"Feels Like an Indie Game"-Evaluation of a Virtual Field Trip Prototype on Radioactive Waste Management Research for University Education.

This article describes the design and evaluation of a virtual field trip on the topic of radioactive waste management research for university education. We created an interactive virtual tour through the Mont Terri underground research laboratory by enhancing the virtual experiment information system, designed for domain experts, with background information, illustrations, tasks, tests, and an improved user interface. To put the tour's content into context, a conventional introductory presentation on the final disposal of radioactive waste was added. A user study with 22 participants proved a good perceived usability of the virtual tour and the virtual field trip's ability to transfer knowledge. These results suggest a benefit of employing virtual field trips in geoscientific university courses. In addition, it is conceivable to use the virtual field trip as a tool for science communication in the context of participatory processes during nuclear waste disposal site selection processes.

CFPy-A Python Package for Pre- and Postprocessing of the Conduit Flow Process of MODFLOW.

The conduit flow process (CFP) for MODFLOW's groundwater flow model is an advanced approach for investigating complex groundwater systems, such as karst, with coupled discrete-continuum models. CFP represents laminar and turbulent flow in a discrete pipe network coupled to a matrix continuum. However, the preprocessing demand is comparatively high to generate the conduit network and is usually performed with graphical user interfaces. To overcome this limitation and allow a scalable, reproducible, and comprehensive workflow, existing and new routines were aggregated to a Python package named CFPy, to allow script-based modeling that harmonizes well with the available and widely used FloPy package. CFPy allows information about the location and geometry of the conduit network to be considered by user-specific approaches or by sophisticated methods such as stochastic conduit network generators. The latter allows the automatic generation of many model variants with differing conduit networks for advanced investigations like multi-model approaches in combination with automatic parameter estimation. Additional postprocessing routines provide powerful control and valuable insights for CFP applications. In this methods note, a general technical description of the approach is complemented with two examples that guide users and demonstrate the main capabilities of CFPy.

A data-driven approach for modelling Karst spring discharge using transfer function noise models.

Karst aquifers are important sources of fresh water on a global scale. The hydrological modelling of karst spring discharge, however, still poses a challenge. In this study we apply a transfer function noise (TFN) model in combination with a bucket-type recharge model to simulate karst spring discharge. The application of the noise model for the residual series has the advantage that it is more consistent with assumptions for optimization such as homoscedasticity and independence. In an earlier hydrological modeling study, named Karst Modeling Challenge (KMC; Jeannin et al., J Hydrol 600:126-508, 2021), several modelling approaches were compared for the Milandre Karst System in Switzerland. This serves as a benchmark and we apply the TFN model to KMC data, subsequently comparing the results to other models. Using different data-model-combinations, the most promising data-model-combination is identified in a three-step least-squares calibration. To quantify uncertainty, the Bayesian approach of Markov-chain Monte Carlo (MCMC) sampling is subsequently used with uniform priors for the previously identified best data-model combination. The MCMC maximum likelihood solution is used to simulate spring discharge for a previously unseen testing period, indicating a superior performance compared to all other models in the KMC. It is found that the model gives a physically feasible representation of the system, which is supported by field measurements. While the TFN model simulated rising limbs and flood recession especially well, medium and baseflow conditions were not represented as accurately. The TFN approach poses a well-performing data-driven alternative to other approaches that should be considered in future studies.

Secure Bluetooth Communication in Smart Healthcare Systems: A Novel Community Dataset and Intrusion Detection System.

Smart health presents an ever-expanding attack surface due to the continuous adoption of a broad variety of Internet of Medical Things (IoMT) devices and applications. IoMT is a common approach to smart city solutions that deliver long-term benefits to critical infrastructures, such as smart healthcare. Many of the IoMT devices in smart cities use Bluetooth technology for short-range communication due to its flexibility, low resource consumption, and flexibility. As smart healthcare applications rely on distributed control optimization, artificial intelligence (AI) and deep learning (DL) offer effective approaches to mitigate cyber-attacks. This paper presents a decentralized, predictive, DL-based process to autonomously detect and block malicious traffic and provide an end-to-end defense against network attacks in IoMT devices. Furthermore, we provide the BlueTack dataset for Bluetooth-based attacks against IoMT networks. To the best of our knowledge, this is the first intrusion detection dataset for Bluetooth classic and Bluetooth low energy (BLE). Using the BlueTack dataset, we devised a multi-layer intrusion detection method that uses deep-learning techniques. We propose a decentralized architecture for deploying this intrusion detection system on the edge nodes of a smart healthcare system that may be deployed in a smart city. The presented multi-layer intrusion detection models achieve performances in the range of 97-99.5% based on the F1 scores.

In Situ Thermometry of Fermionic Cold-Atom Quantum Wires.

We study ensembles of fermionic cold-atom quantum wires with tunable transverse mode population and single-wire resolution. From in situ density profiles, we determine the temperature of the atomic wires in the weakly interacting limit and reconstruct the underlying potential landscape. By varying atom number and temperature, we control the occupation of the transverse modes and study the 1D-3D crossover. In the 1D limit, we observe an increase of the reduced temperature T/T_{F} at nearly constant entropy per particle S/Nk_{B}. The ability to probe individual atomic wires in situ paves the way to quantitatively study equilibrium and transport properties of strongly interacting 1D Fermi gases.

An Approximation of Inner Boundary Conditions for Wells Intersecting Highly Conductive Structures.

Inner boundary conditions describe the interaction of groundwater wells with the surrounding aquifer during pumping and are associated with well-skin damage that limits water production and water derived from wellbore storage. Pumping test evaluations of wells during immediate and early time flow require assignment of inner boundary conditions. Originally, these concepts were developed for vertical well screens, and later transferred to wellbores intersecting highly conductive structures, such as preferential flow zones in fractured and karstic systems. Conceptual models for pumping test analysis in complex bedrock geology are often simplified. Classic analytical solutions generally lump or ignore conditions that limit or enhance well productivity along the well screen at the onset of pumping. Numerical solutions can represent well drawdowns in complex geological settings, such as karst systems, more precisely than many analytical solutions by accounting for additional physical processes and avoiding assumptions and simplifications. Suitable numerical tools for flow simulations in karst are discrete pipe-continuum models that account for various physical processes such as the transient hydraulics of wellbores intersecting highly conductive structures during pumping.

Impact of Integrase Inhibition Compared With Nonnucleoside Inhibition on HIV Reservoirs in Lymphoid Tissues.

BACKGROUND: HIV is produced in lymphoid tissues (LT) and stored on the follicular dendritic cell network in LT. When antiretroviral therapy is started, plasma viremia decays in 2 phases; the first within days of starting therapy and the second over weeks. Raltegravir (RAL), an integrase inhibitor, has been associated with only a single rapid phase of decay, and we speculated this may be due to higher intracellular concentration (IC) of RAL in LT. We have previously measured suboptimal ICs of antiretroviral therapy agents in LT, which were associated with slower decay of both vRNA+ cells and the follicular dendritic cell network pool. SETTING: Outpatient clinic at the Joint Clinical Research Center in Kampala, Uganda. METHODS: We compared the rate of decay in LT in people starting RAL with those starting efavirenz (EFV). RESULTS: There was no difference in the rate of virus decay in LT. The ratio of the ICs of RAL and EFV in lymph node to the concentration of drug that inhibits 95% of virus in blood was 1 log lower in lymph node for EFV and >3 logs lower for RAL. CONCLUSION: These data further highlight the challenges of drug delivery to LT in HIV infection and demonstrate that RAL is not superior to EFV as judged by direct measurements of the source of virus in LT.

Lymphoid tissue fibrosis is associated with impaired vaccine responses.

Vaccine responses vary by geographic location. We have previously described how HIV-associated inflammation leads to fibrosis of secondary lymph nodes (LNs) and T cell depletion. We hypothesized that other infections may cause LN inflammation and fibrosis, in a process similar to that seen in HIV infection, which may lead to T cell depletion and affect vaccine responses. We studied LNs of individuals from Kampala, Uganda, before and after yellow fever vaccination (YFV) and found fibrosis in LNs that was similar to that seen in HIV infection. We found blunted antibody responses to YFV that correlated to the amount of LN fibrosis and loss of T cells, including T follicular helper cells. These data suggest that LN fibrosis is not limited to HIV infection and may be associated with impaired immunologic responses to vaccines. This may have an impact on vaccine development, especially for infectious diseases prevalent in the developing world.

Defining total-body AIDS-virus burden with implications for curative strategies.

In the quest for a functional cure or the eradication of HIV infection, it is necessary to know the sizes of the reservoirs from which infection rebounds after treatment interruption. Thus, we quantified SIV and HIV tissue burdens in tissues of infected nonhuman primates and lymphoid tissue (LT) biopsies from infected humans. Before antiretroviral therapy (ART), LTs contained >98% of the SIV RNA+ and DNA+ cells. With ART, the numbers of virus (v) RNA+ cells substantially decreased but remained detectable, and their persistence was associated with relatively lower drug concentrations in LT than in peripheral blood. Prolonged ART also decreased the levels of SIV- and HIV-DNA+ cells, but the estimated size of the residual tissue burden of 108 vDNA+ cells potentially containing replication-competent proviruses, along with evidence of continuing virus production in LT despite ART, indicated two important sources for rebound following treatment interruption. The large sizes of these tissue reservoirs underscore challenges in developing 'HIV cure' strategies targeting multiple sources of virus production.

Evaluation of Vaginal Drug Levels and Safety of a Locally Administered Glycerol Monolaurate Cream in Rhesus Macaques.

The human immunodeficiency virus epidemic affects millions of people worldwide. As women are more vulnerable to infection, female-controlled interventions can help control the spread of the disease significantly. Glycerol monolaurate (GML), an inexpensive and safe compound, has been shown to protect against simian immunodeficiency virus infection when applied vaginally. However, on account of its low aqueous solubility, fabrication of high-dose formulations of GML has proven difficult. We describe the development of a vaginal cream that could be loaded with up to 35% GML. Vaginal drug levels and safety of 3 formulations containing increasing concentrations of GML (5%w/w, 15%w/w, and 35%w/w) were tested in rhesus macaques after vaginal administration. GML concentration in the vaginal tissue increased as the drug concentration in the cream increased, with 35% GML cream resulting in tissue concentration of ∼0.5 mg/g, albeit with high interindividual variability. Compared with the vehicle control, none of the GML creams had any significant effect on the vaginal flora and cytokine (macrophage inflammatory protein 3α and interleukin 8) levels, suggesting that high-dose GML formulations do not induce local adverse effects. In summary, we describe the development of a highly loaded vaginal cream of GML, and vaginal drug levels and safety after local administration in macaques.

Large number of rebounding/founder HIV variants emerge from multifocal infection in lymphatic tissues after treatment interruption.

Antiretroviral therapy (ART) suppresses HIV replication in most individuals but cannot eradicate latently infected cells established before ART was initiated. Thus, infection rebounds when treatment is interrupted by reactivation of virus production from this reservoir. Currently, one or a few latently infected resting memory CD4 T cells are thought be the principal source of recrudescent infection, but this estimate is based on peripheral blood rather than lymphoid tissues (LTs), the principal sites of virus production and persistence before initiating ART. We, therefore, examined lymph node (LN) and gut-associated lymphoid tissue (GALT) biopsies from fully suppressed subjects, interrupted therapy, monitored plasma viral load (pVL), and repeated biopsies on 12 individuals as soon as pVL became detectable. Isolated HIV RNA-positive (vRNA+) cells were detected by in situ hybridization in LTs obtained before interruption in several patients. After interruption, multiple foci of vRNA+ cells were detected in 6 of 12 individuals as soon as pVL was measureable and in some subjects, in more than one anatomic site. Minimal estimates of the number of rebounding/founder (R/F) variants were determined by single-gene amplification and sequencing of viral RNA or DNA from peripheral blood mononuclear cells and plasma obtained at or just before viral recrudescence. Sequence analysis revealed a large number of R/F viruses representing recrudescent viremia from multiple sources. Together, these findings are consistent with the origins of recrudescent infection by reactivation from many latently infected cells at multiple sites. The inferred large pool of cells and sites to rekindle recrudescent infection highlights the challenges in eradicating HIV.

Antifibrotic therapy in simian immunodeficiency virus infection preserves CD4+ T-cell populations and improves immune reconstitution with antiretroviral therapy.

Even with prolonged antiretroviral therapy (ART), many human immunodeficiency virus-infected individuals have <500 CD4(+) T cells/µL, and CD4(+) T cells in lymphoid tissues remain severely depleted, due in part to fibrosis of the paracortical T-cell zone (TZ) that impairs homeostatic mechanisms required for T-cell survival. We therefore used antifibrotic therapy in simian immunodeficiency virus-infected rhesus macaques to determine whether decreased TZ fibrosis would improve reconstitution of peripheral and lymphoid CD4(+) T cells. Treatment with the antifibrotic drug pirfenidone preserved TZ architecture and was associated with significantly larger populations of CD4(+) T cells in peripheral blood and lymphoid tissues. Combining pirfenidone with an ART regimen was associated with greater preservation of CD4(+) T cells than ART alone and was also associated with higher pirfenidone concentrations. These data support a potential role for antifibrotic drug treatment as adjunctive therapy with ART to improve immune reconstitution.

Modifications to the Conduit Flow Process Mode 2 for MODFLOW-2005.

As a result of rock dissolution processes, karst aquifers exhibit highly conductive features such as caves and conduits. Within these structures, groundwater flow can become turbulent and therefore be described by nonlinear gradient functions. Some numerical groundwater flow models explicitly account for pipe hydraulics by coupling the continuum model with a pipe network that represents the conduit system. In contrast, the Conduit Flow Process Mode 2 (CFPM2) for MODFLOW-2005 approximates turbulent flow by reducing the hydraulic conductivity within the existing linear head gradient of the MODFLOW continuum model. This approach reduces the practical as well as numerical efforts for simulating turbulence. The original formulation was for large pore aquifers where the onset of turbulence is at low Reynolds numbers (1 to 100) and not for conduits or pipes. In addition, the existing code requires multiple time steps for convergence due to iterative adjustment of the hydraulic conductivity. Modifications to the existing CFPM2 were made by implementing a generalized power function with a user-defined exponent. This allows for matching turbulence in porous media or pipes and eliminates the time steps required for iterative adjustment of hydraulic conductivity. The modified CFPM2 successfully replicated simple benchmark test problems.