Previous studies showed that some lamellarin-resembling annelated azaheterocyclic carbaldehydes and related imino adducts, sharing the 1-phenyl-5,6-dihydropyrrolo[2,1-a]isoquinoline (1-Ph-DHPIQ) scaffold, are cytotoxic in tumor cells and may reverse multidrug resistance (MDR) mediated by P-glycoprotein (P-gp). Herein, we synthesized and evaluated for their antiproliferative activity in four tumor cell lines (RD, HCT116, HeLa, A549) and ability of inhibiting P-gp-mediated MDR some ten diversely substituted 1-Ph-DHPIQ derivatives bearing at position 2 carboxylate groups (COOH, COOEt), nitriles (CN) and Mannich bases (e.g., morpholinomethyl derivatives). Lipophilicity parametrization and molecular docking calculations improved the understanding of the structure-activity relationships in cytotoxicity and P-gp inhibition of the investigated 1-Ph-DHPIQs, which led us to disclose a novel Mannich base HCl salt (8b’), which proved to be cytotoxic to all the tested tumor cell lines in the low micromolar range (IC50 < 20 M) and to inhibit in-vitro the efflux pumps P-gp and MRP1 responsible for MDR, with IC50s of 0.45 and 12.1 M, respectively.

Drying grains in a fixed bed can be an interesting alternative to prevent undesirable breaks and fractures of solids due to mechanical shocks, something that cannot be avoided when drying in moving beds. A disadvantage of fixed bed drying is that there can be significant gradients in the critical variables if the layer of particulate solids is thick. This work shows that periodically changing the direction of drying air flow is an effective technique to reduce differences within the bed and allow better uniformity of the product. Drying in a thick layer of 10 cm of sorghum grains was carried out at 50 and 60oC for air flow velocity of 2.1 m.s-1. The results showed that despite increasing the total drying time, the technique actually allowed a significant decrease in the temperature gradients and moisture content of the sorghum grains. The change in direction of the air flow caused the drying front to be displaced, sometimes towards the top, sometimes towards the base of the bed. At 50oC, drying lasted a total of 240 min, bringing the sorghum grains to an average overall moisture content of 0.13 on a dry basis.

The necessity of the dark energy and dark matter in the present universe could be a consequence of the antimatter elimination assumption in the early universe. In this research, I derive a new model to obtain the cosmic horizon radius and the potential cosmic topology utilising a new construal of space geometry inspired by large-angle correlations of the cosmic microwave background (CMB). A version of the Big Bounce theory is utilised to avoid the Big Bang singularity and inflationary constraints, and to tune the initial conditions of the curvature density. The mathematical derivation of a positively curved universe governed by only gravity revealed two cosmic horizon solutions. Although the positive horizon is conventionally associated with the evolution of the matter universe, the negative horizon solution could imply additional evolution in the opposite direction. This possibly suggests that the matter and antimatter could be evolving in opposite directions as distinct sides of the universe, as in the visualised Sloan Digital Sky Survey. The cosmic horizon radius is found to be accountable for the universal space curvature. By implementing this model, we find a decelerated stage of expansion during the first 10 Gyr, which is followed by a second stage of an accelerated expansion; potentially matching the tension in Hubble parameter measurements. In addition, the model predicts a final time-reversal stage of spatial contraction leading to the Big Crunch of a cyclic universe. The predicted density is 1.14. Other predictions are (1) a calculable flow rate of the matter side towards the antimatter side at the accelerated stage; conceivably explaining the dark flow observation, (2) a time-dependent spacetime curvature over horizon evolution, which could influence the galactic rotational speed; possibly explaining the high speed of stars, and (3) evolvable spacetime internal voids at the accelerated stage, which could contribute in continuously increasing the matter and antimatter densities elsewhere in both sides respectively. These findings may indicate the existence of the antimatter as a distinct side, which influences the evolution of the universe instead of the dark energy or dark matter.

This paper provides a comparative study between microwave tomography and synthetic time-reversal imaging techniques as applied to ground penetrating radar (GPR) surveys. The comparison is carried out by processing experimental data collected at a controlled test site, with various types of buried targets at given subsurface depths and representative soil conditions. It is shown that the two techniques allow us to obtain complementary information about position, depth and size of the targets from a single GPR survey.

Temperature influences the life of many organisms in various ways. A great number of them live under conditions, where their ability to adapt to changes in temperature can be vital and largely determine their fitness. Understanding the mechanisms and principles underlying this ability to adapt can be of great advantage, for example, to improve growth conditions for crops and increase their yield. In times of imminent, increasing climate change, this becomes even more important, in order to find strategies and help crops cope with these fundamental changes. There is intense research in the field of acclimation, that comprises fluctuations of various environmental conditions, but most acclimation research focuses on regulatory effects and the observation of gene expression changes within the examined organism. As thermodynamic effects are a direct consequence of temperature changes, these should necessarily be considered in this field of research, but are often neglected. Also, compensated effects might be missed, even though they are equally important for the organism, since they do not cause observable changes, but rather counteract them. In this work, using a systems biology approach, we demonstrate that even simple network motifs can exhibit temperature dependent functional features, resulting from the interplay of network structure and the distribution of activation energies over the involved reactions. The demonstrated functional features are (i) the reversal of fluxes within a linear pathway, (ii) a thermo-selective branched pathway with different flux modes and (iii) the increased flux towards carbohydrates in a minimal calvin cycle that was designed to demonstrate temperature compensation within reaction networks. By this, we expand the scope of thermodynamic modelling of biochemical processes by addressing further possibilities and effects, following established mathematical descriptions of biophysical properties.

A number of experimental tests of time orientability are described as well as clear experimental signatures from non time orientability (time reversal). Some tests are well known, while others are based on more recent theoretical work. Surprisingly, the results all suggest that time is not orientable at a microscopic level; even definitive tests are positive. At a microscopic level the direction of time can reverse and a consistent forward time direction cannot be defined. That is the conclusion supported by a range of well-known experiments. The conflict between quantum theory and local realism; electrodynamics with electric charges; and spin half transformation properties of fermions; can all be interpreted as evidence of time reversal. While particle-antiparticle annihilation provides a definitive test. It offers both a new view of space-time and an novel interpretation of quantum theory with the potential to unify classical and quantum theories.

A variant of the usual formulas for gravitational and electrostatic fields, differing from those by a logarithmic term, is introduced in order to solve some questions connected with a possible atomic contraction phenomenon at large time scale and the so-called hidden mass problem in cosmology. This approach is conceptuallly related to the MOND theory of M. Milgrom but allows a reversal of attracting forces when the distance becomes very small. The asymptotic behavior of solutions of a related dissipative ODE is studied, we obtain that all bounded trajectories converge to a point where the field vanishes.

In this study, we investigate the magnetization behavior of coaxial nanowires fabricated through the sol-gel electrospinning method. Our analysis uncovers a significant reduction in coercivity for CoFe2O4 nanowires when BaTiO3 is used as the shell material, effectively transforming them from hard to soft magnetic. This intriguing behavior is attributed to the magnetization reversal effect at the interface between ferromagnetic and paramagnetic regions, and it is also observed in NiFe2O4 and Fe2O3 nanowires. Surprisingly, introducing a GdBa2Cu3O7 shell induces a similar effect. Additionally, we employ magnetic impedance measurements on the coaxial nanowires, unveiling their potential for magnetic field sensing applications.

The exact, non perturbative, response theory developed within the field of nonequilibrium molecular dynamics, also known as TTCF (Transient Time Correlation Function) applies to quite general dynamical systems. Its key element is called dissipation function, because it represents the power dissipated by external fields acting on the particle system of interest, whose coupling with the environment is given by deterministic thermostats. This theory has been initially developed for time independent external perturbations, and then it has been extended to time dependent perturbations. It has also been applied to dynamical systems of different nature, and to oscillator models undergoing phase transitions, which cannot be treated withe.g. linear response theory. The present work includes time dependent stochastic perturbations, in the theory, using the Karhunen-Loeve theorem. This leads to three different investigations of a given process. One in which a single realization of the stochastic coefficients is fixed, and averages are taken only over the initial conditions, as in a deterministic process. In the second, the initial condition is fixed, and averages are taken with respect to the distribution of stochastic coefficients. In the last investigations, one averages over both initial conditions and stochastic coefficients. We conclude illustrating the applicability of the resulting exact response theory with simple examples.

There is a significant overlap between HIV infection and substance use disorders. Dopamine (DA) is the most abundantly upregulated neurotransmitter in Methamphetamine abuse, with receptors (DRD1-5) that are expressed by neurons as well as by a large diversity of cell types, including innate immune cells that are targets of HIV infection, making them responsive to the hyperdopaminergic environment that is characteristic of stimulant drugs. Therefore, the presence of high levels of dopamine may affect the pathogenesis of HIV, particularly in the brain. The stimulation of HIV-latently infected U1 promonocytes with DA significantly increased viral p24 levels in the supernatant at 24 hrs, suggesting effects on activation and replication. Using selective agonists to different DRDs, we found that DRD1 played a major role in activating viral transcription, followed by DRD4, which increased p24 with a slower kinetic. Transcriptome and systems biology analyses led to the identification of a cluster of genes responsive to DA, where S100A8 and S100A9 were most significantly correlated with the early increase of p24 levels following DA stimulation. Conversely, DA increased the expression of these genes’ transcripts at the protein level, respectively MRP8 and MRP14, which form a complex also known as Calprotectin. Interestingly, MRP8/14 was able to stimulate HIV transcription in latent U1 cells, and this occurred via binding to the receptor for advanced glycosylation end-product (RAGE). Using selective agonists, both DRD1 and DRD4 increased MRP8/14 on the surface and in the cytoplasm, as well as secreted in the supernatants. On the other hand, while DRD1/5 did not affect the expression of RAGE, DRD4 stimulation caused its downregulation, offering a mechanistic for the delayed effect via DRD4 on p24 increase. To cross-validate MRP8/14 as a DA signature with biomarker value, we tested its expression in HIV+ Meth users’ brains and peripheral cells. MRP8/14+ cells were more frequently identified in mesolimbic areas such as basal ganglia of HIV+ Meth+ cases compared to HIV+ non-Meth users or to controls. Likewise, MRP8/14+ CD11b+ monocytes were more frequent in HIV+ Meth users, particularly in participants with detectable viral load in the CSF. Overall, our results suggest that the MRP8 and MRP14 complex may serve as a signature to distinguish subjects using addictive substances in the context of HIV, and that this may play a role in aggravating HIV pathology by promoting viral replication in people with HIV who use Meth.

For decades, sepsis research has been motivated by the idea of a dangerous overreaction of the immune system in sepsis. But is it true that the response to sepsis is dysregulated? This review surveys the history of sepsis trials and found that evidence for dysregulation does not exist in many of the physiologic mechanisms of sepsis. It is time to consider the alternative hypothesis, that sepsis traits are often functional, and do more harm than good. This review discusses the implications of this perspective for the future of sepsis research

Due to a common mode of transmission through infected human blood, hepatitis C virus (HCV) and human immunodeficiency virus (HIV) coinfection is relatively prevalent. In alignment with this, HCV co-infection is associated with an increased size of the HIV reservoir in highly active antiretroviral therapy (HAART)-treated individuals. Hence, it is crucial to comprehend the physiological mechanisms governing the latency and reactivation of HIV in reservoirs. Consequently, our study delves into the interplay between HCV/HIV coinfection in liver cells and its impact on the modulation of HIV latency. We utilized the latently infected monocytic cell line (U1) and the latently infected T cell line (J-Lat) and found that mediators produced by the infection of hepatic stellate cells and hepatocytes with HIV and HCV, respectively, were incapable of inducing latency reversal under the studied conditions. This may favor the maintenance of the HIV reservoir size among latently infected mononuclear cells in the liver. Further investigations are essential to elucidate the role of the interaction between liver cells in regulating HIV latency and/or reactivation, providing a physiologically relevant model for comprehending reservoir microenvironments in vivo.

Quantum effects arising from manifestly broken time-reversal symmetry are investigated using time-dependent perturbation theory in a simple model. The forward time and the backward time Hamiltonians are taken to be different and hence the forward and backward amplitudes become unsymmetrical and are not complex conjugates of each other. The effects vanish when the symmetry breaking term is absent and ordinary quantum mechanical results such as Fermi Golden rule are recovered.

Background: Gut-Brain-Axis provides bidirectional communicational route; imbalance of which can have pathophysiological consequences. It is a frontier in autism research, affects 85% of autistic children (NIH report). Their microbiome has few overall microbes and smaller number of health promising microbes than their neurotypical peers. We hypothesize autism gut might play a role in manifestation of autism behaviours and on treatment, can revert back to normal behaviour considerably. The aim is to better understand to what degree gut microbiota of autism subjects differs from controls and identify bacterial species present exclusively in autism. Materials and Methods: 16s-rRNA-sequence of autism-subjects were retrieved from the American Gut Project Archive. Taxonomic assignment was inferred by similarity based methods using Quantitative Insights Into Microbial Ecology (QIIME). Species abundance was characterized and co-occurrence network was built to infer species interaction using measures of diversity. Statistical parameters were considered to validate the findings. Result: A total of 206 (1.8%) of American Gut Project datasets onstituted of autistic samples. Various bacteria such as Akkermansia sp., and Prevotella sp., were harboured in higher abundance in autistic children with statistical significance than in controls. Conclusion: These findings indicate connecting-link between gut-microbiome-brain-axis and autistic behaviour which can result in improved management

Exploration practices have proven that over mature shale gas exhibits a feature of carbon isotope reversal. The geochemical statistics indicate that the wetness (C2-C5/C1-C5) of shale gas with carbon isotope reversal is less than 1.8%. In addition, the magnitude of carbon isotope reversal (δ13C1- δ13C2) for the over mature shale gas presents a parabolic variation with decreasing wetness. δ13C1-δ13C2 increases with decreasing wetness within a wetness range of 0.9% ~1.8% and then decreases with decreasing wetness at wetness < 0.9%. The CH4 cracking experiment demonstrates that CH4 polymerization occurring in the early stage of CH4 cracking is an important factor involved in isotope reversal of over mature shale gas. Moreover, δ13C1- δ13C2 decreases with an increase in experimental temperature prior to CH4 substantial cracking. The values of δ13C1 and δ13C2 tend to equalize during CH4 substantial cracking. The δ13C1-δ13C2 of mud gas present at different depths during shale gas drilling in Sichuan Basin increases initially, then decreases with further increase in the depth and finally tends to zero, with only a trace hydrocarbon gas being detectable. Statistical data suggests that the shale gas production in Sichuan Basin decreases with the decreasing δ13C1-δ13C2 value and wetness. Thus, δ13C1-δ13C2 and wetness could potentially serve as useful criteria to screen CH4 cracking degree and to determine the largest depth of natural gas exploration. Great care should be taken during shale gas exploration in deeper layers, with wetness and δ13C1-δ13C2 less than 0.2% and 1%, respectively, since very low wetness (<0.2%) and δ13C1-δ13C2 (<1%) might be indicative of CH4 substantial cracking in a geological setting.

This interdisciplinary work presents a novel patent pending method of inertial electrostatic confinement (IEC) fusion called the Nuclear Electromagnetic Shaping Accelerator Reactor (NESAR) that addresses all of the major failure problems with currently known methods of IEC fusion. A brief background of previous IEC methods that generate a negative potential well to accelerate ions for fusion will be reviewed and compared to the NESAR method of magnetic confinement. In addition, a direct comparison will be presented between the NESAR and the tokamak method of fusion. The NESAR method of fusion obtains the plasma oscillation and compression capabilities of a tokamak without producing the catastrophic magnetic reconnection disruptions that currently plague tokamaks. Since the NESAR can oscillate charged particles comparable to the tokamak, this work will briefly review the history of the tokamak, how sawtooth magnetic reconnection occurs, and how the NESAR precludes the occurrence of magnetic reconnection. This work will also review the beginnings of a novel unified field theory that has obtained interest from the Defense Advanced Research Projects Agency (DARPA). This unified field theory is based upon the trajectory of charged particle movements within the NESAR, which is the only concept of magnetic confinement in the world that may allow charge particles to collectively interact relatively to a solitary location. Due to this possible capability, the confined charged particles have the potential to experience curved trajectories; allowing for the effects of curvature deviation to be placed upon the charged particle within the magnetic confines of the NESAR. If charged particles can experience curvature deviation then deviated acceleration is generated; allowing the electromagnet field to be propelled to a higher spatial dimension that could influence spacetime. Finally, this work will review another theory that explains how magnetic pole reversals are observed by the National Aeronautics and Space Administration’s (NASA) coiled magnetic field detectors. This theory requires little to no postulations to be framed and it is purely based upon the trajectory of charged particles within the NESAR, Michael Faraday’s law of induction, and experimental observations of rotating plasmas.

Q-switched laser radiation at wavelengths of 355 nm, 532 nm, and 1064 nm from a Nd: YAG laser was used to generate plasma in laboratory air at the target surface made of compressed nano-silver particles of size 95 ± 10 nm. The emitted resonance spectra from the neutral silver at wavelengths of 327.9 nm and 338.2 nm indicate existence of self-reversal in addition to plasma self-absorption. Both lines were identified in emission spectra at different laser irradiation wavelengths with characteristic dips at the un-shifted central wavelengths. These dips are usually associated with self-reversal. Under similar conditions, plasmas at the corresponding bulk silver target were generated. The recorded emission spectra were compared to those obtained from the nano-material target. The comparisons confirm existence of self-reversal of resonance lines that emerge from plasmas produced at nano-material targets. This work suggests a method for recovery of the spectral line shapes and discusses practical examples. In addition, subsidiary calibration efforts that utilize the Balmer series Hα-line reveal that other Ag I lines at 827.35 nm and 768.7 nm are optically thin under variety of experimental conditions and are well-suited as reference lines for measurement of the laser plasma electron density.

Controlling functional properties of matter and combine them for engineering a functional device is nowadays a common direction of scientific community. For instance, heterogeneous magnetic nanostructures can make use of different types of geometrical and compositional modulations to achieve the control of the magnetization reversal along with the nano-entities and thus enabling the fabrication of spintronic, magnetic data storage and sensing devices, among others. In this work, diameter modulated FeNi nanowires are fabricated paying special effort to obtain sharp transition regions between two segments of different diameters (from about 450 nm to 120 nm), enabling precise control over the magnetic behavior of the sample. Micromagnetic simulations performed on single bi-segmented nanowires predict a double step magnetization reversal where the wide segment magnetization switches near 200 Oe through a vortex domain wall, while at 500 Oe the magnetization of the narrow one is reversed through a corkscrew like mechanism. Finally, these results are confirmed with magneto-optic Kerr effect measurements at the transition of isolated bi-segmented nanowires. Furthermore, macroscopic vibrating sample magnetometry is used to demonstrate that the magnetic decoupling of nanowire segments is the main phenomenon occurring over the entire fabricated nanowires.

The Epithelial-Mesenchymal-Transition (EMT) phenotype, identified as a significant clinical indicator in cancer, manifests as a biological process where cells transition from epithelial to mesenchymal characteristics. Physiologically, EMT plays a crucial role in tissue remodeling, promoting healing, repair, and responding to various tissue damages. This study investigates the impact of BNE-RRC on oral cancer cells (KB) and reveals its significant effects on cancer cell growth, migration, invasion, and EMT. BNE-RRC induces the epithelial-like morphology in KB cells, effectively reversing EMT to Mesenchymal-Epithelial Transition (MET). Extraordinarily, sustained culture of cancer cells with BNE-RRC for 14 days maintains an epithelial status even after treatment withdrawal, suggesting BNE-RRC as a potential therapeutic agent for cancer. These findings highligh the promise of BNE-RRC as a comprehensive therapeutic agent in cancer treatment by inhibiting cancer cell growth, migration, and invasion, while also orchestrating a reversal of the EMT process. The study proposes that BNE-RRC could be effective agent for cancer treatment.

Despite all efforts, the treatment of breast cancer (BC) cannot be considered to be a success story. The advances in surgery, chemotherapy and radiotherapy have not been sufficient. Indeed, the accumulated experience clearly indicates that new perspectives and non-main stream approaches are needed to better characterize the etiopathogenesis and treatment of this disease. This contibution deals with how the new pH-centric anticancer paradigm plays a fundamental role in reaching a more integral understanding of the etiology, etiopathogenesis and treatment of this multifactorial disease. For the first time the armamentarium available for the treatment of the different types and phases of BC is approached here from a Unitarian perspective based upon the hydrogen ion dynamics of cancer. The wide-ranged pH-related molecular, biochemical and metabolic model is able to embrace most the fields and subfields of breast cancer pathology. This single and integrated approach allows to advance a unidirectional program to treatment. Further efforts in this line are likely to first improve the therapeutics of each subtype of this tumor, then every phase of the disease and finally every individual patient.