Search results for: rapid genetic testing

Authors: Inna Kornienko, Svetlana Guryeva, Natalia Danilova, Elena Petersen

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Drug toxicity often goes undetected until clinical trials, the most expensive and dangerous phase of drug development. Both human cell culture and animal studies have limitations that cannot be overcome by improvements in drug testing protocols. Tissue engineering is an emerging alternative approach to creating models of human malignant tumors for experimental oncology, personalized medicine, and drug discovery studies. This new generation of bioengineered tumors provides an opportunity to control and explore the role of every component of the model system including cell populations, supportive scaffolds, and signaling molecules. An area that could greatly benefit from these models is cancer research. Recent advances in tissue engineering demonstrated that decellularized tissue is an excellent scaffold for tissue engineering. Decellularization of donor organs such as heart, liver, and lung can provide an acellular, naturally occurring three-dimensional biologic scaffold material that can then be seeded with selected cell populations. Preliminary studies in animal models have provided encouraging results for the proof of concept. Decellularized Organs preserve organ microenvironment, which is critical for cancer metastasis. Utilizing 3D tumor models results greater proximity of cell culture morphological characteristics in a model to its in vivo counterpart, allows more accurate simulation of the processes within a functioning tumor and its pathogenesis. 3D models allow study of migration processes and cell proliferation with higher reliability as well. Moreover, cancer cells in a 3D model bear closer resemblance to living conditions in terms of gene expression, cell surface receptor expression, and signaling. 2D cell monolayers do not provide the geometrical and mechanical cues of tissues in vivo and are, therefore, not suitable to accurately predict the responses of living organisms. 3D models can provide several levels of complexity from simple monocultures of cancer cell lines in liquid environment comprised of oxygen and nutrient gradients and cell-cell interaction to more advanced models, which include co-culturing with other cell types, such as endothelial and immune cells. Following this reasoning, spheroids cultivated from one or multiple patient-derived cell lines can be utilized to seed the matrix rather than monolayer cells. This approach furthers the progress towards personalized medicine. As an initial step to create a new ex vivo tissue engineered model of a cancer tumor, optimized protocols have been designed to obtain organ-specific acellular matrices and evaluate their potential as tissue engineered scaffolds for cultures of normal and tumor cells. Decellularized biomatrix was prepared from animals’ kidneys, urethra, lungs, heart, and liver by two decellularization methods: perfusion in a bioreactor system and immersion-agitation on an orbital shaker with the use of various detergents (SDS, Triton X-100) in different concentrations and freezing. Acellular scaffolds and tissue engineered constructs have been characterized and compared using morphological methods. Models using decellularized matrix have certain advantages, such as maintaining native extracellular matrix properties and biomimetic microenvironment for cancer cells; compatibility with multiple cell types for cell culture and drug screening; utilization to culture patient-derived cells in vitro to evaluate different anticancer therapeutics for developing personalized medicines.

Keywords: 3D models, decellularization, drug discovery, drug toxicity, scaffolds, spheroids, tissue engineering

Procedia PDF Downloads 303

Authors: Adela Diepoltova, Klara Konecna, Ondrej Jandourek, Petr Nachtigal

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A loss of control over antibiotic-resistant pathogens has become a global issue due to severe and often untreatable infections. This state is reflected in complicated treatment, health costs, and higher mortality. All these factors emphasize the urgent need for the discovery and development of new anti-infectives. One of the most common pathogens mentioned in the phenomenon of antibiotic resistance are bacteria of the genus Staphylococcus. These bacterial agents have developed several mechanisms against the effect of antibiotics. One of them is biofilm formation. In staphylococci, biofilms are associated with infections such as endocarditis, osteomyelitis, catheter-related bloodstream infections, etc. To author's best knowledge, no validated and standardized methodology evaluating candidate compound activity against staphylococcal biofilms exists. However, a variety of protocols for in vitro drug activity testing has been suggested, yet there are often fundamental differences. Based on our experience, a key methodological step that leads to credible results is to form a robust biofilm with appropriate attributes such as firm adherence to the substrate, a complex arrangement in layers, and the presence of extracellular polysaccharide matrix. At first, for the purpose of drug antibiofilm activity evaluation, the focus was put on various conditions (supplementation of cultivation media by human plasma/fetal bovine serum, shaking mode, the density of initial inoculum) that should lead to reproducible and robust in vitro staphylococcal biofilm formation in microtiter plate model. Three model staphylococcal reference strains were included in the study: Staphylococcus aureus (ATCC 29213), methicillin-resistant Staphylococcus aureus (ATCC 43300), and Staphylococcus epidermidis (ATCC 35983). The total biofilm biomass was quantified using the Christensen method with crystal violet, and results obtained from at least three independent experiments were statistically processed. Attention was also paid to the viability of the biofilm-forming staphylococcal cells and the presence of extracellular polysaccharide matrix. The conditions that led to robust biofilm biomass formation with attributes for biofilms mentioned above were then applied by introducing an alternative method analogous to the commercially available test system, the Calgary Biofilm Device. In this test system, biofilms are formed on pegs that are incorporated into the lid of the microtiter plate. This system provides several advantages (in situ detection and quantification of biofilm microbial cells that have retained their viability after drug exposure). Based on our preliminary studies, it was found that the attention to the peg surface and substrate on which the bacterial biofilms are formed should also be paid to. Therefore, further steps leading to the optimization were introduced. The surface of pegs was coated by human plasma, fetal bovine serum, and L-polylysine. Subsequently, the willingness of bacteria to adhere and form biofilm was monitored. In conclusion, suitable conditions were revealed, leading to the formation of reproducible, robust staphylococcal biofilms in vitro for the microtiter model and the system analogous to the Calgary biofilm device, as well. The robustness and typical slime texture could be detected visually. Likewise, an analysis by confocal laser scanning microscopy revealed a complex three-dimensional arrangement of biofilm forming organisms surrounded by an extracellular polysaccharide matrix.

Keywords: anti-biofilm drug activity screening, in vitro biofilm formation, microtiter plate model, the Calgary biofilm device, staphylococcal infections, substrate modification, surface coating

Procedia PDF Downloads 159

Authors: Zeynep Busra Velioglu, Deniz Pulat, Beril Demirbakan, Burak Ozcan, Ece Bayrak, Cevat Erisken

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Bone tissue has the ability to perform a wide array of functions including providing posture, load-bearing capacity, protection for the internal organs, initiating hematopoiesis, and maintaining the homeostasis of key electrolytes via calcium/phosphate ion storage. The most common cause for bone defects is extensive trauma and subsequent infection. Bone tissue has the self-healing capability without a scar tissue formation for the majority of the injuries. However, some may result with delayed union or fracture non-union. Such cases include reconstruction of large bone defects or cases of compromised regenerative process as a result of avascular necrosis and osteoporosis. Several surgical methods exist to treat bone defects, including Ilizarov method, Masquelete technique, growth factor stimulation, and bone replacement. Unfortunately, these are technically demanding and come with noteworthy disadvantages such as lengthy treatment duration, adverse effects on the patient’s psychology, repeated surgical procedures, and often long hospitalization times. These limitations associated with surgical techniques make bone substitutes an attractive alternative. Here, it was hypothesized that a 3D printed scaffold will mimic trabecular bone in terms of biomechanical properties and that such scaffolds will support cell attachment and survival. To test this hypothesis, this study aimed at fabricating poly(lactic acid), PLA, structures using 3D printing technology for trabecular bone defects, characterizing the scaffolds and comparing with bovine trabecular bone. Capacity of scaffolds on human bone marrow stem cell (hBMSC) attachment and survival was also evaluated. Cubes with a volume of 1 cm³ having pore sizes of 0.50, 1.00 and 1.25 mm were printed. The scaffolds/grafts were characterized in terms of porosity, contact angle, compressive mechanical properties as well cell response. Porosities of the 3D printed scaffolds were calculated based on apparent densities. For contact angles, 50 µl distilled water was dropped over the surface of scaffolds, and contact angles were measured using ‘Image J’ software. Mechanical characterization under compression was performed on scaffolds and native trabecular bone (bovine, 15 months) specimens using a universal testing machine at a rate of 0.5mm/min. hBMSCs were seeded onto the 3D printed scaffolds. After 3 days of incubation with fully supplemented Dulbecco’s modified Eagle’s medium, the cells were fixed using 2% formaldehyde and glutaraldehyde mixture. The specimens were then imaged under scanning electron microscopy. Cell proliferation was determined by using EZQuant dsDNA Quantitation kit. Fluorescence was measured using microplate reader Spectramax M2 at the excitation and emission wavelengths of 485nm and 535nm, respectively. Findings suggested that porosity of scaffolds with pore dimensions of 0.5mm, 1.0mm and 1.25mm were not affected by pore size, while contact angle and compressive modulus decreased with increasing pore size. Biomechanical characterization of trabecular bone yielded higher modulus values as compared to scaffolds with all pore sizes studied. Cells attached and survived in all surfaces, demonstrating higher proliferation on scaffolds with 1.25mm pores as compared with those of 1mm. Collectively, given lower mechanical properties of scaffolds as compared to native bone, and biocompatibility of the scaffolds, the 3D printed PLA scaffolds of this study appear as candidate substitutes for bone repair and regeneration.

Keywords: 3D printing, biomechanics, bone repair, stem cell

Procedia PDF Downloads 176

Authors: M. Agostini, A. Sonato, G. Greco, M. Travagliati, G. Ruffato, E. Gazzola, D. Liuni, F. Romanato, M. Cecchini

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Since their first demonstration in the early 1980s, surface plasmon resonance (SPR) sensors have been widely recognized as useful tools for detecting chemical and biological species, and the interest of the scientific community toward this technology has known a rapid growth in the past two decades owing to their high sensitivity, label-free operation and possibility of real-time detection. Recent works have suggested that a turning point in SPR sensor research would be the combination of SPR strategies with other technologies in order to reduce human handling of samples, improve integration and plasmonic sensitivity. In this light, microfluidics has been attracting growing interest. By properly designing microfluidic biochips it is possible to miniaturize the analyte-sensitive areas with an overall reduction of the chip dimension, reduce the liquid reagents and sample volume, improve automation, and increase the number of experiments in a single biochip by multiplexing approaches. However, as the fluidic channel dimensions approach the micron scale, laminar flows become dominant owing to the low Reynolds numbers that typically characterize microfluidics. In these environments mixing times are usually dominated by diffusion, which can be prohibitively long and lead to long-lasting biochemistry experiments. An elegant method to overcome these issues is to actively perturb the liquid laminar flow by exploiting surface acoustic waves (SAWs). With this work, we demonstrate a new approach for SPR biosensing based on the combination of microfluidics, SAW-induced mixing and the real-time phase-interrogation grating-coupling SPR technology. On a single lithium niobate (LN) substrate the nanostructured SPR sensing areas, interdigital transducer (IDT) for SAW generation and polydimethylsiloxane (PDMS) microfluidic chambers were fabricated. SAWs, impinging on the microfluidic chamber, generate acoustic streaming inside the fluid, leading to chaotic advection and thus improved fluid mixing, whilst analytes binding detection is made via SPR method based on SPP excitation via gold metallic grating upon azimuthal orientation and phase interrogation. Our device has been fully characterized in order to separate for the very first time the unwanted SAW heating effect with respect to the fluid stirring inside the microchamber that affect the molecules binding dynamics. Avidin/biotin assay and thiol-polyethylene glycol (bPEG-SH) were exploited as model biological interaction and non-fouling layer respectively. Biosensing kinetics time reduction with SAW-enhanced mixing resulted in a ≈ 82% improvement for bPEG-SH adsorption onto gold and ≈ 24% for avidin/biotin binding—≈ 50% and 18% respectively compared to the heating only condition. These results demonstrate that our biochip can significantly reduce the duration of bioreactions that usually require long times (e.g., PEG-based sensing layer, low concentration analyte detection). The sensing architecture here proposed represents a new promising technology satisfying the major biosensing requirements: scalability and high throughput capabilities. The detection system size and biochip dimension could be further reduced and integrated; in addition, the possibility of reducing biological experiment duration via SAW-driven active mixing and developing multiplexing platforms for parallel real-time sensing could be easily combined. In general, the technology reported in this study can be straightforwardly adapted to a great number of biological system and sensing geometry.

Keywords: biosensor, microfluidics, surface acoustic wave, surface plasmon resonance

Procedia PDF Downloads 289

Authors: Anisa Suraya Ab Razak, Izza Hayat

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Introduction: The diagnosis and management of severe hyponatremia in neuropsychiatric patients present a significant challenge to physicians. Several factors contribute, including diagnostic shadowing and attributing abnormal behavior to intellectual disability or psychiatric conditions. Hyponatraemia is the commonest electrolyte abnormality in the inpatient population, ranging from mild/asymptomatic, moderate to severe levels with life-threatening symptoms such as seizures, coma and death. There are several documented fatal case reports in the literature of severe hyponatremia secondary to psychogenic polydipsia, often diagnosed only in autopsy. This paper presents a case study of acute severe hyponatremia in a neuropsychiatric patient with early diagnosis and admission to intensive care. Case study: A 21-year old Caucasian male with known epilepsy and learning disability was admitted from residential living with generalized tonic-clonic self-terminating seizures after refusing medications for several weeks. Evidence of superficial head injury was detected on physical examination. His laboratory data demonstrated mild hyponatremia (125 mmol/L). Computed tomography imaging of his brain demonstrated no acute bleed or space-occupying lesion. He exhibited abnormal behavior - restlessness, drinking water from bathroom taps, inability to engage, paranoia, and hypersexuality. No collateral history was available to establish his baseline behavior. He was loaded with intravenous sodium valproate and leveritircaetam. Three hours later, he developed vomiting and a generalized tonic-clonic seizure lasting forty seconds. He remained drowsy for several hours and regained minimal recovery of consciousness. A repeat set of blood tests demonstrated profound hyponatremia (117 mmol/L). Outcomes: He was referred to intensive care for peripheral intravenous infusion of 2.7% sodium chloride solution with two-hourly laboratory monitoring of sodium concentration. Laboratory monitoring identified dangerously rapid correction of serum sodium concentration, and hypertonic saline was switched to a 5% dextrose solution to reduce the risk of acute large-volume fluid shifts from the cerebral intracellular compartment to the extracellular compartment. He underwent urethral catheterization and produced 8 liters of urine over 24 hours. Serum sodium concentration remained stable after 24 hours of correction fluids. His GCS recovered to baseline after 48 hours with improvement in behavior -he engaged with healthcare professionals, understood the importance of taking medications, admitted to illicit drug use and drinking massive amounts of water. He was transferred from high-dependency care to ward level and was initiated on multiple trials of anti-epileptics before achieving seizure-free days two weeks after resolution of acute hyponatremia. Conclusion: Psychogenic polydipsia is often found in young patients with intellectual disability or psychiatric disorders. Patients drink large volumes of water daily ranging from ten to forty liters, resulting in acute severe hyponatremia with mortality rates as high as 20%. Poor outcomes are due to challenges faced by physicians in making an early diagnosis and treating acute hyponatremia safely. A low index of suspicion of water intoxication is required in this population, including patients with known epilepsy. Monitoring urine output proved to be clinically effective in aiding diagnosis. Early referral and admission to intensive care should be considered for safe correction of sodium concentration while minimizing risk of fatal complications e.g. central pontine myelinolysis.

Keywords: epilepsy, psychogenic polydipsia, seizure, severe hyponatremia

Procedia PDF Downloads 126

Authors: Zbigniew Czyz, Ksenia Siadkowska, Krzysztof Skiba, Karol Scislowski

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Today’s progress in the rotorcraft is mostly associated with an optimization of aircraft performance achieved by active and passive modifications of main rotor assemblies and a tail propeller. The key task is to improve their performance, improve the hover quality factor for rotors but not change in specific fuel consumption. One of the tasks to improve the helicopter is an active optimization of the main rotor providing for flight stages, i.e., an ascend, flight, a descend. An active interference with the airflow around the rotor blade section can significantly change characteristics of the aerodynamic airfoil. The efficiency of actuator systems modifying aerodynamic coefficients in the current solutions is relatively high and significantly affects the increase in strength. The solution to actively change aerodynamic characteristics assumes a periodic change of geometric features of blades depending on flight stages. Changing geometric parameters of blade warping enables an optimization of main rotor performance depending on helicopter flight stages. Structurally, an adaptation of shape memory alloys does not significantly affect rotor blade fatigue strength, which contributes to reduce costs associated with an adaptation of the system to the existing blades, and gains from a better performance can easily amortize such a modification and improve profitability of such a structure. In order to obtain quantitative and qualitative data to solve this research problem, a number of numerical analyses have been necessary. The main problem is a selection of design parameters of the main rotor and a preliminary optimization of its performance to improve the hover quality factor for rotors. This design concept assumes a three-bladed main rotor with a chord of 0.07 m and radius R = 1 m. The value of rotor speed is a calculated parameter of an optimization function. To specify the initial distribution of geometric warping, a special software has been created that uses a numerical method of a blade element which respects dynamic design features such as fluctuations of a blade in its joints. A number of performance analyses as a function of rotor speed, forward speed, and altitude have been performed. The calculations were carried out for the full model assembly. This approach makes it possible to observe the behavior of components and their mutual interaction resulting from the forces. The key element of each rotor is the shaft, hub and pins holding the joints and blade yokes. These components are exposed to the highest loads. As a result of the analysis, the safety factor was determined at the level of k > 1.5, which gives grounds to obtain certification for the strength of the structure. The construction of the joint rotor has numerous moving elements in its structure. Despite the high safety factor, the places with the highest stresses, where the signs of wear and tear may appear, have been indicated. The numerical analysis carried out showed that the most loaded element is the pin connecting the modular bearing of the blade yoke with the element of the horizontal oscillation joint. The stresses in this element result in a safety factor of k=1.7. The other analysed rotor components have a safety factor of more than 2 and in the case of the shaft, this factor is more than 3. However, it must be remembered that the structure is as strong as the weakest cell is. Designed rotor for unmanned aerial vehicles adapted to work with blades with intelligent materials in its structure meets the requirements for certification testing. Acknowledgement: This work has been financed by the Polish National Centre for Research and Development under the LIDER program, Grant Agreement No. LIDER/45/0177/L-9/17/NCBR/2018.

Keywords: main rotor, rotorcraft aerodynamics, shape memory alloy, materials, unmanned helicopter

Procedia PDF Downloads 162

Authors: Volker Wannack

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Regional, national, and international strategies focusing on hydrogen (H₂) and blockchain are driving significant advancements in hydrogen and blockchain technology worldwide. These strategies lay the foundation for the groundbreaking "Blockchain Based Hydrogen Market (BBH₂)" project. The primary goal of this project is to develop a functional Blockchain Minimum Viable Product (B-MVP) for the hydrogen market. The B-MVP will leverage blockchain as an enabling technology with a common database and platform, facilitating secure and automated transactions through smart contracts. This innovation will revolutionize logistics, trading, and transactions within the hydrogen market. The B-MVP has transformative potential across various sectors. It benefits renewable energy producers, surplus energy-based hydrogen producers, hydrogen transport and distribution grid operators, and hydrogen consumers. By implementing standardized, automated, and tamper-proof processes, the B-MVP enhances cost efficiency and enables transparent and traceable transactions. Its key objective is to establish the verifiable integrity of climate-friendly "green" hydrogen by tracing its supply chain from renewable energy producers to end users. This emphasis on transparency and accountability promotes economic, ecological, and social sustainability while fostering a secure and transparent market environment. A notable feature of the B-MVP is its cross-border operability, eliminating the need for country-specific data storage and expanding its global applicability. This flexibility not only broadens its reach but also creates opportunities for long-term job creation through the establishment of a dedicated blockchain operating company. By attracting skilled workers and supporting their training, the B-MVP strengthens the workforce in the growing hydrogen sector. Moreover, it drives the emergence of innovative business models that attract additional company establishments and startups and contributes to long-term job creation. For instance, data evaluation can be utilized to develop customized tariffs and provide demand-oriented network capacities to producers and network operators, benefitting redistributors and end customers with tamper-proof pricing options. The B-MVP not only brings technological and economic advancements but also enhances the visibility of national and international standard-setting efforts. Regions implementing the B-MVP become pioneers in climate-friendly, sustainable, and forward-thinking practices, generating interest beyond their geographic boundaries. Additionally, the B-MVP serves as a catalyst for research and development, facilitating knowledge transfer between universities and companies. This collaborative environment fosters scientific progress, aligns with strategic innovation management, and cultivates an innovation culture within the hydrogen market. Through the integration of blockchain and hydrogen technologies, the B-MVP promotes holistic innovation and contributes to a sustainable future in the hydrogen industry. The implementation process involves evaluating and mapping suitable blockchain technology and architecture, developing and implementing the blockchain, smart contracts, and depositing certificates of origin. It also includes creating interfaces to existing systems such as nomination, portfolio management, trading, and billing systems, testing the scalability of the B-MVP to other markets and user groups, developing data formats for process-relevant data exchange, and conducting field studies to validate the B-MVP. BBH₂ is part of the "Technology Offensive Hydrogen" funding call within the research funding of the Federal Ministry of Economics and Climate Protection in the 7th Energy Research Programme of the Federal Government.

Keywords: hydrogen, blockchain, sustainability, innovation, structural change

Procedia PDF Downloads 176

Authors: Atish Bagchi, Siva Chandrasekaran

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Background: According to World Bank national accounts data, the estimated global manufacturing value-added output in 2020 was 13.74 trillion USD. These manufacturing processes are monitored, modelled, and controlled by advanced, real-time, computer-based systems, e.g., Industrial IoT, PLC, SCADA, etc. These systems measure and manipulate a set of physical variables, e.g., temperature, pressure, etc. Despite the use of IoT, SCADA etc., in manufacturing, studies suggest that unplanned downtime leads to economic losses of approximately 864 billion USD each year. Therefore, real-time, accurate detection, classification and prediction of machine behaviour are needed to minimise financial losses. Although vast literature exists on time-series data processing using machine learning, the challenges faced by the industries that lead to unplanned downtimes are: The current algorithms do not efficiently handle the high-volume streaming data from industrial IoTsensors and were tested on static and simulated datasets. While the existing algorithms can detect significant 'point' outliers, most do not handle contextual outliers (e.g., values within normal range but happening at an unexpected time of day) or subtle changes in machine behaviour. Machines are revamped periodically as part of planned maintenance programmes, which change the assumptions on which original AI models were created and trained. Aim: This research study aims to deliver a Graph Neural Network(GNN)based hybrid forecasting model that interfaces with the real-time machine control systemand can detect, predict machine behaviour and behavioural changes (anomalies) in real-time. This research will help manufacturing industries and utilities, e.g., water, electricity etc., reduce unplanned downtimes and consequential financial losses. Method: The data stored within a process control system, e.g., Industrial-IoT, Data Historian, is generally sampled during data acquisition from the sensor (source) and whenpersistingin the Data Historian to optimise storage and query performance. The sampling may inadvertently discard values that might contain subtle aspects of behavioural changes in machines. This research proposed a hybrid forecasting and classification model which combines the expressive and extrapolation capability of GNN enhanced with the estimates of entropy and spectral changes in the sampled data and additional temporal contexts to reconstruct the likely temporal trajectory of machine behavioural changes. The proposed real-time model belongs to the Deep Learning category of machine learning and interfaces with the sensors directly or through 'Process Data Historian', SCADA etc., to perform forecasting and classification tasks. Results: The model was interfaced with a Data Historianholding time-series data from 4flow sensors within a water treatment plantfor45 days. The recorded sampling interval for a sensor varied from 10 sec to 30 min. Approximately 65% of the available data was used for training the model, 20% for validation, and the rest for testing. The model identified the anomalies within the water treatment plant and predicted the plant's performance. These results were compared with the data reported by the plant SCADA-Historian system and the official data reported by the plant authorities. The model's accuracy was much higher (20%) than that reported by the SCADA-Historian system and matched the validated results declared by the plant auditors. Conclusions: The research demonstrates that a hybrid GNN based approach enhanced with entropy calculation and spectral information can effectively detect and predict a machine's behavioural changes. The model can interface with a plant's 'process control system' in real-time to perform forecasting and classification tasks to aid the asset management engineers to operate their machines more efficiently and reduce unplanned downtimes. A series of trialsare planned for this model in the future in other manufacturing industries.

Keywords: GNN, Entropy, anomaly detection, industrial time-series, AI, IoT, Industry 4.0, Machine Learning

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Authors: Katie M. Clark, Adriana A. Tienda, Krista C. Paffenroth, Lindsey N. Brigante, Daniel C. Colvin, Jose Maldonado, Erin S. Calipari, Fiona E. Harrison

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Manganese (Mn) is an essential trace element required for human health and is important in antioxidant defenses, as well as in the development and function of dopaminergic neurons. However, chronic low-level Mn exposure, such as through contaminated drinking water, poses risks that may contribute to neurodevelopmental and neurodegenerative conditions, including attention deficit hyperactivity disorder (ADHD). Pharmacological inhibition of the dopamine transporter (DAT) blocks reuptake, elevates synaptic dopamine, and alleviates ADHD symptoms. This study aimed to determine whether Mn exposure in juvenile mice modifies their response to DAT blockers, amphetamine, and methylphenidate and utilize neuroimaging methods to visualize and quantify Mn distribution across dopaminergic brain regions. Male and female heterozygous DATᵀ³⁵⁶ᴹ and wild-type littermates were randomly assigned to receive control (2.5% Stevia) or high Manganese (2.5 mg/ml Mn + 2.5% Stevia) via water ad libitum from weaning (21-28 days) for 4-5 weeks. Mice underwent repeated testing in locomotor activity chambers for three consecutive days (60 mins.) to ensure that they were fully habituated to the environments. On the fourth day, a 3-hour activity session was conducted following treatment with amphetamine (3 mg/kg) or methylphenidate (5 mg/kg). The second drug was administered in a second 3-hour activity session following a 1-week washout period. Following the washout, the mice were given one last injection of amphetamine and euthanized one hour later. Using the ex-vivo brains, magnetic resonance relaxometry (MRR) was performed on a 7Telsa imaging system to map T1- and T2-weighted (T1W, T2W) relaxation times. Mn inherent paramagnetic properties shorten both T1W and T2W times, which enhances the signal intensity and contrast, enabling effective visualization of Mn accumulation in the entire brain. A subset of mice was treated with amphetamine 1 hour before euthanasia. SmartSPIM light sheet microscopy with cleared whole brains and cFos and tyrosine hydroxylase (TH) labeling enabled an unbiased automated counting and densitometric analysis of TH and cFos positive cells. Immunohistochemistry was conducted to measure synaptic protein markers and quantify changes in neurotransmitter regulation. Mn exposure elevated Mn brain levels and potentiated stimulant effects in males. The globus pallidus, substantia nigra, thalamus, and striatum exhibited more pronounced T1W shortening, indicating regional susceptibility to Mn accumulation (p<0.0001, 2-Way ANOVA). In the cleared whole brains, initial analyses suggest that TH and c-Fos co-staining mirrors behavioral data with decreased co-staining in DATT356M+/- mice. Ongoing studies will identify the molecular basis of the effect of Mn, including changes to DAergic metabolism and transport and post-translational modification to the DAT. These findings demonstrate that alterations in T1W relaxation times, as measured by MRR, may serve as an early biomarker for Mn neurotoxicity. This neuroimaging approach exhibits remarkable accuracy in identifying Mn-susceptible brain regions, with a spatial resolution and sensitivity that surpasses current conventional dissection and mass spectrometry approaches. The capability to label and map TH and cFos expression across the entire brain provides insights into whole-brain neuronal activation and its connections to functional neural circuits and behavior following amphetamine and methylphenidate administration.

Keywords: manganese, environmental toxicology, dopamine dysfunction, biomarkers, drinking water, light sheet microscopy, magnetic resonance relaxometry (MRR)

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Authors: Erika T. Fajardo-Ariza, Luis A. Castillo-Sanabria, Andrea Nieto-Veloza, Carlos M. Zuluaga-Domínguez

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The growing emphasis on sustainable food production and preservation has driven the development of innovative solutions to minimize postharvest losses and improve market access for small-scale farmers. This project focuses on designing, constructing, and selecting materials for solar dryers in certain regions of Colombia where inadequate infrastructure limits access to major commercial hubs. Postharvest losses pose a significant challenge, impacting food security and farmer income. Addressing these losses is crucial for enhancing the value of agricultural products and supporting local economies. A comprehensive survey of local farmers revealed substantial challenges, including limited market access, inefficient transportation, and significant postharvest losses. For crops such as coffee, bananas, and citrus fruits, losses range from 0% to 50%, driven by factors like labor shortages, adverse climatic conditions, and transportation difficulties. To address these issues, the project prioritized selecting effective materials for the solar dryer. Various materials, recovered acrylic, original acrylic, glass, and polystyrene, were tested for their performance. The tests showed that recovered acrylic and glass were most effective in increasing the temperature difference between the interior and the external environment. The solar dryer was designed using Fusion 360® software (Autodesk, USA) and adhered to architectural guidelines from Architectural Graphic Standards. It features up to sixteen aluminum trays, each with a maximum load capacity of 3.5 kg, arranged in two levels to optimize drying efficiency. The constructed dryer was then tested with two locally available plant materials: green plantains (Musa paradisiaca L.) and snack bananas (Musa AA Simonds). To monitor performance, Thermo hygrometers and an Arduino system recorded internal and external temperature and humidity at one-minute intervals. Despite challenges such as adverse weather conditions and delays in local government funding, the active involvement of local producers was a significant advantage, fostering ownership and understanding of the project. The solar dryer operated under conditions of 31°C dry bulb temperature (Tbs), 55% relative humidity, and 21°C wet bulb temperature (Tbh). The drying curves showed a consistent drying period with critical moisture content observed between 200 and 300 minutes, followed by a sharp decrease in moisture loss, reaching an equilibrium point after 3,400 minutes. Although the solar dryer requires more time and is highly dependent on atmospheric conditions, it can approach the efficiency of an electric dryer when properly optimized. The successful design and construction of solar dryer systems in difficult-to-access areas represent a significant advancement in agricultural sustainability and postharvest loss reduction. By choosing effective materials such as recovered acrylic and implementing a carefully planned design, the project provides a valuable tool for local farmers. The initiative not only improves the quality and marketability of agricultural products but also offers broader environmental benefits, such as reduced reliance on fossil fuels and decreased waste. Additionally, it supports economic growth by enhancing the value of crops and potentially increasing farmer income. The successful implementation and testing of the dryer, combined with the engagement of local stakeholders, highlight its potential for replication and positive impact in similar contexts.

Keywords: drying technology, postharvest loss reduction, solar dryers, sustainable agriculture

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Authors: S. M. A. Ismail, M. I. Ibrahim, H. Masdar, F. M. Effendi, M. F. Suhaimi, A. Suun

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Introduction: It is generally known that the rehabilitation process is as important as the reconstruction surgery. Several literature has focused on how early the rehabilitation modalities can be initiated after the surgery to ensure a safe return of patients to sports or at least regaining the pre-injury level of function following an ACL reconstruction. Objectives: The main objective is to study and evaluate the outcome of early balance exercises and agility training in sports rehabilitation for patients post ACL reconstruction. To compare between early balance exercises and agility training as intervention and control. (material or non-material). All of them were recruited for material exercise (balance exercises and agility training with strengthening) and strengthening only rehabilitation protocol (non-material). Followed the prospective intervention trial. Materials and Methods: Post-operative ACL reconstruction patients performed in Selayang and Sg Buloh Hospitals from 2012 to 2014 were selected for this study. They were taken from Malaysian Knee Ligament Registry (MKLR) and all patients had single bundle reconstruction with autograft hamstring tendon (semitendinosus and gracilis). ACL injury from any type of sports were included. Subjects performed various type of physical activity for rehabilitation in every 18 week for a different type of rehab activity. All subject attended all 18 sessions of rehabilitation exercises and evaluation was done during the first, 9th and 18th session. Evaluation format were based on clinical assessment (anterior drawer, Lachmann, pivot shift, laxity with rolimeter, the end point and thigh circumference) and scoring (Lysholm Knee scoring and Tegner Activity Level scale). Rehabilitation protocol initiated from 24 week after the surgery. Evaluation format were based on clinical assessment (anterior drawer, Lachmann, pivot shift, laxity with rolimeter, the end point and thigh circumference) and scoring (Lysholm Knee scoring and Tegner Activity Level scale). Results and Discussion: 100 patients were selected of which 94 patients are male and 6 female. Age range is 18 to 54 year with the average of 28 years old for included 100 patients. All patients are evaluated after 24 week after the surgery. 50 of them were recruited for material exercise (balance exercises and agility training with strengthening) and 50 for strengthening only rehabilitation protocol (non-material). Demographically showed 85% suffering sports injury mainly from futsal and football. 39 % of them have abnormal BMI (26 – 38) and involving of the left knee. 100% of patient had the basic radiographic x-ray of knee and 98% had MRI. All patients had negative anterior drawer’s, Lachman test and Pivot shift test during the post ACL reconstruction after the complete rehabilitation. There was 95 subject sustained grade I injury, 5 of grade II and 0 of grade III with 90% of them had soft end-point. Overall they scored badly on presentation with 53% of Lysholm score (poor) and Tegner activity score level 3/10. After completing 9 weeks of exercises, of material group 90% had grade I laxity, 75% with firm end-point, Lysholm score 71% (fair) and Tegner activity level 5/10 comparing non-material group who had 62% of grade I laxity , 54% of firm end-point, Lyhslom score 62 % (poor) and Tegner activity level 4/10. After completed 18 weeks of exercises, of material group maintained 90% grade I laxity with 100 % with firm end-point, Lysholm score increase 91% (excellent) and Tegner activity level 7/10 comparing non-material group who had 69% of grade I laxity but maintained 54% of firm end-point, Lysholm score 76% (fair) and Tegner activity level 5/10. These showed the improvement were achieved fast on material group who have achieved satisfactory level after 9th cycle of exercises 75% (15/20) comparing non-material group who only achieved 54% (7/13) after completed 18th session. Most of them were grade I. These concepts are consolidated into our approach to prepare patients for return to play including field testing and maintenance training. Conclusions: The basic approach in ACL rehabilitation is to ensure return to sports at post-operative 6 month. Grade I and II laxity has favourable and early satisfactory outcome base on clinical assessment and Lysholm and Tegner scoring point. Reduction of laxity grading indicates satisfactory outcome. Firm end-point showed the adequacy of rehabilitation before starting previous sports game. Material exercise (balance exercises and agility training with strengthening) were beneficial and reliable in order to achieve favourable and early satisfactory outcome comparing strengthening only (non-material).We have identified that rehabilitation protocol varies between different patients. Therefore future post ACL reconstruction rehabilitation guidelines should look into focusing on rehabilitation techniques instead of time.

Keywords: post anterior cruciate ligament (ACL) reconstruction, single bundle, hamstring tendon, sports rehabilitation, balance exercises, agility balance

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Authors: Ali Kadir, S. R. Mishra, M. Shamshuddin, O. Anwar Beg

Abstract:

Motivation- Rotating disk bio-reactors are fundamental to numerous medical/biochemical engineering processes including oxygen transfer, chromatography, purification and swirl-assisted pumping. The modern upsurge in biologically-enhanced engineering devices has embraced new phenomena including bioconvection of micro-organisms (photo-tactic, oxy-tactic, gyrotactic etc). The proven thermal performance superiority of nanofluids i.e. base fluids doped with engineered nanoparticles has also stimulated immense implementation in biomedical designs. Motivated by these emerging applications, we present a numerical thermofluid dynamic simulation of the transport phenomena in bioconvection nanofluid rotating disk bioreactor flow. Methodology- We study analytically and computationally the time-dependent three-dimensional viscous gyrotactic bioconvection in swirling nanofluid flow from a rotating disk configuration. The disk is also deformable i.e. able to extend (stretch) in the radial direction. Stefan blowing is included. The Buongiorno dilute nanofluid model is adopted wherein Brownian motion and thermophoresis are the dominant nanoscale effects. The primitive conservation equations for mass, radial, tangential and axial momentum, heat (energy), nanoparticle concentration and micro-organism density function are formulated in a cylindrical polar coordinate system with appropriate wall and free stream boundary conditions. A mass convective condition is also incorporated at the disk surface. Forced convection is considered i.e. buoyancy forces are neglected. This highly nonlinear, strongly coupled system of unsteady partial differential equations is normalized with the classical Von Karman and other transformations to render the boundary value problem (BVP) into an ordinary differential system which is solved with the efficient Adomian decomposition method (ADM). Validation with earlier Runge-Kutta shooting computations in the literature is also conducted. Extensive computations are presented (with the aid of MATLAB symbolic software) for radial and circumferential velocity components, temperature, nanoparticle concentration, micro-organism density number and gradients of these functions at the disk surface (radial local skin friction, local circumferential skin friction, Local Nusselt number, Local Sherwood number, motile microorganism mass transfer rate). Main Findings- Increasing radial stretching parameter decreases radial velocity and radial skin friction, reduces azimuthal velocity and skin friction, decreases local Nusselt number and motile micro-organism mass wall flux whereas it increases nano-particle local Sherwood number. Disk deceleration accelerates the radial flow, damps the azimuthal flow, decreases temperatures and thermal boundary layer thickness, depletes the nano-particle concentration magnitudes (and associated nano-particle species boundary layer thickness) and furthermore decreases the micro-organism density number and gyrotactic micro-organism species boundary layer thickness. Increasing Stefan blowing accelerates the radial flow and azimuthal (circumferential flow), elevates temperatures of the nanofluid, boosts nano-particle concentration (volume fraction) and gyrotactic micro-organism density number magnitudes whereas suction generates the reverse effects. Increasing suction effect reduces radial skin friction and azimuthal skin friction, local Nusselt number, and motile micro-organism wall mass flux whereas it enhances the nano-particle species local Sherwood number. Conclusions - Important transport characteristics are identified of relevance to real bioreactor nanotechnological systems not discussed in previous works. ADM is shown to achieve very rapid convergence and highly accurate solutions and shows excellent promise in simulating swirling multi-physical nano-bioconvection fluid dynamics problems. Furthermore, it provides an excellent complement to more general commercial computational fluid dynamics simulations.

Keywords: bio-nanofluids, rotating disk bioreactors, Von Karman swirling flow, numerical solutions

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Authors: Tanmoy Basu

Abstract:

The dynamic theory of criminal psychology and its physiological effects on human organs presents a novel perspective that bridges the gap between behavioral sciences and medical research, with significant implications for judicial interpretation and global societal impact. This study seeks to explore the intricate interplay between psychological factors driving criminal behavior and their measurable effects on the human body, hypothesizing that psychological stressors inherent in criminal tendencies produce detectable physiological changes. These insights have the potential to reshape approaches to crime prevention, judicial fairness, and rehabilitation strategies worldwide. Criminal psychology, often confined to behavioral and cognitive dimensions, rarely considers its direct impact on human biology. This research proposes that criminal tendencies and behavior's, characterized by heightened psychological stress and deviant mental patterns, trigger physiological responses in the cardiovascular, endocrine, and neurological systems. The scientific questions addressed here are pivotal: Can criminal psychology leave biological imprints? If so, can these markers provide early warning systems or contribute to judicial evaluations of criminal accountability? Addressing these questions can transform the intersection of science, law, and society. Criminological theories traditionally focus on socio-economic, cultural, or psychological triggers for criminal acts. However, emerging research underscores the psychosomatic connections between mental states and bodily health. Psychological stressors such as anxiety, guilt, or fear—common in individuals predisposed to criminal behavior—may lead to systemic changes in hormone levels, cardiovascular strain, and neural activity. Despite these connections, their implications for understanding criminal behavior remain underexplored, leaving a critical gap in the literature. This study adopts a multidisciplinary, mixed-methods approach that combines empirical data collection with theoretical analysis. Neurological imaging, biomarkers, and physiological testing are employed to identify and quantify changes in the human body associated with individuals exhibiting criminal tendencies. These data are correlated with detailed case histories, enabling an integrative perspective on how psychological and physiological factors converge in criminal behavior. Complementary qualitative analyses provide insights into contextual factors, such as socio-environmental stressors, that influence these physiological responses. Preliminary results reveal a strong correlation between criminal psychology and physiological dysfunction. Specifically, individuals displaying persistent criminal tendencies exhibit elevated cortisol levels, irregular heart rate patterns, and abnormal neural activity in regions associated with impulse control and decision-making. These findings suggest that criminal psychology is not merely a cognitive or emotional phenomenon but one with tangible biological markers. The results are interpreted through the lens of judicial applications, suggesting that physiological markers could supplement psychological evaluations in assessing criminal intent and responsibility. This perspective raises ethical considerations about the use of biological data in legal systems, highlighting the need for careful policy-making. The study advocates for integrating scientific activism into judicial frameworks, enabling more evidence-based decisions that consider both psychological and physiological dimensions of criminal behavior. This research holds transformative potential for global society. By recognizing the biological underpinnings of criminal psychology, policymakers can devise more holistic crime prevention strategies and rehabilitation programmed. Furthermore, this understanding promotes equitable judicial interpretations, ensuring that decisions are informed by comprehensive, evidence-based analyses. This comprehensive investigation not only deepens the understanding of criminal psychology but also paves the way for innovative intersections between science, law, and societal reform.

Keywords: behavioral science, criminal psychology, cognitive dimensions, dysfunction, dynamic theory, emotional phenomenon, global societal impact, human organs, judicial interpretation, psychological changes, rehabilitation strategies

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Authors: Alba Prats-Bisbe, Jaume López-Carballo, David Leno-Colorado, Alberto García Molina, Alicia Romero Marquez, Elena Hernández Pena, Eloy Opisso Salleras, Raimon Jané Campos

Abstract:

Neurological disorders are a leading cause of disability and premature mortality worldwide. Neurorehabilitation (NRHB) is a clinical process aimed at reducing functional impairment, promoting societal participation, and improving the quality of life for affected individuals. Virtual reality (VR) technology is emerging as a promising NRHB support tool. Its immersive nature fosters a strong sense of agency and embodiment, motivating patients to engage in meaningful tasks and increasing adherence to therapy. However, the clinical benefits of VR interventions are challenging to determine due to the high heterogeneity among health applications. This study explores a stepwise development approach for creating VR-based tools to assist individuals with neurological disorders in medical practice, aiming to enhance reproducibility, facilitate comparison, and promote the generalization of findings. Building on previous research, the step-by-step methodology encompasses: Needs Identification– conducting cross-disciplinary meetings to brainstorm problems, solutions, and address barriers. Intervention Definition– target population, set goals, and conceptualize the VR system (equipment and environments). Material Selection and Placement– choose appropriate hardware and software, place the device within the hospital setting, and test equipment. Co-design– collaboratively create VR environments, user interfaces, and data management strategies. Prototyping– develop VR prototypes, conduct user testing, and make iterative redesigns. Usability and Feasibility Assessment– design protocols and conduct trials with stakeholders in the hospital setting. Efficacy Assessment– conduct clinical trials to evaluate outcomes and long-term effects. Cost-Effectiveness Validation– assess reproducibility, sustainability, and balance between costs and benefits. NRHB is complex due to the multifaceted needs of patients and the interdisciplinary healthcare architecture. VR has the potential to support various applications, such as motor skill training, cognitive tasks, pain management, unilateral spatial neglect (diagnosis and treatment), mirror therapy, and ecologically valid activities of daily living. Following this methodology was crucial for launching a VR-based system in a real hospital environment. Collaboration with neuropsychologists lead to develop A) a VR-based tool for cognitive rehabilitation in patients with acquired brain injury (ABI). The system comprises a head-mounted display (HTC Vive Pro Eye) and 7 tasks targeting attention, memory, and executive functions. A desktop application facilitates session configuration, while database records in-game variables. The VR tool's usability and feasibility were demonstrated in proof-of-concept trials with 20 patients, and effectiveness is being tested through a clinical protocol with 12 patients completing 24-session treatment. Another case involved collaboration with nurses and paediatric physiatrists to create B) a VR-based distraction tool during invasive techniques. The goal is to alleviate pain and anxiety associated with botulinum toxin (BTX) injections, blood tests, or intravenous placements. An all-in-one headset (HTC Vive Focus 3) deploys 360º videos to improve the experience for paediatric patients and their families. This study presents a framework for developing clinically relevant and technologically feasible VR-based support tools for hospital settings. Despite differences in patient type, intervention purpose, and VR system, the methodology demonstrates usability, viability, reproducibility and preliminary clinical benefits. It highlights the importance approach centred on clinician and patient needs for any aspect of NRHB within a real hospital setting.

Keywords: neurological disorders, neurorehabilitation, stepwise development approach, virtual reality

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