Engineered nanomaterials (ENMs) are of significant relevance due to their unique properties, which have been exploited for widespread applications. Cerium oxide nanoparticles (CeO2-NPs) are one of most exploited ENM in the industry due to their excellent catalytic and multi-enzyme mimetic properties. Thus, toxicological effects of these ENMs should be further studied. Acute and subchronic toxicity of CeO2-NPs were assessed. First an in vitro multi-dose short-term (24h) toxicological assessment was performed in three different cell lines: A549 and Calu3, representing the lung tissue, and 3T3 as an interstitial tissue model. After that, a sub-chronic toxicity assessment (90 days) of these NPs was carried out on a realistic and well stablished reconstituted primary human airway epithelial model (MucilAir™), cultured at the Air-Liquid Interface (ALI), to study long-term effects of these particles. Results showed minor toxicity of CeO2-NPs in acute exposures. However, in subchronic exposures, cytotoxic and inflammatory responses were observed in the human airway epithelial model after 60 days of exposure to CeO2-NPs. These results suggest that acute toxicity approaches may underestimate the toxicological effect of some ENM, highlighting the need of subchronic toxicological studies in order to accurately assess the toxicity of ENM and their cumulative effects in the organism.

All cancer registries constantly show striking differences in cancer incidence by age and among tissues. For example, lung cancer is diagnosed hundreds of times more often at age 70 than at age 20, and this cancer in nonsmokers occurs thousands of times more frequently than heart cancer in smokers. An analysis of these differences using basic concepts in cell biology indicates that cancer is the end-result of the accumulation of cell divisions in stem cells. In other words, the main determinant of carcinogenesis is the number of cell divisions that the DNA of a stem cell has accumulated in any type of cell from the zygote. Cell division, process by which a cell copies and separates its cellular components to finally split into two cells, is necessary to produce the large number of cells required for living. However, cell division can lead to a variety of cancer-promoting errors, such as mutations occurring during DNA replication, chromosome aberrations arising during mitosis, errors in the distribution of cell-fate determinants between the daughter cells, and failures to restore physical interactions with other tissue components. Some of these errors are spontaneous, others are promoted by endogenous DNA damage occurring during quiescence, and others are influenced by pathological and environmental factors. The cell divisions required for carcinogenesis are primarily caused by multiple local and systemic physiological signals rather than by errors in the DNA of the cells. As carcinogenesis progresses, the accumulation of DNA errors promotes cell division and eventually triggers cell division under permissive extracellular environments. The accumulation of cell divisions in stem cells drives not only the accumulation of the DNA alterations required for carcinogenesis, but also the formation and growth of the abnormal cell populations that characterize the disease. This model of carcinogenesis provides a new framework for understanding the disease and has important implications for cancer prevention and therapy.

Natural killer (NK) cell therapy is one of the most promising treatments for Glioblastoma Multiforme (GBM). However, this emerging technology is limited by the availability of sufficient numbers of fully functional cells. Here, we investigated the efficacy of NK cells that were expanded and treated by interleukin-2 (IL-2) and heat shock protein70 (HSP70), both in vitro and in vivo. Proliferation and cytotoxicity assays were used to assess the functionality of NK cells in vitro, after which treated and naïve NK cells were administrated intra-cranially and systemically to compare the potential antitumor activities in our in vivo rat GBM models. In vitro assays provided strong evidence of NK cell efficacy against C6 tumor cells. In vivo tracking of NK cells showed efficient homing around and within the tumor site. Furthermore, significant amelioration of the tumor in rats treated with HSP70/Il-2 treated NK cells as compared to those subjected to non-treated NK cells, as confirmed by MRI, proved the efficacy of adoptive NK cell therapy. Moreover, results obtained with systemic injection confirmed migration of activated NK cells over the blood brain barrier and subsequent targeting of GBM tumor cells. Our data suggest that administration of HSP70/Il-2 treated NK cells may be a promising therapeutic approach to be considered in the treatment of GBM.

This study was to designed to develop sorafenib-loaded polymeric nanoparticles, surface-modified with pluronic F-127 for the effective treatment of hepatocellular (HCC) and renal cell carcinomas (RCC). Poly lactic coglycolic acid (PLGA) was used to encapsulate different concentrations of sorafenib by a simple modified solvent evaporation method applying pluronic F-127 as a surfactant and coating agent. The preformulation and characterization studies were conducted to evaluate the incompatibilities among sorafenib, PLGA and pluronic F-127, and physicochemical properties of the formulations, respectively. The sizes of the coated and plain PLGA nanoparticles were ~140 ± 14.7 nm and ~ 120 ± 10.1 nm, respectively. It has been confirmed from the in vitro release studies that PLGA sustained the release of sorafenib, avoiding the initial burst release, while the in vivo studies demonstared that surface-modified nanoparticles have greater affinity in the target aorgans than plain PLGA nanoparticles and free drug keeping the dose constant (20 mg/kg body weight). The delivery of sorafenib-loaded polymeric PLGA nanoparticles into the target tissues and their pharmacokinetic parameters have been improved significantly compared to the reported formulations.

The pinning force density FpJc,B=Jc×B (where Jc is the critical current density and B is the applied magnetic field) is one of the main parameters that characterize the resilience of a superconductor to carry a dissipative-free transport current in an applied magnetic field. Kramer (1973 J. Appl. Phys. 44 1360), and Dew-Hughes (1974 Phil. Mag. 30 293) proposed a widely used scaling law for the pinning force density amplitude: FpB=Fp,max×p+qp+qppqq×BBc2p×1-BBc2q, where Fp,max, Bc2, p, and q are free-fitting parameters. Since the late 1970-s till now, several research groups have reported experimental data on the dependence of Fp,max on the average grain size, d, in Nb3Sn-based conductors. Godeke (2006 Supercond. Sci. Techn. 19 R68) proposed that the dependence obeys the law Fp,maxd=A×ln1d+B. However, this scaling law has several problems, for instance, the logarithm is taken from a non-dimensionless variable, and Fp,maxd<0 for large grain sizes, and Fp,maxd→∞ for d→0. Here, we reanalysed the full inventory of publicly available Fp,maxd data for Nb3Sn conductors and found that the dependence can be described by Fp,maxd=Fp,max0×exp-dδ law, where the characteristic length, δ, varies within a remarkably narrow range, that is, δ=175±13 nm, for samples fabricated by different technologies. The interpretation of the result is based on the idea that the in-field supercurrent flows within a thin surface layer (thickness of δ) near the grain boundary surfaces (similar to London’s law, where the self-field supercurrent flows within a thin surface layer with a thickness of the London penetration depth, λ, and the surface is a superconductor-vacuum surface). An alternative interpretation is that δ represents the characteristic length of the exponential decay flux pinning potential from the dominant defects in Nb3Sn superconductors, which are grain boundaries.

The Oxford English Dictionary includes 17 definitions for the word “model” as a noun and other 11 as a verb. Therefore, context is necessary to understand the meaning of the word model. For in-stance, “model railways” refer to replicas of railways and trains at a smaller scale and a “model student” refers to an exemplar individual. In some cases, a specific context, like cancer research, may not be sufficient to provide one specific meaning of a model. Even if the context is narrowed, specifically to the research related to the tumour microenvironment, a “model” can be understood in a wide variety of ways, from an animal model, to a mathematical expression. This paper presents a review of the different “models” of the tumour microenvironment grouped by the different def-initions of the word into four categories: model organisms, in vitro models, mathematical models, and computational models. Then, the frequency of different meanings of the word “model” related to the tumour microenvironment is measured from the number of entries in the MEDLINE database of the United States National Library of Medicine at the National Institutes of Health. The frequency of the main components of the microenvironment and the organ-related cancers modelled are also assessed quantitatively with specific keywords. Whilst animal models, in particular xenografts and mouse models are the most common used “models”, the number of entries have been slowly de-creasing. Mathematical models, prognostic and risk models follow in frequency and these have been growing in use.

In this review we look at the developments in the field of artificial intelligence (A.I) and their current impact as well as future implications in the field of cardiology, we as physicians and cardiologists have tried to put our perspective on the rapidly evolving field, In light of the fact that many of the healthcare workers and professionals across the world still find the concept of A.I quite complicated, elusive and somewhat paradoxical, we have tried to simplify the concept of artificial intelligence and make it easy for everyone to understand from all walks of life. The Databases utilized for our review are PubMed, PubMed Central, Google Scholar. The Keywords used for our Data Search are “Artificial Intelligence”, “A.I Cardiology”, “A.I in Cardiovascular Medicine”, “Machine Learning in Cardiology”. We screened all relevant since inception till March 25th and included 44 relevant articles after careful consideration into our paper. We have discussed the implementation of and scope of artificial intelligence across a broad spectrum of applications including cardiovascular imaging and diagnostics like electrocardiograms, echocardiograms, cardiac CT/MRIs to novel cardiac monitoring devices, CRISPR gene editing in cardiology and implementation of artificial intelligence in the field of Cardiovascular Bioprinting. This is the initial review in a series of reviews regarding A.I in Cardiology.

This work investigated the influence of current density, plating solution flow rate, and nozzle outlet-cathode distance on the properties of Ni-diamond composite coatings. A multi-physics field simulation is employed to analyze the interplay between current density, plating solution flow rate, and nozzle outlet-cathode distance on the flow field and electric field distribution. Additionally, particle tracing simulations were incorporated into the model to evaluate the incorporation efficiency of diamond particles during composite electrodeposition. Experimental validation of the findings shows a significant increase in the diamond particle content of the coating. This combined approach provides valuable insights for optimizing the jet electrodeposition process for Ni-diamond composite coatings with superior properties.

Evolutionary algorithms and swarm intelligence algorithms find applicability in reinforcement learning of neural networks due to their independence from gradient-based methods. To achieve successful training of neural networks using these algorithms, careful considerations must be made to select appropriate algorithms due to the availability of various algorithmic variations. In Part1, 2 and 3, the author previously reported experimental evaluations on Evolution Strategy, Genetic Algorithm, and Differential Evolution for reinforcement learning of neural networks, utilizing the Acrobot control task. This article constitutes Part4 of the series of comparative research. In this study, Particle Swarm Optimization is adopted as an instance of major swarm intelligence algorithms. The experimental result shows that PSO performed worse than all of DE, GA and ES. The difference between PSO and DE was statistically significant (p<.01). In addition, PSO exhibited lower capability in exploring solutions in high-dimensional search spaces than DE, GA, and ES did. A larger swarm size compensated for the weakness of PSO in global exploration, thus making itself more beneficial than a larger number of swarm search iterations.

In this study, we propose an efficient field-free line (FFL) generator for mechanically driven FFL-magnetic particle imaging (MPI) applications. The novel FFL generator comprises pairs of Halbach arrays and bar magnets. The proposed design generates high-gradient FFLs with low-mass permanent magnets, realizing fine spatial resolutions in MPI. We investigate the generated magnetic field using simulations and experiments. Our results show that the FFL generator yields a high gradient of 4.76 T/m at a cylindrical field of view of 30 mm diameter and a 70 mm open bore. A spatial resolution of less than 3.5 mm was obtained in the mechanically driven FFL-MPI.

Space exploration introduces astronauts to many challenges such as space radiation and microgravity. Researchers have investigated vitamin C as a potential radiation mitigator and antioxidants for sustaining astronaut health. Building on our own studies, which indicate vitamin C's life-saving radioprotective effects and its potential as a radiation mitigator, our research highlights its promise, even when administered 24 h post-exposure. This is particularly relevant in scenarios where astronauts may be exposed to sudden large solar particle events, potentially resulting in lethal doses of space radiation. The success of vegetable cultivation on the International Space Station using NASA's Veggie system offers fresh, vitamin C-rich food. While approved supplements address somatic function, further research is needed to optimize vitamin C's efficacy in humans and develop antioxidant cocktails for space missions. The variable vitamin C content in vegetables underscores the necessity for utilization of artificial intelligence (AI) to assist astronauts in selecting and cultivating vitamin C-rich vegetables that are best suited to combat high levels of space radiation and microgravity. Particularly, AI algorithms can be utilized in analyzing various factors such as nutritional content, growth patterns, and cultivation methods. In conclusion, vitamin C shows significant potential for mitigating space radiation, and ongoing research aims to enhance astronaut health through optimal dietary strategies.

Nanoparticles are of great importance for various scientific and technological applications, drug discovery, ecology, molecular biology, etc. Size is a basic characteristic of any particle, and dynamic light scattering is beyond competition when measuring particle size in dispersions ranging from nanometers to micrometers. Unfortunately, this method has a serious problem in processing and interpreting experimental data. Instrument noise and polydispersity of the sample lead to the situation when one initial autocorrelation function corresponds to several different particle size distributions. Sometimes these different solutions of the inverse task can be found by changing parameters in the software. Sometimes the scientist cannot be suspicious of possible other solutions, having one result from the program. In this article I demonstrate the problem on model and experimental data using three known programs: CONTIN, the Malvern Zetasizer and DynaLS. I also present my own free program Autocor, which allows to test our own hypotheses about the modality and shape of the particle size distribution by optimizing the parameters of our own models with a small number of degrees of freedom.

Efficient energy extraction in photovoltaic (PV) systems relies on the effective implementation of Maximum Power Point Tracking (MPPT) methods. Conventional MPPT techniques often suffer from slow convergence speeds and suboptimal tracking performance, particularly under dynamic variation of environmental conditions. Smart optimization algorithms (SOA) using metaheuristic optimization algorithms can avoid this limitation inherent in the conventional MPPT methods. The problem of slow convergence of the SOA is avoided in this paper using a novel strategy called Swarm Size Reduction (SSR) utilized with Particle Swarm Optimization (PSO) algorithm, specifically designed to achieve short convergence time (CT) while maintaining exceptional tracking accuracy. The novelty of the proposed MPPT method introduced in this paper is the dynamic reduction of the swarm size of the PSO for improved performance of the MPPT of the PV systems. This adaptive reduction approach allows the algorithm to efficiently explore the solution space of PV systems and rapidly exploit to identify the global maximum power point (GMPP) even under fast fluctuation of uneven solar irradiance and temperature. This pioneering ultra-fast MPPT method represents a significant advancement in PV system efficiency and promotes the wider adoption of solar energy as a reliable and sustainable power source. The novel adaptive PSO algorithm also opens new possibilities for further innovations in optimization-driven applications, extending its potential impact on a diverse range of real-world challenges. The results obtained from this proposed strategy are compared with several optimization algorithms to validate its superiority.

The effect of coal hydrophilic particles in water-glycerol drops on the maximum diameter of spreading along a hydrophobic solid surface is experimentally studied by analyzing the velocity of internal flows by Particle Image Velocimetry. The grinding fineness of coal particles was 45-80 μm and 120-140 μm, their concentration was 0.06 wt.% and 1 wt.%. The impact of particle-laden drops on a solid surface occurred at Weber numbers (We) from 30 to 120. It is revealed the interrelated influence of We and the concentration of coal particles on changes in the maximum absolute velocity of internal flows in a drop within the kinetic and spreading phases of the drop-wall impact. A physical model is formulated for internal convective flows in the longitudinal section of a drop parallel to the plane of the solid wall. The kinetic energy of translational motion of coal particles in a spreading drop compensates for the energy expended by the drop on sliding friction along the wall. At We=120, the inertia-driven spreading of the particle-laden drop is mainly determined by the dynamics of the deformable Taylor rim. An increase in We contributes to more noticeable differences in the convection velocities in spreading drops. When the drop spreading diameter rises at the maximum velocity of internal flows, a growth of the maximum spreading diameter occurs. The presence of coal particles causes a general tendency to reduce the drop spreading.

This paper presents research on the application of trajectory design, optimization, and control to an orbital transfer from Mars-Phobos Distant Retrograde Orbits to the surface of Phobos. Given a Distant Retrograde Orbits and a landing location on the surface of Phobos, landing trajectories for which total Δv for a direct 2-burn maneuver is minimized are computed. This is accomplished through the use of Particle Swarm Optimization in which the required Δv and time of flight are optimization parameters. The non-uniform gravitational environment of Phobos is considered in the computation. Results show how direct transfers can be achieved with Δv in the order of ∼30 m/s.

We derive the stabiliser group of the four-vector, also known as Wigner’s little group, in case of massless particle states, as the maximal solvable subgroup of the proper orthochronous Lorentz group of dimension four, known as the Borel subgroup. In the absence of mass, particle states are disentangled into left and right handed chiral states, governed by the maximal solvable subgroups sol2± of order two. Induced Lorentz transformations are constructed and applied to general representations of particle states. Finally, it is argued how the spin-flip contribution is closely related to the occurrence of nonphysical spin operators.

The dynamics of a low-energy charged particle in an axis-symmetric magnetic field is known to be a regular superposition of periodic–although possibly incommensurate–motions. The projection of the particle orbit along the two non-ignorable coordinates (x,y) may be expressed in terms of each other: y=y(x), yet–to our knowledge–such a functional relation has never been directly produced in literature, but only by way of a detour: first, equations of motion are solved, yielding x=x(t),y=y(t), and then one of the two relations is inverted, x(t)→t(x). In this paper we present a closed-form functional relation which allows to express coordinates of the particle’ orbit without the need to pass through the hourly law of motion.

Nanographene oxide (GOn) constitutes a nanomaterial of high value in the biomedical field. However, large scale production of highly stable aqueous dispersions of GOn is yet to be achieved. In this work, we explored high-power ultrasonication as a method to reduce particle size of GO and characterized the impact of the process in the physico-chemical properties of the material. GOn was obtained with lateral dimensions of 99 ±43 nm and surface charge of −39.9 ± 2.2 mV. High-power ultrasonication enabled an improvement of stability features, particularly by resulting in a decrease of the average particle size, as well as zeta potential, in comparison to GO obtained by low-power exfoliation and centrifugation (287 ± 139 nm; −29.7 ± 1.2 mV). Re-markably, GOn aqueous dispersions were stable for up to 6 months of shelf-time, with a global process yield of 74%. This novel method enabled the production of large volumes of highly con-centrated (7.5 mg mL-1) GOn aqueous dispersions. Chemical characterization of GOn allowed the identification of characteristic oxygen functional groups, supporting high-power ultrasonication as a fast, efficient and productive process for reducing GO lateral size, while maintaining the material’s chemical features.

The information entropy for Smoluchowski coagulation equation is proposed based on statistical mechanics. And the normalized particle size distribution is a lognormal function at equilibrium from the principle of maximum entropy and moment constraint. The geometric mean volume and standard deviation in the distribution function are determined as simple constant. The results reveal that the assumption that algebraic mean volume be unit in self-preserving hypothesis is reasonable in some sense. Based on the present definition of information entropy, the Cercignani’s conjecture holds naturally for Smoluchowski coagulation equation. Together with the proof that the conjecture is also true for Boltzmann equation, Cercignani’s conjecture will holds for any two-body collision systems, which will benefit the understanding of Brownian motion and molecule kinematic theory, such as the stability of the dissipative system, and the mathematical theory of convergence to thermodynamic equilibrium.

Radiotherapy using accelerated charged particles is rapidly growing worldwide. About 85% of the cancer patients receiving particle therapy is irradiated with protons, which have physical advantages compared to X-rays but similar biological response. In addition to the ballistic advantages, heavy ions present specific radiobiological features that can make them attractive for treating radioresistant, hypoxic tumors. An ideal heavy ion should have lower toxicity in the entrance channel (normal tissue), and being exquisitely effective in the target region (tumor). Carbon ions have been chosen because they represent the best combination in this direction. Normal tissue toxicities and second cancer risk are similar to those observed in conventional radiotherapy. In the target region, they have increased relative biological effectiveness and reduced oxygen enhancement ratio compared to X-rays. Some radiobiology properties of densely ionizing carbon ions are so distinct from X-rays and protons that they can be considered as a different “drug” in oncology, and may elicit favorable responses such as increased immune response and reduced angiogenesis and metastatic potential. The radiobiological properties of carbon ions should guide patient selection and treatment protocols to achieve optimal clinical results.

Ammonia (NH3), the most prevalent alkaline gas in the atmosphere, plays a significant role in PM2.5 formation, atmospheric chemistry, and new particle formation. This paper reviews quantification of [NH3] through measurements, satellite-remote-sensing, and modeling reported in over 500 publications towards synthesizing current knowledge of [NH3], focusing on spatiotemporal variations, controlling processes, and quantification issues. Most measurements are through regional passive sampler networks. [NH3] hotspots are typically over agricultural regions like the Midwest US and North China Plain, with elevated concentrations reaching monthly averages of 20 and 74 ppbv, respectively. Topographical effects dramatically increase [NH3] over the Indo-Gangetic Plains, North India and San Joaquin Valley, US. Measurements are sparse over oceans, where [NH3] ≈ few tens of ppbv, variations of which can affect aerosol formation. Satellite-remote-sensing (AIRS, CrIS, IASI, TANSO-FTS, TES) provides global [NH3] quantification in the column and at surface since 2002. Modeling is crucial for improving understanding of NH3 chemistry and transport, its spatiotemporal variations, source apportionment, exploring physicochemical mechanisms, and predicting future scenarios. GEOS-Chem (global) and FRAME (UK) models are commonly applied for this. A synergistic approach of measurements↔satellite-inference↔modeling is needed towards improved understanding of atmospheric ammonia, of concern from the standpoint of human health and the ecosystem.

Quantum turbulence deals with the phenomenon of turbulence in quantum fluids, such as superfluid helium and trapped Bose-Einstein condensates (BECs). Although much progress has been made in understanding quantum turbulence, several fundamental questions remain to be answered. In this work, we investigated the entropy of a trapped BEC in several regimes, including equilibrium, small excitations, the onset of turbulence, and a turbulent state. We considered the time evolution when the system is perturbed and let to evolve after the external excitation is turned off. We derived an expression for the entropy consistent with the accessible experimental data, that is, using the assumption that the momentum distribution is well-known. We related the excitation amplitude to different stages of the perturbed system, and we found distinct features of the entropy in each of them. In particular, we observed a sudden increase in the entropy following the establishment of a particle cascade. We argue that entropy and related quantities can be used to investigate and characterize quantum turbulence.

The availability of high quality surface observations of precipitation and volume observations by polarimetric operational radars make it possible to constrain, evaluate and validate numerical models with a wide variety of microphysical schemes. In this article, a novel particle-based Monte-Carlo microphysical model (called “McSnow”) is used to simulate the outer rain bands of Hurricane Dorian which traversed the densely instrumented precipitation research facility operated by NASA at Wallops Island, Virginia. The rain bands showed steady stratiform vertical profiles with radar signature of dendritic growth layers near −15 °C and peak reflectivity in the bright band of 55 dBZ along with polarimetric signatures of wet snow with sizes inferred to exceed 15 mm. A 2D-video disdrometer measured frequent occurrences of large drops &gt;5 mm and combined with an optical array probe the drop size distribution was well-documented in spite of uncertainty for drops &lt;0.5 mm due to high wind gusts and turbulence. The 1D McSnow control run and four numerical “experiments” were conducted and compared with observations. One of the main findings is that even at the moderate rain rate of 10 mm/h collisional breakup is essential for the shape of the drop size distribution.

The COVID-19 pandemic has disrupted the supply chain for personal protective equipment (PPE) for medical professionals, including N95-type respiratory protective masks. To address this shortage, many have looked to the agility and accessibility of additive manufacturing (AM) systems to provide a democratized, decentralized solution to producing respirators with equivalent protection for last-resort measures. However, there are concerns about the viability and safety in deploying this localized download, print, and wear strategy. Several polymer-based AM processes produce porous parts, and inherent process variation between printers and materials also threaten the integrity of tolerances and seals within the printed respirator assembly. The goal of this paper is to quantitatively measure particle transmission through printed respirators of different designs, materials, and AM processes, and assess the viability of printed respirators as N95 equivalents. Results from this study show that respirators printed using desktop/industrial-scale fused filament fabrication processes and industrial-scale powder bed fusion processes have insufficient filtration efficiency at the size of the SARS-CoV-2 virus, even while assuming a perfect seal between the respirator and the user’s face. Almost all printed respirators provided <60% filtration efficiency at the 100-300 nm particle range. Only one respirator, printed on an industrial-scale fused filament fabrication system provided >90% efficiency as-printed. Post-processing procedures including cleaning, sealing surfaces, and reinforcing the filter cap seal generally improved performance, but no respirator sustained the filtration efficiency of an N95 respirator, which filters 95% of SARS-CoV-2 virus particles. Instead, the printed respirators showed similar performance to various cloth masks. While continued optimization of printing process parameters and design tolerances could be implemented to directly print respirators that provide the requisite 95% filtration efficiency, AM processes are not sufficiently reliable for widespread distribution and local production of N95-type respiratory protection without commensurate quality assurance processes in place. Certain design/printer/material combinations may provide sufficient protection for specific users, but the respirators should not be trusted without quantitative filtration efficiency testing. It is currently not advised to expect printed respirators originating from distributed designs to replicate performance across different printers and materials.

This study was aimed at investigating the effects of roasting and cryogenic milling on particle size, water solubility, and amount of bioactive components in ginseng root. Samples were pulverized by cryogenic milling, and one treatment condition was selected for each size range (10-50 μm, and >50 μm). The selected samples were roasted at different temperatures (160-200 °C) followed by cryogenic milling. Powdered samples were analyzed for their physicochemical characteristics. Results revealed that roasted samples exhibited significantly smaller particle size than controls (not roasted, p<0.05), and the particle size of roasted samples decreased with increase in roasting temperature until flocculation occurred around 180-190 °C. With decrease in particle size of ginseng; water solubility index, antioxidant activity, total polyphenol content, and total polysaccharide content were observed to increase. Ginseng samples showed an increasing trend in antioxidant activity with decreasing particle size (p>0.05) with significantly higher values for all roasted samples compared to the controls (p<0.05). Non-polar ginsenosides such as Rg2(S), Rg2(R), Rg3(S), Rg3(R), and Rh1(S) showed an increase in temperature-dependent manner. This study revealed that roasting at certain temperature range with cryogenic milling has positive effects on ginseng by reducing its particle size, and increasing water solubility and bioactive components.

This study aimed to decrease the particle size of ginseng by roasting and cryogenic milling to increase its water solubility and physiological activity. The samples were roasted for different times (9–21 min) and generated in different sizes (10–50, and > 50 μm). All roasted samples revealed significantly smaller particle sizes than did non-roasted samples based on Sauter mean diameter (D [3,2], p < 0.05). Further, the particle sizes of roasted samples decreased till roasting up to 15 min. In terms of the water solubility index (WSI), antioxidant activity, total polyphenol content (TPC), and total polysaccharides according to particle size, 10-20 μm-sized samples showed the highest values when compared with >50 μm-sized samples. Based on roasting time, WSI values of all samples roasted for up to 15 min were higher than those of the control (not roasted) (p < 0.05). Antioxidant activity and TPC also increased with increasing roasting time. Total polysaccharide content was the highest upon roasting for 15 min except for the 10-20 μm sample. Ginsenoside content of roasted samples >20 μm size was higher than that of the control (not roasted) except after 15 min of roasting. Therefore, roasting and cryogenic milling are effective in producing ginseng root powder.

An analysis is presented of the possible existence of a second anomalous dipole moment of Dirac’s particle next to the angular one. It includes a discussion why, in spite of his own derivation, Dirac has doubted about its relevancy. It is shown why since then it has been overlooked and why it has vanished from leading textbooks. A critical survey is given on the reasons of its reject, including the failure of attempts to measure and the perceived violations of time reversal symmetry and chargeparity symmetry. It is emphasized that the anomalous electric dipole moment of the pointlike electron (AEDM) is fundamentally different from the quantum field type electric dipole moment of an electron (eEDM) as defined in the standard model of particle physics and that its measurement requires different instrumentation. A proposal has been described how to prove or disprove its existence by experiment. Moreover, by reference from literature, the possible impact is discussed in the nuclear domain and in the gravitational domain.

Precipitation processes are technologies commonly used in hydrometallurgical plants to recover metals or to treat wastewaters. Moreover, solid-liquid separation technologies, such as thickening or filtering, are relevant unit operations, included in the precipitation technologies. These methods are strongly dependent on the characteristics of the solid precipitates formed during the specific precipitation reaction. One of these characteristics is the particle size distribution (PSD) of the solid precipitates which are fed into a solid-liquid separation process. Therefore, PSD determination is a typical practice for the characterization of the slurries generated in a precipitation plant. Furthermore, the precipitates generated in these processes have a colloidal or aggregation behavior, depending on the operational conditions. Nevertheless, the conventional methods used to estimate PSD (e.g., laser diffraction and/or ciclosizer) have not been designed to measure particles that tend to aggregate or disaggregate, since they include external forces (e.g., centrifugal, agitation, pumping and sonication). These forces affect the true size of the aggregates formed in a unit operation, thereby losing representativity in terms of aggregates particle size. This study presents an alternative method of measuring the size distribution of particles with aggregation behavior, particularly, by using non-invasive microscopy and image processing and analysis. The samples used have been obtained from an experimental precipitation process by applying sulfidization to treat the cyanide-copper complexes contained in a cyanidation solution. This method has been validated with statistical tools and compared with a conventional analysis based on laser diffraction. Our results show significant differences between the methods analyzed, demonstrating that image processing and analysis by microscopy is an excellent and non-invasive alternative to obtaining size distribution of aggregates in precipitation processes.

It is shown that gravity and quantum physics can be unified upon the basis of a quark description in terms of a gravitational Dirac particle. It requires the awareness of a second elementary dipole moment (isospin) next to the angular moment (spin) of Dirac particles and the awareness of an (unbroken) omnipresent energetic cosmological background field. The unification has been made explicit by an expression that relates the two major gravitational constants of nature (the gravitational constant and Milgrom’s acceleration constant) with the two major nuclear constants of nature (the weak interaction boson and the Higgs boson).

1) Background: Traditionally, complex biological products such as vaccines presented unique challenges to implementation of even rudimentary characterization packages; thus, the product was defined almost exclusively by its manufacturing process. The advances in technology and analytical tools allowed the application of more comprehensive characterization packages for products such as adsorbed combination vaccines, which contain several antigens in a single formulation to protect against more than one disease, and may contain adjuvants and excipients. Aluminum phosphate (AlPO4) is a well-established adjuvant for enhancing the uptake of vaccines and to induce robust immunity against pathogens. During manufacturing, adjuvant is mixed with protein antigens which may in turn impact their higher order structure and stability. 2) Methods: To study the structural changes of protein antigens after adsorption several analytical tools including DLS, FTIR, Fluorescence, LD, and SEM were used. 3) Results: the AlPO4 adjuvant suspension consists of small submicron particles that form a continuous porous surface. Secondary structure alpha-helix and beta-sheet content of DT and TT increased after adsorption to AlPO4 adjuvant, whereas no significant changes were noted for other protein antigens. Interactions were noted between AlPO4 adjuvant and DT, TT, and FHA. 4) Conclusions: here we report for the first time the use of SEM for the visualization of adsorbed multivalent vaccine components. A unique signature profile detected for each multivalent vaccine by FTIR can be used as a lean in-process test to verify vaccine product composition and identity prior to filling.

Underwater Sensor Networks (UWSNs) can enable a broad range of applications such as resource monitoring, disaster prevention, and navigation-assisted. It is especially relevant for sensor nodes location in UWSNs. Global Positioning System (GPS) is not suitable for using in UWSNs because of the underwater propagation problems. Hence some localization algorithms based on the precise time synchronization between sensor nodes have been proposed which are not feasible for UWSNs. In this paper, we propose a localization algorithm called Two-Phase Time Synchronization-Free Localization Algorithm (TP-TSFLA). TP-TSFLA contains two phases, namely, range-based estimation phase and range-free evaluation phase. In the first phase, we address a time synchronization-free localization scheme base on the Particle Swarm Optimization (PSO) algorithm to decrease the localization error. In the second phase, we propose a Circle-based Range-Free Localization Algorithm (CRFLA) to locate the unlocalized sensor nodes which cannot obtain the location information through the first phase. In the second phase, sensor nodes which are localized in the first phase act as the new anchor nodes to help realize localization. Hence in this algorithm, we use a small number of mobile beacons to help achieve location without any other anchor nodes. Besides, to improve the precision of the range-free method, an extension of CRFLA by designing a coordinate adjustment scheme is updated. The simulation results show that TP-TSFLA can achieve a relative high localization ratio without time synchronization.

In this research paper, we address the critical role of data security in the rapidly evolving FinTech sector. We explore the challenges and strategies for establishing robust data security systems, emphasizing the consequences of data breaches and common vulnerabilities. The paper highlights the efficacy of technologies like encryption, blockchain, and cloud security, supported by real-world case studies from leading FinTech companies. Additionally, we examine regulatory frameworks and standards essential for maintaining data security. Concluding with the proposal of an integrated security system model, the paper underscores the synergy between technological innovation, regulatory compliance, and proactive risk management in the FinTech industry

Metal-supported fuel cells (MSCs) offer potential material cost and robustness advantage over anode supported cells (ASCs). Because of the very good thermal shock stability of such MSCs, these can be heated up very quickly. However the challenge co-firing of metal substrate and electrolyte stays still unsolved. The production of the core component, the tape casted metal substrate, with defined shrinkage resulting from modification of metal powders is presented in the paper. This approach leads to an adjustment of the shrinkage mismatch during sintering, between metal and ceramic components, and adjustment of target specifications like porosity, green density and layer thickness.

The Environmental interactions contributed to the processes of settlement and development of the first settlers at southern Peru 15,000 BC. The determination of this process is based on paleoclimatic studies at southern Peru and ethnoarchaeological evidence. The determination of this process is based on paleoclimatic studies of southern Peru and ethnoarchaeological evidence; establishing as a result of this analysis the hypothesis of environmental interaction and territorial occupation of the first hunter-gatherer populations until their consolidation, dominating the geographical space from Tacna. The Disruptive disaster events and their effects on climate during the Peruvian Paleolithic resulted in the origin of local societies that shaped the Tiawanaku societies of the early horizon at Southern Peru and Northern Chile.

Antigen-presenting cells (APCs) are essential for modulating immune responses, and optimizing their differentiation protocols is critical for cell-based immunotherapies. This study compares eight different protocols for differentiating APCs from C57BL/6J mice using GM-CSF and L-929 supernatant. Four groups treated with GM-CSF and four with L-929 supernatant at various concentrations, alongside a control group were evaluated. Flow cytometry was used to analyze the expression of key markers, including MHC II, CD11c, F4/80, and CD11b. Our findings show that GM-CSF resulted in superior differentiation outcomes compared to L-929 supernatant, with higher expression levels of the analyzed markers. This study underscores the importance of considering both cell yield and protein expression quality in selecting differentiation protocols. For researchers developing therapies targeting specific cell populations, these findings demonstrate how different culture conditions influences both the quantity and phenotypic characteristics of differentiated cells. Balancing efficiency and phenotypic fidelity is crucial for optimizing cell-based immunotherapy strategies. Our data provide a valuable reference for future studies and applications involving APC differentiation from bone marrow precursors, ensuring robust foundations for developing advanced immunotherapies. This comprehensive comparison of differentiation protocols offers insights essential for enhancing the effectiveness and cost-efficiency of cell-based therapies.

Macro-autophagy (autophagy hereafter) is an evolutionarily conserved cellular process that has long been recognized as an intracellular mechanism for maintaining cellular homeostasis. It involves the formation of a membraned structure called the autophagosome, which carries cargo that includes toxic protein aggregates and dysfunctional organelles to the lysosome for degradation and recycling. Autophagy is primarily considered and studied as a cell-autonomous mechanism. However, recent studies have illuminated an underappreciated facet of autophagy, i.e., non-autonomously regulated autophagy. Non- autonomously regulated autophagy involves the degradation of autophagic components, including organelles, cargo, and signaling molecules, and is induced in neighboring cells by signals from primary adjacent or distant cells/tissues/organs. This review provides insight into the complex molecular mechanisms governing non-autonomously regulated autophagy, highlighting the dynamic interplay between cells within tissue/organ or distinct cell types in different tissues/organs. Emphasis is placed on modes of intercellular communication that include secreted molecules, including microRNAs, and their regulatory roles in orchestrating this phenomenon. Furthermore, we explore the multidimensional roles of non-autonomously regulated autophagy in various physiological contexts, spanning tissue development and aging, as well as its importance in diverse pathological conditions, including cancer and neurodegeneration. By studying the complexities of non-autonomously regulated autophagy, we hope to gain insights into the sophisticated intercellular dynamics within multicellular organisms, including mammals. These studies will uncover novel avenues for therapeutic intervention to modulate intercellular autophagic pathways in altered human physiology.

Combined radiation with hemorrhage (combined injury, CI), exacerbates hematopoietic acute radiation syndrome and mortality compared to radiation alone (RI). We evaluated the effects of RI or CI on blood cell depletion as a biomarker to differentiate the two. Male CD2F1 mice were exposed to 8.75 Gy γ- radiation (60Co). Within 2 h of RI, animals were bled under anesthesia 0% (RI) or 20% (CI) of total blood volume. Blood samples were collected at 4-5 h and days 1, 2, 3, 7, and 15 after RI. CI decreased WBC at 4-5 h and continued to decrease them until day 3; counts then stayed at the nadir up to day 15. CI decreased neutrophils, lymphocytes, monocytes, eosinophils and basophils more than RI on day 1 or day 2. CI decreased RBCs, hemoglobin and hematocrit on days 7 and 15 compared to RI, whereas Hemorrhage alone returned to the baseline on days 7 and 15. RBCs depleted after CI faster than post RI. Hemorrhage alone increased platelet counts on days 2, 3, and 7, which returned to the baseline on day 15. Our data suggest that WBC depletion may be a biomarker within 2 days post-CI and RBC depletion after 3 days post-CI.

Cell junction that is usually associated with dynamic cytoskeletons is essential for a wide range of cellular activities such as cell migration, cell communication, barrier function and signal transduction. Real-time observation of cell junction facilitates understanding of the mechanisms by which cell junction regulate relevant cellular activities. In this study, we examined the binding capacity of a modified tridecapeptide from Cx43 to cell junction protein ZO-1 and sought to create a fluorescent peptide that could be used to label cell junction. To introduce the fluorescent peptide into the cells, a cell-penetrating peptide was linked to the modified tridecapeptide and synthesized. The binding of the modified tridecapeptide was tested using pull down and immunoprecipitation assay. The ability of the peptide to label cell junction was assessed by adding it to fixed or cultured Caco-2 cells. Testing assay revealed that the Cx43-derived peptide can bind to ZO-1. Besides, the peptide was able to label cell junction of fixed cell, although no obvious cell junction labeling was observed clearly in living cells, probably due to the inadequate affinity. These results indicate that a peptide-based strategy for labeling cell junction may be feasible, and efforts to improve its affinity are warranted in the future.

The multidrug-resistant fungal pathogens belonging to the Candida haemulonii complex and the phylogenetically related species Candida auris are well-known for causing infections that are difficult to treat due to their multidrug-resistance profile. C. auris is even more worrisome due to its ability to cause outbreaks in healthcare settings. These emerging yeasts produce a wide range of virulence factors that facilitate the development of the infectious process. In recent years, the aggregative phenotype has been receiving attention, as it is mainly associated with defects in cellular division and its possible involvement in helping the fungus to escape from host immune responses. In this study, we initially investigated the aggregation ability of 18 clinical isolates belonging to the C. haemulonii species complex and C. auris. Subsequently, we evaluated the effects of physicochemical factors on the fungal aggregation competence. The results demonstrated that cell aggregation was a typically time-dependent event, in which almost all studied fungal isolates exhibited high aggregation after 2 h of incubation at 37°C. The aggregation was not impacted by pH, temperature, -mercaptoethanol (a protein-denaturing agent) and EDTA (a chelator agent). Conversely, proteinase K, trypsin and sodium dodecyl sulfate significantly diminished the aggregation. Collectively, our results demonstrated that the aggregation ability in these opportunistic yeast pathogens is time-dependent, and surface proteins and hydrophobic interactions seem to mediate cell aggregation, since the presence of proteases and anionic detergent affected the aggregation ability. However, further studies are necessary to better elucidate this phenomenon.

Different studies corroborate a role for ceramide synthases and their downstream products, ceramides, in modulation of apoptosis and autophagy in the context of cancer. These mechanisms of regulation, however, appear to be context dependent in terms of ceramides’ fatty acid chain length, subcellular localization, and the presence or absence of their downstream targets. Our current understanding of the role of ceramide synthases and ceramides in regulation of apoptosis and autophagy could be harnessed to pioneer the development of new treatments to activate or inhibit a single type of ceramide synthase, thereby regulating the apoptosis induction or cross talk of apoptosis and autophagy in cancer cells. Moreover, the apoptotic function of ceramide suggests that ceramide analogues can pave the way for the development of novel cancer treatments. Therefore, in the current review paper we discuss the impact of ceramide synthases and ceramides in regulation of apoptosis and autophagy in context of different types of cancers. We also briefly introduce the latest methods to analyze the lipids in biological samples. Finally, we discuss the drug development strategies focusing on the ceramide synthases and ceramides as future therapeutic approaches in cancer therapy.

Apple (Malus x domestica) fruit size is dependent on cell division and cell expansion, processes which are subsequently regulated by plant hormones such as auxins, gibberellins, and cytokinins. In this study, we investigated the role of cell division and cell expansion in apple growth and identified which of the two was more deterministic to final fruit size. Three cultivars of different sizes were selected, namely, ‘Twenty Ounce’ (large-sized), ‘Royal Gala’ (medium-sized), and ‘Crabapple’ (small-sized). Gene expression and cell size analyses were conducted over the course of two consecutive seasons. The expression patterns of three classes of genes were markedly similar across all cultivars. Two cell division markers, namely, MdCDKB2;2 and MdANT2, were discovered to be correlatively expressed as both displayed initially high expression levels, which gradually declined from the early to late stages of growth time course. For cell expansion markers, MdEXP3 was upregulated as the cells expanded, while MdARF106 was expressed in both the cell division and expansion stages. Meanwhile, the ripening related gene MdACO1 was expectedly expressed only during the ending stages associated with ripening. Interestingly, the cell measurements taken regularly from each cultivar throughout the same eperimental timespan showed that cell sizes were unaltered and remained constant from initial pollination at the zeroth Days After Pollination (DAP), to ripening at 120 Days After Full Bloom (DAFB).

The fate of a viral infection in the host begins with various types of cellular responses, such as abortive, productive, latent, and destructive infections. Apoptosis, necroptosis, and pyroptosis are the three major types of regulated cell death mechanisms that play critical roles in viral infection response. Cell shrinkage, nuclear condensation, bleb formation, and retained membrane integrity are all signs of osmotic imbalance-driven cytoplasmic swelling and early membrane damage in necroptosis and pyroptosis. Caspase-driven apoptotic cell demise is considered in many circum-stances as an anti-inflammatory, and some pathogens hijack the cell death signaling routes to initiate a targeted attack against the host. In this review, we selected mechanisms by which viruses interfere with cell death are discussed in-depth and are used to illustrate the general principles and cellular signaling mechanisms of virus-host specific molecule interactions.

Neural stem cell (NSC) based therapies are at the forefront of regenerative medicine strategies to combat illness and injury of the central nervous system (CNS). In addition to their ability to produce new cells, NSCs secrete a variety of products, known as the NSC secretome, that have been shown to ameliorate CNS disease pathology and promote recovery. As pre-clinical and clinical research to harness the NSC secretome for therapeutic purposes advances, a more thorough understanding of the endogenous NSC secretome can provide useful insight into the functional capabilities of NSCs. In this review, we focus on research investigating the autocrine and paracrine functions of the endogenous NSC secretome across life. We also compare the NSC secretome across species, finding signs of conserved parallels between rodent, human and zebrafish NSC secretomes. Throughout development and adulthood, we find evidence that the NSC secretome is a critical component of how endogenous NSCs regulate themselves and their niche. We also find gaps in current literature, most notably in the clinically relevant domain of endogenous NSC paracrine function in the injured CNS. Future investigations to further define the endogenous NSC secretome and its role in CNS tissue regulation are necessary to bolster our understanding of NSC-niche interactions and to aid in the generation of safe and effective NSC-based therapies.

Superantigens are unconventional antigens which recognise immune receptors outside the usual binding sites e.g. complementary determining regions (CDRs), to elicit a response within the target cell. T-cell superantigens crosslink T-cell receptors and MHC Class II molecules on antigen-presenting cells, leading to lymphocyte recruitment, induction of cytokine storms and T-cell anergy or apoptosis among many other effects. B-cell superantigens, on the other hand, bind immunoglobulin receptors on B-cells affecting opsonisation, IgG-mediated phagocytosis, and drive B-cells into apoptosis. Here, through a review of the structural basis for recognition of immune receptors by superantigens, we show that their binding interfaces share specific physicochemical characteristics when compared with other protein-protein interaction complexes. Given that antibody-binding superantigens have been exploited extensively in industrial antibody purification, these observations could facilitate further protein engineering to optimize the use of superantigens in this and other areas of biotechnology.

Syncytium formation, i.e., cell-cell fusion resulting in the formation of multinucleated cells, is a hallmark of infection by paramyxoviruses and other important viruses. This natural mechanism has historically been a diagnostic marker for paramyxovirus infection in vivo and is now widely studied for virus-induced membrane fusion in vitro. However, the role of syncytium formation in within-host dissemination and pathogenicity of viruses remains poorly understood. The diversity of henipaviruses and their wide host range and tissue tropism make them particularly appropriate models to characterize the drivers of syncytium formation and its implications for virus fitness and pathogenicity. Based on the henipavirus literature, we summarized current knowledge on the mechanisms driving syncytium formation, mostly acquired from in vitro studies, and on the in vivo distribution of syncytia. While these data suggest that syncytium formation widely occurs across henipaviruses, hosts and tissues, we identified important data gaps that undermined our understanding of the role of syncytium formation in virus pathogenesis. Based on these observations, we propose solutions of varying complexity to fill these data gaps, from better practices in data archiving and publication for in vivo studies, to experimental approaches in vitro.

Circulating atypical cells (CAC) are released from a primary tumour site into peripheral blood and are indicators of cancer metastasis. CAC occur at very low frequency in circulating blood, and their detection remains challenging. Moreover, white blood cells (WBC) are the major contaminant in enriched CAC samples. Here, we developed matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) as a novel CAC characterization platform. Main spectra profiles (MSP) of normal and cancer cells were generated by MALDI-TOF MS, and a cell-main spectra database was then compiled and analysed using the MALDI Biotyper software. Logarithmic scores accurately predicted distinct cell types. The feasibility of this workflow was then validated using simulated samples, which were prepared by 5,000 WBC of three healthy individuals spiked with varying numbers (3, 6, 12, 25, 50 and 100) of lung, colon, or prostate cancer cells. MALDI-TOF MS was able to detect cancer cells down to six cells over the background noise of 5,000 WBC with significantly higher predictive scores as compared to WBC alone. Further development of cell-MSP database to cover all cancer types sourced from cell lines and patient tumours may enable the use of MALDI-TOF MS as a cancer-screening platform in clinical settings in the future.

Cholinergic innervation in pancreas controls both the release of digestive enzymes to support the intestinal digestion and absorption, as well as insulin release to promote nutrient use in the cells of the body. The effects of muscarinic receptor stimulation are described in detail for endocrine beta cells and exocrine acinar cells separately. Here we describe morphological and functional criteria to separate these two cell types in situ in tissue slices and simultaneously measure their response to ACh stimulation on cytosolic Ca2+ oscillations [Ca2+]c in stimulatory glucose conditions. Our results show that both cell types respond to glucose directly in the concentration range compatible with the glucose transporters they express. The physiological ACh concentration increases the frequency of glucose stimulated [Ca2+]c oscillations in both cell types and synchronizes [Ca2+]c oscillations in acinar cells. The pharmacological ACh concentration further increases the oscillation frequency on the level of individual beta cells, inhibits the synchronization between these cells, and abolishes oscillatory activity in acinar cells. We discuss possible mechanisms leading to the observed phenomena.

Purpose: Myelodysplastic syndromes (MDS) are caused by a stem cell failure, but the relationship between immune dysregulation and the course of disease has not yet been analyzed in detail. Experimental design: To get insights into the pathophysiologic and clinical relevance of the histotopography of immune cell subpopulations in this process, the immune cell infiltrate with focus on its spatial distribution was determined by multispectral imaging (MSI) in 147 bone marrow biopsies from MDS or secondary acute myeloid leukemia (sAML) patients and healthy controls (HC). In addition, the data were correlated to genetic alterations and clinical features of these patients including therapy response. Results: A high inter-tumoral heterogeneity in the frequency and spatial distribution of CD3⁺CD8⁺, CD3⁺CD8^-, CD3⁺FOXP3⁺ T cell subsets, MUM1p⁺CD3^- post-germinal B/plasma cells and CD34⁺ blasts was found in MDS and sAML samples. In HC only few B cells/plasma cells, but no T cell subpopulations were detected in the proximity to CD34⁺ blasts. In contrast, the frequency of these lymphocytes was increased in proximity to CD34⁺ blasts in both MDS and sAML independent of the karyotype, genetic alterations frequently detected in MDS, clinical risk stratification systems or treatment response to hypomethylating agents. Furthermore, an increased frequency of CD3⁺CD8⁺ T cells and MUM1p⁺ CD3^- B cells was found in responders to epigenetic drugs. Conclusions: Thus, we conclude that (i) T cell subsets do not belong to the normal stem cell niche, (ii) the presence of T and B cell subpopulations not directly affect the course of MDS, (iii) lymphocytes in the proximity to CD34⁺ blasts might indicate defective stem cell properties and (iv) the number of lymphocytes is a predictor of therapy response to hypomethylating agents.

Cell free systems are a widely used research tool in systems and synthetic biology and a promising platform for manufacturing of proteins and chemicals. In the past, cell free biology was primarily used to better understand fundamental biochemical processes. Notably, E. coli cell free extracts were used in the 1960s to decipher the sequencing of the genetic code. Since then, the transcription and translation capabilities of cell free systems have been repeatedly optimized to improve energy efficiency and protein yield. Today, cell free systems, in combination with the rise of synthetic biology, have taken on a new role as a promising technology for just in time manufacturing of therapeutically important biologics and high-value small molecules. They have also been implemented in an industrial scale for the production of antibodies and cytokines. In this review, we discuss the evolution of cell free systems, advancements in cell free protein synthesis, and cell free metabolic engineering, and conclude with discussing the importance and feasibility of mathematical modeling in cell free systems.

Cell death resistance is a key feature of tumor cells. One of the main anti-cancer therapies is increasing the susceptibility of cells to death. Cancer cells have developed a capability of tumor immune escape. Hence, restoring the immunogenicity of cancer cells can be suggested as an effective approach against cancer. Accumulating evidence proposes that several anticancer agents provoke the release of danger-associated molecular patterns (DAMPs) that are determinants of immunogenicity and stimulate immunogenic cell death (ICD). It has been suggested that ICD inducers are two different types according to their various activities. Here, we review the well-characterized DAMPs and focus on the different types of ICD inducers and recent combination therapies that can augment the immunogenicity of cancer cells.

Angiogenesis, the sprout and growth of new blood vessels from existing vasculature, is an important process of tumor development for the supply of oxygen and nutrition to cancer cells. Endothelial cell is a critical player in angiogenic process by modulating cell proliferation, cell motility, and cell morphology in the response to pro-angiogenic factors and environments provided by tumor and cancer cells. Recent in vivo and in vitro studies have revealed that gap junction of endothelial cells also participates in the promotion of angiogenesis. Pro-angiogenic factors modulate gap junction function and connexins expression in endothelial cells, whereas endothelial connexins involve in angiogenic tube formation and cell migration of endothelial cells via both gap junction channel function dependent or independent mechanisms. In particular, connexin might have the potential to regulate cell mechanics such as cell morphology, cell migration, and cellular stiffness that are dynamically changed during angiogenic processes. Here, we review the implication for endothelial gap junction and cellular mechanics in vascular angiogenesis.

Alterations in gene expressions are often due to epigenetic modifications that can lead to significant influence on cancer development, growth, and progression. The main epigenetic modifications observed in human are methylation and acetylation. In this regard, the HDAC inhibitors (HDACi) such as SAHA (Vorinostat), which can exert epigenetic alterations through impacting the acetylation status of histones, are in clinical trials as a new class of drugs with promising effects on the cancer growth and metastatic process. The small molecule RG7388 is a newly developed inhibitor that is specific for an oncogene-derived protein called MDM2, which is in clinical trials for the treatment of various types of cancers. One of the common characteristics for these two drugs is their ability to induce p21 expression through distinct mechanisms in MCF-7 and LNCaP cells. This difference was expected trigger cell cycle arrest and cell death through intra-cellular mechanisms that are not identical. Hence, the molecular mechanism whereby SAHA can induce cell cycle arrest and trigger necrosis, apoptosis or necroptosis is still evolving. Similarly, the ability of RG7388 for producing anticancer effect is undergoing thorough investigation, since it can produce p53 dependent and p53 independent effects. In this study we performed experiments to measure the cell cycle arrest effects of SAHA and RG7388 on using MCF-7 and LNCaP cells. The cytotoxicity, cell cycle arrest and apoptosis/necroptosis effects of the treatments were assessed by using Trypan Blue Dye Exclusion (TBDE) method, MTT assay, Fluorescence assay with DEVD-amc fluorogenic substrate and Immunoblotting methods. Our results from MCF-7 and LNCaP cells confirmed that SAHA and RG7388 treatments were able to induce cell death via combination of cell cycle arrest and cytotoxic mechanisms. We are speculating that our findings could lead to the development of newer treatments for breast and prostate cancers using this type of combinations.

Enamel matrix derivative (EMD) is used for periodontal tissue regeneration therapy, and can induce mineralization in dental pulp cells (DPCs). We designed a synthetic peptide (SP) derived from the response of cells to EMD, and investigated the effect of the SP on potentiating osteogenesis in DPCs, which have a critical role of dental pulp homeostasis. DPCs were treated with 0, 10, 100, or 1000 ng/mL SP to determine its effect on cell proliferation, cell migration, cell differentiation, and mineralization. We then examined the molecular effects of the SP, focusing on changes in the mitogen-activated protein kinases (MAPK) signaling pathway in these cells. The SP significantly promoted DPC proliferation and migration. Cultures treated with the SP also showed an enhanced expression of markers of osteogenic differentiation and mineralization. The SP also induced the activation of MAPK signaling pathway components. These results suggest that our SP could promote the dental pulp tissue repair by hard tissue formation and the mineralization through activating MAPK signaling pathway. This study provides the first evidence that SP might be a new material for dental pulp tissue treatment.

TTF1-NP(5,2′,4′-trihydroxy-6,7,5′-trimethoxyflavone nanoparticles), derived from the traditional Changbai Mountain medicinal plant Sorbaria sorbifolia (SS), has been showedits anti-cancer effect in various liver cancer cell types and tissues. The present study was designed to evaluate the antitumor mechanism of the TTF1-NP against HepG2 hepatoma cells and HepG2 cells-induced hepatocarcinoma (HCC) in nude mouse model. Here we demonstrated that TTF1-NP inhibits tube formation of HUVECs and HepG2 cell migration and invasion, and inhibits tumor growth in nude mice implanted with HepG2 cells through the downregulation of STAT3 protein and activation, along with VEGF, KDR, bFGF, MMP2 and MMP9 levels. We further revealed that TTF1-NP decreased the DNA-binding capacity of STAT3. Together our results provide a mechanism by which TTF1-NP suppresses cancer cell migration, invasion and angiogenesis through the action of STAT3 and suggests TTF1-NP as a potential therapy for hepatocellular cancer treatment.

This study empirically analyzes the effectiveness of resource optimization utilizing artificial intelligence (AI) within cloud computing environments. It compares systems that have been transitioned from a Monolithic structure to Microservices Architecture (MSA) with those adopting a simple Rehost strategy, to validate the operational efficiency of two systems whose resource efficiency has been enhanced compared to traditional legacy systems. The research is based on systems that determined resource efficiency post-cloud migration using APM tools. It points out the limitations of traditional heuristic operation methods in resource optimization, which lead to issues such as application performance degradation, resource over-allocation, and increased operational costs. This study aims to overcome the conventional resource optimization standards that depended on the average peak usage of CPU and memory infrastructure, by introducing AI-based optimization tools, and applying on-premise standards to cloud and container environments to achieve resource optimization. The paper emphasizes the importance of resource optimization through AI-based automation tools, exploring the possibilities of resolving real-world application performance issues in cloud environments, reducing unnecessary resource usage costs, and cutting down on labor risks and operational expenses. Through this, it presents strategic directions on how AI technology can offer financial and operational advantages in managing cloud resources.

Al has very good corrosion resistance and corrosion properties. The corrosion resistance of Al cast alloys is different because these alloys contain a lot of elements. Especially in secondary alloys which contain more impurity elements from which Fe is the most common. This study deals with secondary AlSi7Mg0.3 cast alloys which contain more Fe and are affected by a chloride corrosion environment. This environment was selected based on the application of castings in the automo-tive industry. The main object was to research the effect of such an environment on basic me-chanical properties and fatigue properties. The results show that a higher Fe content does not lead to a significant reduction in the properties of the casting and the chloride environment is not so harmful. Therefore, can be stated that the investigated secondary sand-cast experimental materials can replace the primary alloys without losing the required corrosion and mechanical properties.

E-tourism is one of the most important modern services to achieve the development of the tourism sector while relying on sophisticated communication technologies. Certainly, these innovations in the field of tourism have disrupted this sector with new and different dimensions of tourism development. This has led various regions and countries to accelerate the search for the tools that are necessary to achieve excellence and sustainable development in tourism. This research aims to study the development factors of e-tourism to achieve excellence and sustainable development in the tourism of the Ha’il region. Therefore, we applied two analyses: in the first one, we used a statistical analysis based on the survey sent to employees from tourism companies. The objective of this analysis is to determine the main factors of e-tourism to achieve excellence in tourism in the Ha’il region. The results of the statistical analysis have given us the following elements: There are only four main factors that allow authorities to achieve excellence in tourism in the Ha’il region, namely ST, CP, HRS, and SC factors. Then we proceed with a second analysis, to determine the main factors of excellence in tourism that drive the achievement of sustainable development in tourism in the Ha’il region. For this reason, we applied an artificial intelligence method based on the unsupervised machine learning technique. The results obtained from the machine learning technique show that five factors determine the excellence in tourism and reveal the sustainable development of Ha’il’s tourism. These factors are ST, CP, FP, HRS, and GC. Consequently, we consider that all the factors found in both analyses are important to realise excellence in tourism and sustainable development in tourism. However, to achieve sustainable development in tourism in Ha’il, Saudi authorities must develop the three common factors found in the two analyses, namely ST, CP, and HRS.

The effect of the melt cooling rate on the atomic ordering of austenite and, as a consequence, on the martensitic transformation of a nonstoichiometric alloy of the Ni-Mn-In system has been studied. In-situ TEM observations revealed differences in the mechanism of phase transformations of the alloy subjected to different cooling conditions. It is shown that during quenching a high density of antiphase boundaries (APB) is formed and the alloy is in the austenite-martensitic (10M and 14M) state up to a temperature of 120K. In a slowly cooled alloy, a lower APB density is observed, and a two-stage transformation L21/B2 → 10M → 14M occurs in the range of 150–120 K.

Purpose: When it comes to improving citizen service delivery standard and processes, or broadly, management in government (MIG), many reform programs and improvement efforts are ongoing across different ministries, departments, and agencies. This paper is part of a larger empirical research where we are interested to know what those programs and projects are, and how they are doing, and what the gaps are. Design/methodology/approach: Analyzing the publicly available data on the government portal and donors’ website, this article provides an overall idea of current reforms in various places of government. In parallel, field research was conducted through visiting agency offices, observing office environment and mechanisms, and interviewing public managers who are working at district and sub-district level offices of directorates or agencies.Findings: As a trend, state-led development process and the traditional mode of administration have moved to New Public Management based quality and performance approach. All donors have their own strategy framework document like ‘Country Assistance strategy’, ‘Country Operations and Business Plan’, Logical Framework Document, Focus or Priority Streams, etc. Many of the projects are sectoral and agency or ministry specific and have an inherent limitations, due to ‘cadre’ based organizational structural arrangement. So, it is common ‘not to own the projects’, rather ‘using the fund as much as possible anyway within the given project duration’. When the fund ends, implementing units, either government or NGOs, abandon the projects. That is why many projects are actually half done without significant and sustained direction.Originality/value: We can conclude that the typical ‘top-down’ or ‘trickle down’ conception is still dominant in design and implementation of reforms programs and service quality efforts. So, how to reach systemically at the bottom where public managers provide services to citizens, needs even more deliberation.

Policies are adopted and implemented to achieve specific goals. In this regard, the Government of Zambia in 2019 adopted the higher education policy with many objectives which include, the expansion of access to higher education; reduction of gender and other forms of inequity in accessing higher education; the improvement of quality of higher education by increasing funding to higher education institutions, construction, and repair of infrastructure in higher and improvement in the provision of learning materials in higher education institutions (HEIs).This paper, therefore, sought to evaluate the higher education policy of 2019. The four criteria were used namely; effectiveness, equity, policy sustainability, and consistency. Other principles such as political and social acceptability of a policy were not used because the policy is already adopted and being implemented. Further, the principle of efficiency was not used because it would have been problematic to gauge the expenditure against the outcomes.The findings have revealed that the policy to some extent has been effective; some of the objectives such as increased access to higher education and reduction of inequality have been partially achieved. It has been established that the number of students pursuing higher education has been increased to 114,049 in 2020 from 91,969 in 2017. Further, in 2021, 48.5% of scholarships in public universities were awarded to female students while 51.5% were awarded to female students. Further, more students are encouraged to pursue science, technology, engineering, and mathematics (STEM); and more women are pursuing studies in STEM-related fields. However, the policy has not helped to achieve the quality of higher education as funding in public HEIs has not improved. Further, infrastructure remains very poor and inadequate; and access to update and relevant learning materials also remains a challenge in HEIs. However, the policy seems to be duplicated by the recent re-launched Technical Education Vocation Entrepreneurship Training (TEVET) national policy.Given the above findings, it has been recommended that the government among other things improve funding and build infrastructure in public HEIs. There is also a need to harmonise the TEVET national policy with the higher education policy.

Malassezia is a lipid-dependent genus of yeasts known for being an important part of the skin mycobiota. These yeasts have been associated in the development of skin disorders and cataloged as a causal agent of systemic infections under specific conditions, making them opportunistic pathogens. Little is known about the host-microbe interaction of Malassezia spp., and unraveling this implies the implementation of infection models. In this mini review we present different models that have been implemented in the fungal infections study with greater attention in Malassezia spp. infections. These models range from in vitro (cell cultures and ex vivo tissue), to in vivo (murine models, rabbits, guinea pigs, insects, nematodes, and amoebas). We additionally highlight the alternative models that reduce the use of mammals as model organisms, which have been gaining importance in the study of fungal host-microbe interactions. This is due to the fact that these systems have shown to have reliable results, which correlate with those obtained from mammalian models. Example of alternative models are Caenorhabditis elegans, Drosophila melanogaster, Tenebrio molitor, and Galleria mellonella. These are invertebrates that have been implemented in the study of Malassezia spp. infections in order to identify differences in virulence between Malassezia species.

Academic entrepreneurship focuses on commercialization of research. Even though it is practiced worldwide for decades, Bangladesh is a newcomer in this segment. In Bangladesh only 2 Universities have Technology Transfer Offices or TTOs which are established with the sole focus of commercialization of researches of the students and the faculty members of the Universities. This article focuses on worldwide practices of technology transfer and academic entrepreneurial activities and also explores the opportunities and challenges of such entrepreneurs through detail investigation of the existing body of knowledge. Apart from exploring the problems and prospect of academic entrepreneurship in Bangladesh, this article also introduces the concept of Full-Service Knowledge Transfer Office (KTO), which existing literatures do not offer. The authors believe that by establishing such KTOs as a self-sustaining body, it is possible for an academic entrepreneur to stimulate, support and sustain their activities in Bangladesh. The concept of full service KTOs can also become models for other nations, specially the developing ones, to establish and nurture a culture of academic entrepreneurship.

Far-red fluorescent reporter genes can be used for tracking cells non-invasively in vivo using fluorescence imaging. Here, we investigate the effectiveness of the far-red fluorescent protein, E2-Crimson (E2C), for tracking mouse embryonic cells (mESCs) in vivo following subcutaneous administration into mice. Using a knock-in strategy, we introduced E2C into the Rosa26 locus of an E14-Bra-GFP mESC line, and after confirming that the E2C had no obvious effect on the phenotype of the mESCs, we injected them into mice and imaged them over 9 days. The results showed that fluorescence intensity was weak, and cells could only be detected when injected at high densities. Furthermore, intensity peaked on day 4 and then started to decrease, despite the fact that tumour volume continued to increase beyond day 4. Histopathological analysis showed that although E2C fluorescence could barely be detected in vivo at day 9, analysis of frozen sections indicated that all mESCs within the tumours continued to express E2C. We hypothesise that the decrease in fluorescence intensity in vivo was probably due to the fact that the mESC tumours became more vascular with time, thus leading to increased absorbance of E2C fluorescence by haemoglobin. We conclude that the E2C reporter has limited use for tracking cells in vivo, at least when introduced as a single copy into the Rosa26 locus.

NK population is characterized by distinct NK cell subsets which respond differently to the various activating stimuli. For this reason, the determination of the optimal cytotoxic activation of the different NK subsets can be a crucial aspect to be exploited to counter cancer cells in oncologic patients. To evaluate how the triggering of different combination of activating receptors can affect the cytotoxic responses of different NK cell subsets, we developed a microbead-based degranulation assay. By using this new assay, we were able to detect CD107a+ degranulating NK cells even within the less cytotoxic subsets (i.e. resting CD56bright and unlicensed CD56dim NK cells), thus demonstrating its high sensitivity. Interestingly, signals delivered by the co-engagement of NKp46 with 2B4, but not with CD2 or DNAM-1, strongly cooperate to enhance degranulation on both licensed and unlicensed CD56dim NK cells. Of note, 2B4 is known to bind CD48 hematopoietic antigen, therefore this observation may provide the rationale why CD56dim subset expansion correlates with successful hematopoietic stem cell transplantation mediated by alloreactive NK cells against host T, DC and leukemic cells, while sparing host non-hematopoietic tissues and graft versus host disease. The assay further confirms that activation of LFA-1 on NK cells leads to their granule polarization, even if, in some cases, this also takes to an inhibition of NK degranulation, suggesting that LFA-1 engagement by ICAMs on target cells may differently affect NK cell response. Finally, we observed that NK cells undergo a time-dependent spontaneous (cytokine-independent) activation after blood withdrawal, an aspect that may strongly bias the evaluation of the resting NK cell response. Altogether our data may pave the way to develop new NK activation and expansion strategies that target the highly cytotoxic CD56dim NK cells and can be feasible and useful for cancer and viral infection treatment.

In the contemporary era, the movement for women empowerment is not merely a social cause but a transformative force reshaping societies across the globe. The article "Breaking Barriers: Women Empowerment Transforming Societies in Modern Times Building a Better Future" delves into the multifaceted impact of empowering women, highlighting how it transcends individual upliftment and fosters widespread societal progress. It also delves into the transformative impact of women’s empowerment on societies, highlighting successful initiatives, case studies, and personal narratives that illustrate the journey towards gender parity. It examines the challenges and opportunities in this ongoing struggle, emphasizing the need for continued advocacy, education, and policy reform. By fostering an environment where women can thrive, societies can unlock unprecedented potential and build a better, more prosperous future for all. By examining key areas such as education, economic participation, political representation, and social inclusion, the article elucidates how empowering women leads to more equitable, prosperous, and resilient communities. It underscores the importance of dismantling historical and cultural barriers that have long hindered women's potential, while celebrating the strides made towards gender equality. Furthermore, the narrative showcases inspiring stories of women leaders, entrepreneurs, and change-makers who are spearheading efforts to build a better future for all. This exploration not only emphasizes the moral imperative of gender equality but also its critical role in driving sustainable development and global advancement.

The binomial nomenclature system, introduced by Carl Linnaeus in the 18th century, has been fundamental for scientific communication and data management. Despite its utility, some scientific names reflect historical biases and ethical issues, including colonial legacies, racism, sexism, and derogatory terms. Recent debates highlight the need to address these injustices, with arguments both for and against revising such names. Critics argue that extensive revisions could disrupt scientific stability, while proponents emphasize the moral imperative to correct these issues. In this opinion paper, we advocate for the establishment of a dedicated committee within international nomenclature bodies to revise taxonomic names with clear ethical concerns and recommend the use of persistent identifiers to effectively manage and track name changes, mitigating potential disruptions to taxonomy and the science that depends on it. By adopting transparent revision processes and making use of digital technology, we can address ethical issues without remarkable upheaval. Science should not perpetuate historical injustices, and it is vital for the scientific community to proactively address social injustices in nomenclature to mitigate ongoing debates and resistance.

Triple-negative breast cancer (TNBC) is an aggressive and highly metastatic type of tumor. TNBC is often enriched in tumor-infiltrating neutrophils (TINs), which support cancer growth in part by counteracting tumor-infiltrating lymphocytes (TILs). Prior studies identified the enhancer of zeste homolog 2 (EZH2) as a pro-tumor methyltransferase in primary and metastatic TNBC. We hypothesized that EZH2 inhibition in TNBC cells per se would exert anti-tumor activity by altering the tumor immune microenvironment. To test this hypothesis, we used CRISPR to generate EZH2-knockout (KO) and overexpressing lines from parent (wild-type -WT) 4T1 cells, an established murine TNBC model. In vitro, EZH2 KO and OE cells showed little change in replicative capacity and invasiveness, but marked changes in surface marker profile and cytokine/chemokine secretion compared to WT cells. On in vivo injection, EZH2 KO cells showed significantly reduced primary tumor growth and a 10-fold decrease in lung metastasis compared to WT cells, while EZH2 OE cells were unchanged. Compared to WT tumors, TIN:TIL ratios were greatly reduced in EZH2 KO tumors but unchanged in EZH2 OE tumors. Our findings show a tumor-intrinsic role of EZH2 in the 4T1 TNBC model in regulating TIN/TIL poise, primary tumor progression and lung metastasis in vivo.

The Epithelial- Mesenchymal Transition (EMT) is a biological phenomenon associated with explicit phenotypic and molecular changes in cellular traits. Unlike the earlier-held popular belief of it being a binary process, EMT is now thought of as a landscape including diverse hybrid E/M phenotypes manifested by varying degrees of the transition. These hybrid cells can co-express both epithelial and mesenchymal markers and/or functional traits, and can possess the property of collective cell migration, enhanced tumor-initiating ability, and immune/targeted therapy-evasive features, all of which are often associated with worse patient outcomes. These characteristics of the hybrid E/M cells have led to a surge in studies that map their biophysical and biochemical hallmarks that can be helpful in exploiting their therapeutic vulnerabilities. This review discusses recent advances made in investigating hybrid E/M phenotype(s) from diverse biophysical and biochemical aspects by integrating live cell-imaging, cellular morphology quantification and mathematical modeling, and highlights a set of questions that remain unanswered about the dynamics of hybrid E/M states.

Connexin 43 (Cx43) forms gap junctions that mediate the direct intercellular diffusion of ions and small molecules between adjacent cells. Cx43 displays both pro- and anti-tumorigenic properties, but the mechanisms underlying these characteristics are not fully understood. Tunneling nanotubes (TNTs) are long and thin membrane projections that connect cells, facilitating the exchange of not only small molecules, but also larger proteins, organelles, bacteria, and viruses. Typically, TNTs exhibit increased formation under conditions of cellular stress and are more prominent in cancer cells, where they are generally thought to be pro-metastatic and to provide growth and survival advantages. Cx43 has been described in TNTs, where it is thought to regulate small molecule diffusion through gap junctions. Here, we developed a high-fidelity CRISPR/Cas9 system to knockout (KO) Cx43. We found that loss of Cx43 expression was associated with significantly reduced TNT length and number in breast cancer cell lines. Notably, secreted factors present in conditioned medium stimulated TNTs more potently when derived from Cx43-expressing cells than from KO cells. Moreover, TNT formation was significantly induced by inhibition of several key cancer signaling pathways that both regulate Cx43 and are regulated by Cx43, including RhoA kinase (ROCK), protein kinase A (PKA), focal adhesion kinase (FAK), and p38. Intriguingly, drug-induced stimulation of TNTs was more potent in Cx43 KO cells than in wild-type cells. In conclusion, this work describes a novel non-canonical role for Cx43 in regulating TNTs, identifies key cancer signaling pathways that regulate TNTs in this setting, and provides mechanistic insight into a pro-tumorigenic role of Cx43 in cancer.

In this paper a new double-nozzle technique for in-gas-jet laser resonance ionization spectroscopy is proposed. The functionality of this new technique we explored by detailed gas dynamic and Monte Carlo atom-trajectory simulations, which results are presented and discussed. The results of similar computer simulations for JetRIS setup (as a typical representative of the conventional nowadays in-gas-jet technique) are presented and discussed as well. The direct comparison of calculation results for proposed new technique with the conventional one shows that the double-nozzle technique has many advantages compared with that one used in the JetRIS setup at GSI for future high-resolution laser spectroscopic study of heaviest elements. To fully implement the proposed new technique to all existing (or under construction) setups for in-gas-jet laser resonance ionization spectroscopy, it will be enough just replace the used their supersonic nozzle by the miniature double-nozzle device described in the paper.

Refractory materials are used worldwide in process equipment. However, gaseous and liquid process products penetrate the surface layer, and deep into the volume of refractories destructing rather expensive constructions complicated to repair. To address this challenge, there is a need to develop protective coatings for refractory that can limit the penetration of working media and extend their operational lifespan. In this work, the application of gas-dynamic cold spraying (CGDS) to produce a coating on the refractory using fine titanium dioxide (TiO2) particles is explored. These particles are accelerated within a nitrogen flow, passing through a Laval nozzle, and then sprayed onto a fireclay surface. The mechanisms of particle deposition and layer formation on porous surfaces through experiments and numerical simulations were investigated. The geometry of a typical refractory pore was determined, which was then incorporated into Computational Fluid Dynamics (CFD) simulations to model the cold spraying process of porous substrates. As a result, the influence of the particle size on its velocity and angle of penetration into pores was established. Experimental findings demonstrate the effective closure of pores and the formation of a particle layer on the refractory surface. Furthermore, the nanoindentation tests for the refractory samples showcase capabilities for checking coating thickness for porous materials.

This paper presents a new optimization algorithm to control the voltage of power system generators by the simultaneous tuning of the parameters of Automatic Voltage Regulator (AVR) and Power System Stabilizer (PSS) using a new technique called Particle Swarm Optimization with Periodic Oscillating Exponential Decay (PSO - POED). The proposed algorithm was applied to both the Single-Machine Infinite-Bus (SMIB) Power System and the 9-Bus Multi-Machine Power System. The results of the simulation show that the proposed method is efficient and guarantees an improvement in the dynamic stability and convergence rate of the simulations.

Particulate organic carbon (POC) is a pivotal component within the marine carbon cycle, actively involved in diverse biogeochemical processes. This study focuses on Mediterranean as the research region, selecting the most influential factors from 47 potential ones influencing surface POC. Using geographic detector for factor identification, ten primary influencers were identified. Preliminarily optimized random forest (BRF), backpropagation neural network, adaptive boosting, and extreme gradient boosting were utilized to construct POC assessment models. Notably BRF exhibited superior performance in estimating the sea surface POC. Further optimization of RF using the tuneRanger R package resulted in R² of 0.868, mean squared error of 1.119 (mg/m³) ², and mean absolute error of 1.041 (mg/m³). Surface POC concentrations in the Mediterranean for May and June 2017 were estimated. Spatial distribution analysis unveiled higher concentrations in the west, lower in the east, higher in the north, lower in the south, with higher levels near the coast and lower far from the coast. Additionally, the study deliberated on the impact of human activities on surface POC in the Mediterranean. This research contributes a high-precision method for satellite retrieval of surface POC concentrations in the Mediterranean, thereby enriching the understanding of POC dynamics in the area.

Shape-shifting polymers are widely used in various fields such as intelligent switches, soft robots and sensors, which require both multiple stimulus response functions and qualified mechanical strength. In this study, a novel near infrared light (NIR) responsible shape-shifting hydrogel system was designed and fabricated, through embedding vinylsilane modified carbon nanotubes (CNTs) into particle-double network (P-DN) hydrogels by micellar copolymerization. The dispersed brittle Poly(sodium 2-acrylamido-2-methylpropane-1-sulfonate) (PNaAMPS) network of the microgels can serves as sacrificial bonds to toughen the hydrogels, and the CNTs endow it NIR photothermal conversion ability. The results show that the CNTs embedded P-DN hydrogels present excellent mechanical strength, i. e. fracture strength of 312 kPa and fracture strain of 357%. Moreover, an asymmetric bilayer hydrogel, where the active layer contains CNTs, can achieve 0°–110° bending deformation within 10 min under NIR irradiation and can realise complex deformation movement. This study provides a theoretical and experimental basis for the design and manufacture of photoresponsive soft actuators.

Accurate medical image segmentation is paramount for precise diagnosis and treatment in modern healthcare. This research presents a comprehensive study on the efficacy of Particle Swarm Optimization (PSO) combined with Histogram Equalization (HE) preprocessing for medical image segmentation, focusing on Lung CT-Scan and Chest X-ray datasets. Best Cost values reveal the PSO algorithm’s performance, with HE preprocessing demonstrating significant stabilization and enhanced convergence, particularly in complex Lung CT-Scan images. Evaluation metrics, including Accuracy, Precision, Recall, F-Score, Specificity, Dice, and Jaccard, show substantial improvements with HE preprocessing, emphasizing its impact on segmentation accuracy. Comparative analyses against alternative methods, such as Otsu, Watershed, and K-means, confirm the competitiveness of the PSO-HE approach, especially in Chest X-ray images. The study also underscores the positive influence of preprocessing on image clarity and precision. These findings highlight the promise of the PSO-HE approach in advancing the accuracy and reliability of medical image segmentation, paving the way for further research and method integration to enhance this critical healthcare application.

In this paper, the effects on the rheological properties, particle size distribution, and fluorescence properties of red wine were investigated under microwave irradiation, and the mechanism of the effects of microwave irradiation on the sensory properties of red wine was discussed. The results showed that the effect of microwave on the rheological properties in red wine could be fitted by the Power-law model and Carson model, through the analysis of the rheological constants, yield stress, and viscosity coefficient of wine, it was found that microwave treatment could improve leg phenomenon and thickening effect by the change of rheological properties; the particle size distribution in wine indicated that microwave irradiation did change the particle size distribution through friction effect and oxidative polymerization, resulting in the wine’s visual effect and mouthfeel; the wine quality could be improved by enhancing the fluorescence intensity under different microwave conditions, which meant that microwave technology could speed up the formation of fluorescent substances, such as the polymerization of flavan-3-ols. In conclusion, microwave treatment could modify the sensory characteristics of wine, and further provide the theoretical basis for the application of microwave in winemaking.

This paper presents a novel approach for the recognition of multiple sclerosis (MS) using wavelet entropy and a Particle Swarm Optimization (PSO)-based neural network. MS is a complex neurological disorder with diverse clinical manifestations, often challenging to diagnose accurately. In this study, we leverage wavelet entropy (WE) as a feature extraction method to capture intricate patterns within brain imaging data. These extracted features are then employed to train a neural network model optimized through PSO to enhance classification accuracy. Experimental results on a dataset comprising MS and healthy control subjects demonstrate the effectiveness of our proposed approach, viz., WE-PSONN, which achieves a sensitivity of 91.95±1.15, a specificity of 92.36±0.88, a precision of 92.28±0.88, an accuracy of 92.16±0.90. The combination of advanced signal processing techniques and machine learning optimization holds promise for improving the early diagnosis and management of MS, offering potential benefits to both patients and healthcare providers.

In this work, the nearest neighbor distances and Voronoi cell features of the Cu-Ag deposits were analyzed and fitted with Lognormal, Weibull, and Gamma distributions. The nearest neighbor distance distributions of the samples were compared with those of complete spatially random points, showing spatial inhomogenity due to the nucleation exclusion effect. The radial distribution function was calculated, showing both influences from the grain size and the nucleation exclusion effect. Voronoi cells were generated based on the shape of the grains. The size, occupancy, and coordination of the Voronoi cells were examined and fitted. The results show that despite the Cu-Ag deposits seem to be governed by instantaneous nucleation mode, the spatial distribution of the nuclei is more impacted by the nucleation exclusion effect than the Cu-only samples. This behavior is also justified by the grain size distribution generated with Voronoi cell size and occupancy distributions.

This study examines the effects of particle size and heat pipe angle on the thermal effectiveness of a cylindrical screen mesh heat pipe using silver nanoparticles as the test substance. The experiment investigates three different particle sizes (30nm, 50nm, and 80nm) and four different heat pipe angles (0°, 45°, 60°, and 90°) on the heat transmission characteristics of the heat pipe. The results show that the thermal conductivity of the heat pipe increased with an increase in heat pipe angle for all particle sizes, with the highest thermal conductivity attained at a 90° heat pipe angle. Furthermore, the thermal resistance of the heat pipe decreased as the particle size decreased for all heat pipe angles. The thermal conductivity measurements of the particle sizes - 30, 50, and 80 nm - were 250 W/mK, 200 W/mK, and 150 W/mK, respectively. The heat transfer coefficient values for particle sizes 30nm, 50nm, and 80nm were 5500 W/m2K, 4500 W/m2K, and 3500 W/m2K, respectively. The study also found that the heat transfer coefficient increased with increased heat pipe angle for all particle sizes, with the highest heat transfer coefficient obtained at a 90° heat pipe angle.

Diabetes is a serious health problem throughout the world, including in Indonesia. The International Diabetes Federation (IDF) reports that the number of adults with diabetes is increasing every year. The Behavioral Risk Factor Surveillance System (BRFSS) is a survey conducted by the Centers for Disease Control and Prevention (CDC) in the United States. Classification methods in data mining techniques are used to classify diabetics and non-diabetics. The data mining process is carried out by preprocessing, feature selection, and dataset classification stages. In the preprocessing stage, data cleaning, data formatting, and data oversampling are carried out using the Synthetic Minority Over-sampling Technique (SMOTE). Next, the feature selection stage is carried out using the Particle Swarm Optimization (PSO) algorithm to find the best attributes. The dataset classification stage is carried out using the CART Model Decision Tree algorithm. The results of the performance evaluation of the CART algorithm are calculated using the confusion matrix and the MAE value, the results obtained for the CART algorithm without SMOTE and PSO obtained the best accuracy of 75.34% and the MAE value of 0.2466, while the CART algorithm using SMOTE and PSO can increase accuracy by 10 .94% to 86.28% and an MAE value of 0.1372.

In current study, the production of microparticles from fifteen commercial sugarcane pulp (SCP) lunch-boxes into different types of food under different conditions was investigated, where we used DI water, 4% HAc, and 95% EtOH to simulate aqueous, acidic, and fatty foods. Results showed that compared with DI water and 95% EtOH, 4% HAc caused the degradation of sugarcane fibers, resulting in the highest number of microparticles released, which was significantly greater than the specified limit value. It was estimated that consumers might intake a total number of 36,400 ~ 231,700 items per meal per lunch-box, of which the proportion of microparticles with particle size between 100 ~ 500 μm was the largest, with a number of 12,376 ~ 130,795 items. Moreover, of all SCP lunch-box except S-11, Al and Fe are the main metals, ranging between 35.16 ~ 1244.04 and 44.71 ~ 398.52 mg/kg, respectively, followed by Pb, Ti, and Sr. Interestingly, unlike other lunch-boxes, the content of Pb in S-11 was the highest, with a number of 136 mg/kg. This study provides important information that the safeness including both the production of microparticles and the metallic elements should be considered for SCP lunch-boxes when in contact with food.

We still do not have satisfactory answers about the inflationary and accelerating expansions of the universe, the missing mass problem, and the origins of the four fundamental forces and the quantum phenomena. Here, we introduce a new model of matter and space and a postulate on a constant of motion, and then show that an equation of motion derived from the constant of motion could provide new understandings of the above problems. For example, we show that there is a natural inflation scenario and that the co-moving distance to the closest accelerating supernova is clearly given as $c/(\sqrt{3} H)$ ($\sim$8.1 billion ly). In addition, we show that, in a system including a proton and an electron, the equation of motion has eight acceleration terms, some of which are suspected to be responsible for the four fundamental forces and the galaxy rotation anomaly. From further discussion, we conjecture that in order to understand the gravitational and strong interactions and the quantum phenomena, it is necessary to consider the expansion of the universe. The lensing mass distribution is explained, based on another postulate on a method of representing superposition.

We consider a new model of a branching random walk on a multidimensional lattice with continuous time and one source of particle reproduction and death, as well as an infinite number of sources in which, in addition to the walk, only absorption of particles can occur. The asymptotic behavior of the integer moments of both the total number of particles and the number of particles at a lattice point is studied depending on the relationship between the model parameters. In the case of the existence of an isolated positive eigenvalue of the evolution operator of the average number of particles, a limit theorem is obtained on the exponential growth of both the total number of particles and the number of particles at a lattice point.

Syntactic foam has proven to be a good material with a strong structural strength. Understanding filler particle size variation is important in composite material formation especially in syntactic foam because of their numerous applications such as aerospace, marine and structural purposes. In this present work, the effects of particle variation in different sizes (20-24µm, 25-44µm, 45-49µm, and 50-60µm) on the mechanical properties of the syntactic foam composites with focus on flexural strength, modulus, and fracture surfaces were investigated. The particle sizes were varied into five volume fractions (5, 10, 15, 20, and 25vol%). The results shows that highest flexural strength is 89MPa at 5 vol% fraction of 50-60µm particles size variation which is 69% increase than the neat epoxy. This implies that the incorporation of HGM filler volume fraction and size variation has a strong effect on the flexural strength and bending modulus of syntactic foam. The microstructure of the fracture surfaces and the viscoelastic properties was determined and reported accordingly.

In this paper, we investigated the trajectory of the massive particle in the vicinity of a general spherical symmetric black hole. Also, in the framework of general sphericalily symmetric black hole, Pseudo-Newtonian potential (PNP) and effective potentials has been investigated. As an example, static spherically symmetric black hole in f(R) gravity is considered and presented the brief discussion on the structure of spacetime and horizons. We calculated energy and angular momentum in the framework of general relativity as well as in Pseudo-Newtonian theory. A graphical comparison of angular momentum in this both framework has been studied.

In this paper, the definition of information entropy of Smoluchowski coagulation equation for Brownian motion is introduced based on coagulation probability. The expression of entropy is the function of geometric average particle volume and standard deviation with lognormal distribution assumption. The asymptotic solution with moment method shows that the entropy is a monotone increasing function of time, which is equivalence to the entropy based on particle size distribution. the result reveals that the present definition of entropy of Smoluchowski coagulation equation are inadequate because the particle average volume at equilibrium cannot be determined from the principle of maximum entropy. This provides a basis for further exploring the global properties of Smoluchowski coagulation equation.

We report interfacial crystallization in droplets of saline solutions placed on superhydrophobic surfaces and liquid marbles filled with the saline. Evaporation of saline droplets deposited on superhydrophobic surface resulted in the formation of cup-shaped millimeter-scaled residues. The formation of the cup-like deposit is reasonably explained within the framework of the theory of the coffee-stain effect, namely, the rate of heterogeneous crystallization along the contact line of the droplet is many times higher than in the droplet bulk. Crystallization within evaporated saline marbles, coated with lycopodium particles, depends strongly on the evaporation rate. Rapidly evaporated saline marbles yielded dented shells built of a mixture of colloidal particles and NaCl crystals. We relate the formation of these shells to the interfacial crystallization promoted by hydrophobic particles coating the marbles, accompanied with the upward convection flows supplying the saline to the particles, serving as the centers of interfacial crystallization. Convective flows prevail over the diffusion mass transport for the saline marbles heated from below.

With the every passing day, the demand for data traffic is increasing and this demand forces the research community not only to look for alternating spectrum for communication but also urges the radio frequency planners to use the existing spectrum smartly. Cell size is shrinking with the every upcoming communication generation which makes the base station placement planning complex and cumbersome. In order to make the next-generation cost-effective, it is important to design the network in such a way which utilizes minimum number of base stations while ensure coverage and quality of service. This paper aims at develop a new approach using hybrid metaheuristic and metamodel applied in multi-transmitter placement planning (MTPP) problem. We apply radial basis function (RBF) metamodel to assist particle swarm optimizer (PSO) in a constrained simulation-optimization (SO) of MTPP to mitigate the associated computational burden of optimization procedure. We evaluate the effectiveness and applicability of proposed algorithm in a case study by simulating MTPP model with two, three, four and five transmitters.

Particles in classical physics are distinguishable objects, which can be picked out individually on the basis of their unique physical properties. By contrast, in quantum mechanics the standard view is that particles of the same kind (``identical particles'') are completely indistinguishable from each other. This standard view is problematic: Particle indistinguishability is irreconcilable not only with the very meaning of ``particle'' in ordinary language and in classical physical theory, but also with how this term is used in the practice of present-day physics. Moreover, the indistinguishability doctrine prevents a smooth transition from quantum particles to what we normally understand by ``particles'' in the classical limit of quantum mechanics. Elaborating on earlier work, we here discuss an alternative to the standard view that avoids these and similar problems. As it turns out, this alternative approach connects to recent discussions in quantum information theory concerning the question of when identical particles can be considered to be entangled.

This study aims to model grinding of a Polish slag and evaluate the particle size distributions of the products obtained after different grinding times. Then, selected products were alkali activated in order to investigate the effect of particle size on the compressive strength of the produced alkali activated materials (AAMs). Other parameters affecting alkali activation, i.e. temperature, curing and ageing time were also examined. Among the different mathematical models used to simulate the particle size distribution, Rosin-Rammler (RR) was found to be the most suitable. When piecewise regression analysis was applied to experimental data it was found that the particle size distribution of the slag products exhibits multi fractal character. In addition, grinding of slag exhibits non-first-order behavior and the reduction rate of each size is time dependent. The grinding rate and consequently the grinding efficiency increases when the particle size increases, but drops sharply near zero after prolonged grinding periods. Regarding alkali activation, it is deduced that among the parameters studied, particle size (and the respective specific surface area) of the raw slag product and curing temperature have the most noticeable impact on the compressive strength of the produced AAMs.

This paper presents a discrete particle swarm optimization (DPSO) algorithm with heterogeneous (non-uniform) parameter values for solving the dynamic travelling salesman problem (DTSP). The DTSP can be modelled as a sequence of static sub-problems, each of which is an instance of the TSP. We present a method for automatically setting the values of the DPSO parameters without three parameters, which can be defined based on the size of the problem, the size of the particle swarm, the number of iterations, and the particle neighbourhood size. We show that the diversity of parameter values has a positive effect on the quality of the generated results. We compare the performance of the proposed heterogeneous DPSO with two ant colony optimization (ACO) algorithms. The proposed algorithm outperforms the base DPSO and is competitive with the ACO.

Considering the predictions from the standard model of particle physics coupled with experimental results from particle accelerators, we discuss a scenario in which from the infinite possibilities in the Lie groups we use to describe particle physics, nature needs only the lower dimensional representations - an important phenomenology that we argue indicates nature is code theoretic. We show that the quantum deformation of the SU(2) Lie algebra at the fifth root of unity can be used to address the quantum Lorentz group representation theory through its universal covering group and gives the right low dimensional physical realistic spin quantum numbers confirmed by experiments. In this manner we can describe the spacetime symmetry content of relativistic quantum fields in accordance with the well known Wigner classification. Further connections of the fifth root of unity quantization with the mass quantum number associated with the Poincaré Group and the SU(N) charge quantum numbers are discussed as well as their implication for quantum gravity.

The snow melt from the High Atlas is a critical water resource in Morocco. In spite of its importance, monitoring the spatio-temporal evolution of key snow cover properties like the snow water equivalent remains challenging due to the lack of in situ measurements at high elevation. Since 2015, the Sentinel-2 mission provides high spatial resolution images with a 5 day revisit time, which offers new opportunities to characterize snow cover distribution in mountain regions. Here we present a new data assimilation scheme to estimate the state of the snowpack without in situ data. The model was forced using MERRA-2 data and a particle filter was developed to dynamically reduce the biases in temperature and precipitation using Sentinel-2 observations of the snow cover area. The assimilation scheme was implemented using SnowModel, a distributed energy-balance snowpack model and tested in a pilot catchment in the High Atlas. The study period covers 2015-2016 snow season which corresponds to the first operational year of Sentinel-2A, therefore the full revisit capacity was not yet achieved. Yet, we show that the data assimilation led to a better agreement with independent observations of the snow height at an automatic weather station and the snow cover extent from MODIS. The performance of the data assimilation scheme should benefit from the continuous improvements in MERRA-2 reanalyses and the full revisit capacity of Sentinel-2.

Direct georeferencing of airborne pushbroom scanner data usually suffers from the limited precision of navigation sensors onboard of the aircraft. The bundle adjustment of images and orientation parameters, used to perform geocorrection of frame images during the post-processing phase, cannot be used for pushbroom cameras without difficulties: it relies on matching corresponding points between scan lines, which is not feasible in the absence of sufficient overlap and texture information. We address this georeferencing problem by equipping our aircraft with both a frame camera and a pushbroom scanner: the frame images and the navigation parameters measured by a couple GPS/Inertial Measurement Unit (IMU) are input to a bundle adjustment algorithm; the output orientation parameters are used to project the scan lines on a Digital Elevation Model (DEM) and on an orthophoto generated during the bundle adjustement step; using the image feature matching algorithm Speeded Up Robust Features (SURF), corresponding points between the image formed by the projected scan lines and the orthophoto are matched, and through a least-squares method, the boresight between the two cameras is estimated and included in the calculation of the projection; finally, using Particle Image Velocimetry (PIV) on the gradient image, the projection is deformed into a final image that fits the geometry of the orthophoto. We apply this algorithm to five test acquisitions over Lake Geneva region (Switzerland) and Lake Baikal region (Russia). The results are quantified in terms of Root Mean Square Error (RMSE) between matching points of the RGB orthophoto and the pushbroom projection. From a first projection where the Interior Orientation Parameters (IOP) are known with limited precision and the RMSE goes up to 41 pixels, our geocorrection estimates IOP, boresight and Exterior Orientation Parameters (EOP) and produces a new projection which RMSE with the reference orthophoto is around two pixels.

The precise prediction of air contaminant dispersion is essential to the air quality monitoring and the emergency management of the contaminant gases leakage incidents in the chemical industry park. The conventional atmospheric dispersion models can seldom give precise prediction due to inaccurate input parameters. In order to improve the prediction accuracy of dispersion model, two data assimilation methods (i.e. one is merely based on the typical particle filter while the other is a combination of particle filter and expectation-maximization algorithm) are proposed to assimilate the UAV observations into the atmospheric dispersion model. Two emission cases are taken into consideration, the difference between which is the different dimensions of state variables. To test the performances of the proposed methods, experiments corresponding to the two emission cases are designed and implemented. The results show that the particle filter can effectively estimate the model parameters and improve the accuracy of model prediction when the dimension of state variables is low. In contrast, when the dimension of state variables becomes higher, the method of particle filter combining expectation-maximization algorithm performs better in the parameter estimation accuracy and warm-up time. Therefore, the data assimilation methods are able to effectively support the air quality monitoring and emergency management in chemical industry parks.

Cell mechanics is a biophysical indicator of cell state, such as cancer metastasis, leukocyte activation, and cell cycle progression. Atomic force microscopy (AFM) is a widely used technique to measure cell mechanics, where the Young modulus of a cell is usually derived from the Hertz contact model. However, the Hertz model assumes that the cell is an elastic, isotropic, and homogeneous material and that the indentation is small compared to the cell size. These assumptions neglect the effects of the cytoskeleton, cell size and shape, and cell environment on cell deformation. In this study, we investigated the influence of cell size on the estimated Young’s modulus using liposomes as cell models. Liposomes were prepared with different sizes and filled with phosphate buffered saline (PBS) or hyaluronic acid (HA) to mimic the cytoplasm. AFM was used to obtain the force indentation curves and fit them to the Hertz model. We found that the larger the liposome, the lower the estimated Young’s modulus for both PBS-filled and HA-filled liposomes. This suggests that the Young modulus obtained from the Hertz model is not only a property of the cell material, but also depends on the cell dimensions. Therefore, when comparing or interpreting cell mechanics using the Hertz model, it is essential to account for cell size.

Cell-culture meat is a novel concept to replace traditional meat produced from animals, and to satisfy rising food demands due to the world population growth. It is still a young field and requires to solve technical issues including cell sources and types, efficient culture for large scale production, taste and texture for customer satisfaction. The current review summarized traditional beef meat production and evaluation methods for customer satisfaction. In particular, serum biomarkers for beef meat evaluation are discussed, which can be applicated for cell-culture meat production.

The currently available anti-cancer therapies, such as gamma-radiation and chemotherapeutic agents, induce cell death and cellular senescence not only in cancer cells but also in the adjacent normal tissue. New anti-tumor approaches focus on limiting the side effects on normal cells. In this frame, the potential anti-tumor properties of Pulsed Electromagnetic Fields (PEMFs) through irradiation of breast cancer epithelial cells (MCF-7 and MDA-MB-231) and normal fibroblasts (FF95) were investigated. PEMFs had a frequency of 8 Hz, full-square wave type, magnetic flux density of 0.011 T and applied twice daily for 5 days. Data collected showcases that PEMF application decreases the proliferation rate and viability of breast cancer cells while having the opposite effect on normal fibroblasts. Moreover, PEMF irradiation induced cell death and cellular senescence only in breast cancer cells without any effect in the non-cancerous cells. These findings suggest PEMF irradiation as a novel, non-invasive anti-cancer strategy in combination with senolytic drugs, to eliminate both cancer and the remaining senescent cells while simultaneously avoiding the side effects of the current treatments.

Treating relapsed and refractory diffuse large B-cell lymphoma is still challenging for clinicians, but the available CAR-T and bispecific antibodies revolutionized therapy. Autologous stem cell transplantation was the most effective treatment modality previously. The authors report data from a single center over ten years. The retrospective study included 116 patients. There were 53 relapsed, 39 primary refractory cases, 19 had CNS involvement, and 5 received primary consolidation transplants. The median duration of follow-up was 46 months. The median event-free survival was 75 months, and the median overall survival was 105 months for all cases. Five-year overall survival was 59%, and event-free survival was 54%. Pretreatment prognostic factors at diagnosis had no effect on the outcome of transplantation. The authors found no difference between survival in relapsed or refractory cases, and the number of salvage lines or the germinal center / activated B-cell type also did not influence the results. Complete metabolic response before transplant confirmed by 18FDG PET/CT strongly affected survival. The pretransplant creatinine and CRP levels significantly influenced the long-term outcome. The number of stem cells infused did not affect survival, but engraftment within nine days did result in better survival. These data support the finding that the response to salvage therapy did select a better prognostic group who may still benefit from autologous transplantation.

Viruses can induce the fusion of infected and neighboring cells, leading to the formation of syncytia. Cell-cell fusion is mediated by viral fusion proteins on the plasma membrane of infected cells that interact with cellular receptors on neighboring cells. Viruses use this mechanism to spread rapidly to adjacent cells or escape host immunity. For some viruses, syncytium formation is a hallmark of infection and a known pathogenicity factor. For others, the role of syncytium formation in viral dissemination and pathogenicity remains poorly understood. Human cytomegalovirus (HCMV) is an important cause of morbidity and mortality in transplant patients and the leading cause of congenital infections. Clinical HCMV isolates have broad cell tropism but differ in their ability to induce cell-cell fusions, and little is known about the molecular determinants. We developed a system to analyze HCMV glycoprotein B (gB) variants in a defined genetic background. HCMV strains TB40/E and TR were used as vectors to compare the fusogenicity of six gB variants from congenitally infected fetuses with those from three laboratory strains. Five of them conferred the ability to induce fusion of MRC-5 human embryonic lung fibroblasts to one or both backbone strains, as determined by a split GFP-luciferase reporter system. The same gB variants were not sufficient to induce syncytia in infected ARPE-19 epithelial cells, suggesting that additional factors are involved. The system described here allows a systematic comparison of the fusogenicity of viral envelope glycoproteins and may help to clarify whether fusion-promoting variants are associated with increased pathogenicity.