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"Jain, A."
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Tipping the immunostimulatory and inhibitory DAMP balance to harness immunogenic cell death
Induction of tumor cell death is the therapeutic goal for most anticancer drugs. Yet, a mode of drug-induced cell death, known as immunogenic cell death (ICD), can propagate antitumoral immunity to augment therapeutic efficacy. Currently, the molecular hallmark of ICD features the release of damage-associated molecular patterns (DAMPs) by dying cancer cells. Here, we show that gemcitabine, a standard chemotherapy for various solid tumors, triggers hallmark immunostimualtory DAMP release (e.g., calreticulin, HSP70, and HMGB1); however, is unable to induce ICD. Mechanistic studies reveal gemcitabine concurrently triggers prostaglandin E
2
release as an inhibitory DAMP to counterpoise the adjuvanticity of immunostimulatory DAMPs. Pharmacological blockade of prostaglandin E
2
biosythesis favors CD103
+
dendritic cell activation that primes a Tc1-polarized CD8
+
T cell response to bolster tumor rejection. Herein, we postulate that an intricate balance between immunostimulatory and inhibitory DAMPs could determine the outcome of drug-induced ICD and pose COX-2/prostaglandin E
2
blockade as a strategy to harness ICD.
Most chemotherapeutic agents, including gemcitabine, do not elicit immunogenic cell death, a phenomenon associated with the release of damage-associated molecule patterns (DAMPs). Here, the authors show that gemcitabine-treated dying cancer cells express hallmark DAMPs but their immunogenic properties are hindered by the concomitant release of the inhibitory DAMP PGE
2
.
Journal Article
Preferential Mode of gas invasion in sediments: Grain-scale mechanistic model of coupled multiphase fluid flow and sediment mechanics
We present a discrete element model for simulating, at the grain scale, gas migration in brine‐saturated deformable media. We rigorously account for the presence of two fluids in the pore space by incorporating forces on grains due to pore fluid pressures and surface tension between fluids. This model, which couples multiphase fluid flow with sediment mechanics, permits investigation of the upward migration of gas through a brine‐filled sediment column. We elucidate the ways in which gas migration may take place: (1) by capillary invasion in a rigid‐like medium and (2) by initiation and propagation of a fracture. We find that grain size is the main factor controlling the mode of gas transport in the sediment, and we show that coarse‐grain sediments favor capillary invasion, whereas fracturing dominates in fine‐grain media. The results have important implications for understanding vent sites and pockmarks in the ocean floor, deep subseabed storage of carbon dioxide, and gas hydrate accumulations in ocean sediments and permafrost regions. Our results predict that in fine sediments, hydrate will likely form in veins following a fracture network pattern, and the hydrate concentration will likely be quite low. In coarse sediments, the buoyant methane gas is likely to invade the pore space more uniformly, in a process akin to invasion percolation, and the overall pore occupancy is likely to be much higher than for a fracture‐dominated regime. These implications are consistent with laboratory experiments and field observations of methane hydrates in natural systems.
Journal Article
Impact of nuclear deformation of parent and daughter nuclei on one proton radioactivity lifetimes
The influence of nuclear deformation on proton-decay half-lives has been systematically studied in microscopic theoretical frameworks for a wide range of nuclei with Z<82. Correlation between 1p-decay half-lives and the deformed nuclear shapes of both the parent and daughter nuclei is investigated. Since the deformations of proton emitters and their residual nuclei impact the potential barrier and disintegration energy which are crucial for the accurate determination of half-lives, we incorporate these nuclear deformations of both the emitters and residues in a phenomenological manner and propose a new semi-empirical formula to estimate the 1p-decay half-lives. The robustness of this formula is demonstrated by the accurate predictions of the measured values while making it reliable for forecasting the properties of other potential proton emitters. The phenomenon of shape coexistence as observed in several proton emitters and their respective daughter nuclei, is particularly significant in this context due to secondary minima in the potential energy surfaces of both the nuclei. Accounting for these factors significantly affects the estimation of half-lives and branching ratios by introducing additional decay pathways and altering transition probabilities between different nuclear shapes.
Journal Article
Computer aided drug design
Computer based method can help in discovery of leads and can potentially eliminate chemical synthesis and screening of many irrelevant compounds, and in this way, it save time as well as cost. Molecular modeling systems are powerful tools for building, visualizing, analyzing and storing models of complex molecular structure that can help to interpretate structure activity relationship. The use of various techniques of molecular mechanics and dynamics and software in Computer aided drug design along with statistics analysis is powerful tool for the medicinal chemistry to synthesis therapeutic and effective drugs with minimum side effect.
Journal Article
Profiling CARD14 gene expression in Indian Psoriasis patients
Several Genome Wide linkage Studies on psoriasis performed to gain insight of genetic architecture of the disease. Caspase Recruitment Domain-containing family 14 (CARD14) also known as CARMA2 or BIMP2; cytogenic location: 17q25.3, is a scaffold protein that primarily controls the skin epidermis’s nuclear factor kB (NF-kB) signaling pathway activity in skin epidermis, a master gene for inflammation, has been shown to be linked with rare, heritable form of psoriasis. CARD14 is predominantly expressed in keratinocytes and epithelial cells, but also in unidentified dermal cells. For better understanding of molecular processes involved in CARD14 underlying Indian psoriatic patients, we analyzed gene expression of 42 moderates to severe cases of plaque psoriasis and same number of controls using qPCR and its validation through Immunohistochemistry (IHC). This study identifies that the expression of CARD14 in dermal endothelial cells among patients with psoriasis and explores the potential functional consequences associated with an overactive CARD14 gene. Furthermore, the expression data from the western population was consistent with the results of the qPCR validation of the candidate gene. There is a significant correlation between Indian psoriasis vulgaris patients and CARD14 up-regulation, as evidenced by a roughly two-fold shift in lesional tissue expression. This provides insights into the pathways and genes linked to the pathogenesis of psoriasis.
Journal Article
Cluster radioactivity from trans-tin to superheavy region using an improved empirical formula
A simple relation
(
a
Z
c
+
b
)
(
Z
d
/
Q
)
1
/
2
+
(
c
Z
c
+
d
)
of estimation of the half-life of cluster emission is further improved for cluster and
α
-decays, separately, by incorporating isospin of parent nucleus as well as angular momentum taken away by the emitted particle. This improved version is not only found robust in producing experimental half-lives belonging to the trans-tin and trans-lead regions but also elucidates cluster emission in superheavy nuclei over the usual
α
-decay. Considering daughter nuclei around the doubly magic
100
Sn and
208
Pb nuclei for trans-tin and trans-lead (including superheavy) parents, respectively, a systematic and extensive study of 56
≤
Z
≤
120 isotopes is performed for the light and heavy cluster emissions. A fair competition among cluster emission,
α
-decay, spontaneous fission, and
β
-decay is observed in this broad range resulting in a substantial probability of C to Sr clusters from several nuclei, which demonstrates the adequacy of shell effects. The present article proposes a single, improved, latest-fitted, and effective formula of cluster radioactivity that can be used to estimate precise half-lives for a wide range of the periodic chart from trans-tin to superheavy nuclei.
Journal Article
Antenna-coupled photon emission from hexagonal boron nitride tunnel junctions
The ultrafast conversion of electrical signals to optical signals at the nanoscale is of fundamental interest for data processing, telecommunication and optical interconnects. However, the modulation bandwidths of semiconductor light-emitting diodes are limited by the spontaneous recombination rate of electron–hole pairs, and the footprint of electrically driven ultrafast lasers is too large for practical on-chip integration. A metal–insulator–metal tunnel junction approaches the ultimate size limit of electronic devices and its operating speed is fundamentally limited only by the tunnelling time. Here, we study the conversion of electrons (localized in vertical gold–hexagonal boron nitride–gold tunnel junctions) to free-space photons, mediated by resonant slot antennas. Optical antennas efficiently bridge the size mismatch between nanoscale volumes and far-field radiation and strongly enhance the electron–photon conversion efficiency. We achieve polarized, directional and resonantly enhanced light emission from inelastic electron tunnelling and establish a novel platform for studying the interaction of electrons with strongly localized electromagnetic fields.
Efficient conversion of electrical current to photon emission can be acheived in a tunnelling device coupled to a nanostructured optical antenna.
Journal Article
Deep learning model for predicting tunnel damages and track serviceability under seismic environment
Jammu and Kashmir in the northwestern part of the Himalayan region is frequently triggered with moderate to large magnitude earthquakes due to an active tectonic regime. In this study, a mathematical formulation-based Seismic Tunnel Damage Prediction (STDP) model is proposed using the deep learning (DL) approach. The pertinency of the DL model is validated using tunnel damage data from historical earthquakes such as the 1999 Chi-Chi earthquake, the 2004 Mid-Niigata earthquake, and the 2008 Wenchuan earthquake. Peak ground acceleration (PGA), source to site distance (SSD), overburden depth (OD), lining thickness (t), tunnel diameter (Ф), and geological strength index (GSI) were employed as inputs to train the Feedforward Neural Network (FNN) for damage state prediction. The performance evaluation results provided a clear indication for further use in a variety of risk assessment domains. When compared to models based on historical data, the proposed STDP model produces consistent results, demonstrating the robustness of the methodology used in this work. All models perform well during validation based on fitness metrics. The “STD multiple graphs” is also proposed which provide information on damage indexing, damage pattern, and crack predictive specifications. This can be used as a ready toolbox to check the vulnerability in post-seismic scenarios. The seismic design guidelines for tunnelling projects are also proposed, which discuss the damage pattern and suggest mitigation measures. The proposed STDP model, STD multiple graphs, and seismic design guidance are applicable to any earthquake-prone tunnelling project anywhere in the world.
Journal Article
The distribution of soil phosphorus for global biogeochemical modeling
Phosphorus (P) is a major element required for biological activity in terrestrial ecosystems. Although the total P content in most soils can be large, only a small fraction is available or in an organic form for biological utilization because it is bound either in incompletely weathered mineral particles, adsorbed on mineral surfaces, or, over the time of soil formation, made unavailable by secondary mineral formation (occluded). In order to adequately represent phosphorus availability in global biogeochemistry–climate models, a representation of the amount and form of P in soils globally is required. We develop an approach that builds on existing knowledge of soil P processes and databases of parent material and soil P measurements to provide spatially explicit estimates of different forms of naturally occurring soil P on the global scale. We assembled data on the various forms of phosphorus in soils globally, chronosequence information, and several global spatial databases to develop a map of total soil P and the distribution among mineral bound, labile, organic, occluded, and secondary P forms in soils globally. The amount of P, to 50cm soil depth, in soil labile, organic, occluded, and secondary pools is 3.6 ± 3, 8.6 ± 6, 12.2 ± 8, and 3.2 ± 2 Pg P (Petagrams of P, 1 Pg = 1 × 1015g) respectively. The amount in soil mineral particles to the same depth is estimated at 13.0 ± 8 Pg P for a global soil total of 40.6 ± 18 Pg P. The large uncertainty in our estimates reflects our limited understanding of the processes controlling soil P transformations during pedogenesis and a deficiency in the number of soil P measurements. In spite of the large uncertainty, the estimated global spatial variation and distribution of different soil P forms presented in this study will be useful for global biogeochemistry models that include P as a limiting element in biological production by providing initial estimates of the available soil P for plant uptake and microbial utilization.
Journal Article