Direct and dynamic detection of HIV-1 in living cells.

In basic and applied HIV research, reliable detection of viral components is crucial to monitor progression of infection. While it is routine to detect structural viral proteins in vitro for diagnostic purposes, it previously remained impossible to directly and dynamically visualize HIV in living cells without genetic modification of the virus. Here, we describe a novel fluorescent biosensor to dynamically trace HIV-1 morphogenesis in living cells. We generated a camelid single domain antibody that specifically binds the HIV-1 capsid protein (CA) at subnanomolar affinity and fused it to fluorescent proteins. The resulting fluorescent chromobody specifically recognizes the CA-harbouring HIV-1 Gag precursor protein in living cells and is applicable in various advanced light microscopy systems. Confocal live cell microscopy and super-resolution microscopy allowed detection and dynamic tracing of individual virion assemblies at the plasma membrane. The analysis of subcellular binding kinetics showed cytoplasmic antigen recognition and incorporation into virion assembly sites. Finally, we demonstrate the use of this new reporter in automated image analysis, providing a robust tool for cell-based HIV research

Multilayer Environment and Toolchain for Holistic NetwOrk Design and Analysis

The recent developments and research in distributed ledger technologies and blockchain have contributed to the increasing adoption of distributed systems. To collect relevant insights into systems' behavior, we observe many evaluation frameworks focusing mainly on the system under test throughput. However, these frameworks often need more comprehensiveness and generality, particularly in adopting a distributed applications' cross-layer approach. This work analyses in detail the requirements for distributed systems assessment. We summarize these findings into a structured methodology and experimentation framework called METHODA. Our approach emphasizes setting up and assessing a broader spectrum of distributed systems and addresses a notable research gap. We showcase the effectiveness of the framework by evaluating four distinct systems and their interaction, leveraging a diverse set of eight carefully selected metrics and 12 essential parameters. Through experimentation and analysis we demonstrate the framework's capabilities to provide valuable insights across various use cases. For instance, we identify that a combination of Trusted Execution Environments with threshold signature scheme FROST introduces minimal overhead on the performance with average latency around \SI{40}{\ms}. We showcase an emulation of realistic systems behavior, e.g., Maximal Extractable Value is possible and could be used to further model such dynamics. The METHODA framework enables a deeper understanding of distributed systems and is a powerful tool for researchers and practitioners navigating the complex landscape of modern computing infrastructures

The Plurality of Farmers’ Views on Soil Management Calls for a Policy Mix

While soil degradation is continuing to threaten the global agricultural production system, a common understanding of how to encourage sustainable soil management is missing. With this study, we aim to provide new insights on targeted policies that address the heterogeneity of farmers. We scrutinized the plurality of views on soil management among arable farmers in the Austrian (and European) policy context. To do so, we applied Q methodology, a method that identifies different perspectives on a topic present in a population and analyzes this subjectivity statistically. We interviewed 34 arable land farmers who varied in their farming backgrounds. The results yielded four different viewpoints on soil management held by the interviewed farmers: two rather ecocentric perspectives (Nature Participants, Pleasure Seekers) and two rather anthropocentric perspectives (Traditional Food Providers, Profit Maximizers). Our study shows that farmers’ soil management is influenced by more than economic considerations and suggests that a mix of policy approaches is needed to reach all farmers and avoid adverse effects of excluding farmers. We provide several suggestions for policymakers on how to complement agri-environmental policies: appealing to human-nature relationships, offering training and experimentation services, fostering social networks, and raising the social reputation of farmers

Seismicity during and after stimulation of a 6.1 km deep enhanced geothermal system in Helsinki, Finland

In this study, we present a high-resolution dataset of seismicity framing the stimulation campaign of a 6.1 km deep Enhanced Geothermal System (EGS) in Helsinki suburban area and discuss the complexity of fracture network development. Within St1 Deep Heat project, 18 160 m3 of water was injected over 49 days in summer 2018. The seismicity was monitored by a seismic network of near-surface borehole sensors framing the EGS site in combination with a multi-level geophone array located at ≥ 2 km depth. We expand the original catalog of Kwiatek et al. (2019) and provide the community with the dataset including detected seismic events and earthquakes that occurred two month after the end of injection, totalling to 61 163 events. We relocated events of the catalog with sufficient number of available phase onsets and moment magnitudes between Mw −0.7 and Mw 1.9 using the double-difference technique and a new velocity model derived from a post-stimulation vertical seismic profiling campaign. The analysis of the fault network development at reservoir depth of 4.5–7 km is one primary focus of this study. To achieve this, we investigate 191 focal mechanisms of the induced seismicity using cross-correlation based technique. Our results indicate that seismicity occurred in three spatially separated clusters centered around the injection well. We observe a spatio-temporal migration of the seismicity during the stimulation starting from the injection well in northwest (NW) – southeast (SE) direction and in northeast (NE) direction towards greater depth. The spatial evolution of the cumulative seismic moment, the distribution of events with Mw ≥ 1 and the fault plane orientations of focal mechanisms indicate an active network of at least three NW–SE to NNW-SSE orientated permeable zones which is interpreted to be responsible for migration of seismic activity away from the injection well. Fault plane solutions of the best-constrained focal mechanisms as well as results for the local stress field orientation indicate a reverse faulting regime and suggest that seismic slip occurred on a sub-parallel network of pre-existing weak fractures favorably oriented with the stress field, striking NNW-SEE with a dip of 45° ENE, parallel to the injection well.Peer reviewe

Contribution of the μ-opioid receptor system to affective disorders in temporal lobe epilepsy: A bidirectional relationship?

OBJECTIVE Affective disorders are frequent comorbidities of temporal lobe epilepsy (TLE). The endogenous opioid system has been implicated in both epilepsy and affective disorders, and may play a significant role in their bidirectional relationship. In this cross-sectional study, we investigated the association between μ-opioid receptor binding and affective disorders in patients with TLE. METHODS Nine patients with TLE and depression/anxiety underwent $^{11}$ C-carfentanil positron emission tomography (CFN PET) and neuropsychiatric assessment, including the Hospital Anxiety and Depression Scale and the Positive and Negative Affect Schedule. The normalized CFN PET scans were compared with those of 26 age-matched healthy controls. Correlation analyses with affective symptoms were performed by region of interest-based analysis focusing on the limbic circuit and orbitofrontal cortex. RESULTS We observed widely reduced CFN binding potential (BP) in bilateral frontal lobes and striata in patients with TLE compared to healthy controls. In the TLE group, more severe anxiety and negative affect were associated with decreased CFN BP in the posterior cingulate gyrus. SIGNIFICANCE In patients with TLE, interictally reduced binding in the opioid system was associated with higher levels of anxiety and negative affect. We speculate that seizure-related agonist-driven desensitization and downregulation of opioid receptors could be a potential underlying pathomechanism

Modelling geomagnetically induced currents in midlatitude Central Europe using a thin-sheet approach

Geomagnetically induced currents (GICs) in power systems, which can lead to transformer damage over the short and the long term, are a result of space weather events and geomagnetic variations. For a long time, only high-latitude areas were considered to be at risk from these currents, but recent studies show that considerable GICs also appear in midlatitude and equatorial countries. In this paper, we present initial results from a GIC model using a thin-sheet approach with detailed surface and subsurface conductivity models to compute the induced geoelectric field. The results are compared to measurements of direct currents in a transformer neutral and show very good agreement for short-period variations such as geomagnetic storms. Long-period signals such as quiet-day diurnal variations are not represented accurately, and we examine the cause of this misfit. The modelling of GICs from regionally varying geoelectric fields is discussed and shown to be an important factor contributing to overall model accuracy. We demonstrate that the Austrian power grid is susceptible to large GICs in the range of tens of amperes, particularly from strong geomagnetic variations in the east–west direction

Controlling fluid-induced seismicity during a 6.1-km-deep geothermal stimulation in Finland

We show that near–real-time seismic monitoring of fluid injection allowed control of induced earthquakes during the stimulation of a 6.1-km-deep geothermal well near Helsinki, Finland. A total of 18,160 m3 of fresh water was pumped into crystalline rocks over 49 days in June to July 2018. Seismic monitoring was performed with a 24-station borehole seismometer network. Using near–real-time information on induced-earthquake rates, locations, magnitudes, and evolution of seismic and hydraulic energy, pumping was either stopped or varied—in the latter case, between well-head pressures of 60 and 90 MPa and flow rates of 400 and 800 liters/min. This procedure avoided the nucleation of a project-stopping magnitude MW 2.0 induced earthquake, a limit set by local authorities. Our results suggest a possible physics-based approach to controlling stimulation-induced seismicity in geothermal projects.Peer reviewe

Beiträge zur Kenntnis des Gay-Lussacschen Gesetzes

vom Realgymnasiallehrer Leonhard