Elevating zero dimensional global scaling predictions to self-consistent theory-based simulations

We have developed an innovative workflow, STEP-0D, within the OMFIT integrated modelling framework. Through systematic validation against the International Tokamak Physics Activity (ITPA) global H-mode confinement database, we demonstrated that STEP-0D, on average, predicts the energy confinement time with a mean relative error (MRE) of less than 19%. Moreover, this workflow showed promising potential in predicting plasmas for proposed fusion reactors such as ARC, EU-DEMO, and CFETR, indicating moderate H-factors between 0.9 and 1.2. STEP-0D allows theory-based prediction of tokamak scenarios, beginning with zero-dimensional (0D) quantities. The workflow initiates with the PRO-create module, generating physically consistent plasma profiles and equilibrium using the same 0D quantities as the IPB98(y,2) confinement scaling. This sets the starting point for the STEP (Stability, Transport, Equilibrium, and Pedestal) module, which further iterates between theory-based physics models of equilibrium, core transport, and pedestal to yield a self-consistent solution. Given these attributes, STEP-0D not only improves the accuracy of predicting plasma performance but also provides a path towards a novel fusion power plant (FPP) design workflow. When integrated with engineering and costing models within an optimization, this new approach could eliminate the iterative reconciliation between plasma models of varying fidelity. This potential for a more efficient design process underpins STEP-0D's significant contribution to future fusion power plant development.Comment: 12 pages, 13 figures, accepted by Physics of Plasmas 202

Solvent and thermal stability, and pH kinetics, of proline-specific dipeptidyl peptidase IV-like enzyme from bovine serum

Proline-specific dipeptidyl peptidase-like (DPP IV; EC 3.4.14.5) activity in bovine serum has attracted little attention despite its ready availability and the paucity of useful proline-cleaving enzymes. Bovine serum DPP IV-like peptidase is very tolerant of organic solvents, particularly acetonitrile: upon incubation for 1 h at room temperature in 70% acetonitrile, 47% dimethylformamide, 54% DMSO and 33% tetrahydrofuran (v/v concentrations) followed by dilution into the standard assay mixture, the enzyme retained half of its aqueous activity. As for thermal performance in aqueous buffer, its relative activity increased up to 50 ◦C. Upon thermoinactivation at 71 ◦C, pH 8.0 (samples removed periodically, cooled on ice, then assayed under optimal conditions), residual activities over short times fit a first-order decay with a k-value of 0.071±0.0034 min−1. Over longer times, residual activities fit to a double exponential decay with k1 and k2 values of 0.218±0.025 min−1 (46±4% of overall decay) and 0.040±0.002 min−1 (54±4% of overall decay), respectively. The enzyme’s solvent and thermal tolerances suggest that it may have potential for use as a biocatalyst in industry. Kinetic analysis with the fluorogenic substrate Gly-Pro-7-aminomethylcoumarin over a range of pH values indicated two pK values at 6.18±0.07 and at 9.70±0.50. We ascribe the lower value to the active site histidine; the higher may be due to the active site serine or to a free amino group in the substrate

Genetic Risk Score for Essential Hypertension and Risk of Preeclampsia

Preeclampsia is a hypertensive complication of pregnancy characterized by novel onset of hypertension after 20 weeks gestation, accompanied by proteinuria. Epidemiological evidence suggests that genetic susceptibility exists for preeclampsia; however, whether preeclampsia is the result of underlying genetic risk for essential hypertension has yet to be investigated. Based on the hypertensive state that is characteristic of preeclampsia, we aimed to determine if established genetic risk scores (GRSs) for hypertension and blood pressure are associated with preeclampsia

Telehealth in Medicine: Predictions 2023–2024

Each year, Telehealth and Medicine Today asks experts in the field to share their insights into the future and predict how telehealth will influence uptake and healthcare in the new year

Growth characteristics in individuals with osteogenesis imperfecta in North America: results from a multicenter study.

PurposeOsteogenesis imperfecta (OI) predisposes people to recurrent fractures, bone deformities, and short stature. There is a lack of large-scale systematic studies that have investigated growth parameters in OI.MethodsUsing data from the Linked Clinical Research Centers, we compared height, growth velocity, weight, and body mass index (BMI) in 552 individuals with OI. Height, weight, and BMI were plotted on Centers for Disease Control and Prevention normative curves.ResultsIn children, the median z-scores for height in OI types I, III, and IV were -0.66, -6.91, and -2.79, respectively. Growth velocity was diminished in OI types III and IV. The median z-score for weight in children with OI type III was -4.55. The median z-scores for BMI in children with OI types I, III, and IV were 0.10, 0.91, and 0.67, respectively. Generalized linear model analyses demonstrated that the height z-score was positively correlated with the severity of the OI subtype (P < 0.001), age, bisphosphonate use, and rodding (P < 0.05).ConclusionFrom the largest cohort of individuals with OI, we provide median values for height, weight, and BMI z-scores that can aid the evaluation of overall growth in the clinic setting. This study is an important first step in the generation of OI-specific growth curves

Flukicidal effects of abietane diterpenoid derived analogues against the food borne pathogen Fasciola hepatica.

Control of liver fluke infections remains a significant challenge in the livestock sector due to widespread distribution of drug resistant parasite populations. In particular, increasing prevalence and economic losses due to infection with Fasciola hepatica is a direct result of drug resistance to the gold standard flukicide, triclabendazole. Sustainable control of this significant zoonotic pathogen, therefore, urgently requires the identification of new anthelmintics. Plants represent a source of molecules with potential flukicidal effects and, amongst their secondary metabolites, the diterpenoid abietic acids can be isolated in large quantities. In this study, nineteen (19) chemically modified abietic acid analogues (MC_X) were first evaluated for their anthelmintic activities against F. hepatica newly excysted juveniles (NEJs, from the laboratory-derived Italian strain); from this, 6 analogues were secondly evaluated for their anthelmintic activities against adult wild strain flukes. One analogue, MC010, was progressed further against 8-week immature- and 12-week mature Italian strain flukes. Here, MC010 demonstrated moderate activity against both of these intra-mammalian fluke stages (with an adult fluke EC50 = 12.97 µM at 72 h post culture). Overt mammalian cell toxicity of MC010 was inferred from the Madin-Darby bovine kidney (MDBK) cell line (CC50 = 17.52 µM at 24 h post culture) and demonstrated that medicinal chemistry improvements are necessary before abietic acid analogues could be considered as potential anthelmintics against liver fluke pathogen

The Importance of Human FcγRI in Mediating Protection to Malaria

The success of passive immunization suggests that antibody-based therapies will be effective at controlling malaria. We describe the development of fully human antibodies specific for Plasmodium falciparum by antibody repertoire cloning from phage display libraries generated from immune Gambian adults. Although these novel reagents bind with strong affinity to malaria parasites, it remains unclear if in vitro assays are predictive of functional immunity in humans, due to the lack of suitable animal models permissive for P. falciparum. A potentially useful solution described herein allows the antimalarial efficacy of human antibodies to be determined using rodent malaria parasites transgenic for P. falciparum antigens in mice also transgenic for human Fc-receptors. These human IgG1s cured animals of an otherwise lethal malaria infection, and protection was crucially dependent on human FcγRI. This important finding documents the capacity of FcγRI to mediate potent antimalaria immunity and supports the development of FcγRI-directed therapy for human malaria

Kochen-Specker Vectors

We give a constructive and exhaustive definition of Kochen-Specker (KS) vectors in a Hilbert space of any dimension as well as of all the remaining vectors of the space. KS vectors are elements of any set of orthonormal states, i.e., vectors in n-dim Hilbert space, H^n, n>3 to which it is impossible to assign 1s and 0s in such a way that no two mutually orthogonal vectors from the set are both assigned 1 and that not all mutually orthogonal vectors are assigned 0. Our constructive definition of such KS vectors is based on algorithms that generate MMP diagrams corresponding to blocks of orthogonal vectors in R^n, on algorithms that single out those diagrams on which algebraic 0-1 states cannot be defined, and on algorithms that solve nonlinear equations describing the orthogonalities of the vectors by means of statistically polynomially complex interval analysis and self-teaching programs. The algorithms are limited neither by the number of dimensions nor by the number of vectors. To demonstrate the power of the algorithms, all 4-dim KS vector systems containing up to 24 vectors were generated and described, all 3-dim vector systems containing up to 30 vectors were scanned, and several general properties of KS vectors were found.Comment: 19 pages, 6 figures, title changed, introduction thoroughly rewritten, n-dim rotation of KS vectors defined, original Kochen-Specker 192 (117) vector system translated into MMP diagram notation with a new graphical representation, results on Tkadlec's dual diagrams added, several other new results added, journal version: to be published in J. Phys. A, 38 (2005). Web page: http://m3k.grad.hr/pavici

An environmental study of the ultraluminous X-ray source population in early-type galaxies

Ultraluminous X-ray sources (ULXs) are some of the brightest phenomena found outside of a galaxy's nucleus, and their explanation typically invokes accretion of material onto a black hole. Here, we perform the largest population study to date of ULXs in early-type galaxies, focusing on whether a galaxy's large-scale environment can affect its ULX content. Using the AMUSE survey, which includes homogeneous X-ray coverage of 100 elliptical galaxies in the Virgo cluster and a similar number of elliptical galaxies in the field (spanning stellar masses of 108-1012 M ☉), we identify 37.9 ± 10.1 ULXs in Virgo and 28.1 ± 8.7 ULXs in the field. Across both samples, we constrain the number of ULXs per unit stellar mass, i.e., the ULX specific frequency, to be 0.062 ± 0.013 ULXs per 10 10 M ☉ (or about 1 ULX per 1.6 × 10 11 M ☉ of galaxy stellar mass). We find that the number of ULXs, the specific frequency of ULXs, and the average ULX spectral properties are all similar in both cluster and field environments. Contrary to late-type galaxies, we do not see any trend between specific ULX frequency and host galaxy stellar mass, and we show that dwarf ellipticals host fewer ULXs than later-type dwarf galaxies at a statistically meaningful level. Our results are consistent with ULXs in early-type galaxies probing the luminous tail of the low-mass X-ray binary population, and are briefly discussed in context of the influence of gravitational interactions on the long-term evolution of a galaxy's (older) stellar population