Differential regulation of salt tolerance mechanisms in Arabidopsis thaliana and Thellungiella halophila (salsuginea)

PhD ThesisHigh salt concentrations in soil are the leading cause of salt stress restraining crop production in different parts of the globe. It is anticipated that stresses from abiotic factors including salinity will result in over 50% decrease in average yield of major crops under current agricultural practices by 2050. Therefore, extensive work has been conducted during the last 20 years to understand the basic mechanisms for stresstolerance to develop plants that can survive under extreme environmental conditions including salinity. The key mechanisms for salt-tolerance are now well known and they involve osmoregulation via increased production of compatible solutes (e.g. proline, glycine betaine), sequestration of salts in the vacuole, exclusion of salts by the roots and extrusion of salts from the roots and/or leaves as well as alleviation of the negative effects of salt-stress. It is becoming clear that these mechanisms are expressed in most plants, with differential and spatiotemporal regulation of the expression of these mechanisms being the key to the salt-tolerance trait. It is, however, not clear as to what is behind the differential expression of these mechanisms and the research already conducted in this field lacks detail in terms of the responses to salt-stress. This project aimed at exploring in depth the differences in salt-responses shown by two close relatives, Arabidopsis thaliana (salt-sensitive) and Thellungiella halophila (salt-tolerant). It also aimed at understanding the regulatory processes behind the observed differential responses by exploring the regulation of genes playing key roles under salt-stress in the two plant species. Detailed analysis of the kinetics of responses to salt-stress were conducted in the two plant species including physiological responses (growth, photosynthesis), metabolic responses (production of osmoregulators, accumulation of sugars, uptake of salts), gene responses (P5CS1 and SOS1) and role of regulatory components in A. thaliana null mutants (signalling elements and transcription factors). T. halophila showed faster and stronger responses to salttreatment in the regulation of the accumulation of key compatible metabolites such as sucrose, fructose, inositol and proline compared to A. thaliana. The difference in proline accumulation between the two species was mirrored by P5CS1 transcript abundance. Along with P5CS1 gene the SUS3, UGP2, FBA1 and PPC1genes showed higher transcript levels under saline conditions in T. halophila. Analysis of the P5CS1 gene suggests the possibility of the presence of two isogenes in T. halophila as suggested by the promoter regions as well as the numbers of introns. Moreover differential splicing of the P5CS1 transcripts under salt-treatment occurred between T. halophila and A. iii thaliana. Finally targeted screening for potential key signalling elements (protein kinases: NPK15, CPK11 and ORG1) and transcription factors (Rp2.4f) using A. thaliana null-mutants for these genes suggested these components had an indirect role in the regulation of the responses to salt-treatment, probably via the regulation of the metabolic background of the plant. The results suggest that along with differential gene regulation between glycophytes and halophytes, salt tolerance also depends upon the level of metabolic plasticity of the plant to mount rapidly appropriate responses to salt stress and the capacity of the plant to modulate the response

Multi-principal element alloys: Design, properties and heuristic explorations

Computational investigations of structural, chemical, and deformation behavior in high entropy alloys (HEAs), which possess notable mechanical strength, have been limited due to the absence of applicable force fields. First by employing Lennard-Jones (LJ) type potential, we explore the atomic origins of the structural phase transformations (PTs) in AlxCrCoFeNi multi-principal element alloys (MPEAs) using classical molecular dynamics (MD) simulations. We report that the amorphous phase exists above the melting temperatures of the participating elements when the concentration of Al 20 %, while for Al \u3e 20 %, a gradual molten-amorphous phase transition is noted. To extend investigations for mechanical properties, we propose a set of intermolecular potential parameters for a quinary Al-Cr-Co-Fe-Ni alloy, using the available ternary Embedded Atom Method and Lennard-Jones potential in classical molecular-dynamics simulations. The simulation results are validated by a comparison to first-principles Korringa-Kohn-Rostoker (KKR) - Coherent Potential Approximation (CPA) [KKR-CPA] calculations for the HEA structural properties (lattice constants and bulk moduli), relative stability, pair probabilities and high-temperature short-range ordering. The simulation (MD)-derived properties are in quantitative agreement with KKR-CPA calculations (first-principles) and experiments. We study AlxCrCoFeNi for Al ranging from 0 $leq$ x $leq$ 2 mole fraction, and and that the HEA shows large chemical clustering over a wide temperature range for x \u3c 0.5. At various temperatures high-strain compression promotes atomistic rearrangements in Al0:1CrCoFeNi, resulting in a clustering-to-ordering transition that is absent for tensile loading. Large fluctuations under stress, at higher temperatures, are attributed to the thermo-plastic instability in Al0:1CrCoFeNi. With the proposed EAM-LJ potential parameters, we then analyze the dislocation dynamics in the FCC Al0:1CrCoFeNi HEA. During plastic deformation, we find that dislocation nucleation and mobility plays a pivotal role in initially triggering twin boundaries followed by the generation of intrinsic and extrinsic stacking faults in the alloy. At room temperature, we find dislocation annihilation contributes to the shear resistance of the alloy eecting a serration laden plastic ow of stress as uniaxial strain is increased. Designing advanced materials for high-temperature applications is a challenging problem. Traditionally superalloys, especially Ni-based, have been the to-go materials whenever strength, and oxidation/corrosion resistance is required in applications ranging across gas turbines to engines. Refractory elements have a high melting point and are ideal candidates to design refractory based MPEAs. We utilized classical Hume-Rothery rules, like Valence Electron Concentration (VEC), size-effect , alongside density functional theory predicted global stability parameter like formation enthalpy and thermodynamic linear response predicted local stability criteria like short-range order (SRO) to explore the 5D design space in a holistic manner for a quinary refractory MPEA. Our investigation revealed the specific design regimes ideal for enhanced electronic stability alongside desired mechanical strength for a novel refractory alloy series based on Mo-W-Ta-Ti-Zr. Findings suggest that the elastic strength of predicted alloy, composition having greater content of Mo and W (at. %), surpasses current commercial high-temperature alloy (Ti-Zr-Mo). Transport properties of refractory MPEAs are also investigated as a potential new class of high-performance thermoelectric material. Investigations in XTa-MoW MPEAs (X=Ti, V, Nb, Zr) revealed dispersion effects and critical doping concentration that helps in tuning the figure-of-merit (ZT) by a factor of 6 at 1250 K. Further investigations in refractory MPEAs revealed twinning-induced pseudoelasticity in (MoW)0:85(TaTi)7:5Zr7:5. Atomistic insights through structural analysis and role of temperature was carried out in this work. Materials for actuators and bio-medical stents are some of the possible application areas for the predicted pseudoelastic MPEA. We design a robust computational framework that couples the metaheuristic cuckoo search technique with classical molecular dynamics simulations to explore the structure-composition phase space of multicomponent alloys. Thereby the predictive scheme explores a vast materials landscape and accelerates the elemental selection for discovery of novel multicomponent alloys. Structural design of MPEAs is generally based on brute-force Monte-Carlo (MC) techniques which are often computationally demanding and less reliable. We proposed a novel exploratory technique to numerically design initial lattice structures for MPEAs for quantum or atomistic calculations that maintains desired cubic symmetry, at required compositions at a fraction of the computational requirements of current algorithms/frameworks. Structural design of BCC alloy systems from binary to quinay were successfully performed and verified with two different density functional approaches

Enhancing hemophilia A management: emicizumab as a cost-effective adjunct to standard therapy for inhibitor patients

This case report discusses the cost-effectiveness of emicizumab + low dose recombinant factor VIIa (rFVIIa) therapy in management of mild hemophilia A with inhibitors. Initial treatment with recombinant factor VIII was complicated by inhibitor development, leading to recurrent bleeding and hematoma formation. After administering full dose rFVIIa to patient for controlling bleeding episodes initially, patient was transitioned to emicizumab alongside low-dose recombinant factor VIIa, which proved efficacious and cost-effective. This case highlights the potential of emicizumab to alleviate the financial burden on patients and healthcare systems, improving treatment access and outcomes for a broader hemophilia patient population

Automated exploration of prebiotic chemical reaction space: progress and perspectives

Prebiotic chemistry often involves the study of complex systems of chemical reactions that form large networks with a large number of diverse species. Such complex systems may have given rise to emergent phenomena that ultimately led to the origin of life on Earth. The environmental conditions and processes involved in this emergence may not be fully recapitulable, making it difficult for experimentalists to study prebiotic systems in laboratory simulations. Computational chemistry offers efficient ways to study such chemical systems and identify the ones most likely to display complex properties associated with life. Here, we review tools and techniques for modelling prebiotic chemical reaction networks and outline possible ways to identify self-replicating features that are central to many origin-of-life models

Effect of passive smoking as a risk factor for chronic obstructive pulmonary disease in normal healthy women

Background: Environmental tobacco smoke (ETS) is a risk factor for cardiovascular disease, asthma in children and lung cancer. There is a biological plausibility of ETS as a causal factor for COPD. Objectives of the study were to examine the effect of passive smoking on lung function in non-smoking healthy women and to co-relate the effects of passive smoke as a risk factor for COPD.Methods: 50 women between 20-40 years of age exposed to passive smoke at home and workplace were assessed by questionnaire. The pulmonary function tests were performed and the values of FEV1 and FVC were obtained by a spirometer.Results: Out of 50 women, 34 % at workplace, 54% at home and 12% at home and workplace were exposed. Mean age was 30.3 years. Mean±SD of FEV1 was 1.94±0.9, FVC was 2.54±1.06, FEV1/FVC was 73.5±10.06 predicted FEV1 % was 63.2±23.2. FEV1/FVC of women exposed at home and workplace was 70.84 indicating that they have higher chances of developing COPD later in life.Conclusions: Passive smoking represents a serious health hazard that can be prevented by health education campaigns

Accelerating computational modeling and design of high-entropy alloys

With huge design spaces for unique chemical and mechanical properties, we remove a roadblock to computational design of {high-entropy alloys} using a metaheuristic hybrid Cuckoo Search (CS) for "on-the-fly" construction of Super-Cell Random APproximates (SCRAPs) having targeted atomic site and pair probabilities on arbitrary crystal lattices. Our hybrid-CS schema overcomes large, discrete combinatorial optimization by ultrafast global solutions that scale linearly in system size and strongly in parallel, e.g. a 4-element, 128-atom model [a $10^{73+}$ space] is found in seconds -- a reduction of 13,000+ over current strategies. With model-generation eliminated as a bottleneck, computational alloy design can be performed that is currently impossible or impractical. We showcase the method for real alloys with varying short-range order. Being problem-agnostic, our hybrid-CS schema offers numerous applications in diverse fields.Comment: 10 pages, 6 figures, submitted to Nature Computational Scienc

Tuning phase-stability and short-range order through Al-doping in (CoCrFeMn)100-xAlx high entropy alloys

For (CoCrFeMn)$_{100-x}$Al$_{x}$ high-entropy alloys, we investigate the phase evolution with increasing Al-content (0 $\le$ x $\le$ 20 at.%). From first-principles theory, the Al-doping drives the alloy structurally from FCC to BCC separated by a narrow two-phase region (FCC+BCC), which is well supported by our experiments. We highlight the effect of Al-doping on the formation enthalpy and electronic structure of (CoCrFeMn)$_{100-x}$Al$_{x}$ alloys. As chemical short-range order (SRO) in multicomponent alloys indicates the nascent local order (and entropy changes), as well as expected low-temperature ordering behavior, we use thermodynamic linear-response within density-functional theory to predict SRO and ordering transformation and temperatures inherent in (CoCrFeMn)$_{100-x}$Al$_{x}$. The predictions agree with our present experimental findings, and other reported ones.Comment: 27 pages, 9 figures, 1 tabl

Atomistic clustering-ordering and high-strain deformation of an Al0.1CrCoFeNi high-entropy alloy

Computational investigations of structural, chemical, and deformation behavior in high-entropy alloys (HEAs), which possess notable mechanical strength, have been limited due to the absence of applicable force fields. To extend investigations, we propose a set of intermolecular potential parameters for a quinary Al-Cr-Co-Fe-Ni alloy, using the available ternary Embedded Atom Method and Lennard-Jones potential in classical molecular-dynamics simulations. The simulation results are validated by a comparison to first-principles Korringa-Kohn-Rostoker (KKR) - Coherent Potential Approximation (CPA) [KKR-CPA] calculations for the HEA structural properties (lattice constants and bulk moduli), relative stability, pair probabilities, and high-temperature short-range ordering. The simulation (MD)-derived properties are in quantitative agreement with KKR-CPA calculations (first-principles) and experiments. We study AlxCrCoFeNi for Al ranging from 0 ≤ x ≤2 mole fractions, and find that the HEA shows large chemical clustering over a wide temperature range for x \u3c 0.5. At various temperatures high-strain compression promotes atomistic rearrangements in Al0.1CrCoFeNi, resulting in a clustering-to-ordering transition that is absent for tensile loading. Large fluctuations under stress, and at higher temperatures, are attributed to the thermo-plastic instability in Al0.1CrCoFeNi