Background: Low-dose aspirin (LDA) is the backbone for secondary prevention of coronary artery disease, though limited by gastric toxicity. This study was aimed to identify novel metabolites that could predict LDA-induced gastric toxicity using pharmacometabolomics. Methods: Pre-dosed urine samples were collected from male Sprague-Dawley rats. The rats were treated with either LDA (10 mg/kg) or 1% methylcellulose (10 ml/kg) per oral for 28 days. The rats' stomachs were examined for gastric toxicity using a stereomicroscope. The urine samples were analyzed using a proton nuclear magnetic resonance spectroscopy. Metabolites were systematically identified by exploring established databases and multivariate analyses to identify the spectral pattern of metabolites related to LDA-induced gastric toxicity. Results: Treatment with LDA resulted in gastric toxicity in 20/32 rats (62.5%). The orthogonal projections to latent structures discriminant analysis (OPLS-DA) model displayed a goodness-of-fit (R2Y) value of 0.947, suggesting a near-perfect reproducibility, a goodness-of-prediction (Q2Y) of -0.185 with perfect sensitivity, specificity and accuracy (100%). Furthermore, the area under the receiver operating characteristic (AUROC) displayed was 1. The final OPLS-DA model had an R2Y value of 0.726 and Q2Y of 0.142 with sensitivity (100%), specificity (95.0%) and accuracy (96.9%). Citrate, hippurate, methylamine, trimethylamine N-oxide and alpha-keto-glutarate were identified as the possible metabolites implicated in the LDA-induced gastric toxicity. Conclusion: The study identified metabolic signatures that correlated with the development of a low dose Aspirin-induced gastric toxicity in rats. This pharmacometabolomic approach could further be validated to predict LDA-induced gastric toxicity in patients with coronary artery disease.

Nuclear magnetic resonance (NMR) techniques are widely used to identify pure substances and probe protein dynamics. Edible oil is a complex mixture composed of hydrocarbons, which have a wide range of molecular size distribution. In this research, low field NMR (LF-NMR) relaxation characteristic data of various sample oils were analyzed. We also suggest a new method for prediction size of edible oil molecules using LF-NMR relaxation time distributions. According to the relative molecular mass, carbon chain length, transverse relaxation time of different sample oils, combined with oil viscosity and other factors, the relationship between carbon chain length and transverse relaxation time rate was analyzed. Various oils and fats in the mixed fluid are displayed, reflecting the composition information of different oils. To study the correlation between the rotation correlation time and molecular information of oil molecules. The molecular composition of the resulting fluid determines its properties, such as viscosity and phase behavior. The results show that low-field NMR can obtain information on the composition, macromolecular aggregation, and molecular dynamics of complex fluids. Measurements of grease in the free fluid state show that the relaxation time can reflect the intrinsic properties of the fluid. It is shown that the composition characteristics and states of complex fluids can be measured by low-field nuclear magnetic resonance.

Chemical analysis of the organic components in beers has applications to quality control, authenticity and improvements to the flavor characteristics and brewing process. This study aims to show the complementary nature of two instrumental techniques which in combination can identify and quantify the majority of organic components in a beer sample. Nuclear Magnetic Resonance (NMR) was used to provide concentrations of twenty five different organic compounds including alcohols, organic acids, carbohydrates, and amino acids. Calorie content was also estimated for the samples. NMR data for ethanol concentrations were validated by comparison to a Fourier Transform Infrared Spectrometry (FTIR) method. Headspace Solid-Phase Microextraction (SPME) Gas Chromatography Mass Spectrometry (GCMS) was used to identify a range of volatile compounds such as alcohols, esters and hop derived aroma compounds. A simple and inexpensive conversion of a Gas Chromatography Flame Ionization Detector (GC FID) instrument to allow the use of Solid-Phase Microextraction was found to be useful for the quantification of volatile esters.

The clinical characterization of small hepatocellular carcinoma (HCC) lesions in the liver and differentiation from heterogeneous inflammatory or fibrotic background is important for early detection and treatment. Metabolic monitoring of hyperpolarized ¹³C-labeled substrates has been suggested as a new avenue for diagnostic magnetic resonance. The metabolism of hyperpolarized [1-¹³C]pyruvate was monitored in mouse precision-cut liver slices (PCLS) of aged MDR2-KO mice, which served as a model for heterogeneous liver and HCC that develops similarly to the human disease. The relative in-cell activities of lactate dehydrogenase (LDH) to alanine transaminase (ALT) were found to be 0.40 ± 0.06 (n = 3) in healthy livers (from healthy mice), 0.90 ± 0.27 (n = 3) in heterogeneously inflamed liver, and 1.84 ± 0.46 (n = 3) in HCC. Thus, the in-cell LDH/ALT activities ratio was found to correlate with the progression of the disease. The results suggest that the LDH/ALT activities ratio may be useful in the assessment of liver disease. Because the technology used here is translational to both small liver samples that may be obtained from image-guided biopsy (i.e., ex vivo investigation) and to the intact liver (i.e., in a non-invasive MRI scan), these results may provide a path for differentiating heterogeneous liver from HCC in human subjects.

Vitamin E, a potent antioxidant, is a necessary and complex micronutrient for cows. During the transition period, vitamin E deficiency (VED) is among the highest prevalent micronutrient deficits in dairy cows. It may eventually result in oxidative stress and immunological malfunction, and it increases the risk of peripartum disorders. At present, detailed data on blood metabolites in VED cows are limited. Consequently, the purpose of this research was to examine the alterations in the serum metabolic profile of VED cows throughout the early postpartum period. Using comprehensive 1H nuclear magnetic resonance (1H NMR), the alterations in serum metabolic activities of VED cows were analyzed. In total, 28 multiparous Holstein cows were assigned according to serum α-tocopherol (α-Toc) concentrations into a normal (α-Toc ≥ 4 μg/mL, n = 14) and VED (α-Toc < 3 μg/mL, n = 14) groups at 21 days postpartum, and their blood samples were collected for biochemical and 1H NMR analyses. A t-test on independent samples as well as multivariate statistics were used to assess the findings. In comparison with normal cows, VED cows showed significantly worse body condition scores, milk yield, and dry matter intake (p < 0.05). Significantly higher levels of serum non-esterified fatty acids, aspartate aminotransferase, low-density lipoprotein, and malonaldehyde were found in VED-affected cows, as well as lesser concentrations of serum albumin, high-density lipoprotein, and total antioxidant capacity in comparison with normal cows (p < 0.01), while other vitamins and minerals concentrations showed no distinction between the groups (p > 0.05). Furthermore, 24 upregulated serum metabolites were identified under VED conditions. The metabolomics pathway analysis of these metabolites demonstrated that a global metabolic response to VED in cows was represented by changes in 11 metabolic pathways, comprising energy, carbohydrate, and amino acid metabolism. These outcomes suggest that VED cows were more likely to experience a negative energy balance characterized by alterations of common systemic metabolic processes and develop oxidative stress, inflammation, and ultimately liver injury. This study provides the first evidence of metabolic changes in cows with VED.

Multinuclear NMR studies of the gaseous mixtures that involve volatile compounds and ³He atoms are featured in this review. Precise analyses of the ³He and other nuclei resonance frequencies show linear dependences on the gas density. Extrapolation of the gas phase results to the zero-pressure limit gives ν₀(³He) and ν₀(ⁿX) resonance frequencies of nuclei in a single 3-helium atom and nuclei in molecules at a given temperature. The NMR frequency comparison method provides an approach for determining different nuclear magnetic moments. Application of quantum chemical shielding calculations which include a more complete and careful theoretical treatment allows the shielding of isolated molecules to be achieved with great accuracy and precision. They are used for evaluation of nuclear moments without shielding impact on bare nuclei: ^10/11B, ¹³C, ¹⁴N, ¹⁷O, ¹⁹F, ²¹Ne, ²⁹Si, ³¹P, ³³S, ^35/37Cl, ³³S , ⁸³Kr, ^129/131Xe, and ¹⁸³W. On the other hand, new results of nuclear moments were used for reevaluation of absolute nuclear magnetic shielding in molecules under study. Additionally, ³He gas in water solutions of lithium and sodium salts was used for measurements of ^6/7Li and ²³Na magnetic moments and reevaluation of shielding parameters of Li⁺ and Na⁺ water solvated cations. In this paper, guest ³He atoms that play a role in probing the electron density in many host macromolecules are presented as well.

The atomic nucleus contains protons and neutrons surrounded by a structured electron cloud. Some combinations of protons and neutrons induce the nucleus to behave like a microscopic magnet, possessing a unique magnitude and orientation known as the nuclear magnetic moment (µ). When the numbers of protons and neutrons are both even then µ=0, but otherwise each nu-clide’s nuclear magnetic moment is unique. A second unique nuclear physical property relates to the nucleon binding energy (BE), which can be thought of as the energy between protons and neu-trons bound within the nucleus. The sequence of stable nuclides increases one nucleon at a time through 36Ar. The binding energy associated with the addition of each successive nucleon (∆BE) through this progression is unique. The hypothesis here is that the unique non-zero magnetic mo-ment and ∆ binding energy of each nuclide derive from its respective microscopic nuclear struc-ture, analogous to the way that the atomic physical properties of an element ultimately derive from its unique electron orbital structure. By extension, the identification of nuclear periodic pat-terns might eventually inform a theory of nuclear structure. The light, stable nuclides through 36Ar were arranged in ascending order according to atomic mass, and their nuclear magnetic mo-ments and binding energies were evaluated for periodic patterns. Fixed-period lengths from 4 through 18 nuclides per period were considered. These fixed periods, each of equal length, were stacked one upon the other and analyzed for vertical trends. The best evidence of periodicity in both µ and ∆BE converges precisely at the fixed 12-nuclide period. Implications for nuclear structure are discussed.

This contribution is an attempt to reconstruct the favorable atmosphere that prevailed in Lau-sanne in 1986-87 and provided the backdrop of our invention of two-dimensional ion cyclotron resonance mass spectroscopy (2D ICR-MS). To avoid a self-centered histoire d’ancien combattant, we shall try to emphasize the context, the contributions of key players within our nascent research group at UNIL and the established group of Tino Gäumann at EPFL, the role of external speakers, and the open atmosphere that was not yet polluted by bibliometrics, obsessive concern with im-pact factors, and top-down management of research. We shall also explain why the idea of 2D ICR-MS has been ignored for many years and still has a limited impact: different scientific cul-tures in the ICR and NMR communities, different concerns with fundamental vs. applied research, different status of theory and numerical simulations, different levels of commitment of instrument manufacturers, not to mention many theoretical problems that appear to be at least as challenging in ICR as in NMR.

We propose a method of cooling nuclear spin systems of solid-state nanostructures by application of a time-dependent magnetic field synchronized with spin fluctuations. Optical spin noise spectroscopy is considered as the method of fluctuation control. Depending on the mutual orientation of the oscillating magnetic field and the probe light beam, cooling might be either provided by dynamic spin polarization in an external static field or result from population transfer between spin levels without build-up of a net magnetic moment (“true cooling”).

The LiCl and LiNO₃ water solutions in the presence of small amounts of 3-helium have been investigated by means of multinuclear resonance spectroscopy. The resulting concentration dependences of the ³He, ^6,7Li⁺, ¹⁴NO₃^¯ and ³⁵Cl^¯ resonance radiofrequencies are reported in the infinite limit. This data along with new theoretical corrections of shielding lithium ions was analyzed by a known NMR relationship method. Consequently, the nuclear magnetic moments of ⁶Li and ⁷Li were established against that of the helium-3 dipole moment: μ(⁶Li)=+0.822046(5)μ_N and μ(⁷Li)=+3.256418(20)μ_N. The new results were shown to be very close to the previously obtained values of the (ABMR) atomic beam magnetic resonance method. This experiment proves that our helium method is well suited for establishing dipole moments from NMR measurements performed in water solutions. This technique is especially valuable when gaseous substances of the needed element are not available. All shielding constants of species present in water solutions are consistent with new nuclear magnetic moments and these taken as a reference. Both techniques – NMR and ABMR – give practically the same results providing that all shielding corrections are properly made.

In our previous published papers, considering 3 large atomic gravitational constants assumed to be associated with weak, strong and electromagnetic interactions, we have proposed the existence of a nuclear charge of magnitude, e_n=2.95e and developed a nuclear mass formula associated with strong and weak interactions having 4 simple terms and only one energy coefficient. Two important assumptions are, there exists a weak fermion of rest energy 585 GeV and strong coupling constant is the squared ratio of electromagnetic charge and nuclear charge. The aim of this paper is associated with understanding the mystery of quantum of magnetic flux, Planck’s quantum radiation constant and Reduced Planck’s constant. Proceeding further, quark charges, strong coupling constant, nuclear stability, nuclear binding energy, medium and heavy atomic X-ray levels and celestial magnetic moments can be understood in a unified approach. It may also be noted that, by considering integral nature of elementary particle masses, it seems possible to understand the discreteness of angular momentum. Considering our proposed e_n=2.95e=3e as a characteristic nuclear charge, it seems possible to understand the integral nature of quarks electromagnetic charge. With this idea, neutron, proton and pions decay can be understood very easily. In all the cases, up quark of charge (±2e) seems to play a crucial role with the internal transformation of down quark of charge (±e) and external observable elementary basic elementary particles. It needs further study at fundamental level.

Relying on the United Arab Emirates (UAE) extract from the cross-national data sample on the environmental affection and cognition of adolescent students, and seemingly unrelated bivariate weighted ordered probit regression modeling, this study adopts a national perspective to investigate the determinants of adolescent students' awareness and expectations about nuclear power technology and nuclear waste in the UAE. Identification of model parameters is achieved through maximum simulated likelihood estimation. The findings show that each level increase in UAE youth's interest in ecosystem services and sustainability raises their awareness of nuclear electrical power and nuclear waste by 13.5%, while reducing by 2.4% their level of optimism towards the technology. Furthermore, we find significant heterogeneity in youth awareness and expectations about nuclear power technology across the seven Emirates. Accounting for all other factors (including interest in ecosystem services), UAE youth awareness about nuclear electrical power technology appears to not significantly influence their expectations about the evolution of this technology for the next 20 years. Given that the UAE first nuclear power plant ``Barakah'' is scheduled to start operations end of 2019 beginning 2020, and the typical long life-span of nuclear wastes, our results provide important insights for developing sustainable nuclear energy policies and establishing a long-term nuclear energy program in the UAE.

Nuclear technologies have the potential to play a major role in the transition to a global net-zero society. Their primary advantage is the capability to deliver controllable 24/7 energy on demand. However, as a prerequisite for successful worldwide application, significant innovation will be required to create the nuclear systems of the 21st century, the need of the hour. The pros and cons of nuclear are discussed and analysed at different levels – the societal and public recognition as well as the scientific/engineering and economic level – to assure a demand driven development. Based on the analysis of the different challenges a vision for the nuclear system of the 21st century is synthesised consisting of three pillars – unlimited nuclear energy, zero waste nuclear, and accident free nuclear. These three combined visions are then transformed into dedicated and verifiable missions which are discussed in detail regarding challenges and opportunities. In the following a stepwise approach for the development of such a highly innovative nuclear system is described. Essential steps to assure active risk reduction and the delivery of quick progress are derived as answer to the critique on the currently observed extensive construction time and cost overruns on new nuclear plants. The 4-step process consisting of basic studies, experimental zero power reactor, small scale demonstrator, and industrial demonstrator is described. The 4 steps including sub-steps deliver the pathway to a successful implementation of such a ground breaking new nuclear system. The potential sub-steps are discussed with the view not only onto the scientific development challenges, but also as an approach to reduce the regulatory challenges of a novel nuclear technology.

Small-scale facilities play a significant role in the landscape of nuclear physics research in Europe. They address a wide range of fundamental questions and are essential for teaching and training personnel in accelerator technology and science, providing them with diverse skill sets, complementary to large projects. The current status and perspectives of nuclear physics research at small-scale facilities in Europe will be given.

Traditionally there is a gap between reactor operation and the consideration of nuclear waste in the final disposal. Fuel is produced and fuel must be disposed of in the view of the reactor operator, fuel has to be cleaned in the reprocessing and new solid fuel has to be produced in the view of the chemist. iMAGINE is designed to overcome this separation through the breakthrough development applying an optimized, integrative approach from cradle to grave of nuclear energy production as a first step to come as close as possible to the vision of zero waste nuclear power. It is described here the first time all in three the steps: reactor, fuel cycle, waste, providing the ratio behind each of the choices taken to come to the overall solution to open the discussion and thinking process on what could be achieved by a really innovative approach to integrated nuclear energy production. The opportunities regarding the handling of the remaining waste will be discussed with a view on the expectation of the final disposal community, the study ‘Nuclear waste from small modular reactors’, and the IAEA report ‘waste from innovative types of reactors and fuel cycles - a preliminary study. The aim of the is not to find answers to each of the raised points, but to identify first potential approaches and potentially promising ways to go, as well as to stimulate a discussion among experts. In the best case this could lead to a change of track for nuclear to become an even more sustainable and at least as important, trusted technology to help solve the net-zero challenge.

Computationally modelling a nuclear reactor startup core for a benchmark against the existing models is highly desirable for an independent assessment informing nuclear engineers and energy policymakers. This work presents a startup core model of the UK’s first Evolutionary Pressurised Water Reactor (EPR) based on Monte Carlo simulations of particle collisions using Serpent 2, a continuous-energy Monte Carlo reactor physics burnup code. Coupling between neutronics and thermal-hydraulic conditions with the fuel depletion is incorporated into the multi-dimensional branches, obtaining the thermal flux and fission rate (power) distributions radially and axially from the three dimensional (3D) single assembly level to a 3D full core. Shannon entropy is employed to characterise the convergence of the fission source distribution, with 3 billion neutron histories tracked by parallel computing. Source biasing is applied for the variance reduction. Benchmarking the proposed Monte Carlo 3D full-core model against the traditional deterministic transport computation suite used by the UK Office for Nuclear Regulation (ONR), a reasonably good agreement within statistics is demonstrated for the safety-related reactivity coefficients, which creates trust in the EPR safety report.

Molten salt reactors have gained substantial interest in the last years due to their flexibility and their potential for simplified closed fuel cycle operation for massive net-zero energy production. However, a zero-power reactor experiment will be an essential first step into the process delivering this technology. The choice of the optimal reflector material is one of the key issues for such experiments since on the one hand it offers huge cost saving potential due to reduced fuel demand, on the other hand an improper choice of the reflector material can have negative effects on the quality of the experiments. The choice of the reflector material is for the first time introduced through a literature review and a discussion of potential roles of the reflector. The 2D study of different potential reflector materials has delivered a first down selection with SS 304 as representative for stainless steel, lead, copper, graphite, and beryllium oxide. A deeper look identified in addition iron-based material with high Si content. The following evaluation of the power distribution has shown the strong influence of the moderating reflectors creating a massively disturbed power distribution with a peak at the core boundary. This effect has been confirmed through a deeper analysis of the 2D multi-group flux distribution which lead to the exclusion of the BeO and the graphite reflector. The most promising materials identified have been SS 304, lead, and copper. The final 3D Monte-Carlo study demonstrated that all three materials have the potential to reduce the required amount of fuel by up to 60% compared NaCl which has been used in previous studies and is now taken as reference A first cost analysis has identified the SS 304 reflector as the most attractive solution. The results of the 2D multi group deterministic study and the 3D multi group Monte-Carlo study have been confirmed through a continuous energy Monte-Carlo reference calculation showing only minor differences.

Molten salt reactors have gained substantial interest in the last years due to their flexibility and their potential for simplified closed fuel cycle operation for massive net-zero energy production. The importance of a zero-power reactor for the process of developing a new, innovative rector concept like molten salt fast reactor is described here. It is based on historical developments as well as the current demand for experimental results and key factors that are relevant to the success of the next step in the development process of all innovative reactor types. In the systematic modelling & simulation of a zero-power molten salt reactor, the radius and the feedback effects are studied for a eutectic based system, while a heavy metal rich chloride-based system are studied depending on the uranium enrichment accompanied with the effects on neutron flux spectrum and spatial distribution. These results are used to support the relevant decision for the narrowing down of the configurations supported by considerations on cost and proliferation for the follow up 3D analysis to provide for the first time a systematic modelling & simulation approach for a new reactor physics experiment. The expected core volumes for these configurations have been studied using multi-group and continuous energy Monte-Carlo simulations identifying the 35% enriched systems as the most attractive and finally leading to the choice of the heavy metal rich compositions 35% enrichment as the reference system for future studies of the next steps in the zero power reactor investigation. The inter-comparison of the different applied codes and approaches available in the SCALE package has delivered a very good agreement between the results creating trust into the developed and used models and methods.

Molten salt reactors have gained substantial interest in the last years due to their flexibility and their potential for simplified closed fuel cycle operation for massive net-zero energy production. However, a zero-power reactor experiment will be an essential first step into the process of delivering this technology. The topic of the control and shut down for a zero power reactor is for the first time introduced through a literature review and the reduction of the control approaches to a limited number of basic functions with different variations. In the following, the requirements for the control and shutdown system for a reactor experiment are formulated, and based on these assessments, an approach for the shutdown – splitting the lower part of the core with reflector, and an approach for the control – a vertically movable radial reflector are proposed. Both systems will be usable for a zero-power system with a liquid as well as with as a solid core and even more importantly, both systems somehow work on the integral system level without disturbing the central part of the core which will be the essential area for the experimental measurements. Both approaches have been investigated as a singular system as well as their interactions with one another and the sensitivity of the control system. The study has demonstrated that both proposed systems are able to deliver the required characteristics with sufficient shutdown margin and a sufficiently wide control span. The interaction of the system has been shown to be manageable and the sensitivity is on a very good level. The multi-group Monte-Carlo approach has been cross evaluated by a continuous energy test leading to good results, but they also demonstrate that there is room for improvement.

As there exist no repulsive forces in strong interaction, in a hypothetical approach, strong interaction can be assumed to be equivalent to a large gravitational coupling. Based on this concept, strong coupling constant can be defined as a ratio of the electromagnetic force and the gravitational force associated with proton, neutron, up quark and down quark. With respect to the product of strong coupling constant and fine structure ratio, we review our recently proposed two semi empirical relations and coefficients 0.00189 and 0.00642 connected with nuclear stability and binding energy. We wish to emphasize that- by classifying nucleons as ‘free nucleons’ and ‘active nucleons’, nuclear binding energy can be fitted with a new class of ‘three term’ formula having one unique energy coefficient. Based on the geometry and quantum nature, currently believed harmonic oscillator and spin orbit magic numbers can be considered as the lower and upper “mass limits” of quark clusters.

Nuclear technologies have a strong potential and a unique role to play in delivering reliable low carbon energy for a future net-zero society. However, to assure the sustainability required for the long-term success, nuclear will need to deliver innovative solutions as proposed in iMAGINE. One of the most attractive features, but also a key challenge for the envisaged highly integrated nuclear energy system is the need for a demand driven salt clean-up system. The work described provides an insight into the interplay between a potential salt clean-up system and the reactor operation in a plutonium started core in a dynamic approach. The results presented will help to optimize the parameters for the salt clean-up process as well as to understand the differences which appear between a core started with enriched Uranium and Plutonium as the fissile material. The integrated model is used to investigate the effects of the initial fissile material on core size, achievable burnup, and long term operation. Different approaches are tested to achieve a higher burnup in the significantly smaller Pu driven core. The effects of different clean-up system throughputs on the concentration of fission products in the reactor salt and its consequences are discussed for general molten salt reactor design. Finally, an investigation of how a plutonium loaded core could be used to provide fuel for future reactors through fuel salt splitting is presented with the outcome that one Pu started reactor of the same size as a uranium started core could deliver fuel for 1.5 new cores due to enhanced breeding. The results provide an essential understanding for the progress of iMAGINE as well as the basis for inter-disciplinary work required for optimizing iMAGINE.

Nuclear technologies have the potential to play a unique role delivering low carbon energy for a future net-zero society. However, for the long-term success, nuclear will need to deliver innovative solutions as proposed in iMAGINE. One of the key challenges for the envisaged highly integrated nuclear energy system is the need for a demand driven salt clean-up system. The work described provides an insight into the interplay between a potential salt clean-up system and the reactor operation in a dynamic approach. The results provided will help to optimize the parameters for the salt clean-up process by delivering a dynamically calculated priority list identifying the elements with high influence on reactor operation. The integrated model is used to investigate the ideal time for the initiation of the clean-up as well as the effect of different throughput through the clean-up system on criticality as well as on the concentration of the elements in the reactor salt. Finally, a staggered approach is proposed with the idea to phase in the chemical clean-up processes step by step to keep the reactor critical. The results provide an essential step for the progress of iMAGINE as well as the basis for the inter disciplinary work required to bring iMAGINE into real operation.

Following the concept of strong interaction, theoretically, fusion of proton seems to increase the binding energy of final atom by 8.8 MeV. Due to Coulombic repulsion, asymmetry effect, pairing effect and other nuclear effects, final atom is forced to choose a little bit of binding energy less than 8.8 MeV and thus it is able to release left over binding energy in the form of internal kinetic energy or external thermal energy. Thus, in cold fusion, heat release to occur, binding energy difference of final atom and base atom seems to be less than 8.8 MeV. Qualitatively, energy released during cold fusion seems to be approximately equal to 8.8 MeV minus the difference of binding energy of final and base atoms. Based on this idea, under normal conditions, for the case of ₂He⁴, fusion of four protons can liberate (35.2-28.3)=6.9 MeV and it is 3.5 times less than the current estimates. Point to be understood is that, lesser the binding energy of final atom, higher the liberated thermal energy and vice versa. With a suitable catalyst and sufficient hydrogen under suitable pressure, if reactor’s temperature is maintained at (1000 to 1500) ⁰C, there seems a lot of scope for a chain reaction of cold fusion in which light isotopes transform to their next stage with increased proton number or mass number and liberate safe and clean heat energy continuously. By arranging 4 to 6 reactors and charging them periodically in tandem, required thermal energy can be produced continuously. In this new direction, by carefully selecting the base isotope and its corresponding catalyst, experiments can be conducted and ground reality of cold fusion can be understood at various temperature and pressure conditions.

A hand-held laser-induced breakdown spectroscopy device was used to acquire spectral emission data from laser-induced plasmas created on the surface of cerium-gallium alloy samples with Ga concentrations ranging from 0 to 3 weight percent. Ionic and neutral emission lines of the two constituent elements were then extracted and used to generate calibration curves relating the emission line intensity ratios to the gallium concentration of the alloy. The Ga I 287.4 nm emission line was determined to be superior for the purposes of Ga detection and concentration determination.A limit of detection below 0.25% was achieved using a multivariate regression model of the Ga I287.4 nm line ratio versus two separate Ce II emission lines. This LOD is considered a conservative estimation of technique’s capability given the type of the calibration samples available and low power( 5 mJ per 1 ns pulse) and resolving power (λ/∆λ= 4000) of this handheld device. Nonetheless, the utility of the technique is demonstrated via a detailed mapping analysis of the surface Ga distribution of a Ce-Ga sample which reveals significant heterogeneity resulting from the sample production process.

With reference to our earlier published views on large nuclear gravitational constant , nuclear elementary charge and strong coupling constant , in this paper, we present simple relations for nuclear stability range, binding energy of isotopes and magic proton numbers.

The demand for improving the nuclear waste management has since long been identified as one of the major hurdles for widespread use of nuclear energy. Nuclear waste management, through partitioning and transmutation (P&T) has been researched since the 1990ies with partitioning being a pre-requisite for the process. Recently, an innovative approach of reactors directly operating on spent nuclear fuel, iMAGINE, has been proposed which could deliver on the aims of P&T as a side effect to more efficient nuclear energy production in the future. The results shown here confirm that it is possible to achieve the aims of P&T without prior partitioning, but it is certainly less efficient since the high concentration of MAs, required for efficient burning, are impossible to obtain in a short operational time. The proposed nuclear waste management approach will be a long-term effort when it is accomplished without partitioning/separation technologies. However, none of the analyses contradicts this effort – the key points are a) when the technology for treating the waste is possible and reliable, the time horizon will not be a major concern b) the waste management is now intrinsically linked with energy production instead of requiring dedicated costly facilities, delivering a promising economic basis c) the waste management is now associated with long-term energy production and massively improved resource utilization. In summary, the objectives of P&T are achievable without prior partitioning – this is a ground-breaking result. However, the approach will require continued nuclear energy production for a very long time. In case of a nuclear phase-out decision, a much more efficient transmutation scenario would have to be envisaged as already discussed several years ago for Germany.

The pregnane X receptor (PXR) is the main nuclear receptor regulating the expression of xenobiotic metabolizing enzymes and is highly expressed in the liver and intestine. Recent studies have highlighted its additional role in lipid homeostasis, however, the mechanisms of these regulations are not fully elucidated. We investigated the transcriptomic signature of PXR activation in the liver of adult wild-type vs Pxr-/- C57Bl6/J male mice treated with the rodent specific ligand pregnenolone 16α-carbonitrile (PCN). PXR activation increased liver triglyceride accumulation and significantly regulated the expression of 1215 genes mostly xenobiotic metabolizing enzymes. Among the down-regulated genes, we identified a strong peroxisome proliferator-activated receptor α (PPARα) signature. Comparison of this signature with a list of fasting-induced PPARα target genes confirmed that PXR activation decreased the expression of more than 25 PPARα target genes, among which the hepatokine fibroblast growth factor 21 (Fgf21). PXR activation abolished plasmatic levels of FGF21. We provide a comprehensive signature of PXR activation in the liver and identify new PXR target genes that might be involved in the steatogenic effect of PXR. Moreover, we show that PXR activation down-regulates hepatic PPARα activity and FGF21 circulation, which could participate in the pleiotropic role of PXR in energy homeostasis.

Evidence is growing that mankind must learn from nature, a self-sufficient and self-organized system that adopts all the opportunities to develop life and ingeniously makes the most of whatever energy source. Attempting to satisfy the requirements of our energy-consuming world, we cannot afford to disregard any available source of energy, mainly those characterized by zero-CO₂ emissions. In this context an alternative scenario could be opened by the use of the nuclear radiations emitted from naturally occurring or artificially produced radionuclides. Abandoned mines of U, Th and Rare Earths , as well as storage areas of artificially produced isotopes all over the globe are available and affordable sources of radiations that can be converted in electrical power. The transition from laboratory-scale nuclear batteries to large-area converting modules would allow to safely re-use a big amount of already existing radionuclides, converting a trouble into a resource.

Laminopathies are causally associated with mutations on Lamin A gene (LMNA). To date, more than 400 mutations in LMNA have been reported in patients. These mutations are widely distributed throughout the entire gene and are associated with a wide range of phenotypes. Unfortunately, little is known about the mechanisms underlying the effect of the majority of these mutations. This is the case of more than 40 mutations that are located at exon 4. Using CRISPR/Cas9 technology, we have generated a collection of Lmna exon 4 mutants in mouse C2C12 myoblasts. These cell models include different types of exon 4 deletions and the presence of R249W mutation, one of the human variants associated with a severe type of laminopathy (LMNA-associated congenital muscular dystrophy). We have characterized these clones by measuring their nuclear circularity, myogenic differentiation capacity in 2D and 3D conditions, DNA damage, and p-ERK and p-AKT levels. Our results indicate that Lmna exon 4 mutants show abnormal nuclear morphology. In addition, levels and/or subcellular localization of different members of the lamin and LINC complex are altered in all these mutants. Whereas no significant differences were observed for ERK and AKT activities, the accumulation of DNA damage was associated to the Lmna p.R249W mutant myoblasts. Finally, significant myogenic differentiation defects were detected in the Lmna exon 4 mutants. These results have key implications in the development of future therapeutic strategies for the treatment of laminopathies.

The importance of personalized medicine is growing, since there is an urged need to avoid unnecessary and expensive treatments. In nuclear medicine, the theranostic approach is an established tool for a specific molecular targeting in means of diagnostics and therapy. The visualisation of potential targets can help to predict if a patient would benefit from a particular treatment or not. Thanks to the quick development of radiopharmaceuticals and diagnostic techniques, the use of theranostic agents is constantly rising. In this article important milestones of nuclear therapies and diagnostics in the context of theranostics are highlighted. It begins with the well-known radioiodine therapy in patients with thyroid cancer and then guides through different approaches for the treatment of advanced cancer with targeted therapies. The aim of this review is to provide a summary of background knowledge, current applications and advantages of targeted therapies and imaging in nuclear medicine practice.

Nuclear bodies (NBs) are dynamic structures present in eukaryotic cell nuclei. They are not bounded by membranes and are often considered biomolecular condensates, defined structurally and functionally by the localisation of core components. Nuclear architecture can be reorganised during normal cellular processes such as the cell cycle as well as in response to cellular stress. Many plant and animal viruses target their proteins to NBs, in some cases triggering their structural disruption and redistribution. Although not all such interactions have been well characterised, subversion of NBs and their functions may form a key part of the life cycle of eukaryotic viruses that require the nucleus for their replication. This review will focus on Cajal bodies (CBs) and the viruses that target them. Since CBs are dynamic structures, other NBs (principally nucleoli and promyelocytic leukaemia, PML, bodies), whose components interact with CBs, will also be considered. As well as providing important insights into key virus: host cell interactions, studies on Cajal and associated NBs may identify novel cellular targets for development of anti-viral compounds.

At nuclear scale, we present three heuristic relations pertaining to strong and electroweak coupling constants. With these relations, close to beta stability line, it is possible to study nuclear binding energy with a single energy coefficient of magnitude $\left(\frac{1}{{\alpha }_s}\right)\left[\frac{e^2}{4\pi {\epsilon }_0{R}_0}\right]\approx 10.0\text{MeV}\text{.}$ With reference to up and down quark masses, it is also possible to interpret that, nuclear binding energy is proportional to the mean mass of $\left[\left(2m_u+m_d\right)\text{and}\left(m_u+2m_d\right)\right]\approx 10.0\text{MeV}.$

With reference to electromagnetic interaction and Abdus Salam’s strong (nuclear) gravity, 1) Square root of ‘reciprocal’ of the strong coupling constant can be considered as the strength of nuclear elementary charge. 2) ‘Reciprocal’ of the strong coupling constant can be considered as the maximum strength of nuclear binding energy. 3) In deuteron, strength of nuclear binding energy is around unity and there exists no strong interaction in between neutron and proton. $G_s\cong 3.32688\times {10}^{28}{\mathrm{m}}^3{\mathrm{kg}}^{-1}{\sec }^{-2}$ being the nuclear gravitational constant, nuclear charge radius can be shown to be, $R_0\cong \frac{2G_s{m}_p}{c^2}\cong 1.24\mathrm{fm}.$ $e_s\cong \left(\frac{G_s{m}_p^2}{\hslash c}\right)e\cong 4.716785\times {10}^{-19}\mathrm{C}$ being the nuclear elementary charge, proton magnetic moment can be shown to be, ${\mu }_p\cong \frac{e_s\hslash }{2m_p}\cong \frac{e{G}_s{m}_p}{2c}\cong 1.48694\times {10}^{-26}\mathrm{J}{.\mathrm{T}}^{-1}.$ ${\alpha }_s\cong {\left(\frac{\hslash c}{G_s{m}_p^2}\right)}^2\cong 0.1153795$ being the strong coupling constant, strong interaction range can be shown to be proportional to $\exp \left(\frac{1}{{\alpha }_s^2}\right).$ Interesting points to be noted are: An increase in the value of ${\alpha }_s$ helps in decreasing the interaction range indicating a more strongly bound nuclear system. A decrease in the value of ${\alpha }_s$ helps in increasing the interaction range indicating a more weakly bound nuclear system. From $Z\cong 30$ onwards, close to stable mass numbers, nuclear binding energy can be addressed with, ${\left(B\right)}_{A_s}\cong Z\times \left\{\left(\frac{1}{{\alpha }_s}+1\right)+\sqrt{\sqrt{30\times 31}}\right\}\left(m_n-m_p\right)c^2\approx Z\times 19.66\mathrm{MeV}.$ With further study, magnitude of the Newtonian gravitational constant can be estimated with nuclear elementary physical constants. One sample relation is, $\left(\frac{G_N}{G_s}\right)\cong \frac{1}{2}{\left(\frac{m_e}{m_p}\right)}^{10}\left[\sqrt{\frac{G_F}{\hslash c}}/\left(\frac{\hslash }{m_{e}c}\right)\right]$ where $G_N$ represents the Newtonian gravitational constant and $G_F$ represents the Fermi’s weak coupling constant. Two interesting coincidences are, ${\left(m_p/m_e\right)}^{10}\cong \exp \left(1/{\alpha }_s^2\right)$ and $2G_s{m}_e/c^2\cong \sqrt{G_F/\hslash c}.$

A review on several classical, algebraic models in nuclear structure physics, which use symmetries as an important tool, are presented. After a conceptual introduction to group theory, a selection of models is chosen to illustrate the methods and the power of the usage of symmetries. It enables to describe very involved systems in a greatly simplified manner. Some problems are also discussed, when ignoring basic principles of nature, as the Pauli Exclusion principle. We also show that, nevertheless, occasionally one can rescue these omissions. In a couple of representative models, applications of symmetries are explicitly applied, in order to illustrate how extremely complicate systems can be treated. This contribution is meant bas a review on the use of algebraic models in nuclear physics, leading to a better understanding of the articles in the same special volume.

Background: The identification of new cellular receptors has been increasing rapidly. A receptor is called “orphan” if an endogenous ligand has not been identified yet. Methods: Here we review receptors that contribute to prostate cancer and are considered orphan or partially orphan. This means that the full spectrum of their endogenous ligands remains unknown. Results: The orphan receptors are divided into two major families. The first group includes G protein-coupled receptors. Most are orphan olfactory receptors. OR51E1 inhibits cell proliferation and induces senescence in prostate cancer. OR51E2 inhibits prostate cancer growth, but promotes invasiveness and metastasis. GPR158, GPR110 and GPCR-X play significant roles in prostate cancer development and progression. However, GPR160 induces cell cycle arrest and apoptosis. The other major subset of orphan receptors are nuclear receptors. RORα inhibits tumor growth, but RORγ stimulates androgen receptor signaling. PXR contributes to metabolic deactivation of androgens and inhibits cell proliferation. TLX has pro-tumorigenic effects in prostate cancer, while its knockdown triggers cellular senescence and growth arrest. Estrogen-related receptor ERRγ can inhibit tumor growth but ERRα is pro-tumorigenic. Dax1 and Shp are also inhibitory in prostate cancer. Conclusion: There is a “zoo” of relatively underappreciated orphan receptors that play key roles in prostate cancer.

In this paper, a regression model between neutron star crust-core pressure and the symmetry energy characteristics was estimated using the Akaike information criterion and the adjusted coefficient of determination Radj2. Based on the obtained regression function, the most probable value of the transition density, which should characterize the crust-core environment of the sought physical neutron star model, was determined. An anti-correlation was found between this transition density and the main characteristic of the symmetry energy, i.e., its slope L.

: Background: Cartilage harvest and transplantation is a common surgery using costal, auricular, and septal cartilage for craniofacial reconstruction. However, absorption and warping of the cartilage grafts can occur due to inflammatory factors associated with wound healing. Transcriptional factor nuclear factor κB (NFκB) is activated by cytokines, such as interleukin-1 (IL-1), and plays a central role in the transactivation of this inflammatory cytokine gene. Inhibition of NFκB may have anti-inflammatory effects. The aim of this study was to explore the potential of an NFκB decoy oligodeoxynucleotide (Decoy) as a chondroprotective agent. Materials and Methods: Evaluation of safe and efficacious concentrations of Decoy were assessed using rabbit nasal septal chondrocytes (rNSCh) and assays for cytotoxicity, proteoglycan (PG) synthesis, and PG turnover. The efficacious concentration of Decoy determined from the rNSCh was then applied to human nasal septal cartilage (hNSC) in vitro and analyzed for PG turnover, the level of inflammatory markers, and catabolic enzymes in explant-conditioned culture medium. Results: Over the range of Decoy conditions and concentrations, no inhibition of PG synthesis or cytotoxicity was observed. Decoy at 10 μM effectively inhibited PG degradation in the hNSC explant, prolonging PG half-life 63% and decreasing matrix metalloprotease 3 (MMP3) by 70.7% (P = 0.027). Conclusions: Decoy may be a novel chondroprotective therapeutic agent in cartilage transplantation due to its ability to inhibit cartilage degradation due to inflammation cytokines.

Hutchison-Gilford progeria syndrome (HGPS) is an extremely rare genetic disorder caused by the mutant protein progerin, which is expressed by the abnormal splicing of LMNA gene. HGPS affects systemic levels, except cognition or brain development in children, showing that cellular aging can occur in the short term. However, the causes of aging that humanity is working to overcome remain poorly understood. Studying progeria could be useful for unraveling the causes of human aging (as well as fatal age-related disorders). Elucidating the clear cause of HGPS or the development of a therapeutic medicine will provide inconceivable comfort for young patients and enable them to live a normal life. This review aimed to: i) briefly describe how progerin was discovered as the causative agent of HGPS, ii) elucidate the puzzling observation of the absence of primary neurological disease in HGPS, iii) present several studies showing the deleterious effects of progerin and the beneficial effects of its inhibition, and iv) summarize research to develop a therapy for HGPS, and introduce clinical trials for its treatment.

During embryonic development stem cells undergo the differentiation process so that they can specialise for different functions within the organism. Complex programs of gene transcription are crucial for this process to happen. Epigenetic modifications and the architecture of chromatin in the nucleus, by the formation of specific regions of active as well as inactive chromatin, allow the coordinated regulation of the genes for each cell fate. In this mini review, we discuss the current knowledge regarding the regulation of three-dimensional chromatin structure during neuronal differentiation. We also focus on the role played in neurogenesis by the nuclear lamina that ensures the tethering of the chromatin to the nuclear envelope.

Human cytomegalovirus (HCMV) tegument protein pp150 is essential for the completion of final steps in virion maturation. Earlier studies indicated that three pp150nt (N terminal one-third of pp150) conformers cluster on each triplex (Tri1, Tri2A and Tri2B) and extend towards small capsid proteins atop nearby major capsid proteins forming a net-like layer of tegument densities that enmesh and stabilize HCMV capsids. Based on this atomic detail, we designed several peptides targeting pp150nt. Our data show significant reduction in virus growth upon treatment with one of these peptides (pep-CR2) with an IC50 of 1.33 μM. Based on 3D modeling, pep-CR2 specifically interferes with the pp150-capsid binding interface. Cells pre-treated with pep-CR2 and infected with HCMV sequester pp150 in the nucleus indicating a mechanistic disruption of pp150 loading onto capsids and subsequent nuclear egress. To enhance the in-vivo inhibitory potential and bioavailability of pep-CR2, we conjugated it with a carrier molecule (elastin like polypeptide (ELP)). The ELP-pep-CR2 conjugate was expressed in E.coli and purified. Upon treatment with ELP-pep-CR2, HCMV showed significant titer reductions with no significant impact on cell viability. These results indicate that CR2 of pp150 is amenable to targeting by a peptide inhibitor and can be developed into an effective antiviral.

Background: Convectional methods for drug delivery often faces setbacks due to systemic distribution, short half-life and degradation of therapeutics and therefore reduce concentrations of drug available to target tissue. Nanotheranostic provide a novel method for treating and diagnosing diseases Methodology: collection and review of relevant literatureResult: while nanotheranostic offer advantage of personalized medicine and often combines diagnosis and therapy using single molecular approach, nuclear medicine relies on radioactive isotopes to diagnosed and destroys cancer cells. In both cases, nanocarriers such as lipid-based, polymer-based, drug-conjugate, inorganic nanoparticles are used to deliver drugs/probes/isotopes to target site, generating images and thereafter chemotherapy/radiotherapy begins.Conclusion: Nanotheranostic plays important role in diseases diagnostic, therapy, imaging, monitoring of disease progression / response through the use of nanocarriers. This is made possible through nanoparticles/nanocarriers that delivers drug to the target tissues/cells.

The nuclear architecture describes the organization of the various compartments in the nucleus of eukaryotic cells, where a plethora of processes such as nucleocytoplasmic transport, gene expression, and assembly of ribosomal subunits occur in a dynamic manner. During the different phases of the cell cycle, in post-mitotic cells and after oncogenic transformation, rearrangements of the nuclear architecture take place, and, among other things, these alterations result in reorganization of the chromatin and changes in gene expression. A member of the tubulin family, tubulin, was first identified as part of a multiprotein complex that allows nucleation of microtubules. However, more than a decade ago, γ tubulin was also characterized as a nuclear protein that modulates several crucial processes that affect the architecture of the nucleus. This review presents the latest knowledge regarding changes that arise in the nuclear architecture of healthy cells and under pathological conditions and, more specifically, considers the particular involvement of tubulin in the modulation of the biology of the nuclear compartment.

The objective of this work is to evaluate the potential effect of cardiac stress exercise on the accumulation of [¹²³I]IAZA, a radiopharmaceutical used to image focal tissue hypoxia, in otherwise normal myocardium in healthy volunteers, and to determine the impact of exercise on [¹²³I]IAZA pharmacokinetics. The underlying goal is to establish a rational basis and a baseline for studies of focal myocardial hypoxia in cardiac patients using [¹²³I]IAZA. Three healthy male volunteers ran the ‘Bruce’ treadmill protocol, a clinically-accepted protocol designed to expose myocardial ischemia in patients. The ‘Bruce’ criterion heart rate is 85% of [220 – age]. Approximately one minute before reaching this level, [¹²³I]IAZA (5.0 mCi/0.85 mg) was administered as a slow (1–3 min) single intravenous (i.v.) injection via an indwelling venous catheter. The volunteer continued running for an additional 1 min before being transferred to a gamma camera. Serum samples were collected from the arm contralateral to the administration site at pre-determined intervals from 1 min to 45 h post injection and were analyzed by radio HPLC. Pharmacokinetic (PK) parameters were derived for [¹²³I]IAZA and total radioactivity (total[¹²³I]) using compartmental and noncompartmental analyses. Whole-body planar scintigraphic images were acquired from 0.75 to 24 h after dosing. PK data and scintigraphic images were compared to previously published [¹²³I]IAZA data from healthy volunteers rest. Following exercise stress, both [¹²³I]IAZA and total[¹²³I] exhibited bi-exponential decline profiles, with rapid distribution phases [half-lives (t_1/2α) of 1.2 and 1.4 min, respectively], followed by slower elimination phases [t_1/2β of 195 and 290 min, respectively]. Total body clearance (CL_TB) and the steady state volume of distribution (V_ss) were 0.647 L/kg and 185 mL/min, respectively, for [¹²³I]IAZA and 0.785 L/kg and 135 mL/min, respectively, for total[¹²³I]. The t_1/2β, CL_TB and V_ss values were comparable to those reported previously for rested volunteers. The t_1/2α was approximately 4-fold shorter for [¹²³I]IAZA and approximately 3-fold shorter for total[¹²³I] under exercise relative to rested subjects. The heart region was visualized in early whole body scintigraphic images, but later images showed no accumulated radioactivity in this region, and no differences from images reported for rested volunteers were apparent. Minimal uptake of radiotracer in myocardium and skeletal muscle was consistent with uptake in non-stressed myocardium. Whole-body scintigrams for [¹²³I]IAZA in exercise-stressed healthy volunteers were indistinguishable from images of non-exercised volunteers. There was no evidence of hypoxia-dependent binding in exercised but otherwise healthy myocardium, supporting the conclusion that exercise stress at Bruce protocol intensity does not induce measurable myocardial hypoxia. Effects of exercise on PK parameters were minimal; specifically, the t_1/2α was shortened, reflecting increased cardiac output associated with exercise. It is concluded that because [¹²³I]IAZA was not metabolically bound in exercise-stressed myocardium, a stress test will not create elevated myocardial background that would mask regions of myocardial perfusion deficiency. [¹²³I]IAZA would therefore be suitable for the detection of viable, hypoxic myocardium in patients undergoing stress-test-based diagnosis.

Low-energy Coulomb excitation is capable of providing unique information on static electromagnetic moments of short-lived excited nuclear states, including non-yrast states. The process selectively populates low-lying collective states and is therefore ideally suited to study phenomena such as shape coexistence and development of exotic deformation (triaxial or octupole shapes). Historically, these experiments were restricted to stable isotopes. However, the advent of new facilities providing intense beams of short-lived radioactive species has opened the possibility to apply this powerful technique to a much wider range of nuclei. We discuss the observables that can be measured in a Coulomb-excitation experiment, their relation to nuclear structure parameters with an emphasis on the nuclear shape, and present some recent examples of Coulomb-excitation studies that provided outcomes relevant for the Shell Model.

Background: Molecular nuclear medicine, due to hybrid imaging camera systems and new tailored radiopharmaceuticals, has been gained a clinical relevance for diagnosis, therapy and follow-up of solid tumors. Despite numerous literature studies, many new radiopharmaceuticals for imaging tumor microenvironment, have not yet been used, routinely, in oncological clinical practice to monitor treatments. This is due to poor comparability of published studies, due to poor design and methodology, heterogeneous population and prevalence of preclinical studies. Methods: In this systematic review, we described the use of radiopharmaceuticals for evaluation of tumor treatment response by targeting microenvironment. We reviewed studies published from 2000 to 2020, to provide an updated status of research in this topic. Results: There is a growing role of radiopharmaceuticals and nuclear medicine imaging techniques in the management of cancer treatments, especially immunotherapy. Of the 24 papers included, 16 were preclinical studies. Conclusions: New radiopharmaceuticals could have an excellent impact in molecular imaging, leading to better diagnosis and important clinical information for therapy decision making and follow-up of cancer treatments in different solid tumors. Recently developed radiopharmaceuticals may provide great advantage to improve personalized medicine for patients with a great cost-effectiveness ratio.

Orthologs of human glucocorticoid receptor (GR) and human mineralocorticoid receptor (MR) first appear in cartilaginous fishes. Subsequently, the MR and GR diverged to respond to different steroids: the MR to aldosterone and the GR to cortisol and corticosterone. We report that cortisol, corticosterone and aldosterone activate full-length elephant shark GR, and progesterone, which activates elephant shark MR, does not activate elephant shark GR. However, progesterone inhibits steroid binding to elephant shark GR, but not to human GR. Together, this indicates partial functional divergence of elephant shark GR from the MR. Deletion of the N-terminal domain (NTD) from elephant shark GR (truncated GR) reduced the response to corticosteroids, while truncated and full-length elephant shark MR had similar responses to corticosteroids. Swapping of NTDs of elephant shark GR and MR yielded an elephant shark MR chimera with full-length GR-like increased activation by corticosteroids and progesterone compared to full-length elephant shark MR. Elephant shark MR NTD fused to GR DBD+LBD had similar activation as full-length MR, indicating that the MR NTD lacked GR-like NTD activity. We propose that NTD activation of human GR evolved early in GR divergence from the MR.

This short communication makes use of the principle of singular perturbation to approximate the ordinary differential equation (ODE) of prompt neutron (in the point kinetics model) as an algebraic equation. This approximation is shown to yield a large gain in computational efficiency without compromising any significant accuracy in the numerical simulation of primary coolant system dynamics in a PWR nuclear power plant. The approximate (i.e., singularly perturbed) model has been validated with a numerical solution of the original set of neutron point-kinetic and thermal–hydraulic equations. Both models use variable-step Runge–Kutta numerical integration.

The industry of the counterfeit goods is one of the largest underground business in the world and it is rapidly growing. Counterfeits can lead not only to loss of profit for honest producers but also have a negative impact on consumers who receive poor quality goods at an excessive price and may be exposed to health damages and safety issues. Perfume industry is constantly exposed to the problem of counterfeits with the fast developing parallel market of inspired perfumes being an important issue. It prompts for the identification of methods that classify the quality of this type of products. In this paper the application of proton nuclear magnetic resonance spectroscopy is employed for the authentication of perfumery products for the first time. Molecular composition of several types of authentic brand fragrances for women were compared with their cheaper inspired equivalents and fake products. Our approach offers the prospect of a fast and simple method for discrimination and counterfeit detection of perfumes using 1H NMR spectroscopy.

Background: Diabetes is among the most prevalent diseases worldwide, of all the affected individuals a significant proportion of the population remains undiagnosed because of a lack of specific symptoms early in this disorder and inadequate diagnostics. Diabetes and its associated sequela, i.e., comorbidity are associated with microvascular and macrovascular complications. As diabetes is characterized by an altered metabolism of key metabolites and regulatory pathways. Metabolic phenotyping can provide us with a better understanding of the unique set of regulatory perturbations that predispose to diabetes and its associated comorbidities. Methodology: The present study utilizes the analytical platform NMR spectroscopy coupled with Random Forest statistical analysis to identify the discriminatory metabolites of diabetes (DB) and diabetes-related comorbidity (DC) along with the healthy control (HC) subjects. A combined and pairwise analysis was performed, between the serum samples of HC (n=50), and DB (n=38), and DC (n=35) individuals to identify the discriminatory metabolites responsible for class separation. The perturbed metabolites were further rigorously validated using t-test, AUROC analysis to examine the statistical significance of the identified metabolites. Results: The DB and DC patients were well discriminated from HC. However, 15 metabolites were found to be significantly perturbed in DC patients compared to DB, the identified panel of metabolites are TCA cycle (succinate, citrate), methylamine metabolism (trimethylamine, methylamine, betaine), -intermediates; energy metabolites (glucose, lactate, pyruvate); and amino acids (valine, arginine, glutamate, methionine, proline and threonine). The metabolites were further used to identify the perturbed metabolic pathway and correlation of metabolites in DC patients. Conclusion: The 1H NMR metabolomics may prove a promising technique to differentiate and predict diabetes and its comorbidities on their onset or progression by determining the altered levels of the metabolites in serum.

To understand the mystery of final unification, in our earlier publications, we proposed two bold concepts: 1) There exist three atomic gravitational constants associated with electroweak, strong and electromagnetic interactions. 2) There exists a strong elementary charge in such a way that its squared ratio with normal elementary charge is close to reciprocal of the strong coupling constant. In this paper we propose that, can be considered as a compound physical constant associated with proton mass, electron mass and the three atomic gravitational constants. With these ideas, an attempt is made to understand nuclear stability and binding energy. In this new approach, nuclear binding energy can be fitted with four simple terms having one unique energy coefficient with a formula, where is an estimated mean stable mass number. With this new approach, Newtonian gravitational constant can be estimated in a verifiable approach with a model relation of the form, where is the Fine structure constant. Estimated and is 62 ppm higher than the CODATA recommended It needs further investigation. Proceeding further, an attempt is made to fit the recommended quark masses.

Spent nuclear fuel and high-level radioactive waste can be disposed in deep horizontal drillholes in sedimentary, metamorphic, or igneous rocks. Horizontal drillhole disposal has safety, operational, and economic benefits: The repository is deep in the brine-saturated zone far below aquifers in a reducing environment of formations that can be shown to have been isolated from the surface for millions of years; its depth provides safety against inadvertent intrusion, earth¬quakes, and near-surface perturbations; it can be placed close to the reactors and interim storage facilities, minimizing transportation; disposal costs per ton of waste can be kept substantially lower than for mined repositories by its smaller size, reduced infrastructure needs, and staged imple¬mentation; and, if desired, the waste could be retrieved using “fishing” technology. In the proposed disposal concept, corrosion-resistant canisters containing unmodified fuel assemblies from commercial reactors would be placed end-to-end in up to 50 cm diameter horizontal drill¬holes, a configuration that reduces mechanical stresses and keeps the temperatures below the boiling point of the brine. Other high-level wastes, such as capsules containing 137Cs and 90Sr, can be disposed in small-diameter drillholes. We provide an overview of this novel disposal concept and its technology, discuss some of its safety aspects, and compare it to mined repositories and the deep vertical borehole disposal concept.

We would like to suggest that, by considering three virtual gravitational constants assumed to be associated with gravitational, electromagnetic and strong interactions along with a strongly interacting virtual nuclear elementary charge, a workable model of final unification can be developed. In a verifiable approach, Newtonian gravitational constant and Fermi’s weak coupling constant can be interrelated via nuclear and electromagnetic gravitational constants.

The article addresses the issue of reducing the carbon footprint in the formula of the European Union’s New Green Deal using nuclear energy introduced in place of coal. It contains an analysis of the possibilities offered by currently developed concepts of using nuclear energy in the context of existing energy infrastructure in Poland. It indicates the compatibility of coal and nuclear technologies for generating electricity and heat, considering only those with the highest level of technological readiness. The aim of the article is to identify the energy transformation in Poland using nuclear technologies and acquiring, creating and developing knowledge on the subject. It is assumed that the future of coal-nuclear transformation depends on determining where investment processes could take place in Poland, demonstrating the power that can be replaced through transformation, and indicating appropriate coal CPP (Carbon Power Plant) and nuclear NPP (Nuclear Power Plant) technologies with which a roadmap for the development of Polish nuclear energy can be created. The direction of potential actions is shown, whose coordination and implementation requires cooperation between many entities with appropriate knowledge and experience. For the purposes of this article, preliminary research was conducted on the possibilities offered by currently developed concepts in the context of existing energy infrastructure in Poland, its transformation, and the necessary social capital and its sources. The considerations did not take into account power plants and combined heat and power plants that have been liquidated or the use of their remaining infrastructure.

The results of muonographic study of two objects in the cave complex of the unique historical and archaeological memorial, the Holy Dormition Pskovo-Pechersky Monastery, are presented. The experimental technology is based on the use of nuclear emulsion detectors.

Hepatic macrophages act as the liver’s first line of defense against injury. Their differentiation into pro-inflammatory or anti-inflammatory subpopulations is a critical event that maintains a delicate balance between liver injury and repair. In our investigation, we explored the influence of the small heterodimer partner (SHP), a nuclear receptor primarily associated with metabolism, on macrophage differentiation during the innate immune response. During macrophage differentiation, we observed significant alterations in Shp mRNA expression. Deletion of SHP promoted M1 differentiation while interfering with M2 polarization. Conversely, overexpression of SHP resulted in increased expression of peroxisome proliferator activated receptor gamma (Pparg), a master regulator of anti-inflammatory macrophage differentiation, thereby inhibiting M1 differentiation. Upon lipopolysaccharide (LPS) injection, there was a notable increase in the pro-inflammatory M1-like macrophages, accompanied by exacerbated infiltration of monocyte-derived macrophages (MDMs) into the livers of Shp myeloid cell specific knockout (Shp-MKO). Concurrently, we observed significant induction of tumor necrosis factor alpha (Tnfa) and chemokine (C-C motif) ligand 2 (Ccl2) expression in LPS-treated Shp-MKO livers. Additionally, the mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-kB) pathways were activated in LPS-treated Shp-MKO livers. Consistently, both pathways were hindered in SHP overexpression macrophages. Finally, we demonstrated that SHP interacts with p65, thereby influencing macrophage immune repones. In summary, our study uncovered a previously unrecognized role of SHP in promoting anti-inflammatory macrophage differentiation during the innate immune response. This was achieved by SHP acting as a regulator for the Pparg, MAPK and NF-kB pathways.

The Gulong shale oil reservoir is formed in freshwater to slightly saline lacustrine basins, mainly consisting of pure shale geological structure, which is quite different from other shale reservoirs around the world. Currently, the development of Gulong shale oil mainly relies on hydraulic fracturing, while the subsequent shut-in period for imbibition has been proven to be an effective method for enhancing shale oil recovery. To clarify the characteristics of fluid occurrence space and the variation of fluid occurrence during saltwater imbibition in Gulong shale, this paper carried out porosity and permeability tests on Gulong shale cores, and analyzed the fluid occurrence space characteristics and imbibition oil recovery based on nuclear magnetic resonance (NMR). In the porosity and permeability tests, the porosity measured by saturation method was calibrated using NMR T2 spectra. Combined with the identification of fractures in shale cores using micro-CT and the analysis of porosity and permeability parameters, it was found that the permeability of shale cores was related to the development of fractures in shale cores. Through the testing and analysis of NMR T1-T2 two-dimensional spectra of the shale cores before and after saturation with oil, it was found that the shale mainly contains heavy oil, light oil, and clay-bound water, and they were distributed in different positions in the T1-T2 spectrum. Finally, the T1-T2 two-dimensional spectra of the shale core at different imbibition stages were analyzed, and it was found that the saltwater mainly entered the minuscule inorganic pores of clay minerals during the imbibition process, and squeezed the larger-sized inorganic pores containing light oil through the hydration expansion effect, thus expelling the light oil from the shale core and achieving the purpose of enhanced oil recovery.

Somatic cell nuclear transfer (SCNT) is a reproductive biotechnology with great potential in the reproduction of different species of zootechnical interest, including sheep. This study aimed to carry out a bibliometric analysis of scientific papers published on the application of SCNT in sheep reproduction in the period 1997-2023. The search involved the Science Citation Index Expanded and Social Sciences Citation Index databases of the Main Collection of Web of Sciences with different descriptors. A total of 124 scientific papers were analyzed for different bibliometric indicators using VOSviewer software. Since 2001, the number of SCNT-related documents published concerning sheep reproduction increased and has fluctuated in ensuing years. The main authors, research groups, institutions, countries, documents and journals with the highest number of publications related to SCNT in sheep reproduction were identified, as well as the topics that address the research papers according to the terms: somatic cell, embryo, oocyte, gene expression, SCNT, and sheep.

Activated Corrosion Products (ACPs) formation and deposition pose a critical safety issue for nuclear fusion reactors. The working fluid transports the ACPs towards regions accessible to worker personnel. Predicting ACPs formation deposition and transport is fundamental for source term identification, reduction of radiation exposure assessment, maintenance plan definition, design optimization, and waste management. The code OSCAR-Fusion has been developed by the CEA (France) to evaluate the ACPs generation and transport in closed water-cooled loops for fusion application. This work aims at assessing the impact of water chemistry on the transport, precipitation, and deposition of corrosion products for the EU-DEMO divertor Plasma Facing Unit Primary Heat Transfer System. Sensitivity analyses and uncertainty quantification are needed due to the multi-physics phenomena involved in ACPs formation and transport. The OSCAR-Fusion/RAVEN code coupling developed by the Sapienza University of Rome and ENEA has been used. This work presents the perturbation results of different parameters chosen for a closed water-cooled loop considering a continuous scenario of 1888 days. The aim of this work is to assess the variation of build-up of ACPs, perturbing the alkalizing agent concentration into the coolant and the corrosion and release rates of different materials.

Dysfunction of the WW domain-containing adaptor with coiled-coil, WAC, gene underlies a rare autosomal dominant disorder, DeSanto-Shinawi syndrome (DESSH). DESSH is associated with facial dysmorphia, hypotonia, and cognitive alterations, including attention deficit hyperactivity disorder and autism. How the WAC protein localizes and functions in neural cells is critical to understanding its role during development. To understand the genotype-phenotype role of WAC, we developed a knowledgebase of WAC expression, evolution, human genomics, and structural/motif analysis combined with human protein domain deletions to assess how conserved domains guide cellular distribution. Then assessed in a cell type implicated in DESSH, cortical GABAergic neurons. WAC contains conserved charged amino acids, phosphorylation signals, and enriched nuclear motifs, suggesting a role in cellular signaling and gene transcription. Human DESSH variants are found within these regions. We also discovered and tested a nuclear localaization domain that impacts the cellular distribution of the protein. These data provide new insights into the potential roles of this critical developmental gene, establishing a platform to assess further translational studies, including the screening of missense genetic variants in WAC. Moreover, these studies are essential for understanding the role of human WAC variants in more diverse neurological phenotypes, including autism spectrum disorder.

The systems ESTE are running in nuclear crisis centers at various levels of emergency preparedness and response in Slovakia, the Czech Republic, Austria, Bulgaria, and Iran (at NPP monitored by International Atomic Energy Agency, IAEA). ESTE is a decision support system, running 24/7, and serves the crisis staff to propose actions to protect inhabitants against radiation in case of a nuclear accident. ESTE is also applicable as decision support system in case of a malicious act with radioactive dispersal device in an urban or industrial environment. Dispersion models implemented in ESTE are Lagrangean particle model (LPM) and Puff trajectory model (PTM). Described are models approaches as implemented in ESTE. PTM is applied in ESTE for the dispersion calculation near the point of release, up to 100 km from the point of nuclear accident. LPM for general atmospheric transport is applied for short-range, meso-scale and large-scale dispersion, up to dispersion on the global scale. Additionally, a specific micro-scale implementation of LPM is applied for urban scale dispersion modelling too. Dispersion models of ESTE are joined with radiological consequences models to calculate a complete spectrum of radiological parameters - effective doses, committed doses and dose rates by various irradiation pathways and by various radionuclides. Finally, radiation protective measures, like sheltering, iodine prophylaxis, or evacuation, evaluated on the base of predicted radiological impacts are proposed. Dispersion and radiological models of the state-of-the-art ESTE systems are described. Results of specific analyses, like number of particles applied, initial spatial distribution of the source, height of the bottom reference layer, are presented and discussed.

Nuclear lamins are type V intermediate filament proteins that form a filamentous meshwork beneath the inner nuclear membrane. Additionally, a sub-population of A-type and B-type lamins is localized in the nuclear interior. The nuclear lamina protects the nucleus from mechanical stress and mediates nucleo-cytoskeletal coupling. Lamins form a scaffold that partially tethers chromatin at the nuclear envelope. The nuclear lamina also stabilizes protein-protein interactions involved in gene regulation and DNA repair. The lamin-based protein sub-complexes are implicated in both nuclear and cytoskeletal organization, the mechanical stability of the nucleus, genome organization, transcriptional regulation, genome stability, and cellular differentiation. Here we review recent research in the field of nuclear lamins and their role in modulating various nuclear processes and their impact on cell function.

Direct intercellular communication, mediated by gap junctions formed by the connexin transmembrane protein family, is frequently dysregulated in cancer. Connexins have been described as tumour suppressors, but emerging evidence suggests that they can also act as tumour promoters. This feature is connexin- and tissue-specific and may be mediated by complex signalling pathways through gap junctions or hemichannels or by completely junction-independent events. Lung cancer is the number one cancer in terms of mortality worldwide, and novel biomarkers and therapeutic targets are urgently needed. Our objective was to gain a better understanding of connexins in this setting. We used several in silico tools to analyse TCGA data in order to compare connexin mRNA expression between healthy lung tissue and lung tumours and correlated these results with gene methylation patterns. Using Kaplan-Meier plotter tools, we analysed a microarray dataset and an RNA-seq dataset of non-small cell lung tumours in order to correlate connexin expression with patient prognosis. We found that connexin mRNA expression is frequently either upregulated or downregulated in lung tumours. This correlated with both good and poor prognosis (overall survival) in a clear connexin isoform-dependent manner. These associations were strongly influenced by the histological subtype (adenocarcinoma versus squamous cell carcinoma). We present an overview of all connexins but particularly focus on four isoforms implicated in lung cancer: Cx26, Cx30.3, Cx32 and Cx43. We further analysed the protein expression and localization of Cx43 in a series of 72 human lung tumours. We identified a subset of tumours that exhibited a unique strong nuclear Cx43 expression pattern that predicted worse overall survival (p=0.014). Upon sub-stratification, the prognostic value remained highly significant in the adenocarcinoma subtype (p=0.002) but not in the squamous carcinoma subtype (p=0.578). This finding highlights the importance of analysis of connexin expression at the protein level, particularly the subcellular localization. Elucidation of the underlying pathways regulating Cx43 localization may provide for novel therapeutic opportunities.

The acute phase protein serum amyloid A (SAA) is associated with endothelial dysfunction and early-stage atherogenesis. Stimulation of vascular cells with SAA increases gene expression of pro-inflammation cytokines and tissue factor (TF). Activation of the transcription factor, nuclear factor kappa-B (NFkB), may be central to SAA-mediated endothelial cell inflammation, dysfunction and pro-thrombotic responses, while targeting NFkB with a pharmacologic inhibitor, BAY11-7082, may mitigate SAA activity. Human carotid artery endothelial cells (HCtAEC) were pre-incubated (1.5 h) with 10 µM BAY11-7082 or vehicle (control) followed by SAA (10 μg/mL; 4.5 h). Under these conditions gene expression for TF and TNF increased in SAA-treated HCtAEC and pre-treatment with BAY11-7082 significantly (TNF) and marginally (TF) reduced mRNA expression. Intracellular TNF and IL-6 protein also increased in HCtAEC supplemented with SAA and this expression was inhibited by BAY11-7082. Supplemented BAY11-7082 also significantly decreased SAA-mediated leukocyte adhesion to apolipoprotein E-deficient mouse aorta in ex vivo vascular flow studies. In vascular function studies, isolated aortic rings pre-treated with BAY11-7082 prior to incubation with SAA showed improved endothelium-dependent vasorelaxation and increased vascular cGMP content. Together these data suggest that inhibition of NFkB activation may protect endothelial function by inhibiting the pro-inflammatory and pro-thrombotic activities of SAA.

We review the basics of nuclear binding energy scheme assumed to be associated with the existence of a new strong elementary charge associated with square root of reciprocal of the strong coupling constant.

The rhizome of Drynaria fortunei (Kunze ex Mett.) J. Sm., which is known as “Golsebo” in Korea, has been traditionally used to treat various inflammatory conditions, including bone metabolism disorders. It relieves blood extravasation, stops bleeding, repairs broken bone tissue, treats bone fractures, and kills bacteria. Recently, D. fortunei-derived polysaccharides (DFP) have been identified as bioactive compounds that act against numerous human diseases. However, the molecular mechanism underlying the bone metabolism-improving effect of DFP has not been elucidated. In this study, we evaluated the modulatory effects of DFP on the differentiation of bone marrow-derived macrophages into osteoclasts. We performed tartrate-resistant acid phosphatase assays using DFP (different concentrations and molecular weights) to evaluate the degree of bone resorption in the receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis of bone marrow-derived macrophages. DFP significantly inhibited RANKL-induced osteoclastogenesis and suppressed RANKL-mediated overexpression of c-Fos and nuclear factor of activated T cells 1, thereby downregulating osteoclast-specific gene (Atp6v0d2, DC-STAMP, and cathepsin K) expression. DFP has potential as a nutraceutical candidate for treating bone loss diseases, including osteoporosis in postmenopausal women.

Computational methods are essential to support and advance nuclear technologies due to the hazards of handling and analysing highly radioactive materials such as spent nuclear fuel (SNF). However, many such methods, including those thatcan predict SNF compositions and decay heat parameters, require expensive, proprietary software, alongside significant programming experience and computational power for utilisation, severely limiting availability of data and hampering research throughput. Although some datasets are available, many are incomplete or only cover certain fuel systems for older reactor types. Research investigating new methods for SNF recycling, for example, requires compositional and decay heat data for fuel systems not covered by extant data, though analogous source data may be available. With this in mind, we have developed a simple, accessible, and flexible method for extrapolation of isotopic, elemental, and decayheat compositions for SNF at discharge and following decay storage before recycling, based on an extant dataset. This semi-empirical method uses physical and mathematical first principles and can be performed using software accessible to all researchers. This provides outputs accurate to within 1% of reference values interpolated within the range of available data for isotopic compositions, with sensible extrapolations at higher burnups beyond those reported, withoverall elemental outputs accurate to within 0.1%of expected totals. In this publication, we present the developmental methodology, some sample data, the present limitations, and options for future development and expansion of functionality.

The fundamental theory of nuclear interactions, Quantum Chromodynamics (QCD), operates in terms of quarks and gluons at higher resolution. At low resolution the relevant degrees of freedom are nucleons. Two-nucleon Short-Range Correlations (SRC) help to interconnect these two descriptions. SRCs are temporary fluctuations of strongly interacting close pairs of nucleons. The distance between the two nucleons is comparable to their radii and their relative momenta are larger than the fermi sea level. According to the electron scattering experiments held in the last decade, SRCs have far-reaching impacts on many-body systems, the nucleon-nucleon interactions, and nuclear substructure. The modern experiments with ion beams and cryogenic liquid hydrogen target make it possible to study properties of the nuclear fragments after quasi-elastic knockout of a single nucleon or an SRC pair. The first SRC experiment at BM@N (2018) with a carbon beam has shown that detection of an intact 11B nucleus after interaction selects out the quasi-elastic knockout reaction with minimal contribution of initial- and final-state interactions. Also, 25 events of SRC-breakups showed agreement in SRC properties as knows from electron beam experiments. The analysis of the second measurement of SRC at BM@N held in 2022 with an improved setup is currently ongoing. The SRC project at JINR moved to a new experimental area in 2023, where the next measurement is being planned in terms of experimental setup and physics goals.

In this paper a high-power and propellant-free electromagnetic propulsion is proposed based on the General Relativity and nuclear fusion technology. We find that Riemann curvature vanish and geodesic motion is free from gravitational field locally in a special space-time, which demonstrates the feasibility of propellant-free electromagnetic propulsion. To achieve high-power propulsion in Schwarzschild background, we choose current loop as axisymmetric field source and obtain exact solution of Einstein-Maxwell field equation using Killing symmetry and Ernst generation technique. An implementation with superconductor shield is given according to the Meissner effect, calculation implies that the device can be sufficiently free from gravitational field with the aid of existing nuclear fusion engineering.

The importance of genome organization at the supranucleosomal scale in the control of gene expression is increasingly recognized today. In mammals, Topologically Associating Domains (TADs) and the active / inactive chromosomal compartments are two of the main nuclear structures that contribute to this organization level. However, recent works reviewed here indicate that, at specific loci, chromatin interactions with nuclear bodies could also be crucial to regulate genome functions, in particular transcription. They moreover suggest that these nuclear bodies are membrane-less organelles dynamically self-assembled and disassembled through mechanisms of phase separation. We have recently developed a novel genome-wide experimental method, High-salt Recovered Sequences sequencing (HRS-seq), which allows the identification of chromatin regions associated with large ribonucleoprotein (RNP) complexes and nuclear bodies. We argue that the physical nature of such RNP complexes and nuclear bodies appears to be central in their ability to promote efficient interactions between distant genomic regions. The development of novel experimental approaches, including our HRS-seq method, is opening new avenues to understand how self-assembly of phase separated nuclear bodies possibly contributes to mammalian genome organization and gene expression.

The human androgen receptor (AR) is a ligand inducible transcription factor harboring an amino terminal domain (AR-NTD) hosting the ligand independent activation function. AR-NTD is intrinsically disordered and display aggregation properties conferred by the presence of a poly-glutamine (polyQ) sequence of 22 residues. The length of the polyQ sequence, as well as the presence of adjacent sequence motifs modulate this aggregation property. AR-NTD contains also a conserved sequence motif KELCKAVSVSM that displays an intrinsic property to form amyloid fibrils under mild oxidative conditions of its conserved cysteine residue. As peptide sequences with intrinsic ability to oligomerize are reported to have an impact on the aggregation of polyQ tract, we determined the effect of the KELCKAVSVSM on the polyQ stretch in the context of the AR NTD, using Atomic Force Microscopy (AFM). Here, we present evidence for a crosstalk between the amyloidogenic properties of the KELCKAVSVSM motif and the polyQ stretch at the AR NTD.

Nuclear fusion is essential for the sexual reproduction of various organisms, including plants, animals, and fungi. During the life cycle of flowering plants, nuclear fusion occurs three times: once during female gametogenesis and twice during double fertilization, when two sperm cells fertilize the egg and the central cell. Haploid nuclei migrate in an actin filament-dependent manner to become in close contact, then two nuclei fuse. The nuclear fusion process in plant reproduction is achieved by the sequential nuclear membrane fusion events. Recent molecular genetic analyses using Arabidopsis thaliana showed the conservation of nuclear membrane fusion machinery between plants and the budding yeast Saccharomyces cerevisiae. These include the heat shock protein 70 in the endoplasmic reticulum and conserved nuclear membrane proteins. Analyses of A. thaliana mutants of these components show that completion of the sperm nuclear fusion at fertilization is essential for proper embryo and endosperm development.

The transportation sector is a significant source of greenhouse gas emissions. Electric vehicles (EVs) have gained popularity as a solution to reduce emissions, but the high load of charging stations poses a challenge to the power grid. Nuclear-Renewable Hybrid Energy Systems (N-RHES) present a promising alternative to support fast charging stations, reduce grid dependency, and decrease emissions. However, the intermittent problem of renewable energy sources (RESs) limits their application, and the synergies among different technologies have not been fully exploited. This paper proposes a predictive and adaptive control strategy to optimize the energy management of N-RHES for fast charging stations, considering the integration of nuclear, photovoltaics, and wind turbine energy with a hydrogen storage fuel cell system. The proposed dynamic model of a fast-charging station predicts electricity consumption behavior during charging processes, generating probabilistic forecasting of electricity consumption time-series profiling. Key performance indicators and sensitivity analyses illustrate the practicability of the suggested system, which offers a comprehensive solution to provide reliable, sustainable, and low-emission energy to fast-charging stations while reducing emissions and dependency on the power grid.

Intending to analyze the role of nuclear power in an integrated energy system, we used the IESA-Opt-N cost minimization model focusing on four key themes: system-wide impacts of nuclear power, uncertain technological costs, flexible generation, and cross-border electricity trade. We demonstrate that the Levelized Cost of Energy (LCOE) alone should not be used to demonstrate the economic feasibility of a power generation technology. For instance, under the default techno-economic assumptions, particularly the 5% discount rate and exogenous electricity trade potentials, it is cost-optimal for the Netherlands to invest in 9.6 GWe nuclear capacity by 2050. However, its LCOE is 34 €/MWh higher than offshore wind. Moreover, we found that nuclear power investments can reduce demand for variable renewable energy sources in the short term and higher energy independence (i.e., lower imports of natural gas, biomass, and electricity) in the long term. Furthermore, investing in nuclear power can reduce the mitigation costs of the Dutch energy system by 1.6% and 6.2% in 2040 and 2050, and 25% lower national CO₂ prices by 2050. However, this cost reduction is not significant given the odds of higher nuclear financing costs and longer construction times. In addition, this study has shown that lower financing costs (e.g., EU taxonomy support) considerably reduce the relevance of nuclear cost uncertainties on its investments. Furthermore, we demonstrate that the economic feasibility of national nuclear power investments can vary considerably depending on the cross-border electricity trade assumptions. Additionally, we found that lowering the cost of small modular reactors has more impact on their economic feasibility than increasing their generation flexibility. In conclusion, under the specific assumptions of this study, nuclear power can play a complementary role (in parallel to the wind and solar power) in supporting the Dutch energy transition from the sole techno-economic point of view.

Inflammatory bowel disease (IBD) is a chronic inflammation of the gastrointestinal0 tract (GIT), including Crohn’s disease (CD) and ulcerative colitis (UC), which differ in the location and lesion extensions. Both diseases are associated with microbiota dysbiosis, with a reduced population of butyrate-producing species, abnormal inflammatory response, and micronutrient deficiency (e. g. vitamin D hypovitaminosis). Vitamin D (VitD) is involved in immune cell differentiation, gut microbiota modulation, gene transcription, and barrier integrity. Vitamin D receptor (VDR) regulates the biological actions of the active VitD (1α, 25-dihydroxyvitamin D3), and is involved in the genetic, environmental, immune, and microbial aspects of IBD. VitD deficiency is correlated with disease activity and its administration targeting a concentration of 30 ng/mL may have the potential to reduce disease activity. Moreover, VDR regulates functions of T cells and Paneth cells and modulates release of antimicrobial peptides in gut microbiota-host interactions. Meanwhile, beneficial microbial metabolites, e.g. butyrate, upregulate the VDR signaling. In this review, we summarize the clinical progress and mechanism studies on VitD /VDR related to gut microbiota modulation in IBD. We also discuss epigenetics in IBD and the probiotic regulation of VDR. Furthermore, we discuss the existing challenges and future directions. There is a lack of well-designed clinical trials exploring the appropriate dose and the influence of gender, age, ethnicity, genetics, microbiome, and metabolic disorders in IBD subtypes. To move forward, we need well-designed therapeutic studies to examine whether enhanced vitamin D will restore functions of VDR and microbiome in inhibiting chronic inflammation.

The nuclear receptor superfamily comprises a large group of proteins with functions essential for cell signaling, survival and proliferation. There are multiple distinctions between nuclear superfamily classes defined by hallmark differences in function, ligand binding, tissue specificity, and DNA binding. In this review, we utilize the initial classification system, which defines subfamilies based on structure and functional difference. The defining feature of the nuclear receptor superfamily is that these proteins function as transcription factors. The loss of transcriptional regulation or gain of functioning of these receptors is a hallmark in numerous diseases. For example, in prostate cancer the androgen receptor is a primary target for current prostate cancer therapies. Targeted cancer therapies for nuclear hormone receptors have been more feasible than others to develop due to ligand availability and cell permeability of hormones. To better target these receptors, it is critical to understand their structural and functional regulation. Given that late-stage cancers often develop hormone insensitivity, we will explore the strengths and pitfalls of targeting other transcription factors outside of the nuclear receptor superfamily such as the signal transducer and activator of transcription (STAT).

In this study, a tuned mass damper is proposed as a seismic acceleration mitigating technique of an electrical cabinet inside the nuclear power plant. In order to know the mitigation performance, the electrical cabinet and the tuned mass damper were modeled using SAP2000. The sine sweep wave was used to confirm the vibration characteristics of the cabinet over a wide frequency range, and the several various earthquakes were applied to the cabinet to verify the control performance of the tuned mass damper. After analyzing the numerical results, it is summarized that the application of the proposed technique can reduce the acceleration response of the cabinet.

We present simple relations for nuclear stability and nuclear binding energy with respect to three gravitational constants associated with electroweak, strong and electromagnetic interactions.

The human casualties from simulated nuclear detonation scenarios in New Delhi, India are analyzed, with a focus on the distribution of casualties in urban environments and the theoretical application of a nuclear-specific triage system. Model estimates of nuclear war casualties employed ESRI's ArcGIS 9.3, blast and prompt radiation were calculated using the Defense Nuclear Agency's WE program, and fallout radiation was calculated using the Defense Threat Reduction Agency's (DTRA's) Hazard Prediction and Assessment Capability (HPAC) V404SP4, as well as custom GIS and database software applications. ESRI ArcGISTM programs were used to calculate affected populations from the Oak Ridge National Laboratory's LandScanTM 2007 Global Population Dataset for areas affected by thermal, blast and radiation data. Trauma, thermal burn, and radiation casualties were thus estimated on a geographic basis for New Delhi, India for single and multiple (six) 25 kiloton (kt) detonations and a single 1 megaton (1000kt) detonation. Major issues related to the emergency management of a nuclear incident are discussed with specific recommendations for improvement. The consequences for health management of thermal burn and radiation patients is the worst, as burn patients require enormous resources to treat, and there will be little to no familiarity with the treatment of radiation victims.

The current generation of nuclear reactors are evolutionary in design, mostly based on the technology originally designed to power submarines, and dominated by Light Water Reactors. The aims of the GenIV consortium are driven by sustainability, safety and reliability, economics, and proliferation resistance. The aims are extended here to encompass the ultimate and universal vision for strategic development of energy production, the ‘perpetuum mobile’ – at least as close as possible. We propose to rethink nuclear reactor design with the mission to develop a system which uses no fresh resources and produces no fresh waste during operation as well as generates power safe and reliably in economic way. The results of the innovative simulations presented here demonstrate that, from a theoretical perspective, it is feasible to fulfil the mission through the reuse of spent nuclear fuel from currently operating reactors as the fuel for a new reactor. The produced waste is less burdensome than current spent nuclear fuel which is used as feed to the system. However, safety, reliability and operational economics will need to be demonstrated to create the basis for the long term success of nuclear reactors as a major carbon free, sustainable, and applied highly reliable energy source.

In neuroendocrine neoplasms (NENs), the use of new radiopharmaceuticals has improved the accuracy of diagnosis and staging, refined surveillance approaches, and introduced specific and personalized radiation therapies. Nuclear medicine has therefore acquired a crucial role in the management of NENs patients by improving their risk stratification and personalized therapies. Artificial intelligence (AI) and radiomics can enable physicians to further improve the overall efficiency and accuracy of the use of these tools in both di-agnostic and therapeutic settings by improving the prediction of tumor grade, differential diagnosis from other malignancies, assessment of tumor behavior and aggressiveness, and prediction of treatment response. This systematic review aims to describe the state-of-the-art on AI and radiomics applications in molecular imaging of NENs.

Targeted radionuclide therapy is become increasingly prominent as a nuclear medicine subspe-cialty. For many decades, treatment with radionuclides has been mainly restricted to the use of iodine-131 in thyroid disorders. Currently, radiopharmaceuticals, consisting of a radionuclide coupled to a vector that binds to a desired biological target with high specificity, are being de-veloped. The objective is to be as selective as possible at the tumor level, while limiting the dose received at the healthy tissue level. In recent years, a better understanding of molecular mecha-nisms of cancer, as well as the appearance of innovative targeting agents (antibodies, peptides, small molecules) and the availability of new radioisotopes, have enabled considerable advances in the field of vectorized internal radiotherapy with a better therapeutic efficacy, radiation safety and personalized treatments. For instance, targeting the tumor microenvironment, instead of the cancer cells, now appears as particularly attractive. Several radiopharmaceuticals for therapeutic targeting have shown clinical value in severals types of tumors and have been or will soon be approved and authorized for clinical use.

In spite of large-scale investigations of homogeneous single-site metallocene catalysts and systems based on them, the problem of controlling their activity, chemo- and stereoselectivity with the aim of developing efficient methods for the preparation of practically useful products of alkenes transformation, such as dimers, oligomers, and polymers, still remains topical. Here we studied catalytic activity of differently structured zirconocenes (10 examples of cyclopentadienyl and indenyl complexes) and co-catalysts activating the system, namely HAlBui2, MMAO-12 or (Ph3C)[B(C6F5)4] at low activator/Zr ratios in 1-hexene oligomerization reaction. The influence of catalyst structure and system composition on alkene conversion, type of products formed and reaction stereoselectivity was investigated. The composition of hydride intermediates forming in the systems L2ZrCl2 (L2= ansa-Me2CCp2)-HAlBui2-activator was studied by NMR and the participation of biszirconium hydride complex as the precursor of catalytically active sites of the alkene dimerization reaction was shown.

Small modular reactors (SMR) (<300 MW) offer a potentially attractive nuclear energy option for the middle-east region (MER). Currently, the MER uses a significant amount of fossil fuel to process heat applications such as water desalination and in petroleum refineries and chemical plants, besides generating electricity. SMR technologies represent an opportunity to meet future energy demand in the MER. This paper discusses issues related to the future development and use of SMR technology in nuclear-renewable hybrid energy systems for application in the middle east. SMRs have also been examined as part of a resilient hybrid energy system that combines nuclear energy with renewable energy and traditional fossil energy to produce chemicals, fuels, and electricity. This paper presents the results of a techno-economic analysis of a Nuclear-Renewable-Conventional Hybrid Energy System. The paper concludes that SMR technology will be an essential feature of future hybrid energy systems for the MER.

A major challenge in the clinical management of patients with mesial temporal lobe epilepsy (MTLE) is identifying those who do not respond to antiseizure medication (ASM), allowing for the timely pursuit of alternative treatments, such as epilepsy surgery. Here, we investigated changes in plasma metabolites as biomarkers of pharmacoresistance in patients with MTLE. Furthermore, we used the metabolomics data to gain insights into the mechanisms underlying MTLE and response to ASM. We performed an untargeted metabolomic method using magnetic resonance spectroscopy and multi- and univariate statistical analyses to compare data obtained from plasma samples of 28 patients with MTLE compared to 28 controls. The patients were further divided according to response to ASM: 20 patients were refractory to treatment, and eight were responsive to ASM. We only included patients using carbamazepine in combination with clobazam. We compared the group of patients with controls and found that the profiles of glucose (p = 0.01), saturated lipids (p = 0.0002), isoleucine (p = 0.0001), β-hydroxybutyrate (p = 0.0003), and proline (p = 0.02) were different in patients compared to controls (p < 0.05). In addition, lipoproteins (p = 0.05), lactate (p = 0.05), glucose (p = 0.05), unsaturated lipids (p = 0.05), isoleucine (p = 0.05), and proline (p = 0.05), could discriminate between the two groups of patients classified according to response to ASM. The identified metabolites were linked to different biological pathways related to cell energy metabolism, and pathways linked to inflammatory processes and the modulation of neurotransmitter release and activity in MTLE. In contrast, we found that pyruvate metabolism may be linked to resistance to ASM. In conclusion, in addition to insights into the mechanisms underlying MTLE and the response to treatment with ASM, our results suggest that plasma metabolites may be used as biomarkers of disease and response to ASM in patients with MTLE. These findings warrant further studies exploring the clinical use of metabolites to assist in decision-making when treating patients with MTLE.

The crucial stages in the geochemical evolution of the Earth’s crust, ocean, and atmosphere could be explained by the assumed low-energy nuclear reactions (LENR) that are triggered by seismic activity. LENR result in the fission of medium-weight elements accompanied by neutron emissions, involving Fe and Ni as starting elements, and C, N, O as resultants. Geochemical data and experimental evidences support the LENR hypothesis. A spectral analysis of the period 1955-2013 shows common cycles between interannual changes in atmospheric CO2 growth rate and global seismic-moment release, whereas the trending behavior of the atmospheric CO2 was in response to the anthropogenic emissions. Assuming a correlation between such seismic and atmospheric fluctuations, the latter could be explained by cycles of worldwide seismicity, which would trigger massively LENR in the Earth’s Crust. In this framework, LENR from active faults could be considered as a relevant cause of carbon formation and degassing of freshly-formed CO2 during seismic activity. However, further studies are necessary to validate the present hypothesis which, at the present time, mainly aims to stimulate debate on the models which regulates atmospheric CO2.

The present overview of spin-dependent phenomena in nonmagnetic semiconductor microparticles (MPs) and nanoparticles (NPs) with interacting nuclear and electron spins is aimed at covering a gap between the basic properties of spin behavior in solid-state systems and a tremendous growth of the experimental results on biomedical applications of those particles. The first part of the review represents modern achievements of spin-dependent phenomena in the bulk semiconductors from the theory of optical spin orientation under indirect optical injection of carriers and spins in the bulk crystalline silicon (c-Si) – via numerous insightful findings in the realm of characterization and control through the spin polarization – to the design and verification of nuclear spin hyperpolarization in semiconductor MPs and NPs for magnetic resonance imaging (MRI) diagnostics. The second part of the review is focused on the electron spin-dependent phenomena in Si-based nanostructures, including the photosensitized generation of singlet oxygen in porous Si and design of Si NPs with unpaired electron spins as prospective contrast agents in MRI. The experimental results are analyzed by considering both the quantum mechanical approach and several phenomenological models for the spin behavior in semiconductor/molecular systems. Advancements and perspectives of the biomedical applications of spin-dependent properties of Si NPs for diagnostics and therapy of cancer are discussed.

It is known that knockdown of the mitochondrial 18 kDa translocator protein (TSPO) as well as TSPO ligands modulate various functions, including functions related to cancer. To study the ability of TSPO to regulate gene expression regarding such functions, we applied microarray analysis of gene expression to U118MG glioblastoma cells. Within 15 minutes, the classical TSPO ligand PK 11195 induced changes in expression of immediate early genes and transcription factors. These changes also included gene products that are part of the canonical pathway serving to modulate general gene expression. These changes are in accord with reverse transcriptase (RT) real-time -PCR. At the time points of 15, 30, 45, and 60 minutes, as well as 3 and 24 hours of PK 11195 exposure, the functions associated with the changes in gene expression in these glioblastoma cells covered well known TSPO functions. These functions included cell viability, proliferation, differentiation, adhesion, migration, tumorigenesis, and angiogenesis. This was corroborated microscopically for cell migration, cell accumulation, adhesion, and neuronal differentiation. Changes in gene expression at 24 hours of PK 11195 exposure were related to downregulation of tumorigenesis and upregulation of programmed cell death. In the vehicle treated as well as PK 11195 exposed cell cultures, our triple labeling showed intense TSPO labeling in the mitochondria but no TSPO signal in the cell nuclei. Thus, mitochondrial TSPO appears to be part of the mitochondria-to-nucleus signaling pathway for modulation of nuclear gene expression. The novel TSPO ligand 2-Cl-MGV-1 appeared to be very specific regarding modulation of gene expression of immediate early genes and transcription factors.

Spinal muscular atrophy is a neuromuscular disorder caused by mutationsin both copies of the survival motor neuron gene 1 (SMN1) which lead to reduction in the production of the SMN protein. Currently, there are several therapies that have been approved for SMA, with much more undergoing active research. While various biomarkers have been proposed for assessing the effectiveness of SMA treatment, a universally accepted one still hasnot been identified. This study aimed to investigate whether the number of gems in cell nuclei could serve as a potential biomarker for SMA. To gain insight into whether the number of gems in cell nuclei varies based on their SMN genotype and whether the increase in gems number is associated with therapeutic response, we utilized fibroblast cell cultures obtained from a patient with SMA type II and from healthy individual. We have discovered a remarkable difference in the number of gems found in the nuclei of these cells, specifically when counting gems per 100 nuclei. Then the SMA fibroblasts were treated with antisense oligonucleotides the beneficial effects in correcting the abnormal splicing of SMN2 exon 7 have been demonstrated. It was observed that there was a significant increase in the number of gems in the treated cells compared to the intact SMA cells. The results obtained significantly correlate with an increase of full-length SMN transcripts share. Based on our findings, it is evident that the quantity of gems can be regarded as a reliable biomarker for SMA drugs development.

Cancer theragnostics is a novel approach that combines diagnostic imaging and radionuclide therapy. It is based on the use of a pair of radiopharmaceuticals, one optimized for positron emission tomography imaging, through linkage to a proper radionuclide, and the other bearing a beta-emitter isotope that can induce significant damage to cancer cells. In recent years, the use of theragnostics in nuclear medicine clinical practice has increased considerably, and thus investigation has focused on the identification of novel radionuclides that can bind to molecular targets which are typically dysregulated in different cancers. The major advantages of the theragnostic approach include elimination of multi-step procedures, reduced adverse effects to normal tissues, early diagnosis, better predicting responses and personalized patient care. This review aims to discuss emerging theragnostic molecules that have been investigated in a series of human malignancies, including gliomas, thyroid cancer, neuroendocrine tumors, cholangiocarcinoma and prostate cancer, as well as potent and recently introduced molecular targets, like cell-surface receptors, kinases, and cell adhesion proteins. Furthermore, special reference has been made to copper radionuclides as theragnostic agents, and their radiopharmaceutical applications since they present promising alternatives to the well-studied gallium-68 and lutetium-177.

Sedimentation processes have negative socioeconomic and environmental consequences, ranging from eutrophication phenomena, loss of water quality in surface water bodies, effects on the potential for hydroelectric generation, etc. Frequently, anthropic activity is the main cause that enhances these processes through changes in land use that can lead to landscape modifications. Therefore, it is relevant to evaluate this phenomenon and to be able to discriminate the influence of different land uses on the contributions to sediment loads at different scales. The novel Compound Specific Stable Isotopes technique allows the evaluation of sediment inputs associated with different land use changes in a study region. In the present work this technique was used in the Alhajuela Lake sub-basin, within the Panama Canal Watershed. The contribution levels of three (3) representative land uses (forest, pasture and sediment) in the study area were evaluated for the sediments present in sixteen (16) selected mixing points. The main contributions of the sources to the sediments present in the main rivers and tributaries flowing into Alhajuela Lake, in the sub-basin of the same name, were identified. The results obtained are consistent with observations and measurements of sedimentation in the study area.

Multiple myeloma (MM) is an incurable hematological cancer. It is preceded by monoclonal gammopathy of uncertain significance (MGUS), an asymptomatic phase. It has been demonstrated that early detection increases the 5-year survival rate. However, blood-based biomarkers that enable early disease detection are lacking. Metabolomic and lipoprotein subfraction variable profiling is gaining traction to expand our understanding of disease states and, more specifically, for identifying diagnostic markers in patients with hematological cancers. This study aims to enhance our understanding of multiple myeloma (MM) and identify candidate metabolites, allowing for more effective preventative treatment. Serum was collected from 25 healthy controls, 20 patients with MGUS, and 30 patients with MM. 1H-NMR (nuclear magnetic resonance) spectroscopy was utilized to evaluate serum samples. The metabolite concentrations were examined using multivariate, univariate, and pathway analysis. Metabolic profiles of the MGUS patients revealed lower levels of alanine (F.C. = 0.8, p = 0.002), lysine (FC = 0.8, p < 0.001), leucine (FC=0.7, p < 0.001) but higher levels of formic acid (FC=1.6, p ≤ 0.001) when compared to controls. However, metabolic profiling of MM patients compared to controls exhibited decreased levels of total Apolipoprotein-A1 (FC =0.6, p<0.001), HDL-4 Apolipoprotein-A1 (FC = 0.5, p ≤ 0.001), HDL-4 Apolipoprotein-A2 (FC = 0.6, p < 0.001), HDL Free Cholesterol (FC = 0.7, p < 0.001), HDL-3 Cholesterol (FC = 0.5, p ≤ 0.001) and HDL-4 Cholesterol (FC = 0.5, p ≤ 0.001). Lastly, metabolic comparison between MGUS to MM patients primarily indicated alterations in lipoproteins levels: Total Cholesterol (FC = 0.6, p ≤ 0.001), HDL Cholesterol (FC = 0.7, p ≤ 0.001), HDL Free Cholesterol (FC = 0.4, p ≤ 0.001), Total Apolipoprotein-A1 (FC = 0.7, p ≤ 0.001), HDL Apolipoprotein-A1 (FC = 0.7, p ≤ 0.001), HDL-4 Apolipoprotein-A1 (FC = 0.6, p ≤ 0.001) and HDL-4 Phospholipids (FC = 0.6, p ≤ 0.001). This study provides novel insights into the serum metabolic and lipoprotein subfraction changes in patients as they progress from a healthy state to MGUS to MM, which may allow for earlier clinical detection and treatment.

The review starts by highlighting the significance of nuclear power plants in contemporary world, especially its indispensable role in the global efforts to reduce CO2 emissions. Then, it describes the impact of irradiation on microstructure and mechanical properties of reactor structural materials. The main part provides the reader with a thorough overview of crystal plasticity models developed to address the irradiation effects so far. All three groups of most important materials are included. Namely, the Zr alloys used for fuel cladding, austenitic stainless steels used for reactor internals and ferritic steels used for reactor pressure vessel. Other materials, especially those considered for construction of future fission and fusion nuclear power plants, are also mentioned. The review pays also special attention to ion implantation and instrumented nanoindentation which are a common way to substitute costly and time-consuming neutron irradiation campaigns.

Paleoclimate information is key to understanding the climate system and predicting future climate. Currently, stable isotope analysis of whole molecules in tree rings is among the most advanced paleoclimate tools. Still, it only enables reconstructions of one climate parameter at a time (univariate climate reconstruction), a fundamental limitation. Here, we investigated whether this limitation can be overcome by analysing isotope variability at the level of intramolecular carbon positions in tree-ring glucose. We found that drought governs isotope variability at glucose C-1 to C-3, whereas radiation governs isotope variability at glucose C-5 to C-6. These isotope-climate relationships are statistically and mechanistically robust. According to cross-validation analysis, they can be reconstructed with high accuracy and precision. Thus, intramolecular isotope analysis enables multivariate climate reconstructions (proof of concept).

Issues related to safe and abundant energy production have been prominent in recent years. This is particularly tr ue when society considers how to increase the quality of life by providing low-cost energy to citizens. A significant concern of the Gulf Cooperation Council (GCC) relates to the environmental effects of energy production and energy use associated with climate change. Efforts to reduce fossil fuel use and increase the use of renewable energy, together with the price volatility of fossil fuels, have seriously impacted the economics of many of the oil-producing countries, particularly the Gulf States, which has led to efforts to make their economies more diverse and less dependent on oil production.

Central adiposity is one of the significant determinants of obesity-related hypertension risk, which may arise due to the abdominal fat depot's pathogenic inflammatory nature. Pro-inflammatory cytokines and adipokines up-regulation through nuclear factor-kappa B (NF-κB) activation in adipose tissue has been considered an essential function in the pathogenesis of obesity-related hypertension. This study aimed to ascertain the NF-κB inhibitor (SN50) effect on TNF-α and angiotensinogen (AGT) secretion and expression in mediating the anti-inflammatory effect through its impact on NF-κB activity in humans adipose tissue. Primary human adipocytes were isolated from 20 subjects among 10 overweight and 10 obese with and without hypertension and treated with 10ng/ml LPS in the presence and absence of NF-κB inhibitor, SN50 (50μg/ml). TNF-α secretion and NF-κB p65 activity were detected in supernatants extracted from cultured cells treated and untreated with LPS (10ng/ml) and SN50 (50μg/ml) using enzyme-linked immunosorbent assay (ELISA). The western blot technique detected the protein of NF-κB p65 and AGT. Gene expression of TNF-α and AGT was detected in cells and performed using quantitative real-time polymerase chain reaction (RT-PCR). Treatment of AbdSc adipocytes with LPS (10ng/ml) caused a significant increase in NF-κB p65 among overweight and obese subjects with and without hypertension (P= 0.001) at 24 hours incubation. In contrast, SN50-NF-κB inhibitor causes a reduction of NF-κB p65 in overweight (P= <0.001) and obese subjects with and without hypertension (P= 0.001) at 24 hours incubation. Treatment of AbdSc adipocytes with 10ng/ml LPS caused a significant increase in TNF-α secretion in overweight and obese subjects at all-time points (P= <0.001), whereas SN50 leads to a decrease in TNF-α secretion at 3 and 12 hours incubation. Treatment of AbdSc adipocytes with LPS (10ng/ml) caused increased TNF-α and AGT gene expression twofold compared with untreated cells, whereas, in the presence of SN50, it reduces mRNA AGT levels in both groups. Taken together, these adipokines with NF-κB activation may represent essential biomarkers to evaluate hypertension risk and to provide insight into the pathogenesis of obesity-related hypertension.

Sentinel-1A/B radar remote sensing data were applied for the first time to determine the sixth nuclear test, its underground explosion h-bomb location and affected zone in North Korea, on September 3, 2017. Location of epicenters nuclear test were found according to line-of-sight displacement images via its maximum value. Line-of-sight displacement images were obtained by processing in the GMTSAR package in the VirtualBox virtual machine of the Linux Ubuntu 16.04 operation system. In this research, three scenes Sentinel-B data with descending orbits were considered, one after and two before the event (the nuclear test date) scene were used.

The MAP kinase ERK5 contains an N-terminal kinase domain and a unique C-terminal tail including a nuclear localization signal and a transcriptional activation domain. ERK5 is activated in response to growth factors and stresses, and regulates transcription at the nucleus by either phosphorylation or interaction with transcription factors. MEK5-ERK5 pathway plays an important role regulating cancer cell proliferation and survival. Therefore, it is important to define the precise molecular mechanisms implicated in ERK5 nucleo-cytoplasmic shuttling. We previously described that the molecular chaperone Hsp90 stabilizes and anchors ERK5 at the cytosol, and that ERK5 nuclear shuttling requires Hsp90 dissociation. Here, we show that MEK5 or Cdc37 overexpression -mechanisms that induce nuclear ERK5- induced ERK5 SUMO-2 modification at residues Lys6/Lys22 in cancer cells. We also show that overexpression of the SUMO protease SENP2 completely abolished endogenous ERK5 nuclear localization in response to EGF stimulation. Furthermore, mutation of these SUMO sites abolished the ability of ERK5 to translocate to the nucleus and to promote prostatic cancer PC-3 cell proliferation. These results allow us to propose a more precise mechanism: in response to MEK5 activation, ERK5 SUMOylation favors the dissociation of Hsp90 from the complex, allowing ERK5 nuclear shuttling and activation of transcription.

With our long experience in the field of unification of gravity and quantum mechanics, we understood that, when mass of any elementary is extremely small/negligible compared to macroscopic bodies, highly curved microscopic space-time can be addressed with large gravitational constants and magnitude of elementary gravitational constant seems to increase with decreasing mass and increasing interaction range. In our earlier publications, we proposed that, 1) There exist three atomic gravitational constants associated with electroweak, strong and electromagnetic interactions; 2) There exists a strong interaction elementary charge in such a way that, it's squared ratio with normal elementary charge is close to inverse of the strong coupling constant; and 3) Considering a fermion-boson mass ratio of 2.27, quarks can be split into quark fermions and quark bosons. Further, we noticed that, electroweak field seems to be operated by a primordial massive fermion of rest energy 584.725 GeV and hadron masses seem to be generated by a new hadronic fermion of rest energy 103.4 GeV. In this context, starting from lepton rest masses to stellar masses, we have developed many interesting and workable relations. With further study, a workable model of final unification can be developed.

The peptidyl-prolyl isomerases of the cyclophilin type are distributed throughout human cells, including eight found solely in the nucleus. Nuclear cyclophilins are involved in complexes that regulate chromatin modification, transcription, and pre-mRNA splicing. This review collects what is known about the eight human nuclear cyclophilins: PPIH, PPIE, PPIL1, PPIL2, PPIL3, PPIG, CWC27, and PPWD1. Each “spliceophilin” is evaluated in relation to the spliceosomal complex in which it has been studied, and current work studying the biological roles of these cyclophilins in the nucleus are discussed. All eight of the human splicing complexes available in the PDB are analyzed from the viewpoint of the human spliceophilins. Future directions in structural and cellular biology, and the importance of developing spliceophilin-specific inhibitors, are considered.

Nine 2-(1,2-benzothiazol-3-yl)-N-(4-oxo-2-phenyl-1,3-thiazolidin-3-yl) propanamides were designed and synthesized, combining benzisothiazole and 4-thiazolidinone in one frame. The aim of the study was to verify their effectiveness to contrast the inflammatory/oxidative process in which free oxygen and nitrite (ROS and RNS) radicals, advanced glycation products (AGEs), inflammatory cytokines and matrix metalloproteinases (MMPs) are involved. Docking studies of all the compounds were performed in order to explore their binding mode at the MMP-9 protein. An appreciable anti-inflammatory/wound healing effects of the tested compounds was highlighted. Derivative 23, bearing a 4-carboxyphenyl substituent at C2 of the 4-thiazolidinone ring, exhibited the highest activity, being able to inhibit MMP-9 at nanomolar level (IC₅₀ = 40 nM).