This comprehensive overview of the historical milestones in cell culture underscores key breakthroughs that have shaped the field over time. It begins with Wilhelm Roux's seminal experiments in the 1880s, followed by the pioneering efforts of Ross Granville Harrison, who initiated groundbreaking experiments that fundamentally shaped the landscape of cell culture in the early 20th century. Carrel's influential contributions, notably the immortalization of chicken heart cells, mark a significant advancement in cell culture techniques. Holtfreter, Moscona, and Leighton introduced innovations such as 3D cell culture, laying the groundwork for further exploration. The advent of induced pluripotent stem cells by Takahashi and Yamanaka in 2006 was revolutionary, enabling the reprogramming of differentiated cells into a pluripotent state. Since then, recent innovations include spheroids, organoids, and organ-on-a-chip technologies, aiming to mimic the structure and function of tissues and organs in vitro, pushing the boundaries of biological modeling and disease understanding. In this review, we overview the history of cell culture shedding light on the main discoveries, pitfalls and hurdles that were overcome during the transition from 2D to 3D cell culture techniques. Finally, we discussed the future directions for cell culture research that may accelerate the development of more effective and personalized treatments.

As the use of AI in medical imaging has increased, so has the need to explain a model’s results. Segmentation models are one technique used to produce explainable results. Due to larger size and sophistication, segmentation models which operate on 2D data can often produce better results than models operating on 3D data. In the real world, imaging is combined with clinical factors for diagnosis. To replicate this, multimodal models are used which combine image and text modalities. I propose a multimodal arrangement that converts 3D scans to 2D and uses a 2D segmentation model (DeepLabV3) to analyze the images. This is combined with clinical biomarkers to achieve a complete confidence score. Using the Medical Segmentation Decathlon Lung (MSDL) dataset and the LUng CAncer Screening dataset (LUCAS), I achieved a testing Dice coefficient of 0.91 on segmentation with a receiver operating characteristic (ROC), average precision (AP), and F-Score of 0.89, 0.91, and 0.85 respectively on the final multimodal results. This approach raises the F-score from the previously achieved value of 0.508 to 0.85, creating a new baseline of what is achievable with multimodal lung cancer diagnostics and possible methods to achieve these accuracies.

3D Printing /Additive manufacturing holds a promising future in healthcare as it aids in visualizing things and making 3D objects which is very important in different areas of medicine. The concept of one size fits all has failed the quality of care delivered by us in healthcare which demands customised needs for patient care to create 3D printed tissues, make personalized prosthetics, implants and physical models of the human body. The materials used for printing models and other healthcare devices for medical education, patient needs, and prototyping are increasing. The application of different materials for use in healthcare is not studied. New materials are also available for the various applications in healthcare industry. This experimental study was conducted to review the nine distinct 3D printing filament materials like PETG, PA, ABS, PLA, HIPS, PMMA, Ceramic, Carbon Fiber, and (PLA + Metal Composite) with the help of a 3D printed physical model of T-12 thoracic vertebrae using all the abovementioned materials. The evaluation of materials was based on diverse mechanical properties, applications across medical fields, performance metrics, costs, accuracy, and quality. The assessment This study also focuses on comparison of mechanical properties such as tensile strength, compressive strength of the abovementioned materials with human bone. The study also reviews the 3D printing process and explores its utilization in biomedical applications. The Insights about the application of various materials holds a promising future for development of newer materials for healthcare industry.

Current Micro-Computed Tomography (Micro-CT) protocols for microvasculature analysis often necessitate organ dissection and non-clearable contrast agents. We describe a non-destructive technique for achieving high-resolution images of the human coronary microvasculature. Formalin-fixed human hearts were cannulated using venogram catheters designed for balloon occlusion. Catheters were anchored at the aortic root. Hearts were placed in sealable, radiolucent containers filled with insulating polyurethane foam. Iodine potassium iodide (IKI, Lugol's solution;6.3% Potassium Iodide, 4.1% Iodide) was injected into the coronary arteries. Contrast distribution was monitored using a North Star Imaging X3000 Micro-CT scanner with low-radiation settings, followed by high-radiation scans (3600 rad, 60 kV, 900 mA). We successfully imaged two intact human hearts with chronic total coronary occlusions of the right coronary artery. The scans enabled detailed analysis of the vasa vasorum surrounding stenosed and occluded segments. After imaging, both hearts were cleared of iodine and excess polyurethane foam and then returned to their initial formalin-fixed state for indefinite storage. Conclusions: This method allows for the non-destructive, high-resolution micro-CT imaging of coronary microvasculature in intact human hearts, paving the way for 3D microvascular reconstruction in a macrovascular context.

Fused deposition modeling (FDM) is a rather new technology in the production of personalized dosage forms. Melting and printing of polymer–active pharmaceutical ingredient (API) – mixtures can be used to produce oral dosage forms with different dosage as well as release behavior. This process is utilized to increase the bioavailability of pharmaceutically relevant active ingredients that are poorly soluble in physiological medium by transforming them into solid amorphous dispersions (ASD). Release from such ASDs is expected to be faster and higher compared to the raw materials and thus enhance bioavailability. Printing directly from powder while forming ASDs was realized. Different techniques to change release patterns as well as a non-destructive way for determination of API distribution were shown. By measuring the melt viscosities of mixtures printed a rheological model for the printer used is proposed.

The interconnection between the objectives of territorial development and the agro-ecological transition highlights the value of past knowledge in the sustainable management of resources and agro-ecological systems. However, retrospection in rural areas presents difficulties due to a lack of data. This paper contributes to the search for such knowledge from the past by developing an interactive methodology capable of combining heterogeneous sources of information and the activation of local collective memory. Its effectiveness is based on ensuring the interoperability of information and communication in an environment simultaneously shaped by geoinformatics and 3D geo-visualizations. This virtual environment fosters participation and interactivity, supported by representations of the paleo-landscape. Furthermore, synergies were achieved between information sources and their integration into local spatial systems. The application example involved identifying a rice field that existed from the 15th to the 19th century in Thessaly, Greece. It is an interesting case because the location and organization of cultivation in combination with its spatio-temporal coordination ensures the sustainable use of natural resources. It appears that the interplay between information and communication facilitates community participation and the activation of its collective memory as a source of information that enriches the search and local intelligence.

The issue of equipment layout in multi-floor satellites consists of two primary parts: allocating the equipment to the satellite's layers and placing the equipment in each layer individually. In reviewing the past literature in this field, firstly, the issue of assigning equipment to layers is observed in a few articles and next in the layout part, the non-overlapping constraint has always been a challenge, particularly for components that do not have a circular cross-section. In addition to presenting a heuristic method for allocating equipment to different layers of the satellite, this article presents a robust flexible programming model (RFPM) for the placement of equipment at different layers, taking into account the inherent flexibility of the equipment in placement and the subject of uncertainty. This model is based on the existing uncertainty between the distances of cuboid equipment which has not been addressed in any of the previous research, and by comparing its outputs with cases from past studies, it demonstrates a significantly higher efficiency in placing the equipment and meeting the limit of non-overlapping constraints between the equipment. Finally, it would be possible to reduce the design time in the conceptual and preparatory stages, as well as the satellite's overall size, while still satisfying other constraints like stability and thermal limitations, moments of inertia and centre of gravity.

Cycle times at workstations in offsite construction factories fluctuate widely due to various influencing factors. Consequently, relying on average rates, such as length per unit of time, for estimating cycle times proves to be inaccurate, often leading to significant deviations between production schedules and actual operations. To address this issue, this study proposes an estimation system that leverages machine-learning-based prediction, statistical methods, 3D simulation, and computer vision to predict cycle times at the workstation level. Testing of the system on a semi-automated wood-wall framing workstation in a panelized construction factory shows that it reduces the mean absolute error and sum of errors by approximately 36% and 68%, respectively, compared to the fixed rate method. The results also highlight the efficacy of using computer vision data for training machine-learning models for cycle time estimation, the importance of identifying and understanding the factors influencing cycle times, and the impact of random delays on the accuracy of cycle time estimation systems.

Abstract: The widespread and popular use of TADs for orthodontic anchoring has become a daily routine in clinical orthodontic treatment. However, as there have been many accidents over the past decade, safety action is needed to help reduce these accidents. We have advocated using the surgical guide and developed a procedure that can benefit patients and orthodontists. The first part of this paper is about the rationale for making the surgical guide for various implant placements that were observed. Due to their anatomical structure, some placements may require particular attention, which is focused on and discussed in length. The second part deals with fabricating the surgical guide in the laboratory procedure. The data from the intraoral SLT acquisition was extracted, and with the DICOM data from CBCT and in a 3-Shapes software, the guidance was designed. The detailed and step-by-step laboratory procedure, CAD/CAM, and 3D printers to make the surgical guide for TADs are explained. The procedure is performed in an easy-to-understand manner to make using the surgical guide possible for the daily practice of orthodontics (Pubmed).

With a view to sustainable development and circular economy, this work focused on the possibility to valorize a secondary waste stream of recycled carbon fiber (rCF) to produce a 3D printing usable material with PA6,6 polymer matrix. The reinforcing fibers implemented in the present research are the result of a double recovery action: starting with pyrolysis from which long fibers are obtained, used to produce non-woven fabrics and, subsequently, fiber agglomerate wastes obtained from this last process are ground in a ball mill. The effect of a different amount of reinforcement at 5% and 10% by weight on the mechanical properties of 3D printed thermoplastic composites was investigated. Although the recycled fraction was successfully integrated in the production of filaments for 3D printing and therefore in the production of specimens via Fused Deposition Modeling technique, the results showed that fibers did not improve the mechanical properties as expected, due to an unsuitable average size distribution and the presence of a predominant dusty fraction ascribed to the non-optimized ball milling process. PA6,6 + 10 wt.% rCF composites exhibited a tensile strength of 59.53 MPa and a tensile modulus of 2.24 GPa, which correspond to an improvement in mechanical behavior of 21 5 % and 5 21 % compared to the neat PA6,6 specimens, respectively. The printed composite specimens loaded with the lowest content of rCF provided the greatest improvement in strength (+ 9% over the neat sample). Then, a prediction of the “optimum” critical length of carbon fibers was proposed that could be used for future optimizations of the recycled fiber processing.

Supramolecular structures are of great interest due to their applicability in various scientific and industrial fields. These fields of scientific action include promising applications i biomedical areas, in sensing, and in conductive and electrical phases. The sensible definition of supramolecular molecules is being set by investigators, who, because of the different sensitivities of their methods and observational timescales, may have different views as to what constitute these supramolecular structures. Besides, diverse polymers can be found to offer unique avenues for multifunctional systems with properties in medicine industrial applications. Aspects of this review provide different conceptual strategies to address molecular design, properties, and potential applications of self-assembly materials and the use of metal coordination as a feasible and useful strategy for constructing complex supramolecular structures. In this order of appreciations and ideas order, it is that this review report involves classic topics such as hydrogels that range from their relationship with drug delivery systems, to metallo-supramolecular materials, through applications in ophthalmic systems, in applications that require adhesiveness and electrically conductive hydrogels. This review also addresses systems that are largely based on hydrogel chemistry and the enormous opportunities to design very specific structures for applications that demand enormous specificity.

Lesion studies are crucial in establishing brain-behavior relationships, and accurately segmenting the lesion represents the first step in achieving this. Manual lesion segmentation is the gold standard for chronic strokes. However, it is labor-intensive, subject to bias, and limits sample size. Therefore, our objective is to develop an automatic segmentation algorithm for chronic stroke lesions on T1-weighted MR images. Methods: To train our model, we utilized an open-source dataset: ATLAS v2.0 (Anatomical Tracings of Lesions After Stroke). We partitioned the dataset of 655 T1 images with manual segmentation labels into five subsets and performed a 5-fold cross-validation to avoid overfitting of the model. We used a deep neural network (DNN) architecture for model training. Results: To evaluate the model performance, we used three metrics that pertain to diverse aspects of volumetric segmentation including shape, location, and size. The Dice similarity coefficient (DSC) compares the spatial overlap between manual and machine segmentation. The average DSC was 0.65 (0.61- 0.67; 95% bootstrapped CI). Average symmetric surface distance (ASSD) measures contour distances between the two segmentations. ASSD between manual and automatic segmentation was 12mm. Finally, we compared the total lesion volumes and the Pearson correlation coefficient (ρ) between the manual and automatically segmented lesion volumes, which was 0.97(p-value < 0.001). Conclusions: We present the first automated segmentation model trained on a large multicentric dataset. This model will enable automated on-demand processing of MRI scans and quantitative chronic stroke lesion assessment.

Recent improvements within the fields of high-throughput screening and 3D tissue culture have provided the possibility of developing in vitro micro-tissue models that can be used to study diseases and screen potential new therapies. This paper reports a proof of concept study on the use of microvalve-based bioprinting to create laminar MSC-chondrocyte co-cultures as an in vitro model of autologous chondrocyte implantation (ACI), an established cellular therapy for osteoarthritis. Microvalve-based bioprinting uses microvalves to deposit cells suspended in a liquid in a consistent and repeatable manner. In this case MSCs and chondrocytes have been sequentially deposited into an insert based transwell system in order to create a laminar co-culture, with variations in the ratios of the cell types used to investigate the potential for MSCs to stimulate improved repair. Histological and indirect immunofluorescence staining revealed the formation of dense tissue structures within the chondrocyte and MSC-chondrocyte cell co-cultures, alongside the establishment of a proliferative region at the base of the tissue. No stimulatory or inhibitory effect in terms of ECM production was observed through the introduction of MSCs, although the potential for an immunomodulatory benefit remains. This proof-of-concept study therefore provides a novel method to enable the scalable production of therapeutically relevant micro-tissue models that can be used for in vitro research to optimise ACI procedures.

As Automated Driving Systems (ADS) technology gets assimilated into the market, the driver’s obligation will be changed to a supervisory role. A key point to consider is the driver’s engagement in the secondary task to maintain the driver/user in the control loop. The paper’s objective is to monitor driver engagement with a game and identify any impacts the task has on hazard recognition. We designed a driving simulation using Unity3D and incorporated three tasks: No-task, AR-Video, and AR-Game tasks. The driver engaged in an AR object interception game while monitoring the road for threatening road scenarios. From the results, there was less than 1 second difference between the means of gaming task (mean = 2.55s, std = 0.1002s) to no-task (mean = 2.55s, std = 0.1002s). Game scoring followed three profiles/phases: learning, saturation, and decline profile. From the profiles, it is possible to quantify/infer drivers’ engagement with the game task. The paper proposes alternative monitoring that has utility, i.e., entertaining the user. Further experiments AR-Game focusing on real-world car environment will be performed to confirm the performance following the recommendations derived from the current test.

During the night between 9 and 10 September 2017, multiple flash floods associated to a heavy-precipitation event affected the town of Livorno, located in Tuscany, Italy. Accumulated precipitation exceeding 200 mm in two hours, associated with a return period higher than 200 years, caused all the largest streams of the Livorno municipality to flood several areas of the town. We used the limited-area Weather Research and Forecasting (WRF) model, in a convection-permitting setup, to reconstruct the extreme event leading to the flash floods. We evaluated possible forecasting improvements emerging from the assimilation of local ground stations and X- and S-band radar data into the WRF, using the configuration operational at the meteorological center of Tuscany region (LaMMA) at the time of the event. Simulations were verified against weather station observations, through an innovative method aimed at disentangling the positioning and intensity errors of precipitation forecasts. By providing more accurate descriptions of the low-level flow and a better assessment of the atmospheric water vapour, the results demonstrate that assimilating radar data improved the quantitative precipitation forecasts.

The extrusion-based additive manufacturing is a popular fabrication method, which has attracted the attention of various industries due to its simplicity, cheapness, ability to produce complex geometric shapes, and high production speed. One of the effective parameters in this process is the feed of filament that is presented in the production G-code. The feed of filament is calculated according to the layer height, the extrusion width and the length of printing path. All the required motion paths and filling patterns created by commercial software are a set of straight lines or circular arcs that are placed next to each other at a fixed distance. In special curved paths, the distance of adjacent ones is not equal at different points, and due to the weakness of common commercial software, it is not possible to create curved paths for proper printing. Therefore, making a special computer code that can be used to create various functions of curved paths is investigated in this research, and also the feed of filament parameter is studied in detail. Next, by introducing a correction technique, the feed of filament is changed during the curved path to distribute the polymer material uniformly. Finally, composite samples (which have variable stiffness) consisting of curved fibers are produced with the proposed method, and the high quality of printed samples confirm the suggested code and technique.

The integration of 3D city models with Building Information Models (BIM), abbreviated as GeoBIM, facilitates improved data support to several applications, e.g. 3D map updates, building permits issuing, detailed city analysis, infrastructure design, context-based building design, to name a few. To solve the integration, several issues need to be tackled and solved, i.e. harmonization of features, interoperability, format conversions, integration of procedures. The GeoBIM benchmark 2019, funded by ISPRS and EuroSDR, evaluated the state of implementation of tools addressing some of those issues. In particular, in the part of the benchmark described in this paper, the application of georeferencing to Industry Foundation Classes (IFC) models and making consistent conversions between 3D city models and BIM are investigated, considering the OGC CityGML and buildingSMART IFC as reference standards. In the benchmark, sample datasets in the two reference standards were provided. External volunteers were asked to describe and test georeferencing procedures for IFC models and conversion tools between CityGML and IFC. From the analysis of the delivered answers and processed datasets, it was possible to notice that while there are tools and procedures available to support georeferencing and data conversion, comprehensive definition of the requirements, clear rules to perform such two tasks, as well as solid technological solutions implementing them, are still lacking in functionalities. Those specific issues can be a sensible starting point for planning the next GeoBIM integration agendas.

This paper presents the latest developments in microCT, both globally and locally, for supporting the additive manufacturing industry. There are a number of recently developed capabilities which are especially relevant to the non-destructive quality inspection of additive manufactured parts; and also for advanced process optimization. These new capabilities are all locally available but not yet utilized to their full potential, most likely due to a lack of knowledge of these capabilities. The aim of this paper is therefore to fill this gap and provide an overview of these latest capabilities, showcasing numerous local examples.

Selective laser melting (SLM) is one of the widely used techniques in metallic additive manufacturing, in which high-density laser powder is utilized to selectively melting layers of powders to create geometrically complex parts. Temperature distribution and molten pool geometry directly determine the balling effect, and concentrated balling phenomenon significantly deteriorates surface integrity and mechanical properties of the part. Finite element models have been developed to predict temperature distribution and molten pool geometry, but they were computationally expensive. In this paper, the three-dimensional temperature distributions are predicted by analytical models using point moving heat source and semi-ellipsoidal moving source respectively. The molten pool dimensions under various process conditions are obtained from the three-dimensional temperature predictions and experimentally validated. Ti-6Al-4V alloy is chosen for the investigation. Good agreements between the predictions and the measurements are observed. The presented models are also suitable for other metallic materials in the SLM process.

One in 12 babies is born with a rare genetic disease. Sadly, most cases are undetected until later age, missing time for early treatment and opportunity to prevent complications. Humanity has entered a new era where Big Data collected by governments, including 2D and 3D facial scans, are available. Many rare genetic diseases can be identified by artificial intelligence (AI) analysis of the facial photo. Phenotyping AI utilizations facilitate comprehensive and accurate genetic evaluations. AI processing of this Big Data to identify rare genetic diseases could bring unimaginable benefits to healthcare, although this would be a questionable step in terms of citizen privacy and could lead to future "Orwellian" ramifications with government abuse. Going forward, a balance must be found between protecting the privacy of citizens and the enticing use of AI for their health risks and cost savings through prevention. The unimaginable potential of AI early diagnostics from facial photos also raises various ethical and legal concerns. This paper presents concept, protentional methods and legal and other limitations within EU legal framework in contrast with potential benefits. This paper is focused on AI utilization to early diagnostic of rare genetic diseases. Shift of paradigm in the screening for rare genetic diseases in population with AI face analysis is expected to have a significant impact. The potential of AI algorithms utilizations similar to face2gene app in general population or systematically on Big governmental datasets recording facial traits changes in time can have significant impact on public health but at the same time give raise to profound concern as violation of one’s privacy.

Solar radiation impacts diverse aspects of city life, such as harvesting energy with PV panels, passive heating of buildings in winter, cooling loads of air-conditioning systems in summer, and urban microclimate. Urban digital twins and 3D city models can support solar studies in the process of urban planning and provide valuable insights for data-driven decision support. This study examines the calculation of solar incident radiation at the city scale in Sofia using remote sensing data for the large shading context in a mountainous region and 3D vector building data. The building footprints and the terrain are preprocessed using GIS. The solar calculation uses a raytracing algorithm in 3D CAD at the city scale. To evaluate the performance, two cases were considered at the city and district scale, respectively. The total face count of meshes for the simulations constituted approximately 2 000 000 faces. 64379 roofs for the whole city and 4796 buildings for one district were selected. All calculations were performed in one batch and visualized in a 3D web platform. Using a 3D CAD environment establishes a seamless process of updating 3D models and simulations while preprocessing in GIS ensures working with large-scale datasets. The proposed method showed moderate computation time for both cases and could be extended to include reflected radiation and dense photogrammetric meshes in the future.

The importance of detecting and diagnosing the imminence of aneurysm rupture before it occurs cannot be overstated. However, this process is often time-consuming and challenging, with variability in conclusions not uncommon among experts. Furthermore, current state-of-the-art models in medical image segmentation suffer from limited availability of large annotated datasets for training, exacerbated by an immense data imbalance. In most segmentation tasks, 3D segmentation is preferred due to its capacity to leverage more contextual information. However, these models require more data, which is constrained by the aforementioned issues. In the realm of current diagnosis models, those lacking geographic context are notably ineffective. To address these issues, the aim is to develop a model pipeline to accurately detect cerebral intracranial aneurysms and diagnose rupture imminence through 3D magnetic resonance angiography (MRA) and tabular input, augmented with the implementation of neuro-symbolic ai. The utilization of data fusion to tackle the lack of context in tabular models is proposed, leveraging extracted geographical features from a segmentation model. To enhance segmentation results and tackle the data imbalance in aneurysm segmentation, a two-stage model pipeline that extracts contextual geographic features before aneurysm segmentation is suggested. Segmentation results are additionally improved through ensemble techniques and novel preprocessing techniques. Finally, a neuro-symbolic aspect is introduced to enhance model diagnosis, interpretability and performance. The multi-step Integrated Neuro-Symbolic Analysis Pipeline for Cerebral Aneurysm Rupture Diagnosis is introduced.

An 8-months old male American Staffordshire terrier was referred for a no weightbearing lameness of the right pelvic limb, hyperthermia, lethargy and inappetence caused by hematogenous osteomyelitis. Orthopedic, radiographic and tomographic examinations revealed a bone sequestrum of 4 x 1.4 cm and active periosteal reaction of the caudo-lateral cortical in the metaphysis and the distal third of the right femoral diaphysis, medullary osteolysis and interruption of the cranio-medial cortical profile, with involvement of the femoral trochlea leading to a secondary medial patella luxation. Once skeletally mature, after 4 months from surgical debridement and aggressive antibiotic therapy against Klebsiella oxytoca revealed by bacteriological exam, the patient underwent prosthetic surgery for the application of a custom-made patellar groove replacement (PGR) to fill the bone defect and restore the femoral trochlea surface. Despite the serious injury that afflicted the right pelvic limb, the surgery had satisfactory outcomes until the last 18-months postoperative follow up.

СrAss-like phages play an important role in maintaining ecological balance in the human intestine microbiome. However, their lifestyle and genetic diversity are still insufficiently studied. In this study, a novel CrAssE-Sib phage genome belonging to the epsilon сrAss-like phage genomes was found. Detailed analysis indicated that CrAssE-Sib encodes unusual proteins – DNA primase, virion RNA polymerase, prophage antirepressor, and transcriptional repressor, as well as reverse transcriptase (RT) and receptor binding protein (RBP) that are part of diversity-generating retroelement (DGR). Comparative analysis showed that all epsilon сrAss-like phages are divided into two putative genera, which were proposed to name Epsilonunovirus and Epsilonduovirus; CrAssE-Sib belongs to the first of them. RT from CrAssE-Sib and several Epsilonunoviruses contains a specific motif in its fourth domain that was not previously found in RTs from phage and bacterial DGRs. In addition, RBP from CrAssE-Sib and all Epsilonunoviruses has a unique structure. The presence of the conservative prophage repressor and anti–repressors that belong to the lysogenic-to-lytic cycle switches indicate that CrAssE-Sib and other Epsilonunoviruses could be temperate. Epsilon сrAss-like phage substantially differ from other crAss-like phages, including zeta сrAss-like phages. This fact indicates the need to isolate these phages into a separate family.

Recently, nanotechnologies have become increasingly prominent in the field of bone tissue engineering (BTE), offering substantial potential to advance the field forward. These advancements manifest in two primary ways: the localized application of nanoengineered materials to enhance bone regeneration and their use as nano-vehicles for delivering bioactive compounds. Despite significant progress in the development of bone substitutes over the past few decades, it is worth noting that the quest to identify the optimal biomaterial for bone regeneration remains a subject of intense debate. Ever since its initial discovery, poly(lactic-co-glycolic acid) (PLGA) has found widespread use in BTE due to its favorable biocompatibility and customizable biodegradability. This review provides an overview of contemporary advancements in the development of bone regeneration materials using PLGA polymer. The review covers some of PLGA properties with a special focus on modifications of these properties towards bone regeneration. Furthermore, we delve into the techniques for synthesizing PLGA nanoparticles (NPs), the diverse forms in which these NPs can be fabricated, and the bioactive molecules that exhibit therapeutic potential for promoting bone regeneration. Additionally, we addressed some of the current concerns regarding the safety of PLGA NPs, and PLGA-based products available in the market. Finally, we briefly discussed some of the current challenges and proposed some strategies to functionally enhance the fabrication of PLGA NPs towards BTE. We envisage that the utilization of PLGA NP holds significant potential as a potent tool in advancing therapies for intractable bone diseases.

There has been controversy around the mechanical properties of Mg-alloys such as AZ91D and the large variation of these have been seen. The current paper addresses this controversy through specially fabricated samples combined with tensile testing and advanced metallography, including 3D reconstruction of the phases. The results show that despite a more brittle nature of the fracture, the equiaxed microstructure displays a better elongation as compared to a dendritic microstructure. The main conclusion is that this is primarily caused by the nature, or tortuosity, of the Mg17Al12-network in the material.

One of the key pathogenetic links of type 2 diabetes mellitus (T2DM) is the formation of insulin resistance (IR). Besides a wide selection of synthetic antidiabetic drugs, various plant-origin extracts are also available to support the treatment of T2DM. This study aimed to investigate and gain knowledge of the chemical composition and potential IR correction effect of American cranberry (Vaccinium macrocarpon Aiton) leaf extracts and formulate novel 3D-printed oral dosage forms for such extracts. The bioactivity and IR of L-arginine-loaded cranberry leaf extracts were studied in vivo in rats. The cranberry leaf extracts consisted of quinic, 3-caffeoylquinic (chlorogenic), p-coumaroylquinic acids, quercetin 3-O-galactoside, quercetin-3-O-glucoside, quercetin-3-xyloside, quercetin-3-O-arabino-pyranoside, quercetin-3-O-arabinofuranoside, quercetin 3-O-rhamnoside and quercetin-O-p-coumaroyl-hexoside-2 identified by HPLC. In-vivo studies with rats showed that the oral administration of the cranberry leaf extracts had a positive effect on insulin sensitivity coefficients under ITT test, and affected HOMA-IR levels and liver lipid content with experimental IR. A novel 3D-printed immediate-release dosage form was developed for the oral administration of cranberry leaf extracts using polyethylene oxide (PEO) as a carrier gel in a semi-solid extrusion (SSE) 3D printing. In conclusion, American cranberry leaf extracts loaded with L-arginine could find uses in preventing health issues associated with IR.

There is a fast-growing interest in the use of selective laser melting (SLM) for metal/alloy additive manufacturing. Our current knowledge of SLM printed 316 stainless steel (SS316) is limited and sometimes appears sporadic, presumably due to the complex interdependent effects of a large number of process variables of the SLM processing. This is reflected from the discrepant findings in the crystallographic textures and microstructures in this investigation with those reported in the literatures, which also vary itself. The as-printed material is macroscopically asymmetric in both the structures and crystallographic textures. The <101> and <111> crystallographic directions align parallel with the SLM scanning direction (SD) and build direction (BD), respectively. Like-wise, some characteristic low angle boundary features are reported crystallographic, while this investigation unequivocally proves them non-crystallographic since they always maintain an identical alignment with the SLM laser scanning direction irrespective of the matrix material’s crystal orientation. There is also 500±200 nm columnar or cellular features, depending on the cross-section, generally found all over the sample. These columnar or cellular features are formed with walls made of dense packing of dislocations entangled with Mn, Si and O enriched amorphous inclusions. They remain stable after the ASM solution treatments at 1050 °C temperatures, and therefore, are capable of hindering boundary migration events of recrystallization and grain growth. Thus, the nanoscale structures can be retained at high temperatures. Large 2-4 µm inclusions form during the solution treatment, within which the chemical and phase distribution are heterogeneous.

Associations between blood cancer and genetic predisposition, including both inherited variants and acquired mutations and epimutations, have been well characterized. However, the majority of these variants affect noncoding regions, making their mechanisms difficult to hypothesize and hindering the translation of these insights into patient benefits. Fueled by unprecedented progress in next-generation sequencing and computational integrative analysis, studies have started applying combinations of epigenetic, genome architecture and functional assays to bridge the gap between noncoding variants and blood cancer. These complementary tools have not only allowed us to understand the potential malignant role of these variants but also to differentiate key variants, cell types and conditions from misleading ones. Here, we briefly review recent studies that have provided fundamental insights into our understanding of how noncoding mutations at enhancers predispose and promote blood malignancies in the context of spatial genome architecture.

A common task in the immunodetection of structurally close compounds is to analyze the selectivity of immune recognition: it is required to understand the regularities of immune recognition and to elucidate the basic structural elements which provide it. Triazines are compounds of particular interest for such a research due to their high variability and the necessity of their monitoring to provide safety of agricultural products and foodstuffs. We evaluated the binding of 20 triazines with polyclonal (pAb) and monoclonal (mAb) antibodies obtained using atrazine as the immunogenic hapten. A total of >3000 descriptors was used in QSAR analysis of binding activities (pIC50). Comparison of the two enzyme immunoassay systems showed that the system with pAb is much easier to describe using 2D QSAR methodology, while the system with mAb can be described using the 3D QSAR COMFA. Thus, for the 3D QSAR model of the polyclonal antibodies, the main statistical parameter q² (‘leave-many-out’) is equal 0.498, and for monoclonal antibodies q² is equal 0.566. Obviously, in the case of pAb, we deal with several targets, while in the case of mAb the target is one, and therefore it is easier to describe it using specific fields of molecular interactions distributed in space.

Manipulation of micro- and nano-sized objects with optical tweezers is a well established, albeit still evolving technique. While many objects can be trapped directly with focused laser beam(s), for some applications indirect manipulation with tweezers-operated tools is preferred. We introduce a simple, versatile micro-tool operated with holographic optical tweezers. The 40 µm long dumbbell-shaped tool, fabricated with two-photon laser 3D photolithography has two beads for efficient optical trapping and a probing spike on one end. We demonstrate fluids viscosity measurements and vibration detection as examples of possible applications.

Over 2.2 billion people across the globe face significant barriers to accessing essential ophthalmic care, with elderly, rural, and refugee populations being disproportionately affected. These obsta-cles deepen existing disparities in eye care. 3D printing is a novel technology that has the potential to transform the field and improve access through alleviating many patient-specific barriers. This article delves into the evolution of 3D printing within ophthalmology, highlighting its current ap-plications and future potential. It explores various 3D printing techniques and biomaterials, dis-cussing their effectiveness in creating advanced solutions such as bioengineered corneas, ocular prosthetics, and innovative treatments for dry eye syndrome. Additionally, 3D printing has rev-olutionized drug delivery systems for conditions like glaucoma, retinal diseases, and for ocular brachytherapy. Despite its promise, the integration of 3D printing into clinical practice presents challenges, which the article addresses alongside strategies for overcoming them. By mapping out the technological advancements and challenges, this review offers a roadmap for enhancing global eye care accessibility and improving patient outcomes on a global scale.

Due to the manufacturing process of Additive Manufacturing (AM) Parts the mechanical properties cannot be predicted. The scope of the present work is to propose a predictive tool for the mechanical properties of AM parts through the use of Adaptive Neuro-Fuzzy Inference System (ANFIS). The Adaptive Neuro-Fuzzy Inference System (ANFIS) combines neural networks with fuzzy logic to generate a mapping between the inputs and the output. Real data experiments from different AM technologies and materials compose the initial dataset so a detailed investigation is conducted to gain knowledge of how different parameters affect the UTS, the elongation and the Young modulus of each experiment. Experimental data were also use to train, check and verify the methodology. The method is tested for FFF technology, PLA material and 3 point bending stress, with interesting results.

This study aims to demonstrate the possibility of incorporating a natural antioxidant biomolecule, into polymeric porous scaffolds. To this end, Poly-L-Lactic Acid (PLLA) scaffolds were produced using the Thermally Induced Phase Separation (TIPS) technique and additivated with different amounts of Rosmarinic Acid (RA). The scaffolds, with a diameter of 4 mm and a thickness of 2 mm, were characterized with a multi-analytical approach. Specifically, Scanning Electron Mi-croscopy analyses demonstrated the presence of an interconnected porous network, character-ized by a layer of RA at the level of the pore’s surfaces. Moreover, the presence of RA biomole-cules increased the hydrophilic nature of the sample, as evidenced by the decrease in contact angle with water from 128° to 76°. This approach is cost-effective, and it could be customized with different biomolecules, offering the possibility of producing porous polymeric structures con-taining antioxidant molecules. These scaffolds meet the requirements of tissue engineering and could be offered a potential solution to reduce inflammation associated with scaffold implantation thus improving tissue regeneration.

The first paper of this two-part series paper discussed the development of a novel lightweight 3D wood dowel-reinforced glass epoxy hybrid composite material (3DdrFRP) and its manufacturing procedures. It also experimentally compared the performance of scaled utility poles made from conventional 2D E-glass epoxy and 3DdrFRP materials. In the second part, we developed robust finite element (FE) models in LS-DYNA, calibrated them based on experimental results, and used them to simulate the performance of equivalent 2D and 3D poles, proving the integrity of the numerical model. Additionally, we developed a simplified analytical calculation method for engi-neers to determine the stiffness of 3D-DrFRP poles accurately and quickly.

During the last decades the quantitative description of electrical and magnetotransport properties of solid-state materials has been a remarkable challenge in materials science. Recently, the discovery of a novel class of materials, the topological semimetals, has led to a growing interest for the full understanding of their magnetotransport properties. In this review, the strong interplay among topology, band structure and carrier mobility in recently discovered high carriers mobility topological semimetals is discussed and their effect on their magnetotransport properties is outlined. The huge magnetoresistance effect, especially in the Hall transverse configuration, and a new version of a three-dimensional quantum Hall effect observed in high-mobility Weyl and Dirac semimetals are reviewed. The design of novel quantum sensors based on solid-state semimetals is also encouraged.

The expression of the Fasciola hepatica Carboxylesterase type B (CestB) gene is induced in response to the anthelmintic triclabendazole (TCBZ), resulting in a significant increase in enzymatic specific activity. Furthermore, the amino acid sequence of CestB exhibits variations that could lead to substantial amino acid substitutions at the ligand-binding site. These substitutions have the potential to affect the interaction between the ligand and the protein, as well as the catalytic properties of the enzyme. The objective of this study was to identify new CestB polymorphisms in TCBZ-resistant parasites using 3D modeling against the metabolically oxidized form of the anthelmintic TCBZSOX. Our aim was to observe the formation of TCBZSOX-specific binding pockets that could potentially explain the resistance to anthelmintic agents. We identified a CestB polymorphism in a TCBZ-resistant strain of parasites exhibiting three radical amino acid substitutions at positions 147, 215, and 243, resulting in the formation of a TCBZSOX-affinity pocket capable of binding the anthelmintic drug. Additionally, our 3D modeling analysis revealed that these amino acid substitutions also had an impact on the configuration of the CestB catalytic site, affecting the enzyme's interaction with chromogenic carboxylic ester substrates and altering its catalytic properties; however, the identified TCBZSOX-binding pocket was located far from the enzyme's catalytic site, making the enzymatic hydrolysis of TCBZSOX theoretically impossible. Nonetheless, the increased affinity for the anthelmintic may explain a drug-sequestration type of anthelmintic resistance and lays the foundation for the development of a molecular diagnostic tool for identifying anthelmintic resistance in F. hepatica.

The first years of an infant’s life represent a sensitive period for neurodevelopment and see the emergence of nascent forms of executive function (EF), which are required to support complex cognition. Few tests exist for measuring EF during infancy, and the available tests require painstaking manual coding of infant behaviour. In modern clinical and research practice, human coders collect data on EF performance by manually labelling video recordings of infant behaviour during toy or social interaction. Besides being extremely time-consuming, video annotation is known to be rater-dependent and subjective. To address these issues, starting from existing cognitive flexibility research protocols, we developed instrumented toys as a new task instrumentation and data collection tool suitable for infant use. A commercially available device comprising a Barometer and Inertial Measurement Unit (IMU) embedded in a 3D-printed lattice structure was used to detect when and how the infant interacts with the toy. The data collected using the instrumented toys provides a rich dataset describing the sequence of toy interaction and individual toy interaction patterns, from which EF-relevant aspects of infant cognition may be inferred. Such a tool potentially provides an objective, reliable, and scalable method of collecting early developmental data in socially interactive contexts.

Phase imaging of biochemical samples has been demonstrated for the first time at the Infrared Microspectroscopy (IRM) beamline of the Australian Synchrotron using the usually discarded Near-IR (NIR) region of the synchrotron-IR beam. The synchrotron-IR beam at the Australian Synchrotron IRM beamline has a unique fork shaped intensity distribution as a result of the gold coated extraction mirror shape, which includes a central slit for rejection of the intense X-ray beam. The resulting beam configuration makes any imaging task challenging. For intensity imaging, the fork shaped beam is usually tightly focused to a point on the sample plane followed by a pixel-by-pixel scanning approach to record the image. In this study, a pinhole was aligned with one of the lobes of the fork shaped beam and the Airy diffraction pattern was used to illuminate biochemical samples. The diffracted light from the samples was captured using a NIR sensitive lensless camera. A rapid phase-retrieval algorithm was applied to the recorded intensity distributions to reconstruct the phase information corresponding to different planes. The preliminary results are promising to develop multimodal imaging capabilities at the IRM beamline of the Australian Synchrotron.

This article presents, for the first time, the kinetics and the general conversion features of a 3-component system, BT(BC)/iodonium/Amine, based on proposed mechanism of Liu et al, for both free radical polymerization (FRP) of acrylates and the free radical promoted cationic polymerization (CP) of epoxides using the new multi-functional initiator of benzophenone–triphenylamine (BT). The additives, iodonium and EDB, have the dual function of (i) regeneration BT and (ii) produce of extra radicals for improved FRP and CP. Analytic formulas are developed to explore the new features including: (i) the conversion efficacy (CE) of FRP is an increasing function of the light intensity, the effective absorption coefficient, and the concentration sum of each of the components, BT, Iod, amine, for transient state. However, CE at steady-state is independent to the light intensity; (ii) the trifunctional hybrid structures of BT3 leads to larger light absorption than other types of BT; it also provides more active sites for the H-abstraction in the presence of EDB, leading to high CE; (iii) the efficacy of FRP is an increasing function of the amine (EDB) concentration, in contrast to that of CP having an opposite dependence; (iv) the consumption rate of BT3 in the BT3/ Iod/EDB system is slower than that of the BT3/Iod system due to photoredox catalytic cycle, and the larger initiator regeneration (RGE)
in the three-component system. A comprehensive model is also proposed that the CE (for both FRP and CP) is governed by (N_jK_jbI), whereas more complex formulas are developed; where Kj is an effective rate constant proportional to the electron transfer quantum yield, and the combined effects of other coupling rate constants; b is an effective absorption coefficient given by the light absorption and excited state quantum yield.

This study explores the potential to reach a circular economy for post-consumer recycled polyethylene terephthalate (rPET) packaging and bottles by using it as a distributed recycling for additive manufacturing (DRAM) feedstock. Specifically, rPET is processed using only an open source toolchain with fused particle fabrication (FPF) or fused granular fabrication (FGF) processing. In this study, first the impact of granulation, sifting and heating (and their combination) is quantified on the shape and size distribution of the rPET flakes. Then feeding studies were performed to see if they could be printed through an external feeder or needed to be direct printed with a hopper using two Gigabot X machines, one with extended part cooling and one without. Print settings were optimized based on thermal characterization and for the latter which was shown to print rPET directly from shredded water bottles mechanical testing is performed. The results showed that geometry was important for extended feeding tubes and direct printed using a hopper. Further there is a wide disparity in the physical properties of rPET from water bottles depending on source and the history of the material. Future work is needed to enable water bottles to be used as a widespread DRAM feedstock.

Polydimethylsiloxane (PDMS) is one of the most popular elastomers and has been used in different fields, especially in biomechanics research. Among the many interesting features of this material, its hyperelastic behaviour stands out, which allows the use of PDMS in various applications, like the ones that mimic soft tissues. However, the hyperelastic behaviour is not linear and needs detailed analysis, especially the characterization of shear strain. In this work, two approaches, numerical and experimental, were proposed to characterize the effect of shear strain on PDMS. The experimental method was implemented as a simple shear testing associated with 3D digital image correlation and was made using two specimens with two thicknesses of PDMS (2 and 4 mm). A finite element software was used to implement the numerical simulations, in which four different simulations using the Mooney-Rivlin, Yeoh, Gent, and Polynomial hyperelastic constitutive models were performed. These approaches showed that the maximum value of shear strain occurred in the central region of the PDMS, and higher values emerged for the 2 mm PDMS thickness. Qualitatively, in the central area of the specimen, the numerical and experimental results have similar behaviours and the values of shear strain are close. For higher values of displacement and thicknesses, the numerical simulation results move further away from experimental values.

The tumor organoid (tumoroid) model in three-dimensional (3D) culture systems has been developed to reflect more closely the in vivo tumors than 2D-cultured tumor cells. Notably, extracellular vesicles (EVs) are efficiently collectible from the culture supernatant of gel-free tumoroids. Matrix metalloproteinase (MMP) 3 is a multi-functional factor playing crucial roles in tumor progression. However, roles of MMP3 within tumor growth and EVs have not unveiled. Here, we investigated the protumorigenic roles of MMP3 on integrities of tumoroids and EVs. We generated MMP3-knockout (KO) cells using the CRISPR/Cas9 system from rapidly metastatic LuM1 tumor cells. Moreover, we established fluorescent cell lines with palmitoylation signal-fused fluorescent proteins (tdTomato and enhanced GFP). Then we confirmed the exchange of EVs between cellular populations and tumoroids. LuM1-tumoroids released large EVs (300-1000 nm) and small EVs (50-200 nm) while the knockout of MMP3 resulted in the additional release of broken EVs from tumoroids. The loss of MMP3 leads to a significant reduction in tumoroid size and to the development of the necrotic area within tumoroids. MMP3 and CD9 (a category-1 EV marker tetraspanin protein) were significantly down-regulated in MMP3-KO cells and their EV fraction. These weakened phenotypes by MMP3 KO were markedly rescued by the addition of MMP3-rich EVs or conditioned medium (CM) collected from LuM1-tumoroids, which caused a dramatic rise in the expression of MMP3, CD9, and Ki-67 (a marker of proliferating cells) in the MMP3-null/CD9-low tumoroids. Notably, MMP3 enriched in tumoroids-derived EVs and CM deeply penetrated into recipient MMP3-KO tumoroids, resulting in a remarkable enlargement of solid tumoroids, while MMP3-null EVs did not. These data demonstrate that EVs can mediate molecular transfer of MMP3 resulting in increasing the proliferation and CD9+ tumorigenesis, indicating crucial roles of MMP3 in tumor progression.

The present study evaluates the manufacturing parameters effects on the tensile properties of material composed by polylactic acid (PLA) with wood fibers known as Timberfill. The specimens were built through fused filament fabrication (FFF). The influence of four printing parameters (Layer height, Fill density, Printing velocity, and Orientation) are considered through a L27 Taguchi orthogonal array in order to reduce experimental runs. Tensile test is applied to obtain the response variable used as output results to perform the ANOVA calculations. Fill density is the most influential parameter on the tensile strength, followed by building orientation and layer height, whereas the printing velocity shows no significant influence. The optimal set of parameters and levels is found, being 75% fill density, 0○Z-axis orientation, 0.4 mm layer height, and 40 mm/s velocity as the best combination. Applying this combination showed 9.37 MPa in maximum tension. Lastly, five solid Timberfill specimens manufactured via injection molding technology were also tested and the results compared to the printed samples. The values of the elastic modulus, elastic limit, and maximum tension of the injected samples were almost twofold of those were obtained for the FFF samples, but the maximum elongation of injected specimens was fell sharply.

Radio-fluorogenic (RFG) gels become permanently fluorescent when exposed to high-energy radiation with the intensity of the emission proportional to the local dose of radiation absorbed. An apparatus is described, FluoroTome 1, that is capable of taking a series of tomographic images (thin slices) of the fluorescence of such an irradiated RFG gel on-site and within minutes of radiation exposure. These images can then be compiled to construct a 3D movie of the dose distribution within the gel. The historical development via a laboratory-bench prototype to a readily transportable, user-friendly apparatus is described. Instrumental details and performance tests are presented.

Despite improvements in participation in population-based screening programs, colorectal cancer remains a major cause of cancer-related mortality worldwide. Targeted interventions are desirable to reduce the health and economic burden of this disease. Two-dimensional monolayers of colorectal cancer cell lines represent the traditional in vitro models for disease and are often used for diverse purposes, including delineation of molecular pathways associated with disease aetiology or to gauge drug efficacy. The lack of complexity in such models, chiefly the limited epithelial cell diversity and differentiation, attenuated mucus production, lack of microbial interactions and mechanical stresses, has driven interest in development of more holistic and physiologically relevant in vitro model systems. In particular, established ex vivo patient-derived explant and patient-derived tumour xenograft models have been supplemented by progress in organoid and microfluidic organ-on-a-chip cultures. Here we discuss the applicability of advanced culturing technologies, such as organoid systems, as models for colorectal cancer and for testing chemotherapeutic drug sensitivity and efficacy. We highlight current challenges associated with organoid technologies and discuss their future for more accurate disease modelling and personalized medicine.

This study examines the practicality and limitations of using a FANUC CRX-10 iA/l collaborative robot to assemble a product component, highlighting the trade-offs between increased roboisation and reduced manual intervention. Through a detailed case study in the i-Labs laboratory, critical factors affecting precision assembly such as station layout, tooling design and robot programming are discussed. The findings highlight the benefits of robots for non-stop operation, freeing up human operators for higher value tasks despite longer cycle times. In addition, the paper advocates further research into reliable gripping of small components, a current challenge for robotics. The work contributes to open science by sharing partial results and methods that could inform future problem solving in robotic assembly.

The Gulf of Suez is a sedimentary rift-basin with thick evaporites and complex structural settings that presents challenges to achieving quality imaging based on seismic reflection data. Such subsurface settings and the lack of 3D seismic data poses challenges in building reservoir models to guide hydrocarbon exploration and development, especially in southern parts the Gulf of Suez. This study attempts to overcome the challenges of both 2D seismic interpretation and building a static reservoir model of two Miocene reservoir formations, Ras Ghara Field, Southern Gulf of Suez. Integration of well log data analysis of nine wells and regional-tectonics cognizant 2D seismic interpretation of nineteen 2D seismic lines enabled a reliable 3D static reservoir model. The Miocene reservoir characterization reveals heterogeneity in lithofacies distribution, with thick evaporite sequences causing seismic reflection distortions. Significant hydrocarbon accumulations are associated with horst fault blocks. The Miocene reservoirs demonstrate effective porosity of 14-33%, water saturation of 16-65%, and hydrocarbon saturation of 35-84%. Two new prospects are identified based on structure, facies distribution, and petrophysical results, with estimated original oil in place (OOIP) of 2,002,404 stock tank barrels (STB) and 1,175,580 STB for the Kareem Formation, and 6,302,916 STB and 2,841,894 STB for the Rudeis Formation.

Polymer-based (nano)composite foams, especially those having a microcellular structure, containing suitable conductive (nano)fillers, have been shown to act as good shielding materials, hence coming as promising to act as shields in electronic devices, limiting/avoiding electromagnetic interference (EMI) pollution. Nevertheless, due to their high (micro)structural complexity, related to their multiphase nature, there is still a lot of unawareness behind the shielding mechanisms acting in these materials, coming as a necessity to study their microstructure-cellular/porous structure-properties relations, especially in terms of their electrical conductivity and EMI shielding efficiency (EMI SE). To target and control the electrical conductivity through a controlled distribution/dispersion of conductive nanofillers, single or combined (nanohybrids), as there is a direct relation between electrical conductivity and EMI SE, as well as the main EMI shielding mechanisms working on the developed microcellular structure of the foams, which are expected to be absorption-dominated or absorption/multiple reflection-based, are two of the main objectives when combining polymer foaming with the addition of conductive nanofillers. The present review work considers the recent developments and trends on polymer-based foams containing conductive nanofillers, especially carbon-based such as carbon nanotubes or graphene-based materials, as well as similar porous structures created using trending technologies such as 3D printing, for EMI shielding applications. It is divided in different sections, starting with the strategy of microcellular foaming to develop polymer-based foams with enhanced EMI shielding characteristics, especially focusing on technologies and methods using supercritical CO2 (sCO2); continuing with the use of polymer foams as templates to synthesize carbon foams with improved EMI shielding performance for high use temperature applications; the recent strategy of combining different functional (nano)fillers to create hybrid nanofillers/nanohybrids to be used at lower amounts as conductive fillers in polymer foams; the control and selective distribution of the nanofillers in terms of favoring the formation of a more effective conductive network and hence promote the enhancement of the EMI SE; the very recent use of computational approaches to tailor the EMI shielding properties of composite foams; and the very trending possibility of creating cellular components with varied porous structures from these materials using 3D printing; to finish, some future perspectives are discussed.

Single particle analysis with cryogenic electron microscopy (cryo-EM) can determine high resolution structures of macromolecular assemblies. To reconstruct final three-dimension(3D) density map, a reliable initial model is essential and ab-initio reconstruction usually can avoid model bias. The grand challenge for ab-initio reconstruction is to alignment two-dimension(2D) low signal-to-noise ratio(SNR) of particle images with random and unknown parameters. Here we formulate a fast ab initio reconstruction method(named AlignFM) based on Fourier Mellin transform and particle-swarm intelligence optimization(PSO) algorithm. It enables simultaneous 2D alignment and 3D refinement, which can fast generate a reliable 3D map. After experiments on several real datasets. AlignFM shows high performance on fast ab initio reconstruction with a small amount of data.

ORF7b-2 is an accessory protein of the SARS-CoV-2 virus of only 43 amino acids. It has been implicated in various functional hypotheses, some of which predict its involvement as a trans-membrane protein. In this study, ORF7b-2 has often been compared to ORF7b-1 of the SARS virus to highlight differences and similarities with a protein that should have a similar biological role. Structural analysis of ORF7b-2 and its electrostatic characteristics show a polypeptide with both ends negatively charged and a diffuse negative charge over the entire structure. Therefore, its behavior in solution is like that of a weak negative polyelectrolyte, more precisely a polyanion with a net charge of – 4 at neutral pH. Its structure was modeled with two different modeling systems, one of which was ab initio. The two best models are similar, as confirmed by the Ramachandran plot, and show a central alpha-helical structure with two disordered and mobile ends. A normal mode analysis characterized the low-frequency dynamic aspects of the protein. The analysis of the structural shows a rigid central segment with mobile and fluctuating extremities, involved in a conformational equilibrium of the helix ↔ coil type. The calculation of the dipole moment shows its vector is not aligned with the main axis of the structure with an outward tilt of 24°. Molecular dynamics simulations were also conducted and the one in water is in good agreement with the previous results. While, the simulation performed by inserting a pre-oriented dimer (OMP) into a solvated lipid showed the low tendency of the protein to solvate in the apolar environment of the membrane. ORF7b-2 also shows a widespread distribution of negative surfaces that dynamically adjust to changes in structural organization. The BioGrid platform's [Biological General Repository for Interaction Datasets] through the BioGrid COVID-19 Coronavirus Curation Project shows a very large number of experimentally proven physical interactions unique to ORF7b-2, some of them with cytoplasmic proteins. These features of ORF7b-2, evaluated together, suggest a remarkable propensity of ORF7b-2 to interact with multiple molecular partners on both an electrostatic and hydrophobic basis. All this makes it unreasonable that the only biological function of this protein should be that exerted as an intramembrane protein.

The Selective Paste Intrusion (SPI) method is a layer-by-layer additive manufacturing technique that allows for the production of complex geometries in concrete elements by selectively bonding aggregates with cement paste in a particle bed. To create reinforced concrete, the Wire and Arc Additive Manufacturing (WAAM) process shall be integrated into SPI. This technique allows the production of almost free-formed reinforcement and thus complements the advantage of SPI to produce free-formed structures of almost any geometry. However, integration of WAAM into SPI poses a considerable challenge, as high temperatures are generated during the welding process. These temperatures can negatively affect the rheological properties of the cement paste, in turn the penetration behavior of the paste in the particle bed and, subsequently, the mechanical properties of the hardened concrete. A possible passive cooling strategy is to increase the protruding length of the reinforcement bars out of the particle-bed. This requires that the distance of the print nozzle to the particle bed is as well increased, since it must be possible to move it across the reinforcement. The objective was thus to investigate the effect of that distance on print quality and to quantify a maximum allowable distance for an adequate print quality (for the printer setting used) in terms of shape accuracy and concrete strength. Compressive and flexural strength tests as well as geometrical measurements using a 3D scanning method were performed on specimen, printed with varying print nozzle to particle bed distances. It can be stated that for the used SPI print-heads, nozzle-types and parameter settings, the distance between the nozzle and the particle bed should not exceed 50 mm to ensure sufficient print quality in both shape accuracy and mechanical strength.

A refractive lens is one of the simplest, cost-effective and easily available imaging elements. With a spatially incoherent illumination, a refractive lens can faithfully map every object point to an image point in the sensor plane, when the object and image distances satisfy the imaging conditions. However, static imaging is limited to the depth of focus, beyond which the point-to-point mapping can be only obtained by changing either the location of the lens or the imaging sensor. In this study, the depth of focus of a refractive lens in static mode has been expanded using a recently developed computational reconstruction method, Lucy-Richardson-Rosen algorithm (LRRA). The technique consists of three steps. In this first step, the point spread functions (PSFs) were recorded along different depths and stored in the computer as PSF library. In the next step, the object intensity distribution was recorded. The LRRA was then applied to deconvolve the object information from the recorded intensity distributions in the final step. The results of LRRA were compared against two well-known reconstruction methods namely Lucy-Richardson algorithm and non-linear reconstruction.

Accurate localization of road agents is the basis of intelligent transportation systems, which is still difficult to achieve for GNSS positioning in urban areas due to the signal interferences from buildings. Various collaborative positioning techniques are recently developed to improve the positioning performance by the aid from neighboring agents. However, it is still challenging to study their performances comprehensively. The GNSS measurement error behavior is complicated in urban areas and unable to be represented by naive models. On the other hand, real experiment requiring numbers of devices is hard to be conducted, especially for a large-scale test. Therefore, a GNSS realistic urban measurement simulator is developed to provide measurements for collaborative positioning studies. The proposed simulator employs a ray-tracing technique searching for all possible interferences in the urban area. Then, it categorizes them into direct, reflected, diffracted, and multipath signal to simulate the pseudorange, carrier-phase, 〖C/N〗_0, and Doppler shift measurements correspondingly. The performance of the proposed simulator is validated through real experimental comparisons with different scenarios. The proposed simulator is also applied with different positioning algorithms, which verifies it is sophisticated enough for the collaborative positioning studies in the urban area.

In this study, the field measurement-based validation of a novel sediment transport calculation method is presented. River sections with complex bed topography and inhomogeneous bed material composition highlight the need for an improved sediment transport calculation method. The complexity of the morphodynamic features can result in the simultaneous appearance of the gravel and finer sand dominated sediment transport (e.g. parallel bed armoring and siltation) at different regions within a shorter river reach. For the improvement purpose of sediment transport calculation in such complex river beds, a novel sediment transport method was elaborated. The base concept of it is the combined use of two already existing empirical sediment transport models. The method was already validated against laboratory measurements. The major goal of this study is the verification of the novel method with a real river case study. The combining of the two sediment transport models is based on the implementation of a recently presented classification method of the locally dominant sediment transport nature (gravel or sand transport dominates). The results are compared with measured bed change maps. The verification clearly refers to the meaningful improvement in the sediment transport calculation by the novel manner in case of spatially varying bed content.

In this paper the authors describe the architecture of a multidisciplinary data acquisition and visualization platform devoted to the management of coastal environments. The platform integrates heterogeneous data acquisition sub-systems that can be roughly divided in two main categories: remote sensing systems and in-situ sensing systems. Remote sensing solutions include aerial and underwater remote data acquisition while in-situ sensing solutions include the use of RFID tracers, Wireless Sensor Networks and imaging techniques. All the data collected by these subsystems are stored, integrated and fused on a single platform that is also in charge of data visualization. This last task is carried out according to the paradigm of Augmented Virtuality which foresees the augmentation of a virtually reconstructed environment with data collected in the real world. The described solution proposes a novel holistic approach where different disciplines concur, with different data acquisition techniques, to a large scale definition of coastal dynamics, in order to better describe and face the coastal erosion phenomenon. The overall framework has been conceived by the so-called Team COSTE, a joint research team between the Universities of Pisa, Siena and Florence.

This paper presents computer and color vision research focusing on human color perception in VR environments. A VR art gallery with digital twins of original artworks is created for this experiment. In this research, the field of colorimetry and the application of CMYK and RGB color models are applied. The interrelationships of the two colors models are applied to create a color modification of the VR art gallery environment using C# Script procedures. This color-edited VR environment works with a smooth change of color tone in a given time interval. At the same time, a sudden change in the color of the RGB environment is defined in this interval. This experiment aims to record a user's reaction embedded in a VR environment and the effect of color changes on human perception in a VR environment. The research uses lie detector sensors that record the physiological changes of the user embedded in VR. Five sensors are used to record the signal. An experiment on the influence of the user's color perception in a VR environment using lie detector sensors has never been conducted. This research defines the basic methodology for analyzing and evaluating the recorded signals from the lie detector. The presented text thus provides a basis for further research in the field of colors and human color vision in a VR environment and lays an objective basis for use in many scientific and commercial areas.

Induction heating is a fast, reproducible, and efficient heating method used in various manufacturing processes. However, there is no established additive manufacturing (AM) process based on induction heating using wire as feedstock. This study investigates a novel approach to AM based on inductive heating, where a steel wire is melted and droplets are detached periodically using a two-winding induction coil. The process parameters and energy input into the droplets are characterized. The induction generator exhibits sluggish response to the excitation voltage, resulting in a lag in the coil current. The process is captured using a high-speed camera, revealing regular droplet formation and uniform size and shape when operated within an appropriate process window. Larger drops and increased spatter formation occur outside this window. The proposed method allows for the production of droplets with almost spherical shapes. Further analysis and characterization of droplet formation and energy input provide insights into process optimization and overall efficiency.

Gain-scheduled autopilots have emerged as a dominant strategy to achieve adaptive control of coupled, non-linear engineering complexities, owing to an ability to adapt to changing operational conditions and uncertainties. This study focuses on utilizing bilinear interpolation of gain-scheduled autopilots, emphasizing enhanced system performance and robustness. Through a comprehensive investigation and comparative analysis using three disparate cases, advantages over conventional methods are revealed. Strengths and weaknesses of both simple and specialized variants (such as linear, and real-time gain-scheduling) are introduced. Three missile guidance case–studies utilize simulation time and miss distance figures of merit. Potential to achieve precise control across various mission scenarios, while ensuring reduced computational complexity is revealed by nearly two–hundred percent improved missile miss distances with comparable distances traveled and slightly improved computational burden.

Fly ash cement has rarely been used in Japan, mainly because its strength development is slower than ordinary Portland cement. In this research, the effect of the new fly ash cement with both high alite (C3S) cement and fly ash modified by electrostatic belt separation method on cracking resistance of precast concrete prepared by steam curing was studied. The mechanical and shrinkage properties of the proposed fly ash concrete were compared with those of concrete made using OPC cement without fly ash. In order to study the cracking tendency of precast concrete with the proposed fly ash cement, thermal stress analysis was conducted taking into consideration of the experimental data of concrete properties with the different concrete mix proportions. A standard precast concrete box culvert model was used in this 3D FEM analysis and the distribution of temperature and relative humidity in cross section and induced restraint stress during and after steam curing were discussed. Steam-cured concrete with fly ash and high alite cement developed higher compressive strength on the first day of age than concrete with OPC. The proposed fly ash concrete developed high cracking resistance in the early days. On the other hand, the results showed that the drying shrinkage at later ages was the main cause of cracking.

In recent years, researchers in the field of cultural heritage have intensified their efforts to develop new ways to enhance the promotion and accessibility of cultural content in order to attract more audiences using virtual representations of physical objects (digital twins). Therefore, they increasingly include new technologies and digital tools in their operation, since their application both to the general public and among the cultural organisations themselves, is considered particularly effective. Simultaneously, the increasing quality of the produced digitizations has opened up new opportunities for further exploitation of digitization outcomes in a broader context than was initially anticipated. Responding to the growing demand of museum visitors for a personalized digital tour experience, especially in the midst of the recent Covid-2019 pandemic, the v-PalM project aims to develop a digital platform for offering virtual guidance and education services at the Museum of Paleontology and Geology that is hosted at the National Kapodistrian University of Athens. The development of the platform will be based on collecting data through several methods including crowdsourcing, innovative information and communication technologies, taking advantage of content digitization using 3D scanning devices. In this paper, we demonstrate a methodology for the digitization of paleontological findings that can be used for creating digital twins suitable for various scenarios including research, education, and entertainment.

We present a novel passive satellite remote sensing approach for observing the three-dimensional distribution of aerosols emitted from wildfires. This method, called AEROS5P, retrieves vertical profiles of aerosol extinction from measurements of the TROPOMI satellite sensor onboard the Sentinel 5 Precursor mission. It uses a Tikhonov-Phillips regularization which iteratively fits cloud-free near-infrared and visible selected reflectances to simultaneously adjust the vertical distribution and abundance of aerosols. The information on the altitude of the aerosol layers is provided by TROPOMI measurements of the reflectance spectra at the oxygen A-band near 760 nm. In the present paper, we use this new approach for observing the daily evolution of the three-dimensional distribution of biomass burning aerosols emitted by Australian wildfires on 20-24 December 2019. Aerosol optical depths (AOD) derived by vertical integration of the aerosol extinction profiles retrieved by AEROS5P are compared with MODIS, VIIRS and AERONET coincident observations. They show a good agreement in the horizontal distribution of biomass burning aerosols, with a correlation coefficient of 0.86 and a mean absolute error of 0.2 with respect to VIIRS. A fair agreement is found between coincident transects of vertical profiles of biomass burning aerosols derived from AEROS5P and from the CALIOP spaceborne lidar. The mean altitude of these aerosols derived from these two measurements show a good agreement, with a small mean bias (185 m) and a correlation coefficient of 0.83. Moreover, AEROS5P observations reveal the height of injection of the biomass burning aerosols in 3D. The highest injection heights during the period of analysis are coincident with the largest fire radiative power derived from MODIS. Consistency is also found with respect to the vertical stability of the atmosphere.

In this review, we explore a broad-based view of technologies for supporting human activities on the Moon. Primarily, we assess the state of life support systems technology beginning with physicochemical processes, waste processing, bioregenerative methods, food production systems and the robotics and advanced biological technologies that support the latter. We observe that the Moon possesses in-situ resources but that these resources are of limited value in CELSS – indeed, CELSS technology is most mature in recycling water and oxygen, the two resources that are abundant on the Moon. This places a premium on developing CELSS that recycles other elements that are rarified on the Moon including C and N in particular but also other elements such as P, S and K which might be challenging to extract from local resources. Although we focus on closed loop ecological life support systems, we also consider related technologies that involve the application of biological organisms to bioregenerative medical technologies and bioregenerative approaches to industrial activity on the Moon as potential future developments.

The disruption of conventional manufacturing, supply, and distribution channels for medical supplies during the COVID-19 pandemic has caused widespread shortages and catalyzed local efforts to use nontraditional, rapid manufacturing to meet urgent healthcare needs. Here we present a crisis-responsive design framework designed to assist with product development under pandemic conditions. The framework utilizes extensive stakeholder engagement, comprehensive and dynamic needs assessment, local manufacturing, and product testing for the accelerated development of healthcare products. We contrast this framework with traditional medical device manufacturing and discuss relevant regulatory policies. We highlight the applicability of the crisis-responsive framework to a successful local program that designed and supplied face shields for a large US academic hospital. Finally, we make recommendations aimed at improving future resilience to healthcare emergencies. These include continued development of open source designs suitable for rapid manufacturing and changes in regulatory policy that strike a balance between rigidity and uncontrolled innovation.

There is a huge interest in developing novel hollow fiber (HF) membranes able to modulate neural differentiation to produce in vitro blood-brain barrier (BBB) models for biomedical and pharmaceutical research, due to the low cell-inductive properties of the polymer HFs used in current BBB models. In this work, poly(ε-caprolactone) (PCL) and composite PCL/graphene (PCL/G) HF membranes were prepared by phase inversion and were characterized in terms of mechanical, electrical, morphological, chemical, and mass transport properties. The presence of graphene in PCL/G membranes enlarged the pore size and the water flux and presented significantly higher electrical conductivity than PCL HFs. Biocompatibility assay showed that PCL/G HFs significantly increased C6 cells adhesion and differentiation towards astrocytes, may be attributed to their higher electrical conductivity in comparison to PCL HFs. On the other hand, PCL/G membranes produced a cytotoxic effect on the endothelial cell line HUVEC presumably related with a higher production of intracellular reactive oxygen species induced by the nanomaterial in this particular cell line. These results prove the potential of PCL HF membranes to grow endothelial cells and PCL/G HF membranes to differentiate astrocytes, the two characteristic cell types that could develop in vitro BBB models in future 3D co-culture systems.

A variety of techniques have been utilized in metal additive manufacturing (AM) for melt pool size management, including modeling and feed-forward approaches. In a few cases, closed-loop control has been demonstrated. In this research, closed-loop melt pool size control for large-scale, laser-wire based Directed Energy Deposition is demonstrated with a novel modification: site-specific changes to the controller set-point were commanded at trigger points, the locations of which were generated by the projection of a secondary geometry onto the primary 3D-printed component geometry. The present work shows that, through this technique, it is possible to print a specific geometry that occurs beyond the actual toolpath of the print head. This is denoted as an extra-toolpath geometry and is fundamentally different from other methods of generating component features in metal AM. A proof-of-principle experiment is presented in which a complex oak leaf geometry was embossed on an otherwise ordinary double-bead wall made from Ti-6Al-4V. The process is introduced and characterized primarily from a controls perspective with reports on the performance of the control system, the melt pool size response, and the resulting geometry. The implications of this capability, which extend beyond localized control of bead geometry to the potential mitigations of defects and functional grading of component properties, are discussed.

Imaging lidars are one of the hottest topics in the optronics industry. The need to sense the surroundings of every autonomous vehicle has pushed forward a career to decide the final solution to be implemented. The diversity of state-of-the art approaches to the solution brings, however, a large uncertainty towards such decision. This results often in contradictory claims from different manufacturers and developers. Within this paper we intend to provide an introductory overview of the technology linked to imaging lidars for autonomous vehicles. We start with the main single-point measurement principles, and then present the different imaging strategies implemented 8 in the different solutions. An overview of the main components most frequently used in practice is also presented. Finally, a brief section on pending issues for lidar development has been included, 10 in order to discuss some of the problems which still need to be solved before an efficient final implementation.Beyond this introduction, the reader is provided with a detailed bibliography containing both relevant books and state of the art papers.

Nineteen million Americans have significant vision loss. Over 70% of these are not employed full-time, and more than a quarter live below the poverty line. Globally, there are 36 million blind people, but less than half use white canes or more costly commercial sensory substitutions. The quality of life for visually impaired people is hampered by the resultant lack of independence. To help alleviate these challenges this study reports on the development of a low-cost (<$24), open-source navigational support system to allow people with the lost vision to navigate, orient themselves in their surroundings and avoid obstacles when moving. The system can be largely made with digitally distributed manufacturing using low-cost 3-D printing/milling. It conveys point-distance information by utilizing the natural active sensing approach and modulates measurements into haptic feedback with various vibration patterns within the distance range of 3 m. The developed system allows people with lost vision to solve the primary tasks of navigation, orientation, and obstacle detection (>20 cm stationary, moving up to 0.5 m/s) to ensure their safety and mobility. Sighted blindfolded participants successfully demonstrated the device for eight primary everyday navigation and guidance tasks including indoor and outdoor navigation and avoiding collisions with other pedestrians.

This study presents a new form of velocity distribution in laminar liquid flow in rectangular microchannels using the eigenfunction expansion technique. Darcy friction factor and Poiseuille number are also obtained analytically. Due to the symmetry of the solutions, the effects of changing the aspect ratio from 0 to ∞ are also discussed. Using finite element method (FEM), the obtained analytical results are further compared with the 3D numerical simulations for the rectangular microchannels with different range of aspect ratio and pressure gradient, and excellent agreements were found. These findings provide additional insights in interpreting the results of the pressure-driven flows in finite aspect ratio microchannels, in which very precise comparison with the macroscale theory is crucial.

Biomaterials have been the subject of extensive research, with their applications in medicine and pharmacy expanding rapidly. Collagen and its derivatives stand out as valuable biomaterials due to their high biocompatibility, biodegradability, and lack of toxicity and immunogenicity. This review comprehensively examines collagen from various sources, its extraction and processing methods, and its structural and functional properties. Preserving the native state of collagen is crucial for maintaining its beneficial characteristics. The challenges associated with chemically modifying collagen to tailor its properties for specific clinical needs are also addressed. The review discusses various collagen-based biomaterials, including solutions, hydrogels, powders, sponges, scaffolds, and thin films. These materials have broad applications in regenerative medicine, tissue engineering, drug delivery, and wound healing. Additionally, the review highlights current research trends related to collagen and its derivatives. These trends may significantly influence future developments, such as using collagen-based bioinks for 3D bioprinting or exploring new collagen nanoparticle preparation methods and drug delivery systems.

This research will investigate how heat treatments affect the behaviour of 3D printed gears made from Polyamide 6 (PA6), a thermoplastic polymer with excellent mechanical properties. However, imperfect structures can result from the 3D printing process, which involves rapid cooling of the molten polymer. Gears were manufactured from PA6 by means of a dedicated 3D printer and their behaviour in gears was then analysed by means of various specific test protocols. Some of the gears were subjected to annealing heat treatments to determine material behaviour, which was a key aspect of this study. Finite Element Analysis (FEA) was used to investigate the effect of heat treatments on the mechanical properties of PA6 thermoplastic material, specifically in the area of 3D printed gear mechanisms. The simulations included both static and transient conditions to determine the influence of different heat treatments on the mechanical properties of PA6. Through the use of comprehensive FEA, the research investigates the deformation, stress distribution and strain rates in 3D printed gears and elucidates the correlation between the mechanical properties and the contact pressure on the tooth flanks during gear operation. As conclusion the study mainly uses numerical simulations based on mechanical characteristics determined in our laboratory. The contribution of the study lies in the novelty of highlighting, through the results obtained, the influence of heat treatments on wear and mechanical stress related factors.

The construction of tunnels excavated by the conventional method in densely populated urban environments requires an adequate characterization of the loads acting on the primary lining during the excavation process to ensure that the ground is deformed and stresses around the tunnel are relieved, simultaneously complying with the failure and serviceability limits of international standards while minimizing damage to nearby structures. In this paper, common lining design criteria are revisited, through the numerical simulation of an instrumented tunnel section which is part of a 4.5 km long metro line currently under construction in Mexico City. Key needs for improvement in current design approaches are identified. The tunnel was instrumented with load cells, extensometers, and topographical references for convergences and divergences. A three-dimensional finite difference model of the instrumented section was developed, and the load transfer mechanisms between the excavated soil and the primary lining was analyzed. Then, the numerical simulation of the contribution of the secondary lining in the overall stability for sustained load was established, along with the expected ground settlements, which can significantly affect nearby structures. Results gathered from this research are key for updating lining design criteria for urban tunnels built in stiff brittle soils.

ATTO 565, a Rhodamine-type dye, has garnered significant attention due to its remarkable optical properties, such as a high fluorescence quantum yield, it is a relatively stable structure, and has low biotoxicity. ATTO 565 has found extensive applications in combination with microscopy technology. In this review, the chemical and optical properties of ATTO 565 are introduced, along with the principles behind them. Then, the functionality of ATTO 565 in confocal microscopy, stimulated emission depletion (STED) microscopy, single-molecule tracking (SMT) techniques, and fluorescence correlation spectroscopy (FCS) is discussed. These studies demonstrate that ATTO 565 plays a crucial role in areas such as biological imaging and single-molecule localization, thus warranting further in-depth investigation. Finally, we present some prospects and concepts for the future applications of ATTO 565 in the fields of biocompatibility and metal ion detection.

Dendritic spines are essential for synaptic function because they constitute the neurons' postsynaptic compartment that receives the most excitatory input. The extracellularly shorter variant of the presynaptic cell adhesion molecules neurexins, β-neurexins, has been implicated in various aspects of synapse function including neurotransmitter release. However, its role in developing or stabilizing dendritic spines as fundamental computational units of excitatory synapses remained unclear. Here, we show by morphological analysis that the deletion of β-neurexins in hippocampal neurons in vitro and in hippocampal tissue in vivo affects presynaptic dense-core vesicles and, unexpectedly, postsynaptic spine structure. Specifically, we observed that the absence of β-neurexins led to an increase in longer spinous protrusions in vitro and more mature mushroom-type spines in the CA1 region of adult knockout mice. In addition, deletion of β-neurexins caused alterations in spine head dimension and more spines with perforations of their postsynaptic density but no change in the overall number of spines or synapses. Our results indicate that presynaptic β-neurexins play a role across the synaptic cleft, possibly by aligning with postsynaptic binding partners and glutamate receptors via transsynaptic columns.

Synchrotron radiation computed tomography (SRCT) allows more accurate calcified plaque and coronary stenosis assessment as a result of its superior spatial resolution, however, typical micro-computed tomography (micro-CT) systems have even higher resolution. The purpose of this study was to compare performance of high-resolution micro-CT with SRCT in the assessment of calcified plaques and a previously published dataset of coronary stenosis assessment. This experimental study involved micro-CT scanning of three-dimensional printed coronary artery models with calcification in situ used in our previously published SRCT study on coronary stenosis assessment. Measurements of coronary stenosis utilizing both modalities were compared using a paired sample t-test. The degrees of stenosis measured on all but one micro-CT dataset were statistically significantly lower than the corresponding SRCT measurements reported in our previous paper (p&lt;0.0005-0.05). This indicates that the superior spatial resolution of micro-CT was able to further reduce over-estimation of stenosis caused by extensive calcification of coronary arteries and hence false positive results. This study shows that high-resolution micro-CT outperforms SRCT in both calcified plaque and coronary stenosis assessment. This finding will become clinically important for cardiovascular event prediction and enable reclassification of individuals with low and intermediate risk into appropriate risk categories when the technical challenges of micro-CT in clinical practice such as the small field of view and demanding on image processing power are addressed.

As the additive manufacturing industry grows, it is compounding the global plastic waste problem. Distributed recycling and additive manufacturing (DRAM) offers an economic solution to this challenge, but it has been relegated to either small-volume 3D printers (limiting waste recycling throughput) or expensive industrial machines (limiting accessibility and lateral scaling). To overcome these challenges, this paper provides proof-of-concept for a novel open-source hybrid 3D printer that combines a low-cost hanging printer design with a compression screw-based end-effector that allows direct extrusion of recycled plastic waste in large expandable printing volumes. Mechanical testing of the resultant prints from 100% waste plastic, however, showed that combining challenges of non-uniform feedstocks and a heavy printhead for a hangprinter reduced the strength of the parts compared to fused filament fabrication. The preliminary results are technologically promising, however, and provide opportunities to improve on the open source design to help process the volumes of waste plastic needed for DRAM to address the negative environmental impacts of global plastic use.

Victor Vasarely’s (1906-1997) important legacy to the study of human perception is brought to the forefront and discussed. A large part of his impressive work conveys the appearance of striking three-dimensional shapes and structures in a large-scale pictorial plane. Current perception science explains such effects by invoking brain mechanisms for the processing of monocular (2D) depth cues. Here in this study, we illustrate and explain the local effects of 2D color and contrast cues on the perceptual organization in terms of figure-ground assignments, i.e. which local surfaces are likely to be seen as “nearer” or “bigger” in the image plane. Paired configurations are embedded in a larger, structurally ambivalent pictorial context inspired by some of Vasarely’s creations. The figure-ground effects these configurations produce reveal a significant correlation between perceptual solutions for “nearer” and “bigger” when no other monocular depth cues are given in the image. In consistency with previous findings on similar, albeit simpler visual displays, a specific color may compete with luminance contrast in resolving the planar ambiguity of a complex pattern context. Vasarely intuitively understood, and successfully exploited, this kind of subtle context effect in his art, well before empirical investigations had set out to study and explain their genesis in terms of information processing by the visual brain.

One of the most important pieces of equipment used in labs in culturing populations of fruit flies (Drosophila sp.) is that of the “CO₂ gas plate”, which is used to anesthesize individuals during “fly-pushing”. This piece of equipment consists of a box with a porous top into which carbon-dioxide is pumped. Flies placed on its surface are left immobilized, permitting the sorting, categorizing and/or counting of flies during population culturing and experimental assays. Unfortunately, commercially available gas plates are typically expensive. Here, we describe a new design for a gas plate that can be easily produced using a 3D printer and a laser cutter, which we are making freely available to the fly community.

Visualization of volumetric data holds great importance, particularly in medical and biomedical applications. Various imaging techniques, such as FMRI and 3D microscopy, are employed to generate volumetric data, used in medical practice, research, and teaching. Commonly utilized tools like 3D Slicer, Fiji, and MATLAB ® aid in rendering and analyzing 3D images. However, these tools may lack comprehensive rendering functionality and face challenges in handling computational demands as data sizes grow. To address these limitations, this work introduces a GPU-supported renderer with a MATLAB ® interface. This solution gives the user flexible control over rendering parameters and optimizes data transfer through a memory management system. By leveraging the computational power of NVIDIA GPUs, the renderer enables complex and high-quality renderings, enhancing speed and efficiency. It therefore facilitates the analysis and visualization of volumetric data within an integrated environment, namely MATLAB ®, streamlining their workflows. This advancement provides valuable opportunities for researchers and medical professionals to explore and comprehend volumetric data effectively.

Many fields of human activity benefit from the ability to create images of obscured objects placed behind walls and to map their displacement in a noninvasive way. Usually, imaging devices like Synthetic Aperture Radars (SAR) and Ground Penetrating Radars (GPR) use expensive dedicated electronics which results in prohibitive prices. This paper presents the experimental implementation and the results obtained from an imaging system capable of performing SAR imaging and interferometric displacement mapping of targets located behind walls, as well as 3D GPR imaging using a low-cost general-purpose radar sensor. The proposed solution uses for the RF section of the system a K-band microwave radar sensor module implementing Frequency Modulated Continuous Wave operation. The low-cost sensor was originally intended for simple presence detection and ranging for domestic applications. The proposed system was tested in several scenarios and proved to operate as intended for a fraction of the cost of a commercial imaging device.

Jumping side volley has created breathtaking moments and cherished memories for us. Regrettably, a scientific study on the skill has not been found in literature. Relying on talent of athletes to improvise on the fly can hardly be considered a viable learning strategy. This study targets to fill the gap by quantifying factors contributing to develop its coaching method. Using 3D motion capture (12-cameras, 200Hz) and full-body biomechanical modeling, our study aimed to identify elements that govern entrainment of the skill by examining jumping, kicking and falling phases of its execution. Given the rarity of players who have acquired this skill, we found five subjects for the study. Twenty-three trials were captured and quantified. The results unveil the following key elements: 1) the control of trunk rotation during the jumping, 2) the angle between thighs upon take-off, 3) the whip-like control of the kicking leg during airborne, 4) timing between ball motion and limbs’ coordination, and 5) damping mechanism during falling. An accurate kick can only be achieved through repetitive training. This underlines the need for athletes to master a safe landing technique that minimizes risk of injury during practice. Therefore, training should begin with learning a safe falling technique.

Into the frame of the French TANDEM project (Tsunamis in the Atlantic and the English ChaNnel: Definition of the Effects through numerical Modelling) Principia has been working on the development and qualification of two in-house CFD software’s: the 2D EOLE-SV (Saint Venant) model for simulation of large scale tsunami propagation from the source up to coastal scale and the 3D EOLE-NS (Navier-Stokes) model dedicated to tsunami coastal impact modelling. This paper presents a large range of test cases carried out into the frame of the project and dedicated to the validation of numerical codes in various tsunami wave conditions. The main aspects of phenomena such as wave generation, propagation and coastal impact are investigated on academic situations. A real case simulation is concerned as well, the devastating 2011 Tohoku event which is compared with in-situ data.

The inclusion of active materials in 3D-printed objects presents many potential applications in a variety of fields, including medicine and agriculture. Through a new three-phase coating system, we fabricate 3D objects that are printed via fused deposition modeling (FDM), with embedded functional materials. The method, namely Continuous Material Deposition on Filaments (CMDF) is based on passing a filament through a solution in which the functional substance is dissolved together with the polymer from which the filament is made. As model cases, three different types of materials were tested, Rhodamine B, ZnO nanoparticles (NPs), and Ciprofloxacin (Cip) while dissolved or dispersed in a PLA-containing solution. It was found that the properties of the coating materials are not affected by the coating and printing steps and they are maintained on the surface of the printed structure. This enabled, for example, achieving an antibacterial activity by the ZnO NPs and the controlled release of the antibiotics, Cip. Since the approach does not alter the mechanical properties of the printed structures, it offers a simple and convenient method for the introduction of a wide range of materials into 3D-printed objects.

The study addresses the challenge of efficiently peeling pineapples, which have a distinct elliptical form, thick skin, and small eyes that are difficult to detect with conventional automated methods. This results in significant flesh waste. To improve the process, the researchers developed an integrated system combining an enhanced BlendMask method, termed SAAF-BlendMask, and a PCP method. SAAF-BlendMask improves the detection of small pineapple eyes, while PCP ensures accurate posture adjustment for precise path planning. The system uses 3D vision and deep learning technologies, achieving an average precision (AP) of 73.04% and a small object precision (APs) of 62.54% in eye detection, with a path planning success rate reaching 99%. The fully automated electromechanical system was tested on 110 real pineapples, demonstrating a reduction in flesh waste by 11.7% compared to traditional methods. This study highlights the potential of advanced machine vision and robotics in enhancing the efficiency and precision of food processing.

Spatial-structured longitudinal light beams are optical fields sculpted in three-dimensional (3D) space by diffractive optical elements. These beams have been recently suggested for use in im-proving several imaging capabilities, such as 3D imaging, enhancing image resolution, engineering the depth of field, and sectioning 3D scenes. All these imaging tasks are performed using coded aperture correlation holography systems. Each system designed for a specific application is characterized by a point spread function of a different spatial-structured longitudinal light beam. This article reviews the topic of applying certain structured light beams for optical imaging.

The global consumption of vegan foods is experiencing an expressive upward trend, underscoring the critical need for quality control measures based on nutritional and functional considerations. This study aimed to evaluate the functional quality of caviar and salmon analogs food inks, based on pulses combined with nano ingredients. The primary objective of this work was to determine the total antioxidant compounds contained in these samples using a voltammetric technique with a glassy carbon electrode. Approximately 100 mg of samples underwent ethanolic extraction (70%) with 1 hour of stirring. The voltammograms were acquired under specific conditions: 10 mL of phosphate buffer electrolyte with a pH of 3.0; an initial potential (Ei) of 0.0 V; a final potential (Ef) of 1.0 V; a pulse amplitude of 50 mV; and a scan rate of 50 mV s-1. The reference electrode used was Ag/AgCl (KCl 3 mol L-1), and the auxiliary electrode was a platinum wire. The voltammograms revealed prominent anodic current peaks at 0.76-0.78 V, which are attributed to isoflavones. Isoflavones, known secondary metabolites with substantial antioxidant potential commonly found in pulses, were identified. The total isoflavone concentrations obtained ranged from 31.5 to 64.3 mg Eq genistein 100 g-1. The results not only validated the efficacy of the electrochemical sensor for quantifying total antioxidant compounds in the samples but also demonstrated that the concentration of total isoflavones in caviar and salmon analogs fell within the expected limits.

unlike the volume, the expression for the surface area of a regular conoid has not yet been obtained by means of direct integration or a differential geometry procedure. As this non-developable form is relatively used in engineering, the difficulty to determine its surface, represents a serious shortcoming for several problems which arise in radiative transfer, lighting and construction, to cite just a few. In order to solve the problem, I conceived the surface as a set of linearly dwindling ellipses which remain parallel to a circular directrix, a typical problem appears when searching the length of such ellipses. I employed a new procedure which, in principle, consists in dividing the surface into infinitesimal elliptic strips to which we have successively applied Ramanujan’s second approximation for the longitude of the ellipse. In this manner, we can obtain the perimeter of any transversal curve pertaining to the said form as a function of the radius of the directrix and the position of the ellipse’s center on the X-axis. Integrating the so-found perimeters of the differential strips for the whole span of the conoid, an unexpected solution emerges through the newly found number psi (ψ) which seems like a refined approximation to the third decimal of Pi but derived from a definite integral equation. As the strips are in truth slanted in the symmetry axis, their width is not uniform and we need to perform some adjustments in order to complete the problem with sufficient precision, but this is discussed separately in the annexes. Relevant implications for mathematical symmetry applied to multifarious architectural and engineering forms can be derived from this finding

Inhalation is the main route of exposure to airborne pollutants. To evaluate the safety and assess the risks of occupational hazards different testing approaches are used. 3D airway epithelial tissues allow to mimic exposure conditions in vitro, generates human-relevant toxicology data, allows to elucidate mode of action of pollutants. Gilian 3500 pumps equipped with Standard Midget Impingers were used to collect the airborne particulate from woodworking and metalworking environments. EpiAirway™ tissues were used to model half working day (4 h), full working day (8 h), and 3 working day exposures to occupational pollutants. Tissue viability was assessed using MTT assay. RT-qPCR analyses performed to analyze the expression of gelsolin, caspase-3, and IL-6. Tissue morphology was assessed by hematoxylin/eosin staining. Acute exposure to workspace pollutants slightly affected tissue viability and did not change the morphology. Both types of particles suppressed expression of gelsolin, with metalworking samples showing the most pronounced effect. A slight reduction in caspase-3 expression was observed. Particles from metalworking suppressed IL-6 expression. 3D Epithelial tissues can be used to model exposures to airborne pollutants. Exposure to particles from woodworking and metalworking had a minor effect on tissue viability but affected the expression of inflammation and apoptosis-related genes.

Abstract: We review the development and application of an organic polymer-gel capable of producing fixed, three-dimensional fluorescent images of complex radiation fields. The gel consists for more than 99% of γ-ray-polymerized (~15% conversion) tertiary-butyl acrylate (TBA) containing ~100 ppm of a fluorogenic compound, e.g. maleimido-pyrene (MPy). The radio-fluorogenic effect depends on copolymerization of the MPy into growing chains of TBA on radiation-induced polymerization. This converts the maleimido residue, which quenches the pyrene fluorescence, into a succinimido moeity (SPy), which doesn't. The intensity of the fluorescence is proportional to the yield of free-radicals formed and hence to the local dose deposited. Because the SPy moieties are built into the cross-linked polymer matrix the image is fixed. The method of preparing the gel and imaging the radiation-induced fluorescence are presented and discussed. The effect is illustrated with fluorescent images of the energy deposited in the gel by beams of X-rays, electrons and protons as well as a radioactive isotope.

In the evolving landscape of pharmaceutical manufacturing, a comprehensive continuous production process is being crafted for small-scale active pharmaceutical ingredient production. This study focuses on continuous crystallization with separate nucleation and crystal growth units, as well as continuous downstream processing, encompassing filtration, washing, and drying until the formation of free-flowing particles. We introduce a novel continuous nucleator designed based on solubility data and produced via 3D printing, enabling a fast and precise small-scale manufacturing of a nucleator meeting the requirements for nucleation and for the further growth processes. The nucleator was evaluated with regard to its suitability for continuous long-term operation across various coupled crystallizers. As a practical application example it is connected to a slug flow crystallizer to enable high-quality continuous crystallization. Additionally, the full integration of downstream processes using the continuous vacuum screw filter to achieve free-flowing product particles is realized. Even under non-optimized process conditions, with the help of in-situ generation of nuclei free-flowing product particles were successfully obtained. This is particularly useful during drug development when no material is available for seed addition and quickly obtain product for further characterization.

ORF6 is responsible for suppressing the immune response of cells infected by the SARS-CoV-2 virus. It is also the most toxic protein of SARS-CoV-2, and its actions are associated with the viral pathogenicity. Here we study in silico and in vitro the structure of the protein, its interaction with RAE1, and the mechanism of action behind its high toxicity. We show both computationally and experimentally that SARS-CoV-2 ORF6, embedded in the membranes of the endoplasmic reticulum, binds to RAE1 and sequesters it in the cytoplasm, thus depleting its availability in the nucleus and impairing nucleocytoplasmic mRNA transport. This negatively affects the cellular genome stability by compromising the cell cycle progression into the S-phase and by promoting the accumulation of RNA-DNA hybrids. Understanding the multiple ways in which ORF6 affects DNA replication may also have important implications for elucidating the pathogenesis of SARS-CoV-2 and developing therapeutic strategies to mitigate its deleterious effects on host cells.

The 21^st century has witnessed precipitous changes spanning from the way of life to the technologies that emerged. We have entered a nascent paradigm shift (industry 4.0) where science fictions have become science facts, and technology fusion is the main driver. Thus, ensuring that any advancement in technology reach and benefit all is the ideal opportunity for everyone. In this study, disruptive technologies of industry 4.0 was explored and quantified in terms of the number of their appearances in published literature. The study aimed at identifying industry 4.0 key technologies which have been ill-defined by previous researchers and to enumerate the required skills of industry 4.0. Comprehensive literature survey covering the field of engineering, production, and management was done from multidisciplinary databases: Google scholar, ScienceDirect, Scopus, Sage, Taylor & Francis and Emerald insight. Results of the electronic survey showed that 35 disruptive technologies were quantified and 13 key technologies: Internet of things, Big data, 3D printing, Cloud computing, Autonomous robots, Virtual and Augmented reality, Cyber physical system, Artificial intelligence, Smart sensors, Simulation, Nanotechnology, Drones and Biotechnology were identified. Both technical and personal skills to be imparted into the human workforce for industry 4.0 were reported. The study identified the need to investigate the capability and the readiness of developing countries in adapting industry 4.0 in terms of the changes in the education systems and industrial manufacturing settings. The study proposes the need to address integration of industry 4.0 concepts into the current education system.

Biomimicry in additive manufacturing often refers to topology optimization and the use of lattice structures, due to the organic shape of the topology-optimized designs, and the lattices often looking similar to many light-weight structures found in nature such as trabecular bone, wood, sponges, coral, to name a few. Real biomimetic design however involves the use of design principles taken in some way from natural systems. In this work we use a methodology whereby high resolution 3D analysis of a natural material with desirable properties is “reverse-engineered” and the design tested for the purpose. This allows more accurate replication of the desired properties, and adaption of the design parameters to the material used for production (which usually differs from the biological material). One such example is the impact-protective natural design of the glyptodont body armour. In this paper we report on the production of body armour models in metal (Ti4Al4V) and analyze the resulting mechanical properties, assessing their potential for impact protective applications. This is the first biomimetic study using metal additive manufacturing to date.

Different notions of entropy can be identified in different communities: (i) the thermodynamic sense, (ii) the information sense, (iii) the statistical sense, (iv) the disorder sense, and (v) the homogeneity sense. Especially the “disorder sense” and the “homogeneity sense” relate to and require the notion of space and time. One of the few prominent examples relating entropy to geometry and to space is the Bekenstein-Hawking entropy of a Black Hole. Although being developed for the description of a physics object—a black hole—having a mass, a momentum, a temperature, a charge etc. absolutely no information about these attributes of this object can eventually be found in the final formula. In contrast, the Bekenstein-Hawking entropy in its dimensionless form is a positive quantity only comprising geometric attributes like an area A—which is the area of the event horizon of the black hole-, a length L_P—which is the Planck length - and a factor ¼. A purely geometric approach towards this formula will be presented. The approach is based on a continuous 3D extension of the Heaviside function, with this extension drawing on the phase-field concept of diffuse interfaces. Entropy enters into the local, statistical description of contrast respectively gradient distributions in the transition region of the extended Heaviside function definition. The structure of the Bekenstein-Hawking formula eventually is derived for a geometric sphere based on mere geometric-statistic considerations.

Height assignment is an important problem for satellite measurements of Atmospheric Motion Vectors (AMVs) that are interpreted as winds by forecast and assimilation systems. Stereo methods assign heights to AMVs from the parallax observed between observations from different vantage points in orbit while tracking cloud or moisture features. In this paper, we fully develop the stereo method to jointly retrieve wind vectors with their geometric heights from geostationary satellite pairs. Synchronization of observations between observing systems is not required. NASA and NOAA stereo-winds codes have implemented this method and we have processed large datasets from GOES-16, -17, and Himawari-8. Our retrievals are validated against rawinsonde observations and demonstrate the potential to improve forecast skill. Stereo winds also offer an important mitigation for the loop heat pipe anomaly on GOES-17 during times when warm focal plane temperatures cause infra-red channels that are needed for operational height assignments to fail. We also examine several application areas, including deep convection in tropical cyclones, planetary boundary layer dynamics, and fire smoke plumes, where stereo methods provide insights into atmospheric processes. The stereo method is broadly applicable across the geostationary ring where systems offering similar Image Navigation and Registration (INR) performance as GOES-R are deployed.

Tumor growth, progression, and therapy resistance are crucial factors in the prognosis of cancer. Properties of three-dimensional tumor-like organoids (tumoroids) more closely resemble in vivo tumors compared to two-dimensionally cultured cells and are therefore effectively used for assays and drug screening. We here established a repurposed drug for novel anticancer research and therapeutics using a tumoroid-based screening system. We screened 6 pharmacologically active compounds by using an original tumoroid-based multiplex phenotypic screening system with matrix metalloproteinase 9 (MMP9) promoter-driven fluorescence reporter for the evaluation of both tumoroid formation and progression. The effects of one of the hit compounds were examined on tumor formation and progression in vitro and in vivo. Antiparkinson drug benztropine was the most effective compound uncovered by the screen. Benztropine significantly inhibited in vitro tumoroid formation, cancer cell survival, and MMP9 promoter activity. Benztropine also reduced the activity of oncogenic signaling transducers and trans-activators for MMP9, including STAT3, NF-κB, and β-catenin, and properties of cancer stem cells / cancer-initiating cells. Benztropine and GBR-12935 directly targeted the dopamine transporter DAT/SLC6A3, whose genetic alterations such as amplification were correlated with poor prognosis for cancer patients. Benztropine also inhibited tumor growth, circulating tumor cell (CTC) number, and rate of metastasis in a tumor allograft model in mice. In conclusion, we propose the repurposing of benztropine for anticancer research and therapeutics that can suppress tumor progression, CTC, and metastasis of aggressive cancers by reducing key pro-tumorigenic factors.

Glial cells provide physical and chemical support and protection for neurons. Secreted neurotrophic factors, scaffolds and vesicles regulate in addition to normal homeostasis, repair following neural tissue injury or degeneration. We previously demonstrated that human CNS glia have revascularization capacity by inducing endothelial cell sprouting and microchanneling driven by glial cell secreted components. The clinical potential of using secreted factors and vesicles generated by glial cells in conditioned media was shown by their re-normalization of pathological blood vessels and 3D tissue wound healing and remodeling capacity. To identify secreted components of glial cells and how CNS and PNS glial cells differentially regulate neural tissue homeostasis, disease and injury response, we developed a novel culture method for various types of glial cells that allow for isolating and characterizing secreted glial components, free of animal factors and contaminants normally associated with serum-based culture conditions. Our culture method will enable to identify secreted components using ultrasensitive RNA, glycoconjugate and protein analysis technologies. The characterization of glial secreted factors involved microchanneling may help in development of new clinical therapies for glial and neural cells or axons to migrate and reform connections.

Based on the minimum conduction band edge caused by the minimum channel potential resulting from the quasi-3D scaling theory and the 3D density of state (DOS) accompanied by the Fermi-Dirac distribution function on the source and drain sides, a unified semiconductor-device-physics-based ballistic model is developed for the threshold voltage of modern multiple-gate (MG) transistors, including FinFET, W-gate MOSFET, and Nanosheet (NS) MOSFET. It is shown that the thin silicon, thin gate oxide, and high work function will alleviate the ballistic effects and resist the threshold voltage degradation. Besides, as the device dimension is further reduced to give rise to the 2D/1D DOS, the lowest conduction band edge is hence increased to resist the threshold voltage degradation. The nanosheet MOSFET exhibits the largest threshold voltage among the three transistors due to the smallest minimum conduction band edge caused by the quasi-3D minimum channel potential. Compared to P-type MOSFET (P-FET), the N-FET shows more threshold voltage because the electron has a more effective mass than the hole

Article explores participant specific study of muscle inherehit dynamics hidden inside the diognostic electromyography (D-EMG) signals during load pull exercises, aiming to uncover underlying patterns and nonlinear behaviors. Employing a multi-step analytical framework, the study first evaluates signal stationarity through Quantile-Quantile (Q-Q) plot and surrogate data analyses, revealing insights into signal stability. Subsequent use of phase space reconstruction techniques exposes intrinsic dynamics within the EMG signals, visualized through Poincar´e maps, elucidating attractor geometry and system dynamics. Histogram analysis further dissects the Poincar´e maps, offering insights into signal behavior relative to physiological processes. Additionally, the study quantifies the largest Lyapunov exponent from the Poincar´e maps, providing a measure of dynamical complexity within the muscle EMG signals during load pull exercises. By integrating these methods, this research sheds light on the nuanced interplay between EMG signals and muscle activity during dynamic exercises, offering valuable insights for rehabilitation strategies.

Alzheimer’s Disease (AD) has no cure. Earlier, we showed that partial inhibition of mitochondrial complex I (MCI) with small molecule CP2 induces adaptive stress response activating multiple neuroprotective mechanisms. Chronic treatment reduced inflammation, improved synaptic and mitochondrial functions, and blocked neurodegeneration in symptomatic APP/PS1 mice, a translational model of AD. Here, using serial block-face scanning electron microscopy (SBFSEM) and three-dimensional (3D) EM reconstructions combined with Western blot analysis and next-generation RNA sequencing, we demonstrate that CP2 treatment also restores mitochondrial morphology and mitochondria-endoplasmic reticulum (ER) communication in the APP/PS1 mouse brain. Using 3D EM volume reconstructions, we show that mitochondria in AD dendrites exist primarily as mitochondria-on-a-string (MOAS). Compared to other morphological phenotypes, MOAS are extensively enveloped in the ER membranes forming multiple mitochondria-ER contact sites (MERCS) known to contribute to abnormal lipid and calcium homeostasis. CP2 treatment specifically reduced MOAS formation, consistent with improved energy homeostasis in the brain, with concomitant reduction in MERCS, ER stress, and improved lipid homeostasis. These data provide novel information on the role MOAS play in AD and additional support for further development of partial MCI inhibitors as disease modifying strategy for AD.