Under suitable continuity and uniqueness conditions, solutions of an α order Caputo fractional boundary value problem are differentiated with respect to boundary values and boundary points. This extends well-known results for nth order boundary value problems. The approach used is a standard technique and makes heavy use of recent results for differentiation of solutions of Caputo fractional intial value problems with respect to initial conditions and continuous dependence for Caputo fractional boundary value problems.

(1) Background: The compound ytterbium trifluoride is used as a component of several dental materials, and this is reviewed in the current article. (2) Methods: Published articles on this substance were identified from PubMed, and showed that it has been included in a variety of dental restorative materials, including composite resins, glass polyalkenoate cements and calcium trisilicate cements. (3) Results: Ytterbium trifluoride is reported to be insoluble in water. Despite this, its presence is associated with fluoride release from dental materials. There is evidence that it reacts with the components of calcium trisilicate cements to form small amounts of a variety of compounds, including ytterbium oxide, Yb2O3, and calcium-ytterbium fluoride, CaYbF5. In nanoparticulate form, it has been shown to reinforce glass polyalkenoates and it also provides high contrast in X-ray images. (4) Conclusions: Ytterbium trifluoride is a useful component of dental materials, though some of the published findings suggest that there are aspects of its chemistry which are poorly understood.

The rising global population amidst the growing concerns of climate change will have a dire consequence on global food security and socio-economic activities. Wheat is one of the most important staple foods consumed by more than four billion people in the world, but climate change impacts account for a decline of 5.5% in wheat yield and predictions indicate that the production could further dwindle by nearly 30% in 2050, due to trends in temperature, precipitation, and carbon dioxide. An effective annual crop estimate is necessary not only to inform government the status of national food security, but also is used to determine the benchmark on which agricultural commodities are priced in the market. Thus, annual crop monitoring and yield estimate is paramount to determine the amount of wheat imports required to make up for the shortfalls in the national wheat production in South Africa, which has been a net importer of wheat since 1998. A joint project between South Africa and Poland investigated satellite based-crop growth monitoring using Sentinel 2 and determined the most distinguishable crop phenology for an accurate winter wheat classification during the growing season from August – December with Random Forest (RF) algorithm. The winter wheat crop was more accurately identified during the crop ‘heading’ stage in October yielding the highest user’s (75.56%) and producer’s (92.52%) accuracies, despite the relatively lower overall accuracy (78.14%) compared to that of December with OA of 83.58% obtained during the maturity stage. This study, therefore, confirms the suitability of sentinel 2 for an effective phenology-based winter wheat crop classification during the heading stage, reducing the ambiguity of spectral confusion created with surrounding grass and maize crops.

Electroless etching of semiconductors was elevated to an advanced micromachining process by the addition of a structured metal catalyst. Patterning of the catalyst by lithographic techniques facilitates the patterning of crystalline and polycrystalline wafer substrates. Galvanic deposition of metals on semiconductors has a natural tendency to produce nanoparticles rather than flat uniform films. This characteristic makes possible the etching of not only wafers but also particles with arbitrary shape. While it has been widely recognized that spontaneous deposition of metal nanoparticles can be used in connection with etching to porosify wafers, it is also possible to produced nanostructured powders. MACE can be controlled to produce (1) etch track pores with shapes and sizes closely related to the shape and size of the metal nanoparticle, (2) hierarchically porosified substrates exhibiting combinations of large etch track pores and mesopores, and (3) nanowires with either solid or mesoporous cores. This review discussed the mechanisms of porosification, processing advances and the properties of the etch product with special emphasis on the etching of silicon powders.

We utilize how Weber in 1961 initiated the process of quantization of early universe fields to the problem of what may be emitted at the mouth of a wormhole. While the wormhole models are well developed, there is as of yet no consensus as to how, say GW or other signals from a wormhole mouth could be quantized, or made to be in adherence to a procedure Weber cribbed from Feynman, in 1961. In addition, we utilize an approximation for the Hubble parameter parameterized from Temperature using Sarkar’s H ~ Temperature relations, as given in the text . Finally after doing this we go to the Energy as E also ~ Temperature, and from there use E (energy) as ~ signal frequency. This gives us an idea of how to estimate frequency generated at the mouth of a wormhole.

We are using the book “Towards Quantum Gravity with an article by Claus Kiefer as to a quantum gravity interpretation of the density matrix in the early universe. The density matrix we are using is a one loop approximation, with inflaton value and potential terms, like V(phi) using the Padmanabhan values one can expect if the scale factor is a ~ a(Initial) times t ^ gamma , from early times . In doing so, we isolate out presuming a very small initial time step candidates initial time values which are from a polynomial for time values due to the Kiefer Density value.

We are using information from a paper deriving a Lorentz-violating energy-momentum relation entailing an exact mo_mentum cutof as stated by G. Salesi . Salesi in his work allegedly defines Pre Planckian physics, whereas we restrict our given application to GW generation and DE formation in the first 10^-39s to 10^-33s or so seconds in the early universe. This procedure is inacted due to an earlier work whereas referees exhibited puzzlement as to the physical mechanism for release of Gravitons in the very early universe. The calculation is meant to be complementary to work done in the Book “Dark Energy” by M. Li, X-D. Li, and Y. Wang, and also a calculation for Black hole destruction as outlined by Karen Freeze, et. al. The GW generation will be when there is sufficient early universe density so as to break apart Relic Black holes but we claim that this destruction is directly linked to a Lorentz violating energy-momentum G. Salesi derived, which we adopt, with a mass m added in the G. Salesi energy momentum results proportional to a tiny graviton mass, times the number of gravitons in the first 10^-43 seconds

We reduplicate the Book “Dark Energy” by M. Li, X-D. Li, and Y. Wang, given zero-point energy calculation with an unexpected “length’ added to the ‘width’ of a graviton wave just prior to specifying the creation of ‘gravitons’, using the Rosen and Israelit model of a nonsingular universe. In doing so we are in addition to obtaining a wavelength 10^30 times greater than Planck’s length so we can calculate DE, may be able to with the help of the Rosen and Israelit model have a first approximation as to the arrow of time, and a universe with massive gravity. We have left the particulars of the nonsingular starting point undefined but state that the Rosen and Israelit model postulates initial temperatures of 10^-180 Kelvin and also a value of about Planck temperature, at 10^-3 centimeters radii value which may satisfy initial conditions asked by t’Hooft for describing an arrow of time. A key assumption is that the DE is formed at 10^-3 cm, after an expansion of 10^30 times in radii, from the Planck length radius nonsingular starting point. The given starting point for DE in this set of assumptions is where there is a change in the cosmic acceleration, to a zero value, according to Rosen and Israel, with time t = 1.31 times 10^-42 seconds. Which may be where we may specify a potential magnitude, V, which has ties into inflaton physics. The particulars of the model from Rosen and Israelit allow a solution to be found, without discussion of where that nonsingular starting point came from, a point the author found in need of drastic remedies and fixes.

We first of all define the arrow of time. Definition of the arrow of time will allow choosing different initial starting points. One of the issues we will also discuss is the interconnection be-tween the arrow of time, entropy and quantum information. Seth Lloyd in his 2001 work made a linkage between entropy, bits, and information via an axiomatic approach involving time in-tervals. Our take is a bit more general. We will discuss as well the t’Hooft’s statement as to in-itial conditions and times arrow, and how different cosmological models may influence initial conditions. Spoilers alert, if a nonsingular start to expansion existed, this would provide the most straightforward way to avoid a datum from classical relativity. That is, that in the actual equations of classical GR, there is no reason to have time asymmetry. Time asymmetry is built into initial conditions and we will detail several candidates. The first half of the paper brings up cosmology models and forming the arrow of time. The second is related to entropy itself and the problem of information. .

In the pursuit of better treatments, the concept of a chemically-active material, responding to local conditions by causing reactions, or reacting to produce substances that are deemed beneficial, seems laudable. Ultimately, the goal appears to be to recruit natural biological processes such that a natural ‘repair’ is effected. This goal seems to be the reason for prefixing “bio-“ to many terms with a view to advertising the desire, yet without presenting evidence that it has occurred, or indeed that it is capable of occurring, relying instead on non-biological processes to justify the claims. The dogma is such that all work where local ‘responsive’ chemistry is involved must receive the label “bioactive” to legitimize and promote. Nevertheless, the primary evidence adduced is flawed, and the claim must fail. A rethink to restore scientific sense and confidence in the endeavour is essential if real progress is to be made.

Unrecorded alcohol comprises all types of alcohol that is not registered in the jurisdiction where it is consumed. In some countries in Central and Eastern parts of Europe as well as the Balkan, the major amount of unrecorded alcohol consumption may derive from homeproduction of fruit spirits. Some studies found a high prevalence of lead and cadmium in such spirits. This article provides a quantitative comparative risk assessment using the margin of exposure (MOE) methodology for lead and cadmium, compared to ethanol, for unrecorded fruit spirits. For average concentration levels, the lowest MOE (0.8) was calculated for ethanol (alcohol itself). For lead, the MOE was 13 for moderate daily drinking and 0.9 for the worst case. For cadmium, the MOE was 1982 for moderate daily drinking and 113 for the worst case. The results of this study are consistent with previous comparative risk assessments that ethanol itself comprises by far the highest risk of all compounds in alcoholic beverages. Regarding the metal contaminants, the risk of cadmium appears negligible, however, lead may pose an additional health risk in heavy drinking circumstances. Strategies to avoid metal contamination in settings of artisanal homeproduction of spirits need to be developed.

In this work, an operator superquadratic function (in operator sense) for positive Hilbert space operators is defined. Several examples with some important properties together with some observations which are related to the operator convexity are pointed out. Equivalent statements of a non-commutative version of Jensen's inequality for operator superquadratic function are established. A generalization of the main result to any positive unital linear map is also provided.

In quantum gravity perturbation theory in Newton's constant $G$ is known to be badly divergent, and as a result not very useful. Nevertheless, some of the most interesting phenomena in physics are often associated with non-analytic behavior in the coupling constant and the existence of nontrivial quantum condensates. It is therefore possible that pathologies encountered in the case of gravity are more likely the result of inadequate analytical treatment, and not necessarily a reflection of some intrinsic insurmountable problem. The nonperturbative treatment of quantum gravity via the Regge-Wheeler lattice path integral formulation reveals the existence of a new phase involving a nontrivial gravitational vacuum condensate, and a new set of scaling exponents characterizing both the running of $G$ and the long-distance behavior of invariant correlation functions. The appearance of such a gravitational condensate is viewed as analogous to the (equally nonperturbative) gluon and chiral condensates known to describe the physical vacuum of QCD. The resulting quantum theory of gravity is highly constrained, and its physical predictions are found to depend only on one adjustable parameter, a genuinely nonperturbative scale $\xi$ in many ways analogous to the scaling violation parameter $\Lambda_{\bar MS} $ of QCD. Recent results point to significant deviations from classical gravity on distance scales approaching the effective infrared cutoff set by the observed cosmological constant. Such subtle quantum effects are expected to be initially small on current cosmological scales, but could become detectable in future high precision satellite experiments.

Maximally similar sets (MSS) are sets of elements that share a neighborhood in a high-dimensional space defined by symmetric, reflexive similarity relation. Each element of the universe is employed as the kernel of a neighborhood of a given size (number of members), and elements are added to the neighborhood in order of similarity to the current members of the set until the desired neighborhood size is achieved. The set of neighborhoods is then reduced to the set of unique maximally similar sets by eliminating all sets that are permutations of an existing set. Subsequently, the within-MSS variability of attributes associated with the elements is compared to random sets of the same size to estimate the probability of obtaining variability as low as observed. Individual attributes can be compared for effect size by the ratio of within-MSS variability to random set variability, correcting for statistical power as necessary. The analyses performed identify constraints, as opposed to determinants, in the triangular distribution of pair-wise element similarity. In the example given here, the variability in spring temperature, summer temperature, and growing degree days of forest vegetation samples shows the greatest constraint on forest composition of a large set of candidate environmental variables

Sea ice surface roughness affects ice-atmosphere interactions, serves as an indicator of ice age, shows patterns of ice convergence and divergence, affects the spatial extent of summer melt ponds, and ice albedo. We have developed a method for mapping sea ice surface roughness using angular reflectance data from the Multi-angle Imaging SpectroRadiometer (MISR) and lidar-derived roughness measurements from the Airborne Topographic Mapper (ATM). Using an empirical data modeling approach, we derived estimates of Arctic sea ice roughness ranging from centimeters to decimeters meters within the MISR 275-m pixel size. Using independent ATM data for validation, we find that histograms of lidar and multi-angular roughness values are nearly identical for areas with roughness <20 cm but that for rougher regions, the MISR-derived roughness has a narrower range of values than the ATM data. The algorithm is able to accurately identify areas that transition between smooth and rough ice. Because of its coarser spatial scale, MISR-derived roughness data have a variance of about half that ATM roughness data.

In this work, we introduce the class of h-MN-convex functions by generalizing the concept of MN-convexity and combining it with h-convexity. Namely, let M : [0, 1] → [a, b] be a Mean function given by M (t) = M (t; a, b); where by M (t; a, b) we mean one of the following functions: A_t (a, b) := (1 − t) a + tb, G_t (a, b) = a^1−tb^t and H_t (a, b) := $\frac{ab}{ta+\left(1-t\right)b}=\frac{1}{A_t\left(\frac{1}{a},\frac{1}{b}\right)}$ with the property that M (0; a, b) = a and M (1; a, b) = b. Let I, J be two intervals subset of (0, ∞) such that (0, 1) ⊆ J and [a, b] ⊆ I. Consider a non-negative function h : J → (0, ∞), a function f : I → (0, ∞) is said to be h-MN-convex (concave) if the inequality f (M (t; x, y)) ≤ (≥) N (h(t); f (x), f (y)), holds for all x, y ∈ I and t ∈ [0, 1]. In this way, nine classes of h-MN-convex functions are established, and therefore some analytic properties for each class of functions are explored and investigated. Characterizations of each type are given. Various Jensen’s type inequalities and their converses are proved.

In this work, several inequalities of Popoviciu type for h-MN-convex functions are proved, where M and N are denote to Arithmetic, Geometric and Harmonic means and h is a non-negative superadditive or subadditive function.

Subseasonal-to-seasonal (S2S) weather forecasting has improved in recent years, thanks partly to better representation of physical variables in models. For instance, realistic initializations of snow and soil moisture in models yield enhanced predictability on S2S time scales. Snow depth and soil moisture also mediate month-to-month persistence of near-surface air temperature. Here the role of snow depth as predictor of temperature one month ahead in the Northern Hemisphere is probed via two causal pathways. Through the first pathway, snow depth anomalies in month 1 cause snow depth anomalies in month 2, which then cause temperature anomalies in month 2. This pathway represents the snow–albedo feedback, as well as cooling due to insulation, emissivity and heat loss. It is active from fall to summer, and its effect peaks in March/April in the midlatitudes and in May/June at high latitudes. A complementary second pathway, where snow depth anomalies in month 1 cause soil moisture anomalies in month 2, which then cause temperature anomalies in month 2 through soil moisture–temperature feedbacks, is only active in spring and summer. Its effect peaks later in the warm season than the effect of the first pathway. Geographically, snow depth mediates north of, and soil moisture south of, the areas with the highest temperature predictability from snow depth. These results indicate that the two pathways describe complementary physical mechanisms. The first pathway embodies month-to-month persistence of snow depth, and the second pathway represents melting of snow from one month to the next.

Marine cold air outbreaks (MCAOs) are large-scale events in which cold air masses are advected over open ocean. It is well-known that these events are linked to the formation of polar lows and other mesoscale phenomena associated with high wind speeds, and that they therefore in some cases represent a hazard to maritime activities. However, it is still unknown whether MCAOs are generally conducive to higher wind speeds than normal. Here this is investigated by comparing ocean near-surface wind speeds during MCAOs in atmospheric reanalysis products with different horizontal grid spacings, along with two case studies using a convection-permitting numerical weather prediction model. The study regions are the Labrador Sea and the Greenland–Iceland–Norwegian (GIN) Seas, where MCAOs have been shown to be important for air–sea interaction and deep water formation. One of the main findings is that wind speeds during the strongest MCAO events are higher than normal and higher than wind speeds during less severe events. Limited evidence from the case studies suggests that reanalyses with grid spacings of more than 50 km underestimate winds driven by the large ocean–atmosphere energy fluxes during MCAOs. The peak times of MCAO usually occur when baroclinic waves pass over the regions. Therefore, the strong wind episodes during MCAOs generally last for just a few days. However, MCAOs can persist for 50 days or more.

Unsupervised physics-informed deep learning can be used to solve computational physics problems by training neural networks to satisfy the underlying equations and boundary conditions without labeled data. Parameters such as network architecture and training method determine the training success. However, the best choice is unknown a priori as it is case specific. Here, we investigated network shapes, sizes, and types for unsupervised physics-informed deep learning of the two-dimensional Reynolds-averaged flow around cylinders. We trained mixed-variable networks and compared them to traditional models. Several network architectures with different shape factors and sizes were evaluated. The models were trained to solve the Reynolds-averaged Navier-Stokes equations incorporating Prandtl's mixing length turbulence model. No training data were deployed to train the models. The superiority of the mixed-variable approach was confirmed for the investigated high Reynolds number flow. The mixed-variable models were sensitive to the network shape. For the two cylinders, differently deep networks showed superior performance. The best fitting models were able to capture important flow phenomena such as stagnation regions, boundary layers, flow separation, and recirculation. We also encountered difficulties when predicting high Reynolds number flows without training data

To understand the health impacts of “hikikomori” lifestyle and to establish its first comprehensive health profile, a cross-sectional study was designed to measure how well the cases of hikikomori youths of Hong Kong were living, in terms of social, mental and physical aspects. This study involved 104 eligible participants at age 19.02 year-old who had completed the set of questionnaires and a series of anthropometric and physical health measurements. Despite SF36 score of 84.0 indicated good physical functioning in general, participants were lived sedentarily with high incidence of hypertension at 15.4% and prehypertension at 31.7%. Occurrence of hypertension in cases living as hikikomori >6 months was 3-times higher than those newly onset cases. The blood pressure levels were correlated with age and all obesity index parameters measured including waist circumference and body mass index. Half of the hypertensive cases involved the elevation of systolic blood pressure, which suggested higher odds of cardiovascular complications. Participants were mentally stable living with moderate levels of perceived stress and state anxiety, but borderline clinical depression. In conclusion, the hikikomori lifestyle could be a risk behavior that may harm the younger generation physically by promoting obesity and hypertension and probably other chronic illnesses.

Starting with unitary quantum dynamics, we investigate how to add quantum measurements. Quantum measurements have four essential components: the furcation, the witness production, an alignment projection, and the actual choice decision. The first two components still lie in the domain of unitary quantum dynamics. The decoherence concept explains the third contribution. It can be based on the requirement that witnesses reaching the end of time on the wave function side and the conjugate one have to be identical. In this way, it also stays within the quantum dynamics domain. The surjection hypothesis explains the actual choice decision. It is based on a two boundary interpretation applied to the complete quantum universe. It offers a simple way to reduce these seemingly random projections to purely deterministic unitary quantum dynamics, eliminating the measurement problem.

Semisolid casting of Aluminum alloys is growing. For magnesium alloys, Thixomoulding became the dominant process around the world. For aluminium processing, the situation is different as semisolid processing of aluminium is more technically challenging than for magnesium. Today three processes are leading the process implementation, The GISS method, the RheoMetal process and the SEED process. These processes have all strengths and weaknesses and will fit a particular range of applications. The current paper aims at looking at the strengths and weaknesses of the processes to identify product types and niche applications for each process based on current applications and development directions taken for these processes

This brief essay explores both the social and biological dimensions of human sexuality in light of the possibility of a substantial commerce in sexually-enabled robots, and concludes with some potentially strategic considerations for those who find themselves involved with their design, production, and/or marketing.

Field studies were conducted in 2016, 2017, and 2020 in south-central and the Coastal Bend regions of Texas to determine the effects of various biostimulants and soil additives on corn growth and yield. In south-central Texas, the use of pop-up fertilizer (9-30-0 + Zn) either alone or in combination with either 2% N, bifenthrin, or bifenthrin + pyraclostrobin resulted in the greatest corn vigor but a yield response was only noted with pop-up fertilizer alone at 28062 or 46771 ml ha-1 in one year. In the Coastal Bend region, leaf tissue analysis showed that only Fe was affected with the use of any soil additive. Bacillus licheniformis + bacillus megaterium + bacillus pumilus increased Fe leaf tissue content by 20% over the untreated check. Radicoat seed coating at 438 ml ha-1 reduced corn plant stand by 10% and Pseudomonas brassicaceanum reduced corn height when compared with the untreated check; however, no differences in test weight or yield from the untreated check were noted with any soil additive. Little if any impacts of the use of biostimulants or soil amendments were seen in these studies.

People with HIV (PWH) experience higher rates of cardiovascular events (CVEs) compared with the general population. A substantial body of evidence supports that select biomarkers of inflammation (soluble CD14 [sCD14], soluble CD163 [sCD163], highly sensitive C-reactive protein [hs-CRP], interleukin-6 [IL-6]), and coagulation (D-dimer) are elevated in PWH and related to increased rates of CVEs. Our previous work showed that smoking compared with nonsmoking was associated with significantly elevated sCD14, a biomarker of monocyte activation. We aimed to explore the effect of electronic cigarette (EC) provision on inflammatory biomarkers in PWH who smoked daily and then switched to an EC. Nineteen PWH were enrolled in a pilot study in which an EC and e-liquid were provided weekly or 8 weeks. Blood specimens for inflammatory biomarker analysis were obtained at baseline (BL) and at week 8. Biomarker levels were high at BL and did not differ significantly at week 8. There were small nonsignificant reductions in sCD163 and CRP levels. Non-significant increases in IL-6, D-dimer and sCD14 levels were also noted. Use of ECs for 8 weeks does not appear to significantly increase or decrease inflammatory biomarker levels in SWH. Further research with larger samples and a control group is needed.

This study investigated the characteristics of radio-frequency middle-pressure argon plasma used in the atomic layer deposition (ALD) of Al2O3 films. Based on the electrical characteristics, that is current, voltage, and phase shift between them, and stability of plasma plume, the optimum plasma power, allowing reliable switching on the plasma for any step of an ALD cycle, was determined. Spectral measurements were performed to determine the gas temperature and reactive species that could be important in the ALD process. The density of metastable argon atoms was estimated using tunable laser absorption spectroscopy. It was concluded that plasma heating of substrates did not affect film growth and proposed that the crystallization-enhancing effect of plasma was due to the action of OH radicals, produced in the plasma.

The authors present a stereotypical case presentation of x-linked hypophosphatemia (XLH) and provide a review of the pathophysiology and related pharmacology of this condition, primarily focusing on the FDA-approved medication burosumab. XLH is a renal phosphate wasting disorder caused by loss of function mutations in the PHEX gene (phosphate-regulating gene with homologies to endopeptidases on the X chromosome). Typical biochemical findings include elevated serum levels of bioactive/intact Fibroblast Growth Factor 23 (FGF23) which lead to i) low serum phosphate levels, ii) increased fractional excretion of phosphorus, and iii) inappropriately low or normal 1,25-dihydroxyvitamin D (1,25-vitD). XLH is the most common form of heritable rickets and short stature in XLH patients is due to chronic hypophosphatemia. Additionally, XLH patients experience joint pain and osteoarthritis from skeletal deformities, fractures, enthesopathy, spinal stenosis, and hearing loss. Historically, treatment for XLH was limited to oral phosphate supplementation, active vitamin D supplementation, and surgical intervention for cases of severe bowed legs. In 2018, the United States Food and Drug Administration’s (FDA) approved burosumab for the treatment of XLH and this medication has demonstrated substantial benefit compared with conventional therapy. Burosumab binds circulating intact FGF23 and blocks its biological effects in target tissues, resulting in increased serum inorganic phosphate (Pi) concentrations and increased conversion of inactive vitamin D to active 1,25-vitD.

Digital machine intelligence has evolved from its inception in the form of computation of numbers to AI, which is centered around performing cognitive tasks that humans can perform, such as predictive reasoning or complex calculations. The state of the art includes tasks that are easily described by a list of formal, mathematical rules or a sequence of event-driven actions such as modeling, simulation, business workflows, interaction with devices, etc., and also tasks that are easy to do “intuitively”, but are hard to describe formally or as a sequence of event-driven actions such as recognizing spoken words or faces. While these tasks are impressive, they fall short in applying common sense reasoning to new situations, filling in information gaps, or understanding and applying unspoken rules or norms. Human intelligence uses both associative memory and event-driven transaction history to make sense of what they are observing fast enough to do something about it while they are still observing it. In addition to this cognitive ability, all bio-logical systems exhibit autopoiesis and self-regulation. In this paper, we demonstrate how machine intelligence can be enhanced to include both associative memory and event-driven transaction history to create a new class of knowledge-based assistants to augment human intelligence. The digital assistants use global knowledge derived from the Large Language Models to bridge the knowledge gap between various participants interacting with each other. We use the general theory of information and schema-based knowledge representation to create the memory and history of various transactions involved in the interactions.

The benefits of event-driven architecture (EDA) derive from how systems and components are loosely coupled, which can facilitate independent development and deployment of systems, improved scaling and fault tolerance, and integration with external systems, especially in comparison to monolithic architectures. With the advent of new technologies such as containers, and microservices, a new generation of distributed event streaming platforms are commonly used in event-driven architecture for efficient event-driven communication. However, the asynchronous and distributed nature of EDA poses several problems that include handling failures, the dependence of an end-to-end transaction on individual component stability, etc. In this paper, we describe a new approach to designing self-regulating distributed applications with autopoietic and cognitive workflow management. This approach is based on the new science of information processing structures derived from the General Theory of Information. Just as a genome enables self-organizing and self-regulating biological structures, a digital genome enables a specific software application with several components, the ability to use distributed resources and self-regulate the evolution of the system based on functional and non-functional requirements, and best-practice policies that maintain the stability, safety, and survival under non-deterministic fluctuations in the demand for resources. In addition, cognitive workflow management assures end-to-end transaction delivery.

Axions can be stimulated to decay to photons by ambient photons of the right frequency or by photons from decay of neighboring axions. If the axion density is high enough the photon intensity can be amplified, which is a type of lasing or an axion maser. Here we review the astrophysical situations where axion lasing can appear and possibly be detected.

Shell nacre from Pinctada species has been extensively researched for managing bone defects. However, there is a gap in the research on using shell nacre as cement with improved physico-chemical properties. To address this, the current study aimed to develop a chemical curable com-posite shell nacre cement (SNC) using shell nacre powder and an organically modified ceramic resin shell nacre containing ladder-structured siloxane methacrylate (SNLSM). Different amounts of shell nacre (24, 48, and 72 weight(wt)%) were added to the SNLSM resin matrix and the effect on the physicochemical properties of the cement was studied. The composite shell nacre cement SNC 72 containing 72 wt% shell nacre exhibited significantly higher mechanical properties (com-pressive strength >100 MPa, flexural strength > 35 MPa) and low linear polymerization shrinkage (0.4%) than other compositions. SNC 72 was radiopaque and the exotherm generated during the curing of the cement was minimal. Direct contact of cured SNC 72 with L929 cells revealed the non-cytotoxic nature of the cement. Overall, the results of the study proved that the composite SNC 72 would be a promising candidate for bone defect management.

A study was conducted to predict failure stresses, failure locations, and their paths of initiation of perforated polymethyl methacrylate (PMMA) specimens as they were loaded using pins inserted into the holes. First, a series of experiments were conducted for perforated PMMA coupons. There were six different types of coupons. The test specimens had three different widths with a circular hole of a diameter of 8 mm, which was placed at two different locations along the specimen length. All the specimens were loaded using a pin inserted into the hole with three different pins of nominal diameters of 8 mm, 6 mm, and 5 mm, respectively. To predict the failure and compare the results against the experimental data, the recently proposed universal failure criterion was used in the study using finite element analyses. The failure criteria gave acceptable results as compared to the experimental data.

Sea ice roughness can serve as a proxy for other sea ice characteristics such as ice thickness and ice age. Arctic-wide maps that represent spatial patterns of sea ice roughness can be used to better characterize spatial patterns of ice convergence and divergence processes. Sea ice surface roughness can also control and quantify turbulent exchange between sea ice surface and atmosphere and therefore influence surface energy balance at the basin scale. We have developed a data processing system that produces georeferenced sea ice roughness rasters that can be mosaicked to produce Arctic-wide maps of sea ice roughness. This approach starts with Top-of-Atmosphere radiance data from the Multi-angle Imaging SpectroRadiometer (MISR). We used red-band angular data from three MISR cameras (Ca, Cf, An). We created a training data set in which MISR pixels were matched with co-located and concurrent lidar-derived roughness measurements from the Airborne Topographic Mapper (ATM). We used a K-nearest neighbor algorithm with the training data to calibrate the multi-angle data to values of surface roughness and then applied the algorithm to Arctic-wide MISR data for two 16-day periods in April (spring) and July (summer). After georeferencing the roughness rasters, we then mosaicked each 16-day roughness dataset to produce Arctic-wide maps of sea ice roughness for spring and summer. Assessment of the results shows good agreement with independent ATM roughness data, not used in model development. A preliminary exploration of spatial and seasonal changes in sea ice roughness for two locations shows the ability to characterize the roughness of different ice types and the results align with previous studies. This processing system and its data products can help the sea ice research community to gain insights into the seasonal and interannual changes in sea ice roughness over the Arctic.

The study reports about a case of a lung cancer patient with increasing difficulties in falling asleep and frequent periods of wakefulness. Severe dyspnea related to pneumonitis caused as a side effect of immunotherapy worsened the situation. Eventually, fear of falling asleep developed, including panic attacks and anxiety of choking, which was shown to lead to nights of complete wakefulness. The patient did not only sleep poorly; he did not sleep at all at night for several days, as evidenced by the notes he made during the night. Polygraphy showed no evidence of sleep-disordered breathing, but frequent periods of wakefulness and reduced basal saturation around 90% during sleep due to lung changes such as extensive functional failure of the left upper lobe with position-dependent shunts. The authors hypothesized that the symptoms described were causally related to a drop in oxygen saturation in the patient's blood. Therefore, they pursued the goal of finding a measurement technique that is as inexpensive as possible and that the patient can operate without outside assistance and great effort. So the patient started using a low-cost wearable device that allows simultaneous measurements of blood oxygen content, pulse rate and movement intensity. It consists of a finger ring with pulse oximetry sensor and a wristband with the control unit containing a vibration motor. The described device reliably warned of disturbances in oxygen concentration in the blood during the night with its vibration alarm. By use of that device during the whole night at home, the events of reduced oxygen saturation and the anxiety symptoms were reduced. Sleep disturbances with sudden awakenings did not occur when using the device. The patient benefited from the security gained in this way and slept much more peacefully, and he could spend nights without waking up again. In conclusion, wearable oximeters with vibration alarm can be recommended for patients’ home care in lung cancer patients.

In a bid to resolve lingering problems in cosmology, more focus is being tilted towards cosmological models in which physical constants of nature are not necessarily real constants, but varying with cosmic time. In this paper we have study cosmology in nonlinear electrodynamics with the Newton's gravitational constant $G$ not a constant but vary in form of power-law of the scale factor of the universe. The evolution of the scale factor $a (t)$ is studied in this model which depends on nonlinear electrodynamics fine tuning term of $\alpha$. Then we check the stability of the model using the speed of sound.

Simulating the non-perturbative and non-Markovian dynamics of open quantum systems is a very challenging many body problem, due to the need to evolve both the system and its environments on an equal footing. Tensor network and matrix product states (MPS) have emerged as powerful tools for open system models, but the numerical resources required to treat finite temperature environments grow extremely rapidly and limit their applications. In this study we use time-dependent variational evolution of MPS to expore the striking theory of Tamescelli et al. that shows how finite temperture open dyanmics can be obtained from zero temperature, i.e. pure wave function, simulations. Using this approach, we produce a benchmark data set for the dynamics of the Ohmic spin-boson model across a wide range of coupling and temperatures, and also present detailed analysis of the numerical costs of simulating non-equilibrium steady states, such as those emerging from the non-perturbative coupling of a qubit to baths at different temperatures. Despite ever growing resource requirements, we find that converged non-perturbative results can be obtained, and we discuss a number of recent ideas and numerical techniques that should allow wide application of MPS to complex open quantum systems.

It is widely, but not universally, believed that the lipids of the plasma membrane are not uniformly distributed, but that "rafts'' of sphingolipids and cholesterol float in a "sea'' of unsaturated lipids. The physical origin of such heterogeneities is often attributed to a phase coexistence between the two different domains. We argue that this explanation is untenable for several reasons. Further we note that the results of recent experiments are inconsistent with this picture. However they are quite consistent with an alternate explanation, namely that the plasma membrane is an emulsion of the two kinds of regions. To show this, we briefly review a simplified version of this theory and its phase diagram. We also explicate the dependence of the predicted domain size on four physical parameters. Among them are the spontaneous curvature of the membrane and its bending modulus and surface tension. Taking values of the latter two from experiment, we obtain domain sizes for several different cell types that vary from 58 to 88 nm.

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

Rough volatility models are popularized by \cite{gatheral2018volatility}, where they have shown that the empirical volatility in the financial market is extremely consistent with rough volatility. Fractional Riccati equation as a part of computation for the characteristic function of rough Heston model is not known in explicit form as of now and therefore, we must rely on numerical methods to obtain a solution. In this paper, we give a short introduction to option pricing theory and an overview of the current advancements on the rough Heston model.

We show that if $f$ is a non-negative superquadratic function, then $A\mapsto\mathrm{Tr}f(A)$ is a superquadratic function on the matrix algebra. In particular, \begin{align*} \tr f\left( {\frac{{A + B}}{2}} \right) +\tr f\left(\left| {\frac{{A - B}}{2}}\right|\right) \leq \frac{{\tr {f\left( A \right)} + \tr {f\left( B \right)} }}{2} \end{align*} holds for all positive matrices $A,B$. In addition, we present a Klein's inequality for superquadratic functions as $$ \mathrm{Tr}[f(A)-f(B)-(A-B)f'(B)]\geq \mathrm{Tr}[f(|A-B|)] $$ for all positive matrices $A,B$. It gives in particular improvement of Klein's inequality for non-negative convex function. As a consequence, some variants of the Jensen trace inequality for superquadratic functions have been presented.

Freshwater fish represent half of all fish species and are the most threatened vertebrate group. Given their considerable passion and knowledge, aquarium hobbyists can play a vital role in their conservation. CARES is made up of many hobbyist organizations, whose purpose is to encourage aquarium hobbyists to the most endangered or extinct-in-the-wild freshwater fish to help ensure their survival. We found the CARES priority list contains nearly six hundred species from twenty families and two dozen species extinct-in-the-wild. The major families were typically the ones with largest hobbyist affiliations such as killifish, livebearers, and cichlids; which alone were half of CARES species. CARES contained every IUCN threatened species of Pseudomugilidae and Valenciidae, but only one percent of threatened Characidae, Cobitidae, and Gobiidae species. No Loricariidae in CARES were in the IUCN red list as they were not scientifically described. Tanzania and Mexico contained the largest amount of species, with the latter containing the most endemics. A large percent of species were classified differently than the IUCN, including a third of extinct-in-the-wild species classified as least concern by the IUCN. The vast disconnect exemplifies the importance of collaboration and information exchange required between hobbyists, the scientific community, and conservation organizations.

Epidemiological studies indicate an increased risk of cancer from the consumption of very hot foods and beverages. The International Agency for Research on Cancer (IARC) has already recommended threshold values for the maximum drinking temperature of very hot beverages. The contact time and the contact temperature are decisive for the risk of injury when hot media come into contact with human skin. However, measuring the contact temperature is not easily possible in practice. In the present study, a numerical simulation based on the solution of the heat conduction equation was initially used to investigate whether and for what period of time a constant contact temperature is to be expected under oral conditions. For small circular 3-cm food samples (e.g., cooked potatoes) with 2.5 mm thickness in contact with the tongue, the simulation results in a constant contact temperature of 10 s before cooling. With a thickness of 0.5 mm, the contact temperature is only maintained 1 s. Hot beverages, which spread as a thin film and thereby increase their surface area, can therefore be consumed at higher temperatures than solid foods. Furthermore, a simple test technique with a "measuring spoon" was developed. A hot sample is placed on the tongue. Orientating measurements were used to determine which contact temperature was considered to be just comfortable for any period > 10 s and for which period of less than 10 s it was still just bearable. The contact temperature, which was still perceived as tolerable for periods > 10 s, was 46.5 °C. The time spans for the higher contact temperature 48 °C were between 2 and 4 s and for 49 °C between 1 and 2 s. The course of the contact temperatures determined in the experiment over time allows to calculate the corresponding threshold values of consumption temperatures for various foods. Consumption temperatures of about 56 °C for potatoes and 60 °C for cheese are still perceived as tolerable. In view of the fact that the contact temperature is obviously the determining factor for the risk of injury from burns in the oral cavity in addition to the contact time, it makes sense to reference threshold values to the contact temperature rather than to the surface or consumption temperature of a food product, which is current customary practice. If this contact temperature is defined as a threshold value, the surface or consumption temperature for any other food can be calculated.

Human cytomegalovirus (HCMV) is a β-herpes virus that is a significant pathogen within immune compromised populations. HCMV morbidity is induced through viral dissemination and inflammation. Typically, viral dissemination is thought to follow Fenner’s hypothesis where virus replicates at the site of infection, followed by replication in the draining lymph nodes, and eventually replicating within blood filtering organs. Although CMVs somewhat follow Fenner’s hypothesis, they deviate from it by spreading primarily through innate immune cells as opposed to cell free virus. Also, in vivo CMVs infect new cells via cell to cell spread and disseminate directly to secondary organs through novel mechanisms. We review the historic and recent literature pointing to CMV’s direct dissemination to secondary organs and the genes that it has evolved for increasing its ability to disseminate. We also highlight aspects of CMV infection for studying viral dissemination when using in vivo animal models.

This paper proposes an Integrated Fire Management (IFM) framework that can be used to support communities and resource managers in finding effective and efficient approaches to prevent damaging fires, as well as maintain desirable fire regimes in Kenya. Designing and implementing an IFM approach in Kenya calls for a systematic understanding of the various uses of fire and the underlying perceptions and traditional ecological knowledge of the local people. The here proposed IFM framework allows an evaluation of the risks posed by fires, while balancing them with their beneficial ecological and economic effects, and thus developing effective fire management approaches. A case study of the proposed IFM framework was conducted in Gathiuru Forest that is part of the larger Mt. Kenya Forest Ecosystem. Focus group discussions were held with key resource persons, primary and secondary data on socio-economic activities were studied, fire and weather records were analyzed and the current fire management plans were consulted. Questionnaires were used to assess how the IFM is implemented in the Gathiuru Forest Station. The results show that the proposed IFM framework is scalable and can be applied in places with fire-dependent ecosystems as well as in places with fire-sensitive ecosystems in Kenya. The effectiveness is dependent on the active participation, formulation and implementation of the IFM activities by the main stakeholder groups (Kenya Forest Service (KFS), Kenya Wildlife Service (KWS), and the Community Forest Associations (CFA)). The proposed IFM framework helps in implementing cost-effective approaches to prevent damaging fires and maintain desirable fire regimes in Kenya.

In the smart city, information and communications technologies (ICTs) are proposed as solutions to urban challenges, including sustainability concerns. While sustainability commonly refers to economic and environmental dimensions, the concept also contains a social component. Our study asked how smartphone applications (apps) address social sustainability challenges in urban transport, if at all. We focused on transport disadvantages experienced due to low income, physical disability, and language barriers. A review of 60 apps showed that transport apps respond to these equity and inclusion issues in two ways: (a) by employing universal design in general-use apps; including cost-conscious features; and providing language options (b) by specifically developing smartphone apps for persons with disabilities. The article discusses the study by positioning it in the literature of smart cities as well as socially sustainable transport.

Western Iran barb species are scientifically, environmentally, and economically important. Some of them are the largest riverine freshwater species, which will grow in size and weight to 170 cm, and 120 kg respectively. There is little information on taxonomy or environmental status of these species Luciobarbus barbulus is one of the important large species. During the resent year since 2013, in order to find the new record of large barb species, sampling program carried out in western Iran,. Luciobarbus barbulus briefly described by Heckel (1849) but during the time, have been synonymized with other related species or vice versa, other similar species miss-identically have been known as this species. Also the synonymy of Luciobarbus barbulus with L. pectoralis remains uncertain. The possible syntypes of L. barbulus in Vienna Museum (NMW 53957 and NMW 6596) are in too poor condition to be of any value, being mostly bones, and are dried, and. The fleshy lip of NMW 6596, (measures 119.3 mm standard length) fold of the original description could not be discerned, teeth are missing and the dorsal fin is broken off short. In 1997 this was the only syntype recognized. The catalog in Vienna lists only 1 fish, while Heckel's description refers to several fishes!. So designing of Lecotype and re-description of L. barbulus is essential. In this paper the details of description and differences between these species are given.

Western Iran barb species are scientifically, environmentally, and economically important. Some of them are the largest riverine freshwater species, which will grow in size and weight to 170 cm, and 120 kg respectively. Although these species are vulnerable, there is little information on taxonomy or environmental status of the species Luciobarbus barbulus is one of the important large species. In order to find the new record on the present status of large barb species sampling program carried out in western Iran, during the resent year since 2013 to now. This species overlaps in distinction with L. mystaceus, L scheich, and other similar species. In this study re-description of L.barbulus is given. This species differs from L. mystaceus in having thick and very wide fleshy lip, inferior mouth and slightly shorter head. In Luciobarbus barbulus head is more inferior. The details of differences between these species are given. This species is one of stable growing fish without dimorphism, retain its shape from a fingerling species to a giant fish.

We develop an interactive likelihood (ILH) for sequential Monte-Carlo (SMC) methods for image-based multiple target tracking applications. The purpose of the ILH is to improve tracking accuracy by reducing the need for data association. In addition, we integrate a recently developed deep neural network for pedestrian detection along with the ILH with a multi-Bernoulli filter. We evaluate the performance of the multi-Bernoulli filter with the ILH and the pedestrian detector in a number of publicly available datasets (2003 PETS INMOVE, AFL, and TUD-Stadtmitte) using standard, well-known multi-target tracking metrics (OSPA and CLEAR MOT). In all datasets, the ILH term increases the tracking accuracy of the multi-Bernoulli filter.

The dermatological manifestations of Long Covid (LC) have languished in the shadows of chronic fatigue and brain fog. Yet they are all linked by gut dysbiosis and the cytokine triad of TNF-α, IL-1β, and IL-6. The gut microbiome common not only to LC, psoriasis, AA, and vitiligo but also to neurodegenerative disease has been recently described. This gut microbiome induces an altered tryptophan metabolism linked to autoimmune disease. SARS CoV2 invades enterochromaffin cells rich in ACE2 receptors and curtails absorption of the essential amino acid tryptophan and subsequent synthesis of serotonin and melatonin. This review suggests that an etiologic prebiotic (d-mannose)/probiotic (lactobacilli, bifidobacteria)/postbiotic (butyrate) approach to autoimmune skin disease that improves intestinal barrier integrity and that suppresses the triad of TNF-α, IL-6, and IL-1β may enhance or even eliminate the traditional immunotherapy of targeted monoclonal antibodies, Janus kinase inhibitors, and steroids. Health benefits of this approach extend well beyond suppression of autoimmune skin disease.

Individual susceptibility to pulmonary oxygen toxicity (PO2tox) is highly variable and currently lacks a reliable biomarker for predicting pulmonary hyperoxic stress. As nitric oxide (NO) is involved in many respiratory system processes and functions, we aimed to determine if expired nitric oxide (FENO) levels can provide an indication of PO2tox susceptibility in humans. Eight U.S. Navy trained divers volunteered as subjects. The hyperoxic exposures consisted of six- and eight-hour hyperbaric chamber dives conducted on consecutive days in which subjects breathed 100% oxygen at 202.65 kPa. Subjects’ individual variability in pulmonary function and FENO was measured twice daily over five days and compared with their post-dive values to assess susceptibility to PO2tox. Only subjects who showed no decrements in pulmonary function following the six-hour exposure conducted the eight-hour dive. FENO decreased by 55% immediately following the six-hour oxygen exposure (n=8, p<0.0001) and by 63% following the eight-hour exposure (n=4, p<0.0001). Four subjects showed significant decreases in pulmonary function immediately following the six-hour exposure. These subjects had the lowest baseline FENO and the lowest post-dive FENO and had clinical symptoms of PO2tox. Individuals with low FENO were the first to develop PO2tox symptoms and deficits in pulmonary function from the hyperoxic exposures. These data suggest that endogenous levels of NO in the lung may protect against the development of PO2tox.

We reviewed various physical and biological manifestations of an unprecedented large-scale water temperature anomaly that emerged in the Northeast Pacific in late 2013. The anomaly dubbed “The Blob” persisted through 2014-2016, with some signs of its persistence through 2017-2018 and a possible reemergence in 2019. The tentative timeline of The Blob’s successive appearances around the Northeast Pacific is suggestive of its advection by currents around the Gulf of Alaska, along the Aleutians, into the Bering Sea, and eventually to the Bering Strait. During the initial phase of The Blob’s development in 2013-2014, advection along the Polar Front might have played a certain role. The extreme persistence and magnitude of The Blob resulted in numerous and sometimes dramatic ecosystem responses in the eastern Bering Sea. The multi-year duration of The Blob might have preconditioned the Bering Sea for the record low seasonal sea ice extent during the winter of 2017-2018 and disappearance of the cold pool in 2016 and 2018 that profoundly affected zooplankton, invertebrates, fishes, sea birds, and marine mammals. Comparison of time-series of population responses across trophic levels suggests that The Blob lowered primary production during spring, increasing small copepod production and jellyfish, and reducing energy transfer efficiently to higher trophic levels. While the Bering Sea’s water temperature, seasonal sea ice, and cold pool seem to return to the long-term mean state in 2022, it remains to be seen if the Bering Sea ecosystem will completely recover. The two most likely alternative scenarios envision either irreversible changes or hysteresis recovery.

The market for shark fin soup, a fashionable, high-end Chinese dish, has resulted in intensive shark fishing across all oceans. At the same time, 90% of teleost fish stocks are over-exploited, making sharks the most lucrative target: fisheries that have not previously hunted them are now. As top and middle predators, sharks have high ecological value and poor capacity to withstand fishing mortality, but though their numbers are plummeting, the secretive nature of the fin trade, along with the difficulties of obtaining relevant data, obscure their true status. In consumer countries, shark fin is a luxury item and rich consumers are willing to pay high prices. There is little interest in sustainability or legal trade. Thus market demand will continue to fuel the search for sharks and those accessible to fishing fleets are increasingly endangered. Current legal protections are not working, as is clearly seen in the case of the shortfin mako. Claims that sharks can withstand such targeted, industrial hunting and be sustainably fished under these circumstances are shown to be misguided. In the interests of averting a catastrophic collapse across the planet’s aquatic ecosystems, sharks must be given effective protection. We recommend that all sharks, chimaeras, manta rays, devil rays, and rhino rays be protected from international trade through an immediate CITES Appendix I listing. However, a binding international agreement for protection, not only of sharks, but of the loss of biodiversity in general, is what is most needed to allow marine and fresh water ecosystems to recover.

In the search for new 2D materials beyond graphene with similar exemplary properties Stanene the new graphene relative was successfully synthesized and characterized in 2016 [14]. This new material which consists of atomically thin tin (Sn) atoms arranged in a hexagonal lattice has shown great promise in gas sensing applications in its pristine, doped and functionalized forms as evidenced by the recent research outputs following its discovery. Researchers have discovered that with its exotic properties it is highly efficient in the detection of the environmentally harmful gases like SO2, NO2, CO2, NH3 and can serve as a multifunctional gas sensor. In this focused and up-to-date review we aim to group the literature on first principles studies of stanene regards to its application for gas sensing and critically examine the success/failures of its multifunctional gas sensing properties as compared to graphene. We systematically present and discusses how structural deformations, defects and doping effect the gas sensing performance. Despite the impressive progress in the field of gas sensing with stanene shown by first principles calculations, many challenges in large scale synthesis, device fabrication and commercialization need to be addressed. The current review can help understand the current status and drawbacks of stanene and identify future directions in this field.

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

Background: In 80% of patients, COVID-19 presents as mild disease^1,2. 20% of cases develop severe (13%) or critical (6%) illness. More severe forms of COVID-19 present as clinical severe acute respiratory syndrome, but include a T-predominant lymphopenia³, high circulating levels of proinflammatory cytokines and chemokines, accumulation of neutrophils and macrophages in lungs, and immune dysregulation including immunosuppression⁴. Methods: All major SARS-CoV-2 proteins were characterized using an amino acid residue variation analysis method. Results predict that most SARS-CoV-2 proteins are evolutionary constrained, with the exception of the spike (S) protein extended outer surface. Results were interpreted based on known SARS-like coronavirus virology and pathophysiology, with a focus on medical countermeasure development implications. Findings: Non-neutralizing antibodies to variable S domains may enable an alternative infection pathway via Fc receptor-mediated uptake. This may be a gating event for the immune response dysregulation observed in more severe COVID-19 disease. Prior studies involving vaccine candidates for FCoV^5,6 SARS-CoV-1^7-10 and Middle East Respiratory Syndrome coronavirus (MERS-CoV) ¹¹ demonstrate vaccination-induced antibody-dependent enhancement of disease (ADE), including infection of phagocytic antigen presenting cells (APC). T effector cells are believed to play an important role in controlling coronavirus infection; pan-T depletion is present in severe COVID-19 disease³ and may be accelerated by APC infection. Sequence and structural conservation of S motifs suggests that SARS and MERS vaccine ADE risks may foreshadow SARS-CoV-2 S-based vaccine risks. Autophagy inhibitors may reduce APC infection and T-cell depletion^{12 13}. Amino acid residue variation analysis identifies multiple constrained domains suitable as T cell vaccine targets. Evolutionary constraints on proven antiviral drug targets present in SARS-CoV-1 and SARS-CoV-2 may reduce risk of developing antiviral drug escape mutants. Interpretation: Safety testing of COVID-19 S protein-based B cell vaccines in animal models is strongly encouraged prior to clinical trials to reduce risk of ADE upon virus exposure.

The Cochran–Mantel–Haenszel (CMH) methodology is a suite of tests applicable to particular tables of count data. Inference is conditional on the treatment and outcome totals on each stratum being known before sighting the data. The CMH tests are important for analyzing randomised blocks data when the responses are categorical rather than continuous. This overview will first review the traditional CMH tests and then explore new alternative presentations of the ordinal CMH tests. Next the ordinal CMH tests will be extended so they can be used to test for higher moment effects. Finally unconditional analogues of the extended CMH tests will be developed.

We aimed to estimate for the first time the burden of fungal infections in Uruguay. Data on population characteristics and underlying conditions were extracted from the National Statistics Institute, the World Bank, national registries and published articles. When no data existed, risk populations were used to estimate frequencies extrapolating from the literature. Population structure: total 3,444,006; 73% adults; 35% women younger than 50 years. Size of populations at risk: HIV infected 12,000; acute myeloid leukemia 126; hematopoietic stem cell transplantation 30; solid organ transplants 134; COPD 272,006 (19.7% of older than 40); asthma in adults 223,431 (prevalence 9%); cystic fibrosis in adults 48; tuberculosis 613 (incidence 26.2%), lung cancer 1,400 (ASR incidence 27.4). Annual incidence estimations per 100,000: 22.4 invasive aspergillosis, 16.4 candidaemia, 3.7 Candida peritonitis, 1.62 Pneumocystis jirovecii pneumonia, 0.75 cryptococcosis, severe asthma with fungal sensitisation 217, allergic bronchopulmonary aspergillosis 165, recurrent Candida vaginitis 6,323, oral candidiasis 74.5 and oesophageal candidiasis 25.7. Although some under and overestimations could have been made, we expect that at least 127,525 people suffer from serious fungal infections each year. Sporothrichosis, histoplasmosis, paracoccidioidomycosis and dermatophytosis are known to be frequent but no data are available to make accurate estimations. Given the magnitude of the burden of fungal infections in Uruguay, efforts should be made to improve surveillance, strengthen laboratory diagnosis and warrant access to first line antifungals.

Conceal carry weapon (CCW) laws have generated a great deal of public discussion in the past decades, but little social science attention. Scholarly worked on the topic has been focused on finding potential effects of such laws on crime and victimization; little has attempted to explain the trends behind the adoption of the laws. This paper attempts to fill that gap by testing a series of hypotheses grounded in minority threat approaches. Our paper examines whether or not changes in the racial and ethnic composition of a county predict the voting outcome of Missouri’s 1999 conceal-carry referendum. Findings fail to reject the null hypothesis and show the best predictor of the vote within a county was how that county voted in the 2000 Presidential election.

We introduce two symmetric concepts to physics: “distance” (space and time in one) and “wavematter” (electromagnetic wave packet and matter in one). We claim that physics has chosen the wrong concept of time: It is not aware that the time of a moving object flows in a direction other than my time. We provide 15 proofs for our claim by solving 15 mysteries of physics graphically! For example, we prove that length contraction and time dilation are actually geometrical effects in a 4D manifold that we call “Euclidean spacetime” (ES). We prove that the discrepancy in calculating the Hubble constant stems from a systematic error in the redshift measurement. We prove that what I deem wave, deems itself matter, which solves wave–particle duality. We even untangle quantum entanglement without the issue of non-locality. We finally understand why alternative theories of Euclidean relativity have failed: They are all based on four dimensions of space rather than distance. A huge amount of energy was injected into ES at a point that we take as origin. Ever since has this energy been moving radially away at the speed of light. We live in the 3D hypersurface of an expanding 4D hypersphere. Hyperspherical coordinates have the great advantage that they reduce all that is ever happening to just one formula. So, it is the Theory of Everything in these coordinates: “Energy is covering radial distance which, divided by Euclidean time, is equal to the speed of light.” Acceleration and force like gravitation emerge from a rotation of objects in ES and a subsequent projection to 3D space. Matching the symmetry simplifies physics.

The increasingly affordable price point of terrestrial laser scanners has led to a democratization of instrument availability, but the most common low-cost instruments have yet to be compared in terms of the consistency to measure forest structural attributes. Here, we compared two low-cost terrestrial laser scanners (TLS): the Leica BLK360 and the Faro Focus 120 3D. We evaluate the instruments in terms of point cloud quality, forest inventory estimates, tree-model reconstruction, and foliage profile reconstruction. Our direct comparison of the point clouds showed reduced noise in filtered Leica data. Tree diameter and height were consistent across instruments (4.4% and 1.4% error, respectively). Volumetric tree models were less consistent across instruments, with ~29% bias, depending on model reconstruction quality. In the process of comparing foliage profiles, we conducted a sensitivity analysis of factors affecting foliage profile estimates, showing a minimal effect from instrument maximum range (for forests less than ~50 m in height) and surprisingly little impact from degraded scan resolution. Filtered unstructured TLS point clouds must be artificially re-gridded to provide accurate foliage profiles. The factors evaluated in this comparison point towards necessary considerations for future low-cost laser scanner development and application in detecting forest structural parameters.

Bioenergetics, genetic coding, and catalysis are all difficult to imagine emerging without pre-existing historical context. That context is often posed as a “Chicken and Egg” problem; its resolution is concisely described by de Grasse Tyson: “the egg was laid by a bird that was not a chicken”. The concision and generality of that answer furnish no details—only an appropriate framework from which to examine detailed paradigms that might illuminate paradoxes underlying these three life-defining biomolecular processes. We examine experimental aspects here of five examples that all conform to the same paradigm. The paradox in each example is resolved by coupling if, and only if, conditions for two related transitions between levels. One drives, and each restricts fluxes through, or “gates” the other. That reciprocally-coupled gating, in which two gated processes constrain one another, maps onto the formal structure of “strange loops”. That mapping may help unite the axiomatic foundations of genetics, bioenergetics, and catalysis. As a physical analog for Gödel’s logic, biomolecular strange-loops provide a natural metaphor around which to organize these data, linking biology to the physics of information, free energy, and the second law of thermodynamics.

Power spectra always play an important role in the theory of inflation. In particular, the ability to reproduce the galaxy matter power spectrum $ P(k) $ and the CMB temperature angular power spectrum $ C_l $’s to high accuracy is often considered a triumph of inflation. In our previous work, we presented an alternative explanation for the matter power spectrum based on nonperturbative quantum field-theoretical methods applied to Einstein’s gravity, instead of inflation models based on scalar fields. In this work, we review the basic concepts and provide further in-depth investigations. We first update the analysis with more recent data sets and error analysis, and then extend our predictions to the CMB angular spectrum coefficients $ C_l $, which we did not consider previously. Then we investigate further the potential freedoms and uncertainties associated with the fundamental parameters that are part of this picture, and show how recent cosmological data provides significant constraints on these quantities. Overall, we find good general consistency between theory and data, even potentially favoring the gravitationally-motivated picture at the largest scales. We summarize our results by outlining how this picture can be tested in the near future with increasingly accurate astrophysical measurements.

This is the second part of a series of two papers comparing the end of life issues in human and veterinary medicine. This paper adds to the review with additional new references, taking the form of an ethical argument from an independent veterinary perspective. There are some fundamental differences outlined such as patient communication, finance and ‘conflicts of interest’ between animal, owner and veterinarian but many striking similarities between human and veterinary issues such as assessing quality of life and the primary role of the attending veterinarian or doctor being the welfare and care of the patient. Clinical veterinarians are well trained in the ethics of euthanasia and are experienced in its use on a daily basis in the best interest of their animal patients. Doctors in the UK are limited and unwilling to put forward a case for the option of euthanasia for those patients who could face a slow and agonizing death due to refractory symptoms. With advances in medical science being able to significantly prolong the dying process, autonomy for the patient demands a review of the law regarding patient choice in the UK at the end of life.

Not a lot is known about either death or the dying process. Politicians and the medical profession in the UK tend to shy away from interfering with it by not allowing euthanasia as an end of life option for the patient. This is the first paper in a series of two, comparing the situation in human medicine and veterinary medicine, in which euthanasia is well practiced for relieving suffering at the end of life. This first part takes the form of a literature review including best practice around end of life care, its deficiencies and the need for assisted dying. Veterinary surgeons are well trained in the ethics of euthanasia and put it to good use in the best interest of their animal patients. In countries which have legalized physician assisted suicide for the terminally ill reporting indicates that it works well, without increases in involuntary euthanasia and most importantly without intimidation of the vulnerable. However, there is still an ever increasing tendency to overuse sedation and opioids at the end of life, which merits further investigation. With advances in medical science able to significantly prolong the dying process, patient autonomy demands a review of the law in the UK.

Forest canopy structure (CS) controls many ecosystem functions and is highly variable across landscapes, but the magnitude and scale of this variation is not well understood. We used a portable canopy lidar system to characterize variation in five categories of CS along N = 3 transects (140–800 m long) at each of six forested landscapes within the eastern USA. The cumulative coefficient of variation was calculated for subsegments of each transect to determine the point of stability for individual CS metrics. We then quantified the scale at which CS is autocorrelated using Moran’s I in an Incremental Autocorrelation analysis. All CS metrics reached stable values within 300 m but varied substantially within and among forested landscapes. A stable point of 300 m for CS metrics corresponds with the spatial extent that many ecosystem functions are measured and modeled. Additionally, CS metrics were spatially autocorrelated at 40 to 88 m, suggesting that patch scale disturbance or environmental factors drive these patterns. Our study shows CS is heterogeneous across temperate forest landscapes at the scale of 10’s of meters, requiring a resolution of this size for upscaling CS with remote sensing to large spatial scales.

Integrated energy systems (IES) seek to minimize power generating costs in future power grids through the dynamic coupling of different energy technologies. To accommodate fluctuations in load demand due to the penetration of renewable energy sources, flexible operation capabilities must be fully exploited, i.e., even power plants that are traditionally considered as base-load units need to be operated according to unconventional paradigms. Thermomechanical loads induced by frequent power adjustments can accelerate the wear and tear of components. If a unit is flexibly operated without respecting limits on materials and components, the risk of failures of expensive components will eventually increase, nullifying the additional profits ensured by flexible operation. In addition to the limits on power variations (explicit constraints), the solution of the unit dispatch problem needs to meet the limits on temperature, pressure and flow rate variations (implicit constraints). The FARM (Feasible Actuator Range Modifier) module was developed to enable existing optimization algorithms to identify solutions to the unit dispatch problem that are both economically favorable and technologically sustainable. Thanks to the iterative dispatcher-validator scheme, FARM permits addressing all the imposed constraints without excessively increasing the computational costs. In this work, the algorithms constituting the module are described, and the performance was assessed by solving the unit dispatch problem for an IES composed of three units, i.e., Balance of Plant, Gas Turbine, High-Temperature Steam Electrolysis. Finally, FARM module provides dedicated tools for visualizing the response of the process variables of interest during operation transients and a tool aiding the operator at making decisions. These techniques might represent the first step towards the deployment of an Ecological Interface Design (EID) for IES units.

Alveolar Rhabdomyosarcoma (ARMS), an invasive subtype of Rhabdomyosarcoma (RMS), is associated with chromosomal translocation events resulting in one of two oncogenic fusion genes PAX3-FOXO1 or PAX7-FOXO1. ARMS patients exhibit an overexpression of the pleiotropic cytokine Transforming growth factor beta (TGF-β). This overexpression of TGF-β1 causes an increased expression of a downstream transcription factor called SNAIL, which promotes Epithelial to Mesenchymal Transition (EMT). Overexpression of TGF-β also inhibits myogenic differentiation, making ARMS patients highly resistant to chemotherapy. In this review, we first describe different types of RMS and then focus on ARMS and the impact of TGF-β in this tumor type. We next highlight current chemotherapy strategies including a combination of FDA approved drugs vincristine, actinomycin D, and cyclophosphamide (VAC), Cabozantinib, Bortezomib, Vinorelbine, AZD 1775 and cisplatin. Lastly, we discuss chemotherapy agents that target the differentiation of tumor cells in ARMS which include all trans retinoic acid (ATRA) and 5-Azacytidine. Improving our understanding of the role of signaling pathways, such as TGF-β1, in the development of ARMS tumor cells differentiation will help inform more tailored drug administration in the future.

Physics-informed neural networks are a promising method to yield surrogate models of flow fields. We present a metamodeling technique for variable geometries based on physics-informed neural networks. The method was applied to the DU99W350 airfoil at a Reynolds number of 1×10⁵. The model predicted the Reynolds-averaged velocity and pressure field around the airfoil for arbitrary angles of attack between 10.0° and 17.5°. The model was trained with data from CFD simulations for a limited set of angles of attack. Additionally, satisfaction of the a priori known boundary conditions as well as the Reynolds-averaged Navier-Stokes equations were trained. A sensitivity analysis concerning the Reynolds number, the amount and distribution of training data, and the turbulence model was conducted showing the superiority of the pseudo-Reynolds stress method and the demand of labeled training data in the domain. The trained network was capable of predicting the developing flow separation on the suction surface and exhibited excellent agreement with CFD results even in the proximity to the wall for interpolations as well as extrapolations from the labeled data set.

Irrigation scheduling is used by growers to determine the right amount and timing of water application. In most parts of Mozambique, 90% of the total yearly precipitation occurs from November to March. The El Niño Southern Oscillation (ENSO) phenomenon influences the climate in Mozambique and affects the water demand for crop production. The objectives of this work were to quantify the effects of ENSO phenomenon on tomato crop water requirements, and to create the AgroClimate irrigation tool (http://mz.agroclimate.org/) to assist farmers in improving irrigation management. This study was based on daily grid-based climate information from 1983 to 2016 from the Climate Forecast System Reanalysis. Daily crop evapotranspiration was calculated by Hargreaves equation and crop coefficients. This tool is available online and considers different planting dates, ENSO phases, and crop growing season lengths. Irrigation needs varied from less than 250 mm per growing cycle during winter to 550 mm during spring. Both El Niño and La Niña influenced the irrigation scheduling, especially from November to March. El Niño periods were related with increased water demand due to drier and warmer conditions while the opposite was observed for La Niña. The ENSO information might be used to understand climate variability and improve tomato irrigation scheduling in Mozambique.

In this work the influence of the structure forming agent on the composition, morphology and oxygen reduction reaction (ORR) activity of Fe-N-C catalysts was investigated. As structure forming agent (SFA), dicyandiamide (DCDA) (nitrogen source) or oxalic acid (oxygen source) or mixtures thereof were used. For characterization, cyclic voltammetry and rotating disc electrode (RDE) experiments were performed in 0.1 M H2SO4. In addition to this, N2 sorption measurements and Raman spectroscopy were performed for the structural characterization. The role of metal, nitrogen and carbon sources within the synthesis of Fe-N-C catalysts has been pointed out before. Here, we show that the optimum in terms of ORR activity is achieved if both N- and O-containing SFAs are used in almost similar fractions. All catalysts display a redox couple, whereat its position depends on the fractions of SFAs. The SFA has also a strong impact on the morphology: Catalysts that were prepared with a larger fraction of N-containing SFA revealed a higher order in graphitization, indicated by bands in the 2nd order range of the Raman spectra. Nevertheless, the optimum in terms of ORR activity is obtained for the catalyst with highest D/G band ratio. Therefore, the results indicate that the presence of an additional oxygen-containing SFA is beneficial within the preparation.

The goal of this article is to provide a review of the experimental techniques and procedures using vibration methods for the Structural Health Monitoring (SHM) of Polymer-Matrix Composites (PMC). It aims to be a guide for any researchers to carry out vibration experiments. The linear methods are first introduced. But as PMC is a complex material, these classic methods showed some limits, such as low accuracy for small damages, and a high environmental dependency. This is why the nonlinear methods are secondly studied, considering that the complexity of PMC induces a nonlinear behavior of the structure after damage occurrence. The different damage mechanisms are well explained in order to evaluate the potential of each vibration method to detect them.

In this report, we establish a straightforward method for estimating the equilibrium constant for the CK reaction over wide but physiologically and experimentally relevant ranges of pH, Mg2+ and temperature. Our empirical formula for CK Keq” is based on experimental measurements. It can be used to estimate [ADP] when [ADP] is below the resolution of experimental measurements, a typical situation because [ADP] is on the order of micromolar concentrations in living cells, and may be much lower in many in vitro experiments. Accurate prediction of [ADP] is essential for in vivo studies of cellular energetics and metabolism, and for in vitro studies of ATP-dependent enzyme function under near-physiological conditions. With [ADP], we could estimate ΔGATP. Application to actomyosin force generation in muscle provides support for the hypothesis that, when [Pi] varies but not when pH is altered, maximum Ca2+-activated isometric force depends on ΔGATP in both living and permeabilized muscle preparations. Further analysis of the pH studies introduces a novel hypothesis for the role of submicromolar ADP in force generation.

Structural diversity is a key feature of forest ecosystems that influences ecosystem functions from local to macroscales. The ability to measure structural diversity in forests with varying ecological composition and management history can improve the understanding of linkages between forest structure and ecosystem functioning. Terrestrial LiDAR has often been used to provide a detailed characterization of structural diversity at local scales, but it is largely unknown whether these same structural features are detectable using aerial LiDAR data that are available across larger spatial scales. We used univariate and multivariate analyses to quantify cross-compatibility of structural diversity metrics from terrestrial versus aerial LiDAR in seven National Ecological Observatory Network sites across the eastern USA. We found strong univariate agreement between terrestrial and aerial LiDAR metrics of canopy height, openness, internal heterogeneity, and leaf area, but found marginal agreement between metrics that describe heterogeneity of the outer most layer of the canopy. Terrestrial and aerial LiDAR both demonstrated the ability to distinguish forest sites from structural diversity metrics in multivariate space, but terrestrial LiDAR was able to resolve finer-scale detail within sites. Our findings indicate that aerial LiDAR can be of use in quantifying broad-scale variation in structural diversity across macroscales.

Sea level rise (SLR) is a critical consequence of climate change, posing significant threats to coastal regions worldwide. Accurate and efficient assessment of potential inundation areas is crucial for effective coastal planning and adaptation strategies. This study aims to explore the utility of free and open source software for geospatial (FOSS4G) tools for mapping SLR inundation, providing cost-effective solutions that are accessible to researchers and policymakers. We employed a combination of geospatial data, including high-resolution elevation models, tidal data, and projected SLR scenarios. Utilizing widely available FOSS4G tools like QGIS, GDAL/OGR and GRASS GIS we developed an integrated workflow to map inundation extents using a passive bathtub approach for various SLR scenarios. Our findings demonstrate that FOSS4G tools offer reliable and accessible means to map SLR inundation, empowering stakeholders to assess coastal vulnerabilities and devise sustainable adaptation measures. The open-source approach facilitates collaboration and reproducibility, fostering a comprehensive understanding of the potential impacts of SLR on coastal ecosystems and communities.

Recent studies have revealed that several cancer cell types can upregulate inducible nitric oxide synthase (iNOS) and iNOS-derived nitric oxide (NO) after a moderate photodynamic challenge sensitized by 5-aminolevulinic acid (ALA)-induced protoporphyrin-IX. The NO signaled for cell resistance to photokilling as well as greater growth and migration/invasion aggressiveness of surviving cells. On this basis, it was predicted that diffusible NO from PDT-targeted cells in a tumor might enhance growth, migration, and invasiveness of non- or poorly PDT-targeted bystander cells. This was tested using a novel approach in which ALA-PDT targeted cancer cells on a culture dish were initially segregated from non-targeted bystander cells of the same type via impermeable silicone-rimmed rings. Several hours after LED irradiation, the rings were removed, and both cell populations analyzed in the dark for various responses. After a moderate extent of targeted cell killing (~25%), bystander proliferation and migration were evaluated, and both were found to be significantly enhanced. Enhancement corelated with iNOS/NO upregulation in surviving PDT-targeted cancer cells in the following cell type order: PC3 > MDA-MB-231 >U87 > BLM. If occurring in an actual PDT-challenged tumor, such bystander effects might compromise treatment efficacy by stimulating tumor growth and/or metastatic dissemination. Possible mitigation of these negative effects by using pharmacologic inhibitors of iNOS expression or activity as PDT adjuvants will be discussed.

High PM10 concentrations are still a significant problem in many parts of the world. In many countries, including Poland, 50μg/m3 is the permissible threshold for a daily averaged PM10 concentration. The number of people affected by this threshold’s exceedance is challenging to estimate and requires high-resolution concentration maps. This paper presents an application of random forests for downscaling regional model air quality results. As policymakers and other end users are eager to receive a detailed resolution PM10 concentration maps, we propose a technique which utilizes the results of regional CTM (GEM-AQ, with 2.5km resolution) and local Gaussian plume model. As a result, we receive a detailed, 250-meter resolution PM10 distribution, which resembles the complex emission pattern in a foothill area in southern Poland. The random forest results are highly consistent with the GEM-AQ and observed concentration. We also discuss different strategies of data training random forest - using additional features and selecting target variables.

What is the function of cognition? On one influential account, cognition evolved to co-ordinate behaviour with environmental change or complexity (Godfrey-Smith 1996). Liberal interpretations of this view ascribe cognition to an extraordinarily broad set of biological systems – even bacteria, which modulate their activity in response to salient external cues, would seem to qualify as cognitive agents. However, equating cognition with adaptive flexibility per se glosses over important distinctions in the way biological organisms deal with environmental complexity. Drawing on contemporary advances in theoretical biology and computational neuroscience, we cash these distinctions out in terms of different kinds of generative models, and the representational and uncertainty-resolving capacities they afford. This analysis leads us to propose a formal criterion for delineating cognition from other, more pervasive forms of adaptive plasticity. On this view, biological cognition is rooted in a particular kind of functional organisation; namely, that which enables the agent to detach from the present and engage in counterfactual (active) inference.

Alteration of land use and climate change are among the main variables affecting watershed hydrology. Characterizing the impacts of climate variation and land use alteration on water resources is essential in managing watersheds. Thus, in this research, streamflow and baseflow responses to climate and land use variation were modeled in two watersheds, the Upper West Branch DuPage River (UWBDR) watershed in Illinois and Walzem Creek watershed in Texas. The variations in streamflow and baseflow were evaluated using the Soil and Water Assessment Tool (SWAT) hydrological model. The alteration in land use between 1992 and 2011 was evaluated using transition matrix analysis. The non-parametric Mann-Kendall test was adopted to investigate changes in meteorological data from 1980-2017. Our results indicated that the baseflow accounted for almost 55.3% and 33.3% of the annual streamflow in the UWBDR and Walzem Creek watersheds, respectively. The contribution of both land use alteration and climate variability on the flow variation is higher in the UWBDR watershed. In Walzem Creek, the alteration in streamflow and baseflow appears to be driven by the effect of urbanization more than that of climate variability. The results reported herein are compared with results reported in recent work by the authors in order to provide necessary information for water resources management planning, as well as soil and water conservation, and to broaden the current understanding of hydrological components variation in different climate regions.

A careful examination of the fundamentals of electromagnetic theory shows that due to the underlying mathematical assumptions required for Stokes' Theorem, global charge conservation cannot be guaranteed in topologically non-trivial spacetimes. However, in order to break the charge conservation mechanism we must also allow the electromagnetic excitation fields D, H to possess a gauge freedom, just as the electromagnetic scalar and vector potentials $\varphi$ and A do. This has implications for the treatment of electromagnetism in spacetimes where black holes both form and then evaporate, as well as extending the possibilities for treating vacuum polarisation. Using this gauge freedom of D, H we also propose an alternative to the accepted notion that a charge passing through a wormhole necessarily leads to an additional (effective) charge on the wormhole's mouth.

The heavy demand of water resources from the Zarqa River Basin (ZRB) has resulted in a base-flow reduction of the River from 5m³/s to less than 1m³/s. This paper aims at predicting Curve Numbers (CN) as a baseline scenario and proposing restoration scenarios for ZRB. The method includes classifying the soil type and land use, predicting CNs, and proposing CN restoration scenarios. Prediction of existing CNs will be in parallel with the runoff prediction using the US Army Corps of Engineers HEC-1 Model, and Rainfall-Runoff Model (RRM). The models have been set up at the land use distribution of 0.3% water body, 9.3% forest and orchard, 71% mixture of grass, weeds, and desert shrubs, 7.0% crops, 4.0% urban areas, and 8.4% bare soil. The results show that CN under dry condition are 59, 78 under a normal condition and 89 under a wet condition. During vegetation period, CN are 52, 72 and 86 for the dry, normal and wet condition respectively. The restoration scenarios; CN decreases runoff, and increases soil moisture when using the contours, terraces and crop residues. Analyzing results of CN scenarios will be a fundamental tool to support end-users related to their targets to achieve watershed restoration.

It has been declared repeatedly that cancer is a result of molecular genetic abnormalities. However, there has been no working model describing the specific functional consequences of the deranged genomic processes that result in the initiation and propagation of the cancer process during carcinogenesis. We no longer need to question whether or not cancer arises as a result of a molecular genetic defect within the cancer cell. The legitimate questions are: how and why? This article reviews the preeminent data on cancer molecular genetics and subsequently proposes that the sentinel event in cancer initiation is the aberrant production of fused transcription activators with new molecular properties within normal tissue stem cells. This results in the production of vital oncogenes with dysfunctional gene activation transcription properties, which leads to dysfunctional gene regulation, the aberrant activation of transduction pathways, chromosomal breakage, activation of driver oncogenes, reactivation of stem cell transduction pathways and the activation of genes that result in the hallmarks of cancer. Furthermore, a novel holistic molecular genetic model of cancer initiation and progression is presented along with a new paradigm for the approach to personalized targeted cancer therapy, clinical monitoring and cancer diagnosis.

This article argues that there is a consistent description of gravitationally collapsed bodies, including neutron stars above the Tolman-Oppenheimer-Volkoff mass and also supermassive galactic centres, according to which collapse stops before the object reaches its gravitational radius, the density reaching a maximum close to the surface and then decreasing towards the centre. Models for such shell-like objects have been constructed using classic formulations found in the 1939 articles of Oppenheimer-Volkoff and Oppenheimer-Snyder. It was possible to modify the conclusions of the first article by changing the authors’ boundary conditions at r = 0. In the second case we find that the authors’ solution of the field equations needs no changes, but that the choice of their article’s title led many of their successors to believe that it supports the black-hole hypothesis. However, it is easily demonstrated that their final density distribution accords with the shell models found in our articles. Because black holes, according to many formulations, "have no hair", their thermodynamics is rather simple. The kind of collapsar which our models describe are more like main-sequence stars; they have spatiotemporal distributions of pressure, density and temperature, that is they have hair. In this article we shall concentrate on the dynamics of the Oppenheimer-Snyder collapsar; both pressure and temperature are everywhere zero, so there can be no thermodynamics. Only in the time independent case of Oppenheimer-Volkoff type models is it currently feasible to consider some thermodynamic implications; here some valuable new insights are obtained through the incorporation of the Oppenheimer-Snyder dynamics.

Cavitation resulting from underwater explosions in compressible multiphase or multicomp-onent flows presents significant challenges due to the dynamic nature of shock-cavitation-structure interactions, as well as the complex and discontinuous nature of the involved interfaces. Achieving accurate resolution of interfaces between different phases or components, in the presence of shocks, cavitating regions, and structural interactions, is crucial for modeling such problems. Furthermore, pressure convergence in simulations involving shock-cavitation-structure interactions requires accurate algorithms. In this research paper, we employ the diffuse interface method, also known as the interface capturing scheme, to investigate cavitation in various underwater explosion test cases near different surfaces; free surface and a rigid surface. The simulations are conducted using the Unstructured Compressible Navier-Stokes (UCNS3D) finite volume framework employing central-weighted essentially non-oscillatory (CWENO) reconstruction schemes, utilising the five-equation diffuse interface family of methods. Quantitative comparisons are made between the performance of both models. Additionally, we examine the effects of cavitation as a secondary loading source on structures, and evaluate the ability of the CWENO schemes to accurately capture and resolve material interfaces between fluids with minimal numerical dissipation or smearing. The results are compared with existing high-order methods and experimental data, where possible, to demonstrate the robustness of the CWENO schemes in simulating cavitation bubble dynamics, as well as their limitations within the current implementation of interface capturing.

The relationship between culture and the individual is a central focus of social scientific research. This paper examines motivations that mediate between shared culture norms and individual actions. Inspired by the works of Leon Festinger and Melford Spiro, we posit that social network conformation (the perceived adherence of one’s social network with norms) and internalization of cultural norms (incorporation of cultural models with the self-schema) will differentially shape behavior (cultural consonance) depending on the domain and individual characteristics. For the domain of gender roles among Brazilian men, religious affiliation results in different configurations of the individual and culture. Our findings suggest that due to changing and competing cultural models, religious men are compelled to reflexively “think” about what masculinity means to them, rather than subconsciously conform to social (hegemonic) expectations. This study demonstrates the importance of considering the impetus of culturally informed behaviors, and in doing so, provides a methodological means for measuring and interpreting such motivations, an important factor in the relationship between culture and the individual.

This study investigated how broader parental factors including parental happiness, parental play engagement, and parenting stress are related to Korean children’s happiness and weight status across three years via indirect pathways through the children’s energy-related behaviors of healthy and unhealthy food intake, physical activity, and screen time. Data from 1551 Korean parent pairs and 7-yaer-old children in the Panel Study on Korean Children were analyzed. Path analysis and gender-based structural equation modeling were conducted. Maternal happiness was negatively related to child screen time. Maternal play engagement showed positive concurrent associations with child healthy food intake and physical activity and negative associations with screen time. Maternal parenting stress was negatively related to child healthy eating. There was one significant finding related to fathers’ role on children’s energy-related behaviors, happiness, and weight status: the positive association between parental happiness and boys’ unhealthy food intake. Child screen time was positively related to child weight status and negatively to child happiness at each age. Broader maternal parenting factors can serve as a protective factor for childhood happiness and weight status in 7-to 9-year-olds through being associated with a reduction in child screen time.

Pathologic angiogenesis is responsible for much of the vision loss that stems from several chorioretinal vascular diseases including neovascular age-related macular degeneration (nAMD), diabetic retinopathy (DR), and retinal vein occlusion (RVO). Because vascular endothelial growth factor (VEGF) serves as a pivotal angiogenic molecule, it has emerged as the primary target for therapeutic drugs. Current anti-VEGF therapy is dominated by bevacizumab, ranibizumab, and aflibercept, all of which have been available for more than a decade, but new drugs, both biosimilars (Byooviz and Cimerli) and drugs whose primary aim is to decrease treatment burden (brolucizumab, faricimab, and the ranibizumab port delivery system), have been approved. Recent failures (conbercept, abicipar, and KSI-301) emphasize the complexity of drug development and the difficulties faced by innovators. Most therapies under development, including tyrosine kinase inhibitors and gene therapy, include VEGF-A blockade as their primary function and aim to extend durability rather than increase peak efficacy. But even as many new drugs look to extend durability, cost containment with mandated use of biosimilars serves to balance the therapeutic landscape.

AbstractPolyamines (PAs) including putrescine (PUT), spermidine (SPD) and spermine (SPM) are small, versatile molecules with two or more positively charged amino groups. Despite their importance for almost all forms of life, their specific roles in molecular and cellular biology remain partly unknown. The molecular structures of PAs suggest two presumable biological functions: (i) as potential buffer systems and (ii) as interactants with poly-negatively charged molecules like nucleic acids.The present report focuses on the question, whether the molecular structures of PAs are essential for such functions, or whether other simple molecules like small peptides with closely spaced positively charged side chains might be suitable as well. Consequently, we created titration curves for PUT, SPD, and SPM, as well as for oligolysines like tri-, tetra-, and penta-lysine. None of the molecules provided substantial buffering capacity at physiological intracellular pH values. Apparently, the most important mechanism for intracellular pH homeostasis in neurons is not a buffer system but is provided by the actions of the sodium-hydrogen and the bicarbonate-chloride antiporters.In a similar approach we investigated the interaction with DNA by following the extinction at 260 nm when titrating DNA with the above molecules. Again, PUT and tri-lysine were not able to interact with herring sperm DNA, while SPD and SPM were. Obviously, the presence of several positively charged groups on its own is not sufficient for the interaction with nucleic acids. Instead, the precise spacing of these groups is necessary for biological activity.

Tropical cyclones have long been known to be powered by turbulent enthalpy fluxes from the ocean surface and retarded by turbulent momentum fluxes into the surface. Here were review evidence that the development and structure of these storms are also partially controlled by turbulence in the outflow near the storm top. Finally, we present new research that shows that tropical cyclone-like, low-aspect-ratio vortices are most likely in systems in which the bottom heat flux is controlled by mechanical turbulence and the top boundary is insulating.

Cellular therapy has emerged as an attractive option for the treatment of cancer, and adoptive transfer of chimeric antigen receptor (CAR) expressing T cells has gained FDA approval in hematologic malignancy. However, limited efficacy has been observed utilizing CAR-T therapy in solid tumors. Natural killer (NK) cells are crucial for tumor surveillance and exhibit potent killing capacity of aberrant cells in an antigen-independent manner. Adoptive transfer of unmodified allogeneic or autologous NK cells has shown limited clinical benefit due to factors including low cell number, low cytotoxicity and failure to migrate to tumor sites. To address these problems, immortalized and autologous NK cells have been genetically engineered to express high affinity receptors (CD16), CARs directed against surface proteins (PD-L1, CD19, Her2, etc.) and endogenous cytokines (IL-2 and IL-15) that are crucial for NK cell survival and cytotoxicity, with positive outcomes reported by several groups both preclinically and clinically. With a multitude of NK cell-based therapies currently in clinic trials, it is likely they will play a crucial role in next-generation cell therapy-based treatment. In this review we will highlight the recent advances and limitations of allogeneic, autologous and genetically enhanced NK cells used in adoptive cell therapy.

The change in both streamflow and baseflow in urban catchments has received significant attention in the latest decades as a result of their drastic variability. In this research, effects of climate variation and dynamics of land use are measured separately and in combination on streamflow and baseflow in the Little Eagle Creek (LEC) watershed (Indianapolis, Indiana). These effects are examined using land use maps, statistical tests, and hydrological modeling. Transition matrix analysis was used to investigate the change in land use between 1992 and 2011. Temporal trends and changes in meteorological data were evaluated from 1980-2017 using the Mann-Kendall test. Changes in streamflow and baseflow were assessed using the Soil and Water Assessment Tool (SWAT) hydrological model using multiple scenarios that varied in land use and climate change. Evaluation of the model outputs showed streamflow and baseflow in LEC are well represented using SWAT; however, comparing the calibration and validation period showed SWAT performs better for the calibration. During 1992-2011, roughly 30% of the watershed experienced change, typically cultivated agricultural areas became urbanized. Baseflow is significantly affected by the observed urbanization; however, the combination of land and climate variability has a larger effect on the baseflow in LEC. Generally, the variability in the baseflow and streamflow appears to be heavily driven by the response to climate change in comparison to variability due to altered land use. The results reported herein expand the current understanding of variation in hydrological components, and provides useful information for management planning regarding water resources, as well as water and soil conservation in urban watersheds in Indiana and beyond.

Reducing sedentary behaviours can help prevent non-communicable diseases, particularly among young adolescents with long term illnesses or disabilities (LTID). Much of young people’s voluntary sedentary time is related to screen-time behaviours (STBs) such as TV viewing, playing computer games, and using the computer for other activities. Although public health data on adolescents’ STB is growing, information about adolescents with LTID is currently lacking in a European context. The purpose of this study is to compare time on STBs between adolescents with and without LTID in European Countries through the HBSC 2013/14 study. Young adolescents (n = 61,329; boys 47.8%) from 15 European countries reported the time spent on TV viewing, playing computer games, and using the computer for other purposes on weekdays and the weekend. STBs were dichotomised based on international recommendations of less than 2 h per day, and Chi-square tests of independence were performed to investigate differences. STB time was combined to produce a sum score as dependent variable in multiple analysis of covariance with age and family affluence as covariates. There were statistically significant differences in computer gaming among boys and other computer use among girls for both weekdays and weekends, whereby adolescents with LTID reported higher use. In addition, both boys and girls with LTID spent more time on STBs than their same sex peers without LTID (Boys, F = 28.17, p < 0.001; Girls, F = 9.60, p = 0.002). The results of this study indicate a need for preventive strategies to address high levels of STB among young adolescents with LTID and reduce the risk of poor health outcomes associated with higher levels of sedentary behaviour.

1) Background: In service business areas, design enhances the customer experience through the elements which anticipate specific emotional responses of customers. Many service companies are keen to develop and examine design elements from the customer perspective. Furthermore, recently, having considered the significance of customers’ emotional responses by design elements, categorising design elements into manageable dimensions can facilitate the evaluation of design elements. However, design elements and dimensions of design value are not defined in the current service marketing literature, and companies need a measurement tool and managerial guideline to their innovative value creation and compelling service delivery. For these reasons, this research aims to categorise the design value dimensions and propose the managerial implication for the innovative use of design; 2) Methods: This study used the mixed methodology; two stages of interviews and SEM (Structural Equation Modelling); 3) Results: Interview analyses facilitate the identification of design elements in the service delivery process. SEM results underpin the relevance of the categorised design elements and their impact on customer loyalty by comparing different groups (country and time elapsed from experience); and 4) Conclusions: Findings are the fundamentals of developing measuring tool for design and trigger future studies for conceptualising intangible assets.

Work reviews the new isolated isolated cembranoid diterpene derivatives from species belonging to the family Alcyoniidae, which comprises the genera Sarcophyton, Sinularia, and Lobophytum as well as their biological properties, during 2016–2017. The compilation permitted to conclude that much more new cembranoid diterpenes were found in the soft corals of the genus Sarcophyton sp. (33 new compounds) than in those belonging to the genera Lobophytum (17) or Sinularia (8). Several methods have been used for identifying these new compounds, after extraction with organic solvents and fractionation. The fractions obtained, in some cases, were followed by TLC, and again subjected to chromatographic procedures, including semi-preparative HPLC. Beyond the chemical composition, the biological properties were also evaluated, namely anti-microbial against several Gram-positive and Gram-negative bacteria and fungi, anti-inflammatory and anti-tumoral against several types of cancer cells. Although the biological activities detected in almost all samples, they were not outstanding ones.

The International Agency for Research on Cancer (IARC) evaluates “very hot (>65 °C) beverages” as probably carcinogenic to humans. However, there is a lack of research regarding what temperatures consumers actually perceive as “very hot” or as “too hot”. A methodology for organoleptical assessment of such threshold temperatures was developed. The participants were asked to mix a very hot coffee step by step into a cooler coffee. Because of that, the coffee to be tasted was incrementally getting hotter during the test. The participants took a sip at every addition, until they perceive the beverage as too hot for consumption. The protocol was evaluated using 87 participants. Interestingly, the average pain threshold of the test group (67 °C) and the preferred drinking temperature (63 °C) iterated around the IARC threshold for carcinogenicity. The developed methodology was found as fit for the purpose and may be applied in larger studies.

Introduction: Digitalis use in patients with severe heart failure is controversial. We assessed the effects of digitalis therapy on mortality in a large, observational study in recipients of cardiac resynchronization therapy (CRT). Methods: Consecutive patients receiving a CRT-defibrillator in three European tertiary referral centers were enrolled and followed for a median of 28 months. Digitalis use was assessed at the time of CRT implantation. Multivariate Cox-regression model and propensity score matching was used to determine all-cause mortality as primary endpoint. CRT-response (defined as improvement of ≥1 NYHA class), echocardiographic improvement (defined as improvement of LVEF of ≥ 5%), and ICD shocks were assessed as secondary endpoints. Results: The study comprised 552 CRT recipients with standard indications, including 219 patients (40%) treated with digitalis. Compared to patients without digitalis, they had more often atrial fibrillation, poorer LVEF and higher NYHA class (all p ≤ 0.002). Crude analysis of all-cause mortality demonstrated a similar relative risk of death for patients with and without digitalis (HR=1.14; 95% CI 0.88-1.5; p=0.40). After adjustment for independent predictors of mortality, digitalis therapy did not alter the risk for death (adjusted HR=1.04; 95% CI 0.75-1.45; p=0.82). Also, in comparison to 286 propensity score matched patients, mortality was not affected by digitalis intake (propensity adjusted HR=1.11; 95% CI 0.72-1.70; p=0.64). CRT response was predominant in digitalis non-users concerning both improvement of HF symptoms and LVEF (NYHA p<0.01; LVEF p<0.01) while patients on digitalis had more often ventricular tachyarrhythmias requiring ICD shock (p=0.01). Conclusions: Digitalis therapy had no effect on mortality but did negatively affect CRT response and susceptibility to ventricular arrhythmias requiring ICD shock treatment.

Alcohol consumption is now common practice worldwide, and functional brain networks are beginning to reveal the complex interactions observed with alcohol consumption and abstinence. The autonomic nervous system (ANS) has a well-documented relationship with alcohol use, and a growing body of research is finding links between the ANS and functional brain networks. This study recruited everyday drinkers in an effort to uncover the relationship between alcohol abstinence, ANS function, and whole brain functional brain networks. Participants (n=29), 24-60 years-of-age, consumed moderate levels of alcohol regularly (males 2.4 (±0.26) drinks/day, females 2.3 (±0.96) drinks/day). ANS function, specifically cardiac vagal tone, was assessed using the Porges-Bohrer method for calculating respiratory sinus arrhythmia (PBRSA). Functional brain networks were generated from resting-state MRI scans obtained following 3-day periods of typical consumption and abstinence. A multi-task mixed-effects regression model determined the influences of HRV and drinking state on functional network connectivity. Results showed differences in the relationship between the strength of network connections and clustering coefficients across drinking states, moderated by PBRSA. Increases in connection strength between highly clustered nodes during abstinence as PBRSA increases demonstrates a greater possible range of topological configurations at high PBRSA values. This novel finding begins to shed light on the complex interactions between typical alcohol abstinence and physiological responses of the central and autonomic nervous system.

Transport electrification is essential for reducing CO2 emissions, and technologies such as hybrid and range-extended electric vehicles will play a crucial transitional role. Such vehicles employ an internal combustion engine for on-board chemical energy conversion. The Wankel rotary engine should be an excellent candidate for this purpose, offering high power-to-weight ratio, simplicity, compactness, perfect balance, and low cost. Until recently, however, it has not been in production in the automotive market, due, in part, to relatively low combustion efficiency and high fuel consumption and unburnt hydrocarbon emissions, which can be traced to constraints on flame speed, an elongated combustion chamber, and relatively low compression ratios. This work uses large-eddy simulation to study the in-chamber flow in a peripherally ported 225cc Wankel rotary engine, providing insight into these limitations. Flow structures created during the intake phase play a key role in turbulence production but presence of the pinch point inherent to Wankel engine combustion chambers inhibits flame propagation. Two efficiency-enhancement technologies are introduced as disruptive solutions: (i) pre-chamber jet ignition and (ii) the two-stage rotary engine. These concepts overcome the traditional efficiency limitations and show that Wankel rotary engine design can be further enhanced for its role as a range extender in electrified vehicles.

The challenge of campus design, like other aspects of contemporary environmental design, reveals a serious problem in education and practice. The foundational design theories of a century ago have been exposed as an obsolete way of thinking about cities, human nature, biological nature, and even the nature of mathematical and physical structures. Yet in practice, these discredited models persist, obscured by new theoretical language and extravagant “neoplastic” forms, but embodying persistent though untested ideologies and driven by systems inertia. This paper considers the campus design typology (including business campuses, commercial districts, hospitals, and schools) as a design paradigm for pedestrian public space with implications for human flourishing and well-being. We propose a specific human-oriented design method to encourage the well-being of occupants and improve the outcomes for creative development, education, and health.

Extrusion-based additive manufacturing (AM) technologies (i.e., fused filament fabrication, FFF) mostly produce thermoplastic parts. However, producing metallic or ceramic parts by FFF is also a sintered-based AM process. FFF for metallic parts can be divided into five steps: (1) raw materials selection and feedstock mixture (including palletization), (2) filament production (extrusion), (3) production of AM components using the filament extrusion process, (4) debinding, and (5) sintering. These steps are interrelated, where the parameters interact with the other ones and have a key role in the integrity and quality of the final metallic parts. FFF can produce high-accuracy and complex metallic parts, potentially revolutionizing the manufacturing industry and taking AM components to a new level. In the FFF technology for metallic materials, material compatibility, production quality, and cost-effectiveness are the challenges to overcome to make it more competitive compared to other AM technologies, like the laser processes. This review provides a comprehensive overview of the recent developments in FFF for metallic materials, including the metals and binders used, the challenges faced, potential applications, and the impact of FFF on the manufacturing (prototyping and end parts), design freedom, customization, sustainability, supply chain, among others.