Abstract

Base pairs involving post-transcriptionally modified nucleobases are believed to play important roles in a wide variety of functional RNAs. Here we present our attempts toward understanding the structural and functional role of naturally occurring modified base pairs using a combination of X-ray crystal structure database analysis, sequence analysis, and advanced quantum chemical methods. Our bioinformatics analysis reveals that despite their presence in all major secondary structural elements, modified base pairs are most prevalent in tRNA crystal structures and most commonly involve guanine or uridine modifications. Further, analysis of tRNA sequences reveals additional examples of modified base pairs at structurally conserved tRNA regions and highlights the conservation patterns of these base pairs in three domains of life. Comparison of structures and binding energies of modified base pairs with their …

Abstract

Post transcriptionally modified nucleotides play an important structural role in RNA by providing additional chemical diversity to the architecture of the constituent nucleotides. To understand the contribution of these modified nucleotides in tertiary interactions that help in RNA folding, we present a systematic investigation of higher order hydrogen bonded structures involving modified nucleotides using bioinformatics based crystal structural database analysis and quantum chemical calculations. Our analysis reveals that 29% of the modified bases that participate in hydrogen-bonding interactions form higher order motifs, which points towards their importance as RNA building blocks. Although greater geometric variations in such motifs are observed in tRNA, they occur most commonly in rRNA, where they may play a role in RNA folding. Characterization of the optimum geometries and binding strengths of the modified …

Abstract

Reverse Watson-Crick G:C basepairs (G:C W:W Trans) occur frequently in different functional RNAs. This is one of the few basepairs whose gas-phase-optimized isolated geometry is inconsistent with the corresponding experimental geometry. Several earlier studies indicate that through post-transcriptional modification, direct protonation, or coordination with Mg2+, accumulation of positive charge near N7 of guanine can stabilize the experimental geometry. Interestingly, recent studies reveal significant variation in the position of putatively bound Mg2+. This, in conjunction with recently raised doubts regarding some of the Mg2+ assignments near the imino nitrogen of guanine, is suggestive of the existence of multiple Mg2+ binding modes for this basepair. Our detailed investigation of Mg2+-bound G:C W:W Trans pairs occurring in high-resolution RNA crystal structures shows that they are found in 14 different …

Abstract

A novel approach to accurately determine residue-specific noncovalent interaction strengths (ξ) of proteins from NMR-measured fast side chain motional parameters (Oaxis2) is presented. By probing the environmental sensitivity of side chain conformational energy surfaces of individual residues of a diverse set of proteins, the microscopic connections between ξ, Oaxis2, conformational entropy (Sconf), conformational barriers, and rotamer stabilities established here are found to be universal among proteins. The results reveal that side chain flexibility and conformational entropy of each residue decrease with increasing ξ and that for each residue type there exists a critical range of ξ, determined primarily by the mean side chain conformational barriers, within which flexibility of any residue can be reversibly tuned from highly flexible (with Oaxis2 ∼ 0) to highly restricted (with Oaxis2 ∼ 1) by increasing ξ by ∼3 kcal …

Abstract

An understanding of the determinants of the thermal stability of thermostable proteins is expected to enable design of enzymes that can be employed in industrial biocatalytic processes carried out at high temperatures. A major factor that has been proposed to stabilize thermostable proteins is the high occurrence of salt bridges. The current study employs free energy calculations to elucidate the thermodynamics of the formation of salt bridge interactions and the temperature dependence, using acetate and methylguanidium ions as model systems. Three different orientations of the methylguanidinium approaching the carboxylate group have been considered for obtaining the free energy profiles. The association of the two ions becomes more favorable with an increase in temperature. The desolvation penalty corresponding to the association of the ion pair is the lowest at high temperatures. The occurrence of …

Abstract

Predictability of river water temperature is a big argument for many environmental applications, hydrology and ecology research. River water temperature mainly depends on several parameters of water bodies such as streamflow, Dissolved Oxygen (DO), oxidation reduction potential, pollutant temperature, thermal effluent discharges, ground water interactions and its surrounding atmosphere. Commonly, the river water temperature always has been correlated with air temperature as a substitute due to the ease of applicability for rivers with some limitations over detailed meteorological and thermal data. In addition to air temperature the most influencing component of water body is streamflow which is having strong response towards the water temperature. An evaluation of integrated river water temperature and streamflow fluctuations is proposed to evidence biological activity, chemical specimen, oxygen solubility, self-purification capacity of a river system and variation of flows due to hydro-climatic changes. Prediction of river water temperature at various locations over a river basin is vital for the water quality management. The present study aims to estimate the river water temperature (RWT) under air temperature changes and local to regional anthropogenic activities of streamflow over Krishna river basin, India. A standardized multi-linear regression model is developed for predicting river water temperature over various discharge locations of the Krishna river basin. The performance of the model was tested mainly for 8 stations using historical daily data of river temperature, air temperature and river discharges from 1991 to 2005. The attainment of a model is carried out for these stations with air temperature, stream flows are predictors whereas water temperature as predictability component through training, testing. In this study the correlation coefficients between air minimum, maximum and average temperature with river water temperature are determined for selecting the possible air temperature variable to be considered in the analysis. The correlation coefficients are obtained with air minimum temperature (r = 0.541-0.772), air maximum temperature (r= 0.267-0.613) and air average temperature (r = 0.463-0.715) for all stations and it is observed that air minimum has the highest correlation coefficient value and it could be suitable for modeling. The performance of the multi-linear regression model for training and testing was obtained in terms of Root Mean Square Error (RMSE = 0.934 to 4.556), Correlation of determination (R = 0.984 and 0.986).

Abstract

This document describes a web security model to analyse cross origin requests and block them using CORP, a browser security policy proposed for mitigating Cross Origin Request Attacks (CORA) such as CSRF, Clickjacking, Web application timing, etc. CORP is configured by website administrators and sent as an HTTP response header to the browser. A browser which is CORP-enabled will interpret the policy and enforce it on all cross-origin HTTP requests originating from other tabs of the browser, thus preventing malicious crossorigin requests. In this document we use Alloy, a finite state model finder, to formalize a web security model to analyse malicious cross-origin attacks and verify that CORP can be used to mitigate such attacks.

Abstract

On March 27, 2015, Github witnessed a massive DDoS attack, the largest in Github's history till date. In this incident, browsers and users were used as vectors to launch the attack. In this paper, we analyse such browser-based DDoS attacks and simulate them in a lab environment. Existing browser security policies like Same Origin Policy (SOP), Content Security Policy (CSP) do not mitigate these attacks by design. In this paper we observe that CORP (Cross Origin Request Policy), a browser security policy, can be used to mitigate these attacks. CORP enables a server to control cross-origin interactions initiated by a browser. The browser intercepts the cross-origin requests and blocks unwanted requests by the server. This takes the load off the server to mitigate the attack.

Abstract

In this paper we report on a Systematic Literature Review where we explored the notion of semantics in Computer Science (CSE) literature. Our goal was 1) to surface how the idea of semantics has been used and represented, and 2) to surface its publication pattern in CSE. Our automated search in 5 CSE repositories yielded 653 relevant papers, emerging from multiple disciplines and geographies, spanning a period from year 1967 to 2017. We shortlisted 50 representative samples to study. This literature review was motivated by an external Web Accessibility effort in which we wanted to understand how to influence the various meanings that a variety of human end-user could derive by varying the computer rendering of a given content. The results of the SLR indicate that 44% of papers do have their own definition, almost all are formal in their presentation, and 94% of them have a notion of semantics that favors the computer as a processor. We observe the limited human oriented focus on semantics in CSE, and suggest such semantics focus as an area of potential study.

Abstract

Cross origin request attacks (CORA) such as Cross site request forgery (CSRF), cross site timing, etc. continue to pose a threat on the modern day web. Current browser security policies inadequately mitigate these attacks. Additionally, third party authentication services are now the preferred way to carry out identity management between multiple enterprises and web applications. This scenario, called Federated Identity Management (FIM) separates the problem of identity management from the core functionality of an application. In this paper, we construct formally checkable models and design laboratory simulations to show that FIM is susceptible to cross origin attacks. Further, we employ the Cross Origin Request Policy (CORP) to mitigate such attacks.