End-point Energy Research Articles

Senna makki and other active phytochemicals: Myths and realities behind covid19 therapeutic interventions.

This study aims to investigate the binding potential of chemical compounds of Senna in comparison with the experimentally tested active phytochemicals against SARS-CoV-2 protein targets to assist in prevention of infection by exploring multiple treatment options. The entire set of phytochemicals from both the groups were subjected to advanced computational analysis that explored functional molecular descriptors from a set of known medicinal-based active therapeutics followed by MD simulations on multiple SARS-CoV-2 target proteins. Our findings manifest the importance of hydrophobic substituents in chemical structures of potential inhibitors through cross-validation with the FDA-approved anti-3CLpro drugs. Noteworthy improvement in end-point binding free energies and pharmacokinetic profiles of the proposed compounds was perceived in comparison to the control drug, vizimpro. Moreover, the identification of common drug targets namely; AKT1, PTGS1, TNF, and DPP4 between proposed active phytochemicals and Covid19 using network pharmacological analysis further substantiate the importance of medicinal scaffolds. The structural dynamics and binding affinities of phytochemical compounds xanthoangelol_E, hesperetin, and beta-sitosterol reported as highly potential against 3CLpro in cell-based and cell-free assays are consistent with the computational analysis. Whereas, the secondary metabolites such as sennosides A, B, C, D present in higher amount in Senna exhibited weak binding affinity and instability against the spike protein, helicase nsp13, RdRp nsp12, and 3CLpro. In conclusion, the results contravene fallacious efficacy claims of Senna tea interventions circulating on electronic/social media as Covid19 cure; thus emphasizing the importance of well-examined standardized data of the natural products in hand; thereby preventing unnecessary deaths under pandemic hit situations worldwide.

Internal Bremsstrahlung emission during 32P decay

The aim of this work is to experimentally investigate the role of Internal Bremsstrahlung (IB) in the decay of 32P, a pure β-emitter with end-point energy of 1.71 MeV and half-life of 14.28 days. IB is a continuous electromagnetic radiation occurring in β-decay, that had been widely studied in the past years. Its contribution, even if appreciable, is neglected in Monte Carlo (MC) simulation as well as in dosimetric and radiation protection calculations.Ionization current measurements were carried out using a well ionization chamber and compared with MC simulations, performed in the GAMOS (GEANT4-based Architecture for Medicine-Oriented Simulations) framework. Two experimental data sets of 32P IB spectra, taken from the literature, were used to model the IB photon spectral distribution and to include IB emission as an additional source term in MC calculation.Without IB, MC simulations underestimate up to about −18% the measured exposure, whereas the inclusion of IB according to either of the two spectra lead to differences of +2% or +8%. Consequently, the IB process is relevant for high-energy pure β-emitters such as 32P, and its contribution should be considered in all the dosimetric and radioprotection calculations.

Exploring PI3Kγ binding preference with Eganelisib, Duvelisib, and Idelalisib via energetic, pharmacophore and dissociation pathway analyses

Phosphatidylinositol 3-kinase (PI3K) is the central regulator of cellular functions and is suggested as a target for various diseases; thus, effective PI3K inhibitors provide a promising opportunity for the pharmaceutical intervention of many diseases. Among them, PI3Kγ has received more attention because of its essential role in immune signaling. However, the development of novel selective PI3Kγ inhibitors is a major challenge due to the high sequence homology across the class I PI3K isoforms. Therefore, understanding the substrate specificity and receptor-ligand interaction of PI3Kγ would be an appropriate strategy for the rational design of potent γ-selective inhibitors. In this study, by combining various molecular modeling approaches (including classic and enhanced sampling molecular dynamics (MD) simulations, end-point binding free energy calculations, and pharmacophore models), three quinolinone core-containing inhibitors, Idelalisib/CAL-101, Duvelisib/IPI-145, and Eganelisib/IPI-549, were employed to reveal the selective binding mechanisms targeting PI3Kγ. The classic MD and free energy calculations highlight the significant interaction and some key residues for the selective binding against PI3Kγ. Furthermore, the dissociation pathway analysis based on umbrella sampling simulations reveals that hydrophobic interactions are dominant for binding of the three ligands during the dissociation processes, and cooperation between the P-loop and the ligands always exists in the binding/dissociation process. Finally, the pharmacophore model revealed that IPI-549 contains a unique hydrophobic feature, and PI3Kγ exhibits an important hydrogen bond donor feature of hydrogen amide. These findings may provide some important information for the rational design and optimization of PI3Kγ-selective inhibitors.

Photo-neutron cross-section of natGd in the bremsstrahlung end-point energies of 12–16 MeV and 60–70 MeV

Photo-neutron cross-section of natGd in the bremsstrahlung end-point energies of 12–16 MeV and 60–70 MeV

Cross-sections for the 27Al(γ, x)22Na multichannel reaction with the 28.3 MeV difference of reaction thresholds

The bremsstrahlung flux-averaged cross-sections and the cross-sections per equivalent photon were first measured for the photonuclear multichannel reaction at end-point bremsstrahlung gamma energies ranging from 35 MeV to 95 MeV. The experiments were performed with the beam from the NSC KIPT electron linear accelerator LUE-40 using the γ-activation technique. The bremsstrahlung quantum flux was calculated with the GEANT4.9.2 program and was also monitored via the reaction. The flux-averaged cross-sections were calculated using the partial cross-section values computed with the TALYS1.95 code for different level density models. Consideration is given to special features of calculating the cross-sections and for the case of the final nucleus via several partial channels : .

A simple method for estimating the potential of the pyroelectric crystal surface

The potential of the pyroelectric crystal surface has been estimated using experimental data. The temperature of the pyroelectric crystal, the electron current from the crystal surface to the target, and the X-ray spectrum were simultaneously measured. The potential calculated from the temperature and the electron current was compared with the experimental endpoint energy of the X-ray spectrum. The calculated potential reasonably agreed with the experimental endpoint energy.

Calorimeter with Bayesian unfolding of spectra of high-flux broadband x rays.

We report the development of a multipurpose differential x-ray calorimeter with a broad energy bandwidth. The absorber architecture is combined with a Bayesian unfolding algorithm to unfold high energy x-ray spectra generated in high-intensity laser-matter interactions. Particularly, we show how to extract absolute energy spectra and how our unfolding algorithm can reconstruct features not included in the initial guess. The performance of the calorimeter is evaluated via Monte Carlo generated data. The method accuracy to reconstruct electron temperatures from bremsstrahlung is shown to be 5% for electron temperatures from 1 to 50 MeV. We study bremsstrahlung generated in solid target interaction showing an electron temperature of 0.56 ± 0.04 MeV for a 700 μm Ti titanium target and 0.53 ± 0.03 MeV for a 50 μm target. We investigate bremsstrahlung from a target irradiated by laser-wakefield accelerated electrons showing an endpoint energy of 551 ± 5 MeV, inverse Compton generated x rays with a peak energy of 1.1 MeV, and calibrated radioactive sources. The total energy range covered by all these sources ranges from 10 keV to 551 MeV.

Measurements of neutron and photon induced cross sections for the production of medical isotopes of strontium

The cross sections of the 88Sr(n,2n)87Srm, 88Sr(n,p)88Rb, 88Sr(n,α)85Kr, 86Sr(n,2n)85Srm, 86Sr(n,2n)85Srg and 84Sr(n,2n)83Sr nuclear reactions at 14.77 ± 0.17 MeV neutron energy and the average cross sections of the 88Sr(γ,n)87Srm and 86Sr(γ,n)85Srm nuclear reactions at bremsstrahlung of 15 MeV endpoint energy were measured with the activation method and offline gamma-ray spectroscopy. The measured cross sections were reported with a detailed covariance analysis for uncertainty and correlation coefficients. The experimental results were compared with the previously reported experimental data from the EXFOR database and the evaluated data from the TENDL-2019 library. Statistical model calculations were performed with the latest TALYS-1.95 code with optimised input parameters to better reproduce reported experimental data. The measured cross sections were found to be in good agreement with the literature and theoretical calculations. These results highlight the alternate production routes for the medical radioisotopes of 87Srm and 85Srg.

Hit evaluation results in 5-benzyl-1,3,4-thiadiazole-2-carboxamide based SIRT2-selective inhibitor with improved affinity and selectivity

Sirtuin 2 (SIRT2), member of sirtuin family, belongs to class III histone deacetylases (HDACs) and is majorly cytosolic with occasional nuclear translocation. The enzymatic activity of SIRT2 is dependent on nicotinamide adenine dinucleotide (NAD+) and SIRT2 regulates post-translational modifications that are responsible for deacetylation of lysine residues in histone and non-histone substrates. SIRT2, thus affects most likely multiple cellular processes, such as signaling, gene expression, aging, autophagy, and has been identified as potential drug target in relation to inflammation, neurodegenerative diseases and cancer. Therefore, probing potential selective inhibitors is essential for the accurate understanding of enzyme functions. Here, we report a series of heteroaryl-2-carboxamide hybrids bearing substituted benzyl or substituted phenoxy group at the 5-position of the central heterocyclic ring. The synthesized compounds were screened against SIRT1-3 and MCF-7 human breast cancer cell line to evaluate their biological activity. The best SIRT2 inhibition profiles were displayed by ST29 (SIRT2 IC50 = 38.69 μM) and ST30 (SIRT2 IC50 = 43.29 μM) with excellent selectivity against SIRT2 over SIRT1 and SIRT3. Molecular docking study of the synthesized compounds into SIRT2 active site was performed to rationalize the remarkable SIRT2 inhibitory activity. Furthermore, we performed all-atom, explicit-solvent molecular dynamics (MD) simulations and end-point binding free energy calculations using molecular mechanics/generalized Born surface area (MM/GBSA) method to evaluate whether this design strategy was successfully deployed. The results implied that the binding poses and ligand affinities were predicted without significant loss of accuracy. Conclusively, the developed chemotypes were advocated as promising leads for SIRT2 inhibition and required further investigation for SIRT2-targeted drug discovery and development.

Study of 14N(γ,np)3α Reaction for Eγ up to 150 MeV

The reaction 14N(g,np)3a induced by bremsstrahlung photons of endpoint energy Egmax = 150 MeV has been investigated using diffusion chamber, which is placed into the magnetic field. The distribution functions of the reaction yield, the energy and momentum of the final particles from Еg were measured and it was determined that at Еg > 45 MeV, change in the behavior of these functions occurs. The average energy Taver was calculated for the particles with the energy falling within a 1 MeV interval of the total kinetic energy T0 = Eg ‑ Q, where Q is the energy threshold of the reaction (Q = 19.77 MeV). At T0 ~ 20 MeV, the dependence of the contributions from Taver to T0 changes sharply. At T0 > 20 MeV, most of the energy is carried away by nucleons, their relative contribution is equal, and this agrees with the assumption of the quasideuteron interaction mechanism. The momentum distribution distributions for the neutron and proton have a similar form, with a strong shift of the maximum towards higher energies with an increase in the energy of the γ quantum. For a system of 3α‑particles, in each distribution, peak is observed centered at 100 MeV/c, the relative contribution of which smoothly decreases with increasing momentum, and a wide high-energy "tail" appears. The energy and angular correlations of the np‑pair depends on both of the energy Еg and the momentum of the system of 3α‑particles.

Pyroelectric material property considerations for x-ray generation

The method of generating x-rays using the pyroelectric effect has garnered interest for applications that desire portability and low power consumption, particularly for real-time in-field and on-line analyses. However, the x-ray intensity produced by this type of x-ray generator is low and inconsistent compared to conventional x-ray tubes. The properties of several pyroelectric materials, including LiTaO3, LiNbO3, and PMN-xPT, were studied and subsequently tested on an in-house developed x-ray generator to explore their suitability for the application. The production of electrons to subsequently generate x-ray relies on the process of ferroelectric electron emission and field ionization to be dominant over charge compensation via the DC conductivity of the pyroelectric material. Given that the time of temperature change occurs faster than the material's charge relaxation time, it was found that the ratio of the pyroelectric coefficient to relative permittivity determined the performance of the x-ray generator. Thus, the x-ray count rates and end-point energies produced by LiTaO3 showed that it continues to be a strong candidate for such x-ray generation applications.

Работы по ядерной спектроскопий выполненные с участием Монгольских Сотрудников в ЛЯП

Decay schemes of 150-157Er and 148-161Ho have been studied. β-, γ-, X-rays and conversion electrons were investigated and ten new isotopes and isomeric states were identified at the first time. Endpoint energies of β*-spectrum were measured using an intrinsic germanium detector, and Qec values have been obtained. A group of proton emitters of Au, Ir, Re and Ta have been identified, and the proton drip line was determined. Anisotropics of the gamma rays in well deformed Yb isotopes have been measured from the decay of radioactive Lu oriented at at low temperature. Multipole mixing ratio of the hundreds transitions have been deduced, about 170 of them uniquely and unambiguous spin assignments were made for 30 levels. External perturbations of two 171Yb levels have been observed.
 Study of the decay for 112-118In isotopes were the first nuclear physics experimental work in Mongolia. Mini-orange β*-spectrometer was constracted in Dubna for the inner conversion electrons measurements for neutron deficit nuclides. Measured conversion coclTicicnts were used for determination the transition mullipolaritics. A specific method for efficiency calibration of mini-orange spectrometer was applied using the continuous β* -spectrum of 90Sr in energy range from 500 to 2200 keV.

Activation cross section measurements and estimation of photon and neutron induced nuclear reactions for ytterbium isotopes with covariance analysis

The cross sections of the 168Yb(n,2n)167Yb, 174Yb(n,p)174Tm, 173Yb(n,p)173Tm, 174Yb(n,α)171Er, 170Yb(n,2n)169Yb and 176Yb(n,2n)175Yb nuclear reactions at 14.77 MeV neutron energy and the flux weighted average cross sections of the 168Yb(γ,n)167Yb, 170Yb(γ,n)169Yb and 176Yb(γ,n)175Yb nuclear reactions at 10 and 15 MeV bremsstrahlung endpoint energies are measured using offline gamma spectroscopy. The bremsstrahlung photon-induced reactions are reported for the first time at these energies. The results are compared with the evaluated nuclear data from the ENDF/B.-VIII.0, JEFF-3.3 and TENDL-2019 libraries. The theoretical model calculations are performed with the TALYS-1.95 nuclear code with parameters tuned to reproduce the measured data. The measured cross sections are in good agreement with the literature and evaluated data. The results are significant for the experimental nuclear database and reactor technology development.

Computational method for the optimization of quasimonoenergetic laser Compton x-ray sources for imaging applications.

The development of compact quasimonoenergetic x-ray radiation sources based on laser Compton scattering (LCS) offers opportunities for novel approaches to medical imaging. However, careful experimental design is required to fully utilize the angle-correlated x-ray spectra produced by LCS sources. Direct simulations of LCS x-ray spectra are computationally expensive and difficult to employ in experimental optimization. In this manuscript, we present a computational method that fully characterizes angle-correlated LCS x-ray spectra at any end point energy within a range defined by three direct simulations. With this approach, subsequent LCS x-ray spectra can be generated with up to 200 times less computational overhead.

Measurements and estimation of cross sections of neutron and bremsstrahlung induced nuclear reactions for neodymium isotopes with covariance analysis

The cross sections of the nuclear reactions 142Nd(n,2n)141Nd, 148Nd(n,2n)147Nd, 150Nd(n,2n)149Nd, 142Nd(n,2n)141mNd and 146Nd(n,p)146Pr at 14.77 MeV neutron energy and the cross section of the 142Nd(γ,n)141Nd, 148Nd(γ,n)147Nd and 150Nd(γ,n)149Nd nuclear reaction at 10 and 15 MeV bremsstrahlung endpoint energies were measured using offline gamma spectroscopy. The photon-induced cross sections are reported for the first time at 10 MeV and 15 MeV bremsstrahlung endpoint energies. The uncertainties in the measured data were calculated using covariance analysis. The experimental results were compared with the previously reported EXFOR data and with the evaluated nuclear data libraries ENDF/B.-VIII.0, JEFF-3.3, JENDL-4.0, CENDL-3.2 and TENDL-2019. The theoretical nuclear model calculations were performed using the TALYS-1.95 code with default and optimized input parameters tuned to reproduce the present and literature data. The present data are in good agreement with other literature and evaluated data. The results are useful for the development of particle accelerators, reactors and the EXFOR database.

Antineutrino detection for temporal monitoring of fuel burnup in a large nuclear reactor

The objective of this work is to determine if coherent-elastic-neutrino-nucleus scatter (CEνNS) in natural germanium detectors can be used to detect antineutrinos from an AP1000-type fission reactor. In this work, we first modeled the AP1000 core using Monte Carlo N-Particle Transport Code 6.2 (MCNP) to estimate the number of fissions from each fissile isotope in the core. Next, the reactor antineutrino spectrum was computed using the summation method for fuel burnup from 10 to 60 GWd/MTU. It was found that with the increasing fuel burnup, as the 239Pu inventory builds-up in the fuel and the 235U inventory depletes, the contributions from 239Pu to fission is enhanced. Thus, the antineutrino energy spectrum begins to skew more towards lower energies as seen by the quantification of third and fourth central moments. Increased fuel burnup also results in greater antineutrino production. The detection setup assumes a 100-kg CEνNS based natural germanium detector, which is placed outside the reactor containment, 25 m away from the core. The detector has a 100-eV nuclear recoil (NR) threshold and experiences a background level of 100 differential rate units (DRU), per kg.keV.day, due to surrounding radiation interacting in the detector. We then computed the differential pulse height distribution responses for two 235U enrichment cases: 3.3-wt-% and 4.4-wt-% at burnup levels of 10, 20, 40, and 60 GWd/MTU. Overall, the detection rate decreases when the burnup increases. This study indicates that germanium pulse height distribution end-point energies decrease with increasing fuel burnup and become less separable. Thus, we note that the CEνNS detector resolution would need to be higher for more burned fuel. A 16-eV NR is sufficient for distinguishing fresh fuel from that burned to 20 GWd/MTU. We also investigate the ability to detect a difference between burnups: 10 and 20 GWd/MTU, 10 and 40 GWd/MTU, 10 and 60 GWd/MTU, based on the integral detector counts after accounting for background and detection threshold. We determined that fuel burnup deviations can be detected with confidence much greater than 20%, as required by the IAEA, for low likelihood events. For 3.3-wt-% 235U enrichment, the confidence levels to distinguish burnup between 10 and 20 GWd/MTU, 10 and 40 GWd/MTU, 10 and 60 GWd/MTU are 80.60%, 100%, and 100%, respectively. For 4.4-wt% 235U enrichment, but the same three burnup comparisons, the confidence levels decreased marginally to 65.52%, 100%, and 100%, respectively.

Amphiphilic cyclodextrins: Dimerization and diazepam binding explored by molecular dynamics simulations

Amphiphilic cyclodextrins spontaneously aggregate to form different supramolecular assemblies with potential applications in drug release. Herein, we employ extended molecular dynamics simulations in order to characterize the structure and dynamics in explicit solvent of several amphiphilic derivatives of the β-cyclodextrin (β-CD) molecule, with aliphatic chains ester-bound to the wide rim of the hydrophobic cavity. We also study the binding properties considering a typical guest (diazepam) and the dimerization of these macrocyclic systems, assessing the relative stability of the complexes by means of end-point free energy methods. Different lengths (C4, C10, and C14 atoms) are considered for the alkyl side chains included in the amphiphilic β-CD-Cn molecules. According to the simulations, the length of these Cn moieties determines the complexing and aggregation capabilities of the β-CD-Cn systems. Compared to the native β-CD, the alkyl side chains in the β-CD-Cn molecules destabilize the inclusion complexes with diazepam and hinder the access of guest molecules to the hydrophobic cavity. In turn, dimerization is favored in the largest amphiphilic derivatives associated to the hydrophobic interaction between the Cn fragments.

Developing end-point methods for absolute binding free energy calculation using the Boltzmann-quasiharmonic model.

Understanding the physical forces underlying receptor-ligand binding requires robust methods for analyzing the binding thermodynamics. In end-point binding free energy methods the binding free energy is naturally decomposable into physically intuitive contributions such as the solvation free energy and configurational entropy that can provide insights. Here we present a new end-point method called EE-BQH (Effective Energy-Boltzmann-Quasiharmonic) which combines the Boltzmann-Quasiharmonic model for configurational entropy with different solvation free energy methods, such as the continuum solvent PBSA model and the integral equation-based 3D-RISM, to estimate the absolute binding free energy. We compare EE-BQH with other treatments of configurational entropy such as Quasiharmonic models in internal coordinates (QHIC) and in Cartesian coordinates (QHCC), and Normal Mode analysis (NMA), by testing them on the octa acids host-guest complexes from the SAMPL8 blind challenge. The accuracies in the calculated absolute binding free energies strongly depend on the configurational entropy and solvation free energy methods used. QHIC and BQH yield the best agreements with the established potential of mean force (PMF) estimates, with R2 of ∼0.7 and mean unsigned error of ∼1.7 kcal mol-1. These results from the end-point calculations are also in similar agreement with experiments. While 3D-RISM in combination with QHIC or BQH lead to reasonable correlations with the PMF results and experiments, the calculated absolute binding free energies are underestimated by ∼5 kcal mol-1. While the binding is accompanied by a significant reduction in the ligand translational/rotational entropy, the change in the torsional entropy in these host-guest systems is slightly positive. Compared with BQH, QHIC underestimates the reduction of configurational entropy because of the non-Gaussian probability distributions in the ligand rotation and a small number of torsions. The study highlights the crucial role of configurational entropy in determining binding and demonstrates the potential of using the new end-point method to provide insights in more complex protein-ligand systems.

Position sensitive plastic scintillator for beta particle detection

A new segmented plastic scintillator detector Tuike has been developed for recoil-beta tagging experiments at the Accelerator Laboratory of the University of Jyväskylä. The detector consists of individual plastic scintillator bars arranged in two orthogonal layers, and the scintillation light is detected using silicon photomultipliers. Performance of the new detector was tested using fusion-evaporation reaction 40Ca(36Ar, pn)74Rb, and the results are discussed here. It was found that for beta particles seen in the main silicon detector, Tuike can tag high-energy beta particles with a 48(10)% efficiency. An energy calibration method using Compton edges of gamma ray transitions is described in the present work. Tuike was demonstrated to improve the sensitivity to identify weak fusion-evaporation channels associated with beta decays having high beta end-point energy, enabling nuclear structure studies along the N = Z line.

Use of simplified models for theoretical prediction of the interactions between available antibodies and the receptor-binding domain of SARS-CoV-2 spike protein

The negative impact of infectious diseases like COVID-19 on public health and the global economy is evident. This pandemic represents a significant challenge for the scientific community to develop new practical analytical methods for accurately diagnosing emerging cases. Due to their selectivity and sensitivity, new methodologies based on antigen/antibody interactions to detect COVID-19 biomarkers are necessary. In this context, the theoretical, computational modeling reduces experimental efforts and saves resources for rational biosensor design. This study proposes using molecular dynamics to predict the interactions between the Receptor Binding Domain (RBD) of the SARS-CoV-2 spike protein simplified model and a set of highly characterized antibodies. The binding free energy of the antigen/antibody complexes was calculated for the simplified models and compared against the complete SARS-CoV-2 ectodomain to validate the methodology. The structural data derived from our molecular dynamics and end-point free energy calculations showed a positive correlation between both approximations, with a 0.82 Pearson correlation coefficient; t = 3.661, df = 3, p-value = 0.03522, with a 95% confident interval. Furthermore, we identified the interfacial residues that could generate covalent bonds with a specific chemical surface without perturbing the binding dynamics to develop highly sensitive and specific diagnostic devices. Communicated by Ramaswamy H. Sarma.