Abstract

Regional water resource modelling is important for evaluating system performance by analyzing the reliability, resilience and vulnerability criteria of the system. In water resource systems modelling, several uncertainties abound, including data inadequacy and errors, modeling inaccuracy, lack of knowledge, imprecision, inexactness, randomness of natural phenomena, and operational variability, in addition to challenges such as growing population, increasing water demands, diminishing water sources and climate change. Recent advances in modelling techniques along with high computational capabilities have facilitated rapid progress in this area. In India, several studies have been carried out to understand and quantify uncertainties in various basins, enumerate large temporal and regional mismatches between water availability and demands, and project likely changes due to warming. A comprehensive review of uncertainties in water resource modelling from an Indian perspective is yet to be done. In this work, we aim to appraise the quantification of uncertainties in systems modelling in India and discuss various water resource management and operation models. Basic formulation of models for probabilistic, fuzzy and grey/inexact simulation, optimization, and multi-objective analyses to water resource design, planning and operations are presented. We further discuss challenges in modelling uncertainties, missing links in integrated systems approach, along with directions for future.

Abstract

The ultraviolet (UV) radiation-induced DNA lesions play a causal role in many prevalent genetic skin-related diseases and cancers. The damage sensing protein Rad4/XPC specifically recognizes and repairs these lesions with high fidelity and safeguards genome integrity. Despite considerable progress, the mechanistic details of the mode of action of Rad4/XPC in damage recognition remain obscure. The present study investigates the mechanism, energetics, dynamics, and the molecular basis for the sequence specificity of mismatch recognition by Rad4/XPC. We dissect the following three key molecular events that occur as Rad4/XPC tries to recognize and bind to DNA lesions/mismatches: (a) the association of Rad4/XPC with the damaged/mismatched DNA, (b) the insertion of a lesion-sensing β-hairpin of Rad4/XPC into the damage/mismatch site and (c) the flipping of a pair of nucleotide bases at the damage/mismatch site. Using suitable reaction coordinates, the free energy surfaces for these events are determined using molecular dynamics (MD) and umbrella sampling simulations on three mismatched (CCC/CCC, TTT/TTT and TAT/TAT mismatches) Rad4-DNA complexes. The study identifies the key determinants of the sequence-dependent specificity of Rad4 for the mismatches and explores the ramifications of specificity in the aforementioned events. The results unravel the molecular basis for the high specificity of Rad4 towards CCC/CCC mismatch and lower specificity for the TAT/TAT mismatch. A strong correlation between the depth of β-hairpin insertion into the DNA duplex and the degree of coupling between the hairpin insertion and the flipping of bases is also observed. The interplay of the conformational flexibility of mismatched bases, the depth of β-hairpin insertion, Rad4-DNA association energetics and the Rad4 specificity explored here complement recent experimental FRET studies on Rad4-DNA complexes.

Abstract

Construction of buildings without keeping enough setback from plot boundary is very common practise in India. This lead to very closely spaced buildings with practically zero or few mm gap between them. The intension behind this is to utilize the maximum plot area, without knowing the consequences of damage due to pounding during moderateto-severe earthquake shaking. In this study, an attempt is made to check the adequacy of separation distance clause of IS 1893:2016 and also a comparison is made with similar clauses in international codes of practise. For this purpose, four low to mid-rise RC buildings located in seismic zone IV were designed as per IS 456:2000 and IS 1893:2016. These buildings are assumed to be closely spaced with each other, in pair of two, for four different cases. Further, the linear and non-linear time history analysis (NLTHA) were carried out by considering ground motion time histories of three moderate earthquakes recorded in India. From the study, it was found that the separation distance clauses prescribed in IS 1893-2016 are on conservative side

Abstract

In this study, a three-dimensional, four-storied, reinforced concrete (RC) building is designed for seismic zone-IV and seismically evaluated for different infill configurations along with consideration of openings in infills to develop a realistic model. Four models are considered, i.e. model I (full RC-infilled frame without lintel beam), model II (bare frame without lintel beam), model III (full RC-infilled frame with lintel beam) and model IV (bare frame with lintel beam). In this study, we have evaluated the effect of lintel beams on response reduction factor of the frame structure. The nonlinear static adaptive pushover analysis has been done using Seismostruct program. In seismic design, the response reduction factor (R-factor) reduces from the elastic to inelastic strength. The R-factor is one of the design tools to show the level of inelasticity in a structure and so it has significant importance in the earthquake engineering field. The response reduction factor mainly consists of ‘ductility reduction factor’ and ‘over strength factor’, which are evaluated from static adaptive pushover analysis. Ultimately the response reduction factor is obtained for the building and compared with the value recommended by IS 1893 Part-1 (2016). The results depict that the R-factor values of full RC-infilled frames and bare frames with incorporation of lintel beams are higher than other frames without lintel beam. However, R-factor values of bare frames are lower than the corresponding values recommended in the BIS code.

Abstract

Motivated by the RDð
Þ anomalies, we investigate an SO(10) grand unification scenario where a charge −1=3 scalar leptoquark (S1) remains as the only new physics candidate at the TeV scale. This leptoquark along with the Standard Model (SM) Higgs doublet originates from the same ten-dimensional real scalar multiplet in the SO(10) grand unification framework taking its mass close to the electroweak scale. We explicitly show how the gauge coupling unification is achieved with only one intermediate symmetrybreaking scale at which the Pati-Salam gauge group is broken into the SM group. We investigate the phenomenological implications of our scenario and show that an S1 with a specific Yukawa texture can explain the RDð
Þ anomalies. We perform a multiparameter scan considering the relevant flavor constraints on RDð
Þ , FLðD
Þ, PτðD
Þ and Rνν Kð
Þ as well as the constraint coming from the Z → ττ decay and the latest ττ resonance search data at the LHC. Our analysis shows that a single leptoquark solution to the observed RDð
Þ anomalies with S1 is still a viable solution.

Abstract

The Standard Model (SM) when extended with a Leptoquark (LQ) and right handed neutrinos, can have interesting new implications for Higgs physics. We show that the sterile neutrinos can induce a significant boost to the down-type quark Yukawa interactions through a diagonal coupling associated with the quarks and a scalar LQ of electromagnetic charge 1/3. The relative change is much more pronounced in case of the first two generations of quarks as they have vanishingly small Yukawa couplings in the SM. The enhancement in the couplings would also lead to a non-negligible contribution of the quark fusion process to the production of the 125 GeV Higgs scalar in the SM, though the gluon fusion always dominates. However, this may not be true for a general scalar. As an example, we consider a scenario with a SM-gauge-singlet scalar φ where an O(1) coupling between φ and the LQ is allowed. The φqq¯ Yukawa couplings can only be generated radiatively through a loop of LQ and sterile neutrinos. Here, the quark fusion process can have significant cross section, specially for a light φ. It can even supersede the normally dominant gluon fusion process for a moderate to large value of the LQ mass. This model can be tested/constrained at the high luminosity run of the LHC through a potentially large branching fraction of the scalar to two-jets.

Abstract

At the LHC, a TeV-scale leptoquark (LQ) that decays dominantly to a top quark (t) and a light charged lepton (` = e, µ) would form a resonance system of boosted-t + high-pT-`. We consider all possible vector LQ models within the Buchmüller-Rückl-Wyler classifications with the desired decay. We propose simple phenomenological Lagrangians that are suitable for bottom-up/experimental studies and, at the same time, can cover the relevant parameter spaces of these models. In this simplified framework, we study the pair and single production channels of vector LQs at the LHC. Interestingly, we find that, like the pair production, the cross sections of some single production processes also depend on the parameter κ that appears in the gluon-vector LQ coupling. We adopt a search strategy of selecting events with at least one boosted hadronic top quark and exactly two high-pT leptons of the same flavor and opposite sign. This combines events from the pair and single production processes and, therefore, can enhance the discovery potential beyond that of the pair-production-only searches. For 5σ discovery we find that vector LQs can be probed up to 2.55 TeV for 100% branching ratio in the t` decay mode and O(1) new couplings at the 14 TeV LHC with 3 ab−1 of integrated luminosity.

Abstract

An emerging hallmark of cancer is metabolic reprogramming, which presents opportunities for cancer diagnosis and treatment based on metabolism. We performed a comprehensive metabolic network analysis of major renal cell carcinoma (RCC) subtypes including clear cell, papillary and chromophobe by integrating transcriptomic data with the human genome-scale metabolic model to understand the coordination of metabolic pathways in cancer cells. We identified metabolic alterations of each subtype with respect to tumor-adjacent normal samples and compared them to understand the differences between subtypes. We found that genes of amino acid metabolism and redox homeostasis are significantly altered in RCC subtypes. Chromophobe showed metabolic divergence compared to other subtypes with upregulation of genes involved in glutamine anaplerosis and aspartate biosynthesis. A difference in …

Abstract

The transport of water through aquaporins is a dynamic process that involves rapid movement of a chain of water molecules through the pore of the aquaporin. Structures of aquaporins solved using X-ray crystallography have provided some insights into how water is transported through these channels, and how certain structural features of the pore might help exclude other solutes from passing through the pore. However, such techniques provide only a static picture, and a dynamic picture of the transport and selectivity mechanism at work in aquaporins is possible with molecular dynamics (MD) simulations. In MD simulations, the forces between the different atoms in a system are computed, and the atoms are then allowed to move under the influence of these forces. This allows the sampling of different conformations of the molecule being studied, including conformations that are crucial in driving biological phenomena like water transport. Simulation studies have provided insights into a number of aspects of aquaporins, including the role of the asparagine-proline-alanine (NPA) motif and the aromatic/arginine (ar/R) constriction, water transport mechanism, mechanisms defining the selectivity of the channel, interaction with lipids, response to external electric field, and binding of putative drug molecules. This chapter provides a brief review of the current status of computational modeling of aquaporins using MD simulations. Initially, a brief account of force fields and MD simulations is presented followed by an account of how MD simulations have contributed to further our understanding of different aspects of aquaporins.

Abstract

The optical activity of a metal nanocluster (NC) is induced either by an asymmetric arrangement of constituents or by a dissymmetric field of a chiral ligand layer. Herein, we unveil the origin of chirality in Ag29 NCs, which is attributed to the intrinsically chiral atomic arrangement. The X-ray crystal structure of a Ag29(BDT)12(TPP)4 NC (BDT: 1,3-benzenedithiol; TPP: triphenylphosphine) manifested the presence of intrinsic chirality in the outer shell capping the icosahedral achiral Ag13 core. The enantiomers of the Ag29(BDT)12(TPP)4 NC are separated by high-performance liquid chromatography (HPLC) using a chiral column for the first time, showing mirror-image circular dichroism (CD) spectra. The CD spectra are reproduced by time-dependent density functional theory (TDDFT) calculations based on enantiomeric Ag29 models with achiral 1,3-propanedithiolate ligands. The mechanism of chiral induction in the synthesis of Ag29(DHLA)12 (DHLA: a-dihydrolipoic acid) NCs with a chiral ligand system is further discussed with the aid of DFT calculations. The use of the enantiomeric DHLA ligand preferentially leads to a one-handed atomic arrangement which is more stable than the opposite one, inducing the enantiomeric excess in the population of intrinsically chiral Ag29 NCs with CD activity