Search Results (128)

Decentralized finance (DeFi) has been studied mainly as a financial and technological system, while the role of digital entrepreneurial capability in shaping sustainable user traction remains underexplored. This study repositions DeFi as a digitally mediated entrepreneurial ecosystem and examines whether retention-oriented user behavior is associated with three capability dimensions—entrepreneurial visibility, network embeddedness, and organic acquisition efficiency—together with ecosystem-finance conditions such as total value locked and decentralized-exchange activity. Using an exploratory, correlational design with monthly aggregated data from five incumbent DeFi platforms during the post-FTX recovery period (October 2022–September 2023), the analysis combines canonical correlation analysis, partial least squares regression, and ridge regression. Results indicate a significant multivariate association between ecosystem-finance conditions and the entrepreneurial-capability block, and show that returning-visitor behavior is more coherently linked to the predictor set than broad visitor inflow. Entrepreneurial Visibility Capital and Network Embeddedness emerge as the most stable positive correlates of user retention, while Organic Acquisition Efficiency shows a directionally mixed pattern. Because the sample is small, the findings are interpreted as preliminary evidence rather than confirmatory claims. Overall, the study offers an integrative framework that connects DeFi, digital entrepreneurship, and sustainability-oriented business-model research, and identifies the joint configuration of digital capability and financial conditions as a promising direction for future, larger-scale investigation. Full article

The continued evolution of SARS-CoV-2 has enabled an escape from most monoclonal antibodies, yet a subset of broadly neutralizing antibodies targeting three newly identified super-conserved RBD epitopes—SCORE-A, SCORE-B, and SCORE-C—retains remarkable activity against even the most recent JN.1-derived sublineages. Here, we employed an integrated computational framework combining conformational dynamics, mutational scanning, MM-GBSA binding energetics, and frustration profiling to dissect the molecular mechanisms by which XGI antibodies achieve broad neutralization and resistance to immune escape. Structural analysis revealed that all three SCORE epitopes share a common architecture: a highly conserved, minimally frustrated core that provides stable anchoring, flanked by peripheral regions that accommodate antibody-specific variations. Conformational dynamics showed that SCORE-A antibodies (XGI-183) rigidify the lateral epitope while leaving the RBM partially mobile; SCORE-B antibodies (XGI-198, XGI-203) clamp the RBM apex, directly blocking ACE2; and SCORE-C antibodies (XGI-171) allosterically loosen the RBM loop, impairing receptor engagement indirectly. Mutational scanning identified a hierarchical hotspot organization where primary hotspots (e.g., K356, T500, Y380, T385) are evolutionarily constrained and minimally frustrated, while secondary hotspots (e.g., V503, Y508, S383) are neutrally frustrated and represent the principal sites of immune-driven mutations. MM-GBSA decomposition revealed that van der Waals-driven hydrophobic packing dominates binding, with electrostatic interactions providing auxiliary stabilization. Critically, frustration analysis demonstrated that immune escape hotspots reside precisely in zones of neutral frustration—“energetic playgrounds” that permit mutational exploration without destabilizing the RBD—while minimally frustrated cores are evolutionarily locked. The comparative analysis of conformational versus mutational frustration distributions revealed a unifying principle: aligned neutral frustration yields permissive, escape-prone interfaces; decoupling enables the targeting of constrained cores; and the convergence of minimal frustration in both distributions creates invulnerable interfaces. These findings establish that broad neutralization arises not from ultra-high-affinity anchors but from strategic energy distribution across rigid, evolutionarily informed interfaces, providing a roadmap for designing next-generation therapeutics that target the invulnerable cores of viral surface proteins. Full article

The block-and-lock strategy aims to achieve a functional cure for human immunodeficiency virus type 1 (HIV-1) infection by enforcing durable, drug-independent silencing of proviral transcription. Several latency-promoting agents have been described that effectively limit viral reactivation in vitro or in animal models. However, most approaches induce only partial or reversible transcriptional repression and have not yet been translated into safe and effective clinical interventions. This review summarizes the molecular mechanisms underlying block-and-lock strategies and critically evaluates the limitations of current candidate compounds. We highlight recent advances in understanding HIV-1 integration site selection, focusing on the roles of lens epithelium-derived growth factor p75 (LEDGF/p75) and cleavage and polyadenylation specificity factor subunit 6 (CPSF6) in directing proviral integration toward gene-dense, transcriptionally active chromatin. Pharmacological disruption of the LEDGF/p75–integrase interaction by LEDGF/p75 inhibitors (LEDGINs) redirects proviral integration toward less transcriptionally active genomic regions that are more resistant to reactivation. Recent tandem knockout experiments, however, demonstrate that CPSF6 plays a dominant role in guiding HIV-1 integration toward gene-dense, transcriptionally active chromatin. LEDGIN treatment has been linked to the preferential targeting of proviruses to heterochromatin-rich regions within the nuclear interior. By contrast, CPSF6 knockout redirects integration toward peripheral heterochromatin, especially lamina-associated domains (LADs), genomic regions typically exhibiting stronger and more stable transcriptional repression than interior heterochromatin. These findings suggest that therapeutic modulation of CPSF6 may exert a more profound and durable effect on proviral silencing within a block-and-lock framework. Nevertheless, complete CPSF6 ablation is associated with severe cellular toxicity. The challenges associated with CPSF6-related adverse effects and potential strategies to overcome these limitations are discussed. Full article

The Midong Block is currently a primary target for coalbed methane (CBM) exploration and development in Xinjiang. However, fracturing operations in this region generally exhibit low flowback rates, which escalate the risk of reservoir damage and ultimately suppress daily gas production. To elucidate the impact of various geological and engineering factors on flowback efficiency and permeability damage, as well as their underlying mechanisms, this study conducted fracturing fluid flowback simulation experiments. The pulse-decay permeability measurement and weighing methods were employed to quantify the variations in flowback rates and permeability damage intensities under different conditions. Experimental results indicated that the permeability damage rate in the Xishanyao Formation coal samples ranged from 3.12% to 92.86% after flowback, with 92% of the samples exhibiting a flowback rate of less than 10%. This significant impairment was primarily attributed to the synergistic effects of stress-induced fracture closure, clay mineral hydration swelling, and coal fines migration. Specifically, elevated confining pressures and prolonged soaking times exacerbated reservoir damage. A low flowback pressure differential intensified the water locking effect, hindering fluid recovery. Notably, the flowback velocity displayed a U-shaped velocity sensitivity profile. In the low-temperature regime, damage characteristics fluctuated, controlled by competitive thermal–hydro–mechanical (THM) coupling mechanisms. Full article

Human immunodeficiency virus type 1 (HIV-1) is a retrovirus that integrates into the host cell’s DNA as a provirus. Transcription from the provirus is regulated in large part by cellular proteins and epigenetic factors. These may be repressive or permissive to productive infection. The host factors that regulate this balance are therefore attractive targets for HIV-1 therapeutics. Indeed, proviral chromatin is the focus of two of the current HIV-1 cure strategies. “Shock and Kill” uses latency reversal agents to open the provirus’s chromatin, promoting high levels of gene expression that induce the killing of infected cells. “Block and Lock” uses latency promoting agents to induce heterochromatin, blocking transcription and forcing HIV-1 into a state of deep latency. Here, the compounds investigated in both strategies are reviewed, including their chemical structures, mechanisms of action, and clinical results. Finally, the use of CRISPR-Cas therapeutics and the impact of chromatin architecture on its efficacy are discussed. Full article

The energy transition takes a long time and requires a complex process involving stakeholder consensus. This study aims to explore the political, economic, and sociocultural dynamics that emerged during the short-term energy transition between the Moon and Yoon administrations in Korea, assessing the current energy transition, which stands at a crossroads, and provides conclusions and implications to inform future decisions on the findings. To this purpose, a multi-level perspective analytical framework was applied to investigate the two administrations’ conflicting energy transition mechanisms on the level of actors, technologies, and rules/institutions. According to the results, the Moon administration pursued a reconfiguration pathway of limited changes by attempting to phase out nuclear power plants and expand renewable energy, while the Yoon administration promoted a transformation pathway of partial change by abandoning the policy of phasing out nuclear power plants and further expanding existing nuclear energy. Differences in pathways were found to stem from differentiation based on political ideology and political purposes among key actors, rather than socio-technological innovation. This paper argues that Korea’s short-term energy transition was hastily pursued amidst a lack of public discourse, insufficient technological development, and institutional deficiencies, ultimately blocking the pathway to a desirable energy transition and having Korea locked in its existing energy system. This paper also suggests that no single pathway exists to carbon neutrality, and that future administrations can find desirable pathways by overcoming challenges and dilemmas through continuous improvement and adjustment. Full article

This paper presents an all-digital fractional-N phase-locked loop (ADPLL) operating in the 2.86–3.2 GHz range, optimized for IoT and high-frequency RF transceiver applications demanding stringent phase noise performance, fast settling time, and high integration capability. The key innovation lies in the introduction of a bandpass delta-sigma time-to-digital converter (BPDSTDC) that achieves high-resolution phase detection, an extended detection range of ±2$\pi$, and superior noise-shaping characteristics, completely eliminating the complex calibration procedures typically required in conventional TDC designs. The proposed architecture synergistically combines the BPDSTDC with digital down-conversion blocks to extract phase error at baseband, a divider chain integrated with phase interpolators achieving 1/4 fractional resolution to suppress in-band quantization noise, and a wide-bandwidth digital loop filter (>1 MHz) ensuring fast dynamic response and robust stability. The bandpass delta-sigma modulator is implemented with compact resonator structures and a flash quantizer, achieving an optimal balance among resolution, power consumption, and silicon area. The incorporation of highly linear phase interpolators extends fractional frequency synthesis capability without requiring complex digital-to-time converters (DTCs), significantly reducing design complexity and calibration overhead. Fabricated in a 180-nm CMOS technology, the proposed chip demonstrates robust measured performance. The band-pass delta-sigma TDC achieves a low integrated rms timing noise of 183 fs within a 1-MHz bandwidth. Leveraging this low TDC noise, the complete ADPLL exhibits a measured in-band phase noise of −120 dBc/Hz at a 1-MHz offset for a 3.2-GHz output frequency while operating with a loop bandwidth exceeding 1 MHz. This corresponds to a normalized phase noise of −216 dBc/Hz. The system operates from a 1.8-V supply and consumes 10 mW, achieving competitive performance compared with prior noise-shaping TDC-based all-digital PLLs. Full article

The Netherlands is widely recognised as the global leader in water management, with its flood risk management (FRM) infrastructure lauded as being of the best in the world. This status notwithstanding, Dutch FRM primarily maintains established infrastructural practices and experimental applications of NBSs remain less frequent than established structural projects. This paper details and examines the challenges associated with the prevailing ‘business-as-usual’ approach to FRM in The Netherlands, in which traditional ‘grey’ infrastructural techniques are prioritised over innovative ‘green’ nature-based solutions (NBSs). In line with emerging international trends, such as the EU Water Resilience Strategy, NBSs are increasingly advocated as a strategic, complementary layer to enhance the resilience of existing safety frameworks rather than a self-evident replacement for them. Contrary to grey infrastructure, NBSs provide a number of environmental and social co-benefits extending beyond their flood and drought protection utility. The literature on NBSs details the design, effectiveness, and positive socio-economic impact of the operationalisation of such projects for FRM. This notwithstanding, the uptake and practical implementation of NBSs have been slow in The Netherlands. From a legal and policy perspective, this has been attributed to a lack of political will and the corresponding failure to include NBSs in long term FRM planning. Given the long planning horizons associated with FRM (50–100 years), the failure to incorporate NBSs can lead to policy lock-in that blocks future adaptations. Against this backdrop, this paper employs a semi-systematic literature review to clarify the obstacles to implementing NBSs in Dutch FRM and sets a research agenda that charts a course to mainstreaming NBSs in Dutch FRM. Seven core focus areas for future research are identified. The paper concludes by drawing on these identified focus areas to construct a research agenda aimed at systematically addressing each barrier to the practical operationalisation of NBSs in Dutch FRM, emphasising a hybrid green–grey approach which may serve to inspire similar research in other jurisdictions. Full article

Leveraging the complementary strengths of handcrafted radiomics and data-driven deep learning, this work develops and rigorously benchmarks three modeling streams (Models A, B and C) for pancreatic ductal adenocarcinoma (PDAC) detection on multiphase abdominal Computed Tomography (CT) scans. Model A distills hundreds of PyRadiomics descriptors to sixteen interpretable features that feed a gradient-boosted machine learning model, achieving discrimination (external AUC ≈ 0.99) with excellent calibration. Model B adopts a 3-D CBAM-ResNet-18 trained under weighted cross-entropy and mixed precision; although less accurate in isolation, it yields volumetric Grad-CAM maps that localize the tumor and provide explainability. Model C explores two fusion strategies that merge radiomics and deep embeddings: (i) a two-stage “frozen-stream” variant that locks both feature extractors and learns only a lightweight gating block plus classifier, and (ii) a full end-to-end version that allows the CNN’s adaptor layer to co-train with the fusion head. The frozen approach surpasses the single stream, whereas the end-to-end model reports external AUC of 0.987, balanced sensitivity/specificity above 0.93, and a Brier score below 0.05, while preserving clear Grad-CAM alignment with radiologist-drawn masks. Results demonstrate that a carefully engineered deep-radiomic fusion pipeline can deliver accurate, well-calibrated and interpretable PDAC triage directly from routine CT. Our contributions include a stability-verified 16-feature radiomic signature, a novel deep-radiomic fusion design that improves robustness and interpretability across vendors and a fully guideline-aligned, openly released pipeline for reproducible PDAC detection on routine CT. Full article

This paper presents an in-depth study on the structural integrity enhancement and machining process optimization of Anti-lock Braking System (ABS) hydraulic valve blocks, focusing on the transition from the MK60 to the MK100 design. The research combines finite element analysis (FEA), topology optimization, fixture redesign, and coolant technology improvements to achieve significant performance, productivity, and sustainability gains. The MK100 exhibits a mass reduction of 31.6%, an increase in tensile strength by 29.2%, and a fatigue life extension of 35% compared to the MK60. Pressure losses have been reduced by 38.8%, improving braking system responsiveness. On the manufacturing side, fixture redesign increased production capacity from 240 to 480 parts per shift while reducing cycle time from 16 min to 8 min per lot. The transition from a semi-synthetic emulsion coolant (AquaCut EM-X45) to a bio-based oil (BioLube AL-2200) extended coolant replacement intervals from six months to two years, reduced tooling costs, and increased tool life by 25%. These findings demonstrate the feasibility of integrating computational design methods with advanced machining strategies to achieve measurable mechanical and economic benefits in the automotive industry. Full article

Remarkable advances in Quartz-Enhanced Photoacoustic Spectroscopy (QEPAS) made it one of the most effective gas-sensing techniques in terms of sensitivity and selectivity. Consequently, its range of possible applications is continuously expanding, but in some cases is still limited by the cost and/or size of the equipment needed to im-plement a complete QEPAS sensor. In particular, bulky and expensive lab instruments are often used to realize the electronic building blocks required by this technique, which prevents, for instance, integration of the system on board a drone. This work addresses this issue by presenting the development of compact electronic modules for a QEPAS sensor. A very low-noise, fully differential preamplifier for the quartz tuning fork, with digital output and programmable gain, has been designed and realized. A compact FPGA board hosts both an accurate function generation module, which synthesizes the signals needed to modulate the laser source, and an innovative lock-in amplifier based on the CORDIC algorithm. QEPAS sensors based on the designed electronics have been used for the detection of H₂O and CO₂ in ambient air, proving the full functionality of all the blocks. These results highlight the potential of compact electronics to promote portable and cost-effective QEPAS applications. Full article

Self-oscillations convert ambient energy into continuous periodic motion through feedback mechanisms, but their response to external periodic disturbances is not yet fully understood. Through the combination of a photothermally-responsive liquid crystal elastomer fiber and a mass block within a linear light field, we consider a liquid crystal elastomer self-oscillator. Following theoretical modeling of the light-driven self-oscillator under external periodic forcing and numerical simulations, three distinct phase-locking regimes are identified: in-phase, anti-phase, and quadrature synchronizations. Mechanisms are elucidated through time-domain, frequency-domain, and phase-space analyses. Moreover, approximate analytical expressions for the steady-state amplitude–frequency and phase–frequency responses of the self-oscillator under periodic forcing are derived using the multi-scale method. The impact of periodic forcing on the self-oscillator and its response regulation via system parameters is examined. A close correspondence exists between numerical and analytical results. This work investigates the response characteristics of a liquid crystal elastomer self-oscillator under periodic forcing, advances fundamental insights into disturbance rejection in self-oscillators, and delivers practical guidance for their robust operation in complex oscillatory settings. Full article

Understanding gas–water two-phase flow mechanisms in deep tight gas reservoirs is critical for improving production performance and mitigating water invasion. However, the effects of pore-throat-fracture multiscale structures on gas–water flow remain inadequately understood, particularly under high-temperature and high-pressure conditions (HT/HP). In this study, we developed visualizable multiscale throat-pore and throat-pore-fracture physical nanofluidic chip models (feature sizes 500 nm–100 μm) parameterized with Keshen block geological data in the Tarim Basin. We then established an HT/HP nanofluidic platform (rated to 240 °C, 120 MPa; operated at 100 °C, 100 MPa) and, using optical microscopy, directly visualized spontaneous water imbibition and gas–water displacement in the throat-pore and throat-pore-fracture nanofluidic chips and quantified fluid saturation, front velocity, and threshold pressure gradients. The results revealed that the spontaneous imbibition process follows a three-stage evolution controlled by capillarity, gas compression, and pore-scale heterogeneity. Nanoscale throats and microscale pores exhibit good connectivity, facilitating rapid imbibition without significant scale-induced resistance. In contrast, 100 μm fractures create preferential flow paths, leading to enhanced micro-scale water locking and faster gas–water equilibrium. The matrix gas displacement threshold gradient remains below 0.3 MPa/cm, with the cross-scale Jamin effect—rather than capillarity—dominating displacement resistance. At higher pressure gradients (~1 MPa/cm), water is efficiently expelled to low saturations via nanoscale throat networks. This work provides an experimental platform for visualizing gas–water flow in multiscale porous media under ultra-high temperature and pressure conditions and offers mechanistic insights to guide gas injection strategies and water management in deep tight gas reservoirs. Full article

A key direction of the development of modern power systems is the application of a continuously increasing number of grid-forming power converters to provide various system services. One of the possible strategies for the implementation of grid-forming control is a control algorithm based on a virtual synchronous generator (VSG). However, at present, the problem of VSG operation under abnormal conditions associated with an increase in output current remains unsolved. Existing current saturation algorithms (CSAs) lead to the degradation of grid-forming properties during overcurrent limiting or reduce the possible range of current output. In this regard, this paper proposes to use the structure of modified current-controlled VSG (CC-VSG) instead of traditional voltage-controlled VSG. A current vector amplitude limiter is used to limit the output current in the CC-VSG structure. At the same time, the angle of the current reference vector continues to be regulated based on the emerging operating conditions due to the voltage feedback in the used VSG equations. The presented simulation results have shown that it was possible to achieve a wide operating range for the current phase from 0° to 180° in comparison with a traditional VSG algorithm. At the same time, the properties of the grid-forming inverter, such as power synchronization without phase-locked loop controller, voltage, and frequency control, are preserved. In addition, in order to avoid saturation of the voltage controller, it is proposed to use a simple algorithm of blocking and switching the reference signal from the setpoint to the current voltage level. Due to this structure, it was possible to prevent saturation of integrators in the control loops and to provide a guaranteed exit from the limiting mode. The results of adding this structure showed a five-second reduction in the overvoltage that occurs when it is absent. A comparison with conditional integration also showed that it prevented lock-up in the limiting mode. The results of experimental verification of the developed prototype of the inverter with CC-VSG control and CSA are also given, including a comparison with the serial model of the hybrid inverter. The results obtained showed that the developed algorithm excludes both the dead time and the load current loss when the external grid is disconnected. In addition, there is no tripping during overload, unlike a hybrid inverter. Full article

We present a case of unexpected proximal displacement of an intramedullary pin (IMP) during plate–rod repair of a femoral fracture caused by minimally invasive plate osteosynthesis (MIPO), requiring immediate revision. Implant retrieval analysis and ex vivo modelling were performed to characterise the technique failure mode. The case details are reported. Implant retrieval analysis consisted of stereo zoom microscopic examination of the retrieved IMP. Wear patterns formed by conflict with a 2.8 mm, two-fluted surgical drill bit and a 3.5 mm AO locking screw were replicated using a simple paper impression model. The mechanism of pin movement was replicated in a benchtop laminated polyurethane foam block model, and wear patterns produced during drilling and screw insertion were characterised using stereo zoom. The wear pattern visible on the retrieved IMP suggested axial displacement caused by a rack-and-pinion-like mechanism, enacted by contact with either the drill bit or locking screws during placement of the repair construct. Significant axial displacement of the IMP due to conflict with screws during construct placement is possible during the placement of plate–rod fixation. Surgeons should confirm implant positioning if implant conflict is recognised intra-operatively. Full article