Scientists are gradually becoming aware of the challenges in the understanding of the very root mechanisms of massively parallel computations that are observed in literally all scientific disciplines ranging from cosmology, physics, across chemistry, biochemistry, and ending in biology. This leads us to the main motivation and simultaneously to the central thesis of this review: “Can we design artificial, massively-parallel, self-organized, emergent, error-resilient, computational environments?” A large number of simulations along with examples and counter-examples, finalized by a list of the future directions, are giving hints and partial answers to the main thesis. This all together is opening the crucial question whether there is existing a deeper, beyond the Turing machine theoretical description of massively-parallel computing. Important information dealing with this topic is reviewed along with highly expressive animations generated by the open-source, Python software GoL-N24. The perspective, future directions including applications in robotics and biology of this research are discussed in the light of known information.

The COVID-19 pandemic had a significant impact on the mental health of individuals globally, and primary healthcare (PHC) nurses play a critical role in providing mental healthcare services. However, limited research has explored the experiences of PHC nurses in providing mental healthcare services during the COVID-19 pandemic. This study explored the experiences of PHC nurses in providing mental healthcare services during the pandemic in Durban, South Africa. The aim was to identify the challenges faced by healthcare providers and the potential for innovative approaches to improve access to care. A qualitative, exploratory design guided the study, and data were collected through in-depth interviews with twelve PHC nurses purposively selected. Thematic analysis was used to analyse the data. Findings from interviews with primary healthcare nurses reveal that the pandemic exacerbated existing challenges, including medication adherence issues, fear and uncertainty among patients, vaccine hesitancy, decreased clinic visits, and the mental and emotional toll on both patients and healthcare workers. PHC nurses adapted their services by increasing outreach efforts, prioritising patient care, and utilising technology and non-governmental organisations’ (NGO) support. Challenges included reduced patient visits, complexities in healthcare provision, and lack of adequate support. Positive changes observed include increased mental health awareness among healthcare professionals and younger generations. Recommendations include implementing outreach and awareness campaigns, providing accurate information about COVID-19 and vaccinations, and promoting cultural sensitivity in mental healthcare provision.

Thrombosis is characterized by the pathological formation of fibrin clots within a blood vessel, leading to the obstruction of blood flow. Fibrinolytic enzymes from microorganisms have exhibited promising effects to dissolve clots in a more efficient and safe way. Then, the aim of this study was to evaluate the biomass and fibrinolytic enzyme production of Tetradesmus obliquus under autotrophic and mixotrophic conditions using different concentration of corn steep liquor (CSL). Different extraction and precipitating methods were tested, and the enzyme was purified by ion exchange chromatography. More advantageous culture condition was mixotrophic using 0.25% CSL, showing the highest values of biomass productivity (Px = 169.3 ± 44.36 mg∙L-1day-1) and specific growth rate (µmax = 0.17 ± 0.00 day-1), and significant fibrinolytic production (391.34 ± 40.03 U∙mg-1). Moreover, fibrinolytic activity was higher when extracted by homogenization and precipitated using acetone, which exhibited clear zone of fibrin degradation in the fibrinolytic plate assay. Additionally, the purified enzyme showed specific activity of 1176.90 ± 140.37 U∙mg-1 and molecular weight around 97 kDa. Finally, the enzyme has higher enzymatic activity than various fibrinolytic enzymes, and the obtained enzyme has potential to be developed as a therapeutic agent in thrombosis treatment. Additional studies are need to investigate the biochemical properties and biological profile of this enzyme.

In light of the current situation where no testing equipment is available for measuring thermal deformation of objects, this paper proposes a novel method for accurate and precise measurement. The method overcomes the limitations of previous approaches that relied on pitch angle. By utilizing the principle of biplane multiple reflections, a bivariate laser spot displacement analysis algorithm is devised to attain highly precise measurements of bivariate angles. Additionally, a temperature gradient comparison algorithm is introduced to calculate the indicator test results under specific temperature conditions. To validate the effectiveness and reliability of this method, a testing system is constructed and utilized. The results demonstrate that the thermal deformation angle change test achieves an impressive accuracy of 0.015″ and a rate of thermal deformation angle change of 0.3247″/°C. These values are in close agreement with the previously simulated analysis result of 0.359″/°C, with only a relative error of 9.55%. Therefore, the test results confirm the efficacy and reliability of this testing method along with the feasibility of the algorithm processing.

This essay critically discusses the integration of queer theory into human geography while emphasizing its ties to the principles of traditional geography. The need for a separate sub-discipline called queer geography is questioned. At the same time, legitimate concerns about possible departures from the fundamental goals of geography and the risks of anachronistic interpretations in applying modern concepts to historical landscapes are acknowledged. In this discourse, we strongly advocate for values such as freedom of speech, freedom of expression, and international human rights. It is important to emphasize that it is not the intent of this essay to denigrate campaigns for feminism or equality or to disparage the scholarship that emerges from the application of queer theory. On the contrary, we recognize the emergence of gender theories out of a need to advance social justice approaches. We believe that traditional human geography, itself, is capable of comprehensively examining space, time, and the complexity of human experience and offering workable solutions within its established framework. We therefore believe that the inclusion of queer theory can be harmoniously integrated into the contours of human geography, eliminating the need for a separate sub-discipline while preserving the integrity and purpose of the discipline.

In this paper, we succeed to discover the new exact wave solutions to the truncated M-fractional complex three coupled Maccari’s system by utilizing the Sardar sub-equation scheme. The obtained solutions are in the form of trigonometric and hyperbolic forms. These solutions have many applications in nonlinear optics, fiber optics, deep water-waves, plasma physics, mathematical physics, fluid mechanics, hydrodynamics and engineering where the propagation of nonlinear waves is important. Achieved solutions are verified with the use of Mathematica software. Some of the achieved solutions are also described graphically by 2-dimensional, 3-dimensional and contour plots with the help of Maple software. The gained solutions are helpful for the further development of concerned model. Finally, this technique is simple, fruitful and reliable to handle the nonlinear FPDEs.

Quantum-dot cellular automata (QCA) are a promising nanoscale computing technology that exploits the quantum mechanical tunneling of electrons between quantum dots in a cell and electrostatic interaction between dots, in neighboring cells. QCA can achieve higher speed, lower power, and smaller areas than conventional complementary metal–oxide–semiconductor (CMOS) technology. Developing QCA circuits in a logically and physically reversible manner can provide exceptional reductions in energy dissipation. The main challenge of reversible QCA design is to maintain reversibility down to the physical level. The arithmetic logic unit (ALU) is an essential component of the central processing unit (CPU) of a computer. It performs various arithmetic and logical operations on the data that the CPU processes. Current QCA ALU designs are either irreversible or logically reversible; however, they lack physical reversibility, a crucial requirement to increase energy efficiency. In this paper, we present a novel multilayer design for a logically and physically reversible QCA ALU based on majority gates as the key components, which can perform 16 different operations. We use QCADesigner-E software to simulate and evaluate energy dissipation. The proposed logically and physically reversible QCA ALU offers an improvement of 88.8% in energy efficiency. Compared to the next most efficient 16-operation QCA ALU, this ALU uses 51% fewer QCA cells and 47% less area.

One of the hallmarks of microgravity-induced effects in several cellular models is represented by the alteration of oxidative balance with the consequent accumulation of Reactive Oxygen Species (ROS). It is well known that male germ cells are sensitive to oxidative stress and to changes of gravitational force even if published data on germ cell models are scarce. To gain more insights into the mechanisms of male germ cell response to altered gravity, a 3D cell culture model has been established from TCam-2 cells, a seminoma-derived cell line considered the only human cell line available to study in vitro mitotically active human male germ cells. TCam-2 cell spheroids were cultured for 24 hours under unitary gravity (Ctr) or simulated microgravity (s-microgravity) conditions, these last ones were obtained using the Random Positioning Machine (RPM). A significant increase in intracellular ROS and mitochondria superoxide anion levels has been observed after RPM exposure. In line with these results a trend of protein and lipid oxidation increase, and increased pCAMKII expression levels were observed after RPM exposure. The ultrastructural analysis by Transmission Electron Microscopy revealed that RPM-exposed mitochondria appeared enlarged and, even if seldom, disrupted. Notably, even the expression of the main enzymes involved in the redox homeostasis appears modulated by RPM exposure in a compensatory way, being GPX1, NCF1, and CYBB downregulated, whereas NOX4 and HMOX1 upregulated. Interestingly, HMOX1 is involved in the heme catabolism of mitochondria cytochromes, and therefore the positive modulation of this marker can be associated to the observed mitochondria alteration. All together, these data demonstrate TCam-2 spheroid sensitivity to acute SM exposure and indicate the capability of these cells to trigger compensatory mechanisms that allow to overcome the exposure to altered gravitational force.

We previously showed that mice with knockout in the peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1A) gene encoding the PGC-1a protein and nuclear factor erythroid 2 like 2 (NFE2L2) gene, showed some features of the age-related macular degeneration (AMD) phenotype. To further explore the mechanism behind the involvement of PGC-1a in AMD pathogenesis we used young (3-month) and old (12-month) mice with knockout in the PPARGC1A gene and age-matched wild-type (WT) animals. An immunohistochemical analysis showed age-dependent different expression of markers of oxidative stress defense, senescence and autophagy in the retinal pigment epithelium of KO animals as compared with their WT counterparts. Multivariate inference testing showed that senescence and autophagy proteins had the greatest impact on the discrimination between KO and WT 3-month animals, but proteins of antioxidant defense also contributed to that discrimination. A bioinformatic analysis showed that PGC-1a might coordinate the interplay between genes encoding proteins involved in antioxidant defense, senescence and autophagy in the aging retina. These data support importance of PGC-1a in AMD pathogenesis and confirm the utility of mice with PGC-1a knockout as an animal model to study AMD pathogenesis.

Two monoclonal antibodies (mAbs) against human epidermal growth factor receptor 2 (HER2), trastuzumab and pertuzumab, were clinically approved. We previously developed a highly sensitive and specific anti-HER2 mAb, H2Mab-139 (mouse IgG1, kappa). In this study, we produced a defucosylated IgG2a version of anti‑HER2 mAb (H2Mab-139-mG2a-f) to enhance ADCC-mediated antitumor activity. H2Mab-139-mG2a-f exhibits a high binding affinity in flow cytometry with the dissociation constant (KD) determined to be 3.9 × 10‑9 M and 7.7 × 10‑9 M against HER2‑overexpressed Chinese hamster ovary (CHO)-K1 (CHO/HER2) and HER2-positive BT-474 cells, respectively. Moreover, we showed that H2Mab-139-mG2a-f exerted ADCC and complement-dependent cytotoxicity against CHO/HER2 and BT-474 cells in vitro and exhibited potent antitumor activities in the xenograft models. These results indicated that H2Mab-139-mG2a-f exerts antitumor effects against HER2-positive human breast cancers and could be useful for an antibody treatment regimen for HER2-positive human cancers.

In this paper, a new multi parameter iterative algorithm is proposed to address the PageRank problem based on the multi-splitting iteration method described by Gu et al . The proposed method in each iteration needs to solve two linear subsystems by splitting the coefficient matrix, therefore, we consider inner and outer iteration to find the approximate solutions of these linear subsystems. It can be shown that the iterative sequence generated by the multi parameter iterative algorithm finally converges to the PageRank vector when the parameters satisfy the certain conditions. Numerical experiments show that the proposed algorithm has better convergence and numerical stability than the existing algorithms.

In this work, a simple and environmentally friendly process combining low pressure (vacuum) and mechanical compression is proposed to convert recycled polypropylene (PP) foams (28 kg/m3) into low density foams (90-131 kg/m3) having negative tensile and compressive Poisson's ratios (NPR). The effect of processing conditions (vacuum time, temperature, and mechanical pressure) was studied. Based on the optimized conditions, the tensile Poisson’s ratio of the resulting auxetic foams reached −1.50, while the minimum compressive Poisson's ratios was −0.32 for the same sample. The foam structure was characterized via morphological analysis (SEM) to determine any changes related to the treatment applied. Finally, tensile and compressive properties (Young's modulus, strain energy, energy dissipation and damping capacity) are also presented and discussed. It was observed that the mechanical properties of the resulting auxetic foams were improved compared to the original PP foam (PP-O) for all tensile properties in terms of modulus (19.9 to 59.8 kPa), strength (0.298 to 1.43 kPa) elongation at break (28 to 77%), energy dissipation (14.4 to 56.3 mJ/cm3) and damping capacity (12 to 19%). Nevertheless, improvements were also observed under compression in terms of energy dissipation (1.6 to 3.6 mJ/cm3) and damping capacity (13 to 19%). These auxetic foams can find applications in sport and military protective equipment, as well as any energy mitigation system.

Cellular automata (CA) models have emerged as a valuable tool in corrosion management. This manuscript provides an overview of the application of cellular automata models in corrosion research, highlighting their benefits and contributions to understanding the complex nature of corrosion processes. Cellular automata models offer a computational approach to simulate corrosion behavior at the microscale, capturing the intricate interactions between electrochemical reactions, material properties, and environmental factors generating a new vision of predictive maintenance. It discusses the key features of cellular automata, such as the grid-based representation of the material surface, the definition of state variables, and the rules governing cell-state transitions. The ability to model local interactions and emergent global behavior makes cellular automata particularly suitable for simulating corrosion processes. Finally, cellular automata models offer a powerful and versatile approach to studying corrosion processes, expanding models that can continue to enhance our understanding of corrosion and contribute to the development of effective corrosion prevention and control strategies.

Diagnostics is believed to drive about 70% of medical interventions, but this may not be true for all demographics. With more than 30% of the African population living in extreme poverty ($1.9 per day - 2022); and healthcare costs competing unfavorably against unbridled access to antibiotics and herbal concoctions, especially in Sub-Saharan Africa, how do you convince such a people to choose diagnostics first? More importantly, how do you design a medical device targeted at meeting the diagnostic needs of this demographic? In developing diagnostic devices for such a market, what is worth sacrificing? How dire is the need for advanced technologies in devices developed for such a demographic? These are questions that remain unaddressed by the technological breakthroughs and current research in medical device development, especially for infectious disease diagnostics. The objective of this paper is to underscore critical concerns which must be considered in the bid to successfully design medical diagnostic devices for Africa and perhaps, other limited-resource settings. It is also written as a suggestive guidance document for researchers whose interest is in the development of infectious disease diagnostic platforms for rural Africa and similar limited-resource environments.

In this paper, we prove that the sub convexlikeness introduced by V. Jeyakumar [1], and the subconvexlikeness defined in V. Jeyakumar [2] are equivalent in loccallly convex topological spaces. And then, we work with set-valued vector optimization problems and obtain some vector saddle-point theorems and vector Lagrangian theorems.

Infection of liver flukes (Opisthorchis viverrini) is partly due to their suitability for habitats in sub-basin areas, which causes the intermediate host to remain in the watershed system in all seasons. Spatial monitoring of fluke infection at the small -basin analysis scale is important because this can enable analysis at the level of the spatial factors involved and influencing infections. A geographic weighted regression model was developed to analyze the spatial characteristics of liver fluke infection, aiming to 1. analyze the spatial factors associated with human liver fluke infection according to sub-basin boundaries and 2. generate an alternative model for enhancing the effectiveness of preventive public health management to reduce the risk of liver fluke infection in humans. The number of infected persons was obtained from local authorities and converted into a percentage of infected people and generated as raster data with a heat map so that the data were continuous and defined as dependent variables. The independent set consisted of nine variables, both vector and raster data, that correlated the location with the village location of an infected person. The results showed that the variables X5stream, X7ndmi, and X9savi were statistically significantly correlated to the percentage of infected people, with the t-stat and p-value being (-2.068, 1.875, and -2.661) and (0.048, 0.034, and 0.021), respectively. The GWR model was able to increase accuracy more than the comparable models such as OLS, in all tests of the four alternative models, with an accuracy increase in R2 of 7.69% (0.576 to 0.624). This study confirms that the development of spatial models with GWR models can screen for factors associated with liver fluke infection at the level of small spatial units such as sub-basins.

This paper reviews numerical methods used to simulate desiccation cracks in clayey soils. It examines five numerical approaches: Finite Element (FEM), Lattice Boltzmann (LBM), Discrete Element (DEM), Cellular Automaton (CAM), and Phase Field (PFM) Methods. The FEM is widely used to capture moisture diffusion, shrinkage, and cracking during drying. LBM is used to simulate fluid flow in clayey soils, while the DEM focuses on capturing the behavior of individual particles and their interactions. CAM simplifies crack evolution with computational efficiency, while PFM provides a continuous representation of crack formation and propagation. The author discusses the complexity of the problem, the continuum mechanics governing and constitutive equations that describe it, and the influence of various factors such as the multiphase nature of soils, heterogeneity, nonlinearities, coupling, scales of analysis, and computational aspects. The review highlights the characteristics, strengths, and limitations of each method. It emphasizes the importance of appropriate method selection for every problem depending on the aim of the analysis. The article concludes by reviewing the integration of multiple numerical methods to enhance the simulation of desiccation cracks in clayey soils.

The determination and classification of seafloor sediment types are crucial for the exploitation of marine resources, construction of marine engineering, and maintenance of marine ecological en-vironments. Automatic classification of seafloor sediment based on acoustic telemetry data is an important method to quickly understand the type of a large range of sediment. Currently, most studies on sediment classification are based on multi-beam backscattering intensity data, which is a relatively single data type. Besides, the low-dimensional details of standard U-Net gradually weaken in the propagation process, limiting the accuracy of sediment classification. Therefore, this study proposes an automatic classification method of seafloor sediment types based on an im-proved U-Net and K-means clustering algorithm, using multi-beam water depth, sub-bottom profile, and sample test data in the Northern Slope of the South China Sea. Six sediment types, including gravelly muddy sand, sand, silty sand, less muddy silt, muddy silt, and silty mud, were identified in the study area. Additionally, the study area was divided into four sedimentary en-vironment zones, including the shelf sedimentary area, the upper shelf slope break sedimentary area, the lower shelf slope break mixed sedimentary area, and the slope deposition area, based on the results of sediment classification and geological background. The sedimentary environment zones were found to be distributed along the trend of the shelf slope break line. The results of this study not only provide an important supplement to the existing classification methods of seafloor sediments but also contribute to the understanding of the sedimentary environment and process of the Northern Slope of the South China Sea.

Hemoglobin based oxygen carriers (HBOC) as blood substitutes are one of the great hopes of modern transfusion and emergency medicine. After the major safety-relevant challenges of the last decades seem to be largely overcome, current developments have in common that they are affected by degradation and excretion at an early stage in test organisms. Several possible mechanisms that may be responsible for this are discussed in the literature. One of them is CD163, the receptor of the complex of haptoglobin (Hp) and hemoglobin (Hb). The receptor has been shown in various studies to have an affinity for Hb in the absence of Hp. Thus, it seems reasonable that CD163 could possibly also bind Hb within HBOC and cause phagocytosis of the particles. In this work we investigated the role of CD163 for the uptake of our HbMP (hemoglobin sub-micron particles) in monocytes and additionally screened for alternative ways of particle recognition by monocytes. In our experiments, blockade of CD163 by specific monoclonal antibody proved to partly inhibit HbMP-uptake by monocytes. It appears however, that several other phagocytosis pathways for HbMP might exist, independent of CD163 and also Hb.

Abstract: The purpose of this review is to summarize recent knowledge on the main processes that occur during wound healing, including the responses of various cell types and the molecular mechanisms involved. Particular attention is also dedicated to new therapies often involved in the resolution of wounds, whether acute or chronic. Awareness of these dynamics is important for the various professional figures who are confronted with these kinds of problem daily. However, the study of the healing mechanisms has yet to be defined in detail, in fact there are alterations of variously coordinated events which lead to a delayed resolution or, as in the case of keloids, to pathological states consisting in the excessive formation of scars with consequences yet to be seen. to define. Therefore, it is necessary to know the most feasible approaches and the most effective therapies.

Though there has been a decline in the number of new cases of viral hepatitis-induced acute liver failure in Europe and the United States of America, viral hepatitis still remains the leading cause of acute liver failure in Asia-Pacific and South America. However, the epidemiology of viral-hepatitis-induced acute liver failure in sub-Saharan Africa-the world epicenter of viral hepatitis-is unclear. The aim of this review was to collate data on the incidence, prevalence, specific etiologic agents, features/diagnosis, treatment and prognosis of viral-induced acute liver failure in sub-Saharan Africa. One hundred and forty-seven cases of viral-induced acute liver failure were recorded in 11 studies conducted in six countries between 1981-2020. Etiological agents were: Hepatitis viruses A, B, C, and E, as well as Adenovirus, Enterovirus, Parvovirus, Herpes Simplex Virus (HSV) and EBV. HAV was the most frequent in paediatric subjects: (11/16) 69% and (19/30) 63%. HBV was the only etiological agent in the study that only included adults. HEV (genotype 2 in one study) contracted amidst hepatitis E outbreaks was the most commonly reported cause of ALF in pregnant women. Treatment was mainly supportive, and liver transplantation reported only in South Africa. Where reported, case fatality rates were high. In conclusion, viral-hepatitis induced acute liver failure is largely understudied in sub-Saharan Africa. The few available data are consistent with literature from the other parts of the world regarding aetiologic agents. Liver transplantation is not available in most sub-Saharan African countries, and short-term case fatality rates of individuals with acute liver failure could outstrip current rates from the other world regions.

Agroecology is a holistic approach to farming that emphasizes the use of local resources and ecological processes to increase productivity, reduce environmental impact, and enhance resilience. Despite its potential benefits, the adoption of agroecological practices in Sub-Saharan Africa has been slow. This paper examines the opportunities for promoting agroecology in the region, including the growing demand for organic and sustainable food, the availability of local knowledge and resources, and the potential for agroecology to improve rural livelihoods and support climate change adaptation. The premise is that the promotion of agroecology faces several challenges. which include, inadequate policy and institutional support, lack of access to credit and markets, limited extension services, and weak land tenure systems. The paper draws on case studies from across Sub-Saharan Africa to illustrate the opportunities and challenges of promoting agroecology in the region. These case studies highlight the diversity of agroecological practices and the importance of context-specific approaches. Overall, the paper maintains that agroecology has the potential to transform agriculture in Sub-Saharan Africa, but that realizing this potential will require concerted efforts from governments, civil society, and the private sector.

Antisense oligonucleotides (ASONs) have proven potential for the treatment of various diseases. However, their limited bioavailability restricts their clinical application. New structures with improved enzyme resistance stability and efficient drug delivery are needed. In this work, we propose a novel category of ASONs bearing anisamide conjugation at phosphorothioate sites for oncotherapy. ASONs can be conjugated with the ligand anisamide very efficiently and flexibly in solution. The conjugation sites and ligand amount both influence anti-enzymatic stability and cellular uptake, resulting in changes in antitumor activity that are detectable by cytotoxicity assay. T6 (with double end AA-conjugation) was identified as the optimal conjugate, and its antitumor activity and the underlying mechanism were examined further in vitro and in vivo. This paper presents a new strategy for the design of nucleic acid–based therapeutics with improved drug delivery and biophysical and biological efficacy.

The larvicidal potential of olive mill waste water (OMWW) extract against mosquito larvae was evaluated. We exposed second instar Culex laticinctus (Edwards) and Aedes albopictus (Skuse) larvae to increasing OMWW concentrations. In addition, we tested the effects of long term exposure to a low OMWW concentration on larval development. The two mosquito species responded differently to OMWW extracts. Larval Cx. laticinctus showed higher vulnerability to increasing OMWW concentrations in comparison to Ae. albopictus. By contrast, Cx. laticinctus exposed to a low OMWW concentration until pupation did not exhibit survival differences, but rather sex-specific development responses. These trends were not observed in Ae. albopictus whose survival was significantly reduced following long exposer to OMWW extraction. These results showed that OMWW, which is known as agricultural byproduct waste, may be reused as a biopesticide.

Despite exhaustive studies, researchers have made little progress in the field of adoptive cellular therapies for relapsed-refractory acute myeloid leukemia (AML), unlike the notable uptake for B cell malignancies. Various single antigen targeting chimeric antigen receptor (CAR) T cell Phase I trials have been established worldwide and have recruited approximately 100 patients. The high heterogeneity at the genetic and molecular levels within and between AML patients resembles a black hole: a great gravitational field that sucks in everything, considering only around 30% of patients show a response but with consequential off-tumor effects. It is obvious that a new point of view is needed to achieve more promising results. This review first introduces the unique therapeutic challenges of not only CAR T cells but also other adoptive cellular therapies in AML. Next, recent single cell sequencing data for AML to assess somatically acquired alterations at the DNA, epigenetic, RNA and protein levels are discussed to give a perspective on cellular heterogeneity, intercellular hierarchies, and the cellular ecosystem. Finally, promising novel strategies are summarized, including more sophisticated next-generation CAR T, TCR-T and CAR-NK therapies; approaches to tailor the microenvironment and target neoantigens; and allogeneic approaches.

As with every new technology, safety demonstration is a critical component of bringing products to market and gaining public acceptance for cultured meat and seafood. This manuscript develops research priorities from the findings from a series of interviews and workshops with governmental scientists and regulators from food safety agencies in fifteen jurisdictions globally.  The interviews and workshops aimed to identify the key safety questions and priority areas of research. Participants raised questions about which aspects of cultured meat and seafood production are novel, and the implications of the paucity of public information on the topic. Novel parameters and targets may require the development of new analytical methods or adaptation and validation of existing ones, including for a diversity of product types and processes. Participants emphasized that data sharing of these efforts would be valuable, similar to those already developed and used in the food and pharmaceutical fields. Contributions to such databases from the private and public sectors would speed general understanding as well as efforts to make evaluations more efficient. In turn, these resources, combined with transparent risk assessment, will be critical elements of building consumer trust in cultured meat and seafood products.

Cesium lead iodide (CsPbI3) perovskite nanocrystals (NCs) are a promising material for red light-emitting diodes (LEDs) due to their excellent color-purity and high luminous efficiency. However, small-sized CsPbI3 colloidal NCs, such as nanocubes, used in LEDs suffer from confinement effects, negatively impacting their photoluminescence quantum yield (PLQY) and overall efficiency. Here, we introduced YCl3 into the CsPbI3 perovskite, which formed anisotropic, one-dimensional (1D) nanorods. This was achieved by taking advantage of the difference in bond energies between Cl− and I− ions, which caused YCl3 to promote the anisotropic growth of CsPbI3 NCs. The YCl3-based nanorods improved the PLQY and storage stability by passivating the defects reducing the nonradiative recombination rates. When the YCl3-substituted CsPbI3 nanorods are applied to the emissive layer in LEDs, we achieve an external quantum efficiency of ~3.16% which is 1.86-fold higher than the pristine CsPbI3 NCs (1.69%) based LED. Notably, the ratio of horizontal transition dipole moments (TDMs) in the anisotropic YCl3:CsPbI3 nanorods was determined to be 75%, which is higher than the isotropically oriented TDMs in CsPbI3 nanocrystals (67%). This increased TDM ratio led to higher light outcoupling efficiency in nanorods-based LEDs. Overall, the results suggest that YCl3-substituted CsPbI3 nanorods could be promising for achieving high-performance perovskite LEDs.

Bacterial nitroreductase enzymes that convert prodrugs to cytotoxins are valuable tools for creating transgenic targeted ablation models to study cellular function and cell-specific regeneration paradigms. We recently engineered a nitroreductase (“NTR 2.0”) for substantially enhanced reduction of the prodrug metronidazole, which permits faster cell ablation kinetics, cleaner interrogations of cell function, ablation of previously recalcitrant cell types, and extended ablation paradigms useful for modelling chronic diseases. To provide insight into the enhanced enzymatic mechanism of NTR 2.0, we have solved the X-ray crystal structure at 1.85 Angstroms resolution and compared it to the parental enzyme, NfsB from Vibrio vulnificus. We additionally present a survey of reductive activity with eight alternative nitroaromatic substrates, to provide access to alternative ablation prodrugs, and explore applications such as remediation of dinitrotoluene pollutants. The predicted binding modes of four key substrates were investigated using molecular modelling.

Image encryption is increasingly becoming an important area of research in information security and network communications, as digital images are widely used in various applications and are vulnerable to various types of attacks. In this research work, a color image cryptosystem that is based on a 3-layer permutation-substitution network (PSN) is proposed. For every layer, an encryption key and an S-box are generated and utilized. Those are based on a four-dimensional (4D) dynamical Chen system of a fractional-order, the Mersenne Twister, OpenSLL, Rule 30 Cellular Automata and Intel’s MKL. The sequential application of Shannon’s ideas of diffusion and confusion for 3 times guarantees a total distortion of any input plain image, resulting in a totally encrypted one. Apart from the excellent and comparable performance to counterpart algorithms from the literature, showcasing resistance to visual, statistical, entropy, differential, known plaintext and brute-force attacks, the proposed image cryptosystem provides an exceptionally superior performance in 2 aspects: a vast key space of 2^1658 and an average encryption rate of 3.34 Mbps. Furthermore, the proposed image cryptosystem is shown to successfully pass all the tests of the NIST SP 800 suite.

Atopic dermatitis (AD) is a common chronic inflammatory skin disease with high prevalence worldwide, including countries from Asia, Africa and Latin America, and in different ethnic groups. In recent years, more attention on AD heterogeneity associated on multiple factors, including patient’s ethnic background, has been posed, resulting in an increasing body of clinical, genetic, epidemiologic, and immune-phenotypic evidence that delineate differences among racial groups with AD. Filaggrin (FLG) mutations, the strongest genetic risk factor for the development of AD, are detected in up to 50% of European and 27% of Asian AD patients, while very rarely in Africans. The Th2 activation is a common attribute of all ethnic groups, though the Asian endotype of AD is also characterized by an increased Th17-mediated signal whereas African Americans own a strong Th2/Th22 signature and the absence of Th1/Th17 skewing. In addition, the ethnic heterogeneity may own important therapeutic implications as the genetic predisposition may affect treatment response and, thereby, a tailored strategy that better targets the dominant immunologic pathways in each ethnic subgroup may be envisaged. Nevertheless, white patients with AD represent the largest ethnicity enrolled and tested in clinical trials and the most treated in a real-world setting, limiting the investigation about safety and efficacy across different ethnicities. The purpose of this review is to describe the heterogeneity of pathophysiology across ethnicities and its potential therapeutic implications.

Human serum albumin (HSA) is the ultimate, homeostatic determinant of fluid volume (FV) in all compartments of the body. The ability to change the pressure and flow of nutrient medium to cellular structures selectively has clinical significance in almost all areas of clinical medicine. We have shown that present fluid therapy (FT) using either colloid or saline dilutes nutrients. HSA binds and delivers nutrients, a lack of HSA binding causes Albumin Binding Disease (ABD) changing both colloidal pressure and nutrients leading to symptoms of sepsis. A reduction in HSA binding can be through lack of HSA or external ligands taking up binding sites on HSA. Many diseases cause ABD when immunoglobulins, infectious particles and by products bind to HSA including COVID-19 and other bacterial diseases like streptococcus as well as metabolic and cardiac disease due to incorrect pressure and nutrients. To raise HSA binding potential and remove vulnerabilities to these diseases we propose raising HSA. We show how present methods of fluid therapy (FT) are inefficient in that control of both pressure and nutrients forms initial equilibrium in the liver. HSA production and binding to nutrients is maintained at a level by the pressure in hepatocytes with the pancreatic and adrenal hormones moderating. Glucose and Ke-tone production are critical in the management of HSA binding and control of blood, colloidal pressure, and health of cells. Ketones provide a distinct mechanism of liver to lungs-heart metabolism during hypoglycaemia and activity. This known chain of nutrition becomes critical during disease like acute respiratory distress syndrome (ARDS) when ketones may be overproduced. HSA must therefore be infused into the liver to raise HSA levels safely. We investigated the control of HSA as a product of the actions of pressure in hepatocytes and changes in pancreatic and adrenal hormones. We found that in addition to pressure during glucose abundancy HSA is re-leased with ketones on administration of insulin and consider that this mechanism retains HSA moderation. HSA can therefore be increased by increasing insulin in the presence of glucose in the correct amounts. We suggest a protocol to increase FV, blood, lymph volume by infusion of HSA, insulin, and glucose direct to the liver so that the level of HSA stabilises. We suggest this will raise all other nutrients in the new FV, blood, lymph culminating in the creation of new blood cells. We propose that in a clinical situation maintaining this protocol will alleviate the symptoms of ABD and decrease the likelihood of serious illness and death.

The evolutionary transition from single-celled to multicellular individuality requires organismal fitness to shift from the cell-level to the cell group. This reorganization of fitness occurs by allocating the two components of fitness, survival and reproduction, between two specialized cell types in the multicellular group – soma and germ, respectively. How does the genetic basis for such fitness reorganization evolve? One possible mechanism is the co-option of life-history genes present in the unicellular ancestors of a multicellular lineage. Single-celled organisms must regulate their investment in survival and reproduction in response to environmental changes, particularly decreasing reproduction to ensure survival when stressed. Such stress response life-history genes can provide the foundation for the genetic basis for cellular differentiation in multicellular lineages. The regA gene family in volvocine green algae provides a model system to study how this co-option occurs. We discuss the origin and evolution of the volvocine regA gene family, including regA – the gene that controls somatic cell development in the model organism Volvox carteri. We hypothesize that the co-option of life history trade-off genes is a general mechanism involved in the transition to multicellular individuality, making volvocine algae and the regA family a useful template for similar investigations in other lineages.

Despite being well established phenomena, solidification principles are experiencing tough challenges in their application to explain microscale transport phenomena in additive manufacturing melt pool. The problem becomes even more complicated when applied to multicomponent bulk metallic glass matrix composites (BMGMC) whose behavior is dubious and still not fully understood. The aim of the present study is to highlight pathways to overcome these challenges. A comprehensive nucleation and growth model based on original KGT theory and Rappaz modification is proposed encompassing actual transient thermophysical BMGMC data to predict evolving microstructure during additive manufacturing. The model is aimed at pictorial representation of in-situ ductile phase dendrite evolution from melt pool during solidification using two-dimensional cellular automaton (CA) methods. It is proposed to be coded in MATLAB® using commercial simulation code ABAQUS® at back end for macroscopic heat transfer model. The results will be compared with experimental values for validation.

Hepatocellular carcinoma (HCC) is a heterogeneous malignancy with complex carcinogenesis. Although there has been significant progress in the treatment of HCC over the past decades, drug resistance to chemotherapy remains a major obstacle in its successful management. In this study we were able to reduce chemoresistance in cisplatin-resistant HepG2 cells by either silencing the expression of transglutaminase type 2 (TG2) using siRNA or by pre-treatment of cells with the TG2 enzyme inhibitor cystamine. Further analysis revealed that, whereas the full-length TG2 isoform (TG2-L) was almost completely cytoplasmic in its distribution, the majority of the short TG2 isoform (TG2-S) was membrane-associated in both parental and chemoresistant HepG2 cells. Following induction of cisplatin toxicity in non-chemoresistant parental cells, TG2-S together with cisplatin quickly relocated to the cytosolic fraction. Conversely, no cytosolic relocalisation of TG2-S or nuclear accumulation cisplatin was observed following identical treatment of chemoresistant cells, where TG2-S remained predominantly membrane-associated. This suggests that deficient subcellular relocalisation of TG2-S from membranous structures into the cytoplasm may limit the apoptic response to cisplatin toxicity in chemoresistant cells. Structural analysis of TG2 revealed the presence of binding motifs for interaction of TG-S with the membrane scaffold protein LC3/LC3 homologue that could contribute to a novel mechanism of chemotherapeutic resistance in HepG2 cells.

Land resources have been under tremendous anthropogenic pressure with the consequence of their degradation. It is therefore necessary that the land resources must be managed effectively for sustainable development. Different from the developed countries, carbon inventories and data bank to monitor carbon sequestration potential of different ecosystems are unavailable in India. Micro-level studies are essential for sustainable land use management for a land scarce nation like India. To achieve the desirable goal of the present study, a total of 33 tree-based land uses were identified from forested and agricultural landscapes. Of these total land uses, five were in forest landscapes and rest in agricultural landscapes categorized into forest tree plantations (8 land uses), agroforestry (nine land uses), commercial crop plantations (six land uses) and fruit orchards (five land uses). A stratified random nested quadrate sampling method was adopted for vegetation analysis of the different land uses. The SOC, biomass and carbon accumulation in the tree-based land uses were significantly different from each other. Mixed forest soil had the highest amount of SOC, primary nutrients, standing biomass carbon, and ecosystem carbon. Positive correlations were observed between SOC, total standing biomass, litter production, and ecosystem carbon. The sequence of best tree based land uses in terms of total SOC (up to 60 cm depth), total plant biomass, total plant biomass carbon and ecosystem carbon was mixed species forest (126.67, 781.21, 390.61 and 517.27) > sole tree species stands in forest landscape (109.71, 192.56, 96.28 and 205.98) > tea plantations (103.19, 77.07, 38.54 and 141.74) > homegardens (90.34, 97.38, 48.69 and 139.02) > mixed plantation of Anthocephalus cadamba + Swietenia macrophylla (60.07, 111.86, 55.93 and 116.02) > Swietenia macrophylla based agroforestry (62.49, 83.82, 41.91 and 104.40) > mixed plantation of Tectona grandis + Milvus migrans (60.0, 85.97, 42.99 and 102.90). Similarly, the order of the major land uses was forest > commercial crop plantation > forest tree plantations > agroforestry > fruit orchards. The overall average ecosystem carbon accumulation in forests was 3.24 times more than the land uses in agricultural landscapes. The ecosystem carbon accumulation in the tree-based land uses in both forest and agricultural landscape was highly variable and was significantly different from each other. Land use conversion from forest to agriculture can reduce more than half of the carbon stock, but converting into homegardens, tree plantations or agroforestry enhanced carbon storage of the land use systems. The present findings can be used as baseline information for developing prediction models for probable effects of different land use, future intervention and sustainable management of land use systems.

Increased mitotic activity is associated with the genesis and aggressiveness of many cancers. To assess the clinical value of mitotic activity as prognostic biomarker, we performed a pan-cancer study on the mitotic network activity index (MNAI) constructed based on 54-gene mitotic apparatus network. Our pan-cancer assessment on TCGA (33 tumor types, 10,061 patients) and validation on other publicly available cohorts (23 tumor types, 9,209 patients) confirmed the significant association of MNAI with overall survival, progression-free survival and other prognostic endpoints in multiple cancer types, including Lower-Grade Gliomas (LGG), Breast Invasive Carcinoma (BRCA) and many others. We also showed significant association of MNAI with genetic instability, which provides a biological explanation of its prognostic impact at pan-cancer landscape. Futhermore, we found that patients with high MNAI benefit more from anti-PD-1 and Anti-CTLA-4 treatment. In addition, we demonstrated on LGG and BRCA that the multimodal integration of MNAI and the AI-empowerd Cellular Morphometric Subtypes (CMS) significantly improved the predictive power of prognosis compared to MNAI and CMS alone. Our results suggest that MNAI can be used as a potential prognostic biomarker for different tumor types toward different clinical endpoints, and multimodal integration of MNAI and CMS exceeds individual biomarker for precision prognosis.

Background: Visceral leishmaniasis affects approximately 12 million people worldwide. Current existing drugs cause several side effects and resistance, the identification of new therapeutic targets for the development of new drugs is necessary. The vesicular trafficking in the parasite flagellar pocket is essential for parasite survival and proliferation, but little is known about the proteins involved in the endocytic/secretory pathways. In this work, we are describing the characterization of a transporter cargo protein SFT-2/Got-1 like in Leishmania infantum. Material and Methods: Using bioinformatics tools, the putative Got-1 protein A4HSK3 was characterized structurally and phylogenetically. Molecular biology was used to clone and express the protein and confocal fluorescence to determine its subcellular localization. Results: The Got-1 like protein presents four alpha helix TM conserved domains (aa38-aa147) characteristics of the Got-1/SFT-2 family proteins and an important Pen-2 conserved motif LGDYXXF located in the extracellular loop. Confocal microscopy suggests that Got-1/SFT-2 like is localized in the flagellar pocket, and is partially co-localized with the L. infantum presenilin-like protein. Phylogenetically, the Leishmania sp Got-1 like is contained in a subgroup of proteins clearly detached from the other Trypanosomatidae, such as T. cruzi and T. brucei. Conclusions: Our data show the presence of an important transported proteins, and its colocalization with the presenilin aspartyl protease in the flagellar pocket of the L. infantum open new perspectives to identify novel targets, which can be an alternative therapeutic strategy against leishmaniasis.

Ultra-short 230 fs laser pulses of 515 nm wavelength were tightly focused into 700 nm focal spots and utilised in opening ~ 400 nm nano-holes in a Cr etch mask that was tens-of-nm thick. Nano-holes ablated at slightly above the threshold of ablation irradiance became nano-disks and nano-rings at slightly lower pulse energies. Subtle sub-1 nJ pulse energy control was harnessed to pattern large surface areas with controlled nano-alloying of Si and Cr. This technique is extendable to vacuum-free large area patterning of nanolayers by alloying them at distinct locations with sub-diffraction resolution. Such metal masks with nano-hole opening can be used for formation of random patterns of nano-needles with sub-100 nm separation when applied to dry etching of Si.

Metastasis is a systemic condition and the major challenge among cancer types, as it can lead to multiorgan vulnerability. Recently, attention has been drawn to cellular senescence, a complex stress response condition, as a factor implicated in metastatic dissemination and outgrowth. Here, we examine the current knowledge of the features required for cells to invade and colonize secondary organs and how senescent cells can contribute to this process. First, we described the role of senescence in placentation, itself an invasive process which has been linked to higher rates of invasive cancers. Second, we describe how senescent cells can contribute to metastatic dissemination and colonization. Third, we discuss several metabolic adaptations by which senescent cells could promote cancer survival along the metastatic journey. In conclusion, we posit that targeting cellular senescence may have a potential therapeutic efficacy to limit metastasis formation.

In the European Union, the eCall system has been mandatory since March 31, 2018. The system enabled a significant increase in safety on roads and highways, making help faster in the event of an accident. However, based on circuit-switched 2G/3G communications and an onboard device called IVS, it is generally unavailable on legacy vehicles. Some of its limitations tend to be remedied by the future NG eCall based on 4G/5G packet-switched communications. This paper discusses why IVS may be an Achilles’ heel of any future IVS-based eCall and analyzes the advantages of a smartphone-based system. The TEZE system, implemented and installed in Italian highway tunnels, is a first general-purpose safety system, and allows highly reliable smartphone-based emergency calls. It is based on a dedicated low-cost ground infrastructure that allows monitoring of the availability of emergency call service through the mobile radio networks of the operators present inside the tunnels. The system complies with the ISO/IEC 30141:2018 reference standard. Identifying functional/non-functional requirements and their verification criteria provide an overall validation of the analyzed system. The paper concludes by examining some key functionalities for vehicular services that can be implemented in an integrated system based on smartphones and heterogeneous networks.

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

The dynamic interplay of signaling networks in most major cellular processes is characterized by the orchestration of reversible protein phosphorylation. Consequently, analytic methods like quantitative phospho-peptidomics has been pushed forward from a highly specialized edge-technique to a powerful and versatile platform for comprehensively analyzing the phosphorylation profile of living organisms. Despite enormous progress in instrumentation and bioinformatics, a major problem remains a high number of missing values caused by the experimental procedure due to either a random phospho-peptide enrichment selectivity or borderline signal intensities, which both cause the exclusion for fragmentation using the commonly applied data dependent acquisition (DDA) mode. Consequently, an incomplete dataset reduces confidence in the subsequent statistical bioinformatic processing. Here, we successfully applied data independent acquisition (DIA) by using the filamentous fungus Magnaporthe oryzae as model organism and could prove that while maintaining data quality (such as phosphosite and peptide sequence confidence), the data completeness increases dramatically. Since the method presented here reduces the LC-MS/MS analysis from 3 h to 1 h and increases the number of phoshosites identified up to 10-fold in contrast to published studies in fungi, we pushed the phospho-proteomic technique beyond its current limits and could provide a sophisticated resource for investigation of signaling processes in filamentous fungi.

Extracellular vesicles (EV), including exosomes and microvesicles, are released from various cells and alter recipient cell phenotypes and fates by their biomolecules. Here we review current knowledge about tumor EVs and how they prompt malignant cell communication with tumor-associated cells, such as cancer-associated fibroblasts, tumor endothelial cells, and immune cells. We delineate the major pathways and molecular players that influence each step of cancer initiation, progression, and resistance. Of note, cancer exosomes involve immunosuppression by tumor-associated macrophages, myeloid-derived suppressor cells, and regulatory T cells. Moreover, tumor exosomes can induce the apoptosis of killer T cells and immune checkpoint of dendritic cells and attenuate natural killer cells. An in-depth understanding of EV biology is essential to ensure the clinical development of exosome/EV-based therapeutic products, which will be of benefit to exosome manipulation in cancer management.

The epithelial cell adhesion molecule (EpCAM) is a stem cell and carcinoma antigen, which mediates cellular adhesion and proliferative signaling by the proteolytic cleavage. In contrast to low expression in normal epithelium, EpCAM is frequently overexpressed in various carcinomas, which correlates with poor prognosis. Therefore, EpCAM has been considered as a promising target for tumor diagnosis and therapy. Using the Cell-Based Immunization and Screening (CBIS) method, we previously established an anti‐EpCAM monoclonal antibody (EpMab-37; mouse IgG1, kappa). In this study, we investigated the antibody‐dependent cellular cytotoxicity (ADCC), complement‐dependent cytotoxicity (CDC), and an antitumor activity by a defucosylated mouse IgG2a-type of EpMab-37 (EpMab-37-mG2a-f) against an EpCAM‐expressing breast cancer cell line (BT-474). EpMab-37-mG2a-f recognized BT-474 cells with a moderate binding-affinity [a dissociation constant (KD): 2.9x10-8 M] by flow cytometry. EpMab-37-mG2a-f exhibited ADCC and CDC for BT-474 cells by murine splenocytes and complements, respectively. Furthermore, administration of EpMab-37-mG2a-f significantly suppressed the BT-474 xenograft tumor development compared with the control mouse IgG. These results indicated that EpMab-37-mG2a-f exerts antitumor activities against the BT-474 xenograft, and could provide valuable therapeutic regimen for the breast cancers.

The urban population in developing countries, especially sub-Saharan Africa, is rapidly increas-ing. As towns and cities grow, so does the demand for fish protein. While flow-through aqua-culture can provide fresh, healthy and nutritious fish protein, it is plagued by extensive land re-quirement as well as effluent discharge, thus, unsuitable for city regions. Alternatively, small-scale Recirculating Aquaculture System (RAS) could improve food and nutritional security (FNS), livelihoods as well as reduce environmental degradation in urban areas despite land and water constraints. The question however remains - what are the key technical, business and managerial issues, surrounding small-scale RAS in urban farming? This study reviews the RAS prototype of the Sustainable Aquaponics for Nutritional and Food Security in Urban Sub-Saharan Africa (SANFU) II project based on mass balance and stock density, relevant for fish survival and/or availability as well as net cash-flow analyses. The results suggest that small-scale RAS are technically and financially viable only with family labor having proper aquaculture monitoring and management skills. Furthermore, access to adequate equipment and inputs as well as electricity for the recirculating system are crucial. Urban innovation actors will adopt RAS if operations are profitable given that family labor is employed.

Background: Both natural immunity and vaccine-induced immunity to COVID-19 may be useful to reduce the mortality/morbidity of this disease, but still a lot of controversy exists. Aims: This narrative review analyzes the literature about: a) the duration of natural immunity; b) cellular immunity; c) cross-reactivity; d) the duration of post-vaccination immune protection; e) the probability of reinfection and its clinical manifestations in the recovered patients; f) comparisons between vaccinated and unvaccinated in the possible reinfections; g) the role of hybrid immunity; h) the effectiveness of natural and vaccine-induced immunity against Omicron variant; i) comparative incidence of adverse effects after vaccination in recovered individuals vs. COVID-19-naïve subjects. Material and Methods: through multiple search engines we investigated COVID-19 literature related to the aims of the review, published since April 2020 through July 2022, including also the previous articles pertinent to the investigated topics. Results: nearly 900 studies were collected and 238 pertinent articles were included. It was highlighted that the vast majority of individuals after COVID-19 develop a natural immunity both of cell-mediated and humoral type, which is effective over time and provides protection against both reinfection and serious illness. Vaccine-induced immunity was shown to decay faster than natural immunity. In general, the severity of the symptoms of reinfection is significantly lower than in the primary infection, with a lower degree of hospitalizations (0.06%) and an extremely low mortality. Conclusions: this narrative review regarding a vast number of articles highlighted the valuable protection induced by the natural immunity after COVID-19, which seems comparable or superior to the one induced by anti-SARS-CoV-2 vaccination. Vaccination of the unvaccinated COVID-19-recovered subjects may not be indicated. Further research is needed in order to: a) measure the durability of immunity over time; b) evaluate both the impacts of Omicron-5 on vaccinated and healed subjects and of hybrid immunity.

Cells respond to a myriad of stressors by senescing, acquiring stable growth arrest, morphologic and metabolic changes, and a senescence-associated-secretory-phenotype (SASP). The heterogeneity of senescent cells (SnCs) and their SASP is vast, yet poorly characterized. SnCs have diverse roles in health and disease and are therapeutically targetable, making characterization of SnCs and harmonization of their nomenclature a priority. The Cellular Senescence Network (SenNet), a NIH Common Fund initiative, will leverage emerging single cell and spatial-omics to identify and map SnCs in numerous organs across the lifespan of humans and mice. A common coordinate framework will integrate the data, using validated, standardized methods, creating public 4-dimensional SnC atlases. Key SenNet deliverables include development of innovative tools/technologies to detect SnCs, biomarker discovery, common annotations to describe SnCs and extensive public data sets. The goal is to comprehensively understand and map SnCs for diagnostic and therapeutic purposes to improve human health.

Most studies on vaccines of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have focused on antibody, but cellular immunities are also critical. We aimed to evaluate the immune reactions of hemodialysis (HD) patients after the administration of the booster dose from the perspective of both humoral and cellular immunities. Hemodialysis patients (HD group) and age- and sex-matched non-dialysis individuals (control group) receiving three doses of BNT162b2 vaccine were measured for anti-SARS-CoV-2 immunoglobulin (IgG) and T-SPOTⓇ.COVID test (T-SPOT) before, 3 weeks, and 3 months after the booster dose. The HD group had significantly higher SARS-CoV-2 IgG levels 3 weeks and 3 months after the booster dose than the control group, although both groups had no difference in SARS-CoV-2 IgG levels before the booster dose. Moreover, the HD group had significantly higher T-SPOT levels before and 3 weeks after the booster dose than the control group, but the difference was not significantly different 3 months after the booster dose. Furthermore, the incidence rates of local and systemic adverse reactions were significantly higher in the HD group than in the control group. HD patients obtained higher SARS-CoV-2 IgG levels and SARS-COV-2-specific T-cell responses after the booster dose than control.

Silicon is an essential trace nutrient for plant growth and is frequently employed to remediate soils contaminated with heavy metals in agriculture. However, silicon’s role and mechanism in reducing heavy metal toxicity have not been well understood, especially for multi-heavy metals. In this study, the effects of silicon-rich materials (silicate, rice husk biochar (RHB), and bentonite) on growth trait, antioxidant response, and heavy metal accumulation and distribution of wheat grown in two soils polluted by multiple heavy metals (Cd, Zn, Pb, and As) were investigated. The results revealed that the addition of silicon-rich materials enhanced plant growth, improved the photosynthetic attributes in leaf tissues, and decreased the contents of Cd, Zn, Pb, and As in wheat shoots and grains. The examination of the subcellular distribution of heavy metals in plants implied that silicon-rich materials transferred heavy metals as intracellular soluble fractions to the cell walls, indicating the reduction of mobility and toxicity of heavy metals in the plants. In addition, the application of the silicon-rich materials reduced oxidative damage in plants by downregulating plant antioxidant response systems and decreasing the production of malondialdehyde (MDA), ascorbic acid (AsA), and glutathione (GSH). Moreover, fractionation analysis of soil heavy metals showed that silicon-rich amendments could convert bioavailable heavy metals into immobilized forms. The results indicated that silicon-rich materials could remediate multi-heavy metal-polluted soils and promote wheat production.

– Every physical theory involving quantum fields does require a model of the quantum vacuum. The vacuum associated to quantum gravity must incorporate the prescriptions from both the theory of relativity and quantum physics. In this work, starting from the hypothesis of nucleation of sub-Planckian bubbles from a de Sitter vacuum, we study the necessary conditions to obtain baby universes, black holes and particles. The de Sitter-Planck background is described by an “infinite” Quantum Boltzmann statistics that generates fermions and bosons, and manifests itself as a deformation of the geometry that leads to a generalized uncertainty principle and a unified expression for the generalized Compton wavelength and event horizon size, drawing a connection between quantum black holes and elementary particles, the latter seen as a collective organization of the bubbles of the vacuum described by the generalized Compton wavelength. The quantum thermodynamics of black holes is then outlined and the physical history of each bubble is found to depend on the cosmological constant described in terms of thermodynamic pressure. Finally, a suggestive treatment of the Casimir effect is provided in the de Sitter-Planck background with Quantum-Boltzmann statistics and wormholes are explored as bubble coalescence processes.

This paper investigates how agroecology in Africa is researched for two purposes. First, we present evidence of links between agroecology and food and nutrition security in sub-Saharan Africa. Second, we investigate which pathways of influence are dominant in the existing research and which pathways are under-represented. To achieve these objectives we anchor our analysis within feminist economics, thereby making use of the concepts of social reproduction and agency in our analysis of the literature. By employing a systematic literature review of empirical studies from African countries, starting from 1996 to 2020, we consolidate evidence that agroecology has contributed to food and nutrition security by acting toward sustainability at the farm level. However, our review shows in a second step that social and household dimensions of agroecology at the level of households and territories are not well documented in research linking agroecology to food security and nutrition in sub-Saharan Africa. Given that sustainable production practices such as agroecological practices are not mutually exclusive from the social activities of farmers and cultural contexts in which farmers are embedded, it is important to consider social and ecological processes concomitantly when assessing the value of Agroecology programs.

Myocilin is an enigmatic glaucoma-associated glycoprotein whose biological role remains incompletely understood. To gain novel insight into its normal function, we used transposon-mediated transgenesis to generate the first zebrafish line stably overexpressing myocilin [Tg(actb1:myoc-2A-mCherry)]. qPCR showed an approximately four-fold increased myocilin expression in transgenic zebrafish embryos (144 hpf). Adult (13 months old) transgenic animals displayed variable and age-dependent ocular anterior segment alterations. Almost 60% of two-years old male, but not female, transgenic zebrafish developed enlarged eyes with severe asymmetrical and variable abnormalities in the anterior segment, characterized by corneal limbus hypertrophy, and thickening of the cornea, iris, annular ligament and lens capsule. The most severe phenotype presented small or absent ocular anterior chamber and pupils, due to iris overgrowth along with dysplastic retinal growth and optic nerve hypertrophy. Immunohistochemistry revealed increased presence of myocilin in most altered ocular tissues of adult transgenic animals, as well as signs of retinal gliosis, and expanded ganglion cells and nerve fibers. The preliminary results indicate that these cells contributed to retinal dysplasia. Visual impairment was demonstrated in all old male transgenic zebrafish. Transcriptomic analysis of the abnormal transgenic eyes identified disrupted expression of genes involved in lens, muscular and extracellular matrix activities, among other processes. In summary, the developed transgenic zebrafish provides a new tool to investigate this puzzling protein and provides evidence for the role of zebrafish myocilin in ocular anterior segment and retinal biology, through the influence of extracellular matrix organization and cellular proliferation.

Nowadays the practice of developing algorithms to maintain the confidentiality of data shows that there is a lack of some features, such as velocity, predictability, etc. Generating pseudorandom numbers is one such problem that lies in the basement of many algorithms, even in hardware microprograms. An unreliable generator can cause cyberattacks on it, despite the security in the upper layers. At the same time, the algorithm should be fast enough to provide uninterrupted circuit work for the entire system. The paper presents a new algorithm generating pseudorandom numbers on cellular automata, which is not only fast and easy-repeating, but unpredictable enough and can be used in cryptographic systems. Using the NIST statistical test suite for random and pseudorandom number generators (PRNG), it is shown that the presented algorithm is more than three times superior to the state-of-the-art methods and algorithms in terms of ? − ?????. A high level of the presented algorithm’s parallelization allows for implementation it effectively on calculators with parallel structure. CPU-based architecture, FPGA-based architecture, CUDA- based architecture of PRNG and different PRNG implementations are presented to confirm high performance of the proposed solution.

One of the most striking findings in biogerontology in the 2010s was the demonstration that elimination of senescent cells delays many late-life diseases and extends lifespan in mice. This implied that accumulation of senescent cells promotes late-life diseases, particularly through action of senescent cell secretions (the senescence-associated secretory phenotype or SASP). But what exactly is a senescent cell? Subsequent to the initial characterization of cellular senescence it became clear that, prior to aging, this phenomenon is in fact adaptive. It supports tissue remodeling functions in a variety of contexts, including embryogenesis, parturition and acute inflammatory processes that restore normal tissue architecture and function, such as wound healing, tissue repair after infection, and amphibian limb regeneration. In these contexts such cells are normal and healthy, and not in any way senescent in the true sense of the word, as originally meant by Hayflick. Thus, it is misleading to refer to them as “senescent”. Similarly, the common assertion that senescent cells accumulate with age due to stress and DNA damage is no longer safe, particularly given their role in inflammation - a process that becomes persistent in later life. We therefore suggest that it would be useful to update some terminology, to bring it into line with contemporary understanding, and to avoid future confusion. To open a discussion of this issue, we propose replacing the term cellular senescence with remodeling activation, and SASP with RASP (remodeling-associated secretory phenotype).

With the ongoing COVID pandemic, the emergence of a novel omicron variant in November 2021 has chaos the world. Despite mass vaccination, this omicron has spread rapidly raising concerns around the globe. The Omicron variant has a vast array of mutations as compared to another variant of concern with overall 50 mutations where 30 mutations are present in its spike protein. This mutation has led to immune escape and more transmissibility compared to other variants, including Delta. A cluster of mutations (H655Y, N679K, and P681H) present at the omicron spike protein could aid in transmission. Currently, no virus-specific data are available to predict the efficacy of anti-viral and mAbs drugs. However, two monoclonal antibody drugs: Sotrovimab and Evusheld are authorized for emergency use in COVID patients. This virus is not fading away soon. The easiest solution and less expensive measure to fight against this pandemic are following COVID appropriate protocols.There is need to strengthen the level of research for development of potential vaccines and anti-viral drugs. It is also important to monitor and expand genomic surveillance to keep track of the emergence of new variants thus avoiding the spread of new diseases worldwide. This article highlights the emergence of omicron and vast number of mutation in its protein. In addition, recent advancement in drugs approved by FDA to treat COVID patients has been listed and focused in this paper.

The main target of this study was to evaluate the impact of future climate change on the available surface water resources in the Dhidhessa Sub-basin, Abbay Basin, Ethiopia. For the prediction, high-resolution Regional Climate Models (RCMs) from multiple climate models with data from Representative Concentration Pathways (RCPs) prepared by the CCAFS were used. The predictions of future discharge (stream flow) were based on climate scenarios data of baseline period of 1991 to 2020 and for the future with two time windows, 2044 (2030–2059) and 2084 (2070–2099), on a monthly time step after bias correction was conducted to both precipitation and temperature in the future climate under each RCP scenario. After sensitivity analysis, calibration (1994–2011), and validation (2012–2020) of the model for the Dhidhessa Sub-basin with the SUFI-2 program in the SWAT-CUP model, the SWAT model was used to determine water balance and stream flow from the SWAT model system. The SWAT model performed well in predicting stream flow in the Dhidhessa Sub-basins, with a coefficient of determination (R2) ranging from 0.8 to 0.94 and a Nash Sutcliffe value (NSE) ranging from 0.76 to 0.89. The percent decrease in mean annual stream flow from 2044 and 2084 were 10 %, in 2044, and 6.3% in 2084 respectively. The seasonal result under short-term 2044 of stream flow present change significantly decreased in spring, winter, and autumn with 20.2%, 67.4%, and 67.4% respectively. While summer season increased by 43.1%, under short-term 204. In long-term 2084 percent change declined except summer seasons, with 14.7%, 58.1%, and 3.3%, change in spring, winter, and autumn, respectively, and summer, with 51.1% increased and With RCP4.5 (1.64%) and RCP8.5 (2.1%) changed. In the future Dhidhessa stream flow increases and decreases from the baseline era. The decreasing stream flow in 2044 and 2084 will negatively affect agricultural production. This study revealed that any effect on this river resulting in a drop in flow will have a direct impact on ongoing water resource development and socio-economic development of the area.

Gas bubbles present in liquids underpin many natural phenomena and human-developed technologies that improve the quality of life. Since all living organisms are predominantly made of water, they may also contain gas bubbles—introduced both naturally and artificially—that can serve as biomechanical sensors operating in hard-to-reach places inside a living body and emitting signals that can be detected by common equipment used in ultrasound and photoacoustic imaging procedures. This kind of biosensors is the focus of the present article, where we critically review the emergent sensing technologies based on acoustically driven oscillations of gas bubbles in liquids and bodily fluids. This review is intended for a broad biosensing community and transdisciplinary researchers translating novel ideas from theory to experiment and then to practice. To this end, all discussions in this review are written in a language that is accessible to non-experts in specific fields of acoustics, fluid dynamics and acousto-optics.

Abstract: Diabetes mellitus (DM) is associated with severe COVID-19 infection and complications. This study assessed COVID-19 vaccine acceptance and hesitancy in diabetes and explored reasons for nonvaccinating. This was a web-based cross-sectional survey using a mixed-method approach conducted between March-May 2021 corresponding to most SSA countries' early vaccine rollout period. Participants were those aged ≥18 years with self-reported DM in 11 Sub-Saharan African (SSA) countries. Responses to comments on reasons for vaccine hesitancy and facilitators for vaccine uptake were analyzed. Of the 73 participants with DM, 65.8% were males older than 35 years (86.3%), had post-secondary education (90%), and a significant proportion was from South Africa (39.7%), Nigeria (28.8%) and Ghana (13.7%). 64.4% had COVID-19 symptoms, 46.6% were tested for COVID-19, of which 19.2% tested positive. Few participants (6.8%) had taken the COVID-19 vaccination, 65.8% were willing to take the vaccine, while 26.0% either refused or hesitated to take the vaccine. The main reasons identified for not taking the vaccine were: advice from religious leaders, concerns about the vaccine safety, its effects, and efficacy, mistrust of the pharmaceutical companies, the conspiracy theories around the vaccines, the process of production, and the personal belief of the participants. However, participants stated they would take the vaccine if given more education about it, receive positive feedback from those vaccinated, are rewarded for taking the vaccine or if vaccination becomes a condition for travel and employment. The findings of this study showed that uptake of the COVID-19 vaccine was very low in this high-risk group. It is imperative that efforts to increase the uptake of vaccines, such as the provision of education and relevant information, are made.

Synechococcus sp. PCC 11901 reportedly demonstrates the highest, sustained growth of any known cyanobacterium under optimized conditions. Due to its recent discovery our knowledge of its biology, including the factors underlying sustained, fast growth, is limited. Furthermore, tools specific for genetic manipulation of PCC 11901 are not established. Here, we demonstrate that PCC 11901 shows faster growth than other model cyanobacteria, including the fast-growing species Synechococcus elongatus UTEX 2973, under optimal growth conditions for UTEX 2973. Comparative genomics between PCC 11901 and Synechocystis sp. PCC 6803 reveal conservation of most metabolic pathways but PCC 11901 has a simplified electron transport chain and reduced light-harvesting complex. This may underlie its superior light utilization, reduced photoinhibition and higher photosynthetic and respiratory rates. To aid biotechnology applications we developed a vitamin B12 auxotrophic mutant but were unable to generate unmarked knockouts using two negative selectable markers, suggesting that recombinase- or CRISPR-based approaches may be required for repeated genetic manipulation. Overall, this study establishes PCC 11901 as one of the most promising species currently available for cyanobacterial biotechnology and provides a useful set of bioinformatics tools and strains for advancing this field, in addition to insights into the factors underlying its fast growth phenotype.

Cancer stem cells play a crucial role in tumor initiation, metastasis and therapy resistance. Cellular heterogeneity and plasticity challenge the isolation of cancer stem cells. The impact of intratumoral cellular heterogeneity in the context of treatment resistance using a label-free approach remains understudied. Here, we use the sedimentation field-flow fractionation technique to separate, without labeling, cell subpopulations of colorectal cancer cell lines and primary cultures according to their biophysical properties. One of the three cell subpopulations sorted by SdFFF exhibits cancer stem cell traits, including high tumorigenicity in vivo, and a higher frequency of tumor-initiating cells compared to the other subpopulations. In vitro two- and three-dimensional chemosensitivity assays emphasize the therapeutic relevance of this cancer stem cell-like subpopulation due to its chemoresistance. Therefore, our findings highlight a label-free cell sorting approach to reveal intratumoral cellular heterogeneity and its implication in therapy resistance. This approach enables the study of the individualized response of each sorted cell subpopulation by breaking down the tumor, thus offering new perspectives for personalized therapy.

In epithelia, breakdown of tensional homeostasis is closely associated with E-cadherin dysfunction and disruption of tissue function and integrity. In this study, we investigated the effect of E-cadherin mutations affecting distinct protein domains on tensional homeostasis of gastric cancer cells. We used micropattern traction microscopy to measure temporal fluctuations of cellular traction forces in AGS cells transfected with the wild-type E-cadherin or with variants affecting the extracellular, the juxtamembrane, and the intracellular domains of the protein. We focused on the dynamic aspect of tensional homeostasis, namely the ability of cells to maintain a consistent level of tension, with low temporal variability around a set point. Cells were cultured on hydrogels micropatterned with different extracellular matrix (ECM) proteins to test whether the ECM adhesion impacts cell behavior. A combination of Fibronectin and Vitronectin was used as a substrate that promotes the adhesive ability of E-cadherin dysfunctional cells, whereas Collagen VI was used to test an unfavorable ECM condition. Our results showed that mutations affecting distinct E-cadherin domains influenced differently cell tensional homeostasis, and pinpointed the juxtamembrane and intracellular regions of E-cadherin as the key players in this process. Furthermore, Fibronectin and Vitronectin might modulate cancer cell behavior towards tensional homeostasis.

: Urinary schistosomiasis caused by the parasite Schistosoma haematobium is the most common form of schistosomiasis. This parasite has a high potential for genetic exchange within parasite populations giving rise to the genetic diversity that is important for its survival. Genetic differ-ences may lead to some parasite strains being more immunogenic which may have a negative impact on management and control of schistosomiasis. Therefore, understanding these genetic differences in the parasite may lead to better management of the disease. A literature search was done on PubMed, African Journals online and Google scholar using predefined search terms such as urinary schistosomiasis, S. haematobium, genetic diversity in sub-Saharan Africa in com-bination with Boolean operators (AND, OR). The search included studies published from 2000-2020 that emphasised on genetic diversity of Schistosoma haematobium in sub-Saharan Africa. Sixteen studies from 18 sub-Saharan African countries that met the inclusion criteria were se-lected. Most studies conducted in these countries showed a high genetic diversity of Schistosoma haematobium studies with microsatellite markers being the most commonly used method for ge-netic diversity determination. Fisher’s exact test showed that the distribution of genetic diversity in sub-Saharan African regions was not statistically significant (p=0.768). The highest number of studies on genetic diversity of Schistosoma haematobium were conducted in West Africa with Ni-geria and Zimbabwe in Southern Africa conducting the most studies, 4/36 (11%) each. Results obtained show the need for continued monitoring of genetic variations in Schistosoma haemato-bium in sub- Saharan Africa. This will aid in understanding the epidemiology of disease, ad-vancing novel treatment and vaccine strategies.

Human pluripotent stem cells (hPSCs) have widespread potential biomedical applications. There is a need for large-scale in vitro production of hPSCs, and optimal culture methods are vital in achieving this. Physiological oxygen (2% O2) improves key hPSCs attributes, including genomic integrity, viability, and clonogenicity, however, its impact on hPSC metabolism remains un-clear. Here, Selected Ion Flow Tube-Mass Spectrometry (SIFT-MS) was used to detect and quantify metabolic Volatile Organic Compounds (VOCs) in the headspace of hPSCs and their differentiated progeny. hPSCs were cultured in either 2% O2 or 21% O2. Media was collected from cell cultures and transferred into glass bottles for SIFT-MS measurement. The VOCs acetaldehyde and dimethyl sulfide (DMS)/ethanethiol were significantly increased in undifferentiated hPSCs compared to their differentiating counterparts, and these observations were more apparent in 2% O2. Pluripotent marker expression was consistent across both O2 concentrations tested. Transcript levels of ADH4, ADH5, and CYP2E1, encoding enzymes involved in converting ethanol to acetaldehyde, were upregulated in 2% O2, and chemical inhibition of ADH and CYP2E1 decreased acetaldehyde levels in hPSCs. Acetaldehyde and DMS/ethanethiol may be indicators of altered metabolism pathways in physiological oxygen culture conditions. The identification of non-destructive biomarkers for hPSC characterization has the potential to facilitate large-scale in vitro manufacture for future biomedical application.

This paper studies the performance improvement of the IEEE 802.15.4 nonbeacon-enabled mode originated by the inclusion of the Request-To-Send/Clear-To-Send (RTS/CTS) handshake mechanism resulting in frame concatenation. Under IEEE 802.15.4 employing RTS/CTS, the backoff procedure is not repeated for each data frame sent but only for each RTS/CTS set. The maximum throughput and minimum delay performance are mathematically derived for both the Chirp Spread Spectrum and Direct Sequence Spread Spectrum Physical layers for the 2.4 GHz band. Results show that the utilization of RTS/CTS significantly enhances the performance of IEEE 802.15.4 applied to healthcare in terms of bandwidth efficiency.

Alzheimer’s disease (AD) predominantly occurs as a late-onset form (LOAD), involving neurodegeneration and cognitive decline with progressive memory loss. Over time, risk factors and aging promote accumulation of well-known AD pathologies in oxidative stress, amyloid-beta and tau protein pathology, as well as inflammation. Homeostatic glial functions regulate and suppress these AD pathologies; however, other glial states involve increased pro-inflammatory cytokine release and further pathology accumulation. Different stresses can additionally induce cellular senescence, or an irreversible differentiation process resulting in decreased supportive functions and increased, pro-inflammatory cytokine release. While these pathophysiological underpinnings all contribute to LOAD, they require temporal and mechanistic integration. This perspective hypothesizes that when individuals have threshold senescent glia accumulation, they transition from healthy cognition into mild cognitive impairment and LOAD diagnosis. Particularly, senescent microglia are predicted to represent a final threshold required for the tau pathology burden and spreading that corresponds to sustained neurodegeneration and dementia severity. We first explore age-related decline in glia that promote increases in AD pathologies, and then discuss emerging evidence linking oxidative stress, neurons containing tau pathology, and amyloid-beta to microglia, oligodendrocyte progenitor cell, and astrocyte senescence. Our hypothesis proposes that senescent astrocytes and oligodendrocyte progenitors pressure microglia to phagocytose neurons containing tau pathology. The resulting senescent microglia would form neuritic plaques and induce paracrine senescence transitioning into a progressive clinical dementia presentation. This predictive hypothesis can potentially account for why medications used to treat LOAD fail, as previous treatments have not reduced senescent glial burden. It is also coherent with the predominant hypotheses surrounding LOAD, generates testable hypotheses about LOAD, and increases rationale in testing senolytics as targeted treatments for LOAD arrest and reversal.

The quantification of sea surface temperature (SST) through space platforms has revolutionized how we obtain information at a global level. However, the main disadvantage of obtaining SST with satellite images consists of its inherent coarse spatial resolution. One solution could be the use of downscaling algorithms to create sequences of matrices at a higher resolution. We used the same SST data source from the MODIS-Aqua sensor at three spatial resolutions of 9 km, 4.5 km, and 1 km in the Gulf of California. Based on an open-source algorithm, the original SST images were downscaled to 4.5 km, 1 km, 500 m, 250 m, and 125 m per pixel scales. Results indicate a strong linear relationship between the original SST-MODIS data and the modeled data for all spatial resolutions. This study demonstrates the feasibility of an open-source downscaling algorithm to enhance the spatial resolution of SST images in a marginal sea.

Validation of satellite sea surface salinity (SSS) products is typically based on comparisons with in-situ measurements at a few meters depth, that are mostly done at a single location and time. The difference in term of spatio-temporal resolution between the in-situ near-surface salinity and the two-dimensional satellite SSS results in a sampling mismatch uncertainty. The Climate Change Initiative (CCI) project has merged SSS from three satellite missions. Using an optimal interpolation, weekly and monthly SSS and their uncertainties are estimated at a 50 km spatial resolution over the global ocean. Over the 2016-2018 period the mean uncertainty on weekly CCI SSS is 0.13, whereas the standard deviation of weekly CCI minus in-situ Argo salinities is 0.24. Using high resolution SSS simulations, we estimate the expected uncertainty due to the CCI versus Argo sampling mismatch. Most of the largest spatial variability of the satellite minus Argo salinity are observed in regions with large mismatch. A quantitative validation is performed by considering the statistical distribution of the CCI minus Argo salinity normalized by the sampling and retrieval uncertainties. This quantity should follow a Gaussian distribution with a standard deviation of 1, if all uncertainty contributions are properly considered. We find that 1) the sampling mismatch can explain most of the observed differences between Argo and CCI data, especially for monthly products and in dynamical regions (river plumes, fronts), 2) overall, the uncertainties are well estimated in CCI version 3, much better compared to CCI version 2. There are a few dynamical regions where discrepancies remain, and where the satellite SSS, their associated uncertainties and the sampling mismatch estimates should be further validated.

Global malaria epidemiology has changed in the last decade with a substantial increase in cases and death being recorded. Over 90% of global cases and deaths occur in Sub-Saharan Africa (SSA). Tanzania accounts for about 4% of all cases and deaths reported in recent years. It is believed that several factors contribute to the resurgence of malaria, parasite resistance to antimalarials and mosquito resistance to insecticides being at the top of the list. The presence of sub-microscopic infections poses a significant challenge to malaria rapid diagnostic tests (mRDT), particularly in low-endemic areas. Our cross-sectional surveys in Handeni and Moshi, Tanzania assessed the effect of low parasite density on mRDT. A significant difference (P˂0.001) in malaria prevalence by mRDT, light microscopy (LM) and nested polymerase chain reaction (PCR) was found among age groups. In comparison to all other groups, school-age children (5-15 years) had the highest prevalence of malaria. Based on the results of this study, mRDT may miss up to 6% of cases of malaria mainly due to low-density parasitaemia. Routinely used mRDT will likely miss the sub-microscopic parasitemia which will ultimately contribute to the continued spread of malaria and hinder efforts to control and eliminate it.

All fundamental Planck scale symmetries are restored on a global level when a new charge is postulated in a finite, closed, Euclidean discrete space. Gravity emerges as a residual effect of the electromagnetic force in this scenario, resulting in a deterministic toy universe driven by a single input parameter. The model is developed using a constructive approach. Randomness is identified using a Chaintin argument. Aleph0 definite value is tied to the size of the universe. This is not an interpretation of Quantum Mechanics, but a deeper attempt to describe nature.

All fundamental Planck scale symmetries are restored on a global level when a new charge is postulated in a finite, closed, Euclidean discrete space. Gravity emerges as a residual effect of the electromagnetic force in this scenario, resulting in a deterministic toy universe driven by a single input parameter. Randomness is identified using a Chaintin argument. Aleph0 definite value is tied to the size of the universe. This is not an interpretation of Quantum Mechanics, but a deeper attempt to describe nature.

Bone tissue engineering has developed significantly in recent years as the increasing demand for bone substitutes due to trauma, cancer, arthritis, and infections. The scaffolds for bone regeneration need to be mechanically stable and have a 3D architecture with interconnected pores. With the advances in additive manufacturing technology, these requirements can be fulfilled by 3D printing scaffolds with controlled geometry and porosity using a low-cost multistep process. The scaffolds, however, must also be bioactive to promote the environment for the cells to regenerate into bone tissue. To determine if a low-cost 3D printing method for bespoke SiOC(N) porous structures can regenerate bone these structures were tested for osteointegration potential by using human mesenchymal stem cells (hMSCs). This includes checking the general biocompatibilities under the osteogenic differentiation environment (cell proliferation and metabolism). Moreover, cell morphology was observed by confocal microscopy and gene expressions on typical osteogenic markers at different stages for bone formation were determined by real-time PCR. The results of the study showed the pore size of the scaffolds had a significant impact on differentiation. A certain range of pore size could stimulate osteogenic differentiation, thus promoting bone regrowth and regeneration.

Human papillomavirus (HPV) self-sampling (Self-HPV) is a promising strategy to improve cervical cancer screening coverage in low-income countries. However, issues associated with women who prefer conventional HPV clinical-sampling over HPV self-sampling may affect screening participation. To address this issue, our study assessed factors associated with women’s preferences related to Self-HPV. This study was embedded in a large clinical trial recruiting women aged 30–49 years in a primary HPV-based study termed “3T-Approach” (for Test-Triage-Treatment), launched in 2018 at Dschang District Hospital, West Cameroon. Participants were invited to perform a Self-HPV. After the sampling and before receiving the results, participants completed a questionnaire about cervical cancer screening and their preferences and perceptions around Self-HPV. The median age of the 2201 participants was 40.6 (IQR 35–45) years. Most (1693 (76.9%)) preferred HPV self-sampling or had no preference for either method and 508 (23.1%) preferred clinician-sampling. Factors associated with an increased likelihood of reporting a clinician-sampling preference were tertiary educational level (14.4% CI: 12.8–16.1 vs 29.5% CI: 25.6–33.6) and being an employee with higher grade professional or managerial occupations (5.5% CI: 3.8–7.9 vs 2.6% CI: 2.3–2.8). The main reported reason for women preferring clinician-sampling was a lack of “self-expertise”. Most women (>99%) would agree to repeat HPV self-sampling and would recommend it to their relatives. HPV self-sampling in the cultural context of central Africa was well accepted by participants, but some participants would prefer to undergo clinician sampling. Health systems should support well-educated women to increase self-confidence in using HPV self-sampling.

The holy grail of Artificial Intelligence (AI) has been to mimic human intelligence using computing machines. Autopoiesis which refers to a system with well-defined identity and is capable of re-producing and maintaining itself and cognition which is the ability to process information, apply knowledge, and change the circumstance are associated with resilience and intelligence. While classical computer science (CCS) with symbolic and sub-symbolic computing has given us tools to decipher the mysteries of physical, chemical and biological systems in nature and allowed us to model, analyze various observations and use information to optimize our interactions with each other and with our environment, it falls short in reproducing even the basic behaviors of living organisms. We present the foundational shortcomings of CCS and discuss the science of infor-mation processing structures (SIPS) that allows us to fill the gaps. SIPS allows us to model su-per-symbolic computations and infuse autopoietic and cognitive behaviors into digital machines. They use common knowledge representation from the information gained using both symbolic and sub-symbolic computations in the form of system-wide knowledge networks consisting of knowledge nodes and information sharing channels with other knowledge nodes. The knowledge nodes wired together fire together to exhibit autopoietic and cognitive behaviors.

Cellular Nonlinear Networks (CNN) are a concept introduced in 1988 by Leon Chua and Lin Yang as a bio-inspired architecture, capable of massively parallel computation. Later on, CNN have been enhanced by incorporating designs that incorporate memristors to profit from their processing and memory capabilities. In addition, Stochastic Computing (SC) can be used to optimize the quantity of required processing elements; thus it provides a lightweight approximate computing framework, quite accurate and effective, though. In this work, we propose utilization of SC in designing and implementing a memristor-based CNN. As a proof of the proposed concept, an example of application is presented. This application combines Matlab and a FPGA in order to create the CNN. The implemented CNN has then been used to perform three different real-time applications on a 512x512 gray-scale and a 768x512 color image: storage of the image, edge detection, and image sharpening. It has to be pointed out that the same CNN has been used for the three different tasks, with the sole change of some programmable parameters. Results show an excellent capability with significant accompanying advantages, like the low number of needed elements further allowing for a low cost FPGA-based system implementation, something confirming the system’s ability for real time operation.

Ramsey’s economic theory of saving (RTS) estimates how much of its commodities a nation should save to safeguard the well-being of future generations. Since RTS retains many attractive qualities such as simplicity, strength, breadth and generality, here we ask if it would be useful to investigate biophysical issues. Specifically, we focus on a biological topic that lends itself as a backdrop for the study of the imbalance between intake and expenditure, i.e., the evaluation of the multicellular living organisms’ energetic requirements and constraints. Our problem is to find at each time the optimum distribution and the right balance of the cellular energy budget between consumption and storage: how much must a living organism spare to increase its chances of survival over long periods? Suggesting how to find the optimum allocation of the available energy between expenditure and saving at each time, RTS approaches to biological energy budgets may have a wide range of experimental applications, such as: a) optimization of the long-term survival chances of either immortalized cell cultures, or beneficial bacterial colonies and exogenous probiotic mixtures; b) eradication of detrimental biofilms, such as, e.g., heart valves’ Streptococcus colonies; c) novel anti-stress and anti-ageing strategies.

We propose a non-invasive approach to control the quality of spheroids and their fusion into a complex bioconstruct. The proposed method is based on the union of the nutrient concentration change calculated using Fick's law and the "reaction-diffusion" equations, taking into account absorption coefficient with specifying the exact fusion geometry using implicit Function Repre-sentation (FRep) functions. The proposed approach allows us to analyze the viability of cells within the spheroid, predict the fusion of spheroids, and accurately model complex heteroge-neous biostructures as a future task for our research. These results will significantly accelerate the development of such a promising field of additive biotechnologies as 3D bioprinting.

The most important predictors for outcomes after ischemic stroke, that is, for health deterioration and death, are chronological age and stroke severity; gender, genetics and lifestyle / environmental factors also play a role. Of all these, only the latter can be influenced after the event, even though recurrent stroke may be prevented by antiaggregant/anticoagulant therapy, angioplasty of high-grade stenoses, and treatment of cardiovascular risk factors. Moreover, blood cell composition and protein biomarkers such as C-reactive protein or interleukins in serum are frequently considered as biomarkers of outcome. We surveyed protein biomarkers that were reported to be predictive for outcome after ischemic stroke, specifically considering biomarkers that predict long-term outcome (≥3 months) and that are measured over the first days following the event. We classified the protein biomarkers as immune‑inflammatory, coagulation-related, and adhesion-related biomarkers. Some of these biomarkers are closely related to cellular senescence and, in particular, to the inflammatory processes that can be triggered by senescent cells. Moreover, the processes that underlie inflammation, hypercoagulation and cellular senescence connect stroke to cancer, and biomarkers of cancer-associated thromboembolism, as well as of sarcopenia, overlap strongly with the biomarkers discussed here. Finally, we demonstrate that most of the outcome-predicting protein biomarkers form a close-meshed functional interaction network, suggesting that the outcome after stroke is partially determined by an interplay of molecular processes relating to inflammation, coagulation, cell adhesion and cellular senescence.

The demand of high data rate and ubiquitous coverage in heterogeneous cellular (HetNets) is increasing progressively. In order to meet this demand, sophisticated model having applied interference reduction scheme and cell association technique is needed. The small base station (sBS)are deployed inside the broadcasting area of macro base station (mBS), in heterogeneous cellular networks (HetNets). Since mBS has high transmission power therefore a large number of users get connected with mBS. This causes disproportion of load distribution across the HetNets. For load balancing users from high power mBS are migrated to low power sBS to increase network capacity and to decrease the load from mBS. This results in interference in the communication signal because of strong mBS Interference. Hence, we need interference management technique to mitigate interference and user association and to efficiently use sBSs’ resources. Inter-cell interference (ICI) limit the HetNets’ performance. Additionally, there exist deliberate jamming interference which depends on jammers transmission power and its proximity with the target, which notably degrades the network performance. In this paper, we employ reverse frequency allocation scheme (RFA) to reduce inter cell interference, deliberate jamming interference and to accomplish load balancing. The proposed setup is analyzed inquisitively and with the help of simulations. The result shows reduction in interferences as well as balance of load distribution in the network achieved by employing RFA scheme together with cell association.

Critical care of neonates involves substantial usage of antibiotics and exposure to multidrug resistant (MDR) nosocomial pathogens. These pathogens are often exposed to sub-MIC doses of antibiotics which might result in a range of physiological effects. Therefore, to understand the outcome of sub-inhibitory dosage of antibiotics on Staphylococcus populations, nasal swab specimens were collected from 34 neonates admitted to the Sick Newborn Care Unit between 2017-2018, a total of 41 non-repetitive isolates were included in this study. Staphylococcus haemolyticus was the prevalent species (58.54%) with high non-susceptibility to cefotaxime (CTX) (79.16%), gentamicin (87.50%), and meropenem (54.17%). Biofilm forming abilities of S. haemolyticus isolates in the presence of sub-optimal CTX (30μg/mL), the predominantly prescribed β-lactam antibiotic, were then determined by crystal violet assays and extracellular DNA (eDNA) quantitation. CTX was found to significantly enhance biofilm production among the non-susceptible isolates (p-valueWilcoxin test- 0.000008) with increase in eDNA levels (p-valueWilcoxin test- 0.000004). Additionally, no changes in non-susceptibility were observed among populations of two MDR isolates, JNM56C1 and JNM60C2 after >500 generations of growth in the absence of antibiotic selection in vitro. These findings demonstrate that sub-MIC concentration of CTX induces biofilm formation and short-term non-exposure to antibiotics does not alter non-susceptibility among S. haemolyticus isolates.

Viruses are obligate intracellular parasites that are dependent on host factors for their replication. One such host protein, p97 or the valosin-containing protein (VCP), is a highly conserved AAA ATPase that facilitates replication of diverse RNA- and DNA-containing viruses. The wide range of cellular functions attributed to this ATPase is consistent with its participation in multiple steps of the virus life cycle from entry and uncoating to viral egress. Studies of VCP/p97 interactions with viruses will provide important information about host processes and cell biology, but also viral strategies that take advantage of these host functions. The critical role of p97 in viral replication might be exploited as a target for development of pan-antiviral drugs that exceed the capability of virus-specific vaccines or therapeutics.

Cancer is one of the leading causes of death and morbidity with a complex pathophysiology. Traditional cancer therapies include chemotherapy, radiation therapy, targeted therapy, and immunotherapy. However, limitations such as lack of specificity, cytotoxicity, and multi-drug resistance pose a substantial challenge for favorable cancer treatment. The advent of nanotechnology has revolutionized the arena of cancer diagnosis and treatment. Nanoparticles (1-100nm) can be used in the treatment of cancer owing to their specific advantages such as biocompatibility, reduced toxicity, more excellent stability, enhanced permeability and retention effect, and precise targeting. Nanoparticles are classified into several main categories. The nanoparticle drug delivery system is particular and utilizes tumor and tumor environment characteristics. Nanoparticles not only solve the limitations of conventional cancer treatment but also overcome multidrug resistance. Additionally, as new multidrug resistance mechanisms are unraveled and studied, nanoparticles are being investigated more vigorously. Various therapeutic implications of nano-formulations have created brand new perspectives for cancer treatment. However, a majority of the research is limited to in vivo and in vitro studies, and the number of nano-drugs that are approved has not much amplified over the years. In this review, we discuss numerous types of nanoparticles, targeting mechanisms along with approved nanotherapeutics for oncological implications in cancer treatment. Further, we also summarize the current perspective, advantages, and challenges in clinical translation.

In this contribution, we present a high-speed multiplex grating spectrometer based on a spectral coding approach that is founded on principles of compressive sensing. The spectrometer employs a single-pixel InGaAs detector to measure the signals encoded by an amplitude spatial light modulator (digital micromirror device, DMD). This approach leads to a speed advantage and multiplex sensitivity advantage atypical for standard dispersive systems. Exploiting the 18.2 kHz pattern rate of the DMD, we demonstrate 4.2 ms acquisition times for full spectra with a bandwidth of 450 nm (5250 cm-1 – 4300 cm-1; 1.9 µm – 2.33 µm). Due to the programmability of the DMD, spectral regions of interest can be chosen freely, thus reducing acquisition times further, down to the sub-millisecond regime. The adjustable resolving power of the system accessed by means of computer simulations is discussed, quantified for different measurement modes, and verified by comparison with a state-of-the-art Fourier-transform infrared spectrometer. We show measurements of characteristic polymer absorption bands in different operation regimes of the spectrometer. The theoretical multiplex advantage of 8 was experimentally verified by comparison of the noise behavior of the spectral coding approach and a standard line-scan approach.

Lipid composition in the cellular membranes plays an important role in maintaining the struc-tural integrity of cells and in regulating cellular signaling that controls functions of both mem-brane-anchored and cytoplasmic proteins. ATP-dependent ABC and P4-ATPase lipid transport-ers, two integral membrane proteins, are known to contribute to lipid translocation across the li-pid bilayers on the cellular membranes. In this review, we will highlight current knowledge about the role of cholesterol and phospholipids of cellular membrane in regulating cell signaling and how lipid transporters participate this process.

Satellite-based broad-scale (i.e., global and continental) human settlement data offer foundational information for diverse applications spanning climate hazard mitigation, sustainable development monitoring, spatial epidemiology, and demographic modeling. While many human settlement products report exceptional detection accuracies above 85%, there is a substantial blind spot in that product validation is typically centered on large urban areas rather than rural, small-scale settlements that are home to 3.4 billion people. In this study, we make use of a data-rich collection of 30 refugee settlements in Uganda to produce a targeted assessment of small-scale settlement detection by four broad-scale human settlement products: Global Human Settlements Built-Up Sentinel-2 (GHS-BUILT-S2), World Settlement Footprint (WSF), High Resolution Settlement Layer (HRSL), and Geo-Referenced Infrastructure and Demographic Data for Development (GRID3). We measured each product’s areal coverage within refugee settlements, assessed product detection accuracies in comparison to an independent dataset of 317,416 refugee settlement building footprints, and examined agreement between products. For refugee settlements established before 2016, the human settlement products had a low median F1-Score (F1) of 0.24, a high median false alarm rate of 0.59, and tended to only agree at locations of highest building density. Individually, WSF entirely overlooked 8 of the 30 study refugee settlements (median F1=0.17); GHS-BUILT-S2 underestimated the building footprint area by a median 50% (F1=0.15); GRID3 overestimated the building footprint area by a median 280% (F1=0.38); and HRSL underestimated the median area by 7% (F1=0.34). All products suffer from low detection accuracy and high false alarm rates, but GRID3 and HRSL, based on 0.5 meter resolution imagery, offer better detection accuracy than GHS-BUILT S2 and WSF, which are based on 10-30 meter resolution imagery. These results show that human settlement products have far to go in providing an accurate depiction of small-scale refugee settlements and would benefit from incorporating refugee settlements in training and validation of broad-scale human settlement detection.

The theory of the origin of carcinomas suggests that neoplasias from epithelial tissues are the consequence of the reactivation of developmental programs. It proposes a model in which the epithelial cells undergo cellular transitions due to replicative senescence and inflammation towards a mesenchymal-undifferentiated phenotype with cancerous behavior. The conserved pattern of histological progression and the molecular biology of carcinomas is congruent with the view of cancer as a developmental disease. In support of the theory, the experimental literature regarding the molecular, cellular, and histopathological mechanisms associated with epithelial carcinogenesis were aligned according to the premises of the hypothesis. Thereby identified a generic process in the carcinogenesis of the breast, endometrium, prostate, colon, lung, pancreas, bladder, liver, and cervix. Then, is provided a methodology overview of modeling in systems biology derived from previous research testing the hypothesis. The results illustrate the value of the complex systems approach to recover behavior that cannot be inferred only by traditional methods. Specifically, the model suggests that the consistency in the cell types and the directionality of the observed cellular transitions during epithelial carcinogenesis arise from structural constraints in the molecular networks associated with the carcinomas. Overall, the results of the dynamical analysis agree with the premises of the hypothesis and provide an insightful perspective of the potential mechanisms underlying the cellular plasticity displayed during epithelial carcinogenesis. In an era of big data and yet few advances in the underlying causes of chronic diseases, the manuscript also aims to inspire molecular biologists to integrate existing empirical evidence with systems biology modeling in the pursuit of understanding.

The urgent need for effective, safe and equitably accessible vaccines to tackle the ongoing spread of COVID-19 led researchers to generate vaccine candidates targeting varieties of immunogens of SARS-CoV-2. Because of its crucial role in mediating binding and entry to host cell and its proven safety profile, the subunit 1 (S1) of the spike protein represents an attractive immunogen for vaccine development. Here, we developed and assessed the immunogenicity of a DNA vaccine encoding the SARS-CoV-2 S1. Following in vitro confirmation and characterization, the humoral and cellular immune responses of our vaccine candidate (pVAX-S1) was evaluated in BALB/c mice using two different doses, 25 µg and 50 µg. Our data showed high levels of SARS-CoV-2 specific IgG and neutralizing antibodies in mice immunized with three doses of pVAX-S1. Analysis of the induced IgG subclasses showed a Th1-polarized immune response as demonstrated by the significant elevation of spike-specific IgG2a and IgG2b compared to IgG1. Furthermore, we found that immunization of mice with three doses of 50 µg of pVAX-S1 could elicit significant memory CD4+ and CD8+ T cell responses. Taken together, our data indicates that pVAX-S1 is immunogenic and safe in mice and is worthy of further preclinical and clinical evaluation.

This paper shows that the percolation clusters from elementary cellular automata {30, 45, 60, 86, 99, 105, 129, 150, 153, 169, 182, 183, 184, 195 and 225 exhibit strong power law behavior, either under random initial conditions, a single occupied cell, or both. Most of the tail exponents are less than unity, implying diverging means and variances of cluster sizes. The analysis presented here is admittedly coarse in an effort to expedite its dissemination.

Among the different ways to reduce the secondary effects of antineoplastic drugs in cancer treatment, the use of nanoparticles has demonstrated good results due to the protection of the drug and the possibility of releasing compounds to a specific therapeutic target. The α-isoform of folate receptor (FR) is overexpressed on a significant number of human cancers; therefore, folate-targeted crosslinked nanoparticles based on BSA and alginate mixtures and loaded with paclitaxel (PTX) have been prepared to maximizing the proven antineoplastic activity of the drug against solid tumors. Nanometric-range sized particles (169 ± 28nm - 296 ± 57nm), with negative Z-potential values (between -0.12 ± 0.04 and -94.1± 0.4), were synthesized. The loaded PTX (2.63±0.19 - 3.56 ±0.13 µg PTX/mg Np) was sustainably released along 23 and 27h. Three cell lines (MCF-7, MDA-MB-231 and HeLa) were selected to test the efficacy of the folate-targeted PTX-loaded BSA/ALG nanocarriers. The presence of FR on cell membrane led to a significant larger uptake of BSA/ALG-Fol nanoparticles regarding to the equivalent nanoparticles without folic acid on its surface. The cell viability results demonstrated a cytocompatibility of unloaded nanoparticle-Fol and a gradual decrease in cell viability after treatment with PTX-loaded nanoparticles-Fol due to the sustainable PTX release.

:Pulmonary fibrosis is a chronic and fatal lung disease that significantly impacts the aging population globally. To date, anti-fibrotic, immunosuppressive, and other adjunct therapy demonstrate a limited efficacy. Advancing our understanding of pathogenic mechanisms of lung fibrosis provides a future path for the cure. Cellular senescence has gained substantial interest in the past decades due to the increased incidence of fibroproliferative lung diseases in the older age group. Furthermore, the pathologic state of cellular senescence that includes maladaptive tissue repair, decreased regeneration, and chronic inflammation resembles key features of progressive lung fibrosis. This review describes regulatory pathways of cellular senescence and discusses the current knowledge on the senescence of critical cellular players of lung fibrosis, including epithelial cells (alveolar type 2 cells, basal cells, etc.), fibroblasts, and immune cells, their phenotypic changes, and the cellular and molecular mechanisms by which these cells contribute to the pathogenesis of pulmonary fibrosis. A few challenges in the field include establishing appropriate in vivo experimental models and identifying senescence targeted signaling molecules and specific therapy to target senescent cells, known collectively as "senolytic" or “senotherapeutic” agents.

The significance of diversity, composition, and functional attributes of the gut microbiota is recognized in human health and disease. Studies have also shown that the gut microbiota is related to human aging, and a causal relationship between gut microflora dysbiosis and chronic age-related disorders is also becoming apparent. Further, emerging evidence indicates that age-associated changes in the gut microbiome are predictors of human survival and longevity. Recent advances in our understanding of the cellular and molecular aspects of biological aging have revealed a cellular senescence-centric view of the aging process. However, the association between gut microbiome and cellular senescence is only beginning to be understood. The present review provides an integrative view of the emerging relationship between the gut microbiome and cellular senescence in aging and disease. Evidence relating to microbiome-mediated modulation of senescent cells, as well as senescent cells-mediated changes in intestinal homeostasis have been discussed. Unanswered questions and future research directions have also been deliberated to truly ascertain the relationship of the gut microbiome and cellular senescence for developing microbiome-based age-delaying and longevity promoting therapies.

Alzheimer’s disease (AD) is the most common cause of dementia worldwide. Pathological deposits of neurotoxin proteins within the brain, such as amyloid-Beta and hyperphosphorylated tau tangles, are prominent features in AD. The prion protein (PrP) is involved in neurodegeneration via its conversion from the normal cellular form PrPc, to the infection form PrP Sc. Some studies indicated that posttranslationally modified PrPc isoforms plays a fundamental role in AD pathological progression. Several studies have shown that interaction of Aβ oligomers with N-terminal residues of the PrPc protein region appears critical for neuronal toxicity. The PrPc-Aβ binding always occur in AD brains and is never detected in nondemented controls and the binding of Aβ aggregates to PrPc is restricted to the N-terminus of PrPc.

Apoptosis, the programmed and intentional death of senescent, damaged, or otherwise superfluous cells, is the natural end-point for most cells within multicellular organisms. Apoptotic cells are not inherently damaging, but if left unattended they can lyse through secondary necrosis. The resulting release of intracellular contents drives inflammation in the surrounding tissue and can lead to autoimmunity. These negative consequences of secondary necrosis are avoided by efferocytosis—the phagocytic clearance of apoptotic cells. Efferocytosis is a product of both apoptotic cell and efferocyte mechanisms, which cooperate to ensure the rapid and complete removal of apoptotic cells. Herein, the processes used by apoptotic cells to ensure their timely removal, and the receptors, signaling, and cellular processes used by efferocytes to identify, remove, and process the apoptotic cells, are reviewed.

Myr47 lipopeptide consisting of hepatitis B virus (HBV) pre-S1 domain (myristoylated 2-48 peptide) is a commercialized effective anti-HBV drug, preventing the interaction of HBV with sodium taurocholate cotransporting polypeptide (NTCP) on human hepatocytes, of which the activity requires both N-myristoylation residue and specific amino acid sequence. Meanwhile, we recently reported that Myr47 reduces the cellular uptake of HBV surface antigen (HBsAg, subviral particle of HBV) in the absence of NTCP expression (Somiya; et al. Virology 2016, 497, 23–32). In this study, we analyzed how Myr47 reduces the cellular uptake of lipid nanoparticles (including liposomes (LPs) and HBsAg) without NTCP expression. By using Myr47 mutants lacking the HBV infection inhibitory activity, they could reduce the cellular uptake of LPs in an N-myristoylation-dependent manner whereas in an amino acid sequence-independent manner. Moreover, Myr47 and its mutants could reduce the interaction of LPs with apolipoprotein E3 (ApoE3) in an N-myristoylation-dependent manner regardless of their amino acid sequences. From these results, N-myristoyl residue of lipopeptides generally could interfere the LPs/HBsAg-ApoE3 complex formation, thereby reducing the cellular uptake of LPs/HBsAg. When lipid nanoparticles are used as a DDS (drug delivery system) nanocarrier, the surface modification with lipopeptides may be a new method to inhibit unwanted cellular uptake of DDS nanocarriers by non-target cells.

Multicellular life evolved from simple unicellular organisms that could replicate indefinitely being essentially ageless. At this point, life split into 2 fundamentally different cell types: the immortal germline representing an unbroken lineage of cell division with no intrinsic endpoint and the mortal soma which ages and dies. In this review, we describe the germline as clock-free and the soma as clock-bound and discuss aging with respect to 3 DNA-based cellular clocks (telomeric, DNA methylation, and transposable element). The ticking of these clocks corresponds to the stepwise progressive limitation of growth and regeneration of somatic cells that we term, somatic restriction. Somatic restriction acts in opposition to strategies that ensure continued germline replication and regeneration. We thus consider the plasticity of aging as a process not fixed to the pace of chronological time but one that can speed up or slow down depending on the rate of intrinsic cellular clocks. We further describe how germline factor reprogramming might be used to slow the rate of aging and potentially reverse it by causing the clocks to tick backwards. Therefore, reprogramming may eventually lead to therapeutic strategies to treat degenerative diseases by altering aging itself, the one condition common to us all.

Mobile health devices are emerging applications that could help deliver point-of-care (POC) diagnosis, particularly in settings with limited laboratory infrastructure, such as sub-Saharan Africa (SSA). The advent of coronavirus has resulted in an increased deployment and use of mHealth-linked POC diagnostics in SSA. We performed a systematic review and meta-analysis to evaluate the accuracy of mobile-linked point-of-care diagnostics in SSA. Our systematic review and meta-analysis were guided by the Preferred Reporting Items requirements for Systematic Reviews and Meta-Analysis (PRISMA). We exhaustively searched PubMed, Science Direct, Google Scholar, MEDLINE, and CINAHL with full-text via EBSCOhost databases from mHealth inception to March 2021. The statistical analyses were conducted using OpenMeta-Analyst software. All 11 included studies were considered for the meta-analysis. The included studies focused on malaria infections, Schistosoma haematobium, Schistosoma mansoni, soil-transmitted helminths, and trichuris trichiura. The pooled summary of sensitivity and specificity estimates were moderate compared to the gold reference standard. The overall pooled estimates of sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio of mobile-linked POC diagnostic devices were as follows: 0.499 (95% CI: 0.458-0.541); 0.535 (95% CI: 0.401-0.663); 0.952 (95% CI: 0.60-1.324); 1.381 (95% CI: 0.391-4.879); and 0.944 (95% CI: 0.579-1.538), respectively. Evidence shows that mobile-linked POC diagnostics' diagnostic accuracy is presently moderate in detecting infections in sub-Saharan Africa. Future research is recommended to evaluate mHealth devices' diagnostics with excellent sensitivities and specificities in diagnosing diseases in this setting.

The article obtains large deviation asymptotic for sub-critical communication networks modelled as signal-interference-noise-ratio(SINR) random networks. To achieve this, we define the empirical power measure and the empirical connectivity measure, as well as prove joint large deviation principles(LDPs) for the two empirical measures on two different scales. Using the joint LDPs, we prove an Asymptotic equipartition property(AEP) for wireless telecommunication Networks modelled as the subcritical SINR random networks. Further, we prove a Local Large deviation principle(LLDP) for the sub-critical SINR random network. From the LLDPs, we prove the large deviation principle, and a classical McMillan Theorem for the stochastic SINR model processes. Note that, the LDPs for the empirical measures of this stochastic SINR random network model were derived on spaces of measures equipped with the $\tau-$ topology, and the LLDPs were deduced in the space of SINR model process without any topological limitations. We motivate the study by describing a possible anomaly detection test for SINR random networks.

The energy transition requires integration of different energy carriers, including electricity, heat, and transport sectors. Energy modeling methods and tools are essential to provide a clear insight into the energy transition. However, the methodologies often overlook the details of small-scale energy systems. The study states an innovative approach to facilitate sub-national energy systems with 100% renewable penetration and sectoral integration. An optimization model, OSeEM-SN, is developed under the Oemof framework. The model is validated using the case study of Schleswig-Holstein. The study assumes three scenarios representing 25%, 50%, and 100% of the total available biomass potentials. OSeEM-SN reaches feasible solutions without additional offshore wind investment, indicating that they can be reserved for supplying other states’ energy demand. The annual investment cost varies between 1.02 bn – 1.44 bn €/yr for the three scenarios. The electricity generation decreases by 17%, indicating that with high biomass-based combined heat and power plants, the curtailment from other renewable plants can be decreased. Ground source heat pumps dominate the heat mix; however, their installation decreases by 28% as the biomass penetrates fully into the energy mix. The validation confirms OSeEM-SN as a beneficial tool to examine different scenarios for sub-national energy systems.

United Nations Framework Conventions on Climate Change (UNFCC) conventions in their conference of parties (COPs) has continuously considered and agreed reducing emission level in order to minimize the impact of global climate change. Reducing emission due to deforestation and degradation (REDD) ,was considered as one of the major activities in this regard during Kyoto protocol in 2009 which laid foundation for the participating countries to be compensated financially for reduced carbon emission. Mexico convention -2012 required the countries to develop and implement a transparent and consistent monitoring, reporting and verification (MRV) process. Later in Paris agreement-2015, the parties agreed to limit the global warming to 2 degree centigrade and with further efforts to 1.5-degree centigrade furthering entailing the parties to prepare and communicate nationally determined contributions (NDCs) every five years. Nepal aimed to decrease the average annual deforestation rate by 0.05 percent from existing 0.44 percent in the terai region and 0.1 percent in the Chure. Nepal decided to develop its forest reference level (FRL) in national level for the historical period 2000-2010 considering Carbon dioxide and carbon pools above and below ground. As per the Forestry Sector Strategy, Nepal aims to increase carbon stock growth by at least 5% by 2025 as compared to 2015 and decrease mean annual deforestation rate to 0.05. After major change in administrative division in Nepal, forest management responsibility has shifted down to the Sub-national level. But forest resource studies have not been conducted yet in these levels. Despite a small country, Nepal has at least four clear physiological regions. The amount of carbon stock stored by different forest type are different depending upon species distribution, carbon volume and density for each species, and their distribution along ecological and physiological regions. Sal (shorea Robusta), for example, having one of the highest carbon densities, is a major forest types in Nepal. The purpose of this study was to generate forest map of the country, calculate carbon stock, gain and loss, and their rate in each province due to deforestation/afforestation using remote sensing data. Further Sal forest map was generated and its contribution in carbon stock was calculated using averaged national carbon density as well as using regional density method. According to the study, around 5.1 million hectares of Nepali land was forest in 2015 increasing from 4.2 million hectares in 2005. However, Sal forest has decreased during the same period. Province 1 contributed the maximum (130 Tg) and Province 2 the minimum (40Tg) of Carbon stock in 2015. Using the conventional method of calculation with national average density (108.08 t/ha), a total of 36.7T CO2 yr-1 carbon sink was observed in the Country. Whereas, with the new approach of calculation, a total of 44.7 T CO2 e of carbon sink per year was estimated during the same period. This approach holds potential for qualifying as an MRV process of Nepal. The subnational level forest and carbon statistics produced during this study can be important assets for the better forest governance. This can also pave way for policy formation and preparation of action plan for sustainable forest management and intervention strategy and obtaining better financial incentives participating in the reduction of emission due to deforestation and forest degradation (REDD) plus programs.

Early reports demonstrated the presence of cells with stem-like properties in bone marrow, with these cells having both hematopoietic and mesenchymal lineages. Over the years, various investigations have purified and characterized mesenchymal stromal/stem cells (MSCs) from different human tissues as cells with multi-lineage differentiation potential under the appropriate conditions. Due to their appealing characteristics and potential, MSCs are leveraged in many applications including medicine, oncology, bioprinting and as recent as treatment of COVID-19. To date, reports indicate mesenchymal stromal/stem cells have varied differentiation capabilities into different cell types and demonstrate immunomodulating and anti-inflammatory properties. Reports indicate that different MSCs microenvironments or niche and the resulting heterogeneity may influence their behavior and differentiation capacity. The potential clinical applications of mesenchymal stromal/stem cells have led to an avalanche of research reports on their properties and hundreds of clinical trials being undertaken. The future looks bright and promising for mesenchymal stem cell research with many clinical trials under way to prove their utility in many applications and in the clinic. This report provides an update on the potential broader use of mesenchymal stromal/stem cells, review early observations of the presence of these cells in the bone marrow and their magnificent differentiation capabilities and immunomodulation.

In this paper, we propose a multi-zone service control scheme to maximize the performance of each service zone when a large number of cellular service zones and D2D (Device-to-Device) service zones are composed to 5G cellular network. This paper also improves performance of service zone by dividing traffic into real-time traffic and non-real-time traffic in order to minimize traffic interference. Real-time traffic and non-real-time traffic have a significant impact on communication performance. We propose a new self-detection traffic interference control technique to improve the QoS and throughput of D2D and C2D communication in a cellular network, STICS (Self-detecting Traffic Interference Control Scheme). The proposed STICS scheme distinguishes between short-term traffic congestion process and long-term traffic congestion process according to traffic characteristics to detect and control traffic. When the proposed scheme is applied to the 5G-based cellular network environment, it is expected that the traffic type will be efficiently classified by self-detecting the traffic according to the flow. Such classified traffic is less sensitive to communication between the D2D and C2D links, thereby reducing traffic overload. We evaluate the performance of the proposed scheme through simulation and show that the proposed scheme is more efficient than other comparison schemes.