Philippines as an archipelago and tropical country, which is situated near the Pacific ocean, faces uncertain rainfall intensities. This makes environmental, agricultural and economic systems affected by precipitation difficult to manage. Time series analysis of Philippine rainfall pattern has been previously done, but there is no study investigating its probability distribution. Modeling the Philippine rainfall using probability distributions is essential, especially in managing risks and designing insurance products. Here, daily and cumulative rainfall data (January 1961 - August 2016) from 28 PAGASA weather stations are fitted to probability distributions. Moreover, the fitted distributions are examined for invariance under subsets of the rainfall data set. We observe that the Gamma distribution is a suitable fit for the daily up to the ten-day cumulative rainfall data. Our results can be used in agriculture, especially in forecasting claims in weather index-based insurance.

Appropriate animal models of human diseases are a cornerstone in the advancement of science and medicine. To create animal models of neuropsychiatric and neurobehavioral diseases such as ASD necessitates the development of sufficient neurobehavioral measuring tools to translate human behavior to expected measurable behavioral features in animals. Indeed, at least in rodents, adequate neurobehavioral and neurological tests have been developed. Since ASD is characterized by a number of specific behavioral trends with significant severity, animal models of autistic-like behavior have to demonstrate the specific characteristic features, namely impaired social interactions, and communication, restricted, repetitive behavioral patterns with association to several additional impairments such as somatosensory, motor and memory impairments. Thus, an appropriate model must show behavioral impairment of a minimal number of neurobehavioral characteristics using an adequate number of behavioral tests. The proper animal models enable the study of ASD like-behavior from the etiologic, pathogenetic and therapeutic aspects. From the etiologic aspects, models have been developed by the use of immunogenic substances like polyinosinic-polycytidylic acid (PolyIC), Lipopolysaccharide (LPS) and propionic acid or other well-documented immunogens or pathogens, like mycobacterium tuberculosis. Another approach is the use of chemicals like valproic acid, Polychlorinated biphenyls (PCBs), organophosphate pesticides - chlorpyrifos (CPF) and others. These substances were administered either prenatally, generally after the period of major organogenesis, or, especially in rodents, during the early postnatal life. In addition, using modern genetic manipulation methods, genetic models have been created of almost all human genetic diseases that are manifested by autistic like behavior (i.e. fragile X, Rett syndrome, SHANK gene mutation Neuroligin genes and others). Ideally, we should not only evaluate the different behavioral modes affected by the ASD-like behavior but also assess the severity of the behavioral deviations by an appropriate scoring system, as applied to humans.

A power factor correction (PFC) rectifier is compulsory for any electronic circuitry connected to the electrical grid. The majority of PFCs that are utilized are based on a step-up converter that supplies high DC voltage at its output terminal. Electric vehicle battery voltage varies from a few hundred to almost a thousand volts. Thus, an additional conversion step is obligatory when designing an all-brand universal charger. This paper presents a new type of front-end versatile step up / down three voltage level PFC. The rectifier can operate in continuous conduction mode or discontinuous conduction mode. First, the rectifier’s principle of operation is described, and then an innovative rectifier is analyzed for continuous and discontinuous conduction modes. Finally, the proposed theory is experimentally validated in a multiplier-less dual loop mode at discontinuous conduction modes. It was shown that although there is no multiplier use in the control circuitry, the power factor is near unity. It was revealed that the rectifier could swing the output voltage from 50 V to 900 V while the input voltage was 230 Vrms. The innovative topology suits any standard PFC rectifier, three-level voltage supplement, and dual-stage low-voltage power supply.

The physical roots, interpretation, controversies and precise meaning of the Landauer Principle are surveyed. Landauer's principle is a physical principle pertaining to the lower theoretical limit of energy consumption of computation. It states that an irreversible change in information stored in a computer, such as merging two computational paths, dissipates a minimum amount of heat kBTln2 per a bit of information to its surrounding. The Landauer Principle is discussed in the context of fundamental physical limiting principles, such as the Abbe diffraction limit, the Margolus-Levitin limit and the Bekenstein limit. Synthesis of the Landauer bound with the Abbe, Margolus-Levitin limit and Bekenstein limits yields the minimal time of computation, which scales as τmin~hkBT. Decrease in a temperature of a thermal bath will decrease the energy consumption of a single computation, but, in parallel, it will slow the computation. The Landauer principle bridges between John Archibald Wheeler “it from bit” paradigm and thermodynamics. Experimental verifications of the Landauer Principle are surveyed. Interrelation between thermodynamic and logical irreversibility is addressed. Generalization of the Landauer principle to the quantum and non-equilibrium systems is addressed. Landauer Principle represents the powerful heuristic principle bridging the physics, information theory and computer engineering.

A mathematical procedure enabling the transformation of an arbitrary tessellation of a surface into a bi-colored complete graph is introduced. Polygons constituting the tessellation are represented by vertices of the graphs. Vertices of the graphs are connected by two kinds of links/edges, namely, by a green link, when polygons have the same number of sides, and by a red link, when the polygons have a different number of sides. This procedure gives rise to a semi-transitive, complete, bi-colored Ramsey graph. The Ramsey number was established as R_trans (3,3)=5. Shannon entropies of the tessellation and graphs are introduced. Ramsey graphs emerging from random Voronoi and Poisson Line tessellations were investigated. The limits ζ=lim┬(N→∞)⁡〖N_g/N_r 〗, where N is the total number of green and red seeds, N_g and N_r, were found ζ=0.272±0.001 (Voronoi) and ζ= 0.47±0.02 (Poisson Line). The Shannon Entropy for the random Voronoi tessellation was calculated as S= 1.690±0.001 and for the Poisson line tessellation as S =1.265±0.015.

Residual sugars (RS) in wine are the sugars that remain in a wine after fermentation is complete. In some wine styles, such as semi-dry wines, the accurate measurement of the RS concentration is critical for both qualitative and legislative reasons. Brix, measured by a simple refractometer, can give a good estimation of the RS concentration in the must, but during fermentation, the presence of alcohol leads to inaccurate sugar measurements. In order to measure the RS accurately, other more precise techniques are used, most of which are expensive or require professional skills. Therefore, novel approaches for rapid, easy, and practical measurements for estimating the sugar content were suggested over the years. However, most of these methods do not supply an actual measurement of RS but rather give brix values, and those that measure RS involve special equipment, which is less relevant for small wineries. This study suggests a novel model for predicting and controlling the wine's residual sugar. The data the model uses is the initial brix of the must before fermentation and its density during fermentation. The model was created by measuring actual residual sugars during the fermentation of natural and synthetic musts, with various degrees of initial brix levels, while simultaneously measuring their densities and correlating the two measurements. Linear regression between the residual sugar of the wine and its density was obtained for all treatments and repetitions (i.e., different values of must initial brix) with R² values above 0.97. Using the model, one can calculate (before commencing the fermentation) the density values at which the fermentation will reach a particular desired residual sugar value for a specific initial brix level; the model is applicable for the fermentation conditions used in this work, i.e., brix levels of 18-27˚Bx, Saccharomyces cerevisiae strains (fx-33 and fx-10) in common conditions of fermentation regarding temperature and aeration.

Disk galaxies have a typical dimension of few tens of thousands of light years. It follows from the theory of general relativity that any signal originating from the galactic center will be noticed at the outskirts of the galaxy only tens of thousands of years later. This retardation effect is absent in modelling used to calculate rotation curves throughout the entire galaxy and its external gas. The considerable differences between Newtonian action at a distance predictions and observed velocities are currently removed either by assuming dark matter or by suggesting various modifications to the laws of gravity, MOND being a long standing alternative to Newtonian gravity. In previous papers we have shown that applying general relativity in a rigorous fashion without mindlessly neglecting retardation, one can explain the radial velocities of galactic matter without modifying gravity or adding unseen matter. Moreover, it was shown that dark matter effects as they appear in gravitational lensing, the Tully-Fisher relation, and mass estimations based on the virial theorem could also be explained as retarded-gravity effects. In the original main paper on the subject only one galaxy (M33) was analysed in detail. This was later amended somewhat with a published study of eleven galaxies. Here we give a more comprehensive retardation analysis of 143 galaxies of different types from the SPARC Galaxy collection. We show that in most cases we obtain an excellent fit without postulating dark matter or modifying general relativity.

We report positive correlations between letter frequency and symmetry (more symmetric symbols are more frequent) in English and Russian languages and in four types of numerals (Western, Roman, Arabic, and Chinese) with the coefficients of determination of R2=0.899 (English), R2=0.693 (Russian) and R2=0.740 (numerals). For comparison, we studied "symbol-like" 2D colloidal clusters and found negative correlations between frequency and symmetry (R2=0.814 and R2=0.994). While in human-made systems the frequency of using of a symbol is the driving force which leads to symbols simplification and symmetrizing, in natural system, symmetry leads to lower frequency of occurrence because there are fewer ways of building symmetric clusters than asymmetric ones. We interpret these results as a correlation between the symbol as a type and as a token and we attribute this correlation to the inherent iconicity of symbols

Entropic Dynamics (ED) is a framework in which Quantum Mechanics is derived as an application of entropic methods of inference. In ED the dynamics of the probability distribution is driven by entropy subject to constraints that are codified into a quantity later identified as the phase of the wave function. The central challenge is to specify how those constraints are themselves updated. In this paper we review and extend the ED framework in several directions. A new version of ED is introduced in which particles follow smooth differentiable Brownian trajectories (as opposed to non-differentiable Brownian paths). To construct the ED we make use of the fact that the space of probabilities and phases has a natural symplectic structure (i.e., it is a phase space with Hamiltonian flows and Poisson brackets). Then, using an argument based on information geometry, a metric structure is introduced. It is shown that the ED that preserves the symplectic and metric structures -- which is a Hamilton-Killing flow in phase space -- is the linear Schrödinger equation. These developments allow us to discuss why wave functions are complex and the connections between the superposition principle, the single-valuedness of wave functions, and the quantization of electric charges. Finally, it is observed that Hilbert spaces are not necessary ingredients in this construction. They are a clever but merely optional trick that turns out to be convenient for practical calculations.

Yttria stabilized zirconia (Y-TZP) ceramics with drastically reduced yttria content have been introduced by different manufacturers aiming at improving the damage tolerance of ceramic components. In this study an alumina doped 1.5Y-TZP was axially pressed, pressureless sintered in air at 1250–1400 °C for 2 h and characterized with respect to mechanical properties, microstructure and phase composition. The material exhibits a combination of high strength of 1000 MPa and a high toughness of 8.5–10 MPa√m. The measured fracture toughness is, however, extremely depending on measurement protocol. Direct crack length measurements overestimate toughness due to trapping effects. The initially purely tetragonal material has a high transformability of > 80 %, the transformation behavior is predominantly dilatoric, measured R-curve related toughness increments are in good agreement with transformation toughness increments derived from XRD data.

Yttria stabilized zirconia materials are frequently used in mechanical engineering and biomedical applications. Demanding loading conditions require materials combining a high level of strength and fracture toughness. A ready to press alumina doped 2 mol% yttria stabilized zirconia powder was shaped by axial pressing and sintering in air at 1250 - 1500 °C for 2 h. The best combination of strength and toughness value of 7.8 MPa√m. Materials sintered in the middle of the chosen temperature range combine fully density, high transformability and small grain size. Toughness measurements by direct crack length measurements delivered unrealistically high fracture toughness values.

Since the 1970s, the application of microprocessor in industrial machinery and the development of computer systems have transformed the manufacturing landscape. The rapid integration and automation of production systems have outpaced the development of suitable human design criteria, creating a deepening gap where human factor was seen as an important source of errors and disruptions. Today the situation seems different: the scientific and public debate about the concept of Industry 4.0 has raised the awareness about the central role humans have to play in manufacturing systems, to the design of which they must be considered from the very beginning. The future of industrial systems, as represented by Industry 4.0, will rely on the convergence of several research fields such as Intelligent Manufacturing Systems (IMS), Cyber-Physical Systems (CPS), Internet of things (IoT), but also socio-technical fields such as social approaches within technical systems. This article deals with different Human dimensions associated with CPS and IoT and focuses on their conceptual evolution of automatization to improve the sociability of such automated production systems and consequently puts again the human in the loop. Hereby, our aim is to take stock of current research trends, and to show the importance of integrating human operators as a part of a socio-technical system based autonomous and intelligent products or resources. As results, different models of sociability as way to integrate human into the broad sense and/or the development of future automated production systems, were identified from the literature and analysed.

The classical Lotka-Volterra predator-prey model is globally stable and uniformly persistent. However, in real-life biosystems extinction of species due to stochastic effects is possible. In this paper, we consider the classical Lotka-Volterra predator-prey model under stochastic perturbations. For this model, using an analytical technique based on the direct Lyapunov method and a development of the ideas of R.Z. Khasminskii, we find the precise sufficient conditions for the stochastic extinction of one and both species and the precise necessary conditions for the stochastic system persistence. The stochastic extinction occurs via a process known as the stabilization by noise of the Khasminskii type, and, in order to establish the sufficient conditions for extinction, we found the conditions for the stabilization. The analytical results are illustrated by numerical simulations. {\bf Keywords:} stochastic perturbations, white noise, Ito's stochastic differential equation, the Lyapunov functions method, stability in probability, stabilization by noise, stochastic extinction, persistence.

Epithelial ovarian cancer significantly contributes to cancer-related mortality in women, often recurring post-treatment with chemotherapy resistance. Dietary interventions have demonstrated influence on cancer progression; for instance, caloric restriction has exhibited tumor growth reduction and enhanced survival in animal cancer models. This study aims to calculate a transcriptomic signature based on caloric-restriction for ovarian cancer patients and explore its correlation with disease progression. We identified proteins modulated by fasting, intermittent fasting or caloric restriction in human females. Based on their gene expression, we calculated a Non-Fasting Genomic Signature score for ovarian cancer samples from the TCGA database. We examined the association between this genomic profile and clinical characteristics. The non-fasting signature, comprising eight genes, demonstrated higher prevalence in primary ovarian tumors compared to normal tissue. Patients with elevated signature expression exhibited reduced overall survival and increased lymphatic invasion. The mesenchymal subtype, associated with chemotherapy resistance, displayed the highest signature expression. Multivariate analysis suggested the non-fasting genomic signature as a potential independent prognostic factor. Ovarian cancer tumors expressing a “non-fasting” transcriptional profile correlate with poorer outcomes, emphasizing the potential impact of caloric restriction on improving patient survival and treatment response. Further investigations, including clinical trials, are warranted to validate these findings.

Inspired by works of W. H. Zurek and others, a mathematical, physical theory, entirely within a quantum mechanical formalism, is proposed for cognitive processes in terms of an abstract Hilbert-space for the conscious state that is an exact replica of the Hilbert-space for the neuronic physical state. Thus, any actual state of consciousness arises by its formal alignment (identification) with some-one in the set of the neuronic states, with the latter undergoing perpetual changes in the wake of life-long experiences. It is posited that these changes become expressed by an increase in the number of ordered, coherent neuronic states at the expense of the pre-ordinal random neuronic states. Changes, transitions between states are induced by a Gorini-Kossakowski-Sudarshan-Lindblad formalism, which is also instrumental in the effect of the conscious state on bodily actions. The paradigmatic findings of R.N. Shepard (1958 - 2011) and of S. Sternberg (1966 - 2016) for long- and short-term recalls are interpreted within the model.

The field of water management is continually changing. Water has been subject to external shocks in the form of climate change and globalization. Analysis of water management is subject to disciplinary developments and inter-disciplinary interactions. Are these developments well documented in the literature? Initial observations on interdisciplinary literature suggest that results are fragmented, implying that a state-of-the-art review is needed. The objective of this paper is to close this gap by reviewing recent developments in water economics that address the increasing perceptions of water scarcity by looking first at changes in supply and quality of water, and then at impacts of climate change on water extremes. Among responses to such challenges, the paper identifies changes to water use patterns by including and co-managing water from different sources—surface and groundwater, wastewater, and desalinated water. Technological advancements also are among the resources that address water challenges. Water challenges reflect also on management of internationally shared water. A recent surge in scientific work identified international treaties as playing a significant role in water management. The paper reviews recently employed economic tools, such as experimental economics, game theory, institutional economics, and valuation methods. And finally, it explores modeling approaches, including hydro-economic and computable general equilibrium models that are being used to deal with water challenges.

Recent efforts to conceptually design a technologically meaningful electromagnetic retarded engine indicated that this can only be done using the immense charge and current densities which exist in the atomic scale. However, this scale cannot be described by Newtonian physics, and only a quantum description will suffice to describe the dynamics of an electron on this scale properly. Here we study the retarded field quantum engine and highlight the differences between the quantum and the classical retarded engines.

The consistent and continuous growth in the world’s population is creating many challenges for public policymakers in the different life areas, including dealing with the increasing amounts of waste that are generating problems involving air and land pollution and a shortage of land for waste disposal. This study presents the results of public policy on managing municipal waste, as manifested in the quantity and rate of waste collected throughout Israel in recent years and disposed of in the various landfills and in analysis of the political and economic factors affecting this policy. The study combines a quantitative and qualitative approach, where the quantitative study includes analysis of statistical data based on information from the Central Bureau of Statistics, the Ministry of Environmental Protection, the Ministry of Finance, and others, and the qualitative study relies on reading and analyzing primary documents of the different government ministries on Israel’s waste disposal policy and information in the media on this issue. The research findings attest to an increase in the amount of municipal waste dumped in Israel, a merely slight decrease in the rate of landfilling as a proportion of all municipal waste disposal, and a merely slight increase in the rate of municipal waste recycled in recent years. The research conclusions stress the effects of the landfill levy and the Cleanliness Maintenance Fund on one hand, and of the government instability in the Ministry of Environmental Protection, the positivist policy embraced by decision makers in the Ministry of Environmental Protection, and the power struggles between Israel’s different ministries on the other, as the respective economic and political factors affecting Israeli policy on municipal waste management.

Although the water absorption feature (WAF) at 970 nm is not very well-defined, it may be used alongside other indices to estimate the canopy water content. The individual performance of a number of existing vegetation water content (VWC) indices against the WAF is assessed using linear regression model. We developed a new Combined Vegetation Water Index (CVWI) by merging indices to boost the weak absorption feature. CVWI showed a promise in assessing the vegetation water status derived from the 970 nm absorption wavelength. CVWI was able to differentiate two groups of dataset when regressed against the absorption feature. CVWI could be seen as an easy and robust method for vegetation water content studies using hyperspectral field data.

A qualitative analysis of pressure acting within the human eye is presented. The situation emerging within the human eye in rest and human eye of accelerated/training person should be distinguished. When the person is in rest, the hydrostatic pressure is much larger than the Laplace pressure. The dynamic (Bernoulli pressure) emerging from intraocular flows in this case is negligible. The situation is rather different for accelerated or decelerated person. In this case, the dynamical pressure and the water hammer pressure become dominant. Under certain circumstances, the water hammer pressure may be larger than the ultimate tensile strength of retina, choroid and the Bruch membrane‐choroid complex, which may possibly affect the retina. As a recommendation: physical training, which is not accompanied with ultimate acceleration/acceleration of the body, may be performed after posterior vitreous detachment; however, potentially traumatic activities such as boxing or competitive diving should be avoided.

The growing congestion in delivery rooms and maternity wards in Israeli hospitals is the underlying issue of the current study. The study sought to examine various alternatives for an effective public policy aimed at reducing congestion. The choice of Israel as a case study derives from its conspicuous imbalance between supply and demand in the maternity, resulting from the high demand for prenatal and birthing services on one hand and the low supply, both in absolute terms and relative to OECD countries, of medical resources such as physicians, nurses, and hospital beds. The research findings present fertility and birth data for Israel in the last decade, which are leading to increased congestion and crowding in delivery rooms and maternity wards at local hospitals. At the same time, two possible alternatives are proposed for designing and implementing public policy capable of contributing to the regulation of this congestion. One alternative is the option of home birth and the second is promoting the establishment of private birthing centers outside the hospitals. The research conclusions indicate that policy makers in Israel must anticipate the increasing congestion in hospital delivery rooms and maternity wards and expedite efforts at designing alternative solutions before the emergence of a crisis situation that will make it essential to identify immediate solutions. The study recommends exploring and advancing the adoption of the two alternatives simultaneously as part of public policy, in the assumption that the increasing demand for pregnancy and childbirth services in Israeli society will persist and therefore it is necessary to act to increase the supply of childbirth facilities.

Conventional academic debate on sustainability and transformation has begun to be disputed by researchers, policymakers and other stakeholders from the private sector. The complexity of linking sustainability with transformation necessitates the development of new ways of understanding and explaining actors, processes, issues, structures, and outcomes related to transformation to sustainability (T2S). A persistent problem in understanding and managing the T2S is the implied notion of a monolithic transformation to achieve sustainability. This notion underestimates the diversity of actors as well as the historical contexts of transformations. At the same time, achieving T2S is highly dependent on technical solutions as well as policies that can stir needed behavioural change, whereas these technical solutions and policies are not always socially acceptable or politically implementable. Therefore, achieving T2S also calls for evaluating normative foundations of policies and actions needed to advance T2S. This article argues that T2S is composed of different phases, each of which having a different set of actors, resources and audience. This article explains how collective decision can be achieved through multiple levels and types of negotiations that occur in an orchestrated manner. To understand this, this article introduces a theoretical model as an analytical framework to structure how T2S unfolds. This model uses insights from negotiation studies to focus on the actors’ perspectives on T2S. It proposes the division of the transformation process into phases – entry point, learning, sequencing, disrupting and fortifying. Using the Germany’s energy transition (Energiewende), each of these phases is analysed to determine the “quality” of cooperation that can help fulfil the tasks required to master the so-called “cognitive games” of T2S (ripeness game, power game, bargaining game, policy game, scaling game). Moreover, insights are presented to explain how the designated milestone can be achieved that indicates the advancing to the next phase and eventually entrench the transformation process. The lessons and findings resulting from the analysis of the phases of T2S suggest that there is also the need to revisit underlying assumptions on negotiations, sustainability and transformation.

Taiwan's bed and breakfast (B&B) development has been more than 25 years ago, from the first generation of retirement to the B&B industry, serving tourists from all over the world accom-modation, providing breakfast and accommodation mode to the present, after the change of employees from the second generation, more and more attention is paid to the cultivation and cultivation of business ability. With the advent of the era of AI technology networking, the ca-pabilities required for B&B operation are more focused on all aspects of service, and the good marketing ability of B&B can promote a green chimney-free tourism economy, which is also a favorite industry of various governments and the public. This study explores the basic vocational competency indicators required for running a B&B, with (1)EQ emotion management skills, (2)Financial management ability, (3)(SK) technical skills, and (4)Marketing and promotion management capabilities. Through the study method, the K-S Z test was determined by the con-sensus conclusion of expert reliability and validity p value

The hyper-arid environment is characterized by high inter-annual climatic fluctuations. The yearly average rainfall can change substantially for several years, forming wet or dry sub-periods. Observing rainfall trends over a sub-period can lead to a false perception of a change in the trend but may in fact represent a periodic cycle when examined on a larger time scale. We aimed to better characterize the rainfall regime prevailing in the hyper-arid Arava Valley (Israel/Jordan), and to examine the response of vegetation to annual rainfall. We hypothesized that annual and perennial vegetation would respond differently to wet and dry sub-periods, and that grazing activities will impact vegetation growth. We used a time series of monthly rainfall, from which we calculated Standard Precipitation Index (SPI), and calculated proxies of perennial and annual vegetation over the last four decades using Landsat-derived Normalized Difference Vegetation Index (NDVI). We found no clear trend in rainfall amounts during this period, however we did identify wet and dry sub-periods which were statistically distinct in rain and in vegetation patterns from each other. The highest levels of correlation between rainfall and the NDVI derived proxies were found when examining average rainfall over a period of two- three years for the annual vegetation and over four years for perennial vegetation. Using the Mann-Kendall test, we identified a time lag of two to four years, with the proxies of annual vegetation responding faster than the proxies of perennial vegetation, to shifts between wet and dry sub-period. In addition, we found a consistent difference between natural vegetation cover in Jordan (grazed) and Israel (non-grazed), favoring the development of natural vegetation on the Israeli side. We conclude that integrating between long-term remote sensing satellite imagery and climatic records revealed the greater resilience of perennial vegetation in the hyper-arid region to climatic fluctuation, and enabled us to identify the vegetation’s sensitivity to anthropogenic impact.

Water supply policy is closely linked to sustainability as it directly influences the conservation and management of vital natural resources. This policy focuses on developing regulations and designing various activities related to the preser-vation of water resources, which can promote both ecological and economic sustainability. This study focuses on the Challenges of the Israeli Water Sector in Times of Emergency. In a time of growing climate crisis and despite the global warming trend, Israeli citizens routinely enjoy a regular constant supply of clean fresh water, thanks to local desalina-tion plants. Establishment of the desalination plants has become a model of water management for many countries in an era of growing climate crisis. At the same time, Israel’s water sector is faced with challenges and threats related to earthquakes and various states of warfare and security confrontations. In such times of emergency, Israel’s water sector is particularly vulnerable to disruptions of the water infrastructure and it’s adequate operation, by both contamination of the water sources and damage to the desalination plants. This study examines the challenges of the Israeli water sec-tor that require it to contend with these emergency situations in an era of reliance on desalination plants. The research method combines analysis of statistical data extracted from Israel’s Central Bureau of Statistics, Government Water and Sewage Authority, and Meteorological Service, in addition to reading and analyzing primary documents generated by various government ministries and government organs related to Israel’s water policy. The research findings lead to the conclusion that public policy on managing the water sector, manifested in the development and establishment of water desalination plants, has resolved Israel’s water crisis, put an end to its dependency on the amount of precipitation and on natural water sources, and allowed an increase in water production to match the rise in consumption. Nonetheless, as successful as this public policy may be, it does not consider the possibility of extreme scenarios and does not develop the entire range of steps necessary to confront them, and thus undermines the ability of the Israeli water sector to provide its citizens with water in times of emergency.

The limited velocity in a geometry of Lorentzian signature, seem to prevent the universe to reach thermodynamic equilibrium as suggested by the cosmic microwave background. Thus it was suggested that the universe which was initially minuscule has reached a more considerable radius in a short duration by a process known as cosmic inflation. However, to drive such a process have led to the suggestion of an ad-hoc scalar field the inflaton, which has no purpose in nature other than driving the cosmic inflation field and then stopping it once the universe reached the right size. In a recent paper it was shown that rapid expansion can occur without postulating an inflation by following Hawking's suggestion and assuming that primordially the metric of the universe had an Euclidean signature, in which case velocity is not limited and thermalization and rapid expansion are derived without the need to assume an ad-hoc field. However, while in the previous work emphasis was put on the dynamics and physical statistics of the particles in a Euclidean space vs. Lorentzian space in which both spaces were given. No mathematical model was given regarding the development of current Lorentzian space-time from the early Euclidean space-time, and how fundamental problems such as the space-time singularity and the homogeneity of the CMB can be solved in the hybrid Euclidean-Lorentzian picture. This lacuna is to be rectified in the current paper.

The Ramsey theory based approach to the phase transitions of the second order is suggested. The phase transitions of the second order are seen as switching of physical interactions/chemical bonds between the entities forming the primitive cell of the material. Such a switching is typical for a phase change materials. If the energy of the primitive cell is kept constant under the change in the spatial order of the chemical bonds, the phase transition of the second order takes place. The switching of interactions between the entities forming the primitive cell is accompanied by the breaking of the initial symmetry of the cell. The order parameter/the degree of ordering characterizing the ordering within the primitive cell is re-defined. The introduced degree of ordering quantifies ordering of links/interactions/chemical bonds between entities constituting the 2D lattice; whereas, the classical “Landau degree of order” quantifies the symmetry breaking under variation in spatial locations of these entities. The suggested approach is generalized easily for 3D primitive cells. Thermal capacity of the non-symmetrical phase is larger than that of the symmetrical phase. For the primitive cells built of six interacting entities, the Ramsey Theory predicts inevitable appearance of the unstable monochromatic triangles, when the links correspond to attraction or repulsion interactions. The situation becomes different for the primitive cells built of five interacting entities.

In recent years retarded gravity has explained many of the mysteries surrounding the "missing mass" related to galactic rotation curves, the Tully-Fisher relations, and gravitational lensing phenomena. Indeed a recent paper analyzing 143 galaxies, has demonstrated that retarded gravity will suffice to explain the galaxies rotation curves without the need to postulate dark matter for multiple types of galaxies. Moreover, it also demystified the "missing mass" related to galactic clusters and elliptic galaxies in which excess matter wad derived through the virial theorem. Here we give a mathematical criterion which specifies the cases for which retardation is important for gravity (and when it is not). The criterion takes the form of an "uncertainty" relation.

Background: Antibiotic resistance is an urgent issue everywhere in the globe. It is necessary to look into new sources of antibiotics to address this issue. Aim of the study: studying the purification of Corallopyronin B from various soil conditions in Egypt, as well as the antibacterial effectiveness of Corallopyronin B in preclinical animal testing and randomized human clinical trials phases 1/2. Type of the study: Screening experimental study. Methodology: Several soil conditions in Egypt were examined to create bacterial isolates that generated the antibiotic chemical Corallopyronin B. Using reversed-phase HPLC, Myxopyronin B was purified. The test antibiotic's minimum inhibitory concentration( MIC) and in vitro antibacterial activity were ascertained using the paper disc diffusion assay and the broth microdilution technique. Furthermore, in stages 1/2 of randomized clinical trials including human and animal models, pharmacokinetics, adverse drug reactions, and the in vivo antibacterial spectrum were discovered. Results: The soil bacterial isolate Corallococcus coralloides DSM 2259, grown on a Casein yeast peptone( CYP) plate, produced Corallopyronin B from its culture supernatant. At MICs more than 100 mcg/ml, the test antibiotic inhibited the growth of many Gram -ve bacteria, including Escherichia coli, while preventing the growth of numerous Gram +ve bacteria, with MICs ranging from 1 to 10 mcg/ml. Eukaryotic cells, on the other hand, including those in humans and fungi, were unharmed. The test antibiotic was shown to have a bactericidal effect by inhibiting bacterial DNA-dependent RNA polymerase( RNLP). In phases 1/2 of randomized human clinical trials, when 600 mg of the dose per 70 kg of body weight was administered SC, the Cmax was 8.6 mcg/ml at Tmax 1 hour; T1/2 reached 136 min following first-order kinetics of elimination. It stopped acting around 6-7 hours after SC was administered. In the preclinical and randomized human clinical trial phases 1/2, less than 6 percent of experimental candidates had uncommon toxicity, showing reduced bile flow. Protein binding with plasma albumin was detected which reached about 83%. Conclusion: The current work was noteworthy since it involved the production of the bactericidal antibiotic Corallopyronin B from Corallococcus coralloides DSM 2259 which was isolated from several soil environments in Egypt.

Fluorescent bioprobes are invaluable tools for visualizing live cells and deciphering complex biological processes by targeting intracellular biomarkers without disrupting cellular functions. In addition to protein-binding concepts, fluorescent probes utilize various mechanisms, including membrane, metabolism, and gating-oriented strategies. This study introduces a novel fluorescent mechanism distinct from existing ways. Here, we developed a B-cell selective probe, CDrB, with unique transport mechanisms. Through SLC-CRISPRa screening, we identified two transporters, SLCO1B3 and SLC25A41, by sorting out populations exhibiting higher and lower fluorescence intensities, respectively, demonstrating contrasting activities. We confirmed that SLCO1B3, with comparable expression levels in T and B cells, facilitates the transport of CDrB into cells, while SLC25A41, overexpressed in T lymphocytes, actively exports CDrB. The observation suggests that SLC25A41 plays a crucial role in discriminating between T and B lymphocytes. Furthermore, it reveals the potential for reversible localization of SLC25A41 to demonstrate its distinct activity. This study is the first report to unveil a novel strategy of SLC by exporting the probe. We anticipate that this research will open up new avenues for developing fluorescent probes.

Background: Antibiotic resistance is an urgent issue everywhere in the globe. It is necessary to look into new sources of antibiotics to address this issue. Aim of the study: studying the purification of Corallopyronin B from various soil conditions in Egypt, as well as the antibacterial effectiveness of Corallopyronin B in preclinical animal testing and randomized human clinical trials phases 1/2. Type of the study: Screening experimental study. Methodology: Several soil conditions in Egypt were examined to create bacterial isolates that generated the antibiotic chemical Corallopyronin B. Using reversed-phase HPLC, Myxopyronin B was purified. The test antibiotic's minimum inhibitory concentration( MIC) and in vitro antibacterial activity were ascertained using the paper disc diffusion assay and the broth microdilution technique. Furthermore, in stages 1/2 of randomized clinical trials including human and animal models, pharmacokinetics, adverse drug reactions, and the in vivo antibacterial spectrum were discovered. Results: The soil bacterial isolate Corallococcus coralloides DSM 2259, which was grown on a Casein yeast peptone( CYP) plate, produced Corallopyronin B from its culture supernatant. At MICs more than 100 mcg/ml, the test antibiotic inhibited the growth of many Gram -ve bacteria, including Escherichia coli, while also preventing the growth of numerous Gram +ve bacteria, with MICs ranging from 1 to 10 mcg/ml. Eukaryotic cells, on the other hand, including those in humans and fungi, were unharmed. The test antibiotic was shown to have a bactericidal effect by inhibiting bacterial DNA-dependent RNA polymerase( RNLP). In phases 1/2 of randomized human clinical trials, when 600 mg of the dose per 70 kg of body weight was administered SC, the Cmax was 8.6 mcg/ml at Tmax 1 hour; T1/2 reached 136 min following first-order kinetics of elimination. It stopped acting around 6-7 hours after SC was administered. In the preclinical and randomized human clinical trial phases 1/2, less than 6 percent of experimental candidates had uncommon toxicity, which showed up as reduced bile flow. Protein binding with plasma albumin was detected which reached about 83%. Conclusion: The current work was noteworthy since it involved the production of the bactericidal antibiotic Corallopyronin B from Corallococcus coralloides DSM 2259 which was isolated from several soil environments in Egypt.

To achieve n-type doping in diamond, extensive investigations employing first principles have been conducted on various models of phosphorus doping and boron-phosphorus co-doping. The primary focus of this study is to comprehensively analyze the formation energy, band structure, density of states, and ionization energy of these structures. It is observed that within a diamond structure solely composed of phosphorus atoms, the formation energy of an individual carbon atom is excessively high. However, the substitution of two carbon atoms leads to the conversion of diamond into a p-type semiconductor. Upon examining the P-B co-doping structure, it is revealed that the doped impurities exhibit a tendency to form more stable cluster configurations. As the separation between the freely doped atoms and the cluster impurity structure increases, the overall stability of the structure diminishes, consequently resulting in an elevation of the ionization energy. Analysis of the electronic density of states demonstrates that the electron orbit of the B atom makes negligible contributions to the impurity levels during P-B doping.

Atopic dermatitis (AD) is a chronic inflammatory condition which significantly affects quality of life in both patients and their caregivers. Calcineurin inhibitors (CNI) are a class of immunosuppressive drugs predominantly inhibiting T cell mediated immune processes. CNI form complex by binding with immunophilins and in turn inhibit calcineurin and suppress downstream inflammatory pathway. Tacrolimus and pimecrolimus are topical CNI approved for the treatment of mild to severe AD in both children and adults. Application site reactions are frequently seen. They have been issued with black box warning towards increased risk of malignancies but supportive evidence is lacking. Cyclosporine, though highly effective, is used off-label for AD management. It is used for controlling acute flares of AD due to its very rapid onset of action. Nephrotoxicity and hypertension are its serious complications. CNI have not been reported with teratogenicity and may be used conditionally during pregnancy and lactation.

Syntrophic acetate oxidation operates close to the thermodynamic equilibrium and very little is known about the participating organisms and their metabolism. Clostridium ultunense is one of the most abundant syntrophic acetate-oxidising bacteria (SAOB) found in engineered biogas processes operating with high ammonia concentrations. It has been proven to oxidise acetate in cooperation with hydrogenotrophic methanogens. There is evidence that the Wood-Ljungdahl (WL) pathway plays an important role in acetate oxidation. In this study we analysed the physiological and metabolic capacities of C. ultunense on genome scale and conducted a comparative study of all known characterised SAOB, namely Syntrophaceticus schinkii, Thermacetogenium phaeum, Tepidanaerobacter acetatoxydans and Pseudothermotoga lettingae. The results clearly indicated physiological robustness beneficial for anaerobic digestion environments and revealed unexpected metabolic diversity with respect to acetate oxidation and energy conservation systems., Unlike S. schinkii and Th. phaeum, C. ultunense clearly does not employ the oxidative WL pathway for acetate oxidation, as its genome (and that of P. lettingae) lack important key genes. In both those species, a proton motive force is likely formed by chemical protons involving putative electron-bifurcating [Fe-Fe] hydrogenases rather than proton pumps. No genes encoding a respiratory Ech hydrogenase, as involved in energy conservation in Th. phaeum and S. schinkii, were identified in C. ultunense and P. lettingae. Moreover, two respiratory complexes sharing similarities to the proton-translocating ferredoxin:NAD⁺ oxidoreductase (Rnf) and the Na+ pumping NADH:quinone hydrogenase (NQR) were predicted. These might form a respiratory chain involved in reduction of electron acceptors other than protons. However, involvement of these complexes in acetate oxidation in C. ultunense and P. lettingae needs further study. This genome-based comparison provides a solid platform for future meta-proteomics and meta-transcriptomics studies and for metabolic engineering, control and monitoring of SAOB.

A formulation of the Density Functional Theory (DFT) is constructed as an application of the method of maximum entropy for an inhomogeneous fluid in thermal equilibrium. The use of entropy as a systematic method to generate optimal approximations is extended from the classical to the quantum domain. This process introduces a family of trial density operators that are parametrized by the particle density. The optimal density operator is that which maximizes the quantum entropy relative to the exact canonical density operator. This approach reproduces the variational principle of DFT and allows a simple proof of the Hohenberg-Kohn theorem at finite temperature. Finally, as an illustration, we discuss the Kohn-Sham approximation scheme at finite temperature

Natural springs, recognized as biodiversity hotspots and keystone ecosystems, exert positive ecological influences beyond their immediate extent, particularly in dryland environments. The water feeding these springs, largely governed by natural climatic conditions, is susceptible to anthropogenic impacts. The objective of this study was to determine the factors that cause fluctuations in water availability to springs of the hyper-arid Arava Valley (Israel/Jordan). Using the Standard Precipitation Index, we statistically classified the historical record of yearly rainfall for the past four decades into clusters of dry and wet sub-periods. We assessed changes in vegetation cover around the springs using the Landsat-derived Normalized Difference Vegetation Index (NDVI) for each sub-period. To assess the anthropogenic effects, we examined the correlations between vegetation cover, water extraction from the aquifer, and the status of adjacent agricultural plots that share a hydrological connection with the springs. Our findings reveal fluctuations between wet and dry sub-periods over the last four decades. We observed high responsiveness of vegetation cover around the springs to these fluctuating sub-periods. Of the 25 studied springs, 12 were directly influenced by anthropogenic factors — seven experienced a decline in vegetation which we attributed to water extraction from the aquifers, while vegetation increase in five springs was attributed to water seepage from agricultural areas upstream. In conclusion, addressing vital habitats such as natural springs in arid drylands requires a holistic approach that integrates long-term climatic, ecological, and anthropogenic observations.

The performance of two bio inoculants either in single or in combined applications with organic fertilizer was tested to determine their effect on plant growth and yield under normal and unfavorable field conditions such as low pH value and low content of P. Arbuscular Mycorrhiza Fungi ((AMF; three species of Glomus) and the plant growth-promoting bacterial strain Kosakonia radicincitans DSM16656 were applied to barley in two years field experiment with different soil pH levels and available nutrients. Grain yield, content of P, N, K, Mg, and soil microbial parameters were measured. Grain yield and content of nutrients were significantly increased by the applications of mineral fertilizer, organic fertilizer, AMF, K. radicincitans, and combined application of organic fertilizer with AMF and with K. radicincitans over the control under normal growth conditions. Under low pH and low P conditions, only the combined application of the organic fertilizer with K. radicincitans and organic fertilizer with AMF could increase grain yield and content of nutrients of barley over the control.

β-Ga2O3 is a well-known semiconductor material for power devices and other applications. Recently, β-Ga2O3 has also been reported as a scintillator material with a light yield of approximately 8400 ph./MeV, scintillation decay time of <1 μs, and density of 6.44 g/cm3. In this study, 2-inch diameter β-Ga2O3 single crystals were prepared by oxide crystal growth using the cold crucible (OCCC) method under various oxygen partial pressures. In the OCCC method, as in the cold crucible method, a high frequency is applied directly to the oxide materials, which are heated and melted, and the melt is held by the outermost solid material itself that is cooled by water using a copper hearth. In the OCCC method, crystal growth is performed while rotating the seed crystal, as in the Czochralski method, to increase the crystal diameter. The optical properties and radiation responses of the crystals grown under various oxygen partial pressures were evaluated.

The current performance indicator for universal salt iodization (USI) is the percent of households using adequately iodized salt. However, the proportion of dietary salt from household salt is decreasing with the increase in consumption of processed foods and condiments globally. This paper reports on case studies supported by the GAIN-UNICEF USI Partnership Project to investigate processed food industry use of adequately iodized salt in contrasting national contexts. Studies were conducted in Egypt, Indonesia, the Philippines, the Russian Federation, and Ukraine. In all cases, the potential iodine intake from iodized salt in selected food products was modelled according to the formula: Quantity of salt per unit of food product x minimum regulated iodine level of salt at production x average daily per capita consumption of the product. The percent of adult recommended nutrient intake for iodine potentially provided by the average daily intake of bread and frequently consumed foods and condiments was from 10% to 80% at the individual product level. The potential contribution to iodine intake from the use of iodized salt in the processed food industry is of growing significance. National USI strategies should encourage co-operative industry engagement and include regulatory monitoring of iodized salt use in the food industry in order to achieve optimal population iodine status.

Lung cancer is the leading cause of cancer related mortality worldwide. In order to improve its overall survival, early diagnosis is required. Since current screening methods still face some pitfalls, such as high false positive rates for low-dose computed tomography, researchers are still looking for early biomarkers to complement existing screening techniques in order to provide a safe, faster and more accurate diagnosis. Biomarkers are biological molecules found in body fluids, such as plasma, that can be used to diagnose a condition or disease. Metabolomics has already shown to be a powerful tool in the search for cancer biomarkers since cancer cells are characterised by impaired metabolism, resulting in an adapted plasma metabolite profile. The metabolite profile can be determined using nuclear magnetic resonance, or NMR. Although metabolomics and NMR metabolite profiling of blood plasma are still under investigation, there is already evidence for its potential for early-stage lung cancer diagnosis, therapy response, and follow-up monitoring. This review highlights some key breakthroughs in this research field, where the most significant biomarkers will be discussed in relation with their metabolic pathways and in light of the altered cancer metabolism.

Abstract: This article reports the results of an ecological study of cancer incidence rates by state in the US for the period 2016-2020. The goals of this study were to determine the extent to which solar UVB doses still reduced cancer risk compared to findings reported in 2006 for cancer mortality rates for the periods 1950–1969 and 1970-1794 as well as cancer incidence rates for the period 1998–2002 and to determine which factors were recently associated with cancer risk. The cancer data for non-Hispanic white (European American) men and women were obtained from the Centers for Disease Control and Prevention. Indices were obtained for solar UVB at the surface for July 1992, and alcohol consumption, and diabetes and obesity prevalence near the 2016–2020 period. Lung cancer incidence rates were also used in the analyses as a surrogate for smoking, diet, and air pollution. The cancers for which solar UVB is significantly associated with reduced incidence are bladder, brain (males), breast, corpus uteri, esophageal, gastric, non-Hodgkin’s lymphoma, pancreatic, and renal cancer. Lung cancer was significantly associated with colorectal, laryngeal, and renal cancer. Diabetes was also significantly associated with breast, liver, and lung cancer. Obesity prevalence was significantly associated with breast, colorectal and renal cancer. Alcohol consumption was associated with bladder and esophageal cancer. Thus diet has become a very important driver of cancer incidence rates. The role of solar UVB in reducing risk of cancer has been reduced due to people spending less time outdoors, wearing sunscreen that blocks UVB but not UVA radiation, and population increases in overweight and obesity, which lowers 25-hydroxyvitamin D concentrations and generates systemic inflammation, a risk factor for cancer. The dietary approach that would reduce the risk of diabetes, obesity, lung cancer, and, therefore cancer, would be one based mostly on whole-plants and restrictions on red and processed meats and ultraprocessed foods. Solar UVB exposure for a few minutes before applying sunscreen and taking vitamin D supplements would also help reduce risk of cancer.Keywords: alcohol consumption; cancer incidence;

This paper is a study of a generalization of the quantum Riemannian Hamiltonian evolution, previously analyzed by us in our work [6], in the geometrization of quantum mechanical evolution in a Finsler geometry. We find results with dynamical equations governing the evolution of the trajectories defined by the expectation values of position. The analysis appears to provide an underlying geometry described by a geodesic equation, with connection form with a second term which is an essentially quantum effect. These dynamical equations provide a new geometric approach to the quantum evolution where we suggest a definition for "local instability" in the quantum theory.

The rodent collecting duct (CD) expresses a 24p3/NGAL/lipocalin-2 (Lcn2) receptor (Slc22a17) apically to possibly mediate high-affinity reabsorption of filtered proteins by endocytosis, yet its functions remain uncertain. Recently, we showed that hyperosmolarity/-tonicity upregulates Slc22a17 in cultured mouse inner medullary CD cells, whereas activation of toll-like receptor 4 (TLR4) via bacterial lipopolysaccharides (LPS) downregulates Slc22a17. This is similar to the upregulation of Aqp2 by hyperosmolarity/-tonicity and arginine vasopressin (AVP) and downregulation by TLR4 signaling that occur via the transcription factors Nfat5 (TonEBP or OREBP), cAMP-responsive element binding protein (CREB), and nuclear factor-kappa B, respectively. The aim of the study was to determine the effects of osmolarity/tonicity via Nfat5, AVP via CREB and TLR4 signaling on the expression of Slc22a17 and its ligand Lcn2 in the mouse (m) cortical collecting duct cell line mCCD(cl.1). Normosmolarity/-tonicity was 300 mosmol/l whereas addition of 50-100 mmol/l NaCl for up to 72 h induced hyperosmolarity/-tonicity (400-500 mosmol/l). RT-PCR, qPCR, immunoblotting and immunofluorescence microscopy detected Slc22a17 and Lcn2 expression. RNAi silenced Nfat5, and the pharmacological agent 666-15 blocked CREB. Activation of TLR4 occurred with LPS. Similar to Aqp2, hyperosmotic/-tonic media and AVP upregulated Slc22a17 via activation of Nfat5 and CREB, respectively, and LPS/TLR4 signaling downregulated Slc22a17. Conversely, though Nfat5 mediated hyperosmolarity/-tonicity induced downregulation of Lcn2 expression, AVP reduced Lcn2 expression and predominantly apical Lcn2 secretion evoked by LPS, but through a posttranslational mode of action that was independent of cAMP signaling. In conclusion, the hyperosmotic/-tonic upregulation of Slc22a17 in mCCD(cl.1) cells via Nfat5 and by AVP via CREB suggests a contribution of Slc22a17 to adaptive osmotolerance, whereas Lcn2 downregulation could counteract increased proliferation and permanent damage of osmotically stressed cells.

The manuscript delves into the intricacies of food production chains, offering a comprehensive breakdown of their components. Moreover, it sheds light on the initiatives orchestrated by government agencies to endorse sustainable practices and fortify areas of opportunity for producer organizations. While the context paints a broad picture, we contend that, to the best of our knowledge, there exists no comparable publication that succinctly encapsulates the role of government in bolstering food production chains. The document unfolds with a detailed exploration of the interaction mechanisms among the various components of the chain. Subsequently, it introduces a set of twelve elements meticulously outlining the multifaceted role of the government. Each element undergoes thorough scrutiny, fostering a nuanced understanding of the intricate relationship between the food production chain and the government's pivotal role in enhancing stability and efficiency. In conclusion, the manuscript not only lays bare the structural elements of food production chains but also presents a unique and in-depth analysis of the government's role, encapsulated within the framework of twelve essential elements.

Indonesia is an interesting case study for students of sustainable development and sustainable energy due to its ability to connect the multiple “worlds” it has become part of. Indonesia is an important bridge to Muslim countries, the voice of the Global South in the G20 and a main pillar of the 134-country-strong G77. Indonesia’s development trajectory is also key to the achievement of the Paris Climate Agreement as well as of the 2030 Agenda. Students can learn from how Indo-nesia address contradictions that would have been unsurmountable for other countries. Indone-sia’s energy transition offers helpful lessons, because of its aspiration to become a developed country by 2045. This goal is only possible when a country is able to effectively address barriers and caveats to sustainable energy. It is interesting how Indonesia focuses on silver linings and come up with pragmatic solutions to energy-related issues. This is followed by the “teaching guide,” which provides recommendations how the lessons from Indonesia can be embedded into a learning experience. The “learning activation approach” is introduced, which encourages stu-dents to systematically reflect on the complexity of selected contexts and understand this com-plexity by looking at the technical issues and processes that allow decision-making.

Developmental hazard evaluation is an important part of assessing chemical risks during pregnancy. Toxicological outcomes from prenatal testing in pregnant animals result from complex chemical-biological interactions, and while New Approach Methods (NAMs) based on in vitro bioactivity profiles of human cells offer promising alternatives to animal testing, most of these assays lack cellular positional information, physical constraints, and regional organization of the intact embryo. Here, we engineered a fully computable model of the embryonic disc in the compucell3d.org modeling environment to simulate epithelial-mesenchymal transition of epiblast cells and self-organization of mesodermal domains (chordamesoderm, paraxial, lateral plate, posterior/extraembryonic). Cell fate in the model is determined by an autonomous homeobox (HOX) clock driven by morphogenetic signals (e.g., FGF, WNT, ATRA, CDX). Executing the model renders a quantitative cell-level computation of mesodermal subpopulations and consequences of perturbation based on known embryogeny. For example, synthetic perturbation of the control network rendered altered phenotypes (cybermorphs) mirroring experimental mouse embryology, with 50% reductions in FGF4, FGF8 and BMP4 signaling resulting in 86%, 98% and 59% reductions, respectively in the posterior mesodermal population, while ATRA exposure also resulted in a 78% decrease in this population. This model enables integration of in vitro chemical bioactivity data for specific molecular targets with known embryology to test mechanistic veracity and quantitative prediction of altered development.

The energy sector plays an important role in Mexico’s development trajectory. Mexico makes an interesting case study, because it shows how difficult it is to reduce fossil energy dependence despite geographic and climatic conditions that favour renewable energy deployment and use. Resolving path dependencies and the related carbon lock-in are key to Mexico’s sustainable energy transition. This case study aims to identify and discuss how carbon lock-in affects Mexico’s sustainable energy transition. Mexico’s carbon lock-in involves oil and oil-run power plants that are costly to build but relatively inexpensive to operate. This case study identifies potential entry points for transitioning towards sustainable energy in Mexico – resources that can promote the use of clean energy despite carbon lock-in. For example, focusing on electrification – particularly of the carbon-intensive sectors – can help Mexico transit towards sustainable energy despite institutional constraints. Complementing this case study is a teaching guide with recommendations for using Mexico’s energy transition in courses on sustainability. It introduces a “learning activation framework” to identify emerging opportunities that can advance sustainable energy transitions in different cases of carbon lock-in. Finally, the framework also gives students a chance to help dismantle or cope with carbon lock-ins.

This study focused on evaluating the potential of natural fermentation of pea flour (F) to improve the release of antioxidant compounds. Two fermentation conditions of F were performed: 1: 36.4% w/w, 24 h, 30°C (FF1); 2: 14.3% w/w, 24 h, 37°C (FF2); pH values decreased to 4.4-4.7, with a predominance of lactic acid bacteria. An increment of the proteolysis degree (TNBS method) (greater for FF2), polypeptides aggregation and decrease of solubility, increase of < 2 kDa peptides, and increase in the ORAC potency of PBS-soluble fractions after fermentation was demonstrated. After simulated gastrointestinal digestion (SGID, COST-INFOGEST), FF1D and FF2D showed greater proteolysis degrees (63 and 53%) than F1D and F2D (45%), with differences in the molecular composition of the different digests. ORAC and HORAC potencies increased in all cases. FF2D presented the greater ORAC value, with higher activities for > 4 kDa, some in the range 2 to 0.3 kDa. and < 0.10 kDa fractions. Fermentation also increased the 60 % ethanol extracted phenolic compounds, mainly flavonoids, and the ORAC activity. After SGID, the flavan-3-ols disappeared but some phenolic acids increased respect to F. Fermentation in condition 2 was considered the most appropriate to obtain a functional antioxidant ingredient.

Introduction: Fractures in older individuals are often caused by falls, with approximately 90% of hip fractures resulting from falls. The risk of falling increases with age, and while a significant portion of individuals over 65 fall at least once per year, only a small percentage of these falls result in hip fractures. Factors that influence the likelihood of a fracture occurring include the intensity of the fall and the quality of the bone, with lower bone mineral content increasing the risk of fracture. Older women, particularly those in their 70s, are significantly more prone to hip fractures and any type of fracture. Efforts to reduce the likelihood of falls or mitigate the associated trauma are more complex than treating osteoporosis, due in part to a lack of understanding of the causes and contributing factors of falls in older age.Methods: This study analyzed data from patients admitted to Carmel medical center with upper or lower limb fractures between 2017 and 2019 to determine the side of wrist fractures and compare it to patient age in order to examine whether there was a difference in the distribution of sides in distal radius fractures based on age and test the hypothesis that falls are more likely to occur on the left side due to the assumption that dominant hand gross motor skills are better preserved. The study received approval from the Institutional Helsinki Committee and used statistical analysis with a significance level of 0.05. Potential sources of bias include limited availability of reliable data for many patients and the risk of errors in fracture registration or diagnosis, although the small sample size is expected to minimize these biases.Results: In this analysis of patient data from 2019 to 2017, a binomial test found that the probability of breaking the left wrist is significantly greater than the probability of breaking the right wrist (p < 0.05), while a t-test found no difference in the distribution of fractures between the right and left wrists of the distal radius based on age (p = 0.2774). Discussion: The findings of the study are consistent with previous research, and indicate that there is no change in side preference for fractures with age. Conclusion: The probability of breaking the left wrist is approximately 1.5 times greater than the probability of breaking the right wrist.

A novel stationary phase for affinity separations is presented. This material is based on sintered borosilicate glass readily available as semi-finished filter plates with defined porosity and surface area. The material shows fast binding kinetics and excellent long-term stability under real application conditions due to lacking macropores and high mechanical rigidity. The glass surface can be easily modified with standard organosilane chemistry to immobilize selective binders or other molecules used for biointeraction. In this paper, the manufacturing of the columns and their respective column holders by 3D printing is shown in detail. The model system protein A/IgG was chosen as an example to examine the properties of such monolithic columns under realistic application conditions. Several specifications, such as (dynamic) IgG capacity, pressure stability, long-term performance, productivity, non-specific binding, and peak shape, are presented. It could be shown that due to the very high separation speed, 250 mg antibody per hour and column can be collected, which surpasses the productivity of most standard columns of the same size. The total IgG capacity of the shown columns is around 4 mg (5.5 mg/mL), which is sufficient for most tasks in research laboratories. The cycle time of an IgG separation can be less than 1 minute. Due to the glass material's excellent pressure resistance, these columns are compatible with standard HPLC systems. This is usually not the case with standard affinity columns, limited to manual use or application in low-pressure systems. The use of a standard HPLC system also improves the ability for automation, which enables the purification of hundreds of cell supernatants in one day. The sharp peak shape of the elution leads to an enrichment effect, which might increase the concentration of IgG by a factor of 3. The final concentration of IgG can be around 7.5 mg/mL without the need for an additional nanofiltration step. The purity of the IgG was > 95% in one step and nearly 99% with a second polishing run.

The potentiality of cv. Malbec grape pomace (GP) as a functional ingredient in the formulation of bakery foods (muffins, biscuits and cereal bars) was studied. The effect of GP addition on the phenolic compounds (PCs) composition, nutritional and sensory properties were evaluated. The addition of GP increased the content of dietary fiber, proteins, ash, total phenolic content (TPC), antioxidant activity (AA), anthocyanins and non-anthocyanins PCs while decreasing the carbohydrates content. The main PCs given by the GP to supplemented foods were (-)-gallocatechin, quercetin-3-O-glucoside, rutin, caffeic acid, syringic acid and (+)-catechin. For anthocyanins, the acylated derivatives were more stable to heat treatment (baking) in food processing which was evidenced by a higher proportion of these PCs compounds when compared to the same derivatives quantified in GP. In general, when the TPC or individual concentrations of PCs were analyzed in a nutritional or functional context, one portion of the supplemented foods showed levels high enough to satisfy the recommended dose per day of these bioactive compounds. Additionally, the foods were well received by consumers during the sensory evaluation and supplemented biscuits got the highest acceptability. This study demonstrated that GP could be a viable functional ingredient in bakery foods to give nutritionally enhanced properties like TPC, PCs, AA and dietary fiber in consumer’s diets.

Annually, more than 1.5 million preventable new hepatitis B (HBV) infections continue to occur, with an estimated global burden of 296 million individuals living with chronic hepatitis B infection. This substantial health challenge results in over 820,000 annual deaths attributed to complications such as liver cirrhosis and hepatocellular carcinoma (HCC). HBV vaccination remains the cornerstone of public health policy to prevent chronic hepatitis B and its related complications. It serves as a crucial element in the global effort to eliminate HBV, as established by the World Health Organization (WHO), with an ambitious 90% vaccination target by 2030. However, reports on global birth dose coverage reveal substantial variability, with an overall coverage rate of only 46%. This comprehensive review thoroughly examines global trends in HBV vaccination coverage, investigating the profound impact of vaccination on HBV prevalence and its consequences across diverse populations, including both high-risk and general demographics. Additionally, the review addresses the formidable challenges and facilitating factors essential for achieving WHO's HBV vaccination coverage objectives and elimination strategies in the coming decade and beyond.

Clinical screening tests for balance and mobility often fall short of predicting fall risk. Cognitive distractors and unpredictable external stimuli, common in busy natural environments, contrib-ute to this risk, especially in the elderly. Less is known about the effects of upper sensory-motor coordination such as coordinating one’s hand with an external stimulus. We combined move-ment sonification and affordable inertial motion sensors to develop a task for the precise meas-urement and manipulation of full-body interaction with stimuli in the environment. In a double-task design, we studied how a supra-postural activity affected quiet stance. The supra-postural task consisted of rhythmic synchronization with a repetitive auditory stimulus. The stimulus was attentionally demanding because it was being modulated continuously. The participant’s hand movement was sonified in real-time, and their goal was to synchronize their hand move-ment with the stimulus. In the unpredictable condition, the tempo changed at random points in the trial. A separate sensor recorded postural fluctuations. Young healthy adults were compared to elderly participants without known risk of falling. Results supported the hypothesis that su-pra-postural coordination would entrain postural control. The effect was stronger in the elderly, supporting the idea that diminished reserve capacities reduce the ability to isolate postural con-trol from sensory-motor and cognitive activity.

Background: Across the world, antibiotic resistance is a grave problem. To address this issue, it is necessary to investigate new antibiotic sources. Aim of the study: Egypt's diverse soil habitats were used to produce bacterial Myxopyronin B, which was then tested for antimicrobial activity in preclinical animal studies and randomized human clinical trials stages 1/2. Type of the study: Screening experimental study. Methodology: Egypt's various soil conditions were examined for the development of bacterial isolates that produced the antibiotic compound Myxopyronin B. Reversed phase HPLC was used to purify Myxopyronin B. To determine the test antibiotic's minimum inhibitory concentration( MIC) and invitro antibacterial activity, the Broth microdilution method and the Paper disc diffusion assay were utilized. Moreover, in vivo antibacterial spectrum, adverse medication responses, and pharmacokinetics were found in preclinical animal testing stages and phases 1/2 of randomized clinical studies involving volunteer humans. Results: Myxopyronin B was generated from the culture supernatant of Myxococcus SDU36, the main soil bacterial isolate cultured on a Casein yeast peptone plate. With MICs less than 100 mcg/ml, the test antibiotic prevented the growth of several Gram +ve bacteria, whereas, at MICs higher than 100 mcg/ml, it inhibited the development of a small number of Gram -ve bacteria, including Escherichia coli. However, eukaryotic cells—such as those found in fungi and humans—were unaffected. The test antibiotic was seen to inhibit prokaryotic DNA-dependent RNA polymerase( RNLP), indicating its bactericidal activity. Mean Cmax was 9-10 mcg/ ml at mean Tmax 1 hour when 600 mg dose was orally administered in randomized human clinical trials phases 1/2, and T1/2 reached 2.25 hours following first-order kinetics of elimination. Duration of its action was nearly 8 hours after oral administration. Rare toxicity was detected during preclinical and randomized human clinical trials phases 1/2 in the form of mild diarrhea and GI upset in less than 7 % of experimental candidates. It exhibited approximately 90% plasma protein binding, especially with albumin which resulted in prolonged therapeutic action. It showed a concentration dependant antibiotic killing effect. With the concentration-dependent killing pattern, the higher the drug concentration relative to the pathogen minimum inhibitory concentration( MIC), the greater the rate and extent of antimicrobial activity. Conclusion: The present study was promising due to the production of the bactericidal antibiotic Myxopyronin B from Myxococcus sp. SDU36 isolated from different soil environments in Egypt.

Non-coding RNAs (ncRNAs) comprise a diverse class of non-protein coding transcripts that regulate critical cellular processes associated with cancer. Advances in RNA-sequencing (RNA-Seq) have led to the characterization of non-coding RNA expression across different types of human cancers. Through comprehensive RNA-Seq profiling, a growing number of studies demonstrate that ncRNAs, including long non-coding RNA (lncRNAs) and microRNAs (miRNA), play central roles in progenitor B-cell Acute Lymphoblastic Leukemia (B-ALL) pathogenesis. Furthermore, due to their central roles in cellular homeostasis and their potential as biomarkers, the study of ncRNAs continues to provide new insight into the molecular mechanisms of B-ALL. This article reviews the ncRNA signatures reported for all B-ALL subtypes, focusing on technological developments in transcriptome profiling and recently discovered examples of ncRNAs with biologic and therapeutic relevance in B-ALL.

Multicomponent training is recommended for people with dementia living in long-term care homes. Nevertheless, evidence is limited and people with severe dementia are often excluded from trials. Hence, the aim of this study was to investigate (1) the feasibility and (2) the requirements regarding a multicomponent training for people with moderate to severe dementia. The study was conducted as an uncontrolled single arm pilot study with a mixed methods approach. 15 nursing home residents with a mean age of 82 years (range: 75-90 years; female: 64%) with moderate to severe dementia received 16 weeks of multicomponent training. Feasibility and requirements of the training were assessed by a standardized observation protocol. Eleven participants regularly attended the intervention. The highest active participation was observed during gait exercises (64%), the lowest during strength exercises (33%). It was supportive if exercises were task-specific or related to everyday life. This study confirms that a multicomponent training for the target group is (1) feasible and well accepted. To enhance active participation (2) individual instructions and the implementation of exercises related to everyday life is required. The effectiveness of the adapted training should be tested in future randomized controlled trials.

Characterised by the growth of benign tumours, fibropapillomatosis (FP) is a debilitating disease that predominantly afflicts the endangered green turtle (Chelonia mydas). A growing body of histological and molecular evidence has consistently associated FP tumours with Chelonid alphaherpesvirus 5 (ChHV5), leading this virus to be considered the most likely aetiological agent of FP. However, a recent study which detected both ChHV5 and Chelonia mydas papillomavirus 1 (CmPV1) DNA in FP tumour tissues has challenged this hypothesis. The present study aimed to establish the wider prevalence of CmPV1 and co-occurrence with ChHV5 in marine turtles in waters adjacent to the east coast of Queensland, Australia. This comprehensive molecular survey screened a total of 353 samples from 275 foraging turtles using probe-based qPCR. Three sample categories were used in this study: Group A (FP tumours), Group B (non-tumoured skin from turtles with FP tumours) and Group C (non-tumoured skin from turtles without FP tumours). Concurrent detection of ChHV5 and CmPV1 DNA is reported for all three categories, with the highest rate of concurrent detection reported for Group A samples (43.5%). Collectively, these results pivot the way we think about FP; as an infectious disease where two separate viruses may be at play.

Jasmonates (JAs), including jasmonic acid (JA) and its biologically active derivative JA-Ile, are lipid-derived plant signalling molecules. They govern plant responses to stresses, such as wounding and insect herbivory. Wounding elicits a rapid increase of JA and JA-Ile levels as well as the expression of JAR1, coding for the enzyme involved in JA-Ile biosynthesis. Endogenous increase and application of JAs, such as MeJA, a JA methylester, result in increased defence levels, often accompanied by diminished growth. The function of jarin-1 in Arabidopsis thaliana was assessed. To investigate whether jarin-1 does function similarly in other plants, we tested this in Medicago truncatula, Solanum lycopersicum, and Brassica nigra seedlings in a root growth inhibition assay. Application of jarin-1 alleviated the inhibition of root growth after MeJA application in M. truncatula seedlings, proving that jarin-1 is biologically active in M. truncatula. Jarin-1 did not show, however, a similar effect in S. lycopersicum and B. nigra seedlings treated with MeJA. Even JA-Ile levels were not affected by application of jarin-1 in wounded leaf disks from S. lycopersicum. Based on these results, we conclude that the effect of jarin-1 is highly species-specific. Researchers intending to use jarin-1 for studying the function of JAR1 or JA-Ile in their model plants, must test its functionality before use.

Abiotic stress is responsible for significant reduction in crop plant productivity worldwide. Ultraviolet (UV) radiation is a natural component of sunlight and a permanent environmental stimulus. This study investigated the distinct responses of young wheat and einkorn plants to excessive UV-B radiation (180 min at λmax 312 nm) following foliar pretreatment with 1 µM synthetic cytokinin 4PU-30. Results demonstrated that UV radiation significantly amplified hydrogen peroxide levels in both wheat and einkorn, with einkorn exhibiting more pronounced increase compared to wheat. This elevation indicated the induction of oxidative stress by UV radiation in the two genotypes. Intensified antioxidant enzyme activities and increased accumulation of typical stress markers and non-enzyme protectants were evidenced. Transcriptional activity of genes encoding key antioxidant enzymes was also investigated aiming to elucidate the genetic regulation of the antioxidant systems in both wheat and einkorn seedlings. Our results suggested a role for POX1 and POX7 genes in the UV-B tolerance of the two wheat species as well as a cytokinin stimulated UV-B stress response in einkorn mediated through upregulation of the tau subfamily gene GSTU6. Based on these findings it could be concluded that 4PU-30 had the potential of alleviating oxidative stress by attenuating the symptoms of superfluous UV-B illumination in the two examined plant species.

Many physiotherapy treatments begin with a diagnosis process. The patient describes symptoms, upon which the physiotherapist decides which tests to perform until a final diagnosis is reached. The relationships between the anatomical components are too complex to keep in mind and the possible actions are abundant. A trainee physiotherapist with little experience naively applies multiple tests to reach the root cause of the symptoms, which is a highly inefficient process. This work proposes to assist students in this challenge by presenting three main contributions: (1) A compilation of the neuromuscular system as components of a system in a Model-Based Diagnosis problem; (2) The PhysIt is an AI-based tool that enables an interactive visualization and diagnosis to assist trainee physiotherapists; and (3) An empirical evaluation that comprehends performance analysis and a user study. The performance analysis is based on evaluation of simulated cases and common scenarios taken from anatomy exams. The user study evaluates the efficacy of the system to assist students in the beginning of the clinical studies. The results show that our system significantly decreases the number of candidate diagnoses, without discarding the correct diagnosis, and that students in their clinical studies find PhysIt helpful in the diagnosis process.

Deforestation is an important environmental problem in México and a key promoter of regional climate change through modifying the surface albedo. The objective of this research was to characterize the impact of deforestation and land use changes on surface albedo (α) and climate patterns in the Municipality of Tapalpa, Jalisco, México between the years 2014 and 2021. The main land cover types are coniferous forests (CF), oak and gallery woodlands (OGW), and annual agriculture (AA); which represent more than 88% of the regional territory (1066.03 km2). We used 2014 and 2021 Landsat 8 OLI images with topographic and atmospheric correction, in order to develop an inventory of albedo values for each land cover type in both time scenarios. Albedo images were generated by using the equation proposed by Liang in 2001, which is based on the reflectance of the bands 2, 3, 4, 5, and 7. Differences in albedo values were calculated between the years 2014 and 2021, and those differences were correlated with variations in climate parameters, for which we used climate data derived from the WRF model. In addition, the different land use changes found were classified in terms of triggers for increasing or decreasing surface albedo. Results showed that between 2014 and 2021, at least 38 events of land use change or deforestation occurred, with albedo increments between 1 and 11%, which triggered an average increment of 0.57% of the regional surface albedo in comparison to 2014 scenario. From 2014 to 2021, the albedo for CF, OGW, and AA, increased significantly (p&lt;0.001; Mann-Whitney U Test) by 79, 12, and 9%, respectively. In addition, the regional albedo increment was found to be significant and negatively correlated (p&lt;0.01 Spearman’s coefficient) with relative humidity (RH), maximum temperature (Tmax), minimum temperature (Tmin), and diurnal thermal range (DTR). The decrease in the regional values of relative humidity in 2021, occurred even when in that year the annual precipitation levels were higher than those of 2014, hence, reinforcing the fact of a possible climatic effect of the regional albedo changes. Conversion of CF and OGW into AA, perennial agriculture (PA), or grassland (GR) always yielded an albedo increment, whilst the conversion of AA to irrigation agriculture or PA triggered a decrease in albedo, and finally, the pass from GR or AA to protected agriculture caused albedo increase or decrease, depending on the greenhouse covers materials. Reducing deforestation of CF and OGW, conversion of AA or GR into PA, and selecting adequate greenhouse covers could help to mitigate regional climate change.

Previous research has explored different models of synchronous remote learning environments supported by videoconferencing and virtual reality platforms. However, few studies have evaluated the preference and acceptance of synchronous remote learning in a course streamed in an immersive or augmented reality platform. This case study uses ANOVA analysis to examine the engineering students´ preferences for receiving instruction during the COVID19 pandemic in three classroom types: face-to-face, conventional virtual (mediated by videoconferencing) and an immersive virtual classroom (IVC). Likewise, structural equation modeling, was used to analyze the acceptance of the IVC perceived by students, this includes four latent factors: ease of receiving a class, perceived usefulness, attitude towards IVC and IVC use. The findings showed that the IVC used in synchronous remote learning has a similar level of preference to the face-to-face classroom, and higher than the conventional virtual one. Despite the high preference for receiving remote instruction in IVC, aspects such as audio delays that affect interaction still need to be resolved. On the other hand, a key aspect for a good performance of these environments is the dynamics associated with the teaching-learning processes and the instructor´ qualities.

The management of shoulder instability in children and adolescents is a challenging field of orthopaedics. There are several complicating factors which originate from the variable underlying cause that is often a unique combination of traumatic factors, ligamentous laxity, and the pattern of muscle contractility. As the cause is often multifactorial, this makes interpretation of the literature difficult as nomenclature is variable. The purpose of this review is to shed light on the nuances of paediatric and adolescent shoulder instability.

One of the oldest problems in physics is that of calculating the motion of N particles under a specified mutual force: the N-body problem. Much is known about this problem if the specified force is non-relativistic gravity, and considerable progress has been made by considering the problem in one spatial dimension. Here I review what is known about the relativistic gravitational N-body problem. Reduction to one spatial dimension has the feature that gravitational radiation is absent, thereby allowing for a clear comparison between the physics of one-dimensional relativistic and non-relativistic self-gravitating systems. After describing how to obtain a relativistic theory of gravity coupled to N point particles, I discuss in turn the 2-body, 3-body, 4-body, and N-body problems. Quite general exact solutions can be obtained for the 2-body problem, unlike the situation in general relativity in 3 spatial dimensions for which only highly specified solutions exist. The 3-body problem exhibits mild forms of chaos, and provides one of the first theoretical settings in which relativistic chaos can be studied. For N4 other interesting features emerge. Relativistic self-gravitating systems have a number of interesting problems awaiting further investigation, providing us with a new frontier for exploring relativistic many-body systems.

Objectives: As institutions modified medical practices to mitigate the spread of the SARS-CoV-2 virus, providers were forced to modify care through the implementation of telemedicine. The objective of this article is to review the current practices of otolaryngology during the COVID-19 pandemic and the limitations of telemedicine in current practice. Methods: A thorough review of the PubMed and MEDLINE databases was performed for publications between 2020 and 2021. Studies discussing telemedicine in otolaryngology during COVID-19 pandemic were selected. Results: As worldwide cases of COVID-19 continue to oscillate, we must continue to be vigilant in our clinical practice, implementing safe techniques to mitigate the spread of the SARS-CoV-2 virus through the continual use of telemedicine in all specialties of otolaryngology. Trends of increased patient acceptance of the use of telemedicine have been seen across subspecialities, including otolaryngology. Conclusion: Currently there are challenges associated with the implementation of telemedicine in the field of otolaryngology that rely heavily on adjunct physical examination, imaging studies, and specialty procedures. However, telemedicine has tremendous potential and can be adapted to include in the otolaryngologist’s toolbelt during public health emergencies such as the COVID-19 pandemic.

The initial dilution generated by the final disposal of untreated wastewater through a submarine outfall in Santa Marta was examined with a near-field dilution model. Northward and eastward seawater velocity, salinity, and temperature profiles from a 3D hydrodynamic model were used to provide the oceanic conditions to calculate the dilution. At the wastewater discharge site, the upwelling phenomenon occurs two times a year, the major from December to March and the minor in July, eliminating the stratification condition of seawater. The results of the dilution model showed that in these periods the plume reaches the water surface achieving dilutions greater than 100. In addition, the external wave effect on the initial dilution of submarine outfall discharge in Santa Marta was determined. Surface waves increase dilution during the dry period of the year when trade winds increase the surge and start the upwelling phenomenon. The Dilution with/without waves factor is up to 1.90 for the center of the plume on the water column.

Coronavirus Disease-2019 (COVID-19) is an infectious disease caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). There is sufficient experimental evidence to confirm that SARS-CoV-2 infection produces states of ciliary and flagellar dysfunction. However, these studies are unable to explain the observed effects molecularly, because they lack a sufficient understanding of the interaction between human proteins and virus proteins. Using the physical-chemical study of the human interactome in interaction with the SARS-CoV-2 proteome, we found evidence of interactions to explain the experimental effects from a molecular perspective. We found that ten viral proteins interact with key components in the maintenance of the molecular structure of axoneme. Additionally, we evaluated the pulmonary and extrapulmonary pathogenesis of COVID-19 from the point of view of ciliary dysfunction, and warned about other possible complications such as episodes of transient infertility that, due to the limitations of our work, would need verification.

This work presents an alternative to harnessing wind energy with an Electromagnetic Frequency Regulator (EFR) coupled to a hydrostatic transmission and associated with a horizontal axis wind turbine, a bidirectional frequency inverter and a secondary energy source, in a hybridized system. The hydrostatic transmision is composed by a fixed displacement axial piston pump and a variable displacement, swash plate, axial piston motor. Feedback linearization was used as a technique to control the motor geometric displacement, and a prediction algorithm for the steady state rotations of the armature and the electromagnetic field has been developed. A 5\,kW project was simulated on a Scilab platform, with combinations of constant or variable load, and constant or variable wind speed. The results indicated that the system was able to supply the generator load, adapting to fluctuations in wind speed. The possibility of storing wind energy through the inverter has also been proven. The system can accumulate energy in batteries during the fastest wind regimes, to use it when the turbine power is lower than the load.

Structural hydroxide groups in layered magnesium-aluminum double hydroxides were partially replaced by fluoride ions. Fluorinated and fluorine-free materials were used as hosts for two dyes, carminic acid and hydroxyl naphthol blue, resulting in a hybrid pigment color palette. Additionally, the pigments were protected with a magnesium hydroxide phase to prevent the color from fading over time. The color properties of the pigments were significantly influenced by the host of dye, since the presence of fluorine directly influences the acid-base properties of the layered double hydroxides. Finally, the pigments were successfully applied to prepare colored creams.

The barley (Hordeum vulgare) genome comprises over 32,000 genes, with differentiated cells expressing only a subset of genes; the remainder being silent. Mechanisms by which tissue-specific genes are regulated are not entirely understood, although DNA methylation is likely to be involved. DNA methylation patterns are not static during plant development, but it is still unclear whether different organs possess distinct methylation profiles. Methylation-sensitive GBS was used to generate DNA methylation profiles for roots, leaf-blades and leaf-sheaths from five barley varieties, using seedlings at the three-leaf stage. Differentially Methylated Markers (DMMs) were characterised by pairwise comparisons of roots, leaf-blades and leaf-sheaths of three different ages. While very many DMMs were found between roots and leaf parts, only a few existed between leaf-blades and leaf-sheaths, with differences decreasing with leaf rank. Organ-specific DMMs appeared to target mainly repeat regions, implying that organ differentiation partially relies on the spreading of DNA methylation from repeats to promoters of adjacent genes. Furthermore, the biological functions of differentially methylated genes in the different organs correlated with functional specialisation. Our results indicate that different organs do possess diagnostic methylation profiles and suggest that DNA methylation is important for both tissue development and differentiation and organ function.

The genus Rhodotorula includes basidiomycetous oleaginous yeast species. R. babjevae can produce compounds of biotechnological interest such as lipids, carotenoids and biosurfactants from low value substrates such as lignocellulose hydrolysate. High-quality genome assemblies are needed to develop genetic tools and to understand fungal evolution and genetics. Here, we combined short- and long-read sequencing to resolve the genomes of two R. babjevae strains, CBS 7808 (type strain) and DBVPG 8058 at chromosomal level. Both genomes have a size of 21 Mbp and a GC content of 68.2%. Allele frequency analysis indicated tetraploidy in both strains. They harbor 21 putative chromosomes with sizes ranging from 0.4 to 2.4 Mb. In both assemblies, the mitochondrial genome was recovered in a single contig, which shared 97% pairwise identity. The pairwise identity between the majority of chromosomes ranges from 82% to 87%. We found indications for strain-specific extrachromosomal endogenous DNA. 7,591 protein-coding genes and 7,607 associated transcripts were annotated in CBS 7808 and 7,481 protein-coding genes and 7,516 associated transcripts in DBVPG 8058. CBS 7808 has accumulated a higher number of tandem duplications than DBVPG 8058. We identified large translocation events between putative chromosomes and a high genetic divergence between the two strains.

The capacity and the mechanism of the adsorption of aqueous barium (Ba), cobalt (Co), strontium (Sr) and zinc (Zn) by Ecuadorian (NatAllo) and synthetic (SynAllo-1 and SynAllo-2) allophanes were studied as a function of contact time, pH and metal ion concentration using kinetic and equilibrium experiments. The mineralogy, nano-structure and chemical composition of the allophanes were characterized by X-ray diffraction, Fourier transform infrared spectroscopy, transmission electron microscopy and specific surface area analyses. The evolution of adsorption fitted to a pseudo-first-order reaction kinetics, where equilibrium between aqueous metal ions and allophane was reached within < 10 min. The metal ion removal efficiencies varied from 0.7 to 99.7 % at pH 4.0 to 8.5. At equilibrium, the adsorption behavior is better described by the Langmuir model than by the Dubinin-Radushkevich model, yielding sorption capacities of 10.6, 17.2 and 38.6 mg/g for Ba^(2+), 12.4, 19.3 and 29.0 mg/g for HCoO_2^-, 7.2, 15.9 and 34.4 mg/g for Sr^(2+) and 20.9, 26.9 and 36.9 mg/g for Zn^(2+), respectively, by NatAllo, SynAllo-2 and SynAllo-1. The uptake mechanism is based on a physical adsorption process. Allophane holds great potential to remove aqueous metal ions and could be used instead of zeolites, montmorillonite, carbonates and phosphates for wastewater treatment.

Chronic Hepatitis B (CHB) Virus infection is major etiological factor for liver cirrhosis and/ or liver cancer. The viral protein, major contributor in predisposition of chronicity and Hepatocellular Carcinoma (HCC) is Hepatitis B x (HBx) protein. Its dynamic subcellular distribution to an extent determines its multifactorial role. It is a regulatory protein which modulates viral as well as host machinery in favours to HBV persistence. An insight on HBx stabilising factors is critical for therapeutic purpose. The precise role of HBx in the pathogenesis of Chronicity of HBV is not known. Summary: This review comprehensively summarizing different mechanisms and their regulation by HBx protein with respect to chronicity and HCC emphasising viral persistence. Key Messages 1. HBx is a key protein for viral persistence. 2. Dynamic subcellular distribution of HBx determines its function. 3. HBx modulates cellular machinery to favours HBV survival. 4. HBx affects various intermediary mechanisms contributing to disease progression. 5. HBx may be a potent target to prevent the disease progression towards HCC.

Peanut hulls (PH) are an edible food waste that is an underutilized food source for human consumption. While edible and palatable, they are mainly diverted to livestock feed or building materials. Here, we describe existing literature on human food valorization of PHs and propose methods to optimize recapturing nutrients (e.g. protein, fiber, polyphenols) lost by treating PHs as waste. Incorporated into common foods, PHs can be processed into functional ingredients to improve nutrient-density and the corresponding positive health outcomes associated with increases in plant foods. PH valorization can also address additional priorities of the UN Sustainable Development Goals using a Food Systems Approach (FSA) including food waste, increasing economic opportunities for farmers, and increasing the availability of healthy shelf-stable foodstuffs to address food security. Recent advances in sustainable food processing technologies can be utilized to safely incorporate peanut hulls into human food streams. We propose future applications that could make meaningful impacts to food availability and the nutritional composition of common foods. While the limited literature on this topic spans several decades, no global operations exist to incorporate peanut hulls and most publications precede the technological ‘green revolution’. The approaches outlined in this review may help bolster commercialization of this underutilized and nutritious food potentially improving opportunities for multiple global stakeholders.

Cryptococcus neoformans causes meningoencephalitis in immunocompromised individuals, which is treated with Fluconazole (FLC) monotherapy when resources are limited. This can lead to azole resistance, which can be mediated by overexpression of ABC transporters, a class of efflux pumps. ABC pump-mediated efflux of FLC is also augmented in 10-generation old C. neoformans cells. Here, we describe a new ABC transporter Afr3 (CNAG_06909), which is overexpressed in C. neoformans cells of advanced generational age, that accumulate during chronic infection. The delta-afr3 mutant strain showed higher FLC susceptibility by FLC E-Test strip testing and also by a killing test that measured survival after 3 h FLC exposure. Furthermore, delta-afr3 cells exhibited lower Rhodamine 6G efflux compared to the H99 wild type cells. Afr3 was expressed in the Saccharomyces cerevisiae AD-delta strain, which lacks several drug transporters, thus reducing background transport. The AD-delta + Afr3 strain demonstrated a higher efflux with both Rhodamine 6G and Nile Red, even though the FLC MICs were not changed. Characterization of the delta-afr3 mutant revealed unattenuated growth but a prolongation (22%) of the replicative life span. In addition, delta-afr3 exhibited decreased resistance to macrophage killing and attenuated virulence in the Galleria mellonella infection model. In summary, our data indicate that a novel ABC pump Afr3p, which is upregulated in C. neoformans cells of advanced age may contribute to their enhanced FLC tolerance, by promoting drug efflux. Lastly, its role in macrophage resistance may also contribute to the selection of older C. neoformans cells during chronic infection.

Cryptococcus neoformans is a facultative intracellular fungal pathogen. Ten-generation-old (10GEN) C. neoformans cells are more resistant to phagocytosis and killing by macrophages than younger daughter cells. However, mechanisms that mediate this resistance and intracellular parasitism are poorly understood. Here, we identified factors important for the intracellular survival of 10GEN C. neoformans, such as urease activity, capsule synthesis, and DNA content using flow cytometry and fluorescent microscopy techniques. Real-time visualization of time-lapse imaging was applied to determine the phagosomal acidity, membrane permeability, and vomocytosis (non-lytic exocytosis) rate in J774 macrophages that phagocytosed C. neoformans of different generational ages. Our results showed that old C. neoformans exhibited higher urease activity, and enhanced capsule formation, which was supported by an increased Golgi complex. In addition, old C. neoformans were more likely to be arrested in the G2 phase, resulting in the occasional formation of aberrant trimera-like cells. To finish, the advanced generational age of the yeast cells slightly reduced vomocytosis events within host cells, which might be associated with increased phagolysosomal pH and membrane permeability. Altogether our results contribute to a better understanding of the strategies used by old C. neoformans to resist phagosomal killing and suggest that old generation C. neoformans intracellular behavior may be driving cryptococcosis pathogenesis.

Dengue virus is a global health problem most prevalent in tropical and subtropical regions. However, after the approval of two vaccines, Dengvaxia, TV003/TV005 of Takeda, for its prevention, problems were reported, like enhanced risks of infection or less efficiency of protection. Since then, more struggles have been in demand for the development of better vaccines. Here, we conducted a new design through an in-silico strategy. Initially, epitopes were chosen based on their antigenicity, immunogenicity, and binding affinity with MHC molecule, while excluded with allergenicity, toxicity and potential risk of antibody dependent enhancement. Subsequently, a core antigen was constructed with selected epitopes and linked with distinct adjuvant proteins to achieve three candidate vaccines, PSDV-1~3. PSDV-2 was chosen for further validation based on their advantage in physicochemical and structural properties. With a panel of simulations, this artificial protein showed tight binding with pattern recognition receptors, good stability, robust immune induction, and ultimately was confirmed as a high quality vaccine candidate. The plasmid for its recombinant expression was then designed accordingly. With our new design, one more choice was obtained for the effective protection from Dengue virus. Further experimental validations are still require to confirm it protection capacity and safety.

Clinical, pathological, and imaging evidence in multiple sclerosis (MS) shows that inflammation starts early and progresses with age. B cells play a central role in this process, contributing to cytokine production, defective regulatory functions, and abnormal immunoglobulin production, even in the central nervous system. Anti-CD20 (aCD20) therapies, which deplete CD20+ B cells, are effective for both relapsing-remitting (RR) and progressive-relapsing (PR) MS. While effective against MS symptoms and lesions detectable by magnetic resonance imaging, aCD20 therapies can reduce the immune response to COVID-19 vaccination. By using high-parameter flow cytometry, we examined the antigen-specific (Ag+) immune response six months post-third COVID-19 mRNA-vaccination in MS patients with RR and PR forms on aCD20 therapy. Despite lower Ag+ B cell responses and lower levels of anti-SARS-CoV2, both total and neutralizing antibodies, RR and PR patients developed strong Ag+ T cell responses. We observed similar percentages and numbers of Ag+ CD4+ T cells and high proportion of Ag+ CD8+ T cells, with slight differences in T cell phenotype and functionality, that however suggested the presence of differences in immune responses driven by age and disease severity.

Acidic ostreolysin A/pleurotolysin B (OlyA/PlyB, formerly known as ostreolysin (Oly), and basic 20 kDa equinatoxins (EqTs) are cytolytic proteins isolated from the edible mushroom Pleurotus ostreatus and the sea anemone Actinia equina, respectively. Both toxins, although from different sources, share many similar biological activities: (i) colloid-osmotic shock by forming pores in cellular and artificial membranes enriched in cholesterol and sphingomyelin; (ii) increased vascular endothelial wall permeability in vivo and perivascular oedema; (iii) dose-dependent contraction of coronary vessels; (iv) haemolysis with pronounced hyperkalaemia in vivo; (v) bradycardia, myocardial ischemia and ventricular extrasystoles accompanied by progressive fall of arterial blood pressure and respiratory arrest in rodents. Both types of toxins are haemolytic within nanomolar range concentrations, and it seems that hyperkalaemia plays an important role in toxin cardiotoxicity. However, it was observed that the haemolytically more active EqT III is less toxic than EqT I, the most toxic and least haemolytic EqT. In mice, EqT II is more than 30 times more toxic than OlyA/PlyB when applied intravenously. These observations imply that haemolysis with hyperkalaemia is not the sole cause of the lethal activity of both toxins. Additional mechanisms responsible for lethal action of the two toxins are direct effects on heart, coronary vasoconstriction and related myocardial hypoxia. In this review, we appraise the pathophysiological mechanisms related to the chemical structure of OlyA/PlyB and EqTs, as well as their toxicity.

The proliferation and survival signals emanating from the B-cell receptor (BCR) constitute a crucial aspect of mature lymphocyte’s life. Dysregulated BCR signaling is considered a potent contributor to tumor survival in different subtypes of B cell non-Hodgkin lymphomas (B-NHLs). In the last decade, emergence of BCR-associated kinases as rational therapeutic targets has led to the development and approval of several small molecule inhibitors targeting either Bruton's tyrosine kinase (BTK), spleen tyrosine kinase (SYK), or phosphatidylinositol 3 kinase (PI3K), offering alternative treatment options to standard chemoimmunotherapy, and making some of these drugs valuable assets in the anti-lymphoma armamentarium. Despite their initial effectiveness, these precision medicine strategies are limited by primary resistance in aggressive B-cell lymphoma like diffuse large B cell lymphoma (DLBCL) and mantle cell lymphoma (MCL), especially in the case of first generation BTK inhibitors. In these patients, BCR-targeting drugs often fail to produce durable responses, and nearly all cases eventually progress with a dismal outcome, due to secondary resistance. This review will discuss our current understanding of the role of antigen-dependent and antigen-independent BCR signaling in DLBCL and MCL and will cover both approved inhibitors and investigational molecules being evaluated in early preclinical studies. We will discuss how the mechanisms of action of these molecules, and their off/on-target effects can influence their effectiveness and lead to toxicity, and how our actual knowledge supports the development of more specific inhibitors and new, rationally based, combination therapies, for the management of MCL and DLBCL patients.

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

Additive manufacturing processes offer various options to fabricate metal parts, which show numerous ecological and technological advantages compared to formative and subtractive manufacturing methods. Due to quick availability and high accuracy, they are particularly suitable to produce complex prototypes. Metal fused deposition modeling is a relatively new material extrusion additive manufacturing technique based on the widely used fused filament deposition process. This study focuses on the Inconel 625 metal filament from Markforged Inc., it consists of a mixture of metal powder and a binder system, the latter being removed during washing and sintering. In this article, the mechanical properties of printed and sintered Inconel were investigated using tensile testing specimens with three different infill patterns, solid, triangular, and gyroid, printed in flatwise and upright direction. In addition, investigations into the dimensional accuracy of the printed specimens and the sintering shrinkage were carried out. The results showed that neither the dimensional accuracy nor the sintering shrinkage was significantly influenced by the printing orientation. In the context of lightweight engineering, the structures proofed beneficial especially within the elastic region. Generally, triangular infill patterns resulted in higher stiffness, while gyroids led to more ductile specimens. A mass-related evaluation of tensile testing elucidates that with aid of the infill structures weight savings of 40 % resulted in mechanical performance decreased by only 20 % on average.

We propose a novel moving median estimator specifically designed for online detection of threshold crossings in multi-channel signals, such as extracellular neural recordings. This estimator offers two key advantages: a reduced sensitivity to outliers and the elimination of memory requirements for storing arrival times. Furthermore, its design facilitates parallel implementation on FPGAs, making it ideal for real-time processing of multi-channel recordings.

Hemicellulose is one of the most important natural polysaccharides in nature. Hemicellulose from different sources varies in chemical composition and structure, which in turn affects the modification effects and industrial applications. Grain and oil by-products (GOBP) are important raw materials for hemicellulose. This article reviews the modification methods of hemicellulose in GOBP. The effects of chemical and physical modification methods on the properties of hemicellulose biomaterials were evaluated. The potential applications of GOBP hemicellulose in films, hydrogel, Three-dimensional (3D) printing and adsorbent are discussed. Future research directions and recommendations are also proposed to provide theoretical foundations and technical support for the efficient utilization of these by-products.

This study describes the seasonal course of denitrifying and nitrate reducing bacteria in a dimictic mesotrophic lake (Lake Scharmützelsee, Brandenburg, Germany) within a three-year period from 2011 to 2013. The bacterial cell numbers were quantified by fluorescence microscopy, most probable number (MPN) and PCR dependent quantification of the chromosomal 16S rDNA and of the nirS and nirK gene copy number. The highest seasonal differences (up to three orders of magnitudes) has been measured by MPN in the epilimnion. This variation was not reflected by PCR dependent approaches or direct microscopical enumeration. At adverse conditions (low temperature and/or low nitrate concentrations), the differences between MPN and gene copy numbers increased up to five orders of magnitudes and decreased to one magnitude at favorable environmental conditions. These results can be explained best by an increasing ratio of viable but not cultivable (VBNC) cells or dead cells at impairing conditions. In the hypolimnion, the courses of MPN and nir gene copy numbers were similar. This can be explained by higher feeding pressure and therefore smaller amounts of dormant cells. In the pelagial in general, the total cell numbers enumerated by either microscopical or molecular approaches were similar. In the sediment, more than 99 % of the DNA was obviously not related to viable bacteria but was rather “dead DNA” in dead cells or adsorbed to particle surfaces.

The Black population, often treated as ethnically homogenous, faces a constant challenge in accessing and utilizing healthcare services. This study examines the intragroup differences in health-seeking behavior among the multiple ethnic subgroups that comprise the Black community. A cross-sectional study was conducted among 239 adults ≥18 years who self-identified as Black in the United States and Canada. A multiple logistic regression model was fitted to evaluate the relationship between health-seeking behaviors and ethnic origin controlling for selected social and health related factors. The mean age of participants was 38.6 years, 31% were male, and 20% were unemployed. Sixty-one percent reported very good or excellent health status, and 59.7% reported not being treated for chronic disease at the time of the survey. Aging (OR=1.05, CI:1.01–1.09) and being female (OR= 0.30, CI: 0.14–0.65) were associated with favorable health-seeking behaviors. Compared with participants who had earned high school diplomas only, those who reported having earned graduate degrees were 75% less likely to have engaged in favorable health-seeking behavior (OR=0.25, 95% CI: 0.07–0.86). In the Black community of our sample, regardless of ethnic origins or country of birth, the factors associated with health-seeking behavior were age, gender, and educational attainment. Keywords: African American; African; Caribbean; Healthcare Utilization; Ethnic Disparities; Health-seeking behavior; intragroup difference, black populations, ethnic subgroups

Manganese sludge, an industrial waste in the ferroalloy industry, contains various components and holds significant importance for sustainable development through its valorization. This study focuses on characterizing a manganese sludge and investigating its behavior during sulfuric acid leaching. The influence of process conditions, including temperature, acid concentration, liquid to solid ratio, and leaching duration, was examined. The results revealed that Mn, Zn, and K are the main leachable components, and their leaching rates increase with increasing temperature, liquid to solid ratio, and time. However, acid concentration requires optimization. High leaching rates of 90% for Mn, 90% for Zn, and 100% for K were achieved. Moreover, it was found that Pb in the sludge is converted to sulfate during the leaching which yields a sulfate concentrate rich in PbSO4. The leaching process for Mn and Zn species appears to follow a second or -third order reaction, and the calculation of rate constants indicated that Mn leaching kinetics are two to five times higher than those for Zn. Thermodynamic calculations were employed to evaluate the main chemical reactions occurring during leaching.

Hepatitis B virus (HBV) is known to cause severe liver diseases such as acute or chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. Chronic hepatitis B (CHB) infection is a major health problem with nearly 300 million individuals infected worldwide. Currently, nucleos(t)ide analogs (NAs) and interferon alpha are clinically approved treatments for HBV infection. NAs are potent antiviral agents that bind to HBV polymerase and block viral reverse transcription and replication. Besifovir dipivoxil maleate (BSV) is a newly developed NA against HBV in the form of acyclic nucleotide phosphonate that is available for oral administration similar to adefovir and tenofovir. Until now, resistance to BSV treatment has not been reported. In this study, we found a CHB patient who showed viral breakthrough after long-term treatment with BSV. The isolated HBV DNA from patient’s serum were cloned into the replication-competent HBV 1.2mer and the sequence of reverse transcriptase (RT) domain of HBV polymerase were analyzed. We also examined the drug susceptibility of generated clones in vitro. Several mutations were identified in HBV RT domain. A particular mutant harboring ten RT mutations showed resistance to BSV treatment in vitro. The ten mutations include rtV23I (I), rtH55R (R), rtY124H (H), rtD134E (E), rtN139K (K), rtL180M (M), rtM204V (V), rtQ267L (L), rtL269I (I) and rtL336M (M). To further identify the responsible mutations for BSV resistance, we performed in vitro drug susceptibility assay on several artificial clones. As a result, our study revealed that rtL180M (M) and rtM204V (V) mutations, already known as lamivudine-resistant mutations, confer resistance to BSV in the CHB patient.

Abstract: Medication overuse headaches is a frequent phenomenon observed in individuals suf-fering from chronic headaches. It arises due to the excessive consumption of pain-relief medica-tions, resulting in the escalation and continuous persistence of headache symptoms. Nevertheless, the prevalence and distinctive characteristics of medication overuse headaches in the pediatric population have not been comprehensively explored. The primary objective of this research is to delineate the features of medication overuse headaches in children, particularly emphasizing the investigation of its epidemiology and the diagnostic patterns for headaches. We conducted a ret-rospective study by and analyzed the medical records of children and adolescents who were evaluated at outpatient pediatric headache clinic at the Bnai Zion medical center for headache during the period spanning 2007 to 2017. Our study encompassed a cohort of 1008 patients expe-riencing headaches. Among these participants, 268 individuals (26.6%) were diagnosed with mi-graine, 250 (24.8%) exhibited tension-type headaches (TTH), and 490 (48.6%) were classified as having undifferentiated headaches. Out of the whole group, 65 had chronic headaches: 35 (54%) with migraine, 20 (30%) with tension-type headaches (TTH), and 10 (15%) with undifferentiated headache of childhood, with the majority (73%) being female.In summary, medication overuse headaches are a prevalent issue among children grappling with chronic headaches. Intriguingly, they appear to be more pronounced within the tension-type headache (TTH) group compared to migraine sufferers, and exhibit a higher prevalence among females. This study underscores the significance of early detection and careful management of medication overuse headaches in pedi-atric cases, shedding light on its distinct characteristics in the realm of childhood headache disor-ders. Further research is warranted to elucidate the underlying factors contributing to the ob-served gender disparity and the distinct prevalence rates among different headache subtypes.

Lamin A, B and C, the nuclear intermediate-filament proteins, play a role in epigenetic regulation. While Lamin B is expressed in all nucleated cells studied, Lamin A/C are transcribed in most somatic cell types except mature B lymphocytes. Since Epstein-Barr virus (EBV), a human gammaherpesvirus, is associated with tumorigenic processes and is known to alter the epigenotype of its host cells, we studied the expression of the LMNA gene and its epigenetic marks in EBV-carrying human lymphoid cell lines. We observed a high lamin A/C mRNA and protein expression in EBV-immortalized lymphoblastoid cell lines (LCLs) and in group III Burkitt lymphoma (BL) lines where hypomethylated first exons were observed with activating histone marks. In most cell lines with low promoter activity a highly methylated first exon could be detected. Our data showed that methylation of the first exon of LMNA was associated with the downregulation of LMNA expression whereas euchromatic histone marks were enriched at active LMNA promoters in EBV-immortalized LCLs. These data suggest a role for viral latency products to activate LMNAp in EBV-infected latency type III B cells in vitro. Expression of lamin A/C may contribute to the establishment of activated B cell phenotype that needs further explorations.

In this work, zinc oxide (ZnO)/ granular activated carbon (GAC) composites at different ZnO concentration (0.25M-ZnO@GAC, 0.5M-ZnO@GAC, and 0.75M-ZnO@GAC) were prepared by an in-situ hydrothermal method and demonstrated synergistic photocatalytic degradation and ad-sorption of Rhodamine B (RhB). The thermal stability, morphological structure, elemental com-position, crystallographic structure, and textural properties of developed catalysts were charac-terized by thermal gravimetric analysis (TGA/DTG), scanning electron microscopy equipped with energy dispersive-x-ray (SEM-EDS), x-ray diffraction (XRD), and Brunauer–Emmett–Teller (BET) analysis. Successful loading of ZnO onto GAC was confirmed by SEM-EDS and XRD analysis. The BET surface areas of GAC, 0.25M-ZnO@GAC, 0.5M-ZnO@GAC, and 0.75M-ZnO@GAC were 474 m2/g, 450 m2/g, 453 m2/g, and 421 m2/g, respectively. The decrease in GAC could be attributed to the successful loading of ZnO on the GAC surface. Notably, 0.5M-ZnO@GAC exhibited the best photocatalytic degradation efficiency of 82% and 97% under UV-A and UV-C light over 120 min, attributed to improved crystallinity and visible light absorption. The photocatalytic degradation parameters revealed that lowering the RhB concentration, raising the catalyst dosage and pH be-yond the point of zero charge (PZC) would favor the RhB degradation. Photocatalytic reusability was demonstrated over 5 cycles. Scavenger tests revealed that the hydroxyl radicals (•OH), su-peroxide radicals (O2−•), and photoinduced hole (h+) radicals play a major role during the RhB degradation process. Based on the TOC results, the RhB mineralization efficiency of 79.1% was achieved by 0.5M-ZnO@GAC. Additionally, GAC exhibited a strong adsorptive performance towards RhB with adsorption capacity and RhB removal of 487.1 mg/g and 99.5% achieved within 90 min equilibrium time. The adsorption characteristics were best described by pseu-do-second-order kinetics, suggesting chemical adsorption. This research offers a new strategy for the development of effective photocatalyst materials with potential for wider wastewater treat-ment applications.

Background: Despite their generally favorable prognosis, hepatic fibrosis remains a possible complication for hepatitis B virus (HBV) inactive carriers. This study aimed to estimate the prevalence of significant fibrosis and associated risk factors among Omani HBV inactive carriers. Methods: A retrospective study was conducted of 200 Omani HBV inactive carriers visiting a tertiary hospital in Muscat, Oman, between January 2017 and December 2018. Significant fibrosis (stage F2 or higher) was identified using two-dimensional shear-wave elastography. Baseline clinical, laboratory, and radiological data were analyzed to determine associations. Results: Of the total sample, 106 patients (53%) were male, and the mean age was 44.6 ± 9.3 years. The prevalence of significant fibrosis was 20% (n = 40). Male gender (p = 0.007), age ≥60 years (p = 0.024), and fatty changes in liver ultrasound (p = 0.044) were found to be independent factors for significant fibrosis. Conclusion: the prevalence of significant fibrosis was relatively high among a sample of Omani HBV inactive carriers, with several sociodemographic and clinical risk factors identified. Periodic assessment of liver function is needed for patients with these risk factors; moreover, routine biochemical parameters could be useful predictors of disease prognosis. Further research is recommended to substantiate these findings.

The BNT162b2 vaccine is globally used for preventing morbidity and mortality related to COVID-19. Cancer patients have had priority for receiving the vaccine due to their diminished immunity. This study reports the response of administering the 3rd and 4th vaccine doses to can-cer patients receiving active anti-neoplastic treatment. 142 patients have received two doses of the mRNA-based BNT162b2 COVID-19 vaccine, while 76 and 25 patients have received three and four doses, respectively. The efficacy of the humoral response following two vaccine doses was diminished in cancer patients, especially in the group of patients receiving chemotherapy. In a multivariate analysis, patients after three and four BNT162b2 vaccine doses were more likely to have antibody titers in the upper tertile compared to patients after two doses of the vaccine (odds ratio (OR) 7.62 (95% CI 1.38-42.12), p=0.02 and 17.15 (95% CI 5.01-58.7), p<0.01, respective-ly). Unlike the response after two doses, the 3rd and 4th BNT162b2 vaccine booster doses, had an increased efficacy of 95-100% in cancer patients while on active treatment. This result could be explained by different mechanisms including the development of memory B cells.

Hepatitis B virus (HBV) is the dominant risk factor for hepatocellular carcinoma (HCC). HBV X protein (HBx) plays crucial roles in HCC carcinogenesis. HBx interferes with several signaling pathways including Notch1 pathway in HCC. In our study, we found that Notch1 was highly expressed in HCC especially in large HCC. Notch1 and HBx co-localized in HCC and their levels were positively correlated with each other. Notch1 expression was more elevated in HepG2.2.15 than that in HepG2. HBx activated Notch1 pathway in HepG2.2.15. Repression of HBx and Notch1 pathway attenuated the growth of HepG2.2.15. Notch1, ERK and AKT pathways were inhibited after a γ-secretase inhibitor treatment. Dual-specificity phosphatase 1 (DUSP1) and phosphatase and tensin homolog (PTEN) were up-regulated after the γ-secretase inhibitor treatment and Hes1 inhibition. Luciferase reporter assays showed that Hes1 repressed the promoters of DUSP1 and PTEN and this was reverted by γ-secretase inhibitor treatment. Western blotting demonstrated that DUSP1 dephosphorylated pERK and PTEN dephosphorylated pAKT. Collectively, we reported a link among HBx, Notch1 pathway, DUSP1/PTEN, and ERK/AKT pathways, which influenced HCC cell survival and could be a therapeutic target for HCC.

Majority of the studied MADS box members are linked with flowering and fruit traits. However, higher volumes of studies on the type II of their two types so far suggest that florigenic effect of the gene members could just be tip of the iceberg. In current study we used a systematic approach to have general overview on the MADS box members their cross-trait and multifactor associations as well as their pleiotropic potentials based on local reference database curated for MADS box members. While doing so, we screened for the co-occurrence of the terms of interest within the title or abstract of each reference with threshold of 3 hits. Analysis results showed that our approach can retrieve multi-faceted information on the subject of study (MADS box gene members in current case) which could otherwise have been skewed depending on the authors’ expertise and/or volume of literature reference base. Overall, our study discusses on the roles of MADS box members in association with plant organs and traits-linked factors among plant species. Our assessment showed that plants with majority of the MADS box member studies include tomato, apple, rice etc., after Arabidopsis. Furthermore, based on the degree of their multi-trait associations, FLC, SVP, SOC1, etc. are suggested to have relatively higher pleiotropic potential among others in plant growth, development and flowering process. The approach devised in this study is expected applicable for having basic understanding on any study subject of interest regardless of depth prior knowledge.

Iron metabolism plays a crucial role in the management of hemoglobinopathies, particularly in conditions such as β-thalassemia and sickle cell anemia (SCA). This paper describes the mechanisms of iron overload in patients with transfusion-dependent thalassemia (TDT), non-transfusion-dependent thalassemia (NTDT), and SCA, highlighting the distinct paths leading to iron accumulation in each condition. The primary focus of this review article is on the role of genetic modifiers influencing iron metabolism and the variability in iron overload presentation among patients. Genetic mutations in genes such as HFE, HAMP, TFR2, SLC40A1, and others significantly impact iron regulation. These modifiers can exacerbate or ameliorate iron overload, and understanding these genetic factors is important for explaining the diverse disease severity and differences in the mechanism and clinical presentation of iron overload in these patients. The ongoing INHERENT study aims to further elucidate the influence of these genetic modifiers through a comprehensive genome-wide association study, potentially leading to novel therapeutic interventions for managing iron homeostasis in hemoglobinopathy patients.

Ovarian cancer is among the most common causes of female mortality. Despite improvements in diagnostic methods, non-specific symptoms and delayed gynecological exams can lead to late-stage ovarian tumor discovery. In this study, the effect of an anti-cancer compound, 3-amino-N-(3-chloro-2-methylphenyl)-5-oxo-5,6,7,8-tetrahydrothieno[2,3-b]quinoline-2-carboxamide (Compound 1) was examined. Cytotoxicity, apoptosis, and metabolomic changes in ovarian cancer cell lines SK-OV-3 and OVCAR-3, as well as glycosphingolipid (GSL) expression, both on cancer stem cells (CSCs), marked as CD49f+ and non-CSCs (CD49f-) were explored. Treatment with Compound 1 reduced the percentage of CSCs compared to non-treated cells (P &lt; 0.001). The expression of eight GSLs on CSCs and non-CSCs was examined using flow cytometry. Both cell lines showed a change in the glycophenotype of the cells, either up or down of its expression, after the treatment. These findings raise the possibility of specifically targeting CSCs in ovarian cancer therapy. Additionally, treatment of Compound 1 resulted in a statistically significant increase in both early and late apoptosis (P&lt;0.001) suggesting a pivotal role in initiating programmed cell death by the apoptotic pathway. The metabolic analysis revealed that the treated cancer cells showed reduced metabolic activity compared to the control group (P &lt; 0.001)

The main motive of this study was to find an auxiliary application of the discarded agricultural remnants and poultry waste. Rice straw and chicken feathers are disposed off as landfills or incinerated causing pollution and environmental threats after their primary consumption. In this study epoxy composites were made using varying proportions of these raw and alkali treated materials. Flexural strength of the composites decreased till 35% fiber loading, followed by an increase. Chicken feather composites showed increased impact strength with fiber addition. Alkali treatment improved the mechanical properties of rice straw composites. Alkali treated chicken feather composites showed better impact strength but no significant change in flexural strength. Hybrid composites explicated enhanced properties both before and after alkali treatment corroborating noteworthy interfacial adhesion and synergistic effect of these fibers as ascertained from SEM images. The study evinced a better option for averting environmental problems by recycling these disposed materials.

The goal of the paper is to clarify the observed irrationality of decision making in conflict situations considered as one-step games of two players. To solve such situations, we consider the asymmetry in the relation of the players to their own rewards and the rewards of the opponents. Formalization of the decision-making process is based on recently developed non-commutative operators of multivalued logic algebra. The suggested method is applied to solve the well-known Prisoners’ dilemma game and the other situations of conflict, where it results in the expected strategies.

The prevalence of hepatitis B and delta viruses (HBV/HDV) among people who use drugs (PWUD) remains largely unknown. In the context of one Philadelphia-based harm reduction organization (HRO), this study aimed to assess HBV/HDV prevalence and facilitate linkage to care. Participants completed a demographic HBV/HDV risk factor survey and were screened for HBV and reflexively for HDV if positive for HBV surface antigen or isolated core antibody. Fisher’s exact tests and regression were used to understand relationships between risks and HBV blood markers. Of the 498 participants, 126 (25.3%) were susceptible to HBV, 52.6% had been vaccinated against HBV, and 17.9% had recovered from a past infection. Eleven (2.2%) participants tested positive for isolated HBV core antibody, 10 (2.0%) for HBV surface antigen, and one (0.2%) for HDV antibody. History of incarceration was associated with current HBV infection, while transactional sex and experience of homelessness were predictive of previous exposure. This study found high rates of current and past HBV infection, and a 10% HBV/HDV co-infection rate. Despite availability of vaccine, one quarter of participants remained vulnerable to infection. Findings demonstrate the need to improve low-threshold HBV/HDV screening, vaccination, and linkage to care among PWUD. The study also identified gaps in the HBV/HDV care cascade, including lack of point-of-care diagnostics and lack of support for HROs to provide HBV services.