-chromen-4-one 1a-1e with 4,4′-bischloromethyl-diphenyl in dry acetone, anhydrous K2CO3, and PTC (Bu4N+I−) under refluxing conditions. The structures of compounds 2a-2e, 3a-3b, 4a-4c, 5a-6a  & 7 have been characterized from the rigorous analysis of their IR, 1H-NMR, 13C-NMR, ESI-Mass, and elemental analysis. The antibacterial and antifungal activities of the synthesized products were also evaluated against the Klebsiella pneumoniae, Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, Bacillus subtilis, and Aspergillus janus and Penicillium glabrum, respectively. Some of the tested compounds showed significant activity against the above-said microorganisms

Conceptualising Social Value: Perspectives of the Public, Private and Third Sectors in the UK

In present times when economic recession has impacted all the countries in the world to some extent, different approaches have been adopted by governmental and non-governmental organisations to maximise the provision of social benefit. The UK Government, for instance, launched the Social Value Act in 2012 and implemented it in 2013, requiring organisations to create social and environmental value in addition to the economic value during public procurement processes. This act encouraged the collaboration of public, private and third sectors to focus on social value creation for the benefit of beneficiaries. However, the construct of social value remains ambiguous and subjective as it is understood and practiced differently by societal stakeholders, leading to the conduct of this research study. This research study takes a qualitative approach to study the concept of social value within the UK society. The research utilised Q method to understand the construct of social value and interviewed individuals creating social value in the UK to understand the process of social value creation. Results from the Q method indicated four different facets of social value: action-driven, outcomes-driven, sustainability-driven and pluralism-driven social value. The results from the qualitative data provided insights into the process adopted by stakeholders for the creation of social value, which includes three phases: individual and collaborative responses, resource mobilisation and impact on social value creation. Both the studies complemented each other and provided analytical and valuable insight into the construct of social value that can be helpful in future research and/or practice related to social value

Designing and Simulation of a Novel Multiband Antenna for Wireless Communication

ABSTRACT: An antenna is the most important element of any wireless communication. Various antennas for wide band operation have been studied & designed for communication. In this paper, a multibandmicrostrip patch with simple strip line feeding is proposed to support different wireless application. The antenna is fabricated on a FR4 substrate. To obtain multiple bands, multiple square slots are provided with the rectangular patch. The performance of the proposed antenna design is analysed with HFSS(High Frequency Structure Simulator). The relevant antenna performance parameters of the proposed design viz. resonant bands, return loss, gain, and radiation pattern are reported and discussed. The VSWR of the antenna is less than 2 for seven resonant bands in the vicinity of 1.48 GHz, 1.89 GHz, 2.06 GHz ,3.47 GHz, 4.47 GHz, 4.86 GHz and 5.31 GHz. The performance results exhibited by the proposed antenna make it extremely useful for the future generation of wireless broadband communication systems

Reimagining Reproductive Rights Jurisprudence in India: Reflections on the Recent Decisions on Privacy and Gender Equality from the Supreme Court of India

Despite the significant impact of decisions around pregnancy, including abortion, on a woman’s future life and enjoyment of her other human rights, the Indian judiciary has yet to clearly articulate the link between reproductive autonomy and gender equality. Puttaswamy’s recognition of the right to reproductive choice is rooted within the constitutionally protected right to privacy. While the right to privacy has been the basis for ground-breaking judgments on reproductive rights globally, feminist legal theorists have voiced significant critiques as to the limits of privacy, specifically its potential to achieve reproductive autonomy and equality. We explore the applicability of these critiques in India, including concerns voiced by legal scholars regarding the limitations of the right to privacy as a tool for meaningful enjoyment of reproductive autonomy or gender equality as a whole. The post-Puttaswamy decisions of Navtej Johar and Joseph Shine mark a shift in jurisprudence, with the Supreme Court relying on equality-based arguments to reject societal stigmatization and discrimination against the marginalized group in question. In both cases, the court set forth a framework to understand how the rights to privacy, equality, and non-discrimination on the basis of sex and gender intersect. This intersection of rights gives rise to an obligation of states to eliminate laws that reflect discriminatory gender stereotypes, including those pertaining to sexuality. Limits on the right to abortion indirectly or directly marginalize women by controlling their right to bodily autonomy and denying them privacy and equality. Hence, we argue that these cases demonstrate the potential success of arguments for reproductive rights based on equal citizenship. We first lay out the legal framework and jurisprudence of reproductive rights in India before the Puttaswamy decision. We then explore the benefits of having a constitutionally recognized right to privacy and how it can advance reproductive rights. We also examine the drawbacks of using a privacy-based analysis as a foundation for reproductive rights due to its vulnerability to restriction on grounds of compelling state interest. Further, this we engage with feminist critiques of privacy rights as well as equality-based approaches and argue for a framework that takes into consideration meaningful choice and structural barriers to the exercise of reproductive autonomy. We critically examine judgments from comparative and international law that have a strong basis in the right to equality to reflect on how recognition of reproductive rights as an issue of gender justice—beyond just individual choice—could strengthen Indian reproductive rights jurisprudence. In other words, we argue for a reimagination of reproductive rights within an equality framework. Finally, we conclude that the use of an equality-based framework could significantly benefit pregnant persons’ right to reproductive autonomy

A novel approach to track public emotions related to epidemics in multilingual data

Emergence of new epidemic and re-appearance of older diseases causes great impact towards public health. Surveys based techniques which are costly and time-consuming are the most popular methods to measure information related to public health and used in decision making. Early monitoring of these epidemics helps in rapid decision making. Social media platforms provide rich source of information related to public health in forms of blogs, tweets, public posts etc., but these data is in unstructured form contains multiple languages words. This research focused on developing an automatic system for detecting public emotions related to epidemics in multilingual unstructured data to gain deeper understanding of public emotions and health related information. This approach gives timely information related to epidemics, corresponding symptoms, prevention techniques and awareness, which can help government and health agencies for rapid decision making. Experimental analysis of data set provides results that significantly beat the baseline term counting methods used for sentiment analysis