A pragmatic approach for analysis of long-term climate trends for apple growing regions of Himachal Pradesh, India

The study assessed the long-term climate as well as the area and production trends for four representative decades (1985-2020) in three apple growing districts of Himachal Pradesh, India with the objective of understanding the impact of climate change on apple crop. A long term database was prepared for minimum temperature (Tmin), maximum temperature (Tmax) and rainfall, besides area and production for four decades for three districts of Himachal Pradesh, India. Trend analysis indicated that the temperature in apple growing regions of generally showed an increasing trend, whereas, decreasing trend was observed in the precipitation. The minimum temperature in apple growing regions of Kullu, Shimla and Kinnaur districts has shown an increase of 0.82º C, 1.09 º C and 0.03 ºC, respectively and the precipitation (rainfall) in the Kullu, Shimla and Kinnaur districts has shown a decrease by 5.3 mm, 3.3 mm and 0.9 mm, respectively. Increased warming in the mountain regions is elevating temperatures resulting in the reduction of chilling hours,  pre-requisite for apple fruiting. However, in the higher elevation of Shimla, Kullu and Kinnaur districts, in spite of the increase in temperature, the areas are still suitable for apple farming. The study indicated that the area and production of all three districts of study are increasing because growers are slowly shifting to low chilling varieties (Varieties having chilling hours requirement less than 1000 hours).  Also, the present ecosystem at lower elevations will not support high chilling requirement varieties and apple growers will have to shift to either low chilling varieties or alternate crops

Design Principles for Two-Dimensional Molecular Aggregates Using Kasha's Model: Tunable Photophysics in Near and Short-Wave Infrared

Technologies which utilize near-infrared (700 – 1000 nm) and short-wave infrared (1000 – 2000 nm) electromagnetic radiation have applications in deep-tissue imaging, telecommunications and satellite telemetry due to low scattering and decreased background signal in this spectral region. It is therefore necessary to develop materials that absorb light efficiently beyond 1000 nm. Transition dipole moment coupling (e.g. J-aggregation) allows for redshifted excitonic states and provides a pathway to highly absorptive electronic states in the infrared. We present aggregates of two cyanine dyes whose absorption peaks redshift dramatically upon aggregation in water from ~800 nm to 1000 nm and 1050 nm respectively with sheet-like morphologies and high molar absorptivities (e ~ 105 M-1cm-1). We use Frenkel exciton theory to extend Kasha’s model for J and H aggregation and describe the excitonic states of 2-dimensional aggregates whose slip is controlled by steric hindrance in the assembled structure. A consequence of the increased dimensionality is the phenomenon of an intermediate “I-aggregate”, one which redshifts yet displays spectral signatures of band-edge dark states akin to an H-aggregate. We distinguish between H-, I- and J-aggregates by showing the relative position of the bright (absorptive) state within the density of states using temperature dependent spectroscopy. I-aggregates hold potential for applications as charge injection moieties for semiconductors and donors for energy transfer in NIR and SWIR. Our results can be used to better design chromophores with predictable and tunable aggregation with new photophysical properties

The gravitational path integral and trace of the diffeomorphisms

I give a resolution of the conformal mode divergence in the Euclidean gravitational path-integral by isolating the trace of the diffeomorphisms and its contribution to the Faddeev-Popov measure.Comment: 20 pgs

Stochastically Realized Observables for Excitonic Molecular Aggregates

We show that a stochastic approach enables calculations of the optical properties of large 2-dimensional and nanotubular excitonic molecular aggregates. Previous studies of such systems relied on numerically diagonalizing the dense and disordered Frenkel Hamiltonian, which scales approximately as $\mathcal{O}(N^3)$ for $N$ dye molecules. Our approach scales much more efficiently as $\mathcal{O}(N\log(N))$, enabling quick study of systems with a million of coupled molecules on the micron size scale. We calculate several important experimental observable including the optical absorption spectrum and density of states, and develop a stochastic formalism for the participation ratio. Quantitative agreement with traditional matrix diagonalization methods is demonstrated for both small- and intermediate-size systems. The stochastic methodology enables the study of the effects of spatial-correlation in site energies on the optical signatures of large 2D aggregates. Our results demonstrate that stochastic methods present a path forward for screening structural parameters and validating experiments and theoretical predictions in large excitonic aggregates.Comment: 11 pages, 7 figures, as submitted to JP

Iterative in Situ Click Chemistry Assembles a Branched Capture Agent and Allosteric Inhibitor for Akt1

We describe the use of iterative in situ click chemistry to design an Akt-specific branched peptide triligand that is a drop-in replacement for monoclonal antibodies in multiple biochemical assays. Each peptide module in the branched structure makes unique contributions to affinity and/or specificity resulting in a 200 nM affinity ligand that efficiently immunoprecipitates Akt from cancer cell lysates and labels Akt in fixed cells. Our use of a small molecule to preinhibit Akt prior to screening resulted in low micromolar inhibitory potency and an allosteric mode of inhibition, which is evidenced through a series of competitive enzyme kinetic assays. To demonstrate the efficiency and selectivity of the protein-templated in situ click reaction, we developed a novel QPCR-based methodology that enabled a quantitative assessment of its yield. These results point to the potential for iterative in situ click chemistry to generate potent, synthetically accessible antibody replacements with novel inhibitory properties

Molecular docking and inhibition of matrix metalloproteinase-2 by novel difluorinatedbenzylidene curcumin analog

We recently described the synthesis and characterization of a novel difluorinatedbenzylidene analog of curcumin, commonly referred as CDF, which demonstrated significantly enhanced bioavailability and in vivo anticancer activity. CDF targets many factors similar to curcumin, albeit with more potency, as reported previously. To further highlight this differential behavior of CDF, we chose matrix metalloproteinase protein MMP-2 which is involved in the processes of invasion and metastasis of human tumors. Both curcumin and CDF were characterized for their binding characteristics using in silico docking studies; they were also evaluated via biological assays involving gelatin zymography, miRNA analysis, invasion assays and ELISA. CDF was found to inhibit MMP-2 expression and activity in A549 and H1299 NSCLC cells much more effectively than curcumin, validating molecular modeling results. miR-874, an MMP-2-targeting miRNA, was up-regulated by CDF. Thus, it appears that CDF can inhibit MMP-2 through multiple mechanisms. Our results are suggestive of a more potent inhibition of invasion and metastasis by CDF, compared to curcumin, thus warranting its further evaluation as an effective anticancer agent

Epitope Targeting of Tertiary Protein Structure Enables Target-Guided Synthesis of a Potent In-Cell Inhibitor of Botulinum Neurotoxin

Botulinum neurotoxin (BoNT) serotype A is the most lethal known toxin and has an occluded structure, which prevents direct inhibition of its active site before it enters the cytosol. Target-guided synthesis by in situ click chemistry is combined with synthetic epitope targeting to exploit the tertiary structure of the BoNT protein as a landscape for assembling a competitive inhibitor. A substrate-mimicking peptide macrocycle is used as a direct inhibitor of BoNT. An epitope-targeting in situ click screen is utilized to identify a second peptide macrocycle ligand that binds to an epitope that, in the folded BoNT structure, is active-site-adjacent. A second in situ click screen identifies a molecular bridge between the two macrocycles. The resulting divalent inhibitor exhibits an in vitro inhibition constant of 165 pM against the BoNT/A catalytic chain. The inhibitor is carried into cells by the intact holotoxin, and demonstrates protection and rescue of BoNT intoxication in a human neuron model

Semiclassical quantisation of space-times with apparent horizons

Coherent or semiclassical states in canonical quantum gravity describe the classical Schwarzschild space-time. By tracing over the coherent state wavefunction inside the horizon, a density matrix is derived. Bekenstein-Hawking entropy is obtained from the density matrix, modulo the Immirzi parameter. The expectation value of the area and curvature operator is evaluated in these states. The behaviour near the singularity of the curvature operator shows that the singularity is resolved. We then generalise the results to space-times with spherically symmetric apparent horizons.Comment: 52 pages, 4 figure