SARS-CoV-2 is the causative agent for the ongoing COVID19 pandemic, and this virus belongs to the Coronaviridae family. Like other members of this family, the virus possesses a positive-sense single-stranded RNA genome. The genome encodes for the nsp12 protein, which houses the RNA-dependent-RNA polymerase (RdRP) activity responsible for the replication of the viral genome. A homology model of nsp12 was prepared using the structure of the SARS nsp12 (6NUR) as a model. The model was used to carry out in silico screening to identify molecules among natural products, or FDA approved drugs that can potentially inhibit the activity of nsp12. This exercise showed that vitamin B12 (methylcobalamin) may bind to the active site of the nsp12 protein. A model of the nsp12 in complex with substrate RNA and incoming NTP showed that Vitamin B12 binding site overlaps with that of the incoming nucleotide. A comparison of the calculated energies of binding for RNA plus NTP and methylcobalamin suggested that the vitamin may bind to the active site of nsp12 with significant affinity. It is, therefore, possible that methylcobalamin binding may prevent association with RNA and NTP and thus inhibit the RdRP activity of nsp12. Overall, our computational studies suggest that methylcobalamin form of vitamin B12 may serve as an effective inhibitor of the nsp12 protein.

Starting from December 2019, coronavirus disease 2019 (COVID-19) has emerged as a once-in-a-century pandemic with deadly consequences, which urgently calls for new treatments, cures and supporting apparatuses. Remdesivir was reported by World Health Organization (WHO) as the most promising drug currently available for the treatment of COVID-19. Here, we use molecular dynamics simulations and free energy perturbation methods to study the inhibition mechanism of remdesivir to its target SARS-CoV-2 virus RNA-dependent RNA polymerase (RdRp). In the absence of a crystal structure of the SARS-CoV-2 RdRp, we first construct the homology model of this polymerase based on a previously available structure of SARS-CoV NSP12 RdRp (with a sequence identify of 95.8%). We then build the putative binding mode by aligning the remdesivir + RdRp complex to the ATP bound poliovirus RdRp. The putative binding structure is further optimized with molecular dynamics simulations and demonstrated to be stable, indicating a reasonable binding mode for remdesivir. The relative binding free energy of remdesivir is calculated to be -8.28 ± 0.65 kcal/mol, much stronger than the natural substrate ATP (-4.14 ± 0.89 kcal/mol) which is needed for the polymerization. The ~800-fold improvement in the K_d from remdesivir over ATP indicates an effective replacement of APT in blocking of the RdRp binding pocket. Key residues D618, S549 and R555 are found to be the contributors to the binding affinity of remdesivir. These findings demonstrate that remdesivir can potentially act as a SARS-CoV-2 RNA-chain terminator, effectively stopping its RNA reproduction, with key residues also identified for future lead optimization and/or drug resistance studies.

COVID-19 has emerged as deadly pandemic worldwide with no vaccine or suitable antiviral drugs to prevent or cure the disease. Because of the time-consuming process to develop new vaccines or antiviral agents, there has been a growing interest in repurposing some existing drugs to combat SARS-CoV-2. Vitamin D is known to be protective against acute respiratory distress syndrome (ARDS), pneumonia and cytokine storm. Recently it has been used as a repurposed drug for the treatment of H5N1 virus-induced lung injury. Circumstantial evidences indicate that people with low level of vitamin D are more susceptible to SARS-CoV-2. Although, vitamin D was suggested to interfere with viral replication, its interaction with any SARS-CoV-2 protein is unexplored yet. Beside this, ivermectin, a well-known anti-parasitic agent, exhibits potent anti-viral activities in vitro against viruses such as HIV-1 and dengue. Very recently, ivermectin has been found to reduce viral load of SARS-CoV-2 in vitro. We have analyzed available structures of SARS-CoV-2 proteins to identify probable binding partner(s) of vitamin D and ivermectin through knowledge-based docking studies and figured out possible implication of their binding in SARS-CoV-2 infection. Our observations suggest that the non-structural protein nsp7 possesses a potential site to house 25-hydroxyvitamin D3 (VDY) or the active form of Vitamin D, calcitrol. Binding of vitamin D with nsp7 likely to hamper the formation of nsp7-nsp8 complex which is required to bind with RNA dependent RNA polymerase (RdRP), nsp12 for optimal function. On the other hand, potential binding site of ivermectin has been identified in the S2 subunit of trimeric spike(S) glycoprotein of SARS-CoV-2. We propose that deeply inserted mode of ivermectin binding at three inter-subunit junctions may restrict large scale conformational changes of S2 helices which is necessary for efficient fusion of viral and host membrane. Our study, therefore, opens up avenues for further investigations to consider vitamin D and ivermectin as potential drugs against SARS-CoV-2.

The transmission characteristic of COVID-19 is of similar magnitude to severe acute respiratory syndrome-related coronavirus (SARS-CoV) and the 1918 pandemic influenza. The virus is now in more than 100 countries and on nearly all continents. The World Health Organization (WHO) declared the COVID-19 outbreak a pandemic. There is no current evidence from random clinical trials (RCTs) to recommend any specific anti-COVID-19 treatment for patients with suspected or confirmed COVID-19 infection. In order to mitigate the impact of the COVID-19 outbreak, here we propose an innovative superinfection therapeutic (SIT) strategy, which could complement the development of prophylactic vaccines. SIT is based on clinical observations that unrelated viruses might interact in co-infected patients. During SIT, the patient benefit from superinfection with an apathogenic dsRNA virus such as the infectious bursal disease virus (IBDV), which is a powerful activator of the interferon-dependent antiviral gene program. An attenuated vaccine strain of IBDV was already successfully administered to resolve acute and persistent infections induced by two completely different viruses, the hepatitis B (DNA) and C (RNA) viruses (HBV/HCV). Importantly, the epidemiological efficacy of a similar strategy to SIT had already been successfully tested in large controlled trials. Standard live orally administered enterovirus vaccines that stimulate the production of endogenous interferon of the host mitigated the seasonal outbreaks of influenza and other associated acute respiratory infections in 152,042 individuals without adverse reactions.

In this paper, we examine the mathematical and physical consistencies of the three primary couple stress theories: original Mindlin-Tiersten-Koiter couple stress theory (MTK-CST), modified couple stress theory (M-CST) and consistent couple stress theory (C-CST). As has been known for many years, MTK-CST suffers from some fundamental inconsistencies, such as the indeterminacy of the couple-stress tensor. Therefore, despite the fact that MTK-CST has a fundamental position in the evolution of size-dependent continuum mechanics, it is not a reliable theory within continuum mechanics, for example, in developing new size-dependent multi-physics formulations. We also observe that M-CST not only inherits all inconsistences from the original MTK-CST, but also suffers from new additional inconsistencies, such as the introduction of a new non-physical governing equation. These inconsistencies refute the claim of those who state that the couple-stress tensor may be chosen symmetric. Therefore, the apparent success of MTK-CST and M-CST in describing a size-effect for some problems, such as two-dimensional plate and beam bending, is not enough to justify these theories as suitable for general cases. In fact, the symmetric couple-stresses in M-CST create torsional or anticlastic deformation, not bending. On the other hand, C-CST, with a skew-symmetric couple-stress tensor, is the consistent continuum mechanics suitable for solving different size-dependent solid, fluid and multi-physics problems.

The high radio frequency polarization imaging of non-thermal emission from active galactic nuclei (AGN) is a direct way to probe the magnetic field strength and structure in the immediate vicinity of supermassive black holes (SMBHs) and is crucial in testing the jet-launching scenario. To explore the the magnetic field configuration at the base of jets in blazars, we took advantage of the full polarization capabilities of the GMVA (Global Millimeter VLBI Array). With an angular resolution of ~50 micro-arcseconds at 86 GHz, one could reach scales down to ~900 Schwarzschild radii (for a 10^9 solar mass black hole). We present here the preliminary results of our study on the blazar BL Lac. Our results imply that on sub-mas scales the core and central jet of BL Lac is significantly polarized with two distinct regions of polarized intensity. We also noted a great morphological similarity between the 7mm/3mm VLBI images at very similar angular resolution.

As the leader of the largest economy, President of the United States has substantive influence on addressing the global climate change problem. However, presidential election is often dominated by issues other than energy problems. This paper focuses on the on-going 2016 presidential election, examining the energy plans proposed by the leading Democrat and Republican candidates. Our data from the Iowa caucus survey in January 2016 suggests that voters are more concerned about terrorism and economic issues than environmental relative issues. We then compare the Democratic and Republican candidate’s view of American’s energy future, and evaluate their proposed renewable energy targets. We find that the view on renewable energy is polarized between Democratic and Republican candidates, while candidates from both parties agree on the need for energy efficiency. Results from our ordinal least squares regression models suggest that Democratic candidates have moderate to ambitious goals for developing solar and other renewable energy. The Republican candidates favor fossil fuel and they neglect to provide any plan for renewable energy. In addition, this trend of polarization has grown more significant when compared with the past three presidential elections. Our observation suggests that energy issues need to be discussed more to draw broader attention to salient issues of diversifying and decarbonizing the nation’s energy system.

Relativistic shocks are one of the most plausible sites of the emission of strongly variable, polarized multi-wavelength emission from relativistic jet sources such as blazars, via diffusive shock acceleration (DSA) of relativistic particles. This paper summarizes recent results on a self-consistent coupling of diffusive shock acceleration and radiation transfer in blazar jets. We demonstrate that the observed spectral energy distributions (SEDs) of blazars strongly constrain the nature of hydromagnetic turbulence responsible for pitch-angle scattering by requiring a strongly energy-dependent pitch-angle mean free path. The prominent soft X-ray excess (``Big Blue Bump'') in the SED of the BL Lac object AO 0235+164 can be modelled as the signature of bulk Compton scattering of external radiation fields by the thermal electron population, which places additional constraints on the level of hydromagnetic turbulence. It has further been demonstrated that internal shocks propagating in a jet pervaded by a helical magnetic field naturally produce polarization-angle swings by 180$^o$, in tandem with multi-wavelength flaring activity, without requiring any helical motion paths or other asymmetric jet structures. The specific application of this model to 3C279 presents the first consistent, simultaneous modeling of snap-shot SEDs, multi-wavelength light curves and time-dependent polarization signatures of a blazar during a polarization-angle (PA) rotation. This model has recently been generalized to a lepto-hadronic model, in which the high-energy emission is dominated by proton synchrotron radiation. It is shown that in this case, the high-energy (X-ray and $\gamma$-ray) polarization signatures are expected to be significantly more stable (not showing PA rotations) than the low-energy (electron-synchrotron) signatures.

The COVID-19 pandemic affects all parameters, especially health care professionals, drugs and medical supplies. The KERRA is a mixed medicinal plant capsule that is used for the treatment of patients with high fever with food and drug administration approved by FDA Thailand. Recently, KERRA showed quicker recovery for COVID-19 patients. Therefore, it is possible that some ingredients in KERRA could inhibit SARS-CoV-2. In this study, two important replication-related enzymes in SARS-CoV-2, a main protease and an RNA-dependent RNA polymerase (RdRp), were used to study the effect of KERRA. The results showed that KERRA inhibited the SARS-CoV-2 main protease and SARS-CoV-2 RdRp with IC50 values of 49.91 ± 1.75 ng/mL and 36.23 ± 5.23 µg/mL, respectively. KERRA displayed no cytotoxic activity on macrophage cells at concentrations lower than 1 mg/mL and exhibited anti-inflammatory activity. Additionally, KERRA was against a feline coronavirus (feline infectious peritonitis [FIP]) infection with an EC50 value of 134.3 g/mL. This study supports the potential use of KERRA as a candidate drug for COVID-19.

Arthropod-borne flaviviruses represent human pathogens of global medical importance, against which no effective small molecule-based antiviral therapy is currently available. Arbidol (umifenovir) is a broad spectrum antiviral compound approved in Russia and China for prophylaxis and treatment of influenza. This compound showed activity against numerous DNA and RNA viruses. Its mode of action is based predominantly on the impairment of critical steps of virus-cell interaction. Here we demonstrate that arbidol possesses a micromolar inhibition activity (EC50 values ranging from 10.57 ± 0.74 to 19.16 ± 0.29 µM) in Vero cells infected with Zika virus, West Nile virus, and tick-borne encephalitis virus, three medically important representatives of arthropod-borne flaviviruses. Interestingly, no antiviral effect of arbidol is observed in porcine stable kidney cells (PS), human neuroblastoma cells (UKF-NB-6), human hepatoma cells (Huh-7 cells) indicating that the antiviral effect of arbidol is strongly cell-type dependent. Arbidol presents a significant increasing in cytotoxicity profiles when tested in various cell lines in the order: Huh-7 < HBCA < PS < UKF-NB-6 < Vero with CC50 values ranging from 18.69 ± 0.1 to 89.72 ± 0.19 µM. Antiviral activity and acceptable cytotoxicity profiles suggest that arbidol could be a promising candidate for further investigation as a potential therapeutic agent in treating flaviviral infections.

As the natural resources are getting exhausted, the concept of sustainable development of region has received increasing attentions, especially for resource-dependent cities. In this paper an innovative method that emergy analysis and IPAT (Human Impact Population Affluence Technology) model were combined in order to analyze the quantitative relationship of economic growth and energy consumption and further to evaluate its overall sustainability level. Taiyuan, a traditional, resource-dependent city in China, is selected as the case study region. The main results show that total emergy of Taiyuan increased from 9.023× 1023 sej in 2007 to 9.116× 1023sej in 2014, with 38% reduction on non-renewable emergy and 125% growth on imported emergy. Regional emergy money ratio (RMB) was reduced by 48% from 5.31× 1013sej/$ in 2007 to 2.74× 1013sej/$ in 2014, indicating that the increasing speed of consuming resources and energy was faster than the increase of GDP, and that Taiyuan’s money purchasing power declined. The lower emergy sustainability index (ESI) indicates that Taiyuan was explored and produced large quantities of mineral resources, which puts more stress on the environment as a consequence, and that this is not sustainable in the long run. The IPAT analysis demonstrates that Taiyuan sticks to the efforts of energy conservation and environmental protection, in order to promote regional sustainable development, it is necessary to take an integrated effort. Policy insights suggest that resourceful regions should improve include energy and resource efficiency, optimizing energy and resourceful structure.

In this paper, we study the problem of controllability of impulsive neutral evolution integrodifferential equations with state dependent delay in Banach spaces. The main results are completely new and are obtained by using Sadovskii's fixed point theorem, theory of resolvent operators, and an abstract phase space. An example is given to illustrate the theory.

Prompt removal of misfolded membrane proteins and misassembled membrane protein complexes is essential for membrane homeostasis. However, the elimination of these toxic proteins from the hydrophobic membrane environment has high energetic barriers. Transmembrane FtsH is the only known ATP-dependent protease responsible for this task, unlike other well-studied soluble ATP-dependent proteases. The mechanisms by which FtsH recognizes, unfolds, translocates, and proteolyzes its substrates remain unclear. Here, we report the crystal structures of the Thermotoga maritima FtsH periplasmic domain (PD) in an associative trimeric state at a 1.5-1.95 Å resolution. We also describe the pH-dependent oligomerization states of the isolated PD using dynamic light scattering. These observations help us understand how FtsH recognizes membrane-anchored misfolded proteins.

Background: Obesity among pregnant women is common, and their offspring are predisposed to obesity, insulin resistance, and diabetes. Circulating metabolites that are related to insulin resistance and are associated with this decreased tissue-specific uptake are unknown. Here, we assessed metabolite profiles in elderly women and who were either female offspring from obese mothers (OOM) or offspring of lean mothers (OLM). Metabolic changes were tested for associations with metrics for insulin resistance. Methods: 37 elderly women were separated into an elderly offspring from obese mothers (OOM; n = 17) and elderly offspring from lean/normal weight mothers (OLM; n = 20) groups. We measured plasma metabolites using 1H-NMR and also insulin-dependent tissue specific glucose uptake in skeletal muscle were assessed. Associations were made between metabolites and glucose uptake. Results: Compared to the OLM group, we found that the 22:6 docosahexaenoic acid percentage of the total long chain n-3 fatty acids (DHA/FA) was significantly lower in OOM (P = 0.015). DHA/FA associated significantly to skeletal muscle GU (P = 0.031) and M-value in the OLM group only (P = 0.050). Conclusions: DHA/FA is associated with insulin-dependent skeletal muscle glucose uptake and that this association is significantly weakened in the offspring of obese mothers.

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.

We propose a model for gravity based on the gravitational polarization of space. With this model, we can relate the density parameters within the Friedmann model, and show that dark matter is bound mass formed from massive dipoles set up within the vacuum surrounding ordinary matter. Aggregate matter induces a gravitational field within the surrounding space, which reinforces the original field. Dark energy, on the other hand, is the energy density associated with gravitational fields both for ordinary matter, and bound, or induced dipole matter. At high CBR temperatures, the cosmic susceptibility, induced by ordinary matter vanishes, as it is a smeared or average value for the cosmos as a whole. Even though gravitational dipoles do exist, no large scale alignment or ordering is possible. Our model assumes that space, i.e., the vacuum, is filled with a vast assembly (sea) of positive and negative mass particles having Planck mass, called planckions, which is based on extensive work by Winterberg. These original particles form a very stiff two component superfluid, where positive and negative mass species neutralize one another already at the submicroscopic level, leading to zero net mass, zero net gravitational pressure, and zero net entropy, for the undisturbed medium. It is theorized that the gravitational dipoles form from such material positive and negative particles, and moreover, this causes an intrinsic polarization of the vacuum for the universe as a whole. We calculate that in the present epoch, the smeared or average susceptibility of the cosmos equals, , and the overall resulting polarization equals, . Moreover, due to all the ordinary mass in the universe, made up of quarks and leptons, we calculate a net gravitational field having magnitude, . This smeared or average value permeates all of space, and can be deduced by any observer, irrespective of location within the universe. This net gravitational field is forced upon us by Gauss’s law, and although technically a surface gravitational field, it is argued that this surface, smeared value holds point for point in the observable universe. A complete theory of gravitational polarization is presented. In contrast to electrostatics, gravistatics leads to anti-screening of the original source field, increasing the original value, , to, , where is the induced or polarized field. In the present epoch, this leads to a bound mass, , where is the sum of all ordinary source matter in the universe, and equals the relative permittivity. A new radius, and new mass, for the observable universe is dictated by the density parameters in Friedmann's equation, and Gauss’s law. These lead to the very precise values, , and, , respectively, somewhat larger than current less accurate estimates.

In the present work, a novel conductive liquids method of study has been proposed. It is based on the phenomenon of radiofrequency anisotropy of electrolyte solution discovered by us. It arises in response to mechanical or acoustic excitation of the solution. We have observed the phenomenon during the development of an RF polarimetric contactless cardiograph. The electric field vector of the transmitted 433.82 MHz signal rotated after its transition through the pericardial region. That rotation depends on the change of blood acceleration when passing through the chambers of the heart and large vessels. It has also been revealed that rotation occurs after RF wave passage through the physiological saline (0.9% NaCl) subjected to any mechanical excitation inside it like a jet appearing or soundwave passing. No significant difference was detected experimentally between NaCl and KCl solutions behavior. It means that the mechanism of hydrodynamic separation of ions is apparently not suitable to explain the phenomenon. The response we have registered resembles the magnetization process of spin glasses. From the nature of the observed response, we have concluded that a fundamentally new physical effect is discovered. It may provide wide opportunities for remote measurement of the electrolyte solution parameters with polarized radio-frequency signals.

Magneto-electrochemistry (MEC) is a unique paradigm in science, where electrochemical experiments are carried out as a function of an applied magnetic field, creating a new horizon of potential scientific and technological applications. Over the time, detailed understanding of this research domain was developed to identify and rationalize the possible effects exerted by a magnetic field on the various microscopic processes occurring in an electrochemical system, such as: electrolyte properties governed by charge-transfer process (electric conductivity, viscosity, and diffusivity), mass transfer, electrochemical kinetics and on the structure/quality of products formed either at the working electrode or in the electrochemical cell. Particularly, magnetic field controlled chiral architecture obtained from deposited metal, alloys and catalyst and their excellent enantio-recognition in experimental frame is highly appealing. Interestingly, Hall effect was also demonstrated in electrolytic medium via an impressive experimental technique which is being employed for further theoretical understanding in the field of magneto-electrochemical science. Later, a highly reproducible local temperature variation was observed in electrochemical electrolytes exposed to perpendicular magnetic and electric fields. However, until recent studies, none of the above mentioned reports considered the possibility of a spin-dependent related charge-transfer process. Recent experimental and theoretical studies reveal that electron’s transmission through chiral molecules is spin-selective and this effect has been referred to as chiral-induced spin-selectivity (CISS) effect. The CISS effect pave the way for the building up of a system characterized by a net magnetic moment exploiting the spin-filtering ability of chiral molecules. This interplay between chirality and magnetism may shed light on fundamental scientific aspects underlying the enantio-recognition and highly efficient electron-transfer that occurs in biological process.

External quantum efficiency of industrial-grade green InGaN light-emitting diodes (LEDs) has been measured in a wide range of operating currents at various temperatures from 13 K to 300 K. Unlike blue LEDs, the efficiency as a function of current is found to have a multi-peak character, which could not be fitted by a simple ABC-model. This observation correlated with splitting of LED emission spectra into two peaks at certain currents. The characterization data are interpreted in terms of non-uniformity of the LED active region, which is tentatively attributed to extended defects like V-pits. We suggest a new approach to evaluation of temperature-dependent light extraction and internal quantum efficiencies taking into account the active region non-uniformity. As a result, the temperature dependence of light extraction and internal quantum efficiencies have been evaluated in the temperature range mentioned above and compared with those of blue LEDs.

Many systems in nature and laboratories are far from equilibrium and exhibit significant fluc- tuations, invalidating the key assumptions of small fluctuations and short memory time in or near equilibrium. A full knowledge of Probability Distribution Functions (PDFs), especially time- dependent PDFs, becomes essential in understanding far-from-equilibrium processes. We consider a stochastic logistic model with multiplicative noise, which has gamma distributions as stationary PDFs. We numerically solve the transient relaxation problem, and show that as the strength of the stochastic noise increases the time-dependent PDFs increasingly deviate from gamma distributions. For sufficiently strong noise a transition occurs whereby the PDF never reaches a stationary state, but instead forms a peak that becomes ever more narrowly concentrated at the origin. The addition of an arbitrarily small amount of additive noise regularizes these solutions, and re-establishes the existence of stationary solutions. In addition to diagnostic quantities such as mean value, standard deviation, skewness and kurtosis, the transitions between different solutions are analyzed in terms of entropy and information length, the total number of statistically distinguishable states that a system passes through in time.

In this work, we focus on investigating electrothermal flow in a rotating electric field (ROT-ETF), with primary attention paid to the horizontal traveling-wave electrothermal (TWET) vortex induced at the center of the electric field. The frequency-dependent flow profiles in the microdevice are analyzed using different heat transfer models. Accordingly, we address in particular the importance of electrode cooling in ROT-ETF as metal electrodes of high thermal conductivity while substrate material of low heat dissipation capability are employed to develop such microfluidic chips. Under this circumstance, cooling of electrode array due to external natural convection on millimeter-scale electrode pads for external wire connection occurs and makes the internal temperature maxima shift from the electrode plane to a bit of distance right above the cross-shaped interelectrode gaps, giving rise to reversal of flow rotation from a typical repulsion-type to attraction-type induction vortex, which is in good accordance with our experimental observations of co-field TWET streaming at frequencies on the order of reciprocal charge relaxation time of the bulk fluid. These results point out a way to make a correct interpretation of out-of-phase electrothermal streaming behavior, which holds great potential for handing high-conductivity analytes in modern microfluidic systems.

It is extremely fascinating and astonishing that the gravitational field on the surface of a neutron star is with a relativistic mass density of 2.65*10¹⁶~5.87*10¹⁸kgm^-3 which can be larger than the mass density of the neutron star (~10¹⁷kgm^-3).Therefore, it is the author’s first intuitional imagining that this field could directly convert into mass. In so strong a gravitational field, electron and proton could be produced directly from graviton–photon collision. The gravitational field exists in everywhere in our universe. No vacuum that the region of a space is “empty” does exist. A particle is clearly always being acted on by the gravitational field. The quantum vacuum fluctuation and vacuum polarization need be re-understood with the interaction between photon and gravitational field. Therefore, the gravitational field is naturally one of the foundations of modern physics.

Time evolution operators of a strongly ionizing medium are calculated by a time-dependent unitary transformation (TDUT) method. The TDUT method has been employed in quantum mechanical system composed of discrete states. This method is especially helpful for solving molecular rotational dynamics in quasi-adiabatic regimes because the strict unitary nature of the propagation operator allows us to set the temporal step size large; a tight limitation on the temporal step size ($\delta t <<1$) can be circumvented by the strict unitary nature. On the other hand, in a strongly ionizing system where the Hamiltonian is not Hermitian, the same approach cannot be directly applied because it is demanding to define a set of field-dressed eigenstates. In this study, the TDUT method was applied to the ionizing regime using the Kramers-Henneberger frame, in which the strong-field-dressed discrete eigenstates are given by the field-free discrete eigenstates in a moving frame. Although the present work verifies the method for a one-dimensional atom as a prototype, the method can be applied to three-dimensional atoms, and molecules exposed to strong laser fields.

In this paper we address one of the most important topics in the field of Social Networks Analysis: the community detection problem with additional information. That additional information is modeled by a fuzzy measure that represents the possibility of polarization. Particularly, we are interested in dealing with the problem of taking into account the Polarization of nodes in the community detection problem. Adding this type of information to the community detection problem makes it more realistic, as a community is more probably to be defined if the corresponding elements are willing to maintain a peaceful dialogue. The polarization capacity is modeled by a fuzzy measure based on the JDJpol measure of polarization related to two poles. We also present an efficient algorithm for finding groups whose elements are no polarized. Hereafter, we work in a real case. It is a network obtained from Twitter, concerning the political position against the Spanish government taken by several influential users. We analyze how the partitions obtained change when some additional information related to how polarized that society is, is added to the problem.

Favipiravir is a broad-spectrum inhibitor of viral RNA-dependent RNA polymerase (RdRp) currently being used to manage COVID-19 in several countries. By acting as a substrate for RdRp, favipiravir gets incorporated into the nascent viral RNA and prevents strand extension. A high mutation rate of SARS-CoV-2 RdRp may facilitate antigenic drift as an answer to the host immune response, thereby generating resistance of virus to favipiravir. Therefore, it is extremely crucial to predict potential mutational sites in the RdRp and the emergence of structural modifications contributing to drug resistance. Here, we used high-throughput interface-based protein design to generate >100,000 designs and identify mutation hotspot residues in the favipiravir-binding site of RdRp. Several mutants had lower binding affinities to favipiravir, out of which hotspot residues with a high propensity to undergo positive selection were identified. The results showed that the designs retained an average of 97 to 98% sequence identity, suggesting that SARS-CoV-2 can develop favipiravir resistance with just a few mutations. Notably, we observed that out of 134 mutations predicted designs, 63 specific mutations were already present in the CoV-GLUE database, thus attaining ~47% correlation match with the clinical sequencing data. The findings improve our understanding of the potential signatures of adaptation in SARS-CoV-2 against favipiravir and management of COVID-19. Furthermore, they can help develop exhaustive strategies for robust antiviral design and discovery.

Brine-dependent recovery process has seen much global research efforts in the past two decades because of their benefits over other oil recovery methods. The process involves the tweaking of the ionic composition and strength of the injected water to improve oil production. In recent years, several studies ranging from laboratory coreflood experiments by many researchers to field trials by several companies admit to the potential of recovering additional oil in sandstone and carbonate reservoirs. Sandstone and carbonate rocks are composed of completely different minerals, with varying degree of complexity and heterogeneity, but wettability alteration has been widely considered as the consequence rather than the cause of brine-dependent recovery. However, there is no consensus on the cause as several mechanisms have been proposed to relate the wettability changes to the improved recovery. This review paper aims to provide a state-of-the-art development in published research and various efforts of the industry. This review outlines an overview of laboratory and field observations, descriptions of underlying mechanisms and their validity, the complexity of the oil-brine-rock interactions, modelling works, and comparison between sandstone and carbonate rocks. The provided information is intended to provide the reader with up-to-date information, point to relevant studies for those who are new and those implementing either laboratory- or field-scale projects to speed up the process of further investigations in this research area. Overall, the outcome of this review would potentially be of immense benefit to the oil industry.

Our study aims to implement a strategy to reduce the carbon steel corrosion rate in sulfuric acid solution, using an expired drug with adsorption affinity on the metal surface. To investigate the corrosion protection efficiency of an environmental friendly inhibitor, namely neomycin sulfate (NMS), the electrochemical measurements were applied on carbon steel immersed in 1.0 M H₂SO₄ solution with and without NMS. The protective layer formed on the steel surface was studied by atomic force microscopy (AFM). The potentiodynamic polarization and electrochemical impedance spectroscopy (EIS) showed that the presence of the neomycin sulfate in acid solution leads to the decrease in corrosion current density (i_corr) and the increase of polarization resistance (R_p). The mixed mechanism between physical and chemical adsorption of NMS molecules on the steel surface was proposed according to the Langmuir adsorption isotherm. The Atomic Force Microscopy (AFM) indicated that the NMS molecules contributed to a protective layer formation by their adsorption on the steel surface. The AFM parameters such as: root-mean-square roughness (R_q); average roughness (R_a) and maximum peak to valley height (R_p-v) revealed that in the presence of NMS a smoother surface of carbon steel was obtained, compared to the steel surface corroded in sulfuric acid blank solution.

In this paper a microstrip Wilkinson power divider with a 90^° phase delay at one output port is proposed to obtain circular polarization to feed a dual port RFID antenna. The 90^° phase delay was obtained by embedding an extra quarter wavelength at one port of the Wilkinson power divider. The feeding circuit is then mounted on the ground plane of the microstrip antenna feeding the radiating patch directly through the ground plane and dielectric layer thus reducing any fringing effect and resulting a mechanically compact unit. The proposed feeding method offers better expectation of antenna performance with minimal attenuation and coupling losses. The design process generalizes geometric pa- rameters of the Wilkinson power divider for variable port distances. The paper considers both UK and US RFID center frequencies, 870 MHz and 915 MHz respectively. Numeri- cally computed values for geometric design parameters for both frequencies are tabled as future design tools for port distances varying from 18 mm up to 34 mm at 870 MHz and 17 mm up to 32 mm at 915 MHz. Simulation results indicate a return loss (S11) of -20 dB and -26 dB at 870 MHz and 915 MHz operational frequencies respectively at 270^° angled quarter wavelength.

Initial attempts to develop monoclonal antibodies as therapeutics to resolve influenza infections focused mainly on searching for antibodies with the potential to neutralise the virus in vitro with classical haemagglutination inhibition and micro-neutralisation assays. This led to the identification of many antibodies that bind to the head domain of haemagglutinin (HA) which generally have potent neutralisation capabilities that block viral entry or viral membrane fusion. However, this class of antibodies has a narrow breadth of protection in that they are usually strain specific. This led to the emphasis on stalk targeting antibodies which are able to bind a broad range of viral targets that span across different influenza subtypes. Recently, a third class of antibodies targeting the vestigial esterase (VE) domain have been characterised. In this review, we describe the key features of neutralising VE targeting antibodies and compare them with head and stalk class antibodies.

The current SARS- CoV-2 pandemic underscores the importance of understanding the evolution of RNA genomes. While RNA is subject to the formation of similar lesions as DNA, the evolutionary and physiological impacts RNA lesions have on viral genomes are yet to be characterized. Lesions that may drive the evolution of RNA genomes can induce breaks that are repaired by recombination or can cause base substitution mutagenesis, also known as base editing. Over the past decade or so, base editing mutagenesis of DNA genomes has been subject to many studies, revealing that exposure of ssDNA is subject to hypermutation that is involved in the etiology of cancer. However, base editing of RNA genomes has not been studied to the same extent. Recently hypermutation of single-stranded RNA viral genomes have also been documented though its role in evolution and population dynamics. Here, we will summarize the current knowledge of key mechanisms and causes of RNA genome instability covering areas from the RNA world theory to the SARS- CoV-2 pandemic of today. We will also highlight the key questions that remain as it pertains to RNA genome instability, mutations accumulation, and experimental strategies for addressing these questions.

Soil moisture (SM) plays an essential role in environmental studies related to wetlands, an ecosystem sensitive to climate change. Hence, there is the need for its constant monitoring. SAR (Synthetic Aperture Radar) satellite imagery is the only mean to fulfill this objective regardless of the weather. The objective of the study was to develop the methodology for SM retrieval under wetland vegetation using Sentinel-1 (S-1) satellite data. The study was carried out during the years 2015–2017 in the Biebrza Wetlands, situated in northeastern Poland. At the Biebrza Wetlands, two Sentinel-1 validation sites were established, covering grassland and marshland biomes, where a network of 18 stations for soil moisture measurement was deployed. The sites were funded by the European Space Agency (ESA), and the collected measurements are available through the International Soil Moisture Network (ISMN). The NDVI (Normalized Difference Vegetation Index) was derived from the optical imagery of a MODIS (Moderate Resolution Imaging Spectroradiometer) sensor onboard the Terra satellite. The SAR data of the Sentinel-1 satellite with VH (vertical transmit and horizontal receive) and VV (vertical transmit and vertical receive) polarization were applied to soil moisture retrieval for a broad range of NDVI values and soil moisture conditions. The new methodology is based on research into the effect of vegetation on backscatter () changes under different soil moisture and vegetation (NDVI) conditions. It was found that the state of the vegetation may be described by the difference between  VH and  VV, or the ratio of  VV/VH, as calculated from the Sentinel-1 images. The most significant correlation coefficient for soil moisture was found for data that was acquired from the ascending tracks of the Sentinel-1 satellite, characterized by the lowest incidence angle, and SM at a depth of 5 cm. The study demonstrated that the use of the inversion approach, which was applied to the new developed models and includes the derived indices based on S-1, allowed the estimation of SM for peatlands with reasonable accuracy (RMSE ~ 10 vol. %). Due to the temporal frequency of the two S-1 satellites’ (S-1A and S-1B) acquisitions, it is possible to monitor SM changes every six days. The conclusion drawn from the study emphasizes a demand for the derivation of specific soil moisture retrieval algorithms that are suited for wetland ecosystems, where soil moisture is several times higher than in agricultural areas.

Macrophages are cells involved in the primary response to debris derived from wear of implanted CoCr alloys. The biocompatibility of wear particles from a high carbon CoCr alloy produced under polarization in physiological hyaluronic acid (HA) solution was evaluated in J774A.1 mouse macrophages cultures. Polarization was applied to mimic the electrical interactions observed in living tissues. Wear tests were performed in a pin-on-disk tribometer integrating an electrochemical cell in phosphate buffer solution (PBS) and in PBS supplemented with 0.3% HA, physiological synovial fluid concentration, used as lubricant solution. Wear particles produced in 0.3% HA solution showed a higher biocompatibility in J774A.1 macrophages in comparison to those elicited by PBS. A considerable improvement in macrophages biocompatibility in the presence of 0.3 % of HA was further observed by the application of polarization at potentials having current densities typical of injured tissues suggesting that polarization produces an effect on the surface of the metallic material that leads to the production of wear particles that are macrophages biocompatible and less cytotoxic. The results showed the convenience to consider electric interactions together with other particles parameters, as are size and composition, to get a better understanding of the biological effects of the wear products.

In this paper, we analyze the measurements of the normalized radar cross-section(NRCS) in Wave Mode for Chinese C-band Gaofen-3(GF-3) synthetic aperture radar (SAR). Based on 2779 images from GF-3 quad-polarization SAR in Wave Mode and collocated wind vectors from ERA-Interim, we verify the feasibility of using ocean surface wind fields and VV-polarized NRCS to perform normalized calibration. The method uses well-validated empirical C-band geophysical model function (CMOD4) to estimate the calibration constant for each beam. The Amazon rainforest experiment results show that the accuracy of obtained calibration constant meets the requirements. In addition, the relationship between cross-pol NRCS and wind vectors is discussed. The cross-pol NRCS increases linearly with wind speed and it has an approximate cosine modulation with the wind direction when the wind speed is greater than 8m/s. The cross-polarized system noise floor is low enough to ignore it in wind retrieval. Furthermore, we also investigate the properties of the polarization ratio, denoted PR, and show that it is dependent on incidence angle and azimuth angle. Two empirical models of the PR are fitted, one as a function of incidence angle only, the other with additional dependence on azimuth angle. Assessments show that the σ_VV^0 retrieved from new PR models as well as σ_HH^0 is in good agreement with σ_VV^0 extracted from SAR images directly. And it is also shown that considering the azimuth angle can improve polarization conversion accuracy.

Ataxin-2 (human gene symbol ATXN2, protein ATXN2) is the disease protein of Spinocerebellar Ataxia type 2 (SCA2). The large expansions of a polyglutamine (polyQ) stretch above a threshold of ~33 glutamines cause the multi-system nervous atrophy SCA2, while intermediate expansions of 29-32 glutamines contribute to the risk of the motor neuron diseases Amyotrophic Lateral Sclerosis (ALS) and Fronto-Temporal Lobar Dementia (FTLD). To elucidate the cellular function of ATXN2, we further characterized its direct interaction with alpha-Actinin-1 (symbol ACTN1), which had been observed in high-throughput yeast-two-hybrid surveys. An endogenous complex of ATXN2 and ACTN1 proteins was detected by co-immunoprecipitation. In vitro GST-tag pull-down experiments showed that the Calponin-Homology-domain at the N-terminus of ACTN1 binds to the N-terminus of ATXN2. Although an impact of the polyQ expansion on the interaction was not evident in pull-down experiments, a recent characterization of aged Atxn2-CAG100-KnockIn mice provides evidence. Both proteins associated in the cytosol and at the plasma membrane, as determined by sedimentation experiments in mouse brain, and by immunofluorescence microscopy of a transfected monkey cell line and of rat primary hippocampal neurons. In view of the roles of ACTN1 for spine plasticity and postsynaptic receptor control via reassembly of cortical actin, our data help to explain the impaired dendrite maintenance in SCA2.

The role of T cell immunity has been acknowledged in recent vaccine development and evaluation. We tested the humoral and cellular immune responses to Flucelvax®, a quadrivalent inactivated seasonal influenza vaccine containing two influenza A (H1N1 Singapore/GP1908/2015 IVR-180 and H3N2 North Carolina/04/2016) and two influenza B (Iowa/06/2017 and Singapore/INFTT-16-0610/2016) virus strains, using peripheral blood mononuclear cells stimulated by pools of peptides overlapping all the individual influenza viral protein components. Baseline reactivity was detected against all four strains both at the level of CD4 and CD8 responses and targeting different proteins. CD4 T cell reactivity was mostly directed to HA/NA proteins in influenza B strains, and NP/M1/M2/NS1/NEP proteins in the case of the Influenza A strains. CD8 responses to both influenza A and B viruses preferentially targeted the more conserved core viral proteins. Following vaccination, both CD4 and CD8 responses against the various influenza antigens were increased in day 15 to day 91 post vaccination period and maintained a Th1 polarized profile. Importantly, no vaccine interference was detected, with the increased responses balanced across all 4 included viral strains for both CD4 and CD8 T cells, and targeting HA and multiple additional viral antigens.

To obtain an accurate and reproducible experimental results in microbial fuel cell (MFC), it is important to know ‘anode maturation biofilm’ to produce a stable and maximum performance. For this purpose, four single chamber MFCs were tested in this study. The linear sweep voltammetry (LSV) polarization tests illustrated that maximum power densities of three MFCs became stable after 9 weeks. Although there were variations afterwards, such variations were negligible. Average maximum power densities from the 9th to the 17th week were 2,990 mW/m2 (MFC-4), 2,983 mW/m2 (MFC-2), 2,368 mW/m2 (MFC-3) and 837 mW/m2 (MFC-1). Polarization resistance shows that MFC-1 had much larger anode resistance (36.6-85.4 Ω) than the other MFCs (1.7-11.6 Ω). Anodic cyclic voltammetry (CV) shows that current production increased over time and MFC-1 had much smaller current production (24.4 mA) than the other MFCs (31.0-34.9 mA) at 17th week. The increased current production indicates anode biofilm became more mature over time, but overall cell performance did not increased accordingly. Possibly due to the bad inoculation, MFC-1 showed the lowest performance. However, its performance was restored to the initial performance and anode resistance was reduced by 47% at 17th week. This study shows that the optimum anode maturation time is 9 weeks and that bioanode performance is a key factor for MFC performance. This study also shows than LSV polarization and CV tests are accurate and non-destructive measurement methods for diagnosing anode performance.

The interpretation of published experimental results intended to prove the existence of a quantum phenomenon of non-locality involving photonic entangled states did not take into consideration the existence of the quantum Rayleigh conversion of photons in dielectric media. This phenomenon leads to the existence of high levels of correlations between two independent photonic and linearly polarized quantum states generated after the entangled photons have been absorbed through the quantum Rayleigh conversion. Both pure and mixed individual states of polarization result in expressions normally associated with entangled photonic states, providing support for the view that the physical reality of quantum non-locality is highly questionable.

The resistance of cancer cell subpopulations, including cancer stem cell (CSC) populations, to apoptosis-inducing chemotherapeutic agents is a key barrier to improved outcomes for cancer patients. The cationic amphiphilic drug hexamethylene amiloride (HMA) has been previously demonstrated to efficiently kill bulk breast cancer cells independent of tumor subtype or species, but acts poorly toward non-transformed cells derived from multiple tissues. Here we demonstrate that HMA is similarly cytotoxic toward breast CSC-related subpopulations that are resistant to conventional chemotherapeutic agents, but poorly cytotoxic toward normal mammary stem cells. HMA inhibits the sphere-forming capacity of FACS-sorted human and mouse mammary CSC-related cells in vitro, specifically kills tumor but not normal mammary organoids ex vivo, and inhibits metastatic outgrowth in vivo, consistent with CSC suppression. Moreover, HMA inhibits viability and sphere formation by lung, colon, pancreatic, brain, liver, prostate and bladder tumor cell lines, suggesting that its effects may be applicable to multiple malignancies. Mechanistically, HMA elicits the permeabilization of the limiting lysosomal membrane, a hallmark feature of the lysosome-dependent cell death pathway. Our observations expose a key vulnerability intrinsic to cancer stem cells, and point to novel strategies for the exploitation of cationic amphiphilic drugs in cancer treatment.

Time-domain spectroscopy (TDS) in the Terahertz (THz) frequency range is gaining in importance in nondestructive testing of dielectric materials. One application is the layer thickness measurement of a coating layer. To determine the thickness from the measurement data, the refractive index of the coating layer must be known in the surveyed frequency range. For perpendicular incidence of the radiation, methods exist to extract the refractive index from the measurement data itself without prior knowledge. This paper extends these methods for non-perpendicular incidence, where the polarization of the radiation becomes important. Furthermore, modifications considering effects of surface roughness of the coating are introduced. The new methods are verified using measurement data of a sample of Inconel steel coated with yttria-stabilized zirconia (YSZ) and with COMSOL simulations of the measurement setup. To validate the thickness measurements, scanning electron microscopy (SEM) images of the layer structure are used. The results show good agreement with an average error of 1% for the simulation data and under 4% for the experimental data compared to reference measurements.

Naive CD4+ T cells engage cognate peptide MHC-II complexes (pMHC-IIs) to differentiate and acquire one of several T helper (Th) fates whose specific trajectories are guided by a dynamic cytokine milieu that develops in response to antigenic entity. This physiological process is often erroneously conflated with a pathological one termed Th polarization. Using the SPIRAL model, we argue here that unlike Th fate choice, innate signaling alone is insufficient to initiate Th polarization in naive CD4+ T cells, that it instead develops from pre-existing memory CD4+ T cells that express cross-reactive TCRs, and that it inevitably leads to immunopathology.

This research analyzed South Korean companies’ adoption of remote work during the COVID-19 pandemic, by focusing on the dual labor market structure comprising of the primary (large corporations) and the secondary sectors (small and medium enterprises (SMEs)). Companies in the dual labor market were classified as per firm size. We used Statistics Korea’s August supplementary data from the Economically Active Population Survey, covering 2017–2020. This empirical study analyzed the factors affecting remote work in 2020, after the outbreak of the pandemic. The results showed that the probability of large corporations introducing remote work during the pandemic increased by a significantly larger margin than for small and medium-sized firms. This suggests that the polarization within the dual labor market structure between large corporations and SMEs also spilled over into companies’ adoption of remote work, which was initially introduced to prevent the spread of the pandemic. Additionally, the polarization in the use of digital technology is likely to persist even after the pandemic. Hence, based on our analysis of remote work adoption in the dual labor market, this study examined the system and factors of labor-management relations contributing toward such polarization and presented policy directions for the current labor market structure.

Background: Recently we demonstrated that Astragalus polysaccharide (PG2), the active ingredient in dried roots of astragalus membranaceus, ameliorates cancer symptom clusters and improve quality of life (QoL) in patients with metastatic disease by modulating inflammatory cascade, against the background that inflammatory cells including macrophages, dendritic cells (DCs), and cytotoxic T lymphocytes (CTLs) in tumor initiation, metastasis, and progression. Nevertheless, the role of PG2 in the modulation of anticancer immunogenicity and therapeutic response remains relatively underexplored and unclear. Purpose: The present study investigates how and to what extent PG2 modulates cellular and biochemical components of the inflammatory cascade, enhance anticancer immunity, and the therapeutic implication of same in patients with lung cancer. Methods and Results: Herein, we demonstrated that PG2 significantly increased the M1/M2 macrophage polarization ratio in non-small cell carcinoma (NSCLC) H441 and H1299 cells. This PG2-induced preferential pharmacologic up-regulation of tumoral M1 population in vitro, positively correlated with the downregulation of tumor-promoting IL-6 and IL-10 expression in NSCLC cell-conditioned medium, with concomitant marked inhibition of cell proliferation, clonogenicity and tumorsphere formation. Our ex vivo results, using clinical sample from our NSCLC cohort, demonstrated that PG2 also promoted the functional maturation of DCs with consequent enhancement of T cell-mediated anticancer immune responses. Consistent with the in vitro and ex vivo results, our in vivo studies showed that mice treated with PG2 exhibited significant time-dependent depletion of the tumor-associated M2 population, synergistically enhanced the anti-M2-based anticancer effect of cisplatin, and inhibition of xenograft tumor growth in the NSCLC mice models. Moreover, in the presence of PG2, cisplatin-associated dyscresia and weight-loss was markedly suppressed. Conclusion: These results do indicate a therapeutically-relevant role for PG2 in modulating the M1/M2 macrophage pool, facilitating DC maturation, and synergistically enhancing the anticancer effect of conventional chemotherapeutic agent, cisplatin; thus laying the foundation for further exploration of the curative relevance of PG2 as surrogate immunotherapy and/or clinical feasibility of its use for maintenance therapy in patients with lung cancer.

Neurological complications of infection by the mosquito-borne Zika virus (ZIKV) include Guillain-Barré syndrome (GBS), an acute inflammatory demyelinating polyneuritis. GBS was first associated with recent ZIKV epidemics caused by the emergence of ZIKV Asian lineage in South Pacific. Here, we hypothesize that ZIKV-associated GBS relates to a molecular mimicry between viral envelope E (E) protein and neural proteins involved in GBS. Analysis of ZIKV epidemic strains showed that glycan loop (GL) region of the E protein includes an IVNDT motif which is conserved in voltage-dependent L-type calcium channel subunit alpha-1C (Cav1.2) and Heat Shock 70 kDa protein 12A (HSP70 12A). Both VSCC-alpha 1C and HSP70 12A belong to protein families which have been associated with neurological autoimmune diseases in central nervous system. The purpose of our in silico analysis is to point out that IVNDT motif of ZIKV E-GL region should be taken in consideration for the development of safe and effective anti-Zika vaccines by precluding the possibility of adverse neurologic events including autoimmune diseases such as GBS.

In quantum field theory (QFT), it is well known that when Feynman diagrams containing loops are evaluated to account for self interactions, probability amplitude comes out to be infinite which is physically not admissible. So, to make the QFT convergent, various renormalization methods are conventionally followed in which an additional (infinite) counter term is postulated which neutralizes the original infinity generated by diagram. The resulting finite values of amplitudes have agreed with experiments with surprising accuracy. However, proponents of renormalization methods acknowledged that this ad-hoc procedure of subtraction of infinity from infinity to reach at a finite value is not at all satisfactory and there is no physical basis for bringing in the counter term. So, it is desirable to establish a method in QFT which does not generate any infinite term (thus not requiring renormalization), but which predicts same results as conventional methods do. In this paper, we describe such a technique taking self interaction quantum electrodynamics diagram representing electron or photon self energy. In our method, no problem of infinity arises and hence renormalization is not necessary. Still, the dependence of calculated probability amplitude on physical variables in our technique comes out to be same as conventional methods. Using similar procedure, we hope, the problem of non-renormalizability of quantum gravity may be solved in future.

This study presents the B92 Quantum Key Distribution scheme and its optimization and implementation considerations. Simulation software was developed to model and analyze the B92 protocol under varying conditions. Another contribution of this work is investigating how this protocol runs on real quantum computing hardware. New eavesdropping schemes were proposed and modeled.

FeIFeI Fe2(S2C3H6)(CO)6(µ-CO) (1a-CO) and its FeIFeII cationic species (2a+-CO) are the simplest model of the CO-inhibited [FeFe] hydrogenase active site, which is known to undergo CO photolysis within a temperature- dependent process whose products and mechanism are still a matter of debate. Using Density Functional Theory (DFT) and Time-Dependent Density Functional Theory (TDDFT) computations, the ground state and low-lying excited state potential energy surfaces (PESs) of 1a-CO and 2a+-CO have been explored aimed at elucidating the dynamics of the CO photolysis yielding Fe2(S2C3H6)(CO)6 (1a) and Fe2(S2C3H6)(CO)6+ (2a+), two simple models of the catalytic site of the enzyme. Two main results came out from these investigations. First, a-CO and 2a+-CO are both bound with respect to any CO dissociation with lowest free energy barriers around 10 kcal mol-1, suggesting that at least 2a+-CO might be synthetized. Second, focusing on the cationic form, we found at least two clear excited state channels along the PESs of 2a+-CO that are unbound with respect to equatorial CO dissociation.

The high level of dengue virus (DENV) seroprevalence in areas where Zika virus (ZIKV) is circulating and the cross-reactivity between these two viruses have raised concerns on the risk of increased ZIKV disease severity for patients with a history of previous DENV infection. To determine the role of DENV pre-immunity in ZIKV infection, we analysed the T and B cell responses against ZIKV in donors with or without previous DENV infection. Using PBMCs from donors living in an endemic area in Colombia, we have identified, by interferon (IFN)-γ enzyme-linked immunospot (ELISPOT) assay, most of the immunodominant ZIKV T-cell epitopes in the non-structural proteins NS1, NS3 and NS5. Analyses of the T and B-cell responses in the same donors revealed a stronger T-cell response against peptides conserved between DENV and ZIKV, with a higher level of ZIKV-neutralizing antibodies in DENV-immune donors, in comparison with DENV-naïve donors. Strikingly, the potential for antibody mediated enhancement of ZIKV infection was reduced in donors with sequential DENV and ZIKV infection in comparison with donors with DENV infection only. Altogether, these data suggest that individuals with DENV immunity present improved immune responses against ZIKV.

Accumulating evidences demonstrate that the host genome's epigenetic modificationsare essential for living organisms to adapt extreme conditions.DNA methylation, covalent modifications of histone, andinter-association of non-coding RNAs facilitate the cellular manifestation ofepigenetic changes in the genome. Out of various factors involved in the epigenetic programming of the host, miRNA (microRNA) and LncRNA (Long non-coding RNA) are new generationnon-coding molecules that influence a variety of cellular processes like immunity, cellular differentiation, and tumor development. During tumor development, temporal changes in miRNA/LncRNA rheostat influence sterile inflammatory responses accompanied by the changes in the carcinogenic signalling in the host. At the cellular level, this is manifested by the up-regulation of Inflammasome and inflammatory pathways, which promotes cancer-related inflammation. In view of this, we discuss the potential of lncRNA and miRNA directed interventions in regulating inflammation and tumor development in the host.

Breast Cancer (BC) is the second most common type of cancer worldwide and displays the highest cancer-related mortality among women worldwide. Targeted therapies have revolutionized the way BC has been treated in the last decades improving life expectancies of millions of women. Among the different molecular pathways that have been of interest for the development of targeted therapies are the Cyclin-Dependent Kinases (CDK). CDK inhibitors are a class of molecules that already exist in nature and those belonging to the INK4 protein family specifically inhibit the CDK4/6 proteins. CDK4/6 inhibitors specifically block the transition from the G1 to the S phase of the cell cycle by dephosphorylation of the retinoblastoma tumor suppressor protein. In the past four years CDK4/6 inhibitors palbociclib, ribociclib, and abemaciclib received their first FDA approval for the treatment of Hormone Receptor (HR)-positive and Human Epidermal growth factor Receptor 2 (HER2)-negative breast cancer after showing significant improvements in progression-free survival in the PALOMA-1, MONALEESA-2 and the MONARCH-2 randomized clinical trials, respectively. After the encouraging results from these clinical trials, CDK4/6 inhibitors have also been investigated in the other BC subtypes. In HER2-positive BC, combination of CDK4/6 inhibitors with HER2-targeted therapies showed promise in preclinical studies and their clinical evaluation is ongoing. Moreover, in triple-negative BC, CDK4/6 inhibitors efficacy has been investigated in combination with other targeted therapies or immunotherapies. This review summarizes the molecular background and clinical efficacy of CDK4/6 inhibitors as single agents or in combination with other targeted therapies for the treatment of BC. Future directions of ongoing clinical trials and predictive biomarkers will be further debated.

Background and Research Highlights: Despite all the concerns and initiatives, natural resources like forests, as well as biodiversity are decreasing at an alarming rate worldwide. Conservation is considered as one of the major tools to prevent such loss and rapid degradation. Evidence around the world shows the adverse effects of conservation laws and policies on indigenous peoples and other local communities. Objectives: This study was conducted in one of the forest-dependent communities situated in Sundarban (world’s largest mangrove forest) to understand the impact of conservation laws and policies on their livelihood. Materials and Methods: A qualitative methodology was designed to collect data, using focus group discussions and case study with community people, and individual interviews with the personnel from NGOs and relevant government departments. Findings: Strict conservation policies and restrictions in accessing forest resources made lives and livelihoods of the local community insecure and unstable, thus putting the community in a vulnerable situation. The had to leave their traditional mode of income and look for alternative livelihood options. Almost no evidence was found in relation to upkeeping their rights in conservation activities. Prohibited movement, provision of punishment for entering into the forest without proper permission and struggles in everyday life were some of the highlighted issues. They had no participation in conservation activities, management of alternative livelihood options, and even they were not sensitized before putting restrictions. Although they had a history of emotional and physical attachment with the forest, existing activities did not consider these issues. In addition, corruption and abuse of power by law enforcement agencies towards the local community intensified the sufferings. Conclusion: This study argues that the realization of human rights in conservation activities and the sensitization of the implementing stakeholders are prerequisites for ensuring the sustainability of both biodiversity and the affected people.

The aims of this work were to examine the new electrode, based on polymer bacteria modified aluminum electrode for simultaneous production of electricity and degradation of phenol. This electrode is based aluminum modified by bacteria inserted in the polymer matrix, developed in situ on the surface. This electrode, designated subsequently by bacteria-polymer-aluminum, Showed stable response and was characterized with voltametric methods, as cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The experimental results revealed that the prepared electrode could be a feasible for degradation of hazardous phenol pollutants. The sensor was successfully applied to the determination of phenol in a real sample with satisfactory results.

Background: Clinical cases reports with snake accidents show that venom bite induces increased oxidative stress including several markers of lipid peroxidation and other oxidative stress marker in plasma. Methods: The main findings of this work were performed with BthTx-II on paw edema of animals treated with the toxin and biochemical measurement of COX-2, PGE2, MDA and the effects of peroxiredoxin inhibitors on edema and myotoxicity were also evaluated. Results: The results show that edema and myotoxocity induced by PLA2 (BthTx-II) induces a strong mobilization of arachidonic acid and an increase in cellular oxidative stress as measured by increased malondialdehydo (MDA) concentration and protein carbonylation. Thus, these findings establish the strong link between oxidative stress, arachidonic acid mobilization and that these events may explain the presence of oxidative stress markers in snake-bitten patients. Experiments performed with animals previously treated with commercially purchased inhibitors showed enzymes such as thioredoxin (TXN), thioredoxin reductase (TXNRD) and other glutathione (GSH)-related antioxidant defenses could play an essential role controlling and defining the end of edema on the late phase of PLA2 BthTx-II-induced process. Conclusion. This study showed that thioate-dependent antioxidant enzymes play an important role in resolving the edema induced by BthTx-II.

The self-organisation of a fertilised egg to form a blastocyst structure, which consists of three distinct cell lineages (trophoblast, epiblast and hypoblast) arranged around an off-centre cavity, is unique to mammals. While the starting point (the zygote) and endpoint (the blastocyst) are similar in all mammals, the intervening events have diverged. This review examines and compares the descriptive and functional data surrounding embryonic gene activation, symmetry-breaking, first and second lineage establishment, and fate commitment in a wide range of mammalian orders. The exquisite detail known from mouse embryogenesis, embryonic stem cell studies and the wealth of recent single cell transcriptomic experiments are used to highlight the building principles underlying early mammalian embryonic development.

The transfer of protein-encoding genetic information from DNA to RNA to protein, a process formalized as the “Central Dogma of Molecular Biology”, has undergone a significant evolution since its inception. It was amended to account for the information flow from RNA to DNA, the reverse transcription, and for the information transfer from RNA to RNA, the RNA-dependent RNA synthesis. These processes, both potentially leading to protein production, were initially described only in viral systems, and although RNA-dependent RNA polymerase activity was shown to be present, and RNA-dependent RNA synthesisfound to occur, in mammalian cells, its function was presumed to be restricted to regulatory. However, recent results, obtained with multiple mRNA species in several mammalian systems, strongly indicate the occurrence of protein-encoding RNA to RNA information transfer in mammalian cells. It can result in the rapid production of the extraordinary quantities of specific proteins as was seen in cases of terminal cellular differentiation and during cellular deposition of extracellular matrix molecules. A malfunction of this process may be involved in pathologies associated either with the deficiency of a protein normally produced by this mechanism or with the abnormal abundanceof a protein or of its C-terminal fragment. It seems to be responsible for some types of familial thalassemia and may underlie the overproduction of beta amyloid in sporadic Alzheimer’s disease. The aim of the present article is to systematize the current knowledge and understanding of this pathway. The outlined framework introduces unexpected features of the mRNA amplification such as its ability to generate polypeptides non-contiguously encoded in the genome, its second Tier, a physiologically occurring intracellular polymerase chain reaction, iPCR, a Two-Tier Paradox and RNA Dark Matter. RNA-dependent mRNA amplification represents a new mode of genomic protein-encoding information transfer in mammalian cells. Its potential physiological impact is substantial, it appears relevant to multiple pathologies and its understanding opens new venues of therapeutic interference, it suggests powerful novel bioengineering approaches and its further rigorous investigations are highly warranted.

Majorana bound states in topological superconductors have attracted intense research activity in view of applications in topological quantum computation. However, they are not the only example of topological bound states that can occur in such systems. We here study a model in which both Majorana and Tamm bound states compete. We show both numerically and analytically that, surprisingly, the Tamm state remains partially localized even when the spectrum becomes gapless. Despite this fact, we demonstrate that the Majorana polarization shows a clear transition between the two regimes.

A very strong earthquake of magnitude Mw8.2 struck the coastal zone of Alaska (USA), on July 29, 2021. This earthquake was felt around the Gulf of Alaska, on a wide offshore area belonging to USA and Canada. In order to identify an anomalous geomagnetic signal before the onset of this earthquake, we retrospectively analyzed the data collected on the interval June 17 - July 31, 2021, via internet (www.intermagnet.org), at the two geomagnetic observatories, College (CMO) - Alaska and Newport (NEW)-USA, by using the polarization parameter (BPOL) and the strain effect–related to geomagnetic signal identification. Thus, for the both observation sites (CMO and NEW), the daily mean distribution of the BPOL and its standard deviation (STDEV) are carried out using an FFT band-pass filtering in the ULF range (0.001-0.0083Hz). Further on, a statistical analysis based on a standardized random variable equation was applied to emphasize the following: a) the anomalous signature related to Mw8.2 earthquake on the both time series BPOL*(CMO) and BPOL*(NEW); b) the differentiation of the transient local anomalies associated with Mw8.2 earthquake from the internal and external parts of the geomagnetic field, taking the NEW observatory as reference. Finally, on the BPOL*(NEW-CMO) time series, carried out on the interval 07-31 July, 2021, a very clear anomaly of maximum, greater than 1.2 STDEV, was detected on July 22, with 7 days before the onset of Mw8.2 earthquake

Exercise affects various organs. However, its effects on nutrient digestion and absorption in the intestinal tract are not well understood. A few studies have reported that exercise training in-creases the expression of carbohydrate digestion and absorption molecules. Exercise was also shown to increase the concentration of blood glucagon like peptide-2(GLP-2), which regulates carbohydrate digestion and absorption in small intestinal epithelium. Therefore, we investigated the effects of exercise on intestinal digestion and absorption molecules and the levels of GLP-2. 6-wk-old of male mice were divided into 2 groups; sedentary (SED) and low-intensity exercise (LEx). LEx mice were required to run on a treadmill (12.5 m/min, 60 min), whereas SED mice rested. All mice were euthanized 1 h after exercise or rest and plasma, jejunum, ileum, and colon were sampled. Samples were analyzed using EIA and immunoblotting. The levels of plasma GLP-2 and the expression of the GLP-2 receptor, sucrase-isomaltase (SI), and glucose transporter (GLUT2) in the jejunum were increased in LEx group. We showed that acute low-intensity exer-cise affects the intestinal carbohydrate digestion and absorption molecules via GLP-2. Our results suggest that exercise might provide new benefits to the small intestine for people with intestinal frailty.

In this article various heuristic approaches are discussed to solve the dark matter phenomenon by the concept of vacuum polarization. They are compared with a more fundamental approach, based upon an entropy model of the visible universe. They all make use of some kind of gravitational dipole. These dipoles seem to violate Einstein’s equivalence principle between inertial mass and gravitational mass. It is shown how the paradox can be solved by a quantum mechanical principle.

Rett syndrome (RTT), a neurodevelopmental disorder, is mainly caused by mutations in methyl CpG-binding protein 2 (MECP2), which alter the functions of domains to either bind to methylated DNA or interact with a transcriptional co-repressor complex. It has been established that alterations in cyclin-dependent kinase-like 5 (CDKL5) or forkhead box protein G1 (FOXG1) correspond to distinct neurodevelopmental disorders, given that a series of studies have indicated that RTT is also caused by alterations in either one of these genes. We tried to elucidate RTT through evolution and structure assessment of MeCP2, CDKL5, and FOXG1, by focusing on their binding partners and disordered structures. Here, we provide insight into the similarities of the FOXG1 and MECP2 binding partners evolution and function. On the other hand, we suggest that CDKL5 could be a potential candidate for a classical RTT treatment, particularly based on its disordered structure that spans after the catalytic domain to the C-terminus, which shows abundant linear motifs that can bind to molecules with divergent structures of similar affinity. Additionally, we provide insight into the relationship between disordered structure and disease.

Akt1 is a proto-oncogene that is over active in most cancers. Akt1 activation requires phosphorylation at Thr308; phosphorylation at Ser473 further enhances catalytic activity. Akt1 activity is also regulated via interactions between the kinase domain and the N-terminal auto-inhibitory pleckstrin homology (PH) domain. As it was previously difficult to produce Akt1 in site-specifically phosphorylated forms, the contribution of each activating phosphorylation site to auto-inhibition was unknown. Using a combination of genetic code expansion and in vivo enzymatic phosphorylation, we produced Akt1 variants containing programmed phosphorylation to probe the interplay between Akt1 phosphorylation status and the auto-inhibitory function of the PH domain. Deletion of the PH domain increased the enzyme activity for all three phosphorylated Akt1 variants. For the doubly phosphorylated enzyme, deletion of the PH domain relieved auto-inhibition by 295-fold. We next found that phosphorylation at Ser473 provided resistance to chemical inhibition by Akti-1/2 inhibitor VIII. The Akti-1/2 inhibitor was most effective against pAkt1T308 and showed 4-fold decreased potency with Akt1 variants phosphorylated at Ser473. The data highlight the need to design more potent Akt1 inhibitors that are effective against the doubly phosphorylated and most pathogenic form of Akt1.

The open communication is an exigent need for future power system where the time delay is unavoidable. In order to secure the stability of the grid, the frequency must remain within its limited range which is achieved through the load frequency control. The load frequency control signals are transmitted through communication networks which induces time delay that could destabilize the power systems. So, in order to guarantee the stability the delay margin should be computed. In this paper, we present a new method for calculating the delay margin in load frequency control systems. The transcendental time delay characteristics equation is transformed to frequency dependant equation. The spectral radius is used to find the frequencies at which the roots crosses the imaginary axis. The crossing frequencies are determined through the sweeping test and the binary iteration algorithm. A one-area load frequency control system is chosen as case study. The effectiveness of the proposed method has been proved through comparing with the most recent published methods. The method shows its merit with less conservativeness and less computations. The PI controller gains are preferable to be chosen large to reduce the damping, however, the delay margin decreases with increasing the PI controller gains.

Clofazimine and Arbidol have both been reported to be effective in vitro SARS-CoV-2 fusion inhibitors. Both are promising drugs repurposed for treatment of COVID-19 and have been used in several previous and ongoing clinical trials. Small-molecule binding to expressed constructs of the trimeric S2 segment of Spike and the full-length SARS-CoV-2 spike protein were measured using a Surface Plasmon Resonance (SPR) binding assay. We demonstrate that Clofazimine, Toremifene, Arbidol and other Arbidol derivatives bind to the S2 segment of the Spike protein. Clofazimine provided the most reliable and highest quality SPR binding data to S2 over the conditions explored. A molecular docking approach was used to identify the most favorable binding sites on the S2 segment in the prefusion conformation, highlighting two possible small-molecule binding sites for fusion inhibitors. Results from molecular docking and modeling the structure-activity-relationship (SAR) of a newly reported series of Clofazimine derivatives supports the proposed Clofazimine binding site on the S2 segment. When the proposed Clofazimine binding site is superimposed with other experimentally determined coronavirus structures in structure-sequence alignments, the changes in sequence and structure may rationalize the broad-spectrum antiviral activity of Clofazimine in closely related coronavirus such as (SARS-CoV, MERS, hCoV-229E, hCoV-OC43).

In recent years, the photophysical properties of crystalline metal-organic frameworks (MOFs) have become increasingly relevant for their potential application in light-emitting devices, photovoltaics, nonlinear optics and sensing. The availability of high-quality experimental data for such systems makes them ideally suited for a validation of quantum mechanical simulations, aiming at an in-depth atomistic understanding of photophysical phenomena. Here we present a computational DFT study of the absorption and emission characteristics of a Zn-based surface-anchored metal-organic framework (Zn-SURMOF-2) containing anthracenedibenzoic acid (ADB) as linker. Combining band-structure and cluster-based simulations on ADB chromophores in various conformations and aggregation states, we are able to provide a detailed explanation of the experimentally observed photophysical properties of Zn-ADB SURMOF-2: The unexpected (weak) red-shift of the absorption maxima upon incorporating ADB chromophores into SURMOF-2 can be explained by a combination of excitonic coupling effects with conformational changes of the chromophores already in their ground state. As far as the unusually large red-shift of the emission of Zn-ADB SURMOF-2 is concerned, based on our simulations, we attribute it to a modification of the exciton coupling compared to conventional H-aggregates, which results from a relative slip of the centers of neighboring chromophores upon incorporation in Zn-ADB SURMOF-2.

Aim of the presented research was to develop an optical sensing system to investigate the demineralization process of the bones. Optical measurement techniques are widely used and increasingly adapted in biological and biomedical applications due to their non-destructive nature and safety. Optical examination of the bone condition could facilitate clinical trials and improve the safety of patients. The authors used a set of complementary methods: polarization-sensitive optical coherence tomography (PS-OCT) and Raman spectroscopy. To stimulate the process of demineralization and gradual removal of the hydroxyapatite, the test samples of chicken bones were placed into 10% acetic acid. Measurements were carried out in two series. The first one took two weeks with data acquired every day. In the second series, the measurements were made during one day at an hourly interval (after 1, 2, 3, 5, 7, 10, and 24 hours). Raman spectroscopy was used to evaluate the disappearance of the hydroxyapatite. The relation between the content of hydroxyapatite and images recorded using OCT was analyzed and discussed. Moreover, the polarization properties of the bones have been evaluated. Based on OCT images, the retardation angles of the bones have been calculated. This work presents a preliminary study on the mechanism of bone demineralization and confirms the potential of the applied optical methods.

We propose an iterative scheme for feature-based positioning using a new weighted dissimilarity measure with the goal of reducing the impact of large errors among the measured or modeled features. The weights are computed from the location-dependent standard deviations of the features and stored as part of the reference fingerprint map (RFM). Spatial filtering and kernel smoothing of the kinematically collected raw data allow efficiently estimating the standard deviations during RFM generation. In the positioning stage, the weights control the contribution of each feature to the dissimilarity measure, which in turn quantifies the difference between the set of online measured features and the fingerprints stored in the RFM. Features with little variability contribute more to the estimated position than features with high variability. Iterations are necessary because the variability depends on the location, and the location is initially unknown when estimating the position. Using real WiFi signal strength data from extended test measurements with ground truth in an office building, we show that the standard deviations of these features vary considerably within the region of interest and are neither simple functions of the signal strength nor of the distances from the corresponding access points. This is the motivation to include the empirical standard deviations in the RFM. We then analyze the deviations of the estimated positions with and without the location-dependent weighting. In the present example the maximum radial positioning error from ground truth are reduced by 40% comparing to kNN without the weighted dissimilarity measure.

In this paper, we address the energy eigenvalues of two-dimensional Dirac oscillator perturbed by dynamical noncommutative space. We derived the relativistic Hamiltonian of Dirac oscillator in dynamical noncommutative space ($\tau$-space), in which the space-space Heisenberg–like commutation relations and noncommutative parameter are position-dependent. Then used this Hamiltonian to calculate the first-order correction to the eigenvalues and eigenvectors, based on the second quantization and using the perturbation theory. It is shown that the energy shift depends on the dynamical noncommutative parameter $\tau$. Knowing that with a set of two-dimensional Bopp-shift transformation, we mapped the noncommutative problem to the standard commutative one.

Rett syndrome (RTT) is mainly caused by mutations in methyl CpG-binding protein 2, cyclin-dependent kinase-like 5, or forkhead box protein G1. These RTT-causing proteins harbor an intrinsically disordered region (IDR) whose conformation exhibits spatiotemporal heterogeneity, which not only confer versatility to the protein, but also implicates them in diseases. The IDR generally evolves more rapidly than an ordered structure. In this study, we examined the relationship between pathogenic RTT-associated point mutations in RTT-causing proteins and the evolutionary dynamics of sequence features including structural order–disorder, phosphorylation sites, and evolutionary rates. We also analyzed the molecular properties and evolution of proteins that interact with RTT-causing proteins in terms of phylogenetic profiles, tissue specificity, subcellular localization, expression level, and functions. The results indicate that constrained IDRs may function by forming contacts with other regions in the protein sequence causing pathogenic missense mutations likely to arise in the rapidly evolving IDR and affect molecular networks, leading to disease. The results also provide novel insights into the genetic basis for RTT and the evolution of the neocortex in higher vertebrates.

Real-time evolution of the electron densities under excitations in La₂CuO₄ was calculated by the time-dependent density functional theory (TDDFT). The author found, for the first time, under excitations, the electron cloud of Cu²⁺ changes obviously and the characteristic frequencies are 83 meV and 36 meV, respectively, for two different modes. The results are unexpected and close to that of lattice vibrations. The results show that the electron cloud of Cu²⁺ (just like the lattice) can be the electron-pairing medium in high temperature copper oxide superconductors.

We utilize known exact analytic solutions of perfect fluid hydrodynamics to analytically calculate the polarization of baryons produced in heavy ion collisions. Assuming local thermodynamical equilibrium also for spin degrees of freedom, baryons get a net polarization at their formation (freeze-out). This polarization depends on the time evolution of the Quark-Gluon Plasma (QGP), which can be described as an almost perfect fluid. By using exact analytic solutions, we thus can analyze the necessity of rotation (and vorticity) for non-zero net polarization. In this paper we give the first analytical calculations for the polarization four-vector. We use two hydrodynamical solutions; one is the spherically symmetric Hubble flow (a somewhat oversimplified model, to demonstrate the methodology). The other solution which we use is a somewhat more involved one that corresponds to a rotating and accelerating expansion, and is thus well suited to investigate some main features of the time evolution of the QGP created in peripheral heavy-ion collisions (although there are still many numerous features of a real collision geometry that are beyond the reach of this simple model). Finally we illustrate and discuss our results on the polarization.

Results are presented concerning the influence on the water splitting process of enantiopure tartaric acid present in bulk solution. Stainless steel and electrodeposited nickel are used as working electrode (WE) surface. The latter is obtained by electrodeposition on the two poles of a magnet. The influence and role played by the chiral compound in solution has been assessed by comparing the current values, in cyclic voltammetry (CV) experiments, recorded in the potential range at which oxygen evolution reaction (OER) occurs. In the case of tartaric acid and nickel WE a spin polarization of about 4 % is found. The use of the chiral environment (bulk solution) and ferromagnetic chiral Ni electrode allows for observing the OER at a more favourable potential: about 50 mV (i.e. a cathodic, less positive, shift of the potential at which the oxygen evolution is observed).

Phosphodiesterases (PDEs) hydrolyze cyclic nucleotides to modulate multiple signaling events in cells. PDEs are recognized to actively associate with cyclic nucleotide receptors (Protein Kinases, PK) in larger macromolecular assemblies referred to as signalosomes. Complexation of PDEs with PK generates an expanded active site which enhances PDE activity. This facilitates signalosome-associated PDEs to preferentially catalyze active hydrolysis of cyclic nucleotides bound to PK, and aid in signal termination. PDEs are important drug targets and current strategies for inhibitor discovery are based entirely on targeting conserved PDE catalytic domains. This often results in inhibitors with cross-reactivity amongst closely related PDEs and attendant unwanted side effects. Here, our approach targets PDE-PK complexes as they would occur in signalosomes, thereby offering greater specificity. Our developed fluorescence polarization assay has been adapted to identify inhibitors that block cyclic nucleotide pockets in PDE-PK complexes in one mode, and disrupt protein-protein interactions between PDEs and cyclic nucleotide activating protein kinases in a second mode. We tested this approach with three different systems: cAMP-specific PDE8-PKAR, cGMP-specific PDE5-PKG and dual-specificity RegA-RD complexes and ranked inhibitors according to their inhibition potency. Targeting PDE-PK complexes offers biochemical tools for describing the exquisite specificity of cyclic nucleotide signaling networks in cells.

Dengue fever is a viral mosquito-borne infection, a major international public health concern. With 2.5 billion people at risk of acquiring the infection around the world, disease severity is influenced by the immunological status of the individual, seronegative or seropositive, prior to natural infection. Caused by four antigenically related but distinct serotypes, DENV-1 to DENV-4, infection by one serotype confers life-long immunity to that serotype and a period of temporary cross-immunity (TCI) to other serotypes. The clinical response on exposure to a second serotype is complex with the so-called Antibody-Dependent enhancement (ADE) process, a disease augmentation phenomenon when pre-existing antibodies to previous dengue infection do not neutralize but rather enhance the new infection, used to explain the etiology of severe disease. In this paper, we present a minimalistic mathematical model framework developed to describe qualitatively the dengue immunological response mediated by antibodies. Three models are analyzed and compared: i) primary dengue infection, ii) secondary dengue infection with the same (homologous) dengue virus and iii) secondary dengue infection with a different (heterologous) dengue virus. We explore the features of viral replication, antibody production, and infection clearance over time. The model is developed based on body cells and free virus interactions resulting in infected cells activating antibody production. Our mathematical results are qualitatively similar to the ones described in the empiric immunology literature, providing insights on the immunopathogenesis of severe disease. Results presented here are of use for future research directions to evaluate the impact of dengue vaccines.

Contemporary research has found that people with autism spectrum disorder (ASD) exhibit aberrant immunological function, with a shift toward increased cytokine production and unusual cell function. Microglia and astroglia were found to be significantly activated in immuno-cytochemical studies, and cytokine analysis revealed that the macrophage chemoattractant protein-1 (MCP-1), interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), and transforming growth factor β-1 (TGFB-1), all generated in the neuroglia, constituted the most predominant cytokines in the brain. Taurine (2-aminoethanesulfonic acid) is a promising therapeutic molecule able to increase the activity of antioxidant enzymes and ATPase, which may be protective against aluminum-induced neurotoxicity. It can also stimulate neurogenesis, synaptogenesis, and reprogramming of proinflammatory M1 macrophage polarization by decreasing mitophagy (mitochondrial autophagy) and raising the expression of the markers of the anti-inflammatory and pro-healing M2 macrophages, such as macrophage mannose receptor (MMR, CD206) and IL-10, while lowering the expression of the M1 inflammatory factor genes. Taurine also induces autophagy, which is a mechanism that is impaired in microglia cells and is critically associated with the pathophysiology of the ASD. We hypothesize here that taurine could reprogram the metabolism of M1 macrophages that are overstimulated in the nervous system of people suffering from ASD, thereby decreasing the neuroinflammatory process, neuronal death, and improving cognitive functions. Therefore, we think that taurine can serve as an important lead for the development of novel drugs for the ASD treatment.

Sentinel-1 (S1) extra-wide (EW) swath data in cross-polarization (horizontal-vertical, HV or vertical-horizontal, VH) are strongly affected by the scalloping effect and thermal noise, particularly over areas with weak backscattered signals, such as sea surfaces. Although noise vectors in both the azimuth and range directions are provided in the standard S1 EW data for subtraction, the residual thermal noise still significantly affects sea ice detection by the EW data. In this paper, we improve the denoising method developed in previous studies to remove the additive noise for the S1 EW data in cross-polarization. Furthermore, we propose a new method for eliminating the residual noise (i.e. multiplicative noise) at the sub-swath boundaries of the EW data, which cannot be well processed by simply subtracting the reconstructed 2-D noise field. The proposed method of removing both the additive and multiplicative noise was applied to EW HV-polarized images processed using different Instrument Processing Facility (IPF) versions. The results suggest that the proposed algorithm significantly improves the quality of EW HV-polarized images under various sea ice conditions and sea states in marginal ice zone (MIZ) of the Arctic. This is of great support for the utilization of cross-polarization SAR images in wide swaths for intensive sea ice monitoring in polar regions.

River valley bottoms have hydrological, geomorphological, and ecological importance and are buffers for protecting the river from upland nutrient loading coming from agriculture and other sources. They are relatively flat, low-lying areas of the terrain that are adjacent to the river and bound by increasing slopes at the transition to the uplands. These areas have under natural conditions, a groundwater table close to the soil surface. The objective of this paper is to present a stepwise GIS approach for the delineation of river valley bottom within drainage basins and use it to perform a national delineation. We developed a tool that applies a concept called cost distance accumulation with spatial data inputs consisting a river network and slope derived from a digital elevation model. We then used wetlands adjacent to rivers as a guide finding the river valley bottom boundary from the cost distance accumulation. We present results from our tool for the whole country of Denmark carrying out a validation within three selected areas. The results reveal that the tool visually performs well and delineates both confined and unconfined river valleys within the same drainage basin. We use the most common forms of wetlands (meadow and marsh) in Denmark's river valleys known as Groundwater Dependent Ecosystems (GDE) to validate our river valley bottom delineated areas. Our delineation picks about half to two-thirds of these GDE. However, we expected this since farmers have reclaimed Denmark's low-lying areas during the last 200 years before the first map of GDE was created. Our tool can be used as a management tool, since it can delineate an area that has been the focus of management actions to protect waterways from upland nutrient pollution.

Microglia are resident immune cells of the central nervous system such as brain-specific macrophages and also known to regulate the innate immune functions of astrocytes through secretory molecules. This conversation plays an important role in brain functions and homeostasis as well as in neuropathologic disease. In this study, we aimed to elucidate whether astrocytes and microglia can cross-talk to induce microglial polarization and proliferation, which can be further regulated under the brain stroke-mimic microenvironment. Microglia in mixed glial culture increased their survival and proliferation and altered to the M2 microglia, whose role was provided by CD11b-GFAP+ astrocytes by showing approximately tenfold increase in microglia cell proliferation after the astrocyte reconstitution. Furthermore, GM-CSF stimulated microglial proliferation approximately tenfold and induced to CCR7+ M1 microglia, whose phenotype could be suppressed by anti-inflammatory cytokines such as IL-4, IL-10, and Substance-P. Also, astrocyte in the microglia co-culture revealed A2 phenotype, which could be activated to A1 astrocyte by TNFα and IFNγ under the stroke-mimic condition. Altogether, astrocyte in the mixed glial culture stimulated the microglia proliferation and M2 polarization possibly through its acquisition of A2 phenotype, both of which could be converted to M1 microglia and A1 astrocytes under the inflammatory stroke-mimic environment. This study demonstrated that microglia and astrocyte can be polarized to M2 microglia and A2 astrocytes respectively through the cross-talk in vitro and provided a system to explore how microglia and astrocyte may behave in the inflammatory disease milieu after in vivo transplantation.

Objective: To investigate the protein expression levels of cyclin‑dependent kinase subunit 2 (CKS2) and cluster of differentiation (CD) 47 in gastric cancer (GC) and their clinical significances. Methods: A total of 126 GC patients who underwent radical resection were selected as study subjects. Additionally, 32 patients with benign gastric tumor, 42 patients with low-grade intraepithelial neoplasia (LGIEN), and 49 patients with high-grade intraepithelial neoplasia (HGIEN) who underwent surgery were selected as the control groups. Immunohistochemistry was used to detect the expression of CKS2 and CD47 in surgical specimens. We statistically analyzed the clinical significance of the expression of the two factors. Results: (1) The positivity rates for CKS2 in benign gastric tumor tissue, LGIEN tissue, HGIEN tissue, and GC tissue gradually increased, i.e., 6.3% (2/32), 30.9% (13/42), 38.8% (19/49), and 60.3% (76/126), respectively, and the positivity rates for CD47 were 18.8% (6/32), 38.1% (16/42), 46.9% (23/49), and 65.9% (83/126), respectively. (2) High expression of CKS2 and CD47 were associated with tumor diameter, Lauren classification, number of lymph node metastases, and TNM stage. In addition, the immunohistochemical scores for CKS2 and CD47 were positively correlated (r=0.625, P=0.000). (3) The median follow-up time of 126 patients was 46.5 months, and the overall survival rate was 40.5% (51/126). Survival analysis showed that compared with that in the CKS2 (-) group, the overall survival rate for patients in the CKS2 (+) group was significantly worse (25.0% vs 64.0%, 2=15.67, P=0.000) and that compared with the CD47 (-) group, the CD47 (+) group had significantly worse overall survival (30.1% vs 60.5%, 2=15.67, P=0.000). (4) The overall survival rates of CKS2(+)CD47(+) group, CKS2(+)CD47(-) group, CKS2(-)CD47(+) group, and CKS2 (-)CD47 (-) group were 20.0%(13/65), 58.3%(7/12), 57.1%(8/14), 65.7% (23/35), respectively, the prognosis of patients in CKS2(+)CD47(+) group was significantly poor. Conclusion: High expression levels of CKS2 and CD47 were closely related to the occurrence of GC and can be used as independent risk factors to assess the prognosis of patients.

This paper presents two designs of high-efficiency polarizer reflectarray antennas able to generate a collimated beam in dual-circular polarization using a linearly polarized feed, with application to high-gain antennas for data transmission links from a Cubesat. First, an 18 cm x 18 cm polarizer reflectarray operating in the 17.2 - 22.7 GHz band has been designed, fabricated and tested. The measurements of the prototype show an aperture efficiency of 52.7% for right-handed circular polarization (RHCP) and 57.3% for left-handed circular polarization (LHCP), both values higher than those previously reported in related works. Then, a dual-band polarizer reflectarray is presented for the first time, which operates in dual-CP in the frequency bands of 20 and 30 GHz. The proposed antenna technology enables a reduction of the complexity and cost of the feed chain to operate in dual-CP, as a linear-to-circular polarizer is no longer required. This property, combined with the lightweight, flat profile and low fabrication cost of printed reflectarrays, makes the proposed antennas good candidates for Cubesat applications.

Magneto-optic (MO) imaging and sensing are at present the most developed practical applications of thin-film MO garnet materials. However, future component and system-level sensors and imagers technology improvements are still necessary in order to improve sensitivity for a range of established and also the forward-looking applications. These improvements are expected to originate from new material system development. We propose a set of technological modifications for the RF-magnetron sputtering deposition and crystallization annealing of magneto-optic bismuth-substituted iron-garnet films and investigate the improved material properties. Results show that standard crystallization annealing for the as-deposited ultrathin (sputtered 10 nm thick, amorphous phase) films resulted in more than a factor of two loss in the magneto-optical activity of the films in visible spectral region, compared to the liquid-phase grown epitaxial films. Results also show that an additional 10 nm-thick metal-oxide (Bi2O3) protective layer above the amorphous film results in ~2.7 times increase in the magneto-optical quality of crystallized iron-garnet films. On the other hand, the effects of post-deposition oxygen (O2) plasma treatment on the magneto-optical (MO) properties of Bismuth substituted iron garnet thin films material is investigated. Results show that, in the visible part of the electromagnetic spectrum (at 532 nm), the O2 treated (up to 3 minutes) garnet films retain higher specific Faraday rotation and figure of merit than those of non-treated garnet films.

The paper makes a critical assessment of urban development in Nigeria against the backdrop of a rapidly changing population and growth rate. The Authors interrogated the effects of development control- mechanisms through the lenses of identified social anomalies in three selected pilot cities of Nigeria (Kaduna, Abuja FCT, and Lagos). Thematic areas examined include, the state of critical infrastructure, population dynamics, urban sprawl, city polarization, transportation, waste management systems, security/crime and economics. The Authors identified structural transformation of three Nigerian cities with focus on the causes and attendant consequences on urban development. The study found that urban growth has over-stretched the state of critical infrastructure in the cities and the mechanisms of development control seem ineffective in stemming unregulated growth, compromises and unplanned ‘development’. The paper noted that the impact of these developments has overstretched the state of critical infrastructure with far-reaching consequences. The authors conclude with some recommendations for strategic planning and sustainable development strategies aimed at mitigating the problems of urban development in Nigeria.

The discovery of microRNAs (miRNAs) has fundamentally transformed our understanding of gene regulation. The competing endogenous RNA (ceRNA) hypothesis postulates that not only messenger RNAs but also other RNA transcripts, such as long non-coding RNAs and pseudogenes, can act as natural miRNA sponges. These RNAs influence each other’s expression levels by competing for the same pool of miRNAs through miRNA response elements on their target transcripts, thereby modulating gene expression and protein activity. In recent years, these ceRNA regulatory networks have gained considerable attention in cancer research. Several studies have identified cancer-specific ceRNA networks. Nevertheless, prior bioinformatic analyses have focused on long non-coding RNAs-associated ceRNA networks. Here, we identify an extended-ceRNA network (including both long non-coding RNAs and pseudogenes) shared across a group of four hormone-dependent (HD) cancers, i.e., prostate, breast, colorectal, and endometrial cancers, using data from The Cancer Genome Atlas (TCGA). We performed a functional enrichment analysis for differentially expressed genes in the shared ceRNA network of HD cancers, followed by a survival analysis to determine their prognostic ability. We identified two long non-coding RNAs, nine genes, and seventy-four miRNAs in the shared ceRNA network across four HD cancers. Among them, two genes and forty-one miRNAs were associated with at least one HD cancer survival. This study is the first to investigate pseudogene associated ceRNAs across a group of related cancers and highlights the value of this approach to understanding shared molecular pathogenesis in a group of related diseases.

ccJE+Advax is an inactivated cell culture Japanese encephalitis (JE) vaccine formulated with Advax™, a novel polysaccharide adjuvant based on delta inulin. This vaccine has previously shown promise in murine and equine studies and the current study sought to better understand its mechanism of action and assess the feasibility of single dose vaccine protection. Mice immunised with ccJE-Advax had higher serum neutralisation titres than those immunised with ccJE alone or with alum adjuvant. ccJE+Advax induced extraordinarily broad cross-neutralising antibodies against multiple flaviviruses including West Nile virus (WNV), Murray Valley Encephalitis Virus (MVEV), St Louis Encephalitis virus (SLE) and Dengue-1 and -2 viruses. Notably, the DENV-2 cross-neutralising antibodies from ccJE+Advax immunised mice uniquely had no DENV-2 antibody dependent enhancement (ADE) activity, by contrast to high ADE activity seen with DENV-1 cross-reactive antibodies induced by mbJE or ccJE alone or with alum adjuvant. JEV-stimulated splenocytes from ccJE+Advax immunised mice showed increased IL-17 and IFN-γ production, consistent with a mixed Th1 and Th17 response, whereas ccJE-alum was associated with production of mainly Th2 cytokines. There is an ongoing lack of human vaccines against particular flaviviruses, including WNV, SLE and MVEV. Given its ability to provide single-dose JEV protection as well as to induce broadly neutralising antibodies free of ADE activity, ccJE+Advax vaccine could be highly useful in all situations where rapid protection is desirable but ADE needs to be avoided, e.g. during a local outbreak or for use in travellers or the military requiring rapid travel to JEV endemic regions.

Polarization in online social networks has gathered a significant amount of attention in the research community and in the public sphere due to stark disagreements with millions of participants in topics surrounding politics, climate, the economy and other areas where an agreement is required. There are multiple approaches to investigating the scenarios in which polarization occurs and given that polarization is not a new phenomenon but that its virality may be supported by the low cost and latency messaging offered by online social media platforms; an investigation into the intrinsic dynamics of online opinion evolution is presented for complete networks. Extending a model which utilizes the Binary Voter Model (BVM) to examine the effect of the degree of freedom for selecting contacts based upon homophily, simulations show that different opinions are reinforced for a period of time when users have a greater range of choice for association. The facility of discussion threads and groups formed upon common views further delays the rate in which a consensus can form between all members of the network. This can temporarily incubate members from interacting with those who can present an alternative opinion where a voter model would then proceed to produce a homogeneous opinion based upon pairwise interactions.

The light response and resistance switching behavior in BaTiO3 (BTO) films are studied for a symmetric Pt/BTO/Pt structure. The resistance of films as a function of time with and without ultraviolet light has been studied. Furthermore, resistance switching behavior was clearly observed based on the application of 365 nm wavelength ultraviolet light. Consequently, the polarities of resistance switching can be controlled by ultraviolet light when the energy is larger than the band excitation energy. It is proposed that the polarity of the resistance switching is dictated by the competition of the ferroelectricity and oxygen vacancy migration. This provides a new mechanism for modulating the state of ferroelectric resistive memory devices.

Potential dependent special relativity and Gauss's law for the electric field have been used for gravity by assuming vacuum energy to be generated when the energy is a minimum useful expression for vacuum energy has been found. This expression shows that elementary particles are generated by gravity vacuum filling their hollow balls; using Schrödinger equation for spherically symmetric particles vacuum energy is quantized. Treating mass as vibrating spheres thus solving Schrödinger, coordinate harmonic oscillator energy relation has been found.

Parallel decompositions have proved to be powerful tools for the analysis and interpretation of the physical information provided by Mueller matrices experimentally obtained. In this work, the procedure for the so-called arbitrary decomposition of Mueller matrices is validated through its application to a set of representative experimentally determined Mueller matrices. The covariance and passivity criteria required for the physical realizability of the Mueller matrices involved in the parallel decompositions are integrated in the procedure, which ensures the physical consistency of the results presented.

Since its initial development in the 1970’s by Phil Burke and his collaborators, the R-matrix theory and associated computer codes have become the de facto approach for the calculation of accurate data for general electron-atom/ion/molecule collision and photoionization processes. The use of a non-orthonormal set of orbitals based on B-splines, now called the B-spline R-matrix (BSR) approach, was pioneered by Zatsarinny. It has considerably extended the flexibility of the approach and improved particularly the treatment of complex many-electron atomic and ionic targets, for which accurate data are needed in many modelling applications for processes involving low-temperature plasmas. Both the original R-matrix approach and the BSR method have been extended to the interaction of short, intense electromagnetic (EM) radiation with atoms and molecules. Here we provide an overview of the theoretical tools that were required to facilitate the extension of the theory to the time domain. As an example of a practical application, we show results for two-photon ionization of argon by intense short-pulse extreme ultraviolet radiation

Modern radio spectrometers make measurement of polarized intensity as a function of Faraday depth possible. I investigate the effect of depolarization along a model line of sight. I model sightlines with two components informed by observations: a diffuse interstellar medium with a lognormal electron density distribution and a narrow, denser component simulating a spiral arm or H~{\sc ii} region, all with synchrotron-emitting gas mixed in. I then calculate the polarized intensity from 300-1800 MHz and calculate the resulting Faraday depth spectrum. The idealized synthetic observations show far more Faraday complexity than is observed in Global Magneto-Ionic Medium Survey observations. In a model with a very nearby H~{\sc ii} region observed at low frequencies, most of the effects of a ``depolarization wall'' are evident: the H~{\sc ii} region depolarizes background emission and less (but not zero) information from beyond the H~{\sc ii} region reaches the observer. In other cases, the effects are not so clear, as significant amounts of information reach the observer even through significant depolarization, and it is not clear that low-frequency observations sample largely different volumes of the interstellar medium than high-frequency observations. The observed Faraday depth can be randomized such that it does not always have any correlation with the true Faraday depth.

Zinc protection of galvanized steel is initially dissolved in alkaline solutions. However, passive layer is formed over time which protects the steel from corrosion. The behavior of galvanized steel exposed to strong alkaline solutions (pH values of 12.7) with a fixed concentration of sulfate ion of 0.04M is studied. Electrochemical measurement techniques such as corrosion potential, linear polarization resistance and electrochemical impedance spectroscopy are used. Synergistic effect of sulfate ion is also studied together with other anions such as chloride Cl- or bicarbonate ion HCO3- and with other cations such as calcium Ca2+, ammonium NH4+ and magnesium Mg2+. Presence of sulfate ions can depassivate the steel, leading to corrosion density of 0.3 µA/cm2 at the end of the test. The presence of other ions in the solution increases this effect. The increase in corrosion density caused by cations and anions responds to the following order (greater to lesser influence): NH4+&gt;Ca2+&gt;Mg2+ and HCO3- &gt;Cl- &gt;SO42-.

With reference to our recently proposed Planck Scale White Hole Cosmology (PS-WHC) or Flat Space Cosmology (PS-FSC), we make an attempt to quantify galactic dark matter and flat rotation speeds in terms of galactic visible matter and cosmic mass. Considering recently observed dwarf galaxies having very little dark matter and assuming a time dependent reference mass unit of $M_X\cong \left(\mbox{3.0 to 4.0}\right)\times 10^{38}$ kg, we suggest an empirical relation for galactic dark matter $M_d$ via galactic visible mass $M_v$ as,$M_d \cong \frac{M_v^{3/2}}{M_X^{1/2}}$. This relation helps in fitting flat rotation speeds starting from 8 km/sec (for Segue 2) to 500 km/sec (for UGC12591). Modifying MOND's galactic flat rotation speed relation with Hubble mass $M_0\cong \left(\frac{c^3}{2GH_0}\right)$ of the universe, ratio of galactic flat rotation speed $V_G$ to speed of light $c$ can be shown to be approximately $\frac{V_G}{c} \cong 0.5 \left(\frac{M_v}{M_0}\right)^{1/4}$. Considering the sum of galactic dark matter and visible matter, ratio of galactic flat rotation speed to speed of light can be shown to be approximately $\frac{V_G}{c}\cong 0.25 \left(\frac{M_v+M_d}{M_0}\right)^{1/4}$. With further study, dark matter's nature, effect and distribution can be understood in terms of visible matter's extended gravity and extended theories of gravity can be understood with 'distance cosmic mass' rather than the empirical 'minimum acceleration'.

I demonstrate that the ionization energy (IE) and the electron affinity (EA) of organic molecular crystals can be predicted from first-principles. Here, I describe the induced electronic polarization and the electrostatic effects upon crystalline IE and EA. I also demonstrate that the electronic polarization mainly originates from the screened coulomb interaction inside the crystalline bulk phase, and that the electrostatic contribution to IE and EA crucially depends on the orientation of the molecule at the surface. The former is well described by the GW approximation, while the latter is reasonably estimated by the difference in frontier orbital energy between the gas phase and the surface at the level of a generalized gradient approximation to the density functional theory. The present methodology enables to demonstrate the impact of the electrostatic effect upon the energy level of the injected charge at a multi-monolayer surface of an organic semiconductor thin film.

This article presents results of the polarization laser studies of the optical and microphysical characteristics of the high-level clouds (HLC). The high-altitude matrix polarization lidar (HAMPL; Tomsk, Russia) is described. HAMPL measures vertical profiles of all elements of the backscattering phase matrix (BSPM) of the HLC. Based on the joint analysis of lidar and radiosonde observations it is shown that the spatial structure of the HLC containing oriented ice crystals is inhomogeneous in the horizontal wind direction. It includes local areas with oriented particles; the sizes of such areas are estimated together with the most probable meteorological conditions of their formation. The shortcomings of the radiosonde observations performed closest to the location of the HAMPL are described. The applicability of the ERA5 reanalysis data of the European Centre for Medium-Range Weather Forecasts for use as an alternative source of information on the vertical profiles of meteorological quantities for the interpretation of HLC lidar sensing data in Western Siberia was checked.

A theoretical nonlocal thermoelastic model for studying the effects of the thermal conductivity variability on a rotating nanobeam has been described in the present article. The theory of thermal stress is employed using the Euler–Bernoulli beam model and generalized heat conduction with phase lags. It is believed that the thermal conductivity of the current model varies linearly according to temperature. Due to variable harmonic heat, the considered nanobeam excited and was subjected to a time-varying exponential decay load. Using the Laplace transform process, the analytical solutions for displacement, deflection, thermodynamic temperature and bending moment of rotating nanobeams are provided in final forms and a numerical example has been taken to address the problem. A comparison of the stated results was displayed and additionally, the influences of non-local parameters and varying load were analyzed and examined. We also investigate how the linear changes in the temperature of physical properties can influence both the static and dynamic responses to the rotating nanobeam.

Theories of quantum gravity suggest that Lorentz invariance, the fundamental symmetry of the Theory of Relativity, may be broken at the Planck energy scale. While any deviation from conventional Physics must be minuscule in particular at attainable energies, this hypothesis motivates ever more sensitive tests of Lorentz symmetry. In the photon sector, astrophysical observations, in particular polarization measurements, are a very powerful tool because tiny deviations from Lorentz invariance will accumulate as photons propagate over cosmological distances. The Standard-Model Extension (SME) provides a theoretical framework in the form of an effective field theory that describes low-energy effects due to a more fundamental quantum gravity theory by adding additional terms to the Standard Model Lagrangian. These terms can be ordered by the mass dimension d of the corresponding operator and lead to a wavelength, polarization, and direction dependent phase velocity of light. In this paper, we analyze optical polarization measurements from 63 Active Galactic Nuclei (AGN) and Gamma-ray Bursts (GRBs) in order to search for Lorentz violating signals. We derive the first set limits on each of the 10 individual birefringent coefficients of the minimal SME with d = 4, with 95% confidence limits on the order of 10⁻³⁴ on the dimensionless coefficients.

Mexico shows a high birth prevalence of congenital hypothyroidism (CH) due to thyroid dysgenesis (TD). PAX8 defects underlie only 1% of these cases and NKX2-1 does not seem to be involved. Here, we analyzed other TD-related genes in 128 non-related Mexican patients (females 77.3%; 6 months to 16.6 years) with non-syndromic CH-TD diagnosis established by clinical evaluation, thyroid hormone serum profiling, and scintigraphy (74%) or ultrasonography (26%). We performed Sanger sequencing of FOXE1, NKX2-5, and TSHR and evaluated copy number variations (CNVs) in TSHR, FOXE1, PAX8, and NKX2-1 by multiplex ligation-dependent probe amplification. Odds ratios for TD risk were explored for FOXE1 polyalanine stretches [polyAla-rs71369530] in cases and controls (N=116). Five rare missense changes cataloged as benign (NKX2-5:p.(Ala119Ser)-rs137852684), of unknown significance (FOXE1:p.(Ala335Gly)-rs543372757; TSHR:p.(Asp118Asn)-rs1414102266), and likely pathogenic (FOXE1:p.(Gly124Arg)-rs774035532; TSHR:p.(Trp422Arg)-rs746029360) accounted for 1.5% (N=2/128) of clinically relevant genotypes (supported in part by protein modeling) in CH-TD. No CNVs were identified, nor did polyAla &gt;14 alanines in FOXE1 significantly protect against TD. The present and previously published data collectively show that small clinically relevant germline variants in PAX8, FOXE1, and TSHR are found in only a very small proportion (2.5%) of isolated CH-TD Mexican patients.

Based on the Expected Utility Theory and Regret Theory, the Extended Regret Theory (ERT) is proposed in this paper to study the optimal pricing strategy of retailers in e-commerce environment. Taking the diversity of sales channels and the uncertainty of consumers in e-commerce environment into consideration, author of the paper designs an extended regret utility function which comprehensively considers both pessimistic and optimistic attitudes of decision makers in retailing industry to describe their regret-avoidance behavior. According to the sensitivity analysis, it is found that the optimal retail price decreases as the consumer price sensitivity coefficient increases, yet does not show variation with changes of the consumers pessimism degree. Moreover, the optimal retail price(s) obtained under EUT, ERT and combination of EUT and ERT represent the same.

Understanding the detailed timing of crop phenology and their variability enhances grain yield and quality by providing precise scheduling of irrigation, fertilization, and crop protection mechanisms. Advances in information and communication technology (ICT) provide a unique opportunity to develop agriculture-related tools that enhance wall-to-wall upscaling of data outputs from point-location data to wide-area spatial scales. Because of the heterogeneity of the worldwide agro-ecological zones where crops are cultivated, it is unproductive to perform plant phenology research without providing means to upscale results to landscape-level while safeguarding field-scale relevance. This paper presents an advanced, reproducible, and open-source software for plant phenology prediction and mapping (PPMaP) that inputs data obtained from multi-location field experiments to derive models for any crop variety. This information can then be applied consecutively at a localized grid within a spatial framework to produce plant phenology predictions at the landscape level. This software supports the development of process-oriented and temperature-driven plant phenology models by intuitively and interactively leading the user through a step-by-step progression to the production of spatial maps for any region of interest. Maize (Zea mays L.) was used to demonstrate the robustness, versatility, and high computing efficiency of the resulting modeling outputs of the PPMaP. The framework is implemented in R, providing a flexible and easy‐to‐use GUI interface. Since this allows appropriate scaling to the larger spatial domain, the software can effectively be used to determine the spatially explicit length of growing period (LGP) of any variety.

The modern era of polarimetric radar begins with radiowave propagation research starting in the early 1970s with applications to measurement and modeling of wave attenuation in rain and depolarization due to ice particles along satellite-earth links. While there is a rich history of radar in meteorology after World War II, the impetus provided by radiowave propagation requirements lead to high quality antennas and feeds. Our journey starts by describing the key institutions and personnel responsible for development of weather radar polarimetry. The early period was dominated by circularly polarized radars for propagation research and at S-band for hail detection. By the mid-to late 70s, a paradigm shift occurred which led to the dominance of linear polarizations with applications to slant path attenuation prediction as well as estimation of rain rates and inferences of precipitation physics. The period from early 1980s to 1995 can be considered as the “golden” period of rapid research that brought in meteorologists, cloud physicists and hydrologists. This article describes the evolution of this technology from the vantage point of the authors. Their personal reflections and “behind the scenes” descriptions offer a glimpse into the inner workings at several key institutions which cannot be found elsewhere.

The magnetic polarization tensor has a promising capability of determining the geometry and material properties of metallic samples. In this paper, a novel computation method is proposed to estimate the magnetic polarization tensors for the metallic samples using the boundary element method. In this method, the metallic sample is placed in a uniformly distributed magnetic field. Based on assumptions that the excitation frequency and/or the conductivity of the sample is very high, the metallic sample is regarded as a perfect electrical conductor (PEC). Therefore, the scattered field at a certain distance can be simulated. By utilising the boundary element method, the magnetic polarization tensor can be derived from the simulated scattered field. The theoretical calculation is presented and simulations and experiments have been carried out to validate the proposed method. The results from the simulation are matched with the analytical solution for the case of sphere samples. Moreover, there is a good agreement between the simulation results and the experimental results for the copper cylindrical samples.

The article presents an analysis of monthly precipitation totals based on the GPCC database, and monthly mean temperatures (NOAA data) for 377 catchments distributed across the globe. The analysis included 110-year data sequences from 1901 to 2010 calculated from grid data with a spatial resolution of 0.5°x 0.5° longitude and latitude. Long-term sequences of precipitation and temperature were used to assess the polarization of climatic phenomena. The noticeable impact of polarization in the area of extreme changes in temperature and precipitation is related to anthropogenic factors such as greenhouse gas emissions, deforestation and pollution, which affect ecosystem functioning, biodiversity, water resources and economies. The paper demonstrates the existence of trends related to the polarization of temperature and precipitation phenomena. The measures of polarization used in science are discussed. A simple measure of polarization was proposed and applied to both long-term sequences of monthly precipitation totals and monthly mean temperature. Due to the nature of the proposed polarization measure, other characteristics of the precipitation and temperature sequences are also presented as background for the discussion of the polarization index. The paper presents, for a selection of several hundred catchments from around the world, analyses of the assessment of precipitation and temperature trends using non-parametric tests. The trend analyses use Mann -Kendall tests at the 5% significance level. A Pettitt test was used to determine the trend change point for precipitation and temperature data. The whole is supported by rich graphical analyses and the results are presented tabularly.