Accelerating the Gillespie τ-Leaping Method Using Graphics Processing Units

The Gillespie τ-Leaping Method is an approximate algorithm that is faster than the exact Direct Method (DM) due to the progression of the simulation with larger time steps. However, the procedure to compute the time leap τ is quite expensive. In this paper, we explore the acceleration of the τ-Leaping Method using Graphics Processing Unit (GPUs) for ultra-large networks ( reaction channels). We have developed data structures and algorithms that take advantage of the unique hardware architecture and available libraries. Our results show that we obtain a performance gain of over 60x when compared with the best conventional implementations

p53 Transactivation and the Impact of Mutations, Cofactors and Small Molecules Using a Simplified Yeast-Based Screening System

The p53 tumor suppressor, which is altered in most cancers, is a sequence-specific transcription factor that is able to modulate the expression of many target genes and influence a variety of cellular pathways. Inactivation of the p53 pathway in cancer frequently occurs through the expression of mutant p53 protein. In tumors that retain wild type p53, the pathway can be altered by upstream modulators, particularly the p53 negative regulators MDM2 and MDM4. promoter, ii) single copy, chromosomally located p53-responsive and control luminescence reporters, iii) enhanced chemical uptake using modified ABC-transporters, iv) small-volume formats for treatment and dual-luciferase assays, and v) opportunities to co-express p53 with other cofactor proteins. This robust system can distinguish different levels of expression of WT and mutant p53 as well as interactions with MDM2 or 53BP1.We found that the small molecules Nutlin and RITA could both relieve the MDM2-dependent inhibition of WT p53 transactivation function, while only RITA could impact p53/53BP1 functional interactions. PRIMA-1 was ineffective in modifying the transactivation capacity of WT p53 and missense p53 mutations. This dual-luciferase assay can, therefore, provide a high-throughput assessment tool for investigating a matrix of factors that can influence the p53 network, including the effectiveness of newly developed small molecules, on WT and tumor-associated p53 mutants as well as interacting proteins

The Toll-Like Receptor Gene Family Is Integrated into Human DNA Damage and p53 Networks

In recent years the functions that the p53 tumor suppressor plays in human biology have been greatly extended beyond “guardian of the genome.” Our studies of promoter response element sequences targeted by the p53 master regulatory transcription factor suggest a general role for this DNA damage and stress-responsive regulator in the control of human Toll-like receptor (TLR) gene expression. The TLR gene family mediates innate immunity to a wide variety of pathogenic threats through recognition of conserved pathogen-associated molecular motifs. Using primary human immune cells, we have examined expression of the entire TLR gene family following exposure to anti-cancer agents that induce the p53 network. Expression of all TLR genes, TLR1 to TLR10, in blood lymphocytes and alveolar macrophages from healthy volunteers can be induced by DNA metabolic stressors. However, there is considerable inter-individual variability. Most of the TLR genes respond to p53 via canonical as well as noncanonical promoter binding sites. Importantly, the integration of the TLR gene family into the p53 network is unique to primates, a recurrent theme raised for other gene families in our previous studies. Furthermore, a polymorphism in a TLR8 response element provides the first human example of a p53 target sequence specifically responsible for endogenous gene induction. These findings—demonstrating that the human innate immune system, including downstream induction of cytokines, can be modulated by DNA metabolic stress—have many implications for health and disease, as well as for understanding the evolution of damage and p53 responsive networks

Fundamental Phenomena and Applications of Swift Heavy Ion Irradiations

Peer reviewe

Double-Wall Carbon Nanotube Hybrid Mode-Locker in Tm-doped Fibre Laser: A Novel Mechanism for Robust Bound-State Solitons Generation

The complex nonlinear dynamics of mode-locked fibre lasers, including a broad variety of dissipative structures and self-organization effects, have drawn significant research interest. Around the 2 μm band, conventional saturable absorbers (SAs) possess small modulation depth and slow relaxation time and, therefore, are incapable of ensuring complex inter-pulse dynamics and bound-state soliton generation. We present observation of multi-soliton complex generation in mode-locked thulium (Tm)-doped fibre laser, using double-wall carbon nanotubes (DWNT-SA) and nonlinear polarisation evolution (NPE). The rigid structure of DWNTs ensures high modulation depth (64%), fast relaxation (1.25 ps) and high thermal damage threshold. This enables formation of 560-fs soliton pulses; two-soliton bound-state with 560 fs pulse duration and 1.37 ps separation; and singlet+doublet soliton structures with 1.8 ps duration and 6 ps separation. Numerical simulations based on the vectorial nonlinear Schr¨odinger equation demonstrate a transition from single-pulse to two-soliton bound-states generation. The results imply that DWNTs are an excellent SA for the formation of steady single- and multi-soliton structures around 2 μm region, which could not be supported by single-wall carbon nanotubes (SWNTs). The combination of the potential bandwidth resource around 2 μm with the soliton molecule concept for encoding two bits of data per clock period opens exciting opportunities for data-carrying capacity enhancement.M.C. acknowledges the support of EU Horizon2020 Marie S.-Curie IF MINDFLY project. A.E.B. acknowledges the support of Russian Science Foundation (grant 14-21-00110). M.A.A. acknowledges the support of Ministry of Higher Education Sultanate of Oman. T.H. acknowledges the support of Royal Academy of Engineering Fellowship (Graphlex). The support by the Marie-Curie Inter-national Research Staff Exchange Scheme “TelaSens” project, Research Executive Agency Grant No. 269271, Programme: FP7-PEOPLE-2010-IRSES and European Research Council through the FP7-IDEAS-ERC grant ULTRALASER are gratefully acknowledged

Reconstruction of B→ρℓνℓB \to \rho \ell \nu_\ell decays identified using hadronic decays of the recoil BB meson in 2019 -- 2021 Belle II data

We present results on the semileptonic decays $B^0 \to \rho^- \ell^+ \nu_\ell$ and $B^+ \to \rho^0 \ell^+ \nu_\ell$ in a sample corresponding to 189.9/fb of Belle II data at the SuperKEKB $e^- e^+$ collider. Signal decays are identified using full reconstruction of the recoil $B$ meson in hadronic final states. We determine the total branching fractions via fits to the distributions of the square of the "missing" mass in the event and the dipion mass in the signal candidate and find ${\mathcal{B}(B^0\to\rho^-\ell^+ \nu_\ell) = (4.12 \pm 0.64(\mathrm{stat}) \pm 1.16(\mathrm{syst})) \times 10^{-4}}$ and ${\mathcal{B}({B^+\to\rho^0\ell^+\nu_\ell}) = (1.77 \pm 0.23 (\mathrm{stat}) \pm 0.36 (\mathrm{syst})) \times 10^{-4}}$ where the dominant systematic uncertainty comes from modeling the nonresonant $B\to (\pi\pi)\ell^+\nu_\ell$ contribution

Measurement of the B_{s}^{0}→μ^{+}μ^{-} Branching Fraction and Effective Lifetime and Search for B^{0}→μ^{+}μ^{-} Decays.

A search for the rare decays B_{s}^{0}→μ^{+}μ^{-} and B^{0}→μ^{+}μ^{-} is performed at the LHCb experiment using data collected in pp collisions corresponding to a total integrated luminosity of 4.4  fb^{-1}. An excess of B_{s}^{0}→μ^{+}μ^{-} decays is observed with a significance of 7.8 standard deviations, representing the first observation of this decay in a single experiment. The branching fraction is measured to be B(B_{s}^{0}→μ^{+}μ^{-})=(3.0±0.6_{-0.2}^{+0.3})×10^{-9}, where the first uncertainty is statistical and the second systematic. The first measurement of the B_{s}^{0}→μ^{+}μ^{-} effective lifetime, τ(B_{s}^{0}→μ^{+}μ^{-})=2.04±0.44±0.05  ps, is reported. No significant excess of B^{0}→μ^{+}μ^{-} decays is found, and a 95% confidence level upper limit, B(B^{0}→μ^{+}μ^{-})<3.4×10^{-10}, is determined. All results are in agreement with the standard model expectations

Measurement of the B+c meson lifetime using B+c→J/ψμ+νμX decays

The lifetime of the $B_c^+$ meson is measured using semileptonic decays having a $J\!/\!\psi$ meson and a muon in the final state. The data, corresponding to an integrated luminosity of $2\mathrm{~fb^{-1}}$, are collected by the LHCb detector in $pp$ collisions at a centre-of-mass energy of $8\,\mathrm{TeV}$. The measured lifetime is $$\tau = 509 \pm 8 \pm 12 \mathrm{~fs},$$ where the first uncertainty is statistical and the second is systematic