In bioprocess development, the host and the genetic construct for a new biomanufacturing process are selected in the early developmental stages. This decision, made at the screening scale with very limited information about the performance of the selected cell factory in larger reactors, has a major influence on the performance of the final process. To overcome this, scaledown approaches are essential to run screenings that show the real cell factory performance at industrial like conditions. We present a fully automated robotic facility with 24 parallel mini-bioreactors that is operated by a model based adaptive input design framework for the characterization of clone libraries under scale-down conditions. The cultivation operation strategies are computed and continuously refined based on a macro-kinetic growth model that is continuously re-fitted to the available experimental data. The added value of the approach is demonstrated with 24 parallel fed-batch cultivations in a mini-bioreactor system with eight different Escherichia coli strains in triplicate. The 24 fed-batches ran under the desired conditions generating sufficient information to define the fastest growing strain in an environment with varying glucose concentrations similar to industrial scale bioreactors.

This article argues for five correctives to the current ethical debate about speciesism, and proposes normative, conceptual, methodological and experimental avenues to move this debate forward. Firstly, it clarifies the Principle of Equal Consideration of Interests and points out limitations of its scope. Secondly, it disambiguates between ‘favouritist’ and ‘species-relative’ views about moral treatment. Thirdly, it argues that not all moral intuitions about speciesism should be given equal weight. Fourthly, it emphasizes the importance of empirical research to corroborate statements about ‘folk speciesism’. Fifthly, it disambiguates between the moral significance of species and the moral status of their individual members. For each of these issues, it is shown that they have either been overlooked, or been given inapt treatment, in recent contributions to the debate. Building on the correctives, new directions are proposed for ethical inquiry into the moral relevance of species and species membership.

A study on the selection of hyperelastic constitutive model for polymeric materials is performed using a hybrid experimental-computational approach. Bis-GMA polymer is used as a case study of hyperelastic material to describe the polymer characteristics by determining its Poisson’s ratio and its valid range of the hyperelastic stress-strain curves. These two parameters are then used to determine the hyperelastic constitutive model by using the hybrid approach. Several uniaxial compression tests along with their finite element simulations are implemented in a systematic way, to identify the polymer behavior under the compressive loading conditions. Nano-indentation experiments are conducted to verify the hyperelastic behavior of the polymer. The experimental and computational evidences confirm that the Poisson’s ratio of Bis-GMA is 0.40 and the appropriate hyperelastic constitutive model for this polymer is of a second order polynomial. It is shown that, the results can be used to determine the true stress-strain curve of hyperelastic materials.

Background: Absolute uterine factor infertility (AUFI) is a kind of infertility that is completely attributable to uterine absence (surgical or congenital for women with Mayer-Rokitansky-Küster-Hauser syndrome: MRKH) or anatomic or functional abnormality that prevents embryo implantation or completion of pregnancy to term. Until recently, the only viable option to parenthood for couples with AUFI were adoption or surrogacy. Since a first attempt of uterus transplant (UTx) in 2000, nine babies were born from women with a transplanted uterus from 2014, eight of which in Sweden, and one in the United States. These promising results are raising immense hopes for the women with AUFI and there is optimism about the possibility for UTx to become part of clinical care even though, besides encouraging results, the procedure has also resulted in increased risks and harms for both the donors and recipients and increased risks of premature birth for the fetus. At present UTx is still considered as experimental and requiring more research and safety assessment before becoming a therapeutic option for AUFI. The transition from experimental procedure to therapeutic care would result in less strict ethical scrutiny for UTx and in the possibility for patients to get reimbursement for the procedure by the relevant healthcare insurance or public healthcare providers. In turn, an increase in the number of UTx performed yearly by specialized surgical teams would result in a general improvement of the “field strength”. However, at present it is difficult to establish the amount of evidence that we need in order to consider UTx as no longer experimental but routine clinical practice. The literature on UTx provides recommendations on the different outcomes that should be monitored in this experimental phase but no study is anticipating the number of subjects that should be followed and for how long. Conclusion: As for other transplants that have become routine practice, like renal transplant and heart transplant, it is likely that the decision on “routine practice readiness” will result from available cumulated evidences, from expert capacity to find a consensus on best practices and on political considerations as well, including pressures form patients and patient groups.

This paper presents experimental identification and vibration suppression of a flexible manipulator with non-collocated piezoelectric actuators and strain sensors using optimal multi-poles placement control. To precisely identify the system model, a reduced order transfer function with relocated zeros is proposed, and a first-order inertia element is added to the model to compensate the non-collocation. Comparisons show the identified model match closely with the experimental results both in the time and frequency domains, and a fit of 97.2% is achieved. Based on the identified model, a full-state multi-poles placement controller is designed, and the optimal locations of the closed loop poles are determined. The feasibility of the proposed controller is validated by simulations. Moreover, the controller is tested for different locations of the closed loop poles, and an excellent performance of the optimal locations of the closed loop poles is shown. Finally, the effectiveness of the proposed controller is demonstrated by experiments. Results show that the vibrations of the expected modes are significantly diminished. Besides, vibrations of the higher modes are also slightly suppressed. Accordingly, multi-mode vibrations of the manipulator are well attenuated, and the tip displacement converges quickly with the proposed method.

Immunology and microbiology research in the West Indies has witnessed remarkable growth and innovation, playing a pivotal role in advancing our understanding of immune mechanisms, disease pathogenesis, and therapeutic interventions. This manuscript presents a comprehensive exploration of key areas in West Indian immunology research, spanning from the utilization of bacterial proteins as antibody reagents to the intricate realms of clinical immunology and disease management. The utilization of bacterial immunoglobulin-binding proteins (IBPs), including protein A (SpA), protein G (SpG), and protein L (SpL), has revolutionised serological diagnostics in the region. promise in early disease detection and precision medicine. Microbiological studies in the Caribbean region have shed light on antimicrobial resistance patterns, particularly the emergence of extended-spectrum beta-lactamases (ESBLs), guiding antimicrobial stewardship programs and informing therapeutic strategies. Clinical immunology research has elucidated the molecular pathways underlying immune-mediated disorders, leading to tailored management strategies for conditions such as severe combined immunodeficiency (SCID), neuropsychiatric lupus erythematosus (NPLE), and others. In summary, West Indian immunology and microbiology research has made significant contributions to global healthcare, fostering collaboration, innovation, and improved patient outcomes.

Viral co-infections, where a host is infected by multiple viruses simultaneously, are common in the human population. Human viral co-infections can lead to complex interactions between viruses and the host immune system, affecting the clinical outcome and posing challenges for treatment. Understanding the types, mechanisms, impacts, and identification methods of human viral co-infections is crucial for the prevention and control of viral diseases. In this review, we first introduce the significance of studying human viral co-infections and summarize the current research progress and gaps in this field. We then classify human viral co-infections into four types based on the pathogenic properties and species of the viruses involved. Next, we discuss the molecular mechanisms of viral co-infections, focusing on virus-virus interactions, host immune responses, and clinical manifestations. We also summarize the experimental and computational methods for identifying viral co-infections, emphasizing the latest advances in high-throughput sequencing and bioinformatics approaches. Finally, we highlight the challenges and future directions in human viral co-infection research, aiming to provide new insights and strategies for the prevention, control, diagnosis, and treatment of viral diseases. This review provides a comprehensive overview of the current knowledge and future perspectives on human viral co-infections, and underscores the need for interdisciplinary collaborations to address this complex and important topic.

The Sei Dareh Bridge is a cable-stayed bridge located in West Sumatra Province, Indonesia. The bridge, which crosses the Batanghari River, has a main span of 123 meters long and 9 meters wide. Traffic load is transmitted through 24 prestressed cables to a 42.4-meter-high pylon made of concrete. The bridge deck and traffic loads are directly supported by steel box girders as main beams that are reinforced laterally with cross beams IWF 800.300.16.24 and stringers IWF 350.350.12.19. This paper discusses static and dynamic testing on the bridge which aims to assess its feasibility before it is opened to the public. Based on the test, it was concluded that a static load of 73% could not be achieved because the deflection that occurred was beyond the allowable deflection. This is exacerbated by a loud clanging sound on the ST2-X1 prestressed cable when loading to 240 tons or 58% of the targeted load. In addition, this bridge is included in the "lazy bridge" category because it takes 24 hours to return to an undeformed condition after loading. As a recommendation for this bridge, it is necessary to carry out a structural health monitoring system (SHMS) regularly on bridge slabs and cables.

Exposure of experimental rodents to controlled cycles of light, food, and temperature is important when investigating alterations in circadian cycles that profoundly influence health and disease. However, applying such stimuli simultaneously is difficult in practice. Our aim was to design, build, test, and open-source describe a simple device that subjects a conventional mouse cage to independent cycles of physiologically relevant environmental variables. The device is based on a box enclosing the rodent cage to modify the light, feeding, and temperature environments. The device provides temperature-controlled air conditioning (heating or cooling) by a Peltier module and includes programmable feeding and illumination. All functions are set by a user-friendly front panel for independent cycle programming. Bench testing with a model simulating the CO2 production of mice in the cage showed: a) suitable air renewal (by measuring actual ambient CO2), b) controlled realistic illumination at the mouse enclosure (measured by a photometer), c) stable temperature control, and d) correct cycling of light, feeding, and temperature. The cost of all the supplies (retail purchased by e-commerce) was < 300 US$). Detailed technical information is open-source provided, allowing for any user to reliably reproduce or modify the device. This approach can considerably facilitate circadian research since using one of the described low-cost devices for any mouse group with a given light-food-temperature paradigm allows for all the experiments to be performed simultaneously, thereby requiring no changes in the light/temperature of a general-use laboratory.

To study the heat and mass transfer characteristics of an evaporative cooler for cooling high-temperature working fluids such as supercritical carbon dioxide, an experimental device of the evaporative cooler was built, and a corresponding test system was constructed. Then, the experimental study was carried out based on the orthogonal test method, and the law and extent of the influence of water flow in the tube, spray water flow rate, inlet water temperature in the tube, and air flow rate on heat dissipation, cooling efficiency, and heat and mass transfer coefficients have been obtained. The correlation equations of the heat and mass transfer coefficients were obtained by fitting the orthogonal experimental data, and the validity of the correlation equations was confirmed by the verification experiment.

Artworks play a fundamental role in the cultural and economic asset of communities, enforcing their identity and helping the social integration. Despite their importance, they are not always adequately protected against degradation, which can be induced by the aging, atmospheric and human-induced occurrence, and catastrophic events. Earthquakes certainly represent one of the main risks for art goods; however, traffic, construction works, and shipment can also represent a threat for art goods. Therefore, the assessment of the vulnerability of art collection to dynamic excitations plays a crucial role in their conservation, and it has been collecting an increasing attention by researchers, academics, and Museums’ managers. This work focuses on the vulnerability of the art collections exhibited at the Museum “Gaio Cilnio Mecenate” in Arezzo. Namely, it aims at assessing the effective dynamic loading experienced by the artworks, which is a function of the dynamic propagation plaid by the foundation soil, by the building and by the displayers used for exhibition. In this study the dynamic properties of some of the displayers used for exhibiting the art collections are investigated by performing an experimental survey. The analysis of the experimental data lead to assess the proper frequencies of the displayers, which have been compared to the ones of the building and the foundation soil of the Museum.

This paper presents the experimental and numerical study on a ductile beam-column connection between a composite reinforced concrete truss (CRCT) beam and Concrete Filled Tube (CFT) column subjected to bending and shear loads. Two experimental models with different beam-column joint testing schemes, extracted from the same prototype three-dimensional structure designed according to the rules of the capacity design provided by seismic code, were subjected to quasi-static cyclic tests by applying gravitational loads and the horizontal seismic force. The main objective of this paper is to verify the experimental ductile behavior of both specimens and to simulate the experimental global and local response by nonlinear static analysis considering different modelling approaches. The comparison between the experimental and numerical results highlights, for both models considered, the ductile and dissipative capacity of the connection system, designed following the criterion of the hierarchy of resistances proposed by the current Italian code. Different experimental setup showed similar results demonstrating the repeatability of the test and its reproducibility through the nonlinear numerical analysis.

The cold-formed steel sections are becoming popular for different steel structures because it has a high resistance against the different straining actions with minimum weight compared with hard steel sections. Recently, the perforated cold-formed steel (PCFS) sections are used in many applications such as storage perforated uprights racks. Experimental research into the behaviour of steel storage rack uprights subjected to axial compression is presented in this paper. The material qualities of cold-formed steel uprights were determined by tensile tests. The seventeen perforated specimens were examined under axial compression, with five different cross-sections, three different web heights and thicknesses, and varying lengths. The study's goals are to find out how perforations affect the performance and failure mode of steel storage rack uprights, discuss the interaction of distortional and global buckling, and verify the accuracy of using the Direct Strength Method (DSM) for predicting the ultimate strength of uprights failing in buckling interactions for perforated uprights. It is found that the failure modes of perforated specimens with stiffeners generally cannot be well predicted by the Direct Strength Method. But when the modifications proposed by Xianzhong Zhao etc. al. are used, their accuracy is acceptable.

Nowadays, energy saving is considered a key issue worldwide, as it brings a variety of benefits: reducing greenhouse gas emissions, reducing demand for energy imports, and lowering costs on a household and economy-wide level. Researchers and building designers are looking to optimize building efficiency by means of new energy technologies. Changes in existing buildings can also be made to reduce energy consumption and costs. These may include the usage of new heat transfer fluids based on nanofluids. In this work, an extended experimental campaign (from February 2020 to March 2021) has been carried out on an educational building in the Campus of University of Salento, Lecce – Italy, in order to evaluate the increase in performance of the HVAC system, due to the usage of a nanofluid. The results show that, under optimal operating conditions, plant performance improves more than 10%, with average daily peaks of about 15%.

Air change rate is an important parameter for quantification of ventilation heat losses and also affects the indoor climate of buildings. Indoor air quality is significantly associated with ventilation. If air change isn't sufficient, trapped allergens, pollutants and irritants can degrade the indoor air quality and affect the well-being of a building's occupants. Many studies on ventilation and health have concluded that lower air change rates can have a negative effect on people’s health and low ventilation may result in an increase in allergic diseases. Quantification of air change rate is complicated, since it is affected by a number of parameters, of which the one of the most variable is the air-wind flow. This study aims to determination and comparison of values of the air change rate in two methods - by quantifying of aerodynamic coefficient Cp = Cpe - Cpi – so called aerodynamic quantification of the building and the methodology based on experimental measurements of carbon dioxide in the selected reference room in apartment building.

The explosive emergence of wireless technologies and standards, covering licensed and unlicensed spectrum bands has triggered the appearance of a huge amount of wireless technologies, with many of them coexisting in the same band. Unfortunately, the wireless spectrum is a scarce resource, and the available frequency bands will not scale with the foreseen demand for new capacity. Certain parts of the spectrum, in particular the license-free ISM bands, are overcrowded, while other parts, mostly licensed bands, may be significantly underutilized. As such, there is a need to introduce more advanced techniques to access and share the wireless medium, either to improve the coordination within a given band, or to explore the possibilities of intelligently using unused spectrum in underutilized (e.g., licensed) bands. Therefore, in this paper, we present an open source SDR-based framework that can be employed to devise disruptive techniques to optimize the sub-optimal use of radio spectrum that exists today. Additionally, we describe three use cases where the proposed framework can be employed along with intelligent algorithms to achieve improved spectrum utilization.

Rigid-hulled inflatable boats are extremely practical and popular nowadays. They offer a effective conciliation among usability and costs. Their stable and seaworthy behaviour is guaranteed by performing hydroplaning hulls coupled with unsinkable inflated tubes. At the same time, their design is often based on tradition and preconceptions. Rarely, the design assumptions are validated by the reality or, even, by deeper investigations. In this article, both numerical methods and experimental mechanics techniques are proposed as an essential way for supporting the designers in their decisive tasks. Three different situations are detailed where a numerical or an experimental approach shows its benefit inside the engineering design process: firstly permitting to investigate the behaviour of materials driving the fiberglass selection; then measuring the levels of stress and strain in the hull during sailing; finally, using all available information as a base for developing numerical models of the hull slamming in waves. Even if the discussion is focused on a rigid inflatable boat, large part of its considerations is relevant beyond this special case.

Precision and accuracy estimation is an important index used to reflect the measurement performance and quality of a measurement system. To reveal the significance and connotations of the precision and accuracy estimation index of a close-range photogrammetry system, several common precision and accuracy estimation methods used in close-range photogrammetry are explained from a theoretical perspective, and the mechanism of the internal coincidence precision estimation and the external coincidence accuracy estimation are deduced, respectively. Through detailed experimental design and testing, the validity and reliability of the proposed precision and accuracy estimation methods are verified, which provides strong evidence for the quality control, optimisation, and evaluation of the measurement results from a close-range photogrammetry system. At the same time, it has significance for the further development of precision and accuracy estimation analysis of close-range photogrammetry systems.

This research evaluates the effect of varying hexagonal opening angles on the flexural and shear capacity of castellated beams. This study is conducted through experimental and numerical approaches using WF 150.75.5.7 steel profiles. The hexagonal opening angles are varied to 20°, 30°, 45°, 55°, and 60°. Experimental testing results show that beams with a 20° opening angle have higher flexural and shear capacities compared to larger opening angles. Numerical testing results are consistent with experimental results, showing more uniform deformation patterns and stress distribution at smaller opening angles. These findings contribute significantly to the design of more efficient and effective castellated beams in modern structural applications, particularly in constructions requiring high flexural and shear capacities.

Corrugated board is a composite material characterized by strong orthotropy in both the elastic and plastic phases. Additionally, due to its layered structure, which consists of alternately arranged flat and wavy layers of paper, its mechanics becomes complicated. Therefore, a precisely selected set of laboratory tests is needed to correctly identify all the necessary material parameters of cardboard. The work attempts to define a full set of laboratory tests in order to determine material parameters describing the linear-elastic, orthotropic behavior of cardboard and the basic parameters defining popular plasticity criteria, such as the asymmetric orthotropic Hoffman criterion. For this purpose, sensitivity analysis and numerical models of several selected basic laboratory tests were used. Since the aim of the work is to choose appropriate laboratory tests necessary to correctly determine the material parameters of corrugated board (not its individual layers), the numerical models do not contain detailed cardboard geometry, but only its homogenized representation in the form of the flat shell models. All numerical models are based on the nonlinear finite element method and constitutive modelling in the form of UMAT subroutines implemented in the ABAQUS software. Based on the analyses, appropriate measurements and laboratory tests were indicated that are most sensitive to the material parameters sought.

The oxidative coupling of methane (OCM) to produce ethane and ethylene (C2 compounds) as platform chemicals involves complex chemistry with reactions both in the gas phase and on the catalyst surface, resulting in a distribution of products at the expense of C2 selectivity. This work uses experimental data from a variety of mixed metal oxides on supports at different reaction conditions (temperature, contact time, and reactant flow rates) to train a random forest regressor that predicts methane conversion and C2 selectivity (key performance indicators (KPIs)), and deploys it to locate optimal conditions that maximize C2 yield for a catalyst. Investigating the regressor interpretability via feature importance reveals that the choice of metals and support are crucial to C2 selectivity predictions, while the predictions of methane conversion are driven by the reaction conditions. The machine learning (ML) regressor is used as a surrogate to develop performance curves for each of the catalysts via a multi-objective optimization routine that seeks to maximize the KPIs in the decision space of reaction conditions, is seen to locate optimal conditions at which the maximum C2 yields for catalysts are predicted to be 15%, higher on average. Analyzing the catalysts in the space of their performance curves with respect to a popular OCM catalyst, Mn-Na2WO4/SiO2, reveals distinct patterns based on intrinsic properties of metals and supports. Further, the decision space with catalyst descriptors and reaction conditions is optimized for high C2 yields using the ML surrogate, in a static multi-objective optimization routine, and an adaptive Bayesian routine, where the latter was found to have a wider field focus in proposing catalyst formulations and conditions. Transition metal oxides on a variety of supports were proposed but not their lanthanide oxide counterparts.

Most shear tests are performed as standard three- or four-point bending tests, i.e., on one-way simply supported specimens subjected to concentrated loads. The major disadvantage is that these conditions usually do not correspond to the support and load condition of real structures. Structural members such as beams or slabs, are often multi-span components and subjected to distributed loads. As a consequence, the complex shear behavior, including crack kinematics, shear transfer mechanisms, and shear capacity, is studied almost only simply supported members with concentrated load. Positive impacts on the shear behavior resulting from continuous systems and distributed loads are thus neglected in the derivation of calculation models and in the development of design specifications. To incorporate the effect of continuous members and distributed loading conditions, more experimental investigations are necessary. Therefore, a total of 16 bending shear tests on CFRP reinforced concrete members without shear reinforcement were carried out. The tests specimens were tested as simply supported beams or as simply supported beams with loaded cantilever to simulate the continuous system with concentrated and distributed loads. Furthermore, the shear slenderness was varied by using different span lengths and degrees of restraint in the systems with intermediate support. All test specimens were made of high-strength concrete and were reinforced with a multilayer grid-like CFRP reinforcement in longitudinal direction. There was no shear reinforcement installed in the investigated shear span. This paper focuses the influence of the support conditions and load arrangements on crack development as well as on shear strength.

Paratuberculosis (PTB) is a chronic granulomatous enteritis caused by Mycobacterium avium subsp. paratuberculosis (MAP) that affects a wide variety of domestic and wild animals. It is considered as one of the diseases with the highest economic impact in the ruminant industry. Despite many efforts and intensive research, PTB control is still controversially discussed and diagnostic and immunoprophylactic tools lack great limitations. Thus, models play a crucial role in understanding the pathogenesis of infection and disease, and in testing novel vaccine candidates. Here, we review the potential and limitations of different experimental approaches currently used in PTB research, focusing on laboratory animals and cell based models. The aim of this review is to offer a vision of the models that have been used and what has been achieved or discovered with each one so that the reader can choose the best model to answer their scientific questions and prove their hypotheses. Also, we bring forward new approaches that we consider worth exploring in the near future.

The shear factor of ore drawing is one of the important factors affecting the formation of underground debris flow, and it has an important contribution to the formation of underground debris flow. The purpose of this paper is to study the effect of mining shear factor on underground debris flow in natural caving method. Based on the research background of the underground debris flow in Plan copper mine, this paper analyzes the characteristics of the slurry material structure of the underground debris flow, the influence of drawing shear factor on formation mechanism of underground debris flow is analyzed. The results show that the slurry of the underground debris flow in Plan mine is not only a pseudoplastic fluid but also a thixotropic fluid. It is indicated that once there is shearing force in drawing, it will deform, and its viscosity will decrease with the increase of shear rate and time. It is considered that the shear force produced by the flow of ore particles first produces shear action on the paste in the shear boundary region of ore drawing, it is reduced in viscosity and increased in fluidity, so that its “Activation” and then become a flowable paste, along with the bulk ore flow through the mouth. The continuous ore drawing process will continuously shear the new moraine slurry in the ore drawing channel and continuously “Activate” the moraine slurry in the ore drawing channel, finally, a certain scale and destructive down-hole debris flow accident. This paper is the first to study the effect of ore drawing shear factor on the formation mechanism of underground debris flow. It not only broadens the research field of debris flow, but also fills up the deficiency of systematic research on underground debris flow, and provides theoretical guidance for the prevention and control of underground debris flow.

We conducted the meander evolution experiments incorporating the effects of riparian vegetation and the series of upper vortex flow disturbances induced by a scour pit simultaneously. Two employed nonlegume plants with salinity and alkalinity resistance, had uniform degrees of seedling normal growth and different lengths of root networks. Our results show that riparian vegetation in general can consolidate the single-thread channel planform without branching outward under the flooding flow conditions. Transverse point bars on inner banks were instead by downstream scroll bars in overall channel for long, unless the coupling of riparian vegetation and flood scour. Shallow-rooted plant was inadequate to resist the inner-bank cutting effect brought by the upper vortex flow. Deep-rooted plant can stabilize the bank-lines and thalweg significantly, but that was susceptible to locally low vegetation coverage. Using evolutionary spectral analysis based on thalweg, we found streamwise high-frequency distribution of bed topography mainly concentrated downstream the bifurcation interface in unvegetated scenario when faced with a flood, shrank to the upper isolated turning interface in shallow-rooted scenario, and conversely stood out along the bare roots disturbed region in deep-rooted scenario. This experimental study expands a much wider understanding of vegetation effects in hydro-bio-geomorphological systems engineering.

A mechanical ventilation system is a big support for breathing complications, in which an external solution is quite necessary to keep oxygen compensation in the patients. Its knowledge is well widespread and different equipment has been developed. However, they are very expensive and their quantity in medical centers is not sufficient, especially in Peru. Hence, it has been required to develop new methods to provide oxygen by a low cost equipment; Protofy, a research group from Spain, designed one of the first low cost mechanical ventilation systems which was medically validated by its government. In this sense, a redesign of the mechanical ventilation system was carried out according to the local requirements and available technology, a different airbag resuscitator with different properties and geometry, but maintaining its working concept based on a cam compression mechanism. Sensors and a display were added to improve the performance with a control algorithm for the rotation frequency and to show the ventilation curves over time to the medical staff. It was necessary to develop a mathematical model to relate the behavior between ventilation curves for a patient and physical variables of the design, especially in the epidemic COVID 19, that many countries are dealing with at the time research is being conducted. The mechanical ventilation system was redesigned, fabricated, and tested measuring its ventilation curves over time. Results indicate that this redesign provides a sturdy equipment able to work during a longer lifetime than the original. The replicability of the ventilation curves behavior is assured, while the mechanism dimensions are adapted for a particular airbag resuscitator. The mathematical model of the whole system can predict satisfactorily the ventilation curves over time and was used to provide the air pressure, volume, and flow as a function of the rotation angle measured by sensors.

Background: The use of animal models for biomedical research provides us with a convenient and feasible route to establish causal relationships by recapitulating the temporal sequence of events in a controlled environment with a potential to manipulate the variables at multiple levels including genetic, protein, physiological or environmental. Objectives: The current review was conducted to gain insights into various animal models for the SARS-CoV-2 virus. Material and Methods: A literature review (PUBMED, PUBMED Central, PMC, Google Scholar, Google search engine) following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines performed in early April 2020 revealed 9 articles of interest. Search terms included covid 19, covid-19, novel corona virus, SARS-CoV-2, animal models, experimental models, laboratory models & covid 19 animal models. Two independent reviewers extracted the data; the third reviewer was involved in case of discrepancy. Results: SARS-CoV-2 shares an identical receptor binding domain with the SARS-CoV virus and has a superior binding affinity to the host ACE2. Based on this, the role of rhesus macaques, golden Syrian hamsters, transgenic hACE2 mice and ferrets as animal models have been studied. All four animals are susceptible to infection with SARS-CoV-2 with variable clinical presentation but universal recovery. The respiratory tract is primarily involved in all four models. Involvement of intestines was also seen in at least one study in each animal. Transfer to naïve animals in close contact has been documented in case of hamsters and ferrets. Seroconversion was documented in all although the role of convalescent sera was tested in hamsters only, with positive results though. Air-borne transmission was documented in ferrets and the possibility of feco-oral transmission was suggested for hamsters. The possibilities of recurrence and re-infection were ruled out by experiments upon the rhesus macaques. The fulfilment of Koch’s postulates has been highlighted. Discussion: The various studies available on animal models have been able to establish models of infection and transmission that recapitulate different aspects of disease in humans. However, the response between different animals and the same animal in different experiments is not completely coherent. Some of them do not manifest the disease clinically while others behave differently at molecular and immunological levels. Moreover, the physiology of these animals is not identical to human beings and the findings may not be extrapolated to human beings in an ‘as-is’ manner. Conclusions: The review acknowledges the achievements made by these experiments in a short span of time and highlighted the urgent need for a deeper dive in search of a quintessential animal model which can be studied for efficacy and safety of newer drugs and vaccines before a make-shift from the petri-dish to the human body can be contemplated.

The “Crisis of Reproducibility” has received considerable attention both within the scientific community and without. While factors associated with scientific culture and practical practice are most often invoked, I propose that the Crisis of Reproducibility is ultimately a failure of generalization with a fundamental scientific basis in the methods used for biomedical research. The Denominator Problem describes how limitations intrinsic to the two primary approaches of biomedical research, clinical studies and pre-clinical experimental biology, lead to an inability to effectively characterize the full extent of biological heterogeneity, which compromises the task of generalizing acquired knowledge. Drawing on the example of the unifying role of theory in the physical sciences, I propose that multi-scale mathematical and dynamic computational models, when mapped to the modular structure of biological systems, can serve a unifying role as formal representations of what is conserved and similar from one biological context to another. This ability to explicitly describe the generation of heterogeneity from similarity addresses the Denominator Problem and provides a scientific response to the Crisis of Reproducibility.

With the rapid development of modern industrial technology, ultra-high-speed motors have demonstrated tremendous application potential in fields such as aerospace, high-speed machining, and micro-mechanical systems due to their high efficiency, high power density, and compact structure. However, the design of ultra-high-speed motors faces numerous challenges, particularly under mechanical boundary constraints, how to balance the interactions among electromagnetic performance, thermodynamic characteristics, mechanical strength, and other multi-physical fields has become a key factor limiting performance enhancement. This study first establishes a multi-physical field coupling model for ultra-high-speed motors, comprehensively considering the mutual influences of electromagnetic fields, temperature fields, and stress fields. Through finite element analysis, precise simulations are conducted on the electromagnetic distribution, heat conduction, mechanical stress, and rotor dynamics characteristics within the motor. Based on this, the impact of various design parameters (such as rotor structure, material selection, and cooling methods) on motor performance is investigated, revealing the variation laws of motor performance under multi-physical field coupling. With mechanical boundary constraints taken into account, this paper proposes an optimization design method for high-speed motors based on a multi-physical field coupling model. Initial samples are obtained through MaxPro experimental design, and a Kriging surrogate model is used for fitting. Subsequently, the NSGA-2 algorithm is employed for optimization design. During the optimization process, RMAE and RAAE are adopted for accuracy evaluation, and the Kriging model is iteratively updated based on the evaluation results until the optimal design of the ultra-high-speed motor is completed. This optimization design method enhances the overall performance of the motor while ensuring its mechanical boundary conditions and reducing the computational load during the optimization process. Experimental results demonstrate that the proposed multi-physical field coupling optimization design method can significantly improve the efficiency and power density of ultra-high-speed motors. This study not only provides theoretical support and technical guidance for the design of ultra-high-speed motors but also offers new ideas and methods for motor research and development in related fields. In the future, more efficient and intelligent optimization design algorithms will be explored to continuously advance ultra-high-speed motor technology.

This study presents a comprehensive investigation on an innovative mechanical system inspired by recent advancements in metamaterials, more specifically the work is focused on Origami-type structures for their intriguing mechanical properties. Originating from the specific fields such as aerospace for their lightweight and foldable characteristics, Origami mechanical devices exhibit unique non-linear stiffness, in particular, when suitably designed, they show Quasi-Zero Stiffness (QZS) characteristics within a specific working range. The QZS property, aligned with the High Static Low Dynamic (HSLD) stiffness concept, suggests promising applications such as a low-frequency mechanical passive vibration isolator. The study explores the vibration isolation characteristics of Origami-type suspensions, with a particular emphasis on their potential application as low-frequency passive vibration isolators. The Kresling Origami Module (KOM) has been selected for its compactness and compatibility with 3D printers. A detailed analysis using 3D CAD, Finite Element Analysis, and experimental testing have been carried out. The investigation includes the analysis of the influence of geometric parameters on the non-linear Force-Displacement curve. Multibody simulations validate the low-frequency isolation properties within the QZS region, and disparities in dynamic properties beyond the QZS range. The study underscores the transformative potential of Origami-type metamaterials in enhancing low-frequency vibration isolation technology. It also highlights challenges related to material properties and loading mass variations, providing valuable insights for future developments in this promising field.

Isotopes at the limits of nuclear existence are of great interest for their critical role in nuclear astrophysical reactions and their exotic structure. Experimentally, exotic nuclides are challenging to address due to low production cross-sections, overwhelming amounts of contamination, and lifetimes typically less than a second. To this end, a Multiple-Reflection Time-of-Flight mass spectrometer at the TITAN-TRIUMF facility was built to determine atomic masses. This device is a preferred tool to work with exotic nuclides due to its ability to resolve the species of interest from contamination and short measurement cycle times enabling mass measurements of isotopes with millisecond half-lives. With a relative precision of order $10^{-7}$, we demonstrate why the TITAN MR-TOF MS is the tool of choice for precision mass surveys for nuclear structure and astrophysics. The capabilities of the device are showcased in this work including new mass measurements of short-lived tin isotopes ($^{104-107}$Sn) approaching the proton dripline as well as $^{89}$Zr, $^{90}$Y, and $^{91}$Y. The last three illustrate how the broadband surveys of MR-TOF MS reach beyond the species of immediate interest.

Promoting the use of solar energy resources has always faced the challenges of instability and supply-demand mismatch. The key to solving these issues is to efficiently store and utilize solar energy resources using high-performance heat storage devices. This study designed a high-performance shell-and-tube phase change thermal storage device and established a numerical model using ANSYS software to summarize the device's dynamic melting law. To verify the accuracy of the numerical simulation, a performance testing platform for the phase change thermal storage device was built to investigate the impact of factors such as inlet water temperature, inlet water flow rate, type of heat storage, and initial temperature of the device, and to reveal the change law of the device's performance. The results show that the inlet water temperature has the most significant impact on the device's heat storage and release performance. When the device's heat storage or release is used for heating, changing the inlet water flow rate has a weak and limited effect on the device's performance. However, when the device's heat release is used to provide domestic hot water, increasing the makeup water temperature and reducing the inlet water flow rate can significantly improve the device's effective heat release. Furthermore, based on the experimental validation of the model's correctness, this study further simulated and studied the impact of different factors on the device's heat storage process to optimize its structural design and provide technical references for the device's actual operation and installation. The results show that the placement of fins has a negligible effect on the performance of the heat storage device while reducing the fin spacing and increasing the fin thickness can significantly improve the melting efficiency of the phase change material (PCM). Additionally, the heat storage characteristics of the device are significantly better in the vertical installation mode than in the horizontal installation mode. This study provides theoretical guidance and technical references for the design and use of phase change thermal storage devices.

Previously we have shown that the combination of radiotherapy with human-umbilical-cord-derived mesenchymal stem-cell therapy significantly reduces the size of the xenotumours in mice, both in the directly irradiated tumour and in the distant non-irradiated tumour or in its metastasis. We have also shown that exosomes secreted from mesenchymal stem-cells pre-irradiated with 2 Gy are quantitatively, functionally and qualitatively different from the exosomes secreted from non-irradiated mesenchymal cells and also that proteins, exosomes and microvesicles secreted by mesenchymal cells suffer a dramatic change when cells are activated or non-activated, with the amount of protein present in the exosomes of the pre-irradiated cells being 1.5-fold times greater compared to those from non-irradiated cells. This finding correlates with a dramatic increase in the anti-tumour activity of the exosomes secreted by pre-irradiated mesenchymal-cells. After the proteomic analysis of the load of the exosomes released from both irradiated and non-irradiated cells, we conclude that annexin A1 is the most important and significant difference between the exosomes released by the cells in either status. Knowing the role of annexin A1 in the control of hypoxia and inflammation which is characteristic of acute-distress-respiratory syndrome, we have designed a hypothetical therapeutic strategy, based on the transplantation of mesenchymal stem cells stimulated with radiation, to alleviate the symptoms of patients who, due to pneumonia caused by COVID-19, require the care of an intensive care unit for patients with life-threatening conditions. With this hypothesis, we would seek to improve the patients’ respiratory capacity and increase the expectations of their cure.

5G heterogeneous network overlaid by millimeter-wave (mmWave) access employs mmWave meshed backhauling as a promising cost-efficient backhaul architecture. Due to the nature of mobile traffic distribution in practice which is both time-variant and spatially non-uniform, dynamic construction of mmWave meshed backhaul is prerequisite to support the varying traffic distribution. Focusing on such scenario of outdoor dynamic crowd (ODC), this paper proposes a novel method to control mmWave meshed backhaul for efficient operation of mmWave overlay 5G HetNet through Software-Defined Network (SDN) technology. Our algorithm is featured by two functionalities, i.e., backhauling route multiplexing for overloaded mmWave small cell base stations (SC-BSs) and mmWave SC-BSs’ ON/OFF status switching for underloaded spot. In this paper, the effectiveness of the proposed meshed network is confirmed by both numerical analyses and experimental results. Simulations are conducted over a practical user distribution modeled from measured data in realistic environments. Numerical results show that the proposed algorithm can cope with the locally intensive traffic and reduce energy consumption. Furthermore, a WiGig (Wireless Gigabit Alliance certified) device based testbed is developed for Proof-of-Concept (PoC) and preliminary measurement results confirm the proposed dynamic formation of the meshed network’s efficiency.

Polymer flooding is one of the most successful chemical EOR methods, and is primarily implemented to accelerate oil production by sweep improvement. However, other benefits have extended the utility of polymers. During the last decade, it has been evaluated for an increasing number of fields, both offshore and onshore. This is a consequence of improved polymer properties, which extends the use to HTHS (high temperature high salinity) conditions and of improved understanding of flow mechanisms such as for heavy oil mobilization. A key issue in understanding polymer performance is to control and predict in-situ porous medium rheology. The first part of this paper reviews recent developments in understanding polymer flow in porous medium. Especially, polymer in-situ rheology and injectivity is discussed. The second part of this paper reports polymer flow experiments using the most applied polymer for EOR processes, HPAM (partially hydrolyzed polyacrylamide). The experiments address high rate near-wellbore behavior (radial flow) as well as reservoir rate steady state flow (linear flow) and discuss differences observed in terms of flow conditions. In addition, impact of oil on polymer rheology was investigated, and compared to single-phase polymer flow in Bentheimer sandstone rock material. Presence of oil leads to a reduction in apparent viscosity.

Road-embedded inductive power transfer (IPT) systems have the potential to accelerate the electrification of the transportation sector. For these systems to be economically viable however, they need to have a similar durability and lifespan compared to that of asphalt roads. One area that has lacked investigation is thermally induced stresses in a primary IPT pad, which is caused by the increase in temperature of the pad when it is energized and the differing thermal expansion of the materials within. This paper presents an experimental and a finite-element based methodology for investigating the thermal-mechanical behaviour of a ¼-scale double-D pad, which was energized while suspended in air, as well as energized when embedded in pavement. A focus was placed on the measurement and prediction of strains in the magnetic ferrite cores because of their brittleness. Ferrite strains were measured using a combination of resistive strain gauges and non-metallic Fibre Bragg Grating (FBG) sensors. Coupled electromagnetic-thermal-structural simulations were conducted to predict temperature and strains in the system, with temperature-dependent properties obtained through physical testing. At an ambient temperature of 50°C, the temperature in the middle of the copper litz wire coil was predicted to be 100°C in both the suspended and embedded case. There was excellent correlation to experimental results, with a difference of less than 10% for most temperature measurements. When energized, the pad was predicted to experience an upward bow due to its temperature rise, resulting bending strains in the ferrite cores. At an ambient temperature of 50°C, maximum tensile strain in the ferrites of the embedded pad was measured to be 62 microstrain (με), with a root-mean square error that was 18 με across three sensors. The experimental and validated numerical methodology can be applied to full-scale operational IPT pads to analyse and improve their thermal-mechanical performance.

Memory and emotion, fundamental components of our mental existence, are highly vulnerable to psychiatric disorders like post-traumatic stress disorder (PTSD). This condition has been linked to serotonin (5-HT) metabolism disruptions. Over 95% of the 5-HT precursor tryptophan (Trp) is metabolized through the Trp-kynurenine (KYN) metabolic pathway, but little is known about its role in behavior. Kynurenine aminotransferases are responsible for the production of the Trp-KYN metabolite kynurenic acid. The gene aadat codes for mitochondrial kynurenine aminotransferase isotype 2. We generated CRISPR/Cas9-induced aadat knockout (kat2−/−) mice to examine the consequence of the gene deletion on negative valence in emotion, memory, and motor function in males 8 weeks of age and compared them to their wild-type counterparts. The forced swim test showed increased depression-like behaviors in transgenic mice. Anxiety and memory tests showed no significant differences. The transgenic mice had fewer center field and corner entries, shorter ambulation distances, and fewer jumping counts in the open field test. Overall, the transgenic mice exhibit depression-like behavior in a learned helplessness model, emotional indifference, and motor deficits. Here we present the first evidence that the deletion of the aadat gene triggers depression-like behaviors, uniquely associated with despair experience rather than adverse-conditioned memory. These findings have profound implications, opening avenues for further exploration into the main causes of experience-based depression linked to despair. This investigation has the potential to advance our understanding of these complex conditions and pave the way for improved therapeutic strategies by elucidating the relationship between Trp metabolism and the pathogenesis of PTSD.

The pharmacokinetic profile of fat-soluble vitamins A, E, K1, and D3 co-administered with liquid paraffin or water in an experimental rat model was investigated. Animals received a solution of the four vitamins orally through a probe, followed 10 minutes later by the administration of either the liquid paraffin product dissolved in water (Emuliquen Simple®) or water (control). Vitamin formulations were 20, 50, 0.30 and 0.10 mg/kg for vitamins A, E, K1, and D3, respectively. Blood samples were collected before dosing and at 0.17, 1, 2, 4, 8, and 24 hours post-dosing. Vitamin concentrations were quantified by liquid chromatography coupled with mass spectrometry. No relevant differences in the absorption of vitamins in terms of AUC0-last (area under the curve up to the last measurable concentration) or Cmax in the absence or presence of co-administration of the liquid paraffin product were observed. The difference of these parameters between the treatment groups for all vitamins was in the range of bioequivalence (≤ 20%). The liquid paraffin-based laxative product did not interfere with the absorption of vitamins A, E, K1, and D3 that are ingested in the diet, which is clinically relevant due to the high prevalence of functional constipation in children and adults.

Ultra-large cold-water pipes (CWP) may present structural instability phenomenon under complex and variable operating conditions, and the current theoretical analysis rarely takes into account the influence of multiple key parameters at the same time, resulting in some errors between the prediction results and the actual deformation behavior of the pipe. Considering this issue, this paper establishes a computational analysis model of the mechanical performance of the CWP based on the Euler-Bernoulli beam theory, considering the effect of waves, the clump weight at the bottom, internal flow and sea current, and gives a time-dependent solution of the mechanical response of the pipe with the action of multiple key parameters using the differential quadrature method (DQM). Additionally, the correctness and validity of the theoretical model are well verified by comparing the numerical solution with the theoretical results. Finally, to study the effects of operating conditions on the mechanical response of the pipe, the effects of waves, the clump weight, internal flow and sea current on the lateral deflection and maximum bending moment of the pipeline are discussed based on numerical simulation and orthogonal experimental method. The results show that changing the wave strength and internal flow velocity has little effect on the lateral deflection of the CWP, and the clump weight at the bottom can effectively suppress the lateral deflection of the pipeline, but increasing the current velocity can significantly increase the lateral deflection of the pipeline, which can lead to the instability of the pipe. Nevertheless, the effects of waves, the clump weight, internal flow and sea current on the maximum bending moment of the pipeline are basically the same, all of them increase sharply at first, and then decrease gradually until they level off, and the differences in the effects are mainly reflected in the different locations of the pipe sections. This paper suggests the design guidance of CWP in aspect of dynamic response depending on the operating condition.

Course-based Undergraduate Research Experiences (CUREs) in high-enrollment, introductory classes are a 37 potentially transformative approach to retaining more students in STEM majors. We developed and piloted a CURE 38 in the introductory biology courses at the University of Washington. This CURE focuses on analyzing experimental 39 evolution of antibiotic resistance in Escherichia coli and generates data on two topics relevant to clinical practice: 40 compensatory mutations and cross-drug effects. By studying mutations in central cellular machinery that confer drug 41 resistance, students not only gain insight into fundamental cellular phenomena, but also recognize the molecular 42 basis of a medically important form of evolutionary change, connecting genetics, microbiology, and evolution.

Results from a behavioral economic laboratory experiment are used to enhance our understanding of public health decisions made during the COVID-19 pandemic. The identification of systematic biases from optimal decision theory found in controlled experiments could help inform public policy design for future public health crises. The laboratory and the shelter-in-place decisions made during COVID-19 included elements of risk, uncertainty and ambiguity. The lab findings found individuals adopt different decision rules depending on both personal attributes and on the context and environment in which the decision task is conducted. Key observations to consider in the context of the COVID-19 decision environment include the importance of past experience, the ability to understand and calculate the odds of each action, the size and differences in economic payoffs given the choice, the value of information received, and how past statistical independent outcomes influence future decisions. The academic space encompassing both public health and behavioral economics is small, yet important, particularly in the current crisis. The objective of continued research in this area would be to develop a more representative model of decision-making processes, particularly during crisis, that would serve to enhance future public health policy design.

Abstract: Passive acoustic monitoring (PAM) is a non-invasive technique to supervise the wildlife. Acoustic surveillance is preferable in some situation such as in the case of marine mammals, when the animals spend most of their time underwater, making it hard to obtain their images. Machine learning is very useful for PAM, for example, to identify species based on audio recordings. But some care should be taken to evaluate the capability of a system. We define PAM-filters as the creation of the experimental protocols according to the dates and locations of the recordings, aiming to avoid the use of the same individuals, noise and recording devices in both training and test sets. A random division of a database present accuracies much higher than accuracies obtained with protocols generated with PAM-filter. Although we use the animal vocalizations, in our method we convert the audio into spectrogram images, after that, we describe the images using the texture. Those are well-known techniques for audio classification, and they have already been used for species classification. Also, we perform statistical tests to demonstrate the significant difference between accuracies generated with and without PAM-filters with several well-known classifiers. The configuration of our experimental protocols and the database were made available online.

Current industrial trends bring new challenges in energy absorbing systems. Polymer materials as the traditional packaging material seem to be promising due to their low weight, structure and production price. Based on the review, the linear low-density polyethylene material was identified as the most promising material for absorbing impact energy. The current paper addresses the identification of the material parameters and the development of a Constitutive material model to be used in future design by virtual prototyping. The paper deals with the experimental measurement of the stress-strain relations of the linear low-density polyethylene under static and dynamic loading. The quasi-static measurement is realized in two perpendicular principal directions and is supplemented by a test measurement in the 45 degrees direction, i.e. exactly between the principal directions. The quasi-static stress-strain curves are analyzed as an initial step for dynamic strain rate dependent material behavior. The dynamic response is tested in the drop tower using a spherical impactor hitting the flat material multi-layered specimen at two different energy levels. The strain rate dependent material model is identified by optimizing the static material response obtained in the dynamic experiments. The material model is validated by the virtual reconstruction of the experiments and by comparing the numerical results to the experimental ones.

This work describes a new transducer prototype for continuous monitoring both in the structural and geotechnical fields. The transducer is synthetically constituted by a wire of optical fiber embedded between two fiber tapes (fiberglass or carbon fiber) and glued by a matrix of polyester resin. The fiber optical wire ends have been connected to a control unit whose detection system is based on Brillouin optical time-domain frequency analysis. Three laboratory tests were carried out to evaluate the sensor's reliability and accuracy. In each experiment, the transducer was applied to a sample of inclinometer casing sets in different configurations and with different constraint conditions. The experimental data collected were compared with theoretical models and with data obtained from the use of different measuring instruments to perform validation and calibration of the transducer at the same time. Several diagrams allow comparing the transducer and highlighting its suitability for monitoring and maintenance of structures. The characteristic of the transducer suggests its use as a mixed system for reinforcing and monitoring, especially in lifetime maintenance of critical infrastructures such as transportation and service networks, and historical heritage.

Chronic diseases are still known as incurable diseases, and we suspect that the medical research model is unfit for characterizing chronic diseases. In this study, we examined accuracy and reliability required for characterizing chronic diseases, reviewed implied presumptions in clinical trials and assumptions used in statistical analysis, examined sources of variances normally encountered in clinical trials, and conducted numeric simulations by using hypothetical data for several theoretical and hypothetical models. We found that the sources of variances attributable to personal differences in clinical trials can distort hypothesis test outcomes, that clinical trials introduce too many errors and too much inaccuracies that tend to hide weak and slow effects of treatments, and that the means of treatments used in statistical analysis have little or no relevance to specific patients. We further found that a large number of uncontrolled co-causal or interfering factors normally seen in human subjects can greatly enlarge the means and the variances of the experimental errors, and the use of high rejection criteria (e.g., low p values) further raises the chances of failing to find treatment effects. As a whole, we concluded that the research model using clinical trials is wrong on multiple grounds, under any of our realistic theoretical and hypothetical models, and that misuse of statistical analysis is most probably responsible for failure to identify treatment effects for chronic diseases and to detect harmful effects of toxic substances in the environment. We proposed alternative experimental models involving the use of single-person or mini optimization trials for studying low-risk weak treatments.

The details of antigen-antibody interactions and the identification of epitopes are critical for the development of monoclonal antibody drugs. Ab42 is a native human-derived anti-CFH monoclonal antibody. In this study, the interaction between antigen pCFH and antibody (Ab42) was theoretically demonstrated by molecular docking and MD simulation, combined with free energy calculation and computational alanine scanning (CAS), and key amino acids and epitopes were identified. Experimental alanine scanning (EAS) was then carried out to verify the results of the calculation, and our results indicated that Ab42 antibody forms hydrogen bonds and interacts hydrophobically with pCFH through the Tyr315, Ser100, Gly33, and Tyr53 residues on its CDR, while the main pCFH epitopes are located at the six sites of Pro441, Ile442, Asp443, Asn444, Ile447, and Thr448. In conclusion, this study has explored the mechanism of antigen-antibody interaction from both theoretical and experimental aspects, and our results have important theoretical significance for the design and development of relevant antibody drugs.

The challenge posed by multi-drug resistance (MDR) of pathogenic organisms, spectacularly manifested in the 6 “ESKAPE” bacterium (two Gram-positive, four Gram-negative) species, should invoke new comprehensive strategies, and needs cooperation of scientists with medical, veterinary and natural science background. This review is aimed at informing newcomers, coming from the field of biology and genetics, about problems related to rapidly emerging, new multi-drug resistant, pathogenic, bacteria. Unlike persistence, the antibiotic resistance is inherited. A functioning “resistance gene” makes a susceptible organism resistant to a given antibiotic, encoding for polypeptides capable of acting either as decomposing enzymes, or acting as trans-membrane pumps, or membrane structure components capable of modifying the permeability implementing a «by pass» mechanism enabling the antibiotic molecule to reach its cellular target(s). A functioning “sensitivity gene” encode for a polypeptide, capable (directly or indirectly) of transferring toxic molecules into target cells, or of metabolizing non-transferable to transferable, or non-toxic molecules to toxic derivatives. A gene of a normal function could act as a “sensitivity” gene in the presence of antibiotics of chemical structures similar to the natural substrate of the gene product, (enzyme or binding/ trans-membrane protein). The Agrocin 84 story is a good example. Multi-drug resistance is a phenotypic consequence of the sequential accumulation of mutations, and/or up-take of plasmids or genomic islands carrying resistance genes from the environment via horizontal gene transfer, mediated by conjugative plasmid or bacteriophage carrying mobile genetic elements. Both multi-drug resistance and collateral sensitivity are evolutionary products. Some revealed evolutionary process and their Lamarckian and Darwinian interpretations are discussed. Toolkits of comparative full-genome sequencing, genomics, experimental evolution and population genetics may provide perspectives for overcoming the invincibility of multi-drug panresistance. The status of some recently emerging pathogenic bacterium species with zoonic features and of veterinary background is also discussed.

Background: Pediatric Rapid Response Teams (RRTs) are expected to significantly lower pediatric mortality in healthcare settings. This study evaluates RRTs' effectiveness in decreasing cardiac arrests and unexpected Pediatric Intensive Care Unit (PICU) admissions. Methods: A quasi-experimental study (2014-2017) at King Abdulaziz University Hospital, Jeddah, Saudi Arabia, involved 3,261 pediatric inpatients, split into pre-intervention (1,604) and post-intervention (1,657) groups. The intervention entailed pediatric specialists collaboratively managing acute decompensations following set protocols. Results: RRT was activated 471 times, primarily for respiratory distress (29.30%), sepsis (22.30%), clinical anxiety (13.80%), and hematological abnormalities (6.7%). Family concerns triggered 0.1% of activations. Post-RRT implementation, unplanned PICU admissions significantly reduced (RR = 0.552, 95% CI 0.485-0.628, P < 0.0001), and non-ICU cardiac arrests were eliminated (RR = 0). Patient care improvement was notable, with a -9.61 coefficient for PICU admissions (95% CI: -12.65 to -6.57, P < 0.001) and a -1.641 coefficient for non-ICU cardiac arrests (95% CI: -2.22 to -1.06, P < 0.001). Sensitivity analysis showed mixed results for PICU admissions, while zero-inflation Poisson analysis confirmed a reduction in non-ICU arrests. Conclusions: The deployment of pediatric RRTs is associated with fewer unexpected PICU admissions and non-ICU cardiopulmonary arrests, indicating improved PICU management. Further research using robust scientific methods is necessary to conclusively determine RRTs' clinical benefits.

Confined masonry (CM) is a construction system which consists of masonry wall panels enclosed by vertical and horizontal reinforced concrete confining elements. The presence of these confining elements distinguishes CM from unreinforced masonry system and makes this technology suitable for construction of structures in regions subjected to intense seismic or wind actions. CM construction has been used in many countries and regions, and has performed well in past earthquakes. The purpose of the paper is to review past research studies related to the seismic in-plane and out-of-plane behaviour of CM structures. The authors have identified the key design and construction parameters which were considered in past research studies and have performed statistical analyses to establish their influence on the seismic performance of CM buildings. For the purpose of this study the authors have compiled databases of previous experimental studies on CM wall specimens which were used for statistical analyses. Finally, the paper discusses research gaps and needs for future research studies which would contribute to the understanding of seismic behaviour and failure mechanisms of CM walls.

Building envelope can play a crucial role in building improvement efficiency and the adoption of Phase Change Materials (PCMs) coupled with transparent elements may (i) allow a better control of the heat flows from/to the outdoor environment, (ii) increase the exploitation of solar energy at building scale and (iii) modulate the light transmission to avoid glare effects. Starting from a literature review of experimental works, this research identifies the main possible integration of PCM in transparent/translucent building envelope components (in glazing, in shutters and in multilayer façade system) drawing a global picture potentials and limitations of these technologies. Transparent envelopes with PCMs have been classified from the simplest “zero” technology, which integrates the PCM into the double glass unit (DGU), to more complex solutions – with different numbers of cavities of the glass (TGU), different position of PCM layer (internal/external shutter), and in combination with other materials (TIM, aerogel, prismatic solar reflector, PCM curtain controlled by an electric pump). The results of the analysis are resumed in a SWOT (strengths, weakness, opportunities and threats) analysis table to underline strengths and weaknesses of transparent building envelope components with PCMs, and to indicate opportunities and threats for future research and building application.

Simulations of the pump response time refer to the determination of the time constant of the transient process when the flow and pressure change. The changes mentioned in the standards are precisely defined and prescribed by the "MIL-P-19692E" norms. The simulation showed that the time constants are within the permissible limits prescribed by these norms. The diagram shows the responses for the considered pump and for the case when the flow changes from Qn to Qmin and changes from Qmin to Qn. The time constants t1 and t2 are defined on the diagrams, with the parameters that the pump has. In addition, the standards define the pressure jump that occurs during the transient process as well as time constants. From the flow change diagram, it can be seen that the flow change is also very fast and takes place in time intervals shorter than 0.1 s. By evaluating the size of the time constants, t1 and t2, it can be concluded that they have a value below 0.05 s, which meets the regulations in that area. Also, the size of the jump pressure meets the regulations because it is only 1.2 M Pa above the nominal pressure.

This article is some review of results that were obtained at 2007-2021 years development of “The Information as Absolute” concept and the informational physical model, which is based on the concept; including a number of fundamental physical problems are briefly considered in framework of the conception and the model. Recently in physics there are several publications, that present lists of the problems. However, those lists are essentially incomplete, for at least two reasons. Firsts of all, a number of phenomena are studied traditionally by philosophy, and so corresponding problems are usually considered to be “metaphysical”. However, they relate also to some concrete physical phenomena. For example, physics evidently studies Matter, and so the metaphysical problems “what is ontology of Matter”, “what is “Space”, “Time” and a few other physical phenomena and notions as well, are really a Meta-physical problems “what does physics study?” There are other fundamental physical problems, which are not considered as such in physics, and are absent in the “fundamental problems lists”. Those include the problems, which really exist, yet are incorporated into standard physical theories, and so are fundamental “implicitly”, which in physics are “solved by default” ‒ and mostly erroneously. Note, though, that a number of “Meta-physical”, and concrete fundamental, problems more in detail are considered in the paper “The Informational Conception and Basic Physics”, https://arxiv.org/abs/0707.4657, v5 (2021), so this paper is, in certain sense, an expanded conclusion of this paper, which includes, correspondingly, more in detail consideration of some more general physical problems; and, besides, in this article, the problem “what are Gravity and Electric Forces” is essentially clarified comparing with the arXiv 2021 paper version above, and additionally initial model of Nuclear Force is presented. Besides, the concrete problem “What is Life”, and the rational cosmological model, where a few vague points in standard cosmology rather probably are rationally clarified, while the fundamental problem “matter – antimatter asymmetry” in Matter is solved with rather large probability, are considered, and one of recently published rather complete “lists of fundamental problems” is commented in Appendix.

Genes that affect adaptive traits have been identified, but our knowledge of the genetic basis of adaptation in a more general sense (across multiple traits) remains limited. We combined population-genomic analyses of evolve and resequence experiments, genome-wide association mapping of performance traits, and analyses of gene expression to fill this knowledge gap, and shed light on the genomics of adaptation to a marginal host (lentil) by the seed beetle Callosobruchus maculatus. Using population-genomic approaches, we detected modest parallelism in allele frequency change across replicate lines during adaptation to lentil. Mapping populations derived from each lentil-adapted line revealed a polygenic basis for two host-specific performance traits (weight and development time), which had low to modest heritabilities. We found less evidence of parallelism in genotype-phenotype associations across these lines than in allele frequency changes during the experiments. Differential gene expression caused by differences in recent evolutionary history exceeded that caused by immediate rearing host. Together, the three genomic data sets suggest that genes affecting traits other than weight and development time are likely to be the main causes of parallel evolution, and that detoxification genes (especially cytochrome P450s and beta-glucosidase) could be especially important for colonization of lentil by C. maculatus.

The field of water management is continually changing. Water has been subject to external shocks in the form of climate change and globalization. Analysis of water management is subject to disciplinary developments and inter-disciplinary interactions. Are these developments well documented in the literature? Initial observations on interdisciplinary literature suggest that results are fragmented, implying that a state-of-the-art review is needed. The objective of this paper is to close this gap by reviewing recent developments in water economics that address the increasing perceptions of water scarcity by looking first at changes in supply and quality of water, and then at impacts of climate change on water extremes. Among responses to such challenges, the paper identifies changes to water use patterns by including and co-managing water from different sources—surface and groundwater, wastewater, and desalinated water. Technological advancements also are among the resources that address water challenges. Water challenges reflect also on management of internationally shared water. A recent surge in scientific work identified international treaties as playing a significant role in water management. The paper reviews recently employed economic tools, such as experimental economics, game theory, institutional economics, and valuation methods. And finally, it explores modeling approaches, including hydro-economic and computable general equilibrium models that are being used to deal with water challenges.

In photolithography process, nanometer level precise, wavefront aberration models enable the machine to be able to meet the overlay (OVL) drift and critical dimension (CD) specifications. Software control algorithms take as input these models and correct any expected wavefront imperfections before reaching the wafer. In such way a near optimal image is exposed on the wafer surface. Optimizing the parameters of these models though, involves several time costly sensor measurements which reduce the throughput performance, in terms of exposed wafers per hour, of the machine. In that case, photolithography machines come across the trade-off between throughput and quality. Therefore one of the most common Optimal Experimental Design (OED) problems in photolithography machines (and not only) is how to choose the minimum amount of sensor measurements that will provide the maximum amount of information. Additionally, each sensor measurement corresponds to a point on the wafer surface and therefore we must measure uniformly around the wafer surface as well. In order to solve this problem, we propose a Sensor Marks Selection Algorithm which exploits Genetic Algorithms. The proposed solution first selects a pool of points that qualify as candidates to be selected in order to meet the uniformity constraint. Then, the point that provides the maximum amount of information, quantified by the Fisher based criteria of G, D and A-Optimality, is selected and added to the measurement scheme. This process though is considered "greedy", and for this reason Genetic Algorithms (GA) are exploited to further improve the solution. By repeating in parallel the "greedy" part several times we get an initial population that will be the input to our GA. This meta-heuristic approach outperforms the "greedy" approach significantly. The proposed solution is applied in a real life semiconductors industry use case and achieves interesting industry and academical results as well.

Magnetic resonance elastography (MRE) has revealed sexual dimorphism in brain stiffness in healthy individuals and multiple sclerosis (MS) patients. In the animal model of MS, experimental autoimmune encephalomyelitis (EAE), we showed previously that inflammation-induced brain softening was associated with alterations of the extracellular matrix (ECM). However, it remained unclear whether the brain ECM presents sex-specific properties that can be visualized by MRE. Therefore, we aimed here at quantifying sexual dimorphism in brain viscoelasticity in association with ECM changes in healthy and inflamed brains. Multifrequency MRE was applied to the midbrain of healthy and EAE mice of both sexes to quantitatively map regional stiffness. To define differences in brain ECM composition, gene expression of the key basement membrane components laminin (Lama4, Lama5), collagen (Col4a1, Col1a1) and fibronectin (Fn1) was investigated by RT-qPCR. We showed that the healthy male cortex expressed less Lama4, Lama5, Col4a1 but more Fn1 (all p < 0.05) than the healthy female cortex, which was associated with 9% softer properties (p = 0.044) in that region. At peak EAE, cortical softening was similar in both sexes compared to healthy tissue, with an 8% difference remaining between males and females during EAE (p < 0.001). Cortical Lama4, Lama5 and Col4a1 expression increased 2 to 3-fold in EAE in both sexes while Fn1 decreased only in males (all p < 0.05). No significant sex differences in stiffness were detected in other brain regions. In conclusion, sexual dimorphism in the ECM composition of cortical tissue in the mouse brain is reflected by in vivo stiffness measured with MRE and should be considered in future studies by sex-specific reference values.

The today competitive advantage of Ready-made garment industries depends on the ability to improve the efficiency and effectiveness of resource utilization. Ready-made garment industries have long historically adopted fewer technological and process advancement as compared to automotive, electronics and semiconductor industries. Simulation modeling of garment assembly line system has attracted a number of researchers as one way for insightful analysis of system behaviour and improving its performance. However, most of simulation studies have considered ill-defined experimental design which cannot fully explore the assembly line design alternatives and does not uncover the interaction effects of the input variables. Simulation metamodeling is an approach to assembly line design which has recently been of interest to so many researchers. However, its application in garment assembly line design has never been well explored. In this paper, simulation metamodeling of trouser assembly line with 72 operations has been demonstrated. The linear regression metamodel technique with resolution-V design was used. The effects of five factors: bundle size, job release policy, task assignment pattern, machine number and helper number on the production throughput of the trouser assembly line were studied. The increase of 28.63% of the production throughput was achieved for the best factors’ setting of the metamodel.

Abstract—In the present paper the static and fatigue analysis of plates with holes is conducted. Structures are made of 2D woven roving composites. The parametrization of convex holes is proposed. Experimental results of specimens without holes and with different shapes of notches under static and fatigue tensile loads are presented. The fatigue behaviour of structures is analysed with the use of the low cycle fatigue method. The attention is focused on the nonlinear deformations of 2D woven roving structures leading to the scatter of results. The analysis is supplemented by the numerical finite element modeling. The agreement between experimental and finite element modeling is very good. Since we do not intend to repeat in the abstract the review of the existing literature I would like to emphasize only that the present work is a continuation and extension of the results discussed in the literature – see the next sections of the paper. The finite element modeling of plates with holes is presented in details by Muc [1], Muc, Ulatowska [2] and Muc, Romanowicz [3] including also the problems of the accuracy. The mesh correctness and accuracy is discussed in Ref [2] where the results are compared to the analytical results illustrated in the Soviet Union literature. The experimental results and the form of specimens are shown by Pandita et al. [4] and they are fundaments for our present experimental investigations. Two parametrical description of static and fatigue behaviour of plates with holes characterizes the goal and the novelty of the paper. The analysis demonstrates how those parameters affect on the variations of static and fatigue failure loads. In addition, it should be emphasized that the fuzzy approach is employed herein to reduce the number of experimental data and to avoid statistical analysis of experimental results – see e.g. Muc [5]. In the mesoscale modeling and using the fuzzy approach it is possible to achieve a very good description of static and fatigue behavior of plates with convex holes subjected to tension.

The paper presents a proposal for an in-house mathematical model of a liquid flat-plate solar collector. The proposed model is a one-dimensional distributed parameter model enabling simulations of the collector operation under arbitrarily variable boundary conditions. The model is based on the solution of energy balance equations for all components of the collector. The formulated differential equations are solved iteratively using an implicit difference scheme. In order to obtain a stable numerical solution, it is necessary to use appropriate steps of the time and spatial division. These were found by comparing the results obtained from the model with the results of the analytical solution available in the literature for the transient state, which constitutes the novelty of the present study. The accuracy of the results obtained from the model was verified experimentally by comparing the measured and the calculated history of the fluid temperature at the outlet of the collector. The calculation of the collector time constant is proposed in the paper as an example of the model practical application. The results of the time constant calculation were compared with the values obtained experimentally on the test stand. This is another novelty of the presented research. The analysed collector instantaneous efficiency was then calculated for selected outdoor conditions. The presented mathematical model can also be used to verify the correctness of the collector operation. Comparing, on an ongoing basis, the measured and the calculated values of the fluid temperature at the collector outlet, conclusions can be drawn about the process of solar glass fouling or glycol gelling. The model's simplicity and the low computational demands enable such comparisons in an online mode.

The purpose of water treatment through ultraviolet (UV) radiation is to interrupt the development and multiplication of microorganisms by preventing their growth and reproduction.Ultraviolet treatment has become a very affordable solution to produce clean water of optimal quality in regions where access to drinking water is essential. The experimental water treatment unit is powered by a photovoltaic (PV) source. It incorporates a discharge lamp used to generate ultraviolet radiation, which is harnessed to address bacteriological issues related to water quality. This lamp is continuously powered by a photovoltaic (PV) source through an inverter and an electronic ballast. The water treatment system also includes a motor pump designed to draw contaminated water from the input reservoir, a flow control valve to adjust flow rates as needed, and a filter aimed at enhancing the quality of the contaminated water. The water circulates between the input reservoir (contaminated water) and the output reservoir (treated water) through the UV lamp. The relationship between the intensity of the UV lamp and the water flow rate can ensure an adequate water quality.

A quantitative analysis of X-ray emission from an electron cyclotron resonance (ECR) plasma was performed to probe the spatial properties of electrons having energy for effective ionisation. A series of measurements were taken by INFN-LNS and ATOMKI, capturing spatially and spectrally resolved X-ray maps as well as volumetric emissions from argon plasma. Comparing the former with model generated maps (involving space-resolved phenomenological electron energy distribution function and geometrical efficiency calculated using ray-tracing MC routine) furnished information on structural aspects of the plasma. Similarly, fitting a model composed of bremsstrahlung and fluorescence to the volumetric X-ray spectrum provided valuable insight into the density and temperature of confined and lost electrons. The latter can be fed back to existing electron kinetics models for simulating more relevant energies, consequently improving theoretical X-ray maps and establishing the method as an excellent indirect diagnostic tool for warm electrons, required for both fundamental and applied research in ECR plasmas.

A large body of evidence, replicated in many mouse models of Alzheimer Disease (AD), demonstrated the therapeutic efficacy of oral rapamycin. Administration of m-TOR inhibitors (mTOR-Is), early after the clinical onset, greatly diminished cognitive impairment, amyloid angiopathy, intracellular beta Amyloid and neurofibrillary tangles load. The daily intake of rapamycin has always been 2.24g/Kg/24h. In humans the maximal tolerated oral dose is a few milligrams/day, and at this dosage patients are severely immunosuppressed. Thanks to rapalogs’ scarce CNS-related side effects, we administered intracerebroventricularly (ICV) high doses of the mTOR-I everolimus in a mouse model of AD (3xTg-AD) without significant systemic effects. The instability of the liquid formulation at body temperature (BT) made the treatment very short. Nevertheless, the efficacy of the treatment was high and much longer lasting than expected. In order to set up a thermostable, translational liquid formulation of mTOR-Is, we loaded everolimus in distearoylphosphatidylethanolamine-polyethylene glycol 2000 (DSPE-PEG2000) micelles by the thin layer method. The formulation we obtained maintained over 95% of activity after 14 days at BT. We can envision short, potentially periodic ICV treatments in AD patients which replicate results obtained on animal models. The treatment could benefit also Tuberous Sclerosis and Multiple Sclerosis patients.

Pulmonary hypertension (PH) has a high mortality, and few treatment options. Adaptive immune mediators of PH in mice challenged with antigen/particulate matter (antigen/PM) has been the focus of our prior work. We identified key roles of type 2 and type 17 responses in C57BL/6 mice. Here, we focused on type 2 response related cytokines, specifically Resistin-like-molecule (RELM)α, a critical mediator of hypoxia-induced PH. Because of strain differences in the immune responses to type 2 stimuli, we compared C57BL/6J and BALB/c mice. A model of intraperitoneal antigen sensitization with subsequent, intranasal challenges with antigen/PM (ovalbumin and urban ambient PM2.5) or saline was used in C57BL/6 and BALB/c wild type or RELMα-/- mice. Vascular remodeling was assessed by histology, right ventricular (RV) pressure, RV weights and cytokines were quantified. Upon challenge with antigen/PM2.5, both C57BL/6 and BALB/c mice developed pulmonary vascular remodeling; these changes were more prominent in the C57BL/6 strain. Compared to wild type mice, RELMα-/- had significantly reduced pulmonary vascular remodeling in BALB/c, but not in C57BL/6 mice. RV weights, RV IL-33 and RV ST2-IL-33-receptor were significantly increased in BALB/c wild type mice, but not in BALB/c-RELMα-/- or in C57BL/6-wild type or C57BL/6-RELMα-/- mice. RV systolic pressures (RVSP) were higher in BALB/c compared to C57BL/6J mice, and RELMα-/- were not different from their respective wild type controls. In BALB/c mice, RELMα was a key contributor to antigen/PM2.5 induced pulmonary vascular remodeling, RV thickening and RV cytokine responses, highlighting the significance of the genetic background. The RELMα-/- animals demonstrated significantly decreased expression of RELMβ and RELM which makes these mice comparable to a situation where human RELMα levels would be significantly modified, as humans only have one RELM molecule.

Time-series analysis is a widely used technique across various fields and industries, as it helps in understanding, predicting, and forecasting the behavior of data points over time. These fields include but are not limited to finance, economics, healthcare, transportation, etc. In the case of this paper, we have focused on finance. Predicting future values of financial time series offers several benefits. Accurate forecasts can help investors make better decisions about their investments. To predict future values, deep learning algorithms are commonly used since it is an effective method with complex data. In this study, we conduct a study that investigates the use of different data pre-processing techniques on deep learning algorithms in predicting the time series values. To conduct this experimental study, we utilize an open source software, which using long short-term memory technique as the representative deep learning technique, published in github software code repository platform. With this study, we investigate the effects of autoencoder and discrete wavelet transform data pre-processing techniques in time-series prediction. We discuss the details of the experimental study and report our results. The results show that time series prediction (using backtesting methodology) without any data pre-processing leads to 12.6% for mean absolute percentage error. The results also show that, time series prediction with the data preprocessing techniques (Wavelet Transform and Stacked Autoencoder) lead to 3.4%

Laser Powder Bed Fusion (L-PBF)-based manufacturing is a growing area of research, with a particular focus on evaluating constraints in printed products. This research emphasises the importance of considering various factors—including mechanical properties and support structures—that influence the final product during the design phase. Specifically, the design of microchannel heat exchangers is highlighted, where all constraints are critical. This article will present a method for analysing channel pressure limitations and report findings about mechanical properties loss from examining tube porosity. This includes a summary of results and the establishment of an experimental device system.

This paper introduces an innovative theoretical framework for quantum-inspired data embeddings, grounded in foundational concepts of quantum mechanics such as superposition and entanglement. This approach aims to advance semi-supervised learning in contexts characterized by limited labeled data by enabling more intricate and expressive embeddings that capture the underlying structure of the data effectively. Grounded in foundational quantum mechanics concepts such as superposition and entanglement, this approach redefines data representation by enabling more intricate and expressive embeddings. Emulating quantum superposition encodes each data point as a probabilistic amalgamation of multiple feature states, facilitating a richer, multidimensional representation of underlying structures and patterns. Additionally, quantum-inspired entanglement mechanisms are harnessed to model intricate dependencies between labeled and unlabeled data, promoting enhanced knowledge transfer and structural inference within the learning paradigm. In contrast to conventional quantum machine learning methodologies that often rely on quantum hardware, this framework is fully realizable within classical computational architectures, thus bypassing the practical limitations of quantum hardware. The versatility of this model is illustrated through its application to critical domains such as medical diagnosis, resource-constrained natural language processing, and financial forecasting—areas where data scarcity impedes the efficacy of traditional models. Experimental evaluations reveal that quantum-inspired embeddings substantially outperform standard approaches, enhancing model resilience and generalization in high-dimensional, low-sample scenarios. This research marks a significant stride in integrating quantum theoretical principles with classical machine learning, broadening the scope of data representation and semi-supervised learning while circumventing the technological barriers of quantum computing infrastructure.