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At least 145 records · Page 8

Time-dependent oral absorption models

The plasma concentration-time profiles following oral administration of drugs are often irregular and cannot be interpreted easily with conventional models based on first- or zero-order absorption kinetics and lag time. Six new models were developed using a time-dependent absorption rate coefficient, ka(t), wherein the time dependency was varied to account for the dynamic processes such as changes in fluid absorption or secretion, in absorption surface area, and in motility with time, in the gastrointestinal tract. In the present study, the plasma concentration profiles of propranolol obtained in human subjects following oral dosing were analyzed using the newly derived models based on mass balance and compared with the conventional models. Nonlinear regression analysis indicated that the conventional compartment model including lag time (CLAG model) could not predict the rapid initial increase in plasma concentration after dosing and the predicted Cmax values were much lower than that observed. On the other hand, all models with the time-dependent absorption rate coefficient, ka(t), were superior to the CLAG model in predicting plasma concentration profiles. Based on Akaike's Information Criterion (AIC), the fluid absorption model without lag time (FA model) exhibited the best overall fit to the data. The two-phase model including lag time, TPLAG model was also found to be a good model judging from the values of sum of squares. This model also described the irregular profiles of plasma concentration with time and frequently predicted Cmax values satisfactorily. A comparison of the absorption rate profiles also suggested that the TPLAG model is better at prediction of irregular absorption kinetics than the FA model. In conclusion, the incorporation of a time-dependent absorption rate coefficient ka(t) allows the prediction of nonlinear absorption characteristics in a more reliable manner.

Non-NASA Center↗

Expected sensitivity to 128 Te neutrinoless double beta decay with the CUORE TeO 2 cryogenic bolometers

The CUORE experiment is a ton-scale array of TeO 2 cryogenic bolometers located at the underground Laboratori Nazionali del Gran Sasso of Istituto Nazionale di Fisica Nucleare (INFN), in Italy. The CUORE detector consists of 988 crystals operated as source and detector at a base temperature of ~ 10 mK. Such cryogenic temperature is reached and maintained by means of a custom built cryogen-free dilution cryostat, designed with the aim of minimizing the vibrational noise and the environmental radioactivity. The primary goal of CUORE is the search for neutrinoless double beta decay of 130 Te , but thanks to its large target mass and ultra-low background it is suitable for the study of other rare processes as well, such as the neutrinoless double beta decay of 128 Te. This tellurium isotope is an attractive candidate for the search of this process, due to its high natural isotopic abundance of 31.75%. The transition energy at (866.7 ± 0.7) keV lies in a highly populated region of the energy spectrum, dominated by the contribution of the two-neutrino double beta decay of 130 Te. As the first ton-scale infrastructure operating cryogenic TeO 2 bolometers in stable conditions, CUORE is able to achieve a factor > 10 higher sensitivity to the neutrinoless double beta decay of this isotope with respect to past direct experiments.

128-Te↗

Field Theory of the Fermi Function

The Fermi function F ( Z , E ) accounts for QED corrections to beta decays that are enhanced at either small electron velocity β or large nuclear charge Z . For precision applications, the Fermi function must be combined with other radiative corrections and with scale- and scheme-dependent hadronic matrix elements. We formulate the Fermi function as a field theory object and present a new factorization formula for QED radiative corrections to beta decays. We provide new results for the anomalous dimension of the corresponding effective operator complete through three loops, and resum perturbative logarithms and π enhancements with renormalization-group methods. Our results are important for tests of fundamental physics with precision beta decay and related processes. Published by the American Physical Society 2024

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗

The crack problem in bonded nonhomogeneous materials

The plane elasticity problem for two bonded half planes containing a crack perpendicular to the interface was considered. The effect of very steep variations in the material properties near the diffusion plane on the singular behavior of the stresses and stress intensity factors were studied. The two materials were thus, assumed to have the shear moduli mu(o) and mu(o) exp (Beta x), x=0 being the diffusion plane. Of particular interest was the examination of the nature of stress singularity near a crack tip terminating at the interface where the shear modulus has a discontinuous derivative. The results show that, unlike the crack problem in piecewise homogeneous materials for which the singularity is of the form r/alpha, 0 less than alpha less than 1, in this problem the stresses have a standard square-root singularity regardless of the location of the crack tip. The nonhomogeneity constant Beta has, however, considerable influence on the stress intensity factors.

Erdogan, Fazil↗

The crack problem in bonded nonhomogeneous materials

The plane elasticity problem for two bonded half planes containing a crack perpendicular to the interface was considered. The effect of very steep variations in the material properties near the diffusion plane on the singular behavior of the stresses and stress intensity factors were studied. The two materials were thus, assumed to have the shear moduli mu(o) and mu(o) exp (Beta x), x=0 being the diffusion plane. Of particular interest was the examination of the nature of stress singularity near a crack tip termination at the interface where the shear modulus has a discontinuous derivative. The results show that, unlike the crack problem in piecewise homogeneous materials for which the singularity is of the form r/alpha, 0 less than alpha less than 1, in this problem the stresses have a standard square-root singularity regardless of the location of the crack tip. The nonhomogeneity constant Beta has, however, considerable influence on the stress intensity factors.

Erdogan, F.↗

Model-Independent Determination of Nuclear Weak Form Factors and Implications for Standard Model Precision Tests

We analyze the recoil corrections in superallowed beta decays of T = 1, J P = 0 + nuclei by fixing the mean square charged weak radius model independently using the data of multiple charge radii across the nuclear isotriplet. By comparing to model estimations, we argue that the existing theory uncertainty in the statistical rate function f might have been substantially underestimated. Here, we discuss the implications of our proposed strategy for precision tests of the standard model, including a potential alleviation of the first-row CKM unitarity deficit, and motivate new experiments for charge radii measurements.

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗

MHD stability and disruptions in the SPARC tokamak

SPARC is being designed to operate with a normalized beta of $β_N$ = 1.0, a normalized density of $n_G$ = 0.37 and a safety factor of $q_{95}$ ≈ 3.4, providing a comfortable margin to their respective disruption limits. Further, a low beta poloidal $β_p$ = 0.19 at the safety factor $\textit{q}$ = 2 surface reduces the drive for neoclassical tearing modes, which together with a frozen-in classically stable current profile might allow access to a robustly tearing-free operating space. Although the inherent stability is expected to reduce the frequency of disruptions, the disruption loading is comparable to and in some cases higher than that of ITER. The machine is being designed to withstand the predicted unmitigated axisymmetric halo current forces up to 50 MN and similarly large loads from eddy currents forced to flow poloidally in the vacuum vessel. Runaway electron (RE) simulations using GO+CODE show high flattop-to-RE current conversions in the absence of seed losses, although NIMROD modelling predicts losses of ~80 %; self-consistent modelling is ongoing. A passive RE mitigation coil designed to drive stochastic RE losses is being considered and COMSOL modelling predicts peak normalized fields at the plasma of order 10 –2 that rises linearly with a change in the plasma current. Massive material injection is planned to reduce the disruption loading. A data-driven approach to predict an oncoming disruption and trigger mitigation is discussed.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗

Observations of multiple nucleus galaxies

Disturbed galaxies with two nuclei display the final state of the interaction process of two galaxies (Kollatschny et al., 1986; Fricke and Kollatschny, 1989). A few of these double nucleus galaxies contain Seyfert nuclei. Making the assumption that the Seyfert galaxies Mkn 231 and Mkn 273 are galaxies in the final state of merging, having strong tidal arms but unresolved nuclei, one can estimate that 4 percent of all Seyfert galaxies are in the merging process. The luminosities of multiple nucleus Seyfert galaxies are extremely high in comparison to morphologically undisturbed Seyfert galaxies. In a table, mean values of the visual and blue luminosities and of the far-infrared and radio (6 cm) luminosities as well as the H alpha fluxes are listed for both classes are shown. In addition, the authors have separated Seyfert 1 and Seyfert 2 galaxies. In all cases the luminosities of double nucleus Seyfert galaxies are higher by a factor of more than two with respect to undisturbed Seyfert galaxies. This result might be explained by higher luminosities in the early phases of a Seyfert's life-under the assumption that the nonthermal activity is triggered by tidal interaction-and/or additional strong starburst phenomena. Due to strong nuclear absorption, the UV spectra of these Seyfert nuclei are unusually weak. Corresponding to the Seyfert survey, the authors obtained the H alpha and far infrared radiation (FIR) luminosities as well as the (0III)5007/H beta line ratios of a small sample of non-Seyfert nuclei in double nucleus galaxies. The direct image and the velocity field of the double starburst galaxy Mkn 788 (Kollatschny et al., 1986) are shown. The authors compared their measurements with those of normal interacting galaxies of Keel et al. (1985) and Bushouse (1987). The mean FIR luminosity per nucleus in multiple systems is the same as that of interacting galaxies. But the mean H alpha luminosities as well as the (OIII)/H beta line ratios are higher by a factor of 1.5-2 than those of normal interacting galaxies.

Kollatschny, W.↗

Neural network based prediction of no-wall β N limits due to ideal external kink instabilities

Multi-layer perceptron based neural networks (NNs) are trained to predict the Troyon no-wall beta limits due to the onset of low-n (n = 1 – 3, n is the toroidal mode number) ideal external kink instabilities in tokamak plasmas. It is revealed that a well-trained NN can predict the n = 1 no-wall beta limit within 10% relative error. The NN performance is somewhat worse for the n = 2 and 3 no-wall beta limits, but still a relative error within 20% is achievable. The trained NNs well reproduce the known dependences of the no-wall beta limits on the plasma pressure (pressure peaking factor) and current (plasma internal inductance) profiles. Other scalings are further easily established with NNs, for parametric dependences such as on the aspect ratio, the elongation and triangularity of the plasma boundary shape. These NN-based Troyon beta limit predictors can be incorporated into integrated modeling platforms, or directly implemented as a real time stability estimator for the purpose of disruption avoidance or mitigation during experiments.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗

Data for "Plasma shape effects on the Alfvén eigenmode spectrum through Alfvén slow-magnetosonic wave coupling"

electron density profile as a function of normalized poloidal flux: psinorm ne(10^20/m^3) dne/dpsiN Pressure profile as a function of normalized poloidal flux: psinorm ptot(KPa) dptot/dpsiN scaled to oftain beta=5% at magnetic axis Magnetic safety factor profile as a function of normalized poloidal flux: psinorm q_profile All needed to perform the NOVA calculations.

Alfven waves↗

Diabetes and hypertension are related to amyloid-beta burden in the population-based Rotterdam Study

Abstract Higher vascular disease burden increases the likelihood of developing dementia, including Alzheimer’s disease. Better understanding the association between vascular risk factors and Alzheimer’s disease pathology at the predementia stage is critical for developing effective strategies to delay cognitive decline. In this work, we estimated the impact of six vascular risk factors on the presence and severity of in vivo measured brain amyloid-beta (Aβ) plaques in participants from the population-based Rotterdam Study. Vascular risk factors (hypertension, hypercholesterolaemia, diabetes, obesity, physical inactivity and smoking) were assessed 13 (2004–2008) and 7 years (2009–2014) prior to 18F-florbetaben PET (2018–2021) in 635 dementia-free participants. Vascular risk factors were associated with binary amyloid PET status or continuous PET readouts (standard uptake value ratios, SUVrs) using logistic and linear regression models, respectively, adjusted for age, sex, education, APOE4 risk allele count and time between vascular risk and PET assessment. Participants’ mean age at time of amyloid PET was 69 years (range: 60–90), 325 (51.2%) were women and 190 (29.9%) carried at least one APOE4 risk allele. The adjusted prevalence estimates of an amyloid-positive PET status markedly increased with age [12.8% (95% CI 11.6; 14) in 60–69 years versus 35% (36; 40.8) in 80–89 years age groups] and APOE4 allele count [9.7% (8.8; 10.6) in non-carriers versus 38.4% (36; 40.8) to 60.4% (54; 66.8) in carriers of one or two risk allele(s)]. Diabetes 7 years prior to PET assessment was associated with a higher risk of a positive amyloid status [odds ratio (95% CI) = 3.68 (1.76; 7.61), P < 0.001] and higher standard uptake value ratios, indicating more severe Aβ pathology [standardized beta = 0.40 (0.17; 0.64), P = 0.001]. Hypertension was associated with higher SUVr values in APOE4 carriers (mean SUVr difference of 0.09), but not in non-carriers (mean SUVr difference 0.02; P = 0.005). In contrast, hypercholesterolaemia was related to lower SUVr values in APOE4 carriers (mean SUVr difference −0.06), but not in non-carriers (mean SUVr difference 0.02). Obesity, physical inactivity and smoking were not related to amyloid PET measures. The current findings suggest a contribution of diabetes, hypertension and hypercholesterolaemia to the pathophysiology of Alzheimer’s disease in a general population of older non-demented adults. As these conditions respond well to lifestyle modification and drug treatment, further research should focus on the preventative effect of early risk management on the development of Alzheimer’s disease neuropathology.

van Arendonk, Joyce (ORCID:0000000172941633)↗

Coupled-Cluster Calculations of Neutrinoless Double- β Decay in Ca 48

We use coupled-cluster theory and nuclear interactions from chiral effective field theory to compute the nuclear matrix element for the neutrinoless double-$\beta$ decay of $^{48}$Ca. Benchmarks with the no-core shell model in several light nuclei inform us about the accuracy of our approach. For $^{48}$Ca we find a relatively small matrix element. We also compute the nuclear matrix element for the two-neutrino double-$\beta$ decay of $^{48}$Ca with a quenching factor deduced from two-body currents in recent ab initio calculation of the Ikeda sum rule in $^{48}$Ca [Gysbers et al., Nat. Phys. 15, 428 (2019)].

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗

Progress in extending high poloidal beta scenarios on DIII-D towards a steady-state fusion reactor and impact of energetic particles

To prepare for steady-state operation of future fusion reactors (e.g. the International Thermonuclear Experimental Reactor and China Fusion Engineering Test Reactor (CFETR)), experiments on DIII-D have extended the high poloidal beta ( β P ) scenario to reactor-relevant edge safety factor q 95 ~ 6.0, while maintaining a large-radius internal transport barrier (ITB) using negative magnetic shear. Excellent energy confinement quality ( H 98y2 > 1.5) is sustained at high normalized beta ( β N ~ 3.5). This high-performance ITB state with Greenwald density fraction near 100% and q min ≥ 3 is achieved with toroidal plasma rotation V tor ~ 0 at ρ ≥ 0.6. This is a key result for reactors expected to have low V tor . At high β P (≥1.9), large Shafranov shift can stabilize turbulence leading to a high confinement state with a low pedestal and an ITB. At lower β P (<1.9), negative magnetic shear in the plasma core contributes to turbulence suppression and can compensate for reduced Shafranov shift to continue to access a large-radius ITB and excellent confinement with low V tor , consistent with the results of gyrofluid transport simulations. These high- β P cases are characterized by weak/no Alfvén eigenmodes (a.e.) and classical fast-ion transport. At high density, the fast-ion deceleration time decreases and Δ β fast is lower; these reduce a.e. drive. The reverse-shear Alfvén eigenmodes are weaker or stable because the negative magnetic shear region is located at higher radius, away from the peaked fast-ion profile. Resistive wall modes can be a limitation at simultaneous high β N , low internal inductance, and low rotation. Analysis suggests that additional off-axis external current drive could provide a more stable path at reduced q 95 . Based on a DIII-D high- β P plasma with large-radius ITB, two scenarios are proposed for CFETR Q = 5 steady-state operation with ~1 GW fusion power: a lower-$l_i$($l_i$ ~ 0.66) and a higher-$l_i$($l_i$ ~ 0.75) case. Using a Landau closure model, multiple energetic particle (EP) effects on the a.e. stability are analyzed modifying the growth rate of the a.e.s triggered by the neutral-beam-injection EPs and alpha particles, although the stabilizing/destabilizing effect is weak for the cases analyzed. The stabilizing effects of the combined EP species β , energy, and density profile in CFETR need further investigation.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗

Improvements to a Response Surface Thermal Model for Orion

A study was performed to determine if a Design of Experiments (DOE)/Response Surface Methodology could be applied to on-orbit thermal analysis and produce a set of Response Surface Equations (RSE) that predict Orion vehicle temperatures within 10 F. The study used the Orion Outer Mold Line model. Five separate factors were identified for study: yaw, pitch, roll, beta angle, and the environmental parameters. Twenty-three external Orion components were selected and their minimum and maximum temperatures captured over a period of two orbits. Thus, there are 46 responses. A DOE case matrix of 145 runs was developed. The data from these cases were analyzed to produce a fifth order RSE for each of the temperature responses. For the 145 cases in the DOE matrix, the agreement between the engineering data and the RSE predictions was encouraging with 40 of the 46 RSEs predicting temperatures within the goal band. However, the verification cases showed most responses did not meet the 10 F goal. After reframing the focus of the study to better align the RSE development with the purposes of the model, a set of RSEs for both the minimum and maximum radiator temperatures was produced which predicted the engineering model output within +/-4 F. Therefore, with the correct application of the DOE/RSE methodology, RSEs can be developed that provide analysts a fast and easy way to screen large numbers of environments and assess proposed changes to the RSE factors.

Miller, Stephen W.↗

Constraints on the Gas Content of the Fomalhaut Debris Belt: Can Gas-Dust Interactions Explain the Belt's Morphology?

Context. The 440 Myr old main-sequence A-star Fomalhaut is surrounded by an eccentric debris belt with sharp edges. This sort of a morphology is usually attributed to planetary perturbations, but the orbit of the only planetary candidate detected so far, Fomalhaut b, is too eccentric to efficiently shape the belt. Alternative models that could account for the morphology without invoking a planet are stellar encounters and gas-dust interactions. Aims. We aim to test the possibility of gas-dust interactions as the origin of the observed morphology by putting upper limits on the total gas content of the Fomalhaut belt. Methods. We derive upper limits on the CII158 microns and OI 63 microns emission by using non-detections from the Photodetector Array Camera and Spectrometer (PACS) onboard the Herschel Space Observatory. Line fluxes are converted into total gas mass using the non-local thermodynamic equilibrium (non-LTE) code radex. We consider two different cases for the elemental abundances of the gas: solar abundances and abundances similar to those observed for the gas in the Beta Pictoris debris disc. Results. The gas mass is shown to be below the millimetre dust mass by a factor of at least approx. 3 (for solar abundances) respectively approx. 300 (for Beta Pic-like abundances). Conclusions. The lack of gas co-spatial with the dust implies that gas-dust interactions cannot efficiently shape the Fomalhaut debris belt. The morphology is therefore more likely due to a yet unseen planet (Fomalhaut c) or stellar encounters.

Fomalhaut b↗

Development of a Response Surface Thermal Model for Orion Mated to the International Space Station

A study was performed to determine if a Design of Experiments (DOE)/Response Surface Methodology could be applied to on-orbit thermal analysis and produce a set of Response Surface Equations (RSE) that accurately predict vehicle temperatures. The study used an integrated thermal model of the International Space Station and the Orion Outer mold line model. Five separate factors were identified for study: yaw, pitch, roll, beta angle, and the environmental parameters. Twenty external Orion temperatures were selected as the responses. A DOE case matrix of 110 runs was developed. The data from these cases were analyzed to produce an RSE for each of the temperature responses. The initial agreement between the engineering data and the RSE predictions was encouraging, although many RSEs had large uncertainties on their predictions. Fourteen verification cases were developed to test the predictive powers of the RSEs. The verification showed mixed results with some RSE predicting temperatures matching the engineering data within the uncertainty bands, while others had very large errors. While this study to not irrefutably prove that the DOE/RSM approach can be applied to on-orbit thermal analysis, it does demonstrate that technique has the potential to predict temperatures. Additional work is needed to better identify the cases needed to produce the RSEs

Miller, Stephen W.↗

Improvements to a Response Surface Thermal Model for Orion Mated to the International Space Station

This study is an extension of previous work to evaluate the applicability of Design of Experiments (DOE)/Response Surface Methodology to on-orbit thermal analysis. The goal was to determine if the methodology could produce a Response Surface Equation (RSE) that predicted the thermal model temperature results within +/-10 F. An RSE is a polynomial expression that can then be used to predict temperatures for a defined range of factor combinations. Based on suggestions received from the previous work, this study used a model with simpler geometry, considered polynomials up to fifth order, and evaluated orbital temperature variations to establish a minimum and maximum temperature for each component. A simplified Outer Mold Line (OML) thermal model of the Orion spacecraft was used in this study. The factors chosen were the vehicle's Yaw, Pitch, and Roll (defining the on-orbit attitude), the Beta angle (restricted to positive beta angles from 0 to 75), and the environmental constants (varying from cold to hot). All factors were normalized from their native ranges to a non-dimensional range from -1.0 to 1.0. Twenty-three components from the OML were chosen and the minimum and maximum orbital temperatures were calculated for each to produce forty-six responses for the DOE model. A customized DOE case matrix of 145 analysis cases was developed which used analysis points at the factor corners, mid-points, and center. From this data set, RSE s were developed which consisted of cubic, quartic, and fifth order polynomials. The results presented are for the fifth order RSE. The RSE results were then evaluated for agreement with the analytical model predictions to produce a +/-3(sigma) error band. Forty of the 46 responses had a +/-3(sigma) value of 10 F or less. Encouraged by this initial success, two additional sets of verification cases were selected. One contained 20 cases, the other 50 cases. These cases were evaluated both with the fifth order RSE and with the analytical model. For the maximum temperature predictions, 12 of the 23 components had all predictions within +/-10 F and 17 were within +/-20 F. For the minimum temperature predictions, only 4 of the 23 components (the four radiator temperatures), were within the 10 F goal. The maximum temperature RSEs were then run through 59,049 screening cases. The RSE predictions were then filtered to find 55 cases that produced the hottest temperatures. These 55 cases were then analyzed using the thermal model and the results compared against the RSE predictions. As noted earlier, 12 of the 23 responses were within +/-10 F at 17 within +/-20 F. These results demonstrate that if properly formulated, an RSE can provide a reliable, fast temperature prediction. Despite this progress, additional work is needed to determine why the minimum temperatures responses and 6 of the hot temperature responses did not produce reliable RSEs. Recommend focus areas are the model itself (arithmetic vs. diffusion nodes) and seeking consultations with statistical application experts.

Miller, StephenW.↗

An integrated multi-omics approach identifies the landscape of interferon-α-mediated responses of human pancreatic beta cells

Proinflammatory cytokines are important mediators of pancreatic beta cell dysfunction and demise in the early stages of type 1 diabetes (T1D). Interferon-a (IFNa), a type I interferon member, is expressed in the islets of T1D individuals and it is expression and signaling is regulated by both genetic (T1D risk variants) and environmental factors (viral infections) associated to T1D. We presently characterized human beta cells responses to IFNa by combining ATAC-seq, RNA-seq and proteomics assays. The initial beta cell response to IFNa was characterized by major chromatin remodeling, followed by marked changes in transcriptional and translational regulation. IFNa-induced changes in alternative splicing (AS) and first exon usage increased the diversity of transcripts expressed by beta cells. This, combined with changes observed on protein modification/degradation, ER stress and MHC class I, may significantly expand the peptide repertoire presented by beta cells to the immune system. On the other hand, beta cells up-regulated checkpoint proteins, such as PDL1 and HLA-E, that may protect them against the autoimmune assault. Data mining of the present multi-omics analysis led to the identification of two compound classes that revert IFNa effects on human beta cells and may be translated to clinical trials.

60 APPLIED LIFE SCIENCES↗