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.

Nerve agents have recently been used in battlefield operations, espionage wars and terrorist attacks. These compounds, like some pesticides, cause organophosphate poisoning. The rapid, non-contact detection of a sarin simulant has been demonstrated at the Diagnostics and Metrology Laboratory of the Italian National Agency for New Technologies, Energy and Sustainable Economic Development using laser photoacoustic spectroscopy, an infrared absorption technology. The first measurements, carried out with an experimental system based on a quantum cascade laser and developed for the assessment of food authenticity in the “fingerprint region”, show that a detection limit of 1 nanolitre is within the reach of the instrument when chemometric analysis is applied.

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.

Inflammatory processes play major roles in carcinogenesis and progression of hepatocellular carcinoma (HCC) derived from non-alcoholic steatohepatitis (NASH). But there are no therapies for NASH related HCC, especially focusing on these critical steps. Previous studies reported that farnesyltransferase inhibitors (FTIs) have anti-inflammatory and anti-tumor effects. However, the influence of FTIs on NASH-related HCC has not been elucidated. In HCC cell lines, HepG2, Hep3B, and Huh-7, we confirmed expression of hypoxia-inducible factor (HIF)-1α, an accelerator of tumor aggressiveness and the inflammatory response. We established NASH-related HCC models under inflammation and free fatty acid burden and confirmed that HIF-1α expression was increased under both conditions. Tipifarnib, which is an FTI, strongly suppressed increased HIF-1α, inhibited cell proliferation, and induced apoptosis. Simultaneously, intracellular interleukin-6 as an inflammation marker was increased under both conditions and significantly suppressed by tipifarnib. Additionally, tipifarnib suppressed expression of phosphorylated nuclear factor-κB and transforming growth factor-β. Finally, in a NASH-related HCC mouse model burdened with diethylnitrosamine and a high fat diet, tipifarnib significantly reduced tumor nodule formation in association with decreased serum interleukin-6. In conclusion, tipifarnib has anti-tumor and anti-inflammatory effects in a NASH-related HCC model and may be a promising new agent to treat this disease.

The sources of dark matter and its spatial distribution is not in the typical standard model. The study thought to induct the physical causalities with empirical evidence on the theory of black hole and white hole juxtapose. The research applied a mixed method of data analysis and observational cosmology. With the cosmological observations on the traces of white holes, the research finds that the accretion phenomenon of black holes is largely contributed by its thermonuclear binding with the white hole. The antimatter saturated plasma of cold fusion and hot fission are key to the phenomenon of black hole and white hole juxtapose. The force between the black hole and the white hole is stronger than the strong force, and sheds new directions on cosmological and gravitation studies. The research concludes that black holes are white hole entropy. The higher order of the universe in matter forms can exist beyond the observed force. The thermal arrow of time is critical to future general relativity dependent instrumentation discoveries.

Transcription factors must scan genomic DNA, recognize the cognate sequence of their control element(s), and bind tightly to them. The DNA recognition process is primarily carried out by their DNA binding domains (DBD), which interact with the cognate site with high affinity and more weakly with any other DNA sequence. DBDs are generally thought to bind to their cognate DNA without changing conformation (lock-and-key). Here we used nuclear magnetic resonance and circular dichroism to investigate the interplay between DNA recognition and DBD conformation in the Engrailed homeodomain (EnHD), as model case for the homeodomain family of eukaryotic DBDs. We found that the conformational ensemble of EnHD is rather flexible and becomes more structured as ionic strength increases following a Debye-Hückel’s dependence. Our analysis indicates that EnHD’s response to ionic strength is mediated by a built-in electrostatic spring-loaded latch that operates as conformational transducer. We also found that, at moderate ionic strengths, EnHD changes conformation upon binding to cognate DNA. This change is of larger amplitude and somewhat orthogonal to the response to ionic strength. As a consequence, very high ionic strengths (e.g. 700 mM) block the electrostatic-spring-loaded latch and binding to cognate DNA becomes lock-and-key. However, the interplay between EnHD conformation and cognate DNA binding is robust across a range of ionic strengths (i.e. 45 to 300 mM) that covers the most physiologically-relevant conditions. Therefore, our results demonstrate the presence of a mechanism for the conformational control of cognate DNA recognition on a eukaryotic DBD. This mechanism can function as a signal transducer that immediately locks the DBD in place upon encountering the cognate site during active DNA scanning. The electrostatic-spring-loaded latch of EnHD can also enable the fine control of DNA recognition in response to local/temporal changes in ionic strength induced by variate physiological processes.

Toxicologically relevant levels of the psychoactive ∆9-tetrahydocannabinol (∆9-THC) as well as high levels of non-psychoactive cannabinoids potentially occur in CBD (cannabidiol) oils. For consumer protection in the fast-growing CBD oil market, facile and rapid quantitative methods to determine the cannabinoid content are crucial. However, the current standard method, i.e., liquid chromatography combined with tandem mass spectrometry (HPLC-MS/MS), requires a time-consuming multistep sample preparation. In this study, a quantitative nuclear magnetic resonance spectroscopy (qNMR) method for screening cannabinoids in CBD oils was developed. Contrary to the HPLC-MS/MS method, this qNMR features a facile sample preparation, i.e., only diluting the CBD oil in deuterochloroform. Pulse length-based concentration determination (PULCON) enables a direct quantification using an external standard. The signal intensities of the cannabinoids were enhanced during the NMR spectra acquisition by means of multiple suppression of the triglycerides which are a major component of the CBD oil matrix. The validation confirmed linearity for CBD, cannabinol (CBN), ∆9-THC and ∆8-THC in hemp seed oil with sufficient recoveries and precision for screening. Comparing the qNMR results to HPLC-MS/MS data for 46 commercial CBD oils verified the qNMR accuracy for ∆9-THC and CBD but with higher limits of detection. The developed qNMR method paves the way for increasing the sample throughput as a complementary screening before HPLC-MS/MS.

Cornea severe inflammation produces opacity or even perforation, scarring, and angiogenesis, resulting in blindness. The cornea can be used to study the effect of new anti-angiogenic chemopreventive agents. We researched the anti-angiogenic effect of two extracts, Methanol (Met) and Hexane (Hex), from the seed of Cucurbita argyrosperma, in the inflamed corneas. The corneas of Wistar rats were alkali-injured and treated intragastrically for seven successive days. Clinical manifestation as opacity score, corneal neovascularization (CNV) area, re-epithelialization percentage, and histological evaluation were performed. Inflammatory (COX-2, NF-κB, and IL-1β), and angiogenic (VEGF-A, VEGFR1, VEGFR2) markers were assessed by immunohistochemistry. Cox-2, Il-1β, and Vegf-a mRNA levels were also determined. After treatments, we observed slim corneal thickness with lower opacity scores and low cell infiltration compared to untreated rats. Treatment also accelerated wound healing and decreased CNV area. The staining of inflammatory and angiogenic factors was significantly decreased. These effects are related to a down-expression of Cox-2, Il-1β, and Vegf. These results suggest that intake of C. argyrosperma seed can be used to attenuate the angiogenesis secondary to inflammation in corneal chemical damage.

In our recent publications pertaining to 4G model of final unification and based on strong and electroweak interactions, we have developed a completely new formula for estimating nuclear binding energy. With reference to currently believed Semi Empirical Mass Formula (SEMF), we call our formula as ‘Strong and Electroweak Mass Formula’ (SEWMF). Our formula constitutes 4 simple terms and only one energy coefficient of magnitude 10.1 MeV. First term is a volume term, second term seems to be a representation of free nucleons associated with electroweak interaction, third term is a radial term and fourth one is an asymmetry term about the mean stable mass number. Considering this kind of approach, nuclear structure can be understood in terms of strong and weak interactions and cold nuclear fusion like complicated concepts can be understood in a theoretical approach positively. In this paper, by considering the accountability of we are making an attempt to improve the applicability and effectiveness of SEWMF. Number 0.00125 being a workable electroweak coefficient for Z=6 to 132 and A=2Z to 3.5Z, number of free nucleons assumed to be associated with electroweak interaction can be expressed as Improved asymmetry term can be expressed as, where represents the light house like stable mass number. With reference to old version, our improved binding energy formula can be expressed as, We are working on its possible modification for mass numbers less than the stable mass numbers. Following this approach, it is possible to show that nuclear binding energy scheme is associated with strong and weak interactions and is practically independent of Coulombic repulsions. Proceeding further, currently believed cold nuclear fusion assumed be associated with hydrated metals can be understood and can be confirmed with strong and weak interactions independent of coulombic repulsions. We are very confident to say that our approach will certainly motivate modern science community in this new direction.

The different systems in the nuclear power plants (NPP) are critical and complex which requires a continuous rigorous monitoring for both normal and abnormal conditions. However, due to the nonlinearity of the dynamic behavior of these systems, implementation of artificial intelligence within the NPP components is crucial to enhance the monitoring and the predictability of the key operating parameters trend. On the other hand, lessons learned from large nuclear accident proves that a remote real-time coordination between the different stakeholders involved in the safety of the nuclear reactor is needed. This remote feature can be implemented in the existing power plants by embedding a mobile computing networks within the plant components. This network will send early warning and transmit the NPP data on real-time to different authorities such as the regulatory authority and the decision-making committees, to enhance the interpretability of the nuclear event and deliver a collaborative decision which in return mitigate the risk associated with these events and increase the overall safety of the plant. The integration of AI and mobile computing in NPP would be most of interest in countries where nuclear reactors data are challenged to reach during an accident. For instance, during the meltdown of Chernobyl, the Soviet government covered the accident from the news in an attempt to contain the consequences but there was a spread of radioactive contamination to some other Europe countries. Therefore, in the case of such scenario the implementation of mobile computing and AI would result in different outcomes as the European countries would be notified through the mobile networking and the spread of contamination would be forecasted by the AI algorithms. In this paper, we examine the different modern AI and mobile computing technologies, the different potential application, the associated features and challenges, and future work direction.

This study focused on hydrolysis of cosmetic fillers hyaluronic acid (HA) and kinetics of the HA hydrolysis using the homogenate of the red king crab hepatopancreas. Turbidimetric analysis of the reaction mixture revealed a bell-shaped time dependence of aggregation formation. It was shown that the obtained homogenate has the similar activity to the commercially available hyaluronidase. The atomic force microscopy (AFM) examination found that the HA fillers were represented by spherical-like structures. These structures were destroyed under the action of the homogenate of the red king crab hepatopancreas. NMR of the reaction mixture showed that HA degradation lasts for some days, but a maximum rate of the reaction is detected in the first hours of incubation. The preparation with hyaluronidase activity obtained from the red king crab hepatopancreas could be used as potentially safe product for treating filler complications.

This article is some review of results that were obtained at 2007-2021 years development of “The Information as Absolute” concept and the informational physical model, which is based on the concept; including a number of fundamental physical problems are briefly considered in framework of the conception and the model. Recently in physics there are several publications, that present lists of the problems. However, those lists are essentially incomplete, for at least two reasons. Firsts of all, a number of phenomena are studied traditionally by philosophy, and so corresponding problems are usually considered to be “metaphysical”. However, they relate also to some concrete physical phenomena. For example, physics evidently studies Matter, and so the metaphysical problems “what is ontology of Matter”, “what is “Space”, “Time” and a few other physical phenomena and notions as well, are really a Meta-physical problems “what does physics study?” There are other fundamental physical problems, which are not considered as such in physics, and are absent in the “fundamental problems lists”. Those include the problems, which really exist, yet are incorporated into standard physical theories, and so are fundamental “implicitly”, which in physics are “solved by default” ‒ and mostly erroneously. Note, though, that a number of “Meta-physical”, and concrete fundamental, problems more in detail are considered in the paper “The Informational Conception and Basic Physics”, https://arxiv.org/abs/0707.4657, v5 (2021), so this paper is, in certain sense, an expanded conclusion of this paper, which includes, correspondingly, more in detail consideration of some more general physical problems; and, besides, in this article, the problem “what are Gravity and Electric Forces” is essentially clarified comparing with the arXiv 2021 paper version above, and additionally initial model of Nuclear Force is presented. Besides, the concrete problem “What is Life”, and the rational cosmological model, where a few vague points in standard cosmology rather probably are rationally clarified, while the fundamental problem “matter – antimatter asymmetry” in Matter is solved with rather large probability, are considered, and one of recently published rather complete “lists of fundamental problems” is commented in Appendix.

Cisplatin (CDDP), carboplatin (CP), and oxaliplatin (OXP) are three platinating agents clinically approved worldwide for use against a variety of cancers. They are canonically known as DNA damage inducers; however, that is only one of their mechanisms of cytotoxicity. CDDP mediates its effects through DNA damage-induced transcription inhibition and apoptotic signalling. In addition, CDDP targets the endoplasmic reticulum (ER) to induce ER-stress, the mitochondria via mitochondrial DNA damage leading to ROS production, and the plasma membrane and cytoskeletal components. CP acts in a similar fashion to CDDP by inducing DNA damage, mitochondrial damage, and ER stress. Additionally, CP is also able to upregulate micro-RNA activity, enhancing intrinsic apoptosis. OXP, on the other hand, at first induces damage to all the same targets as CDDP and CP, yet it is also capable of inducing immunogenic cell death via ER stress and can decrease ribosome biogenesis through its nucleolar effects. In this comprehensive review, we provide detailed mechanisms of action for the three platinating agents, going beyond their nuclear effects to include their cytoplasmic impact within cancer cells. In addition, we cover their current clinical use and limitations, including side effects and mechanisms of resistance.