Effects of GS-CA1 on nuclear envelope-associated early HIV-1 infection steps

Abstract The novel HIV-1 drugs GS-CA1 and the recently approved lenacapavir (GS-6207) target the viral structural protein capsid (CA). However, their multiple mechanisms of action have not been fully characterized. Here, we investigated the effects of GS-CA1 on the early stages of HIV-1 infection, specifically the steps involving the nuclear envelope, in comparison to the antiviral cytokine IFN-β. Mass spectrometry data indicated that nuclear envelope proteins were only modestly affected by either GS-CA1 treatment or HIV-1 infection, but combining the two had a more significant impact, altering the levels of many proteins including proteasomal components. GS-CA1 induced a small but clear accumulation of HIV-1 capsid cores at nuclear pores, as seen by microscopy, whereas IFN-β caused a strong accumulation of HIV-1 cores at the nuclear envelope but not specifically at nuclear pores. These observations are consistent with GS-CA1 inhibiting the nuclear translocation of HIV-1 capsid cores through nuclear pores

Penalty mechanism in transactive energy: A mechanism design approach for day-ahead markets

Ensuring incentive compatibility mechanisms to enforce market obligations is crucial in deploying a transactive energy system. While previous studies have reported adopting penalty mechanisms for market compliance, these studies did not generally analyse the incentive compatibility property of mechanism design. Neglecting this mechanism design property can lead to inefficient market outcomes and economic losses for system operators. This paper analyses self-enforcing policies to verify whether they comply with the incentive compatibility property in a one-shot market architecture. Additionally, it provides a comprehensive introduction to the phases of mechanism design – ex-ante, interim, and ex-post – and their relationship with key design principles: individual rationality, efficiency, budget balance, and incentive compatibility, highlighting expected outcomes at each phase. A case study demonstrates how a strategy-proof mechanism significantly influences individual rationality, efficiency, and budget balance, offering practical insights for improving decision-making frameworks in electricity markets. Moreover, the findings reveal that adopting a non-strategy-proof mechanism undermines the long-term viability of transactive energy systems. This work provides actionable recommendations for system operators and policymakers on implementing mechanisms that prevent strategic behaviour from agents

Individuals with chronic low back pain show impaired adaptations of lumbar extensor muscle reflex amplitude during unexpected perturbations

Abstract Purpose This study investigated the adaptability of trunk muscle responses to a series of unexpected external perturbations in patients with chronic low back pain (LBP). Methods Thirty-seven adult participants, including 19 without LBP (control group) and 18 with chronic LBP, were submitted to 15 repetitions of trunk perturbations applied in a posterior-to-anterior direction, inducing trunk flexion. High-density surface electromyography (HDsEMG) was used to analyze lumbar muscle reflex amplitude. A two-way repeated measures ANOVA (2 × 2) was conducted to compare group differences and the effect of trial repetition over time (first five trials vs. last five trials of perturbations). Results Significant interaction effects were found on both sides (Left: p = 0.038; Right: p = 0.007). Post hoc comparisons revealed a decrease in response amplitude only in the control group between the first and last five perturbations, with reductions of 5.0% on the left side (p = 0.026, Bonferroni corrected) and 5.7% on the right side (p = 0.030, Bonferroni corrected). In contrast, individuals with chronic LBP showed no significant adaptation through repetition in the reflex response amplitude of the lumbar extensor muscles (post hoc both sides: p > 0.05). Conclusion Individuals with chronic LBP fail to adapt reflex amplitudes to repeated perturbations, possibly due to impaired proprioception, reduced motor variability and neuroplastic changes observed in individuals with chronic LBP. These changes might limit their ability to optimize responses to repeated perturbations, potentially compromising spinal stability and increasing functional cost