Center Of Core Research Articles

Acceptability of Long-Acting Cabotegravir + Rilpivirine in a Large, Urban, Ambulatory HIV Clinic.

Outside of randomized controlled trials (RCTs), there are limited data regarding the acceptability of injectable long-acting cabotegravir + rilpivirine (LA-CAB+RPV) among persons living with HIV (PLWH). To evaluate acceptability, we describe participant-reported outcomes (PRO) of LA-CAB+RPV among a population underrepresented in RCTs. Ruth M. Rothstein Core Center (CORE), large urban HIV clinic in Chicago, Illinois, USA. We interviewed PLWH prescribed LA-CAB+RPV who receive primary care at CORE. PRO endpoints included treatment satisfaction, tolerability of injections, reasons for switching to LA-CAB+RPV, and unexpected effects of LA-CAB+RPV. Mean and standard deviations (mean±SD) and proportions (%) are reported. Among respondents (N=150), 67% identified as Non-Hispanic Black, 24% Hispanic, 56% male; the average age was 43 years (SD:13.2), and 37% were ≥50 years old. Most respondents (93%) completed ≥3 injection appointments at the time of interview. The most common reasons for switching to LA-CAB+RPV were no longer wanting to take pills (89%) and trouble taking their pills daily (58%). Treatment satisfaction was high (6.7±0.5 out of 7). Two-thirds (61%) reported an unexpected aspect of their life improved. Pain from injections was common (98%), with a mean pain score of 4.3 out of 10. Among those reporting pain, half (47%) reported pain decreased after initial injection. Among participants reporting pain score >6 (n=36), most (78%) reported no improvement since initial injection. We found high treatment satisfaction with LA-CAB+RPV in a diverse population. Participants reported moderate injection pain, which improved with time. Results suggest injectable LA-CAB+RPV will be met with acceptability across diverse participant populations.

Study on potential burnable poison materials for a small modular block-type HTGR design using MgO-BeO as a composite-based moderators

Preliminary analysis of MgO-BeO composite material used as a moderator in a 50 MWt block-type high-temperature gas-cooled reactor (HTGR) was performed in our previous study. The target burnup of 80 GWd/t was achieved with a uniform fuel composition of 17 wt% 235U enrichment and 6 kg of heavy metal per fuel block. However, this resulted in high excess reactivity and a peak in axial power distribution at the core center. Therefore, this study aims to reduce excess reactivity by incorporating burnable poison (BP) material and optimize the axial power profile by introducing a nonuniform fuel composition in the core. Neutronic calculations were performed using the Monte Carlo MVP3.0 code developed by the Japan Atomic Energy Agency (JAEA). In this study, three fuel enrichments of 235U, ranging from 15 wt% to 20 wt%, were distributed across the core while maintaining a constant fuel packing fraction of 45 %. The results showed that the higher power density distribution shifted from the core’s center to its upper part, leading to lower power density in the bottom region than the top. In addition, excess reactivity was reduced by inserting BP rods. Several parametric calculations were performed to achieve minimal excess reactivity without compromising the burnup target. The results showed that the BP rod with a radius of 0.7 cm and 12 wt% of Gd2O3 can reduce the excess reactivity from 25.5 %Δk/k to 13.47 % Δk/k.

First map of D2H+ emission revealing the true centre of a prestellar core: Further insights into deuterium chemistry

Context. IRAS 16293E is a rare case of a prestellar core being subjected to the effects of at least one outflow. Aims. We want to disentangle the actual structure of the core from the outflow impact and evaluate the evolutionary stage of the core. Methods. Prestellar cores being cold and depleted, the best tracers of their central regions are the two isotopologues of the trihydrogen cation that are observable from the ground: ortho-H2D+ and para-D2H+. We used the Atacama Pathfinder EXperiment (APEX) telescope to map the para-D2H+ emission in IRAS 16293E and collected James Clerk Maxwell Telescope (JCMT) archival data of ortho-H2D+. We compared their emission to that of other tracers, including dust emission, and analysed their abundance with the help of a 1D radiative transfer tool. The ratio of the abundances of ortho-H2D+ to para-D2H+ can be used to estimate the stage of the chemical evolution of the core. Results. We have obtained the first complete map of para-D2H+ emission in a prestellar core. We compare it to a map of ortho-H2D+ and show their partial anti-correlation. This reveals a strongly evolved core with a para-D2H+/ortho-H2D+ abundance ratio towards the centre for which we obtain a conservative lower limit from 3.9 (at 12 K) to 8.3 (at 8 K), while the high extinction of the core is indicative of a central temperature below 10 K. This ratio is higher than predicted by the known chemical models found in the literature. Para-D2H+ (and indirectly ortho-H2D+) is the only species that reveals the true centre of this core, while the emission of other molecular tracers and dust are biased by the temperature structure that results from the impact of the outflow. Conclusions. This study is an invitation to reconsider the analysis of previous observations of this source and possibly questions the validity of the deuteration chemical models or of the reaction and inelastic collisional rate coefficients of the H+3 isotopologue family. This could impact the deuteration clock predictions for all sources.

Deployment and performance of a Low-Energy-Threshold Skipper-CCD inside a nuclear reactor

Charge Coupled Devices (CCD) are being used for reactor neutrino experiments and have already demonstrated their potential in constraining new physics models. The prospect of a Skipper-CCD experiment looking for standard and beyond standard model (BSM) physics in a nuclear reactor has been evaluated for different benchmark scenarios. Here, we report the first installation of a 2-g Skipper-CCD inside the containment building of a 2 GWth nuclear power plant and analyze its performance throughout its first 18 months of operation. The sensor was successfully deployed at Atucha II, in Argentina, 12 meters away from the center of the reactor core. We discuss the challenges involved in the commissioning of the detector and present data acquired during reactor ON and reactor OFF periods, with the sensor functioning with a sub-electron readout noise of 0.17 e−. Based on an exposure of 56.8 g day reactor ON and two reactor OFF data sets with a total exposure of 118.1 g day we characterize the system and evaluate the sensitivity to CEvNS. We achieved a background rate of 33 kdru and a low threshold of 45 eVee. The ongoing efforts to improve sensitivities to CEvNS and BSM interaction are also discussed.

AFROCENTRIC PEDAGOGY APPROACH IN THE CURRICULUM OF EDUCATIONAL SYSTEM RENEWAL IN AFRICA: A CASE OF SOUTH AFRICA

The purpose of this paper is to conceptualize in greater detail the educational system approach that is being imposed into African countries, South Africa as a case in point. Over the past years, Sub-Saharan countries have and still experience indoctrinated educational system in which the content is mimicked from purported hegemonic states such UK, USA and other western counties inter alia. The problem of education retrogrades from the prior independence of African countries in the early 1960s wherein, the colonial masters organized and silently played a crucial role in shaping the formation of education in Africa; and not much has changed in terms of education since then. A particular concern is that the system of education might have designed to impoverish African people and perpetuate dependency to the western nations. Hence, at the core center of the educational system is the curriculum which seem to be inevitable and requires an alteration, particularly in South Africa. Therefore, the outlook of this paper is to critique and interrogate the system of education in South Africa looking at the socio-economic development and a continuous alteration in respect of the curriculum. The paper shows that for the realization of African renaissance, ideals of Africa Agenda 2063 and accelerated development, the system of education must be transformed and be Africanized to benefit the people of Africa. The paper uses literature-based approach as a methodological framework in order to analyze the status quo of education in South Africa. The paper concludes and recommends that the transformation of current educational system requires an alteration to the inclusive of indigenous knowledge to vigorously respond to socio-economic woes in Africa. Furthermore, the paper advocates for indigenous knowledge consideration in the incessant curriculum renewal.

Real-world trends in acute viral hepatitis in Japan: A nationwide questionnaire-based survey.

The actual incidence of acute viral hepatitis in Japan remains unclear. We aimed to investigate trends in the incidence of acute hepatitisB and C infections in Japan. A nationwide, multicenter, retrospective questionnaire-based survey was conducted. Participating hospitals received questionnaires through nationwide geographically distributed regional core centers certified as specialists in hepatitis treatment. The questionnaire included hospital size and the number of patients diagnosed with acute hepatitisB or C during each fiscal year (FY) from 2015 to 2022. The sex distribution in each FY was also documented. Comparisons were made before and during the COVID-19 era (2015-2019 vs. 2020-2022), and between populous and non-populous prefectures. Responses to the questionnaires were obtained from 127 institutions in 29 prefectures covering eight regions in Japan. A median of 127.0 patients with acute hepatitisB (interquartile range [IQR] 106.5-131.8 patients) were reported during each FY, and the incidence significantly decreased during the fiscal years 2020-2022 compared with the fiscal years 2015-2020 (median 96.0 [IQR 91.0-103.0] patients vs. 131.0 [IQR 128.0-134.0] patients; p=0.03). A median of 10.0 (IQR, 7.8-13.5) patients were reported with acute hepatitisC during each FY. The proportions of men in acute hepatitis B and C were significantly higher in populous prefectures. Populous prefectures had a higher proportion of men among viral hepatitis patients than non-populous prefectures. Estimating the high-risk populations in each area could provide insights to advance the elimination of viral hepatitis.

NuSTAR Observation of the TeV-detected Radio Galaxy 3C 264: Core Emission and the Hot Accretion Flow Contribution

3C 264 is one of the few FRI radio galaxies with detected TeV emission. It is a low-luminosity active galactic nucleus (LLAGN) and is generally associated with a radiatively inefficient accretion flow (RIAF). Earlier multiwavelength studies suggest that the X-ray emission originates from a jet. However, the possibility that the RIAF can significantly contribute to the X-rays cannot be ruled out. In particular, hard X-ray emission ≳10 keV has never been detected, making it challenging to distinguish between X-ray models. Here we report a NuSTAR detection up to 25 keV from 3C 264. We also present subpixel deconvolved Chandra images to resolve jet emission down to ∼0.″2 from the center of the unresolved X-ray core. Together with a simultaneous Swift observation, we have constrained the dominant hard X-ray emission to be from its unresolved X-ray core, presumably in its quiescent state. We found evidence of a cutoff in the energy around 20 keV, indicating that at least some of the X-rays from the core can be attributed to the RIAF. The Comptonization model suggests an electron temperature of about 15 keV and an optical depth ranging between 4 and 7, following the universality of coronal properties of black hole accretion. The cutoff energy or electron temperature of 3C 264 is the lowest among those of other LLAGNs. The detected hard X-ray emission is at least an order of magnitude higher than that predicted by synchrotron self-Compton models introduced to explain γ-ray and TeV emission, suggesting that the synchrotron electrons might be accelerated to higher energies than previously thought.

Flat top coverage pattern maintaining via boundary subarray elements thinning

AbstractThis paper aims to study the effect of eliminating some elements from the original planar array (OPA) to generate a useful flat‐top coverage pattern (FTCP) using a genetic algorithm. The study involves dividing the fully planar array (i.e., OPA) into two regions with an unequal number of elements. The first region includes the elements located in the core (center) of the array, and the remaining elements are the second region, and their location is within the boundary (side) of the array. Only the elements of the first region are included in the optimization process, while the elements of the second region are eliminated in the form of a specific geometric composition without affecting the FTCP generation. Comparing the OPA that N×M elements with the first region (active subarray) elements, it is noted that the number of elements has been reduced from N×M to (N − 2x) × (M − 2y) to reduce the complexity of the system as much as possible without affecting the performance in general. Different boundary subarray shapes are presented in this paper with different numbers of elements. The obtained results showed the effectiveness of the proposed method in generating FTCP close to its counterpart in the OPA.

Enhancing fuel breed-burn performance in a sodium-cooled fast reactor using a novel reactivity control method

This study aims to enhance the fuel cycle and fissile breeding performance of a sodium-cooled fast breeder reactor (FBR) by utilizing minor actinides (MAs) as a means of reactivity control alongside partially-inserted control rods. Choosing the PFBR-500 as the reference design, four core models, designated as Cases A, B, C, and D, utilizing various proportions of minor actinides (MAs) were built and simulated using OpenMC. The MA concentrations were optimized to compensate for the withdrawal of control rods and ensure the same initial reactivity for all cores. Burnup analysis over 365 EFPDs revealed a significant increase in cycle length and burnup for the modified cores along with a modest rise in breeding ratio. Notably, Case C, employing 3.45 wt.% MAs in the 88 inner-core fuel subassemblies achieved an extra 62.25 EFPDs cycle length, a 33.74% rise in single-cycle burnup, and a 3.86% increase in breeding gain compared to the reference. Loading MAs into the inner-core region proved to be more effective in enhancing both fertile-to-fissile conversion (thus extending the cycle length and fuel burnup) and transmutation than utilizing MAs throughout the core due to greater neutron flux at the core center. While Case D utilizing 2.2 wt.% MAs both in the inner and outer core fuel subassemblies had the highest overall MA loading, it demonstrated lower increments in cycle length, burnup, and breeding gain compared to Case C. Case C also exhibited the highest overall destruction rate (approximately 24%/y) for Np and Am isotopes, and successfully transmuted around 24.08 kg 237Np, 9.33 kg 241Am and 3.82 kg 243Am over the course of a single year. The addition of MAs also achieved a slight flattening of the axial and radial flux profile and a decrease in the flux peaking factor. However, it slightly lowered the beta-effective, Doppler constant, and control rod assembly worth, and shifted the coolant void reactivity worth to the positive side.

The Relationship between Urban Form and Infrastructure: A Case Study of Finiq Municipality

This paper explores the complex relationship between urban form and infrastructure within the Finiq Municipality, shedding light on the evolution of its urban centers over the last three decades. The urban form of Finiq is deeply influenced by its infrastructure, especially the road system and transport networks. Understanding this relationship is essential for sustainable urban development. The main purpose of this study is to analyze the historical development patterns of Finiq Municipality, compact centers, distributed core centers, distributed centers, and linearly dis- tributed settlements and their impact on its current urban form. Evaluating these different development models, the study seeks to identify the challenges and opportunities for the future of the linear urban form as typical for the Finiq Municipality. This research uses a comprehensive approach, utilizing historical analysis, literature review, and qualitative assessment. These methods provide insights into the dynamics between ur- ban form and infrastructure, enabling a thorough examination of past, present, and possible future scenarios. The analysis highlights the important role of infrastructure in shaping the urban form of Finiq Municipality. The findings of this study contribute to the field of architecture by emphasizing the importance of understanding the interaction between urban form and infrastructure. By recognizing the challenges and opportunities presented by different development models, urban planners, and policymakers can make informed decisions to promote sustainable urban development. This research highlights the need for integrated approaches to infrastructure planning and urban design to create livable, resilient cities.

(Invited) Novel Brush Design for Post CMP Cleans

Chemical Mechanical Polishing (CMP) process is one of the key processes in semiconductor wafer processing. A sub 10nm wafer fabrication process may require more than 40 dielectric and metal CMP steps. As CMP process requirements get more stringent, CMP slurries are formulated with smaller and smaller metal oxide abrasive particles. The abrasive particles may also be surface modified or doped with other metal oxides. Post CMP cleaning chemistry formulations are designed to remove polish byproducts, pad residues and abrasive particles from wafer surface. Chemical composition and PH are tuned for modulating wafer surface-particle interactions so brushes can mechanically “sweep” them off the surface. PVA brushes, used of post CMP cleans, are a highly porous network of crosslinked polyvinyl acetate with pore size in the range of 30 – 100 um and 80% - 90% porosity, depending on the type of brush being used. While PVA brushes have largely met the process capability requirements, they have limitations for advanced cleans such as nano-particle removal. As CMP process continues to expand to new dielectric and metal films for different process steps in wafer fabrication, there is a need for customized brush material and surface design for optimal cleaning efficiency.We discuss a new engineered post CMP brush design that shows high efficiency in nano-particle cleans and allows high level of material tunability. New brush design is an engineered composite with an open cell microporous core, overlaid with engineered fibers in form of loops. Brush design is compatible with existing post CMP cleans. Figure 1(a) shows the new design, where in DIW enters the brush through the center of microporous core and flows outwards to the surface. As water exits the surface, it flows over and across the loops and contacts the wafer surface. Flow resistance through core and loops can be independently tuned, which allows better fluid distribution and more effective cleans. Figure 1(b) show a close-up schematic of interaction between loop and particle. Flexing of the loops on brush surface provides improved contact as well as cleaning ability Brush design can be optimized for chemical and mechanical properties with choice of fiber material, fiber diameter and loop height. Figure 2 shows the Zeta potential of PVA and different loop materials. The fiber material maybe selected such that zeta potential of the loops can enhance mechanical action in removing particle. Mechanical action of the Loops can be modeled as a cantilever and force on the particle is exerted by flexing of the loops.Deflection of loops can be approximated with flexure stiffness of rods with point load at free end. For initial purposed loop is approximated as single element. The equation can be rewritten to calculate cleaning force P at the free end for given loop deflection (Y), P = 3EIY/L3 (1)Where E is elastic modulus, I = moment, L = length of fiber and for rod shapes; I = Pi*(r4/4)The adhesion of particles on the surface is due to the effect of van der Waals and electrostatic forces. The total adhesion force on the surface can be written as: F=F vdw + F edl (2) where Ft is total adhesion force, Fvdw is the van der Waals force, and Fedl is the electrostatic force.Fvdw = AR/6r2 (3)Where A is the Hamaker constant, R is particle radius, r is the separation distanceFor effective removal of particles, P >/= F (4)Flex force and adhesion force were modeled based on equation (1) and (3) and are shown in Figure 3. New brush design was used for post CMP cleaning of silicon dioxide wafers polished with ceria slurry. Two different brush designs were tested for cleaning efficiency. Modeling data and comparison with experimental results is presented. Figure 1

Estimation of the injection criteria for magnetic hyperthermia therapy based on tumor morphology

Intratumoral multi-injection strategy enhances the efficacy of magnetic nanoparticle hyperthermia therapy (MNPH). In this study, criteria for the selection of injections and their location depending on the tumor shape/geometry are developed. The developed strategy is based on the thermal dosimetry results of different invasive 3D tumor models during MNPH simulation. MNPH simulations are conducted on physical tumor tissue models encased within healthy tissue. The tumor shapes are geometrically divided into a central tumor region containing maximum tumor volume and a peripheral tumor portion protruding in any random direction. The concepts of core and invasive radius are used to geometrically divide the tumor volume. Primary & secondary injections are used to inject MNP fluid into these respective tumor regions based on the invasiveness of the tumor. The optimization strategy is devised based on the zone of influence of primary & secondary injection. Results indicate that the zone of influence of secondary injection lies between 0.7 and 0.8 times the radial distance between the center of the tumor core and branch node point (extreme far endpoint on the invasive tumor surface). Additionally, the multi-injection strategy is more effective when the protrusion volume exceeds 10% of the total volume. The proposed algorithm is used to devise multi-injection strategies for arbitrarily shaped tumors and will assist in pre-planning magnetic nanoparticle hyperthermia therapy.

Baseline design of laser fusion research reactor with MW class laser facility

We propose a sub-ignition/burning reactor which is named the Laser-fusion Subcritical Power Reactor Engineering Method (L-Supreme). The reliabilities of L-Supreme in a MW class laser facility are assessed with respect to the following points: a reactor core, a target chamber, a target delivery system, an Exhaust Detritiation System (EDS), and neutron shielding. The Japan Establishment for Power-laser Community Harvest (J-EPoCH) would be applied as a MW class laser facility. A non-cryogenic glass balloon target filled with gaseous deuterium-tritium (DT) is contained in a target capsule. A chain-type magazine system might be used for a mass supply of the target capsules. Each target capsule is delivered to the center of a reactor core at 1 Hz. A batch of 10 000 laser shots would realize 0.22 MJ fusion power. The amount of tritium per batch is 1.51 × 1012 Bq. During laser experiments, unburned tritium is evacuated and transferred into an Exhaust Detritiation System (EDS). An evacuation rate of more than 0.1 m3 s−1 is required in order to recover less than 5000 Bq m−3 of the threshold of tritium concentration within 1 h. For safety, emergency situations such as tritium leakage in facilities are examined. The EDS works by internal circulation processes. Assuming leakage of tritium for a batch, an air circulation flow rate of 4100 Nm3 h−1 is required in an experimental hall for recovering less than 5000 Bq m−3 within 48 h. A primary and secondary neutron shield concept are proposed and would provide full neutron shielding. We conclude that it is possible to construct the L-Supreme system by marshalling current technologies.

Trapping of isotropic droplets by disclinations in nematic liquid crystals controlled by surface anchoring and elastic constant disparity.

Linear defects such as dislocations and disclinations in ordered materials attract foreign particles since they replace strong elastic distortions at the defect cores. In this work, we explore the behavior of isotropic droplets nucleating at singular disclinations in a nematic liquid crystal, predesigned by surface photopatterning. Experiments show that in the biphasic nematic-isotropic region, although the droplets are attracted to the disclination cores, their centers of mass shift away from the core centers as the temperature increases. The shift is not random, being deterministically defined by the surrounding director field. The effect is explained by the balance of interfacial anchoring and bulk elasticity. An agreement with the experiment can be achieved only if the model accounts for the disparity of the nematic elastic constants; the so-called one-constant approximation, often used in the theoretical analysis of liquid crystals, produces qualitatively wrong predictions. In particular, the experimentally observed shift towards the bend region around a +1/2 disclination core can be explained only when the bend constant is larger than the splay constant. The described dependence of the precise location of a foreign inclusion at defect cores on the elastic and surface anchoring properties can be used in rational design of microscale architectures.

Numerical study on the neutronics-thermal-mechanics coupling characteristics of the heat pipe nuclear reactor core

A heat pipe nuclear reactor is compact and flexible to supply electricity power to remote areas. In the process of designing this reactor, to avoid failure caused by extreme temperature or stress in the reactor core, the calculation of the neutronics, thermal, and mechanics and evaluation of their coupling effect is necessary. In this study, a numerical simulation method on the neutronics-thermal-mechanics coupling developed by the code OpenMC and MOOSE Multiphysics is verified. The results show the maximum temperature is near the center of the reactor core in both the axial and radial directions, while the position of the maximum stress depends on the constraint type of the entire model. The results also reveal that the feedback from the thermal field to the nuclear reaction cross-section of the neutronics field is slight. This research provides a valuable numerical simulation method for designing the core region of a heat pipe reactor.

Flux creep and flux pinning behavior in Cu-doped FeSe0.4Te0.6 single crystals

This paper presents the preparation and comparative study of the superconducting properties and magnetic flux dynamics of FeSe and Fe1-xCuxTe0.6Se0.4 (x = 0, 0.005, 0.01, 0.015) single crystals, with the aim of investigating the origin of the second peak in FeTe0.6Se0.4. The Cu element significantly suppresses the superconducting transition temperature (Tc) of Fe1-xCuxTe0.6Se0.4 from 14.5 K at x = 0 to 9.23 K at x = 0.015, which is close to the 9 K of FeSe, while also suppressing the second peak effect. Additionally, the critical current density anisotropy (γ) is reduced. Dynamic relaxation rates (Q) indicate a crossover from rapid single-vortex pinning near the second peak to collective pinning, linking fast and slow magnetic flux relaxation with the second peak effect. By comparing the pinning properties of FeSe and Fe1-xCuxTe0.6Se0.4 (x = 0, 0.005, 0.01, 0.015), it is found that the second peak effect is closely related to the transition from δl - pinning to δTc - pinning in Fe1-xCuxSe0.4Te0.6 (x = 0, 0.005, 0.01, 0.015). While surface pinning centers dominate in FeSe, the pinning in Fe1-xCuxSe0.4Te0.6 (x = 0, 0.005, 0.01, 0.015) originates from the interaction between the core and normal centers. Furthermore, the electronic transport properties of the FeSe and Fe1-xCuxSe0.4Te0.6 (x = 0, 0.005, 0.01, 0.015) series are also studied. Te substitution suppresses the nematic transition in FeSe, while Cu substitution suppresses the superconducting transition in Fe1-xCuxSe0.4Te0.6 (x = 0, 0.005, 0.01, 0.015) and reduces the residual resistivity. Additionally, the upper critical field is reduced from 150 T in FeSe0.4Te0.6 to 41 T in Fe0.085Cu0.015Se0.4Te0.6, but still higher than the 12.5 T observed in FeSe.

HCN as a probe of the inner disc in a candidate proto-brown dwarf

ABSTRACT The detection of Keplerian rotation is rare among Class 0 protostellar systems. We have investigated the high-density tracer HCN as a probe of the inner disc in a Class 0 proto-brown dwarf candidate. Our ALMA high angular resolution observations show the peak in the HCN (3–2) line emission arises from a compact component near the proto-brown dwarf with a small bar-like structure and a deconvolved size of ∼50 au. Radiative transfer modelling indicates that this HCN feature is tracing the innermost, dense regions in the proto-brown dwarf where a small Keplerian disc is expected to be present. The limited velocity resolution of the observations, however, makes it difficult to confirm the rotational kinematics of this feature. A brightening in the HCN emission towards the core centre suggests that HCN can survive in the gas phase in the inner, dense regions of the proto-brown dwarf. In contrast, modelling of the HCO+ (3–2) line emission indicates that it originates from the outer pseudo-disc/envelope region and is centrally depleted. HCN line emission can reveal the small-scale structures and can be an efficient observational tool to study the inner disc properties in such faint compact objects where spatially resolving the disc is nearly impossible.

A Learning Health System to Generate and Accelerate Innovation: The HealthPartners Institute

The HealthPartners Institute is a research and education division embedded within HealthPartners — a nonprofit, member-governed integrated health system. The Institute aims to generate and accelerate innovation for the HealthPartners health system, its patients and members, and the communities it serves. It has taken a formal, organized approach to building the necessary capabilities, infrastructures, relationships, and tools to do so. This article outlines an innovative approach by which the HealthPartners Institute created an environment conducive to accelerated system performance. Key components of building this organizational milieu include (1) integration, (2) strategic planning, (3) democratization of knowledge (especially internally generated knowledge), (4) funding, and (5) a capability to listen to diverse perspectives from both within the organization and the community at large. In recent years, based on a 2023 survey of the HealthPartners Senior Strategy team, nearly two thirds of 34 respondents (61%) have seen more connections between their work and the work of the Institute, and just over half (52%) report that the Institute has become more relevant to their work. Notably, care delivery is the area to which respondents (78%) find the Institute brings the most value, followed by our patients (74%), HealthPartners as a whole (70%), and our community (70%). In addition, a series of multiyear federally funded trials involving patients with uncontrolled hypertension collectively represent an example of clinical and financial impact. This collaborative effort involving system division partnerships through the Institute’s core research department and centers of excellence compared usual hypertension care with an intervention that combined home blood pressure telemonitoring and pharmacist-led telephone care and found that the intervention group not only had lowered blood pressure and reduced cardiovascular disease events, but that for every US$1.00 spent the program realized US$1.82 in averted cardiovascular disease event costs. Efforts such as these advance system performance through a closer connection between the Institute and the health system’s strategic multiyear goals, shared leadership among major research portfolios and the care delivery service lines, preprofessional clinical education aligned with workforce needs, systemwide implementation of clinical simulation, aligned and integrated financial operations, and compliance and integrity programs. Based on these experiences and results, the authors present several themes that may support acceleration of progress toward achieving a high-performing learning health system. Future development will include focus on the generation and quantification of value for internal and external stakeholders, strategic alignment of priorities to enhance value, and continued focus on workforce development.

LES of the upper plenum of the liquid metal fast reactor under the forced flow conditions

A Large Eddy Simulation (LES) of the upper plenum of the E-SCAPE (European SCAled Pool Experiment) facility under the normal operations has been conducted to gain deeper insights into the thermal hydraulics phenomena in liquid metal fast reactors (LMFRs). The results unravel the overall flow features in the upper plenum, the thermal instability in the above core structure region and the impact of the jets from the barrel holes on the large flow circulation and thermal mixing.The above core structure region is represented using a homogeneous porous model. It is shown that during the normal operations, most of the hot stream of the lead bismuth eutectic (LBE) from the core center rises to the top and disperses from the upper barrel holes. Conversely, the cold LBE spread out from the lower barrel holes. Mixing between the two streams only affect the fluids leaving from the middle heights demonstrating limited mixing. These jets help to create a large circulation in the upper plenum region which prevents any thermal stratification. At the interface between the hotter and colder streams, there are unsteady large-scale structures resulting in a mixing layer in the thermal field. This strong mixing is not conventional turbulence and potentially cannot be captured by Reynolds Averaged Navier Stokes average (RANS) modelling.The flow in the upper plenum is dominated by the influences of the different types of jets, which include some free jets issued horizontally or angled upwards and some jets impinging onto the structures in the plenum. The jets overall behave similar to ‘standard’ jets, though significant interactions between the top and bottom jets and the background circulations have strong influences at later stages of the jets, typically after four jet diameters leading to the jets not reaching self-similarity. In addition, the turbulence that is observed in the upper plenum is largely generated by the jet flows and hence the distribution of turbulence is very non-uniform. Away from the jets, turbulence is minimal with the mixing largely driven by the large-scale circulation.

Partially Differentiated Ileal and Rectal Human CFTR-F508del Enteroids Secrete Fluid in Response to cAMP and cGMP: Targeted Preclinical Studies of Pharmaco-Therapy of CF Constipation

Introduction: Treatment of Cystic Fibrosis (CF) patients with Trikafta is prolonging life. This has allowed the importance of other causes of morbidity in these patients to become clearer and to emphasize the need to improve their quality of life by developing additional treatments. Chronic constipation is one such continuing unsolved medical issue for patients with CF even on Trikafta. In general, approaches to treat chronic constipation include increasing intestinal fluid secretion that involves inhibiting intestinal NaCl absorption and/or stimulating intestinal Cl secretion, with inhibition of the latter being the primary defect in CF. Drug development efforts have mostly aimed to improve CFTR function and control pancreatic insuffciency. We have recently reported an enterocyte population in the human ileal and colon that is present between the crypt Cl− secretory cells and the mature small intestinal villus or colonic surface Na+ absorptive cells that contain both DRA and CFTR. This population is called partially differentiated enterocytes. This study was undertaken to derive a strategy to stimulate intestinal fluid secretion from partially differentiated enterocytes in the F508del-CF-patient population by enhancing residual CFTR F508del activity using drugs that stimulate cAMP and cGMP. Methods: Ileal and rectal enteroids from F508del CF patients and healthy subjects (HS/normal) were studied. Enteroids were maintained in growth media containing Wnt3A, R-spondin, and Noggin (undifferentiated/UD); induced to partially differentiate (3d-DF) or fully differentiate (6d-DF) by removal of growth factors (Wnt3A and R-spondin) for 3 or 6 days, respectively. Forskolin-induced swelling (FIS) assay and live cell microscopy were used to determine fluid secretion in enteroids. A relative increase in organoid surface area over a time series of 60 min was measured to quantify FIS response. mRNA expression was determined using qRT-PCR. Results: Compared to HS enteroids, F508del enteroids had significantly higher mRNA expression of LGR5, and Ki67 in the UD state. Expression of goblet cell marker MUC2 and enteroendocrine (EEC) marker ChgA increased with differentiation in both HS and F508del, while 6d-DF F508del enteroids had a significantly higher ChgA compared to 6d-DF enteroids from HS. UD F508del enteroids had significantly higher expression of phosphodiesterase-3a (PDE3a) than HS enteroids, which further increased with differentiation, but did not change in HS. While UD and 6d-DF F508del rectal and ileal enteroids did not swell when exposed to cAMP (forskolin) and cGMP (linaclotide), 3d-DF F508del enteroids showed a swelling response when exposed to cAMP (forskolin) and cGMP (linaclotide). Fluid secretion from 3d-DF F508del enteroids was ~50% (cAMP) and ~67% (cGMP) of the response of intestinal enteroids from HS enteroids. Combinations of CFTR correctors and potentiators mimicking the makeup of Trikafta only partially enhanced fluid secretion in F508del CF enteroids as compared to HS. However, cGMP (linaclotide) additively enhanced Trikafta-induced fluid secretion from 3d-DF F508del enteroids. Conclusions: CFTR F508del can be stimulated by cAMP and cGMP in partially differentiated enterocyte populations. Our findings identify a novel role of the partially differentiated ileal and rectal enterocyte populations which behave in a way that offers the potential to improve treatment for CF constipation. Funding: This study is partly supported by Cystic Fibrosis Foundation grant CF-SINGH20G0, National Institutes of Health grants R01-DK-116352 and P30-DK-89502 (the Hopkins Basic and Translational Research Digestive Diseases Research Core Center). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.