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Amorphous solid dispersion formulation of pimobendan for bioavailability enhancement: A comprehensive study on miscibility, interactions, and in vitro dissolution behavior
No full textopen access articleAmorphous solid dispersions (ASDs) of poorly soluble pimobendan (PIMO) in cellulose matrices, including hydroxypropyl methylcellulose acetate succinate (HPMCAS-HG, HPMCAS-MG, HPMCAS-LG), polyvinylpyrrolidone-vinyl acetate (PVPVA64), and polyvinylpyrrolidone (PVPK30), were investigated, aiming to identify the optimal polymer to enhance its solubility and stability of the drug product. The results indicated that the miscibility between PIMO and the selected polymers can be predicted by Hansen solubility parameters and Flory-Huggins interaction parameters, with the ranking order of PVPVA64 > PVPK30 > HPMCAS. Fourier transform infrared (FTIR) spectroscopy analysis revealed significant interactions between PIMO and these polymers. Recrystallization inhibition and dissolution performance were ranked as HPMCAS-HG > HPMCAS-MG > HPMCAS-LG > PVPK30 > PVPVA64. Additionally, the results also indicated that HPMCAS-HG had superior stability compared to PVPVA64 and PVPK30 under elevated humidity, as confirmed by differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD) analysis. These findings provide a theoretical basis for selection of the optimal polymer for design of PIMO ASDs
Getting back to block teaching: developing a university active teaching and learning model
No full textIn recent years, De Montfort University (DMU) has made strides in enhancing its offer to students with the introduction of a block curriculum model. This was a major change programme for DMU across our campuses and over 80% of our students now study in Block mode. Student survey results point to positive gains across a range of measures. To date the focus of this change programme has been on the curriculum delivery. The university deployed curriculum sprints to revalidate our programmes, thereby ensuring our courses moved over to block mode in a timely way. More recently, the university has turned its attention to Block pedagogy as we recognised that a unified set of core teaching expectations has been lacking, leaving new academic staff reliant on peer support and communities of practice. To address this gap, DMU developed its Active Teaching and Learning Model informed by key academic literature. This model identifies seven principles of good teaching practice: building community and belonging, encouraging engagement and attendance, ensuring relevant and experiential learning, delivering prompt and useful feedback, offering diverse learning approaches, maintaining high expectations, and respecting diversity. The model serves as a practical framework to embed active teaching and learning to maximise the benefits of block curriculum
Navigating Cloud Computing Security: Strategies, Risks, and Best Practices
No full textThis research analyzes cloud computing environments' inherent security and privacy risks. It examines crucial aspects of cloud security, including data encryption, access control mechanisms, identity management, and the implementation of firewalls and intrusion detection systems. The study emphasizes the significance of regular security audits, compliance checks, and the development of robust data backup and disaster recovery plans. Furthermore, it highlights the importance of employee training and awareness in mitigating security threats. The paper delves into the complexities of secure APIs, segmentation, isolation strategies, and the necessity of regular system updates and patching. Additionally, it examines the evolving landscape of cloud security through the lenses of Cloud Security Posture Management (CSPM), the Shared Responsibility Model, and Zero Trust Architecture. This comprehensive approach provides valuable insights into enhancing security measures in cloud computing, thereby safeguarding sensitive data and maintaining user trust in an era where data security is paramount
Maternal B12 deficiency during pregnancy dysregulates fatty acid metabolism and induces inflammation in human adipose tissue
No full textopen access articleBackground
Adipose tissue (AT) responds to excess calorie intake; however, the deficit in micronutrients accompanied by the modern lifestyle is often overlooked. Micronutrient deficiency in pregnancy, particularly vitamin B12 (B12), is commonly associated with higher adiposity, dyslipidemia, and type 2 diabetes (T2D). Studies have demonstrated that dyslipidemia can trigger pro-inflammatory status. However, the release of the pro-inflammatory factors in a tissue-specific micronutrient deficient environment is unexplored. Therefore, we investigated the role of B12 deficiency on lipid metabolism and inflammatory mediators in both in vitro and ex vivo models including human pre-adipocytes, primary adipocytes, mature human white AT (WAT), and its association with metabolic risk.
Methods
Paired abdominal subcutaneous and omental WAT (ScWAT and OmWAT) were chosen based on serum B12 (< 150 pM) from 115 Caucasian pregnant women. Human primary Sc adipocytes from women with different BMI (lean, overweight, obese, morbidly obese) and pre-adipocyte cell line (Chub-S7) were differentiated in various concentrations of B12. Serum B12, folate, lipids, cytokines, biochemical parameters, gene expression, intracellular triglyceride (TG), and mitochondrial function were assessed.
Results
In pregnant women with low B12 levels, BMI and serum TG were significantly higher, and high-density lipoprotein (HDL) was lower (p < 0.05). B12 deficiency in both depots of AT correlated with higher expression of genes in fatty acid (FA) synthesis, elongation, desaturation, TG synthesis, and reduced fatty acid oxidation (FAO) (p < 0.05). In vitro adipocytes with low B12 demonstrated that TG synthesis utilizing radiolabeled FA was higher and mitochondrial function was impaired. We also found that the expression of pro-inflammatory cytokines in AT was increased, and circulatory cytokines inversely associated with serum B12 (p < 0.05).
Conclusions
Our novel data highlights that B12 deficiency dysregulates lipids and induces inflammation in AT and circulation, which could contribute to adipocyte dysfunction exacerbating cardiometabolic risk during pregnancy
Enhancing Structural Efficiency with Robust Evolutionary Topology Optimization (RETO) for Sustainable Engineering
No full textThe file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.The Evolutionary Topology Optimization (ETO) method was enhanced by incorporating robust optimization techniques and used to improve the structural efficiency and sustainability. By optimizing the material distribution within a given design space, this approach reduces material usage and promotes cost-effectiveness and environmentally conscious design. The integration of robust design principles ensures that optimized structures remain resilient to variations in environmental and loading conditions. A major challenge in robust topology optimization for achieving smooth boundaries and addressing the dimensionality in uncertainty problems is overcome by integrating ETO with sparse grid collocation (SGC), which significantly reduces the computational time and post-processing work. The methodology is validated by presenting numerical examples involving 2D beams subjected to uncertain loads and materials, and outperforms traditional methods such as RTO-XFEM and Monte Carlo. The results highlight the capability of ETO to lower the compliance mean values and standard deviations, thereby attesting to its efficiency and robustness
Perception of the Importance of Inherited Genetics and Lifestyle on the Development of Chronic Diseases: A UK Cross‐Sectional Survey
No full textopen access articleBackground and Aims
There is emerging evidence that genes, lifestyles and environment play a prominent role in the development of non-communicable diseases. Currently, there is not information on people's perception of inherited genetics vs. lifestyle on disease development. Knowing people's belief on disease etiology will better inform public health strategies for the adoption of a healthy lifestyle.
Methods
Individuals aged 18 years and over were recruited in 2019 among the UK population and 363 participants completed an anonymous questionnaire. The main outcomes assessed were perception of importance of inherited genes and lifestyle on the development of diseases. T-tests and χ2 were used.
Results
The score for the importance of inherited genes in disease development was significantly lower than the lifestyle score (7.5 ± 1.7 vs. 8.5 ± 1, p 0.05).
Conclusion
Overall, participants were well aware of the importance of lifestyle as a determinant risk factor for chronic disease development. This is an important step toward adopting a healthy lifestyle
Sleep supports consolidation of newly learned mathematical concepts.
No full textThe file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.Within mathematical cognition the development of conceptual knowledge is seen as critical to developing understanding. Sleep has been well established to play a role in the consolidation of newly learned information and schema-based information but has yet to be explored within mathematical cognition. Across three experiments participants (N = 167) were assigned to a sleep or wake group and then viewed lectures on either p-values, t-test, or z-scores. The sleep group watched the lecture at 9pm, completed an immediate recall task to explain the concept, then a second recall task 12h later at 9am. The wake groups watched the lecture at 9am, and completed an immediate recall task then a second recall task 12h later at 9pm. Written responses were then assessed using a comparative judgement task by subject experts. Across all three experiments, results showed that participants in the sleep group retained their knowledge from the immediate recall to 12 hours later, while in the wake group, participants’ knowledge declined significantly between sessions. These results suggest that sleep may be involved in an important process of maintaining the information learned from statistical concepts
Density estimation with LLMs: a geometric investigation of in-context learning trajectories
No full textLarge language models (LLMs) demonstrate remarkable emergent abilities to perform in-context learning across various tasks, including time series forecasting. This work investigates LLMs’ ability to estimate probability density functions (PDFs) from data observed in-context; such density estimation (DE) is a fundamental task underlying many probabilistic modeling problems. We leverage the
Intensive Principal Component Analysis (InPCA) to visualize and analyze the in-context learning dynamics of LLaMA-2 models. Our main finding is that these LLMs all follow similar learning trajectories in a low-dimensional InPCA space,
which are distinct from those of traditional density estimation methods like histograms and Gaussian kernel density estimation (KDE). We interpret the LLaMA
in-context DE process as a KDE with an adaptive kernel width and shape. This custom kernel model captures a significant portion of LLaMA’s behavior despite having only two parameters. We further speculate on why LLaMA’s kernel width and shape differs from classical algorithms, providing insights into the mechanism of in-context probabilistic reasoning in LLMs
Foliation adjunction
No full textWe present an adjunction formula for foliations on varieties and we consider applications of the adjunction formula to the cone theorem for rank one foliations and the study of foliation singularities
Li⁺ concentration and morphological changes at the anode and cathode interphases inside solid-state lithium metal batteries
No full textIrregular Li heterostructure growth at the interphase between the solid electrolyte and anode
reduces solid-state Li metal battery (SSLMB) performance, but the fundamental cause is still
elusive. Measuring and imaging Li+ ion diffusion in operando inside an SSLMB using a
commercially standard cell configuration are extremely challenging because the ultra-light Li
element exhibits a minute signal-to-noise ratio using most x-ray-related characterization methods,
and the weak x-ray signals of Li+ are buried by strong signals of other heavy transition metal
elements in the cathode and battery enclosure. Here, we pioneer novel operando correlative
imaging of coupling x-ray Compton scattering with computed tomography (XCS-CT), which is
able to quantify the interplay between spatially resolved Li+ ion diffusion kinetics and Li0 metal
structure growth at the interphases of both the anode and cathode sides inside a full-cell SSLMB
using a solid polymer electrolyte (SPE) and commercially standard cell configuration during
(dis)charging. We show a 61% increase in the efficiency of extracting Li+ ions from the cathode
LiNi0.6Mn0.2Co0.2O2 to the anode during charging at 0.1 C compared with at 1 C due to restricted
Li+ ion diffusion at the higher rate inside SSLMB. However, this led to the formation of a more
irregular interfacial morphology, consisting not only of Li0 dendrites, but also sub-surface pore
formation at the anode/SPE interphase. We find that surprisingly, the irregular Li0
structure
initiation and growth are accelerated during the first Li stripping step, not the Li plating step, and
the root cause is the onset imbalance of Li+ ion diffusion and redox reactions between the anode
and cathode. These insights highlight the benefits of asymmetric charging and discharging rates as
a promising solution to improving SSLMB performance with SPEs. The operando correlative
XCS-CT imaging technique has the potential to study the relationship between active ion
concentrations and buried morphological changes for a variety of battery chemistries