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Effect of sodium taurodeoxycholate on PEO-PPO-PEO triblock copolymer F127 with incorporated SNAP : Insights into micellization, gelation, and nitric oxide release
No full textWe report the first incorporation of S-nitroso-N-acetylpenicillamine (SNAP) into micellar systems of the poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) triblock copolymer Pluronic® F127 for nitric oxide (NO) delivery and show how sodium taurodeoxycholate (NaTDC) modulates F127 micellization and gelation. Using differential scanning calorimetry, small-angle X-ray scattering, rheology, dynamic light scattering, UV–vis spectroscopy, and chemiluminescence NO analysis, we identify two NaTDC-dependent regimes. At low NaTDC/F127 ratios (MR ≤ ∼1.2), NaTDC associates with F127 micelles, lowering the critical micellization temperature and modestly compacting the PPO cores. At higher ratios (MR ≥ ∼3.8), micellization becomes less cooperative, small bile salt–rich complexes form, and at 25 wt% F127, the gel nanostructure transitions from face-centered cubic phase to body-centered cubic phase and eventually loses long-range order (MR ∼6.2). SNAP load does not alter micellization, locates at the core–corona interface, and shows enhanced solubility that depends more on F127 concentration than on NaTDC. Thermal NO release from SNAP (25 °C, dark) follows second-order kinetics, slowing as F127 concentration increases (1–25 wt%), resulting in prolonged NO release. These findings contribute to advancing the understanding of the behavior of PEO-PPO-PEO/NaTDC micellar systems, by demonstrating how NaTDC regulates micellization and gelation. Moreover, the finding that F127 concentration controls SNAP stability and NO-release kinetics, makes the F127/NaTDC system a potential modular platform for sustained and localized NO delivery
Contesting agrarian futures : Structural contradictions and collective struggle among smallholder farmers
No full textAgriculture remains central to global debates on livelihoods, development, and sustainability, particularly across the Global South where it is widely promoted as a pathway to poverty reduction, food security, and economic transformation. Yet, despite decades of reform, agricultural development continues to generate uneven and contradictory outcomes. Policies framed around inclusion, rural transformation, and sustainability often reproduce inequality, marginalise smallholders, and erode ecological foundations. In this thesis, I argue that these outcomes are not primarily the result of isolated failures of policy design or implementation but arise from structural contradictions embedded in the internal logic of a dominant neoliberal-productivist paradigm that prioritises productivity, market integration, and private-sector-led growth. I examine Ghana’s agricultural development trajectory as an empirically rich case through which to interrogate these contradictions. Smallholder farmers produce the majority of Ghana’s food, yet remain constrained by insecure land access, uneven market relations, ecological vulnerability, and limited political voice. Grounded in critical realism, I employ immanent critique to evaluate agricultural policies against their own stated commitments, showing how internal tensions undermine their objectives. I use the Capability Approach (CA) as a normative and evaluative framework to assess the consequences of these contradictions in terms of farmers’ substantive freedoms rather than narrow indicators of productivity or income. Empirically, the analysis draws on a mixed-methods research design combining policy analysis, qualitative fieldwork, survey data, and a case study of the Food Sovereignty Platform’s (FSP) resistance to Ghana’s Plant Variety Protection Bill.In the analysis, I identify recurring manifestations of contradiction across Ghana’s flagship agricultural policies, including inclusion without redistribution, productivity pursued without ecological sustainability, and market integration implemented in the absence of structural safeguards. These dynamics translate into uneven and constrained capabilities among smallholders. At the same time, I show that these conditions also generate pressures for collective political mobilisation. Survey evidence indicates that land access constraints, seed insecurity, and infrastructural deficits function as politicising pressures within farmer organisations. The FSP case demonstrates how such pressures are aggregated into counter-hegemonic coalitions that contest dominant agrarian paradigms and articulate alternative pathways centred on food sovereignty, agroecology, and farmer autonomy.This thesis contributes to debates on agrarian transformation by demonstrating how Ghana’s agricultural development paradigm embodies structural contradictions. It extends the CA by situating capability expansion within processes of political struggle and institutional contestation, and it advances critical realist scholarship by empirically integrating structure and agency. In the analysis, I offer a multi-scalar explanation of how struggles over agrarian futures emerge and why just and sustainable agricultural transformation depends on both structural change and organised farmer agency
Identifying 20 homogeneous clusters of acute patients discharged with nonspecific diagnoses through k-prototypes mixed data clustering
No full textAβ antibodies target not only amyloid plaques but also distinct brain cells and vessels
No full textBACKGROUNDAmyloid beta (Aβ) antibodies are the only therapies to slow cognitive decline in Alzheimer's disease (AD). Yet the sites where antibodies engage Aβ in the brain and mechanisms that lower Aβ are not fully understood. Defining Aβ antibody localizations in the brain is essential to understand how immunotherapy is beneficial for AD.METHODSN-terminal Aβ antibody 6E10 was injected via three different routes into different AD mouse models. N-terminal Aβ antibodies were empirically shown as most effective in AD mice. Antibody localization was examined in the brain after injections. Glymphatic dynamics were also evaluated.RESULTSAs expected, Aβ antibody 6E10 bound to plaques but remarkably also localized to vulnerable neurons, such as hippocampal CA1 pyramidal cells, as well as microglia, astrocytes, oligodendrocytes, perivascular macrophages, and blood vessels. Antibodies did not alter glymphatic function.DISCUSSIONWe provide detailed localizations of antibodies in AD mouse brains, offering insights into targets of Aβ antibody-based immunotherapy.HighlightsAmyloid beta (Aβ) antibody 6E10 shows broad distribution across plaques and multiple cellular/vascular compartments in different Alzheimer's disease (AD) mouse models.Localization of antibody 6E10 in AD mice was detected in selective neurons, astrocytes, microglia, perivascular macrophages (PVMs), and oligodendrocytes/oligodendrocyte precursor cells, and at the external aspects of blood vessels.Intracellular human-specific Aβ antibody 6E10 appears related to phagocytic activity, as PVMs and microglia in wild-type mice also contained 6E10, or to intracellular Aβ, as 6E10 in neurons, and oligodendrocytes were only detected in AD mice.Aβ antibody injections by different routes failed to augment glymphatic circulation in AD mice
Image enhancements by CLAHE and gamma correction do not improve diagnostic accuracy in teledermoscopy: a retrospective cohort study
No full textTeledermoscopy (TDS) offers an efficient alternative to face-to-face assessment of suspicious skin lesions. Although diagnostic accuracy in TDS is relatively high, further improvement is desirable to reduce the risk of overlooked skin cancers and unnecessary interventions of benign lesions. Image enhancement (IE), i.e. digital modification of different parameters of an image, may potentially improve visualisation and thereby diagnostic accuracy. Several tools for IE were reviewed through two workshops and two were eventually selected for the study: Contrast Limited Adaptive Histogram Equalisation (CLAHE) for contrast enhancement and Gamma Correction for brightness adjustment. A retrospective randomized clinical study was performed in which 1997 TDS cases were distributed to 13 assessors with varying dermoscopic experience, who assessed lesions either with access to IE-tools (IE-group) or without (control group). Diagnostic accuracy for malignant vs. benign and melanoma-group vs. non-melanoma-group lesions was compared using chi-square tests. A generalized linear mixed model (GLMM) with assessor as a random intercept and adjustment for image quality was applied to account for assessor-dependent variance. Management recommendations were analyzed using both graded intervention levels relative to a gold standard and a stricter harm–benefit framework, assessing inappropriately under-management of malignant and over-management of benign lesions. No significant differences were found between the groups regarding malignant/benign classification. For melanoma differentiation, specificity was slightly, but significantly lower in the IE group compared to the control group (86.3; 95% confidence interval (CI) 83.8–88.5 vs. 89.9%; 95% CI 87.6–91.8, respectively, p = 0.02) while sensitivity remained unchanged. GLMM analyses confirmed these findings. No significant differences were observed in appropriateness of management recommendations or diagnostic confidence. Use of the IE tools CLAHE and Gamma Correction did not improve diagnostic performance in TDS assessments. These findings do not support routine clinical use of these IE tools for the purpose of improving diagnostic assessment of skin lesions
Cryptic Ontogenetic Changes in the Ventral Coloration of a Color Polymorphic Wall Lizard (Podarcis muralis)
No full textMany animals undergo irreversible ontogenetic color changes (OCCs), yet these changes are often overlooked despite their potential ethological relevance. The problem is compounded when OCCs involve wavelengths invisible to humans. Wall lizards can perceive ultraviolet (UV) light, and their conspicuous ventral and ventrolateral coloration—including UV-reflecting patched—likely serves social communication. Here, we describe OCCs in the ventral (throat and belly) and ventrolateral (outer ventral scales, OVS) coloration of juvenile common wall lizards (Podarcis muralis) as perceived by conspecifics. We measured reflectance in hatchling and yearling lizards raised under semi-natural conditions and used visual modeling to estimate chromatic distances within individuals and across life stages (i.e., hatchlings, yearlings, and adults). Hatchlings typically exhibit UV-enhanced white (UV+white) on their ventral surfaces (throat, belly, and OVS), a color that is likely discriminable to conspecifics from the most frequent adult colors in the throat (i.e. orange, yellow, and UV-reduced white; UV−white) and OVS (i.e., UV-blue). The prevalence of UV+white decreases with age, with the decline being less pronounced in female bellies. OCCs to UV-blue in the OVS are more apparent in males than in females and appear delayed relative to changes in the throat and belly. While throat colors in yearlings are indistinguishable to conspecifics from adult throat colors, yearling UV-blue patches remain chromatically distinct from those of adults. This delay may reflect variations in the mechanisms of color production or distinct selective pressures acting on these patches. Overall, our results show that OCCs in P. muralis fulfill a key requirement for social signals by being perceptible to conspecifics. This supports the hypothesis that OCCs may play a role mediating interactions between juveniles and adults, as well as delaying the onset of colors involved in social communication
Multi-input/multi-output switched-linear system identification from input–output data
No full textIn this paper, we propose a scheme to identify discrete-time, multi-input/multi-output switched-linear systems (MIMO-SLSs) from input-output measurements. The key step is an observer-based transformation to a switched auto-regressive with exogenous input (SARX) model. This transformation converts the state-space (SS) identification problem into a MIMO-SARX identification problem by compressing infinite strings of system Markov parameters into finite strings of observer Markov parameters. We study switch and discrete state (submodel) identifiability and derive persistence of excitation conditions for hybrid inputs to recover discrete-states. Switching sequence and discrete-states are estimated in the observer domain by solving a convex-sparse optimization problem followed by two different subspace algorithms. Local-mode clustering then reveals discrete-states. A detailed numerical example illustrates performance of the proposed scheme
Pathways to quality of life : Roles of customer orientation, organizational commitment, leadership, and job engagement among hotel staff facing job insecurity
No full textThis study examined pathways to quality-of-life (QOL) among hotel staff facing job insecurity, considering the roles of customer orientation, organizational commitment, leadership, and job engagement. A research model was developed and tested using path analysis on survey data, comparing groups with high and low job insecurity. Results showed the model explained 43.3 % of variance in QOL. Customer orientation, organizational commitment, and transformative leadership had significant indirect effects on QOL through job satisfaction. Job engagement aspects had mixed direct and indirect effects. The high and low job insecurity groups showed some differences in path coefficients. Necessary condition analysis found customer orientation, dedication, and absorption were necessary for QOL in the full sample. Sufficient configurations for high QOL differed between job insecurity groups. Deep learning comparing alternative models supported the research model. Findings highlight the importance of job satisfaction as a mediator, reveal nuances in effects of job engagement, and demonstrate differences based on job insecurity level. This study provides insights for enhancing hotel employees’ well-being in the face of job insecurity. Implications for hotel management are discussed
Causation and Breach of Positive Obligations under the ECHR: Correcting the Past, Preventing the Future
No full textThis chapter explains that the causation inquiry performed by the European Court of Human Rights for determining breach of positive obligations has to be understood in light of the normative structural considerations that underpin state responsibility under the European Convention on Human Rights (ECHR). In particular, the responsibility system is not shaped by the corrective justice rationale that is backward-looking and where correlativity and clarity in the relationship between different actors is key. The ECHR responsibility system is rather outcome-driven where the formulation of standards meant to guide future-state conduct shapes the legal review performed by the Court. The formulation of the mere exposure to risks as the harm (i.e. the undesirable outcome that should have been avoided or mitigated) and the formulation of absence of risk prevention or risk mitigation, as the relevant omissions for the establishment of responsibility, further reveals the normative underpinnings of the system. This reinforces a flexible approach to causation. The approach is guided by the idea that ascribing responsibility to the State for harmful outcomes is not that contentious. It is not perceived as contentious since the State has a functional role. The remedies envisioned by the ECHR responsibility system also pull the system away from the corrective justice rationale and, accordingly, away from stringency in the causation inquiry for the establishment of breach. In particular, even if breach of the positive obligation established (a conclusion facilitated by the flexible causation standard), States have discretion what remedies to choose. Concrete measures as measures to correct the past wrongful conduct (i.e. the wrongful omissions) are not ordered by the Court with the conclusion in the judgment of breach