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    Lives versus livelihoods in the middle ages: The impact of the plague on trade over 400 years

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    To what extent did outbreaks of bubonic plague disrupt trade? We estimate the impact of epidemics on trade between regional wheat markets over four centuries — from the Black Death in the 14th century, until the medieval form of the plague became extinct in the 17th century. Using a gravity model, we find that outbreaks had a statistically significant, but relatively modest, impact on local variations in wheat prices. The results provide quantitative evidence on the extent to which epidemics disrupted markets and trade in pre-industrial Europe

    Kinematic Changes of the Trunk and Lower Limbs During Voluntary Lateral Sway Postural Control in Adults with Low Back Pain

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    Voluntary lateral weight shifting is essential for gait initiation. However, kinematic changes during voluntary lateral weight shifting remain unknown in people with low back pain (LBP). This study aims to explore the differences in kinematics and muscle activation when performing a voluntary lateral weight shifting task between patients with LBP and asymptomatic controls without pain.Methods: Twenty-eight participants volunteered in this study (14 in both the LBP group and the control group). The Sway Discrimination Apparatus (SwayDA) was used to generate a postural sway control task, mimicking lateral weight shifting movements when initiating gait. Kinematic parameters, including range of motion (ROM) and standard deviation of ROM (Std-ROM) of the lumbar spine, pelvis, and lower limb joints, were recorded using a motion capture system during lateral weight shifting. The electroactivity of the trunk and lower limb muscles was measured through surface electromyography using root mean square (RMS). The significant level was 0.05. An independent t-test was employed to compare kinematic parameters, and muscle activation between the LBP group and the control group. A paired-sample t-test, adjusted with Bonferroni correction (significant level of 0.025), was utilized to examine differences between the ipsilateral weight shifting towards side (dominant side) and the contralateral side.The results of kinematic parameters showed significantly decreased ROM and std-ROM of the ipsilateral hip in the transverse plane (tROM=-2.059, p=0.050; tstd-ROM=-2.670, p=0.013), as well as decreased ROM of the ipsilateral knee in the coronal plane (t=-2.148, p=0.042), in the LBP group compared to the control group. For the asymptomatic controls, significantly larger ROM and ROMstd were observed in the hip and knee joints on the ipsilateral side in contrast to the contralateral side (3.287≤t≤4.500, 0.001≤p≤0.006), but no significant differences were found between the two sides in the LBP group showed significantly lower RMS of the biceps femoris than the control group (tRMS = −2.186, p = 0.044). Discussion: Patients with LBP showed a conservative postural control pattern, characterized by reduced ROM of ipsilateral joints and diminished activation of the biceps femoris. These findings suggested the importance of voluntary postural control assessment and intervention to maximize recovery

    Quantitative Detection of Biological Nanovesicles in Drops of Saliva Using Microcantilevers

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    Extracellular nanovesicles (EVs) are lipid-based vesicles secreted by cells and are present in all bodily fluids. They play a central role in communication between distant cells and have been proposed as potential indicators for the early detection of a wide range of diseases, including different types of cancer. However, reliable quantification of a specific subpopulation of EVs remains challenging. The process is typically lengthy and costly and requires purification of relatively large quantities of biopsy samples. Here, we show that microcantilevers operated with sufficiently small vibration amplitudes can successfully quantify a specific subpopulation of EVs directly from a drop (0.1 mL) of unprocessed saliva in less than 20 min. Being a complex fluid, saliva is highly non-Newtonian, normally precluding mechanical sensing. With a combination of standard rheology and microrheology, we demonstrate that the non-Newtonian properties are scale-dependent, enabling microcantilever measurements with a sensitivity identical to that in pure water when operating at the nanoscale. We also address the problem of unwanted sensor biofouling by using a zwitterionic coating, allowing efficient quantification of EVs at concentrations down to 0.1 μg/mL, based on immunorecognition of the EVs’ surface proteins. We benchmark the technique on model EVs and illustrate its potential by quantifying populations of natural EVs commonly present in human saliva. The method effectively bypasses the difficulty of targeted detection in non-Newtonian fluids and could be used for various applications, from the detection of EVs and viruses in bodily fluids to the detection of molecular clusters or nanoparticles in other complex fluids

    Material-enabled damage inspection of multifunctional shape memory alloy tufted composite T-joints

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    The through-the-thickness reinforcement of carbon-epoxy composite joints with shape memory alloy (SMA) tufts has shown significant improvement of the mechanical strength, fracture toughness, and delamination resistance. This study explores the thermal-electric properties of SMA filaments tufted in composite T-joints to exhibit multiple functionalities including material-enabled thermographic inspection and structural health monitoring via in-situ strain sensing. Infrared thermography image analysis was performed on both pristine and damaged T-joint specimens subject to pull-off testing. Experimental results showed that the heat generated by SMA tufts measured by an infrared camera provided accurate indication of delamination perpendicular to the tuft direction. SMA tufts were also used as strain sensors embedded within the T-joint. Local changes of the electrical resistance in SMA filaments, both separately and within the joint, were observed during pulling loads. Digital Image Correlation measurements exhibited good correlation between electrical resistance variations and the opening of delamination. These results pave the way for the development of multifunctional composite joining systems combining enhanced through-the-thickness damage tolerance and self-sensing capabilities

    Recent Progress and Prospect of Metal–Organic Framework-Based Nanozymes in Biomedical Application

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    A nanozyme is a nanoscale material having enzyme-like properties. It exhibits several superior properties, including low preparation cost, robust catalytic activity, and long-term storage at ambient temperatures. Moreover, high stability enables repetitive use in multiple catalytic reactions. Hence, it is considered a potential replacement for natural enzymes. Enormous research interest in nanozymes in the past two decades has made it imperative to look for better enzyme-mimicking materials for biomedical applications. Given this, research on metal–organic frameworks (MOFs) as a potential nanozyme material has gained momentum. MOFs are advanced hybrid materials made of inorganic metal ions and organic ligands. Their distinct composition, adaptable pore size, structural diversity, and ease in the tunability of physicochemical properties enable MOFs to mimic enzyme-like activities and act as promising nanozyme candidates. This review aims to discuss recent advances in the development of MOF-based nanozymes (MOF-NZs) and highlight their applications in the field of biomedicine. Firstly, different enzyme-mimetic activities exhibited by MOFs are discussed, and insights are given into various strategies to achieve them. Modification and functionalization strategies are deliberated to obtain MOF-NZs with enhanced catalytic activity. Subsequently, applications of MOF-NZs in the biosensing and therapeutics domain are discussed.Finally, the review is concluded by giving insights into the challenges encountered with MOF-NZs and possible directions to overcome them in the future. With this review, we aim to encourage consolidated efforts across enzyme engineering, nanotechnology, materials science, and biomedicine disciplines to inspire exciting innovations in this emerging yet promising field

    γH2AX in mouse embryonic stem cells: Distribution during differentiation and following γ-irradiation

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    Phosphorylated histone H2AX (γH2AX) represents a sensitive molecular marker of DNA double-strand breaks (DSBs) and is implicated in stem cell biology. We established a model of mouse embryonic stem cell (mESC) differentiation and examined the dynamics of γH2AX foci during the process. Our results revealed high numbers of γH2AX foci in undifferentiated mESCs, decreasing as the cells differentiated towards the endothelial cell lineage. Notably, we observed two distinct patterns of γH2AX foci: the typical discrete γH2AX foci, which colocalize with the transcriptionally permissive chromatin mark H3K4me3, and the less well-characterized clustered γH2AX regions, which were only observed in intermediate progenitor cells. Next, we explored responses of mESCs to γ-radiation (137Cs). Following exposure to γ-radiation, mESCs showed a reduction in cell viability and increased γH2AX foci, indicative of radiosensitivity. Despite irradiation, surviving mESCs retained their differentiation potential. To further exemplify our findings, we investigated neural stem progenitor cells (NSPCs). Similar to mESCs, NSPCs displayed clustered γH2AX foci associated with progenitor cells and discrete γH2AX foci indicative of embryonic stem cells or differentiated cells. In conclusion, our findings demonstrate that γH2AX serves as a versatile marker of DSBs and may have a role as a biomarker in stem cell differentiation. The distinct patterns of γH2AX foci in differentiating mESCs and NSPCs provide valuable insights into DNA repair dynamics during differentiation, shedding light on the intricate balance between genomic integrity and cellular plasticity in stem cells. Finally, the clustered γH2AX foci observed in intermediate progenitor cells is an intriguing feature, requiring further exploration

    Preparation and characterization of 3D printed texture-modified food for the elderly using mung bean protein, rose powder, and flaxseed gum

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    This study is aimed to evaluate the applicability of using flaxseed gum (FG) as a texture-modified agent for preparing dysphagia-oriented foods containing mung bean protein (MBP) and rose powder (RP) via 3D printing. Rheological and texture profiles, 3D printability, swallowing easiness/difficulty and in vitro digestion of ink formulations with different FG concentration (0%–1.5%) were evaluated. Inks containing 0.3%–1.2% FG showed uniform texture, improved viscosity, elastic modulus (G′), and fracture/yield stress than the one containing only MBP + RP. Further increase of FG content to 1.5% enhanced the incompatibility between MBP and FG and caused their microphase separation, which compromised inks’ printability and stability of the printed shapes. Ink containing 0.9% FG showed desirable printing performance and self-supporting ability, and could be classified as level 4-pureed/extremely thick dysphagia-specific food. FG addition of 0.9% did not impede the digestion of MBP and retained a higher percentage of total phenolics during simulated gastrointestinal digestion

    Fertiliser supplementation with a biostimulant complex of fish hydrolysate, Aloe vera extract, and kelp alters cannabis root architecture to enhance nutrient uptake

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    Biostimulants are non-nutritive fertiliser additives which have demonstrated improvements to growth outputs of various agricultural crops. As a result, they have gained attention as sustainable components in cultivation practices, particularly in the rapidly emerging cannabis spheres, including medicinal and industrial cannabis cultivation. One point of focus to cannabis cultivators is the plant's efficiency of nutrient utilisation, attributed to the growth vigour and activity of roots. Despite the interest in this topic, due to the concealment of plant roots within substrates, exploration of plant roots is generally challenging and as such has hampered understanding of the impacts of biostimulants to plant root activity and associated nutrient utilisation efficiency. This project aimed to characterise the impacts and modes of action of the biostimulants kelp, Aloe vera extract, and fish hydrolysate to cannabis growth through exploration of their impacts individually, and as a biostimulant complex (BC). To overcome the limitations of root analyses, substrate-free hydroponic growth systems such as aeroponics, deep water culture (DWC), and the Root-TRAPR system were utilized. These systems allowed for the measurement of changes in root architecture and nutrient utilisation induced by the biostimulants. The results demonstrated that application of BC significantly enhanced root development, as indicated by increased root branching (P = 0.038) and increased total length (P = 0.046). In addition, BC treatment resulted in significant increases in the uptake of phosphorous (P = 0.038) and potassium (P = 0.040) by the plant. Metabolite and phytohormone profiling revealed that kelp and Aloe vera extract induced general plant stress-response mechanisms, whilst fish hydrolysate induced mechanisms associated with the plant pathogen defence response. However, when applied together as BC, the induced molecular mechanisms were associated with phosphorous deficiency without induction of general stress response mechanisms, potentially driving the increased uptake of phosphorous observed. These novel characterisations of biostimulant mechanisms and efficacies provide valuable insights to establishing optimised usage of biostimulants within cannabis cultivation, leading to increased production efficiency through sustainable practises

    Coupled dynamic instability of graphene platelet-reinforced dielectric porous arches under electromechanical loading

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    Graphene platelet-reinforced dielectric porous (GPLRDP) arches are a kind of multifunctional structures, which can be used to design various dielectric resonators and soft robotic components. This work studies the coupled dynamic instability of GPLRDP arches under electromechanical loading. It is assumed that the presence of voids is uniformly distributed in the arch structure, while graphene platelets (GPLs) are uniformly dispersed inside the skeleton of such voids. The effective medium theory (EMT) is used to determine the effective dielectric permittivity and Young's modulus of such structures. Based on the Hamilton principle, the governing equations of this problem are formulated. The differential quadrature method (DQM) and the Bolotin method are then used for solving the arch system to identify the coupled dynamic instability region. In this study, we observe the coupling effect of parametric and forced resonance phenomena. A series of numerical experiments are also carried out to examine the influence of porosities, GPL weight fractions, boundary conditions, and electrical voltage levels on the critical excitation frequency and coupled dynamic instability behavior of GPLRDP arches. It is found that the coupled dynamic instability region becomes wider and shifts to low frequency as the effect of porosity increases. When the signal amplitude of AC frequency is within a certain range, there is an abrupt increase of the critical excitation frequency under a high level of DC voltage. The numerical results of this work demonstrate that the location and size of the coupled dynamic instability region can be actively controlled by adjusting the material and structural parameters

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