Abstract

We developed a set of conformationally locked molecules each of which makes a single CH⋯O H-bond/short contact and has different electron density at the acceptor oxygen atom. The downfield shift of the 1H NMR signals due to the hydrogen involved in the CH⋯O H-bond varied from 0.93–1.6 ppm, and the magnitude of Δδ is in correlation with the hybridization state of the acceptor oxygen and with the CH⋯O H-bond strengths quantified using a computational method.

Abstract

Urea-assisted denaturation of protein and RNA has been shown to be a valuable tool to study their stabilities and folding phenomena. It has been shown that stacking interactions between nucleobases and urea are one of the driving forces of denaturation. In this study, the ability of urea to form unconventional stacking interactions with RNA bases is investigated by performing high-level quantum calculations (RI-MP2/aug-ccpVDZ level) on a few thousands of model systems. Four systems were considered based on the RNA nucleobases (GUA, ADE, CYT, and URA) for the investigation. For each system, a set of models were designed to study the role of hetero-atoms/groups of the nucleobases on stacking interactions with urea moiety with respect to every possible pair. Several plane-parallel complexes were generated with urea on top of aromatic systems to exhaustively study all possible factors for urea-nucleobases stacking interactions. Energy decomposition analysis (EDA), atoms in molecules (AIM) and natural bond orbital (NBO) analysis were performed to gain better insights on non-covalent stacking interactions. Dispersion component was found to be heavily stabilizing, while the EHF was found to be repulsive for all the four systems indicating lack of hydrogen bonding (HB) type interactions and presence of dispersion type interactions. Amide and carbonyl groups of urea molecule were found to play a major role in favourable stacking interactions. We demonstrate that along with functional groups present on the nucleobases, the orientation of urea molecules plays a vital role in stabilizing the urea-nucleobase non-covalent interactions. The proposed study quantifies and provides a comprehensive theoretical description of urea nucleobase unconventional stacking interactions which helps to unravel urea driven RNA unfolding mechanism.

Abstract

We compute the top quark threshold contributions to the γγ production at the LHC. They appear when the invariant mass of the photon pair, Mγ γ just exceeds two times the mass of the top quark and induce some feature in the Mγ γ distribution. We determine the magnitude of this threshold effect and characterize this feature with a simple empirical fitting function to show that it is possible to observe this effect at the LHC in future. We also explore some possible improvements that may enhance its significance.

Abstract

Alzheimer’s disease (AD) is a neurodegenerative disorder contributing to rapid decline in cognitive function and ultimately dementia. Most cases of AD occur in elderly and later years. There is a growing need for understanding the relationship between ageing and AD to identify shared and unique hallmarks associated with the disease in a region and cell-type specific manner. Although genomic studies on AD have been performed extensively, the molecular mechanism of disease progression is still not clear. The major objective of our study is to obtain a higher-order network-level understanding of ageing and AD, and their relationship using the hippocampal gene expression profiles of young (20-50yrs), ageing (70-99yrs) and AD (70-99yrs). The hippocampus is vulnerable to damage at early stages of AD and altered neurogenesis in the hippocampus is linked to the onset of AD. We combined the weighted gene co-expression network and weighted protein-protein interaction network-level approaches to study the transition from young to ageing to AD. The network analysis revealed the organization of co-expression network into functional modules that are cell-type specific in ageing and AD. We found that modules associated with astrocytes, endothelial cells and microglial cells are upregulated and significantly correlate with both ageing and AD. The modules associated with neurons, mitochondria and endoplasmic reticulum are downregulated and significantly correlate with AD than ageing. The oligodendrocytes module does not show significant correlation with neither aging nor disease. Further, we identified ageing- and AD-specific …

Abstract

In response to developmental and environmental conditions, cells exit the mitotic cell cycle and enter the meiosis program to generate haploid gametes from diploid germ cells. Once cells decide to enter the meiosis program they become irreversibly committed to the completion of meiosis irrespective of the presence of cue signals. How meiotic entry and commitment occur due to the dynamics of the regulatory network is not well understood. Therefore, we constructed a mathematical model of the regulatory network that controls the transition from mitosis to meiosis in Schizosaccharomyces pombe. Upon nitrogen starvation, yeast cells exit mitosis and undergo conjugation and meiotic entry. The model includes the regulation of Mei2, an RNA binding protein required for conjugation and meiotic entry, by multiple feedback loops involving Pat1, a kinase that keeps cells in mitosis, and Ste11, a transcription activator …

Abstract

Cells switch between quiescence and proliferation states for maintaining tissue homeostasis and regeneration. At the restriction point (R-point), cells become irreversibly committed to the completion of the cell cycle independent of mitogen. The mechanism involving hyper-phosphorylation of retinoblastoma (Rb) and activation of transcription factor E2F is linked to the R-point passage. However, stress stimuli trigger exit from the cell cycle back to the mitogen-sensitive quiescent state after Rb hyper-phosphorylation but only until APC/CCdh1 inactivation. In this study, we developed a mathematical model to investigate the reversible transition between quiescence and proliferation in mammalian cells with respect to mitogen and stress signals. The model integrates the current mechanistic knowledge and accounts for the recent experimental observations with cells exiting quiescence and proliferating cells. We show that Cyclin E:Cdk2 couples Rb-E2F and APC/CCdh1 bistable switches and temporally segregates the R-point and the G1/S transition. A redox-dependent mutual antagonism between APC/CCdh1 and its inhibitor Emi1 makes the inactivation of APC/CCdh1 bistable. We show that the levels of Cdk inhibitor (CKI) and mitogen control the reversible transition between quiescence and proliferation. Further, we propose that shifting of the mitogen-induced transcriptional program to G2-phase in proliferating cells might result in an intermediate Cdk2 activity at the mitotic exit and in the immediate inactivation of APC/CCdh1. Our study builds a coherent framework and generates hypotheses that can be further explored by experiments.

Abstract

There has been a significant rise in FinTech mobile app offerings in India for the past 3-4 years. These mobile apps have become disruptive means of managing daily financial transactions. Given the variety of offerings, the usability of these FinTech applications across different age groups is still unclear. In this paper, we explore the usability of FinTech mobile apps across different age groups through a quantitative survey and a more focused study on factors impacting the geriatric population on adopting FinTech mobile apps in India. In addition, we propose a framework called UMETRIX to evaluate the usability of mobile apps to determine the adoption rate among geriatric population.

Abstract

Domain specific search engines (DSSE) are gaining popularity because of better search relevance and domain specificity. The growth of IT and internet led to increase of cyber attacks, however, lack of DSSE for Security is making users refer multiple sites for security information. We demonstrate SIREN, a search engine for ’Information and Cyber Security’ with subdomain coverage, classification and site credibility for ranking search results. As part of our demonstration, we also automated identification of seed URLs (34,007) and related child URLs (400,726) of the security domain using Artificial Bee Colony algorithm. We also evaluated functional and non-functional parameters of available open source software stack that can be used for building other DSSEs.

Abstract

The increasing usage of smart-phones has resulted in mobile applications replacing or supplementing traditional web-based applications. Given the limitations of the form factor in smartphones, usability can be considered as one of the important attributes that determine the success of a mobile application. The measures available for assessing the usability of mobile applications tend to focus more on human aspects and less on the functional aspects of usability. As part of this paper, we propose a usability evaluation framework to identify functional usability issues specific to mobile applications. This framework use usability guidelines and code analysis to improve the usability of a mobile application. As a proof of concept, we have built an end-to-end system using the framework to validate and verify usability issues in Android mobile applications. We also generate code recommendations to implement failed usability guidelines.

Abstract

Software systems often serve as the agents of operation for both enterprise systems and embedded systems. Engineering such systems is a knowledge-centric activity. A clear understanding of the relationship between knowledge, systems and engineering can help us to establish firm theoretical foundations for software and systems engineering.