Bacteria that have become resistant to antibiotics, also known as superbugs,pose a huge threat to the human population. This is because these developed resistance to antibiotics. Antibiotics are a type of medicine that fights bacteria by either killing it or preventing it from growing. Although antibiotics make the once deadly now easily treatable, they can become ineffective as bacteria develop resistance to the antibiotic, causing diseases to become potentially fatal once more. Thus, scientists are rushing to find solutions in this arms race against evolving bacteria by either evolving current antibiotics or discovering new stands to fight evolving bacteria. In order to discover whether bacteria can develop resistance to household antibiotics, a controlled experiment was conducted. This was done by growing bacteria on agar plates with antibiotic ointments applied (in dilution series) to see if antibiotic resistance could build. Theorizing that by lowering the concentration of over the counter antibiotics, resistant bacteria would be selected and my bacterial population would evolve antibiotic resistance.In conclusion of the experiment antibiotic resistance did appear as a trait, but the level of it was inconsistent across the different bacteria populations.

Steroid hormone production by adrenal cortex, gonads and placenta (so called glandular steroidogenesis) is responsible for the endocrine control of the body’s homeostasis and organized by a feedback regulatory mechanism based on the hypothalamus-pituitary-steroidogenic gland axis. On the other hand, recently discovered extraglandular steroidogenesis occurring locally in different tissues is rather linked to paracrine or autocrine signaling and it is independent of the control by the hypothalamus and pituitary. Bone cells, such as bone-forming osteoblast, osteoblast-derived osteocytes and bone-resorbing osteoclasts respond to steroid hormones produced by both glandular and extraglandular steroidogenesis. Recently, new techniques to identify steroid hormones as well as synthetic steroids and steroidogenesis inhibitors have been introduced, which greatly empowered steroid hormone research. Based on recent literature and new advances in the field, here we review the local role of steroid hormones in regulating bone homeostasis and skeletal lesion formation. The novel idea of extraglandular steroidogenesis occurring within the skeletal system raises the possibility of the development of new therapies for the treatment of bone diseases.

Clinching is a manufacturing method of mechanical joining two or more materials without the use of heat or additional components. This process relies on high plastic deformation to create a secure bond. Clinching technology is widely used for joining various grades and thickness of materials. Especially in the automotive industry, clinching is an alternative to spot resistance welding. However, the load-bearing capacity of clinched joints is comparatively lower when compared to resistance spot welded joints. This research aimed to enhance the load-carrying capacity of clinched joints. Experimental tests were conducted on clinched joints with locally modified microstructures to optimize their placement within the joint. The microstructure distribution in the clinched joint region was analysed using light and scanning electron microscopy, as well as microhardness measurements. Two material grades, micro-alloyed steels HX420LAD+Z and dual-phase ferritic-martensitic steels HCT600X+Z, were tested. Each grade underwent five groups of ten samples, subject to identical experimental conditions of local heating by resistance spot welding (RSW) and clinching. The application of RSW to the clinched joint area resulted in increase of load-bearing capacity for both joined types of materials.

Socioeconomic conditions and social attitudes are known to represent epidemiological determinants. Credible knowledge on socioeconomic driving factors of the COVID-19 epidemic is still incomplete. Based on a linear random effects regression, a predictive model is derived to estimate COVID-19 incidence in German rural districts from local socioeconomic factors and popularity of political parties in terms of their share of vote. Thereby, time series provided by Germany's public health institute (Robert Koch Institute) of weekly notified 7-day incidences per 100,000 inhabitants per district from the outset of the epidemic in 2020 up to December 1, 2021, have been used to construct the dependent variable. Local socioeconomic conditions including share of votes, retrieved from the Federal Statistical Office of Germany, have been used as potential risk factors. Popularity of the right-wing party Alternative for Germany (AfD) bears a considerable risk of increasing COVID-19 incidence both in terms of predicting the maximum incidences during three epidemic periods (alternatively, cumulative incidences over the periods are used to quantify the dependent variable) and in a time-continuous sense. Thus, districts with high AfD popularity rank on top in the time-average regarding COVID-19 incidence. The impact of the popularity of the Free Democrats (FDP) is markedly intermittent in the course of time showing two pronounced peaks in incidence but also occasional drops. A moderate risk emanates from popularities of the Green Party (GRÜNE) and the Christian Democratic Union (CDU/CSU) compared to the other parties with lowest risk level. Socioeconomic parameters like \emph{per capita} income, proportions of protection seekers and social benefit claimants, and educational level have negligible impact. To the contrary, incidence significantly increases with population density. In order to effectively combat the COVID-19 epidemic, public health policymakers are well advised to account for social attitudes and behavioural patterns reflected in local popularities of political parties, which are conceived as proper surrogates for these attitudes. Whilst causal relations between social attitudes and the presence of parties remain obscure, the political landscape in terms of share of votes constitutes at least viable predictive "markers" relevant for public health policy making.

Scale invariance is expected in empty Universe models, while the presence of matter tends to suppress it. As shown recently, scale invariance is certainly absent in cosmological models with densities equal to or above the critical value ρ_c = 3(H₀)²/(8πG). For models with densities below ρc, the possibility of limited effects remains open. If present, scale invariance would be a global cosmological property. Some traces could be observable locally. For the Earth-Moon two-body system, the predicted additional lunar recession would be increased by 0.92 cm/yr, while the tidal interaction would also be slightly increased. The Earth-Moon distance is the most systematically measured distance in the Solar System, thanks to the Lunar Laser Ranging (LLR) experiment active since 1970. The observed lunar recession from LLR amounts to 3.83 (±0.009) cm/yr; implying a tidal change of the length-of-the-day (LOD) by 2.395 ms/cy. However, the observed change of the LOD since the Babylonian Antiquity is only 1.78 ms/cy, a result supported by paleontological data, and implying a lunar recession of 2.85 cm/yr. The significant difference of (3.83-2.85) cm/yr = 0.98 cm/yr, already pointed out by several authors over the last two decades, corresponds well to the predictions of the scale-invariant theory, which is also supported by several other astrophysical tests.

Epidemiological data indicate that 5.8% of cancer deaths world-wide are attributable to alcohol consumption. The risk of cancer is higher in tissues in closest contact on ingestion of alcohol, such as the oral cavity, pharynx and esophagus. The risk of these cancers is increased even in people who have only one alcoholic drink per day. However, since ethanol is not mutagenic and the carcinogenic metabolite of ethanol (acetaldehyde) is mostly produced in the liver, it is not clear why alcohol use preferentially exerts a local carcinogenic effect. It is well known that ethanol causes cell death at the concentrations present in alcoholic beverages; however, this effect has been overlooked probably because dead cells cannot give rise to cancer. Here I discuss that the cytotoxic effect of ethanol on the cells lining the oral cavity, pharynx and esophagus activates the division of the stem cells located in deeper layers of the mucosa to replace the dead cells. Every time stem cells divide, they become exposed to unavoidable errors associated with cell division (e.g., mutations arising during DNA replication and chromosomal alterations occurring during mitosis) and also become highly vulnerable to the genotoxic activity of endogenous and exogenous DNA-damaging agents (e.g., reactive oxygen species, acetaldehyde and tobacco carcinogens). Alcohol consumption probably increases the risk of developing cancer of the oral cavity, pharynx and esophagus by promoting the accumulation of cell divisions in the stem cells that maintain these tissues in homeostasis. Because the cytotoxic activity of ethanol is concentration-dependent, the risk of these cancers will not only increase with increasing amounts of ethanol, but also with increasing concentrations; an ounce of whisky is probably more carcinogenic when taken undiluted than when taken mixed with non-alcoholic beverages. The local cytotoxic effect of ethanol can also explain the known synergistic effect of alcohol and tobacco use on the risk of these cancers. Understanding the mechanisms of carcinogenicity of alcohol is important to reinforce the epidemiological evidence and to raise public awareness of the strong link between alcohol consumption and cancer.

Non-destructive, accurate, and timely approach for crop yield prediction at field scale is vital for precision agriculture. This study aimed to investigate the appropriate wavelengths and their combinations to explore the new SIs derived from UAV hyperspectral images in predicting yield during the growing season of spring maize. The best wavelengths and new SIs, including the difference spectral index, ratio spectral index, and normalized difference spectral index forms, were obtained by the contour maps constructed by the coefficient of determination (R2) from the linear regression models between the yield and all possible SIs screening out from the 450-950 nm wavelengths. The results showed that the most sensitive wavelengths were 640-714 nm at WJQ, 450-650 nm and 750-950 nm at SKS, and 450-700 nm and 750-950 nm at FJJ. The new SIs established here were different across the three experimental fields, and their performance on maize yield prediction were generally better than that of the published SIs. In addition, the new SIs presented different response to various N fertilization levels. This study demonstrated the potential of exploring new spectral characteristics from remote sensing technology for predicting field-scale crop yield in spring maize cropping systems before harvest.

Polysulfides are endogenously produced in mammals and generally associated with protective functions. Our aim was to investigate the effect of dimethyl trisulfide (DMTS) in a mouse model of acute stress. DMTS activates transient receptor potential ankyrin 1 (TRPA1) channels and leads to neuropeptide release, potentially that of substance P (SP). We hypothesize that DMTS might inhibit the degrading enzymes of endocannabinoids, so this system was also investigated as another possible pathway for mediating the effects of DMTS. Trpa1 gene wild type (WT) and knock out (KO) mice were used to confirm the role of the TRPA1 ion channel in mediating the effects of DMTS. C57BL/6J, NK1 gene KO, and Tac1 gene KO mice were used to evaluate the effect of DMTS on the release and expression of SP. Some C57BL/6J animals were treated with AM251, an inhibitor of the cannabinoid CB1 receptor, to elucidate the role of the endocannabinoid system in these processes. Open field test (OFT) and forced swim test (FST) were performed in each mouse strain. Tail suspension test (TST) was performed in TRPA1 WT and KO animals. C-FOS immunohistochemistry was carried out on TRPA1 WT animals. DMTS treatment increased the number of highly active periods and decreased immobility time in the FST in WT animals, but had no effect on Trpa1 KO mice. DMTS administration induced neuronal activation in stress-related brain areas such as the locus coeruleus, dorsal raphe nucleus, lateral septum, paraventricular nucleus of the thalamus, and paraventricular nucleus of the hypothalamus. DMTS may have a potential role in the regulation of stress-related processes, and the TRPA1 ion channel may also be involved in mediating the effects of DMTS. DMTS can be an ideal candidate for further study as a potential remedy in stress-related disorders.

Prolactin (PRL) is a pleiotropic hormone released from lactotrophic cells of the anterior pituitary gland that also originates from extrapituitary sources and plays an important role in regulating lactation in mammals, as well as other actions. Acting in an endocrine and paracrine/autocrine manner, PRL regulates the hypothalamic-pituitary-ovarian axis, thus influencing the maturation of ovarian follicles and ovulation. This review provides a detailed discussion of the current knowledge on the role of PRL in the context of ovulation and ovulatory disorders, particularly with regard to hyperprolactinemia, which is one of the most common causes of infertility in women. Much attention has been given to the PRL structure and the PRL receptor (PRLR), as well as the diverse functions of PRLR signaling under normal and pathological conditions. The hormonal regulation of the menstrual cycle in connection with folliculogenesis and ovulation, as well as the current classifications of ovulation disorders, are also described. Finally, the state of knowledge regarding the importance of TIDA (tuberoinfundibular dopamine), KNDγ (kisspeptin/neurokinin B/dynorphin) and GnRH (gonadotropin-releasing hormone) neurons in PRL- and kisspeptin (KP)-dependent regulation of the hypothalamic-pituitary-gonadal (HPG) axis in women is reviewed. Based on this review, a rationale for influencing PRL signaling pathways in therapeutic activities accompanying ovulation disorders is presented.

Atrial fibrillation (AF) is an increasingly recognized comorbidity in patients with can-cer. Indeed, cancer patients have a significantly higher incidence of AF than that ob-served in the general population. A reciprocal relationship between these two diseases has been observed, as much as some assume AF as a marker for occult cancer screen-ing, especially in older adults. The pathophysiological mechanisms are many and var-ied, including the underlying pro-inflammatory state, specific treatments (chemo and radiotherapy) and surgery. The therapeutic management of patients with cancer and AF involves the same rhythm and frequency control strategies as the general popula-tion; however, the numerous interactions with chemotherapeutics, which lead to a sig-nificant increase in side effects, as well as the extreme fragility of the patient should be considered. Anticoagulant therapy is also a complex challenge to address, as bleeding and stroke risk scores have not been fully assessed in this subpopulation. Furthermore, in large studies establishing the efficacy of direct oral anticoagulants (DOACs), cancer patients have been underrepresented. In this review, we elaborate on mechanisms linking AF to cancer patients with a particular focus on therapeutic challenges in this population.

Atrial fibrillation (AF) is an increasingly recognized comorbidity in patients with cancer. Indeed, cancer patients have a significantly higher incidence of AF than that observed in the general population. A reciprocal relationship between these two diseases has been observed, as much as some assume AF as a marker for occult cancer screening, especially in older adults. The pathophysiological mechanisms are many and varied, including the underlying pro-inflammatory state, specific treatments (chemo and radiotherapy) and surgery. The therapeutic management of patients with cancer and AF involves the same rhythm and frequency control strategies as the general population; however, the numerous interactions with chemotherapeutics, which lead to a significant increase in side effects, as well as the extreme fragility of the patient should be considered. Anticoagulant therapy is also a complex challenge to address, as bleeding and stroke risk scores have not been fully assessed in this subpopulation. Furthermore, in large studies establishing the efficacy of direct oral anticoagulants (DOACs), cancer patients have been underrepresented. In this review, we elaborate on mechanisms linking AF to cancer patients with a particular focus on therapeutic challenges in this population.

Immune Checkpoint Inhibitors are monoclonal antibodies that are used to treat over one in three cancer patients. While they have changed the natural history of disease, prolonging life and preserving quality of life, they are highly active in less than 40% of patients, even in the most responsive malignancies such as melanoma, and cause significant autoimmune side effects. Licenced biomarkers include tumour Programmed Death Ligand 1 expression by immunohistochemistry, microsatellite instability, and Tumour Mutational Burden, none of which are particularly sensitive or specific. Emerging tumour and immune tissue biomarkers such as novel immunohistochemistry scores, tumour, stromal and immune cell gene expression profiling, and liquid biomarkers such as systemic inflammatory markers, kynurenine/tryptophan ratio, circulating immune cells, cytokines and DNA are discussed in this review. We also examine the influence of the faecal microbiome on treatment outcome and its use as a biomarker of response and toxicity.

CO2 geological sequestration in coal seams can achieve the dual objectives of CO2 emission reduction and enhanced coalbed methane production, making it a highly promising carbon capture and storage technology. However, the injection of CO2 into coal reservoirs in the form of supercritical fluid (ScCO2) leads to complex physicochemical reactions with the coal seam, altering the properties of the coal reservoir and impacting the effectiveness of CO2 sequestration and methane production enhancement.In this paper, theoretical calculations based on ReaxFF-MD were conducted to study the interaction mechanism between ScCO2 and the macromolecular structure of both low-rank and high-rank coal, to address the limitations of experimental methods. The reaction of ScCO2 with low-rank coal and high-rank coal exhibits significant differences. At swelling stage, the low-rank coal experiences a decrease in aromatic structure and aliphatic structure, high-rank coal shows an increase in aromatic structure and a decrease in aliphatic structure, while swelling phenomenon is more pronounced in high-rank coal. At dissolution stage, low-rank coal is initially decomposed into two secondary molecular fragments, and then recombine to form new molecular structure, the aromatic structure increased and the aliphatic structure decreased. In contrast, high-rank coal occurs stretches-breakage-movement-reconnection, a reduction in aromatic structure and an increase in aliphatic structure.The primary reasons for these variations lie in distinct molecular structure compositions and the properties of ScCO2, leading to different reaction pathways of functional group and aromatic structure. The reaction pathways of functional groups and aromatic structures in coal can be summarized as follows: the breakage of the O-H bond in hydroxyl groups, the breakage of the C-OH bond in carboxyl groups, transformation of aliphatic structures into smaller hydrocarbon compounds or formation of long-chain alkenes, and various pathways involving broken, rearrangement, recombination of aromatic structures. In low-rank coal, there is a higher abundance of oxygen-containing functional groups and aliphatic structures. The breakage of O-H and C-OH chemical bonds results in the formation of free radical ions, while some aliphatic structures detach to produce hydrocarbons. Additionally, some of these aliphatic structures combine with carbonyl groups and free radical ions to generate new aromatic structures. Conversely, in high-rank coal, the lower content of oxygen-containing functional groups and aliphatic structures, along with stronger intramolecular forces, results in fewer chemical bond breakages and makes it less conducive to the formation of new aromatic structures.These results elucidate the specific deformations of different chemical groups, offering a molecular-level understanding of the interaction between CO2 and coal.

Abstract Issue Addressed: Men’s Sheds (‘Sheds’) have been identified as inherently health promoting and as potential settings to engage ‘hard-to-reach’ men in more structured health promotion initiatives. However, little is known about the sociodemographic or health and wellbeing characteristics of Shed members (‘Shedders’) on which such initiatives might be based. This study captures a baseline cross sectional analysis of Shedders (n=384) who participated in ‘Sheds for Life’, a health promotion initiative tailored to Sheds. Methods: Objective health measure, (body composition, blood pressure, blood lipids) captured via health screening as well as sociodemographic and health and wellbeing measures (physical activity, subjective wellbeing, mental health, social capital, cooking and diet) via questionnaires were assessed. Results: Participants were mostly over 65 years, retired with limited educational attainment. The majority were in the ‘at-risk’ categories for objective health measures, with most being referred to their GP following health screening. Older Shedders were also more likely to meet physical activity guidelines. Mental wellbeing was positively correlated with life satisfaction and increased social capital and these were also positively correlated with physical activity. Conclusions: Findings highlight the potential of Sheds in reaching a ‘hard-to-reach’ and ‘at-risk’ cohort of men. Despite a high prevalence of ‘at-risk’ objective health measures, participants report their health in positive terms. Future health promotion initiatives should capitalise on the inherent health promoting properties of Sheds. So what? Findings raise important implications for prioritising and designing health promotion initiatives in Shed settings.

This article analyzes local level normative regulations aimed at directly or indirectly conserving the urban landscape in rural areas. Using a discursive analysis methodology on regulatory documents being enforced in a series of localities assigned to a tourism promotion program, evidence suggests that promotional activity retroactively influences the phraseology of these municipal regulations. The results obtained point to the existence of perpetuating historicist approaches within the current regulations, which appear to largely derive from the search for success in the tourism market and the resulting benefits to the local economy.

Distribution System Operators (DSOs) are adapting to changing energy demands and the shift toward renewable and decentralized energy. Circularity is increasingly relevant for DSOs as their distribution systems age and need replacing. Taking circular action, however, is generally regarded as challenging as the current circular economy (CE) landscape is highly fragmented and rarely touches the implementation level. A longitudinal case study at Dutch DSO Liander on the circu-larity of distribution transformers was used to understand empirical success factors for taking circular action and to generate prescriptive knowledge on the operationalization of circularity. Six design propositions for circular action were formulated that suggest to 1) initiate small-scale cir-cularity experiments, 2) involve technical and strategic experts, 3) synergize circularity with more urgent, primary goals 4) translate circular initiatives bottom-up and top-down, 5) collaborate with other DSOs, and 6) create multidisciplinary teams. At DSO Liander, selecting the right interventions depending on the changing context contributed to operationalizing circularity for distribution transformers and achieving circularity targets. The generalizable design propositions could assist other DSOs in optimizing their strategy toward circular action.

In the present study, a simple approximation expression is given for the relationship between the period and amplitude of a simple pendulum under magnetic action. The analytical solution presented for the given problem. Two numerical quadrature methods Simpson's and Boole's method were utilized to demonstrate a new approximation of the problem. The results of the numerical quadrature have been compared to the exact solution. Absolute and relative mistakes of the problem have been presented. The Matlab program 2013R has created a numerical method that is used to analyze the outcome, It has been determined that the comparison's outcomes attest to the method's suitability and correctness. Moreover, the results show that numerical solution is suitable for the problem.

A three-dimensional vector field model is proposed, whose dimensions are the Hansen Solubility Parameters: dispersion parameter (δD), polarity parameter (δP), and hydrogen bonding parameter (δH). The vector space that defines the field has the peculiarity of having the dispersion vector with a magnitude of 2, as its base vector, while polarity and hydrogen bonding vectors have a magnitude of 1. A substance is characterised as a position vector, and the interaction between two substances is determined by calculating the vector difference of both, known as the interaction vector. Interaction among substances may involve solubility, swelling, cracking, surface tension, interface tension, and any physical phenomena where intermolecular energies of dispersion, polarity or hydrogen bonding come into play. This paper studies free surface energy (surface and interfacial tension). It has been found that free surface energy is directly proportional to the square of the magnitude of the interaction vector. The proportionality constant, τ, is expressed in length units, has a value of 0.025 nm, and does not depend on the chemical nature of the substance or state of matter (solid, liquid or gas). Constant value τ appears universal and aligns with the thickness of interfaces, thereby supporting Guggenheim's hypothesis. This hypothesis asserts that interfaces possess actual thickness and are not merely mathematical surfaces, as originally postulated by Gibbs. Moreover, it also has been found that interface thickness, τ, is approximately equal to half of the Bohr radius, a0, which is defined by universal constants. Because the solubility parameters of thousands of substances are known and can be easily determined from molecular structure, a good approximation of the surface and interfacial tension of any given substance can now be calculated. It has also been found that contact angles of sessile droplets in three-phased systems can be calculated from the interaction vectors of the implicated substances.

Spraying various liquids (primarily aqueous solutions of various substances) is widely used in various technological processes. For most of them, high dispersibility and narrow droplet size distribution are essential. This facilitates ultrasonic spray technique. However, the higher the dispersity of droplets produced by ultrasonic spray, the lower the spray productivity. To solve this problem, we proposed a method of multistage spraying, consisting in generation of a large number of particles of large initial size (to ensure high productivity) and their subsequent destruction by propagation in a periodic ultrasonic field (to ensure small droplet sizes at high productivity). To experimentally determine the capabilities of this technique, a tubular emitter in the shape of a cylinder of stepped-variable cross-section was designed. Configuration of the ultrasonic field inside the emitter (22.2 kHz; 182 dB) implements three-stage spraying (the number of sputtering stages corresponds to the number of anti-nodes along the emitter axis). The effectiveness of proposed and developed technique suitable for generation of droplets sized less than 40 µm with performance exceeding the known ultrasonic spray techniques at least 10 times has been confirmed in the course of conducted research.

The second external cause of death from unintentional injuries is falls in people over 60, a worldwide public health problem. Associated factors are identified early in Primary Health Care. Thus, we analyze professional narratives about older adults/old age and the organization of services in the presence of fall-inducing frailty. A structured narrative was applied under the following stages: understanding the context; setting/plot/character analysis; and interpretive synthesis. Data were collected from August to November 2022, distributing 21 health professionals in three Narrative Focus Groups. In the analyses, the collective conceptions dialogued with Bourdieu’s Epistemology of field, habitus, and capital. Among the results, technical and common sense representations of older adults were simultaneously observed, along with the belief of old age as a problematic life stage. Care is centered on the installed disease/ailment. Encouraging autonomy and self-care emerges in integrative health practices, which older adults underestimate. Professionals access the lives of older adults according to their habitus, which, in turn, is structured (structuring) in the disputes for installed capital. Thus, the care provided disregards subjectivities and symbolic systems associated with falls.

Studying the two famous old problems that why the moon can move around the Sun and why the orbit of the Moon around the Earth cannot be broken off by the Sun under the condition that calculating with F=GMm/R^2, the attractive force of the Sun on the Moon is almost 2.2 times that of the Earth. We found that the planet and moon are unified as one single gravitational unit which results in that the Sun cannot have the force of F=GMm/R^2 on the moon. The moon is moved by the gravitational unit orbiting around the Sun. It could indicate that the gravitational field of the moon is limited inside the unit and the gravitational fields of both the planet and moon is unified as one single field interacting with the Sun. The findings are further clarified by reestablishing Newton’s repulsive gravity.

The constant ħ is elevated to a dynamical field, coupling to other fields, and itself, through the Lagrangian density derivative terms. The spatial and temporal dependence of ħ falls directly out of the field equations themselves. Three solutions are found: a free field with a tadpole term; a standing-wave non-propagating mode; a non-oscillating non-propagating mode. The first two could be quantized. The third corresponds to a zero-momentum classical field that naturally decays spatially to a constant with no ad-hoc terms added to the Lagrangian. An attempt is made to calibrate the constants in the third solution based on experimental data. The three fields are referred to as actons. It is tentatively concluded that the acton origin coincides with a massive body, or point of infinite density, though is not mass dependent. An expression for the positional dependence of Planck’s constant is derived from a field theory in this work that matches in functional form that of one derived from considerations of Local Position Invariance violation in GR in another paper by this author. Astrophysical and Cosmological interpretations are provided. A derivation is shown for how the integrand in the path integral exponent becomes Lc/ħ(r), where Lc is the classical action. The path that makes stationary the integral in the exponent is termed the “dominant” path, and deviates from the classical path systematically due to the position dependence of ħ. The meaning of variable ħ is seen to be related to the rate of time passage along each path increment. The changes resulting in the Euler-Lagrange equation, Newton’s first and second laws, Newtonian gravity, Friedmann equation with a Cosmological Constant, and the impact on gravitational radiation for the dominant path are shown and discussed.

The storm of November 12th-13th, 2019 provoked the displacements of boulders in a central Mediterranean rocky coast; with reference to a selected area, prone to the boulder production and geomorphologically monitored for years, a field-oriented study approach was applied for the phenomenon, by collating data concerning pre-storm locations and kinematics of these boulders. The number of displaced boulders is 11, that is, in terms of morphological imprint of a specific storm, one of the major study cases for the Mediterranean. In addition, based on widely used hydrodynamic equations, the minimum wave height required to displace the boulders is assessed. The values conform with the expected values for the wave climate dominating during the causative meteorological event and give a measure of the energy of the storm slamming the coast. Boulder dislodgements usually have plays a key role in determining the rate of the coastal recession, likely also in the investigated area. In view of an adverse climate evolution with a possible increase of energy and frequency of severe storms, the results deriving from the study of this morphodynamics should be considered for the hazard assessment and coastal management.

The magnetic field of the earth plays an important role in the ecosystem, and the magnetic field of celestial bodies is also important in the formation of cosmic large-scale structures, but the origin and evolution of the celestial magnetic field is still an unresolved mystery. Many hypotheses to explain the origin have been proposed, but there are some insurmountable difficulties for each one. At present, the theory widely accepted in scientific society is the dynamo model, it says that, the movement of magnetofluid inside celestial bodies, which can overcome the Ohmic dissipative effect and generate persistent weak electric current and macroscopic magnetic field. However, this model needs an initial seed magnetic field, and the true values of many physical parameters inside the celestial body are difficult to obtain, and there is no stable solution to the large range of fluid motion. These are all difficulties for the dynamo model. Furthermore, it is difficult for the dynamo to explain the correlation between the dipole magnetic field and angular momentum of a celestial body. In this paper, by calculating the interaction between spin of particles and gravity of celestial body according to Clifford algebra, we find that a rotational celestial body provides a field $\Omega^\alpha$ for spins, which is similar to the magnetic field of a dipole, and the spins of charged particles within the celestial body are arranged along the flux line of $\Omega^\alpha$, then a macroscopic magnetic field is induced. The calculation shows that the strength of $\Omega^\alpha$ is proportional to the angular momentum of the celestial body, which explains the correlation between the magnetic intensity and angular momentum. The results of this paper suggest that further study of the effects of internal variables such as density, velocity, pressure and temperature of a celestial body on $\Omega^\alpha$ may provide some new insights into the origin and evolution of celestial magnetic field.

In this paper, we investigate the Hawking radiation process by using the quantum tunneling phenomenon of massive spin-1 (W-bosons) and spin-0 particles from (2+1) dimensional Black Hoke with quintessential and magnetic field. For this purpose, using Hamilton-Jacobi ansatz, we apply the WKB approximation to the field equations of massive charged vector particles. We get the required tunneling rate of radiated particles and obtain their corresponding Hawking temperature $T_h$. In order to study the quantum gravity effects, we utilize the generalized Proca and Klein-Gordan equations incorporating the generalized uncertainty principle (GUP) and recover the accompanying quantum corrected temperature $T'_{h}$.

Background: This study aimed to investigate the association between the internal derangement of the temporomandibular joint (TMJ), in particular the severity of disc displacement (DD), and the presence of generalized joint hypermobility (GJH) in growing patients evaluated on magnetic resonance images (MRI). The study also investigated the relationship between the stages of DD severity and age. Methods: This cross-sectional study has been conducted on a pre-orthodontic population (8-16 years). The GJH was assessed with the Beighton test (cutoff ≥ 4) and the final sample of 56 patients was divided into two groups: a Study Group, 30 subjects with GJH, and a Control Group, 26 subjects without GJH. The disc position was evaluated on MRI and the severity of DD was classified in four stages. Pearson's χ2 Test was performed for the analysis of the statistical correlation. Results: A statistically significant relationship between GJH and disc position was found, in particular a disc displacement with reduction (DDwR) and DD severity. It also emerged a positive association between the severity of DD and age, that increased with increasing age. Conclusions: Growing patients with GJH have a higher risk of developing DD and with more severe stages. The risk of developing DD and the severity increases with increasing age.

Biological control, a well-established plant protection method, has garnered substantial attention in recent decades. Various approaches, including biological control agents (BCA), catch crops, biofumigation, sticky traps, and pheromones, have been extensively explored. While the effectiveness of these methods varies depending on specific circumstances, their collective significance has grown amid mounting pressures to curtail or eliminate conventional synthetic plant protection products. Previous review articles have highlighted the synergistic benefits of using two or more BCAs simultaneously, yet limited information exists regarding the concurrent use of diverse biological control methods. This comprehensive review incorporates a thorough literature search to assess the synergistic potential of concurrently employing two or more of these methods, followed by a discussion on perspectives of holistic management and mimicking of complex natural systems, shedding light on the vast potential and need for further research in this domain.

The high-power Asymmetric half-bridge Converter (AHBC) LED constant current driver controlled by digital current mode is a fourth-order system. Static operating point, parasitic resistance, load characteristics, sampling effect, modulation mode and loop delay will have great influence on its dynamic performance. In this paper, the small-signal pulse transfer function of the driver is established by the discrete-time modeling method for the two operating points corresponding to the three modulation modes of the trailing edge, leading edge and double edge. And, the effects of parasitic parameters, delay effect, sampling effect and load effect are fully considered in modeling. For a large number of complex exponential matrix operations, the first order Taylor formula is used for approximate calculation after the coefficient matrix is obtained by substituting the data. Then, Matlab software is used to compare and analyze the discrete-time model and the discrete-average model. The results show that the proposed discrete-time model can more accurately characterize the resonant peak and high-frequency dynamic characteristics, and is very suitable for the design of high frequency digital controller.

Isolation of new plant-derived lactic acid bacteria (LAB) is highly prioritized in developing novel starter cultures for plant-based fermentation. This study explores the diversity of LAB in Danish flowers and their potential use for plant-based food fermentation. 46 flower samples under 34 genera were collected for LAB isolation. By introducing an enrichment step, in total of 61 LAB strains were isolated and identified by using MALDI-TOF and 16S rRNA sequencing. These strains represent 24 species across 9 genera, predominantly Leuconostoc mesenteroides, Fructobacillus fructosus, Apilactobacillus ozensis, and Apilactobacillus kunkeei. Phenotypic screening for exo-cellular polysaccharide production revealed that 40 strains exhibited sliminess or ropiness on sucrose containing agar plate. HPLC analysis confirmed that all isolates produced exo-cellular polysaccharides containing glucose, fructose or galactose as sugar monomer. Therefore, the strains were glucan, fructan and galactan producers. The suitability of these strains for plant-based fermentations was characterized by using almond, oat and soy milk. The results showed successful acidification in all three types of plant-based matrices but only observed texture development in soy by Leuconostoc, Weissella, Lactococcus, Apilactobacillus, and Fructobacillus. The findings highlight the potential of flower-derived LAB strains for texture development in soy-based dairy alternatives.

We report the negative effective mass metamaterials based on the electro-mechanical coupling exploiting plasma oscillations of a free electron gas. The negative mass appears as a result of vibration of a metallic particle with a frequency of ω which is close to the frequency of the plasma oscillations of the electron gas m_2 relatively to the ionic lattice m_1. The plasma oscillations are represented with the elastic spring k_2=ω_p^2 m_2, where ω_p is the plasma frequency. Thus, the metallic particle vibrated with the external frequency ω is described by the effective mass m_eff=m_1+(m_2 ω_p^2)/(ω_p^2-ω^2 ) , which is negative when the frequency ω approaches ω_p from above. The idea is exemplified with two conducting metals, namely Au and Li embedded into various matrices. The one-dimensional lattice built of the identical metallic micro-elements m_eff connected by ideal springs k_1 representing various media such as polydimethylsiloxane and soda-lime glass is treated. The optical and acoustical branches of longitudinal modes propagating through the lattice are elucidated for various ratios ω_1/ω_p . The 1D lattice built of the thin metallic wires giving rise to the low frequency plasmons is treated. The possibility of the anti-resonant propagation, strengthening the effect of the negative mass occurring under  = p = 1 is addressed.

That how to improve the sensitivity and the detection ability of the Large-caliber sensor is critical to satisfy the requirement of heavy vehicle wear condition monitoring. In this paper, we introduced the LC resonance principle to the design of sensor with large flow channel (7mm). The resonant exciting coil increases the impedance change of the exciting circuit caused by wear particles which magnify the current difference between the two exciting coils and improve the sensitivity of the sensor. The resonant induction coil greatly suppresses the interference signals and magnifies the weak induced electromotive force which is beneficial to enhance the detection ability. In order to boost the detectability for different materials particles, a phase controlled variable-frequency exciting system (PCVFES) was adopted to automatically switch the exciting frequency between 284kHz for ferromagnetic particles and 420KHz for non-ferromagnetic particles. For the weak signal detection, based on the essential characteristic of the signal, we apply a simpler method that modified lock-in amplifier (MLIA) rather than the conventional algorithms (Wavelet transform, EMD). Results show that using these methods the sensitivity and the detection ability of the sensor are significantly improved and the 75μm iron particles and 220μm copper particles were successfully detected which realizes the initial abnormal wear monitoring for the large flow project.

Fibroblast growth factor 14 (FGF14) is a member of the intracellular FGFs, a group of proteins with roles in neuronal ion channel regulation and synaptic transmission. We have previously demonstrated that a male Fgf14-/- mouse model recapitulates salient endophenotypes of synaptic dysfunction and behaviors associated with schizophrenia (SZ). As the underlying etiology of SZ and its sex-specific onset remain elusive, the Fgf14-/- model provides a valuable tool to interrogate pathways that might be related to the disease mechanism. Here, we performed label free quantitative proteomics and bioinformatics to identify enriched pathways at the proteome level in the male and female hippocampi from Fgf14+/+ and Fgf14-/- mice. We discovered that many differentially expressed proteins in Fgf14-/- animals are associated with SZ. In addition, measured changes in the proteome and signaling pathways were predominantly sex-specific with the male Fgf14-/- being distinctly enriched for pathways associated with neuropsychiatric disorders and addiction and the female exhibiting modest changes. In the male Fgf14-/- mouse the major protein changes that could in part explain the previously described neurotransmission and behavioral phenotype of this model were loss of ALDH1A1 and PRKAR2B. ALDH1A1 has been shown to mediate an alternative pathway for GABA synthesis, while PRKAR2B is essential for dopamine 2 receptor signaling, which is the basis of current antipsychotics. Collectively, our results provide new insights in the role of FGF14 and support the use of the Fgf14-/- mouse as a useful preclinical model of SZ for generating hypothesis on the disease mechanism, sex-specific manifestation and therapy.

The Chromogranin A (CgA)-derived peptide Catestatin (CST: hCgA352-372) is highly conserved (>90% in 90% species) in mammalian species. The highest-evolved primates show 58.8% similarity with the lowest-evolved monotremes. CST was initially identified as a physiological brake in catecholamine secretion by inhibiting nicotinic-cholinergic signaling. CST also inhibits desensitization of catecholamine secretion, indicating that CST can act both as a cholinergic antagonist (short-term) and as a cholinergic agonist (long-term). The long-term effect sustains catecholamine secretion during stressful situations. CST is now established as a pleiotropic hormone: it affects the cardiovascular system by lowering blood pressure and cardiac contractility, enhancing baroreflex sensitivity, increasing heart rate variability, and promoting angiogenesis; and it increases insulin sensitivity by reducing inflammation, inhibiting hepatic glucose production, attenuating endoplasmic reticulum stress, and inducing glycogen production. The present review will highlight the important direct and indirect effects of CST, CST1-15 (aka cateslytin), D-CST1-15 (where L-amino acids were changed to D-amino acids), and human variants of CST (Gly364Ser-CST and Pro370Leu-CST) on microbial growth inhibition and their potential as therapy for antibiotic-resistant pathogenic microbes.

Proprotein convertase subtilisin/Kexin type 9 (PCSK9) is a proteolytic enzyme that indirectly regulates serum LDL cholesterol by destroying LDL receptors. In clinical studies, the main role of the proprotein convertase subtilisin/Kexin type9 (PCSK9) inhibitor in cholesterol regulation was elucidated. It is produced in the liver but is also present in the kidney and intestine. It prevents HMGCo from synthesizing cholesterol. SREBP-2 is a reductase that is induced by statins. In a dose-dependent manner, increasing SREBP-2 levels enhanced LDL-R and PCSK9 gene expression. At the minimum, two procedures have been developed to overcome the plasma level of PCSK9. This is the LDLR test, polyclonal antibodies, and sentience oligonucleotide. Lower dosage statin treatment with a proprotein convertase subtilisin/Kexin type9 inhibitor will be most efficient in lowering LDL and avoiding statin adverse effects. In multiple long-term trials, statins have been found to reduce cardiovascular mortality by 30% and stroke incidence by 20%. In this way, we conclude the role of PCSK9 in hypercholesterolemia.

The creative potential of homo sapiens is the biological basis of his spirituality. To take into account factor of spirituality in analysis of global problems of demography and ecology used analogies of chemical kinetics. Stable in the historical time, population of people was modeled by open thermodynamic system, equilibrium state of which depends on climate and geophysics. The demography of creative potential was divided into two geographical zones - north and south. Process of society sapientation was formalized by introducing into logistic equation of Verhulst, in addition to a couple of parents, at least one more teacher from among educated people. Stationary solution of the modified kinetic equations determines optimal demography for sustainable development of population in accordance with its education index. The solution of the demographic, energy and environmental problems of mankind is determined by the level of world creative potential, the growth of which is currently limited by the consumption paradigm.

Von Hippel-Lindau disease (VHL) is a multiple organ neoplastic syndrome with autosomal dominant transmission, complete penetrance, and variable expression caused by mutations in the VHL gene. Although VHL disease is hereditary in many cases, new mutations cause up to 20 % of the incidence. Mutations in VHL may cause the development of cysts and tumors in many organs, including brain and spinal cord hemangioblastoma, renal cell carcinoma (RCC), retinal heman-gioblastoma (RH), pheochromocytoma, epididymal and broad ligament cystadenomas, endo-lymphatic sac tumor, pancreatic neuroendocrine tumors, and renal and pancreatic cysts. VHL is a syndrome associated with functional inactivation of the Von Hippel–Lindau protein (pVHL). pVHL is a tumor suppressor mainly known for its role as a regulator of hypoxia-inducible factor (HIF) activity. The prevalence of VHL disease is between 1 in 39 000 and 1 in 91 000 individuals in different regional populations. Here, we review the etiology, epidemiology, pathophysiology, genetics, clinical manifestations, diagnosis, and current treatments, as well as the molecular aspects of this disease. We also discuss the animal models used to study this disease, VHL biomarkers, and current VHL clinical trials for VHL according to NIH.

it still undergoes corrosion when exposed to corrosive environments. This paper proposes an evaluation method for assessing the corrosion level of SPCC steel specimens using traditional eddy current testing (ECT), along with two different machine learning approaches. The objective is to classify the corroded state of the specimens into two states: a less corroded state (state-1) and a highly corroded state (state-2). Generative and discriminative models were implemented for classification. The generative classifier was based on the Gaussian mixture model (GMM), while the discriminative model was based on the logistic regression model. The models used features based on the absolute maximum of the perturbation magnetic field components at two different frequencies. The performance of the classifiers was evaluated using metrics such as absolute error, accuracy, precision, recall, and F1 score. The results indicate that high classification accuracy can be achieved based on both methods using traditional eddy current testing.

Gastric outlet obstruction (GOO) poses a common and challenging clinical scenario, characterized by mechanical blockage in the pylorus, distal stomach, or duodenum, resulting in symptoms such as nausea, vomiting, abdominal pain, and early satiety. Its diverse etiology encompasses both benign and malignant disorders. The spectrum of current treatment modalities extends from conservative approaches to more invasive interventions, incorporating procedures like surgical gastroenterostomy (SGE), self-expandable metallic stents (SEMS) placement, and the advanced technique of endoscopic ultrasound-guided gastroenterostomy (EUS-GE). While surgery is favored for longer life expectancy, stents are preferred in malignant gastric outlet stenosis. The novel EUS-GE technique, employing a lumen-apposing self-expandable metal stent (LAMS), combines the immediate efficacy of stents with the enduring benefits of gastroenterostomy. Despite its promising outcomes, EUS-GE is a technically demanding procedure requiring specialized expertise and facilities.

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.

Nanoparticles (NPs) have uniform chemical composition, size, and morphology. Microorganisms are of great interest in Nanoparticle synthesis. The green production of nanomaterials occurs either intracellularly or extracellularly. Gold and silver nanoparticles are mostly synthesised by the enzymatic degradation of metal ions. The produced NPs are characterized by different instruments such as ultraviolet visible, dynamic light scattering, x-ray diffraction, scanning electron microscope, transmission electron microscope, etc. Our review discusses the various biomedical applications of gold and silver nanoparticles synthesized by microbes via intracellular and extracellular mechanisms.

Earth Observation (EO) techniques have significantly evolved over time, covering a wide range of applications in different domains. The scope of this study is to review the research conducted on EO in the Eastern Mediterranean, Middle East, and North Africa (EMMENA) region and to identify the main knowledge gaps. We searched through the Web of Science database for papers published between 2018 and 2022 for EO studies in the EMMENA. We categorized the papers in the following thematic areas: Atmosphere, Water, Agriculture, Land, Disaster Risk Reduction (DRR), Cultural Heritage, Energy, Marine Safety and Security (MSS) and Big Earth Data (BED); 6647 papers were found with the highest number of publications in the thematic areas of BED (27%) and Land (22%). Most of the EMMENA countries are surrounded by sea, yet there was a very small number of studies on MSS (0.9% of total number of papers). This study detected a gap in fundamental research in the BED thematic area. Other future needs identified by this study are the limited availability of very high resolution and near real time remote sensing data, the lack of harmonized methodologies and the need for further development of models, algorithms, early warning systems and services.

Osteoarthritis (OA) is the most common degenerative joint disease that causes chronic pain and disability. Different innate immune components, including macrophages, T cells, and neutrophils, participate in osteoarthritis pathophysiology. Neutrophils are the most abundant circulating leukocytes with multiple specialized functions contributing to innate and adaptive immune functions. Although neutrophils produce proinflammatory cytokines and chemokines, reactive oxygen species (ROS), matrix-degrading enzymes, and neutrophil extracellular traps (NET) that promote joint degradation as the first recruit cells in an inflamed joint, these cells also play an important role in joint repair by regulating the immune response, releasing anti-inflammatory factors, and activating some protective genes. In this review, various aspects of neutrophil biology, their role in inflammation and its association with osteoarthritis, and possible therapeutic approaches to target neutrophils for the treatment of osteoarthritis are described. Understanding neutrophil heterogeneity and their mechanisms of action in joint inflammation, provides a potential strategy for OA management.

Lack of reliable information on PTC industry in Sri Lanka is hampering the advancement of the technology. Hence, this study attempted to assess the current status of PTC industry in Sri Lanka in order to ascertain the type and the level of interventions needed to broaden the horizons of the industry. Data of last 05 years were collected through qualitative research methods including a questionnaire-based survey, personal interviews, etc. and personal interviews to identify product diversity, R&D, available facilities, production capacity, and markets. Information was analyzed qualitatively using descriptive statistical software to assess the current status, and identify gaps, challenges and opportunities. COVID pandemic and the economic crisis had a heavy toll on the PTC industry. Six major challenges experienced by business owners were identified as increasing capacity, opportunities to build market linkages, demand fluctuations, issues relating to awareness and insufficient support given by the government. Proper identification and screening of mother plants, determining the production capacities and marketing, knowledgeable and skilled human resources, were identified as important contributory factors for success. Development strategies identified mainly include instinctive decision making and government support. Embracing the significant trade achievements through resource reallocation, prioritization and improvisation processes at individual, family group, inter-organizational levels and across these levels need to be regulated through a responsible authority. These interpretations and recommendations of this research can be utilized both by the policy makers and public and private sector organizations for decision making purposes targeting commercial scale advancements.

Attempts to use computers to aid in the detection of breast malignancies date back more than 20 years. Despite significant interest and investment, this has historically led to minimal or no significant improvement in performance and outcomes with traditional computer aided detection. However, recent advances in artificial intelligence and machine learning are now starting to deliver on the promise of improved performance. There are at present more than 20 FDA approved AI applications for breast imaging, but adoption and utilization are widely variable and overall low. Breast imaging is unique and has aspects that create both opportunities and challenges for AI development and implementation. Breast cancer screening programs worldwide rely on screening mammography to reduce the morbidity and mortality of breast cancer and many of the most exciting research and available AI applications focus on cancer detection for mammography. There are however multiple additional potential applications for AI in breast imaging including decision support, risk assessment, breast density quantitation, workflow and triage, quality evaluation, response to neoadjuvant chemotherapy assessment, and image enhancement. In this review the current status, availability, and future directions of investigation of these applications are discussed, as well as the opportunities and barriers to more widespread utilization.

Staphylococcus aureus (S. aureus), particularly Methicillin-resistant S. aureus (MRSA), is a life-threatening pathogen that causes a variety of infections in hospital and community settings. It poses a significant risk and challenge for global health that hinders our ability to control and treat bacterial infections. Recently, the emergence and spread of variant strains of bacteria, misuse of the limited available options of effective antibiotics, spread of fake drugs, and climate change that increased the contact between humans and animals’ populations carrying different bacterial has significantly increased the incidence of Multi-Drug Resistance strains (MDR). This in turn, has created a severe problem in the infection control treatment of S. aureus infected patients. Treatment options for MRSA infection are increasingly limited and complicated. Unfortunately, different strains of MRSA are showing tolerance and resistance toward vancomycin, which is the standard of care for complicated MRSA. Therefore, it is crucial now to invest developing new effective anti-biotics and synergies, develop and implement national action plans for the management of an-tibiotic resistance, as well as improving our understanding of the antimicrobial resistance mechanisms. Here, in this review we explain the main mechanisms of antibiotic resistance in MRSA and describes different approaches to manipulate it in MRSA, providing a basis for de-signing effective drugs, and shedding some light on the evolution of S. aureus.

Sustainable teacher development is the key to the success in the program of Master of Translation and Interpretation (MTI) but there was limited research on their current situation and needs in China. In this study 514 teachers from 32 provinces, municipalities and autonomous regions across China were investigated by means of quantitative questionnaires and online interviews concerning their current situation of career development and this research presented a comprehensive description of their age, academic qualifications and professional title. Also this study expounded the current situation and difficulties in academic research, teaching, translation practice and staff training. The findings were as follows. 1：In spite of reasonable age structure, approximately 50% of them had less than three years’ teaching experience in MTI. 2: There was a rise in the number of MTI teachers with doctoral degree but they found it hard to offer students professional guidance. 3: A large proportion of MTI teachers were in a slow stream of promotion in the title of professional post. 4: The proportion of the academic achievements related to translation in all the research projects and papers was small. 5: A majority of them worked as part-time translators. 6: About half of the teachers were not very satisfied with the effectiveness in their staff training program. Therefore it is suggested that more opportunities be provided for the MTI teachers to conduct translation practice in the professional sector and more researches be needed to thoroughly understand their requirement in terms of career development with a view to bridging the gap between content in the teacher training and their actual needs.

Natural compounds have diverse structures and are present in different forms of life. Metabolites such as tannins, anthocyanins, and alkaloids, among others, serve as a defense mechanism in live organisms and are undoubtedly compounds of interest for the food, cosmetic and pharmaceutical industries. Plants, bacteria, and insects represent a source of biomolecules with diverse activities, poorly studied in many cases. To use these molecules for different applications, it is essential to know their structure, concentrations, and biological activity potential. In vitro techniques that evaluate the biological activity of the molecules of interest have been developed since the 1950s. Currently, different methodologies have emerged to overcome some of the limitations of these traditional techniques, mainly the reduction of time and costs. However, emerging technologies continue to appear due to the urgent need to expand the analysis capacity of a growing number of reported biomolecules and the lack of therapeutic options to treat various diseases. This review presents an updated summary of the conventional and current methods to evaluate natural compounds' biological activity, including a diagram that summarizes the minimum techniques essential for correctly assessing molecules with biological potential.

Tumor cells evolve in a complex and heterogeneous environment composed of different cell types and an extracellular matrix. Current 2D culture methods are very limited in their ability to mimic the cancer cell environment. In recent years, various 3D models of cancer cells have been developed, notably in the form of spheroids/organoids, using scaffold or cancer-on-chip devices. However, these models have the disadvantage of not being able to precisely control the organization of multiple cell types in complex architecture and are sometimes not very reproducible in their production, and this is especially true for spheroids. Three-dimensional bioprinting can produce complex, multi-cellular, and reproducible constructs in which the matrix composition and rigidity can be adapted locally or globally to the tumor model studied. For these reasons, 3D bioprinting seems to be the technique of choice to mimic the tumor microenvironment in vivo as closely as possible. In this review, we discuss different 3D-bioprinting technologies, including bioinks and crosslinkers that can be used for in vitro cancer models, and the techniques used to study cells grown in hydrogels; finally, we provide some applications of bioprinted cancer models.

Ethanol produced from various biobased sources (bioethanol) has been gaining high attention lately due to its potential to cut down net emissions of carbon dioxide while reducing burgeoning world dependence on fossil fuels. Global ethanol production has increased more than six-fold from 18 billion liters at the turn of the century to 110 billion liters in 2019 (1,2). Sugar cane and corn have been used as the major feedstocks for ethanol production. Lignocellulosic biomass has recently been considered as another potential feedstock. This paper reviews recent developments and current status of commercial production of ethanol across the world. The review includes the ethanol production processes used for each type of feedstock, both currently practiced at commercial scale and newly developed technologies, and production trends in various regions and countries in the world.

Acute lymphoblastic leukemia is the most common malignancy in children and is characterized by numerous genetic and epigenetic abnormalities. Epigenetic mechanisms, which involve DNA methylations and histone modifications, result in the heritable silencing of genes without a change in their coding sequence. Emerging studies are increasing our understanding of the epigenetic role of leukemogenesis and have demonstrated the potential of DNA methylations and histone modifications as a biomarker for lineage and subtypes classification, predicting relapse, and disease progression in ALL. Epigenetic abnormalities are relatively reversible when treated with some small molecule-based agents compared to genetic alterations. In this review, we conclude the genetic and epigenetic characteristics in ALL and discuss the future role of DNA methylation and histone modifications in predicting relapse, finally focus on the individual and precision therapy targeting epigenetic alterations.

Lynch syndrome (LS) is an autosomal dominant genetic condition caused by mutations in the DNA mismatch repair (MMR) genes in the germline. Colorectal cancer and/or LS-associated cancer are more likely in people who carry pathogenic mutations in these genes. Cancers of the endometrium, small intestine, stomach, pancreas, and biliary tract, ovarian, brain, upper urinary tract, and skin are among the cancer types linked to LS. The criteria for a clinical diagnosis of LS, as well as the processes for genetic testing to identify carriers of pathogenetic mutations in MMR genes, have been known for a long time. The precise description of the pathogenicity associated with MMR genetic variants is critical in the mutation detection analysis, especially in order to enroll mutation carriers in endoscopic surveillance programs that are more suited to them. As a result, this may aid in the improvement of LS-related cancer prevention efforts. In this review, we discuss recent advances in the molecular genetics of LS.

On estimation scales ranging from 0.1 nm to 100 nm, the nanoscale is part of the capacitance components of the physical-synthetic and natural environment. Dimensionality, morphology, structure, uniformity, and agglomeration are all used to classify nanoparticles. Its functionality and effect on the environment and species are influenced by its shape and morphology. The priority research is to determine the effects of nanoparticles on any biological entity that is necessary when designing nanotechnology-based biotechnological and biomedical products. Bacteria have a remarkable ability to reduce metal ions, making them one of the most promising candidates for nanoparticle biosynthesis. Nanoparticles have been researched in the biomedical field for antimicrobial, biosensor, diagnostic imaging, and drug delivery applications. These natural technologies appear to be capable of producing stable nanoparticles with well-defined dimensions, morphologies, and compositions by optimizing reaction conditions and selecting the best bacteria. This work includes a list of the most commonly used microorganisms and associated Nanoparticles, as well as a discussion of current biotechnology and biomedical developments.

Geomagnetic induced current (GIC) is a ground end manifestation associated with the space weather perturbations that should be greatly taken into account by the society. Although the GICs implication to the power system is not regular, it can cause large scale of system failure. In equatorial, the power system is considered safe since the most intense of geomagnetic storm happened in high latitude. However, the internal damage due to GICs which finally led to the South African power system failure has totally changed the normal perception. Therefore, a preliminary investigation on the GICs activity in equatorial region is performed to understand the space weather impact to the power system. Time derivative of the horizontal magnetic field component (dB/dt) is done to indicate the GICs activity value based on Faraday’s law. All the reported power failures are compiled to produce the threshold value of dB/dt, which possibly cause the harmful effect to the system. Then, dB/dt analysis is extended to show the pattern of GICs activity in function of magnetic latitude and local time. The results reveal that power network in equatorial region has possibly suffered by GIC. Plus, high number of intense GIC activity in this region occurred during dayside.

COVID-19 disease outbreak was started in the December, 2019 in the Wuhan city of China which is also known as the largest transportation hub of China. During the spring festival of China the situation become epidemic. Soon, the virus is imported to many regions including the low income countries. Till now, 234073 infected reported cases of the COVID-19 in the world with the total of 9840 deaths (March 20, 2020). The common symptoms of the COVID-19 are the cough, high fever, sore throat, fatigue and breathlessness. The disease is found to be mild in most of the people, some of cases reported to the pneumonia also with multi organ dysfunction and acute ARDS (acute respiratory distress syndrome). It is found that the incubation period for the infection is 2-14 days which is usually 4 days in maximum of cases. India has reported 283 cases of COVID-19 infections till now with 4 deaths. India is still at stage 2 on local transmission as per WHO report 60. WHO reported 60 clearly stated that there is no community transmission occurred in India yet which can be prevented by the avoiding mass gathering and proper screening of the people. Govt. of India has taken many initiatives to minimize the spread of COVID-19 infection in the country. The infection rate of the COVID-19 in India remains low related to population size of the country. It is because of fast government action to quarantine the suspected people and shut down all its borders. There is a great slowdown in the global economy due to COVID-19 attack which is likely to costs around $1 trillion. The spread of COVID-19 infection can be reduced by minimizing the H-H transmissions. Still there is need of Anti-n-CoV drug development which can replace the supporting therapies for the treatment of infection.

Currently, electromagnetic and radar methods are the most common non-destructive tests for non-destructive rebar location in structures.. Both methods have some advantages, disadvantages and limitations. This article is an attempt to describe possibilities of particular methods with emphasizing their advantages and limitations. The first stage of tests included results from tests conducted on a lintel beam made of autoclaved aerated concrete (AAC) and reinforced with small-diameter rebars and rebars placed close to each other. The second stage consisted in testing nine lightweight concrete specimens, each with three bars having a diameter of 10, 16 and 20 mm at three different space arrangements, to determine the effect of bar diameter and spacing on the measurement accuracy. The reinforcement of lintels and specimens was tested with two different electromagnetic scanners and a ground-penetrating radar (GPR) device. Received results from direct tests were compared with results from non-destructive tests (NDT). NDT tests conducted in such an element were found to perform the correct assessment of the concrete cover, and at the same time to give ambiguous results with reference to shape and number of rebars.

Biodiversity monitoring is a seminal key for understanding the delivery of ecosystem functions and services. Mediterranean forests and woodlands harbor the vast majority of regional vascular plant diversity, and hence, they are a good surrogate for detecting changes in biodiversity linked to global change. In this work, we present a database resulting from the study of vascular plant diversity in multi-scale plots of 0.1 ha, measured around the first decade of this century and located in Mediterranean forest environments. Diversity profiles are calculated from Hill numbers (0, 1 and 2) for local (α) and regional (ϒ) diversity, as well as multiplicative calculation of differential diversity (β). Main Mediterranean forests sampled had a medium coverage of 51 % and stand dominant height of 10.6 m being monospecific in two thirds of the cases. Local diversity reaches its highest values ​​(around 78 species per 0.1 ha) in Holm oak dehesas, with values ​​below 50 species for the set of the most productive forest stands dominated by species of the genus Pinus. As regards the contribution to regional diversity, it is the broadleaf formations that contribute the most, with stone pine forests and dehesas in an intermediate position, and pine forests contributing the lowest in species richness terms.

We give a bilocal field theory description of a composite scalar with an extended binding potential, that reduces to the Nambu–Jona–Lasinio (NJL) model in the pointlike limit. This provides a description of the internal dynamics of the bound state and features a static internal wave-function, ϕ(⃗r), in the center-of-mass frame that satisfies a Schr¨odinger-Klein-Gordon equation with eigenvalues m2. We analyze the “coloron” model (single perturbative massive gluon exchange) which yields a UV completion of the NJL model. This has a BCS-like enhancement of its interaction, ∝ Nc the number of colors, and is classically critical with gcritical remarkably close to the NJL quantum critical coupling. Negative eigenvalues for m2 lead to spontaneous symmetry breaking, and the Yukawa coupling of the bound state to constituent fermions is emergent.

Control of autonomous robot motion in radial mass density field is presented. In that sense the robot motion is described as the function of the radial mass density parameters. The radial mass density field is between the maximal radial mass density and the minimal radial mass density. Between these two limited values one can use n points (n = 1, 2, . . . nmax) and calculate the related radial mass density for each point. The radial mass density is maximal at the minimal gravitational radius and minimal at the maximal gravitational radius. This conclusion is valid for Planck scale, but also for the scales that are less or higher of that one. Using the ratio of the Planck mass and Planck radius it is generated energy conservation constant with value κ = 0.99993392118. Further, in this theory it is possible to connect Planck’s and gravitational parameters as functions of the maximal (or minimal) radial mass density. In that sense the autonomous robot motion in radial mass density field is important for the control of the robot motion at micro and nano scales.

Considerable efforts have been devoted to modifying gravity, which aim to elucidate the possible existence or nature of dark matter and energy, describe observational data more effectively, and formulate quantum gravity. In addition, despite the immense success of the quantum field theory, the framework requires renormalization techniques and breaks down at high energies. Recently, the Planck legacy 2018 release has confirmed the existence of an enhanced lensing amplitude in the cosmic microwave background power spectra, which prefers a positively curved early Universe with a confidence level higher than 99%. This study considers the implied curvature of the early Universe as the curvature of “the background or 4D conformal bulk as a manifestation of vacuum energy” and distinguishes it from the localized curvature that is induced in the bulk by the presence of celestial objects that are regarded as ”4D relativistic cloud-worlds.” Analogously, because gravity appears to emerge owing to spacetime curvature and does not exhibit critical characteristics shared by other fields, it has been incorporated as the local curvature of the bulk affecting the embedded quantum fields that are regarded as propagating “4D relativistic quantum clouds.” To consider the effects of the bulk on embedded clouds, this paper presents interaction field equations in terms of brane-world modified gravity and the perspective of geometrization of the quantum mechanics wherein gravity is manifested by the curvature of 4D conformal bulk as an indicator of the field strength of vacuum energy on the embedded 4D relativistic clouds in addition to the boundary interactions, which could remove the singularities and satisfy a conformal invariance theory. A visualization of the evolution of the 4D relativistic cloud-worlds over the conformal spacetime of the 4D bulk is presented, whereas the standard said theories can be recovered from the interaction field equations.

Fractals and multifractals are well-known trademarks of nonlinear dynamics and classical chaos. The goal of this work is to tentatively uncover the unforeseen path from multifractals and selfsimilarity to the framework of effective field theory (EFT). An intriguing finding is that the partition function of multifractal geometry includes a signature analogous to that of gravitational interaction. Our results also suggest that multifractal geometry may offer insights into the non-renormalizable interactions presumed to develop beyond the Standard Model scale.

Orientational dependence of the IR absorbing amide bands of silk is demonstrated from two orthogonal longitudinal and transverse microtome slices only $\sim 100$~nm thick. A scanning near-field optical microscopy (SNOM) which preferentially probes orientation perpendicular to the sample's surface was used. Spatial resolution of silk-epoxy boundary was defined with a $\sim 100$~nm resolution while the spectra were collected by a $\sim 10$~nm tip. Ratio of the absorbance of the amide-II C-N at 1512~cm$^{-1}$ and amide-I C=O $\beta$-sheets at 1628~cm$^{-1}$ showed sensitivity of SNOM to the molecular orientation. SNOM characterisation is complimentary to the far-field absorbance which is sensitive to the in-plane polarisation. Volumes with cross sections smaller than 100~nm can be characterised for molecular orientation. A method of absorbance measurements at four angles of slice cut orientation, which is equivalent to the four polarisation angles absorbance measurement is proposed.

_{Superconducting foams of YBa$_2$Cu$_3$O$_y$ (YBCO) are proposed as trapped field magnets or supermagnets. The foams with an open-porous structure are light-weight, mechanically strong and can be prepared in large sample sizes. The trapped field distributions were measured using a scanning Hall probe on various sides of an YBCO foam sample after field-cooling in a magnetic field of 0.5 T produced by a square Nd-Fe-B permanent magnet. The maximum trapped field (TF) measured is about 400 G (77 K) at the bottom of the sample. Several details of the TF distribution, the current flow and possible applicatons of such superconducting foam samples in space applications, e.g., as active elements in flux-pinning docking interfaces (FPDI) or as portable strong magnets to collect debris in space, are outlined.}

This paper introduces an innovative nanotechnology-based approach that provides a pathway to enhance the energy release efficiency of nanoenergetic materials (nEMs) by harnessing self-synchronized collective atomic vibrations and phonon wave resonance within the transition domains between nanocomponents, without altering the material composition. The key innovation involves incorporating finely-tuned 2D-ordered linear-chain carbon-based multilayer nano-enhanced interfaces as programmable nanodevices into the transition domains using advanced multistage processing and assembly techniques. These programmable nanodevices enable precise control over self-synchronized collective atomic vibrations and phonon wave propagation, leading to synergistic effects. To activate and optimize these effects, a combination of various methods is employed, including energy-driven initiation of allotropic phase transformations, surface acoustic wave-assisted micro/nano-manipulation, heteroatom doping, directed self-assembly using high-frequency electromagnetic fields, and data-driven inverse design approaches. By leveraging a data-driven inverse design strategy and uncovering hidden structure-property relationships, we maximize energy release efficiency using the carbon nano-materials genome approach derived from multifactorial neural network-based predictive models. This approach not only unlocks new functionalities in nEMs but also improves environmental performance and safety levels. By pioneering transformative pathways for nEMs through harnessing phonon wave resonance in low-dimensional nanocarbon transition interfaces, this research brings significant advancements in the field.

The elevated or depressed transition temperatures observed in cuprate and pnictide superconductors and other exotic superconductors pose a challenge in the context of explaining them through the traditional Bardeen-Cooper-Schrieffer (BCS) models of superconductivity. A significant obstacle in understanding this phenomenon can be addressed by considering an alternative electron distribution. Our investigation has identified an anyonic distribution, where the occupancy of a site created by removing a hole is filled by an electron. In heavy fermion superconductors (HFSs) block spins must be included in the distribution. The interplay, that is, resonance between superconducting electrons within the conventional BCS framework and independent charge density waves (CDWs) might contribute to driving the high-transition-temperature superconductors (HTSCs).

A tunable near-infrared surface plasmon resonance (SPR) biosensor based on gate-controlled graphene plasmons is investigated theoretically. The novel characteristics of chemical potential sensing make the proposed sensor promising in the application of ultra-sensitive and highly specific biosensing technology. The sensitivity of chemical potential sensing in wavelength interrogation mode can be calculated to be 1.5, 1.89, 2.29, 3.21, 3.73 and 4.68 nm/meV respectively at the central wavelength of 1100, 1200, 1310, 1550, 1700 and 1900 nm. The much smaller full width half maximum (FWHMs) comparing with that of 2D nanomaterial-enhanced metal SPR sensors indicates higher figure of merit. The sensitivity of chemical potential sensing in gate voltage interrogation mode also can be calculated to be 156.9822, 143.6147, 131.0779, 111.0351, 101.3415 and 90.6038 mV/meV respectively at the incident wavelength of 1100, 1200, 1310, 1550, 1700 and 1900 nm. It can be estimated theoretically that the limit of detection (LOD) in DNA sensing of the proposed sensor can reach femtomolar level and even attomolar level, comparable to and even lower than that of 2D nanomaterial-enhanced metal SPR sensors with AuNPs as a sensitivity enhancement strategy. The feasibility of preparation and operation of this new concept SPR biosensor is also analyzed and discussed.

Background: We aimed to determine the splenic stiffness (SS) values in healthy individuals as measured by 3 Tesla magnetic resonance elastography (3T MRE) and to investigate the possible effects of parameters such as age, sex, spleen volume, diameter, and parenchyma thickness on SS.Methods: A total of 54 healthy volunteers were included in this cross-sectional study. Participants' age and sex information were recorded, in addition to spleen craniocaudal and anteroposterior diameter, cortical thickness, spleen volume, and SS, which were measured using 3T magnetic resonance imaging and MRE. Results: Twenty-nine male and 25 female subjects with a mean age of 54.78±15.40 years were included in the study. Mean cradiocaudal diameter was 10.46±1.16 cm, anteroposterior diameter was 9.88±1.29 cm, parenchyma thickness was 4.08±0.67 cm, SS was 3721.94±709.69 Pascal (Pa), and median spleen volume was 292.54 (239.40-311.00) cm³. A significant positive correlation was observed between age and SS (r=0.779, p<0.001). The SS values were not associated with sex, craniocaudal diameter, anteroposterior diameter, parenchymal thickness, or volume.Conclusion:Age should be considered when using SS in the diagnosis and staging of relevant diseases such as portal hypertension and esophageal varices. Our results should be confirmed by future studies using 3T MRE in larger populations.

Background: We aimed to determine the splenic stiffness (SS) values in healthy individuals as measured by 3 Tesla magnetic resonance elastography (3T MRE) and to investigate the possible effects of parameters such as age, sex, spleen volume, diameter, and parenchyma thickness on SS. Methods: A total of 54 healthy volunteers were included in this cross-sectional study. Participants' age and sex information were recorded, in addition to spleen craniocaudal and anteroposterior diameter, cortical thickness, spleen volume, and SS, which were measured using 3T magnetic resonance imaging and MRE. Results: Twenty-nine male and 25 female subjects with a mean age of 54.78±15.40 years were included in the study. Mean cradiocaudal diameter was 10.46±1.16 cm, anteroposterior diameter was 9.88±1.29 cm, parenchyma thickness was 4.08±0.67 cm, SS was 3721.94±709.69 Pascal (Pa), and median spleen volume was 292.54 (239.40-311.00) cm3. A significant positive correlation was observed between age and SS (r=0.779, p<0.001). The SS values were not associated with sex, craniocaudal diameter, anteroposterior diameter, parenchymal thickness, or volume Conclusion:Age should be considered when using SS in the diagnosis and staging of relevant diseases such as portal hypertension and esophageal varices. Our results should be confirmed by future studies using 3T MRE in larger populations.

Objectives: The purposes of this study were to 1) analyze the disruption of intracardiac flow by flow components and kinetic energy (KE) parameters in single ventricle physiology patients and compare with controls; 2) investigate left ventricular diastolic dysfunction in terms of 4D flow parameters in repaired Fontan (rFontan) group; 3) compare intracardiac flow parameters in morphologic LV and RV rFontan patient groups. Methods: Twenty-five rFontan patients (age: 10±3, M/F: 15/10) and fourteen controls (age: 10±2, M/F: 8/6) were prospectively recruited. All underwent cine and 4D flow cardiovascular magnetic resonance (CMR) on 3.0T scanner. Cardiac function and inter-ventricular mechanical dyssynchrony were analyzed using cine images. From 4D flow CMR, ventricular flow components were assessed: direct flow, retained inflow, delayed ejection flow and residual volume. Global and regional blood flow KE parameters, normalized to end-diastolic volume (EDV) were analyzed for functional single ventricle (FSV). Left ventricular (LV) diastolic dysfunction was assessed on echocardiography guidelines. Results: In comparison of rFontan vs. controls, median FSV residual volume (28% vs. 23%, P= 0.034) were higher in rFontan; median FSV direct flow (32% vs. 40%, P=0.005) and delayed ejection flow (17% vs. 24%, P=0.024) were lower in rFontan. FSV KEiEDV parameters were all lower in rFontan (all P<0.05). No significant differences were observed for flow components and KE parameters between patients with and without inter-ventricular dyssynchrony. FSV direct flow (AUC=0.76, Sensitivity=86%, Specificity=70%) was an independent predictor of LV diastolic dysfunction. Residual volume and E-wave KEiEDV were significantly different between morphologic RV and morphologic LV patient group. Conclusions: The changed flow pattern and decreased KE may be hemodynamic disturbances and impaired ventricular filling in rFontan patients. Reduced direct flow is associated with LV diastolic dysfunction. Morphologic right ventricular subgroup is worse than morphologic left ventricular group in terms of the intracardiac hemodynamics.

The success of total hip arthroplasty depends on the experience of the surgeon, and one of the ways the surgeon currently determines the final implant insertion depth is to listen to the change in audible pitch of the hammering sound. We investigated the use of acoustic vibration emissions as a novel method for insertion quality assessment. A non-invasive contact microphone-based measurement system for insertion depth estimation, fixation and fracture detection was developed using a simplified in vitro bone/implant (n=5). 2583 audio recordings were analysed in vitro to obtain energy spectral density functions. Out of the four main resonant peaks under in vitro conditions, broach insertion depth statistically correlates to increasing 3rd and 4th peak frequencies. Degree of fixation was also observed as higher goodness of fit (0.26-0.78 vs. 0.12-0.51 between two broach sizes, the latter undersized). Finally, however, the moment of fracture could not be predicted. A cadaver in situ pilot study suggests comparable resonant frequencies in the same order of magnitudes with the bone model. Further understanding of the signal patterns are needed for an early warning system diagnostic system for imminent fractures, bone damage, improving accuracy and quality of future procedures.

Surface Plasmon Resonance (SPR) based sensors have the advantage of being label-free, enzyme-free and real-time. However, their spreading in multidisciplinary research is still limited and almost confined to prism-coupled devices. Plasmonic gratings, combined with a simple and cost-effective instrumentation, have been poorly developed compared to prism-coupled system mainly due to their lower sensitivity. Here we describe the optimization and signal enhancement of a sensing platform based on phase-interrogation method, which entails the exploitation of a nanostructured sensor. This technique is particularly suitable for integration of the plasmonic sensor in a lab-on-a-chip platform and can be used in a microfluidic circuit to ease the sensing procedures and limit the injected volume. The careful optimization of most suitable experimental parameters by numerical simulations leads to a 30 to 50% enhancement of SPR response, opening new possibilities for applications in the biomedical research field while maintaining the ease and versatility of the configuration.

We study the resonant dipole-dipole interaction energy between two uniformly accelerated identical atoms, one excited and the other in the ground state, prepared in a correlated Bell-type state, and interacting with the scalar field or the electromagnetic field nearby a perfectly reflecting plate. We suppose the two atoms moving with the same uniform acceleration, parallel to the plane boundary, and that their separation is constant during the motion. We separate the contributions of vacuum fluctuations and radiation reaction field to the resonance energy shift of the two-atom system, and show that Unruh thermal fluctuations do not affect the resonance interaction, which is exclusively related to the radiation reaction field. However, nonthermal effects of acceleration in the radiation-reaction contribution, beyond the Unruh acceleration-temperature equivalence, affect the resonance interaction energy. By considering specific geometric configurations of the two-atom system relative to the plate, we show that the presence of the mirror significantly modifies the resonance interaction energy between the two accelerated atoms. In particular, we find that new and different features appear with respect to the case of atoms in the free space, related to the presence of the boundary and to the peculiar structure of the quantum electromagnetic field vacuum in the locally inertial frame. Our results suggest the possibility to exploit the resonance interaction between accelerated atoms, as a probe for detecting the elusive effects of atomic acceleration on radiative processes.

Background: Since 2010, Burkina Faso has developed and initiated community-based management of childhood illnesses. Following the increased presence of community health workers and the adoption of free community health care, this study aims to assess community satisfaction with curative care administered by community health workers. Methodology: It was a descriptive and analytical cross-sectional study. Data were collected in the health districts of Boussé and Boussouma from 20 February to 30 March 2023 for quantitative data and from 12 to 30 January 2024 for qualitative data using a questionnaire (household survey) and an interview grid (focus groups). Analyses were conducted using SPSS IBM 25 and Nvivo 14. Results: Households benefit from oral curative care when using CHWs, but are not satisfied with the temporal accessibility of these community health workers. Temporal accessibility and awareness during care have a significant influence on household satisfaction. Conclusion: Curative care by community health workers is effective, but its use could be improved by addressing the unavailability of community health workers, inputs and better communication during care.

Xanthone derivatives, a class of natural compounds abundantly found in plants such as mangosteen (Garcinia mangostana) and certain herbs, have garnered substantial interest due to their diverse pharmacological properties, including antioxidant, anti-inflammatory, and anti-cancer activities. Recent investigations have unveiled their potential as modulators of enzymatic activity, prompting exploration into their effects on hyaluronidase-mediated HA degradation, and their effects in topical treatment of telangiectasia and rosacea. Telangiectasia and rosacea are common dermatological conditions characterized by chronic skin inflammation, vascular abnormalities, and visible blood vessels, resulting in significant cosmetic concerns and impaired quality of life for affected individuals. This review aims to provide a comprehensive overview of the current understanding regarding the interplay between mechanisms of action by which xanthone derivatives exert their therapeutic effects, including the inhibition of pro-inflammatory cytokines, modulation of oxidative stress pathways, and regulation of vascular endothelial growth factors. Furthermore, we will discuss the implications of harnessing xanthone derivatives as therapeutic agents for mitigating vascular dysfunction and its associated pathologies, thereby offering insights into future research directions and therapeutic strategies in the field of vascular biology.

We studied the magnetostriction coefficients, λs, Curie temperature, Tc, and their dependence on annealing conditions in Fe47Ni27Si11B13C2 and Co67Fe3,9Ni1,5B11,5Si14,5Mo1,6 amorphous glass-coated microwires with rather different character of hysteresis loops. A positive λs≈20x10-6is observed in as-prepared Fe47Ni27Si11B13C2, while low and negative λs ≈-0.3x10-6 is ob-tained for Co67Fe3,9Ni1,5B11,5Si14,5Mo1,6 microwire. Annealing affects the magnetostriction coeffi-cients and Curie temperatures, Tc, of both Fe47Ni27Si11B13C2 and Co67Fe3,9Ni1,5B11,5Si14,5Mo1,6 glass-coated microwires in a similar way. Observed dependencies of hysteresis loops, λs and Tc on annealing conditions are discussed in terms of superposition of internal stresses relaxation and structural relaxation of studied microwires. We observed linear λs dependence on applied stress, σ, in both studied microwires. A decrease with applied stress is observed for Co-rich mi-crowires with negative magnetostriction coefficient. In contrast, a linear increase of the magne-tostriction coefficient with applied stress is observed for Fe-Ni- rich microwires with positive magnetostriction coefficient. Observed results are discussed in terms of influence of internal stresses and short range atomic rearrangements induced by annealing on hysteresis loops, magnetostriction coefficients and Curie temperatures of studied microwires.

Repeated fires cause peatlands to degrade. Fire management has been carried out, but fires continue to occur, especially during the dry season. Through social capital that applies in the community based on the local wisdom of the Banjar people in environmental management, it is hoped that peatland fires can be overcome in this area. This research aims to analyze the social capital of the Banjar people in mitigating land fires based on local wisdom and the environment. The sample in this study was 250 people who live in an area prone to fires on peatlands in Banjarbaru, South Kalimantan, Indonesia. There are three variables in this study, namely Trust (T), Network (N) and Norm (N). There are 33 Likert scale questions (1-4, strongly agree-strongly disagree). We also conducted interviews with 20 members of the Fire Care Community (MPA) to obtain information about the social capital of the Banjar community in mitigating land fires. The analysis used is Structural Equation Modeling (SEM). The study results show norms have the greatest influence on disaster mitigation of peatland fires compared to trust and social networks. Norms in the community in the form of values from peatlands, rules, norms and sanctions regulate the community more to deal with the problem of peatland fires than trust and social networks

With growing global concern of food and water insecurity, an efficient method to monitor irrigation projects is essential, especially in the developing world, where irrigation performance is often suboptimal. In Nepal, the irrigated area has not been objectively recorded, although their assessment has substantial implications on national policy, project’s annual budgets, and donor fund-ing. Here we present the application of Landsat images to measure irrigated areas in Nepal for the past 17 years to contribute to the assessment of the irrigation performance. Landsat 5 TM (2006-2011) and Landsat 8 OLI (2013-2022) images were used to develop a machine-learning model which classifies irrigated and non-irrigated areas in study areas. The random forest classification achieved overall accuracy of 82.2% and kappa statistics of 0.72. For the class of irrigation areas, the producer’s accuracy and the consumer’s accuracy were 79% and 96%, respectively. Our regionally trained machine-learning model outperforms the existing global cropland map, highlighting the need of such models for local irrigation project evaluations. We assess irrigation project performance and its drivers by combining long-term changes in satellite-derived irrigated area with local data related to irrigation performance, such as annual budget, irrigation service fee, crop yield, precipitation, and main canal discharge.

South rear-edge populations of widely distributed temperate and boreal tree species such as birches (Betula pubescens and B. pendula) are considered particularly vulnerable to climate warming, and at the same time they constitute genetic reservoirs of drought-adapted ecotypes. Here, we compared radial growth patterns and responses to climate, river or dam flows and a drought index of rear-edge (southernmost) populations (Toledo Mountains, central-southern Spain) with populations located in northern Spain of B. pubescens and B. pendula. Then, we per-formed a comparative analysis across Europe of B. pendula populations. The main climatic con-straint of birch growth was high summer water deficit, although the effect of local hydrological conditions was particularly important in rear-edge populations. We found declining growth trends in rear-edge stands since the early 21st century, related to decreasing water availability and increasing aridity. Our results also suggested distinct growth patterns and climate-growth associations of B. pendula across Europe that show how populations further south and in warmer locations were more sensitive to the drought. In conclusion, drought-induced growth decline can be exacerbated by local human land uses leading to reduced river inflow, thus endangering birch populations at their southern distribution limit. Protection of endangered rear-edge birch populations requires adequate management of local water resources.

The local and global order in dense packings of linear, semi-flexible polymers of tangent hard spheres are studied by employing extensive Monte Carlo simulations at increasing volume fractions. Chain stiffness is controlled by a tunable harmonic potential for the bending angle whose intensity dictates the rigidity of the polymer backbone as a function of the bending constant and equilibrium angle. The studied angles range from acute to obtuse ones, reaching the limit of rod-like polymers. We analyze how packing density and chain stiffness affect the ability of chains to self-organize at the local and global levels. The former corresponds to crystallinity as quantified by the Characteristic Crystallographic Element (CCE) norm descriptor, while the latter is computed through the scalar orientational order parameter. In all cases, we identify the critical volume fraction for the phase transition and gauge the established crystal morphologies, developing a complete phase diagram as a function of packing density and equilibrium bending angle. A plethora of structures is obtained, ranging from random hexagonal closed packed morphologies of mixed character and almost perfect face centered cubic (FCC) and hexagonal close-packed (HCP) crystals at the level of monomers, to nematic mesophases, with prolate and oblate mesogens at the level of chains. For rod-like chains, hysteresis is observed between the establishment of long-range nematic order and crystallization, while for right-angle chains both transitions are synchronized. A comparison is also provided against the analogous packings of monomeric and fully flexible chains of hard spheres.

E-petitioning is a useful object of study for observing the potential emergence of a new relationship to politics and new forms of political participation. Access to a dataset of hundreds of thousands of users of an electronic petitioning platform, provides the opportunity to overcome a certain number of limitations that are associated with traditional methods of studying political participation, since it allows us to focus on the reality of the signatories’ behaviour rather than on their declarations. We follow the traces left by the petitioners on this site to better understand the process of dissemination of an online petition, and its linked with offline activities. Our examination of the three most signed petitions in the ‘environment’ category, combining an analysis of their petitioning dynamics and an analysis of the comments attached to them, allows us to show: firstly, that there is an interwoven relationship between the local anchoring of the mobilisation and the processes of dissemination by which petitions extend from local signatories to signatories who are geographically more distant; and secondly, that it is not accurate to imagine that just anyone can sign any petition, since petitioning dynamics proceed from one person to the next, whether these dynamics start from a pre-existing local anchorage on the ground, or act through a platform effect which is dependent on the attractiveness of the petition in question.

Monsoon winds drive upwelling along the eastern coast of India during the south-west (SW) monsoons. These winds also provide alongshore windstress (AWS) resulting in positive cross-shore Ekman transport (ET) from March to the end of September. While instances of high ET and sea surface temperature based upwelling index (UI_SST) were observed along two parts of the coast: between Kashinagara and Kakinada in the north, and between Kavali and Point Calimere in the south. The UI_SST illustrated a much poorer agreement with local ET in the northern section, where the onset of UI_SST preceded the rise of ET and the subsidence of UI_SST signals occurred during a period of rising ET. Additionally, negative sea surface height anomalies (SSHAs), typically associated with coastal upwelling, were also missing through most of the upwelling period. A complex empirical orthogonal function (CEOF) analysis revealed two coherent modes of SSHA variation. The first mode showed a SSHA signature spatio-temporally coincident with the first upwelling and downwelling Kelvin waves closely associated with the equatorial zonal winds that drive them. The second CEOF mode, with a coastal SSHA pattern similar to the SSHA signatures of coastal upwelling, was associated with local offshore ET along the Indian east coast. The CEOF analysis exhibited the triggering of coastal upwelling in April and its suppression from June by coastally trapped Kelvin waves along the northeastern coast of India, while local AWS driven ET was the primary driver of coastal upwelling along the southeastern coast. The second CEOF mode also exhibited a coherent negative coastal SSHA signature excited by local AWS driven ET during the upwelling period. This study examined the spatio-temporal variability of premonsoon and SW monsoon coastal upwelling along the western Bay of Bengal and its relation to remotely forced coastal Kelvin waves.

Due to slow progression and susceptibility to radical forms of treatment low-grade PC is associ-ated with high overall survival (OS). With the clinical progression of PC the therapy is getting more complex. The immunosuppressive tumor microenvironment (TME) makes PC a difficult target for most immunotherapeutics. Its general immune resistance is established by i.e. immune evasion through Treg cells, synthesis of immunosuppressive mediators, and defective expression of surface neoantigens. The success of sipuleucel-T in clinical trials initiated several other clinical studies that specifically target the immune escape of the tumor and eliminate the immunosuppres-sive properties of TME. In the settings of PC treatment, this can be commonly achieved with radi-ation therapy (RT). Also, focal therapies usually applied for localized PC, such as high-intensity focused ultrasound (HIFU) therapy, cryotherapy, photodynamic therapy (PDT), or irreversible electroporation (IRE) were shown to boost anti-cancer response. Nevertheless, the present guide-lines restrict their application to localized and low-grade PC. This review explains how RT and focal therapies enhance the immune response. We also provide data supporting the combination of RT and focal treatments with immune therapies.

Debris-flows are recurrent events on mountain- and hill- slopes, and they have been the object of numerous field investigations and sampling, however most of this work reposes on imagery and outcrop analysis, in such a way that there are still only a handful of studies investigating the internal architecture of these events’ deposits. In the present contribution, we aims at underneath the internal structure of a portion of a debris-flow deposit that was accessible in the aftermath of the 2018 heavy-rainfall debris-flows in Hiroshima Japan. Using a Ramac Pro-Ex GPR with 500 MHz and 800 MHz antenna, a set of longitudinal and transversal transects was used to characterize the deposit. The results demonstrated that a set of subhorizontal layers have filled the valley, and interacting with local terrace edges, these layers have piled up and overcome the obstacle. Across the valleys, a set of trough suggest the presence of channels that were also filled during the event. Finally, in the channel post-event, a set of radargram “cross-bedded units” shows that the final deposition in the channel was of a more dilute flow, typical of a Newtonian flow. This set of units was not to be found at the surface of the post-event pseudo-surface, suggesting that the flow ended as a debris-flow on this surface, and that it is only when the flow dug the final channel that the nature of the flow returned from debris-flow to Newtonian flow.

Abstract: Due to their rapid evolution and their impact on health care, be-ta-lactamases, protein degrading beta-lactam antibiotics, are used as generic model of protein evolution. Therefore, we investigated the mutation effects in two distant beta-lactamases TEM-1 and CTX-M-15. Interestingly we found a site with a complex pattern of genetic interactions. Mutation G251W in TEM-1 is in-activating the protein’s function just as the reciprocal mutation W251G in CTXM-15. Phylogenetic analysis revealed that mutation G has been entrenched in TEM-1 background: while rarely observed throughout the phylogeny it is es-sential in TEM-1. Using a rescue experiment in TEM-1 G251W mutant, we could identify sites that alleviates the deviation from G to W. While few of these muta-tions could potentially involve local interactions, most of them were found on distant residues in the 3D structure. Many well-known mutations having an impact on protein stability, such as M182T, were recovered. Our results there-fore suggest that entrenchment of an amino acid may rely on diffuse interactions among multiple sites with a major impact on protein stability.

Many models with structures of matter associated with a structure of extra spatial dimensions have been proposed in recent decades. On employing a further generalisation from the local 4-dimensional spacetime form to a general form for proper time, we describe how matter fields resembling the Standard Model of particle physics can be accommodated far more directly than with a higher-dimensional spacetime theory. The successful identification of key features of visible matter in this non-spatial sector of extra dimensions in turn motivates seeking a candidate for dark matter residing in the original extra spatial dimension sector, and provides a close guide for the explicit form this invisible matter might take. We describe how such Standard Model and dark matter sectors in different extra-dimensional branches of generalised proper time are gravitationally connected through their common root in the local 4-dimensional spacetime and consider further possible mutual interactions and implications in comparison with existing dark matter models. A yet further possible branch of generalised proper time can be connected with dark energy models, hence in principle accounting for all three major components of cosmological structure within this framework.

Fiber optic sensors cannot measure damage; for getting information about damage from strain measurements, additional strategies are needed, and several alternatives have been proposed. This paper discuss two independent concepts: the first one is based on detecting the new strains appearing around a damage spot; the structure does not need to be under loads; the technique is very robust, damage detectability is high, but it requires sensors to be located very close to the damage, so it is a local technique. The second approach offers a wider coverage of the structure, it is based on identifying the changes caused by the damage on the strains field in the whole structure for similar external loads. Damage location does not need to be known a priori, detectability is dependent upon the sensors network density, damage size and the external loads. Examples of application to real structures are given.

This paper presents novel feature descriptors and classification algorithms for automated scoring of HER2 in Whole Slide Images (WSI) of breast cancer histology slides. Since a large amount of processing is involved in analyzing WSI images, the primary design goal has been to keep the computational complexity to the minimum possible level and to use simple, yet robust feature descriptors that can provide accurate classification of the slides. We propose two types of feature descriptors that encode important information about staining patterns and the percentage of staining present in ImmunoHistoChemistry (IHC) stained slides. The first descriptor is called a characteristic curve which is a smooth non-increasing curve that represents the variation of percentage of staining with saturation levels. The second new descriptor introduced in this paper is an LBP feature curve which is also a non-increasing smooth curve that represents the local texture of the staining patterns. Both descriptors show excellent interclass variance and intraclass correlation, and are suitable for the design of automatic HER2 classification algorithms. This paper gives the detailed theoretical aspects of the feature descriptors and also provides experimental results and comparative analysis.

Alena Tensor is a recently discovered class of energy-momentum tensors that provides mathematical framework in which, as demonstrated in previous publications, the description of a physical system in curved spacetime and its description in flat spacetime with fields are equivalent. The description of a system with electromagnetic field based on Alena Tensor can be used to reconcile physical descriptions. 1) In curvilinear description, Einstein Field Equations were obtained with Cosmological Constant related to the invariant of the electromagnetic field tensor, which can be interpreted as negative pressure of vacuum, filled with electromagnetic field. 2) In classical description for flat spacetime, three densities of four-forces were obtained: electromagnetic, gravity, and the force responsible for the Abraham-Lorentz effect (radiation reaction force). Obtained connection of Einstein tensor with gravity and radiation reaction force, after transition to curvilinear description, excludes black hole singularities. There was obtained Lagrangian density and generalized canonical four-momentum, containing electromagnetic four-potential and a term responsible for other two forces. In this description charged particles cannot remain at complete rest and should have spin, their energy results from the existence of the energy of the magnetic moment and the density of this energy is part of the Poyting four-vector. The distribution of charged matter was expressed as polarization-magnetization stress-energy tensor, what may explain why gravity is invisible in QED. 3) In quantum picture, QED Lagrangian density simplification was obtained, and the Dirac, Schrödinger and Klein-Gordon equations may be considered as approximations of the obtained quantum solution. Farther use of Alena Tensor in unification applications was also discussed.

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

Insulin icodec of Novo Nordisk is a novel long-acting insulin analogue that exhibits an extended duration of action, providing a promising treatment option for individuals with diabetes. It has been reported that the incorporation of fatty acid moieties into insulin icodec plays a crucial role in its prolonged action, as these fatty acid chains facilitate the formation of stable hexameric structures, thereby delaying insulin absorption and promoting sustained release. Yet, the underlying biophysics still is elusive of the roles of the three site-specific mutations (Y14A\_E, Y37B\_H, F46B\_H) of insulin icodec in its prolonged activity. Thus, through a comprehensive structural and biophysical analysis of the insulin (both native and icodec) structures bound to its receptor, this article delves deep into the biophysics underlying the molecular design of insulin icodec, and identified a delicate biophysical mechanism through which two missense mutations of insulin icodec (Y37B\_H and F46B\_H) contribute to its prolonged duration of action. Overall, this structural and biophysical investigation provides valuable insights into the mechanisms underlying the relationship between three site-specific mutations and prolonged duration of action of insulin icodec, while understanding these modifications at a structural and biophysical level can aid in the rational design of future long-acting insulin analogues, offering further enhanced therapeutic options for diabetic patients.

A biofilm is any syntrophic consortium of microorganisms in which cells adhere to one another and, in some cases, to a surface. These adherent cells become encased in a slimy extracellular matrix made up of extracellular polymeric substances (EPSs). Until now, the use of commercial disinfectants remains the main strategy to control biofilm-mediated problems. This mini review summarizes common antibiofilm mode of actions taken by disinfectants and how water channels in microbial biofilms contribute to disinfectant resistance.

The success of boron neutron capture therapy (BNCT) depends mainly on sufficient spatial biodistribution of boron (B-10) localized around or within neoplastic cells to produce a high dose gradient between the tumor and healthy tissue. Contrary to what is usual in radiotherapy, BNCT proposes treatment planning directed at the cell rather than the tumor mass. However, it is not yet possible to precisely determine the concentration of B-10 in a specific tissue in real-time using non-invasive methods. Some critical issues still need to be resolved if BNCT is to become a valuable, minimally invasive, and efficient cancer treatment. This review article provides an overview of the funda-mental principles, recent advances, and future directions of BNCT as a cell-targeted cancer therapy. The main emphasis is on topics related to biological dosimetry, methods for assessing boron concentration, mechanisms of action of BNCT, and its physical bases for clinical implementation.

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

Hydroxychloroquine, a known antiviral metabolite of chloroquine, is increasingly used along with antibiotic azithromycin for the treatment of COVID-19 infection. In about one month India, the world’s largest manufacturer, delivered hydroxychloroquine for treating COVID-19 to over 50 countries. The therapy is being used across the world both for patients staying at home at the early phase of symptoms, as well as for patients hospitalized. We summarize achievements as of late April 2020, review possible modes of action and suggest avenues for the quick scale-up of production of hydroxychloroquine.

Epigenetic changes are a hallmark of short- and long-term transcriptional regulation, and hence instrumental in the control of cellular identity and plasticity. Epigenetic mechanisms leading to changes in chromatin structure, accessibility for recruitment of transcriptional complexes, and interaction of enhancers and promoters all contribute to acute and chronic adaptations of cells, tissues and organs to internal and external perturbations. Similarly, the peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) is activated by stimuli that alter the cellular energetic demand, and subsequently controls complex transcriptional networks responsible for cellular plasticity. It thus is of no surprise that PGC-1α is under the control of epigenetic mechanisms, and constitutes a mediator of epigenetic changes in various tissues and contexts. In this review, we summarize the current knowledge of the link between epigenetics and PGC-1α in health and disease.

Food systems will need to undergo considerable transformation. To be better prepared for and resilient to uncertainty and disturbances in the future, resource users and managers need to further develop knowledge about the food and farming system, with its dominating feedback structures and complexities, and to test robust and integrated system-based solutions. This paper investigates how participatory system dynamics modeling can be adapted to groups at the community level with low or no formal educational background. The paper also analyzes the refinement of workshop participants’ mental models as a consequence of a participatory system dynamics intervention. For this purpose, we ran two workshops with small-scale farmers in Zambia. Analysis of workshop data and post-workshop interviews shows that participatory system dynamics is well adaptable to support an audience-specific learning-by-doing approach. The use of pictures, objects and water glasses in combination with the basic aspects of causal loop diagramming makes for a well-balanced toolbox. Participants acquire understanding that is also relevant beyond systems thinking in that is offers a range of practical insights such as a critical evaluation of common food security strategies.

Antarctica has attracted increasing interest in understanding its microbial communities, metabolic potential, and as a source of microbial hydrolytic enzymes with industrial applications, for which advances in next-generation sequencing technologies have greatly facilitated the study of unculturable microorganisms. In this work, soils from seven sub-Antarctic islands and Union Glacier were studied using a whole-genome shotgun metagenomic approach. The main findings were that the microbial community at all sites was predominantly composed of the bacterial phyla Actinobacteria and Cyanobacteria, and the families Streptomycetaceae and Pseudonocardiaceae. Regarding the xenobiotic biodegradation and metabolism pathway, genes associated with benzoate, chloroalkane, chloroalkene, and styrene degradation were predominant. In addition, putative genes encoding industrial enzymes with predicted structural properties associated with improved activity at low temperatures were found, with catalases and malto-oligosyltrehalose trehalohydrolase being the most abundant. Overall, our results show similarities between soils from different Antarctic sites with respect to more abundant bacteria and metabolic pathways, especially at higher classification levels, regardless of their geographic location. Furthermore, our results strengthen the potential of Antarctic soils as a source of industrially relevant enzymes.

The performance of OpenFOAM in strong scaling tests on HPC systems with AMD EPYC processors exhibits a pronounced superlinear speedup. Simple test cases show superlinear speedups of over 300%, which significantly impacts the efficient use of computing resources. With the last generation of HPC architectures, a superlinear speedup of about 10% to 20% was well expected and accepted by CFD users. The measured superlinear speedup is much more pronounced and withstands the communication overhead to even larger scales. A detailed performance analysis of OpenFOAM follows, employing various High-Performance Computing (HPC) architectures, including AMD, ARM and Intel systems. The performance metric FVOPS (Finite VOlumes solved Per Second) is introduced to compare the performance of Computational Fluid Dynamics (CFD) applications when varying the grid size, as occurs in a strong scaling test. The achievable FVOPS depends on various factors, including the simulation type, boundary conditions, and especially the grid size of a use case. Analysing FVOPS on a single node level with varying grid size shows a significant difference in performance and cache utilization, which explains the large superlinear speedups seen in the strong scaling tests. Furthermore, FVOPS can be used as a simple benchmark to determine the optimal number of grid elements per rank to simulate a given use case at peak efficiency on a given platform, resulting in time, energy, and cost savings. The FVOPS metric also facilitates the direct comparison between different HPC architectures. The tests using AMD, ARM, and Intel processors show a peak in performance when employing around 10,000 grid elements per core. The presence of a large L3 cache on AMD processors is particularly advantageous, as indicated by L3 cache miss rates observed on AMD EPYC processors. Our results suggest that future HPC architectures with larger caches and higher memory bandwidth would benefit the CFD community.

A diagnosis of typical chronic lymphocytic leukemia (CLL) requires the presence of ≥5000 clonal B-lymphocytes/μL with the coexistence of CD19, CD20, CD5, and CD23 and the restriction of light chain immunoglobulin, and the lack of expression of antigens CD22 and CD79b. Atypical CLL (aCLL) can be distinguished from typical CLL morphologically and immunophenotypically. Atypical CLL cells are defined as prolymphocytes; morphologically, these present as deeply-clefted lymphocytes which are larger than those in typical CLL, with condensed chromatin and without prominent nucleoli. However, current aCLL diagnostics rely more on immunophenotypic characteristics rather than atypical morphology. Immunophenotypically, atypical CLL differs from classic CLL in the lack of expression of one or fewer surface antigens, most commonly CD5 and CD23, and the patient does not meet the criteria for a diagnosis of any other B-cell lymphoid malignancy. Morphologically atypical CLL has more aggressive clinical behavior and worse prognosis than classic CLL. Patients with aCLL are more likely to display markers associated with poor prognosis, including trisomy 12, unmutated IGVH, and CD38 expression compared with classic CLL. However, no standard or commonly-accepted criteria exist for differentiating aCLL from classic CLL and the clinical significance of aCLL is still under debate. This review summarizes the current state of knowledge on the morphological, immunophenotypic and genetic abnormalities of aCLL.

Current sources play an essential role in tissue excitation used in bioelectrical impedance spectroscopy. Most investigations use Howland current sources that, despite their practicality and simplified implementation, have operating frequency limitations and dependence on the load impedance due to theirs narrow output impedance, specially at higher frequencies. The objective of this work is to propose model for a robust current-controlled sinusoidal oscillator. The oscillator is based on fully analog electronics, which enables controlling oscillation phase and amplitude by using a voltage reference. The mathematical model is based on Pyragas control application to the classical harmonic oscillator. From the modelling process, it was build an oscillator topology based on second-generation current carriers and on transconductance amplifiers. The reference signal (Fsync) was a sinusoidal voltage source having a frequency of 1MHz and an amplitude of 1Vpp. The oscillator output current synchronized the oscillations’ phase and amplitude with Fsync, regardless of their magnitude before the control signal acted in the circuit at t≈13.5μs. SPICE simulations using ideal components have confirmed the successful operation of the proposed oscillator. This type of oscillator can be implemented in SOIC, then allowing oscillation control interface with logic circuits.

Colorectal cancer (CRC) is the third most common type of cancer and the second leading cause of cancer deaths worldwide. Surgery or surgery plus radiotherapy and/or chemotherapy for patients with metastatic CRC (mCRC) were accepted as the main therapeutic strategies until the early 2000s, when targeted drugs, like cetuximab and bevacizumab were developed. The use of targeted drugs in clinical practice has significantly increased patients’ overall survival. To date, the emergence of several types of targeted drugs has opened new possibilities and revealed new prospects for mCRC treatment. Therapeutic strategies are continually being updated to select the most suitable targeted drugs based on the results of clinical trials that are currently underway. This review discusses the up-to date molecular evidence of targeted therapy for mCRC and summarizes the Food and Drug Administration-approved targeted drugs including the results of clinical trials. We also explain their mechanisms of action and how these affect the choice of a suitable targeted therapy.