Over the past several decades, extensive measurements of the cosmic-ray spectrum have been performed to investigate its composition, energy spectrum, and angular dependence. These observations are strongly influenced by the geographical location of the detector due to variations in the geomagnetic field and atmospheric conditions. Among the secondary cosmic ray particles, muons play a crucial role, as their observed spectrum provides an important input for tuning Monte Carlo event generators used in the prediction of atmospheric neutrino spectrum. A prototype of the magnetized Iron CALorimeter (ICAL), known as mini-ICAL, was constructed near Madurai, Tamil Nadu, India (9°57’N, 77°16’E, 160 m above sea level). The detector consists of 11 layers of 4 m × 4 m, 5.6 cm thick iron plates, interleaved with 4 cm gaps to house 10 layers of Resistive Plate Chambers (RPCs) of active area 1.74 m × 1.85 m.Using this setup, cosmic muon data were collected and analysed to study the dependence of the muon spectrum on momentum, zenith angle, and azimuthal angle, separately for μ+ and μ−. Notably, only a limited number of such measurements exist near the geomagnetic equator, where the cutoff rigidity varies from 17 GeV to 30 GeV for the inclination from 0 to 60 degree zenith angle in the eastern direction. The results obtained from mini-ICAL are compared with simulations of extensive air showers using CORSIKA, and tuned parameters of different phenomenological hadronic interaction models will be presented in this paper.
FLT3 is a critical therapeutic target for acute myeloid leukemia (AML), and its inhibition remains a key strategy in AML management. In this study, we optimized the known compound CHEMBL4444839 to design a novel analogue, CHEMBL4444839-Analogue, showing improved pharmacological and structural characteristics. Pharmacokinetic profiling evaluation revealed that the analogue had enhanced drug-likeness, metabolic stability, and intestinal permeability, along with reduced predicted toxicity. Molecular docking revealed that CHEMBL4444839-Analogue exhibited a binding energy of −10.4 kcal/mol versus −8.7 kcal/mol for the parent compound, forming additional hydrogen bonds and hydrophobic contacts with GLU661, CYS694, LEU818, and PHE830 in the ATP binding pocket. Molecular dynamics simulation over 100 ns demonstrated lower average RMSD (1.78 Å vs 2.34 Å) and reduced RMSF fluctuations at the activation loop and DFG-out region, indicating enhanced conformational stability. Free energy calculations confirmed higher thermodynamic stability of the analogue versus CHEMBL4444839. The analogue also restricted domain motion and improved residue correlation, indicating better stabilization of FLT3 in its inactive conformation. Incorporation of a fluorocyclobutane moiety significantly contributed to enhanced rigidity and optimized interaction geometry, collectively establishing CHEMBL4444839-Analogue as a more promising and selective FLT3 inhibitor for AML therapy. Docking of CHEMBL4444839 and its designed analogue was performed to analyze binding interactions and guide structural modifications. Pharmacokinetic and toxicity parameters were predicted using SwissADME, ADMETlab 2.0, and ProTox-II. Molecular dynamics simulations were executed with GROMACS 2023 using the CHARMM36 force field to assess conformational stability, followed by MM-PBSA and dynamic cross-correlation analyses. The integrated computational results demonstrated that CHEMBL4444839-Analogue achieved stronger binding affinity, reduced flexibility, and superior stability compared to the parent molecule, validating its potential as an optimized FLT3 inhibitor candidate for further biochemical and therapeutic evaluation.
We present a new method for deriving the dynamics of chemical reaction networks using the Laplacian matrix of the corresponding species-reaction graph, in contrast to previous works that use the Laplacian of the graph of complexes. Species-reaction graphs are bipartite graphs that contain two sets of vertices, one representing species and the other representing reactions, connected by directed edges that indicate relationships between them. Our approach starts by assigning appropriate edge weights to this bipartite graph, which are then used to compute the weighted graph Laplacian. This Laplacian reformulation of the system of differential equations governing the network dynamics emphasizes the flow of information throughout the chemical reaction network considered as causal network. As an application of this framework, we introduce a novel model reduction technique based on the Kron reduction of the weighted Laplacian matrix associated with the species-reaction graphs. Our systematic approach involves identifying nodes for deletion while preserving the bipartite structure, followed by constructing the Kron-reduced model. To demonstrate the effectiveness of our method, we apply it to a complex biochemical network, showing how model simplification facilitates analysis and interpretation of these systems.
The one-loop cohomology of N=4 SYM is conjectured to be isomorphic to the exact cohomology. As a result, its truncations are expected to be subrings of the exact cohomology. We study the superconformal index restricted over one such truncation known as the BMN truncation. We present a systematic algorithm to compute the BMN index using the method of residues. We compute the BMN index for SU(N) SYM for N = 2,...,6 in closed form. It is expressed as a rational function of the fugacity. A term of the type (1-x) in the denominator indicates the presence of a bosonic generator counted with fugacity x. We find a rich and universal set of such terms in the denominator showing an interesting bosonic Fock space in the spectrum of protected operators. This Fock space cannot be explained as coming from the non-interacting supersymmetric graviton gas far away from the black hole as in the grey-galaxy solutions because the charges of the bosonic generators are not compatible with those of the supersymmetric gravitons. This suggests a novel microstructure within the supersymmetric black hole itself. We also examine the indices of S-dual pairs SO(2N+1) and Sp(N) SYM. Although their full 1/16-BPS indices coincide, we find discrepancies in their BMN-sector indices. As the BMN indices restricted to the graviton sector are expected to be the same, this mismatch allows us to identify non-graviton cohomologies. We explicitly find one of them in the SO(7) theory that is responsible for the mismatch of the BMN index. We also show that indices restricted to other one-loop cohomology truncations, in general, do not match under S-duality. If the conjecture of exactness of one-loop cohomology is correct, this suggests the presence of new cohomology subrings that match under S-duality with the letter-based truncations of the one-loop cohomology. This offers a way to check the one-loop exactness conjecture.
The tensionless limit probes the very high energy regime of string theory in contrast to the well studied point-particle limit which reduces to Einstein gravity. Tensionless strings sweep out null worldsheets in the target space and hence are also called null strings. This article aims to provide a comprehensive review of tensionless null string theory beginning with the initial work of Schild, and continuing to the foundational work of Isberg et al. (ILST) and then focussing on developments in the past decade.Recent work centres on the emergence of the Carrollian Conformal Algebra as residual worldsheet symmetries of the ILST action and the identification of tensionless limit as a worldsheet Carrollian limit on the string worldsheet. Carrollian structures are used to address the classical and quantum aspects of the null string. In the classical theory, the aforementioned limit agrees with the analysis from the ILST action. Symmetries, constraints, mode expansions computed from both perspectives match nicely providing a robust cross-check of the analyses. We discuss closed and open null strings as well as their supersymmetric cousins.The quantum null string comes with several surprises, the foremost of which is the emergence of three consistent quantum theories from the ILST action. We detail the canonical quantisation and the spectrum of the triumvirate of theories. We discuss the novelties of the quantum null theories and the effect compactification has on them. We also discuss Carroll strings, applications of these ideas to strings approaching black holes and give a quick overview of other related developments.
