The development of hybridoma technology for producing monoclonal antibodies (mAbs) by Kohler and Milstein (1975) counts as one of the major medical breakthroughs, opening up endless possibilities for research, diagnosis and for treatment of a whole variety of diseases. Therapeutic mAbs were introduced three decades ago. The first generation of therapeutic mAbs of murine origin showed high immunogenicity, which limited efficacy and was associated with severe infusion reactions. Subsequently chimeric, humanized, and fully human antibodies were introduced as therapeutics, these mAbs were considerably less immunogenic. Unexpectedly humanized mAbs generally show similar immunogenicity as chimeric antibodies; based on sequence homology chimeric mAbs are sometimes more “human” than humanized mAbs. With the introduction of the regulatory concept of similar biological medicines (biosimilars) a key concern is the similarity in terms of immunogenicity of these biosimilars with their originators. This review focuses briefly on the mechanisms of induction of immunogenicity by biopharmaceuticals, mAbs in particular, in relation to the target of the immune system. The development of the hybridoma technology to produce monoclonal antibodies (mAbs) by Kohler and Milstein counts as one of the major medical breakthroughs of the 20th century. It opened endless possibilities, not only for research, but also to diagnose, prevent, and treat a whole variety of diseases .Initially this discovery led to the introduction of many mAbs in biomedical research and as diagnostic tools relatively fast, but their development as therapeutics was relatively slow. It took 11 years before the murine mAb OKT-3 was officially approved for the prevention of allograft rejection after transplantation  and anotThere were many reasons why only two mAbs were introduced into the clinic in the 17 years after the development of the technology by Kohler and Milstein. The main problem was that initially only murine derived mAbs were available for clinical use which lack of Fc-functions in humans that are important attributes for, for instance, anticancer activity . HoweverSeveral innovations have been introduced in the original hybridoma-based technology by genetic engineering . It enabTransgenic animals expressing the human Ig locus, phage display technologies and different methods to immortalize human B cells allow mAbs based on completely human derived DNA sequences . The expHumanization has reduced the sometimes extreme immunogenicity associated with murine mAbs, but also the so-called human mAbs have shown to induce antibodies that sometimes have clinical implications . In thisThe persistence of immunogenicity of human mAbs is no surprise and reflects the experience of over 150 years with biologics as medicines . The firHowever, the second generation of medically-used biologics which were natural products of human origin introduced in the 50-ties of the last century like growth hormone extracted from human pituitary glands and the plasma derived clotting factors, also proved to be immunogenic in the majority of patients. Their immunogenicity was explained by the lack of immune tolerance for these biologics in the children who needed growth hormone or a clotting factor as substitution because of an inborn deficiency for these proteins.The introduction of third generation of biologics during the seventies and eighties of the last century, produced by genetic engineering technologies allowing the production of human proteins, like the human insulins, epoetins, interferons, and others intended for use in patients with a normal immune tolerance to these products.Surprisingly, the great majority of these products appeared to be immunogenic in some patients, with an incidence varying between <1% up to the majority of patients depending on the product. It then became clear that there are two different mechanisms by which these anti-drug antibodies (ADA) are induced by biopharmaceuticals . These tIf the biopharmaceutical is of foreign origin, as is the case with animal derived antisera, the antibody response is comparable to a vaccination reaction. Often a single injection with a “non-human” product is sufficient to induce high levels of neutralizing antibodies. Like the antibodies induced by a vaccine, these antibodies may persist for a considerable length of time. Another hallmark of this type of immunogenicity is the induction of memory cells leading to a booster reaction seen when a patient is re-challenged with the product asparaginase and streptokinase, both of microbial origin, are examples of biopharmaceuticals which are in clinical use today which show this “vaccine” type of immunogenicity.However, the great majority of biopharmaceuticals are homologues of human proteins of which there is, in general, a high level of immune tolerance in patients. To break B cell tolerance and induce antibodies, prolonged exposure to proteins is necessary. It may take months of chronic treatment before patients start producing antibodies directed against the homologues protein. This type of immune reaction is also milder compared with the immune reaction to non-human proteins. The antibodies are mainly only binding and their clinical effect in most cases is minimal. They disappear relatively quickly when treatment is stopped and there is no memory reaction after re-challenge.To induce a classical “vaccine-like” immune reaction a degree of non-self is necessary, which is mainly determined by the amino-acid sequence and secondary and tertiary structure of the protein. It is based on the classical activation of the immune system by immune competent cells presenting epitopes of the non-human proteins by their MHC molecules. This activates T cells, which help to activate B cells to produce antibodies. Initially, IgM antibodies of broad specificity and relatively low affinity are formed. By isotype switching and affinity maturation, B cells’ clones will be induced, capable of producing IgG molecules with high affinity as well as memory B cells. As the trigger for this type of immune response is within the structure of the molecule, this immunogenicity can be considered an intrinsic property of the biopharmaceutical.Basic research, mainly in immune tolerant transgenic mice and in studies with biopharmaceuticals in clinical use showing immunogenicity, indicated that process and product related impurities are triggers for breaking B-cell tolerance . As thesHowever, the most convincing extrinsic immunogenic determinant identified is protein aggregation. Apparently aggregates may present as the multimeric array form structures capable of directly interacting with, and activating B cells . This meWhen tolerance is broken by a biopharmaceutical, the antibody response is often weak with low levels antibodies with low affinity. As it does not need the activity of T-helper cells, isotype switching and affinity maturation is limited and, also, no memory cells are induced. In most cases prolonged treatment is necessary for the antibodies to appear and often the antibody response declines upon further treatment.This distinction between the vaccine type fulminant immunogenicity reaction and the more restricted and weak antibody response based on breaking tolerance is not absolute: the level of tolerance to proteins, as well as the ability to respond to an immunogen, differ between individual patients. As with many biopharmaceuticals both types of reactions can be seen in the patient population. In hemophilia A the immunogenic response is dependent on the genetic defect in the factor VIII gene . If the Box 1Nature of the BiopharmaceuticalSize and structural complexitySequence variation from endogenous proteinAggregatesPost-translational & chemical modification .Neoepitopes due to denaturation or fragmentationAdjuvant potential of inactive ingredientsOther impurities Target Disease and PopulationPatient characteristics such as genetic backgroundComorbidityNatural tolerance to proteinPre-existing immunodeficiencyUse of immunosuppressive drugs or chemotherapy Treatment RegimenRoute of administrationDoseFrequency of treatmentDuration of treatmentThe changing pattern of immunogenicity seen during the different steps of humanization of mAbs used resembles the differences seen in immunogenic response of the different generations of biopharmaceuticals . The strα-1,3-galactose, of mAbs produced in mammalian cells, like CHO cells, has been implicated in hypersensitivity reactions. However, these antibodies were not induced by the mAb but were pre-existing “natural”’ IgE antibodies, induced by an endemic tick infection or other pre-exposure galactose-α-1,3-galactose, explaining the regional distribution of the hypersensitivity reaction [In contrast with the expectations, mAbs completely derived from human sequences (fully human antibodies) proved to be still immunogenic. Thus, other factors than the presence of murine sequences determine the immunogenicity of mAbs. Unlike most other biopharmaceuticals, most therapeutic mAbs (depending on the IgG subclass) have immune modulating activity residing in their Fc parts. Fc functions include macrophage and complement activation, which may boost an antibody response. Removal of N-linked glycosylation at the Fc part of the immunoglobulin reduces these functions and was shown to lead to a diminished immunogenicity . Howeverreaction .Antibodies induced by humanized mAbs are predominantly directed to the CDR-regions, which determine their specificity. These anti-idiotypic antibodies may represent the natural antibodies, which, according to the network theory of Jerne are formed to regulate the antibody responses . The antWhether the immunogenicity of mAbs can also be explained by the extrinsic immunogenicity of monoclonal therapeutic products has not been studied in as much detail as with other biopharmaceuticals, like epoetins and interferons.There is good experimental evidence about the importance of aggregation. Association between aggregates in immunoglobulin products and immunogenicity (and the induction of tolerance by de-aggregated immunoglobulin products) was already described more than 50 years ago . There aIn addition to the intrinsic and extrinsic immunogenicity of monoclonal antibody products, a number of treatment and patient characteristics may modulate this immune response. An increase in the number of injections and higher doses are associated with a higher immune response, but this seems not necessarily true for all monoclonal antibody products. In some cases, chronic treatment and higher doses have been reported to be less immunogenic than episodic treatment and/or lower dose . The indAs with other biopharmaceuticals, the subcutaneous route of administration of mAbs is linked with a higher incidence of immunogenicity than and the intravenous route of administration . AdditioEstablishing the biological and clinical consequences of immunogenicity of biopharmaceuticals is hampered by both the lack of standardization of the assays and a consensus when to consider a patient antibody positive. This makes it difficult to compare results from different studies and also to develop guidelines about the proper follow-up of antibody positive patients. The antibody response varies greatly between individual patients. A low level of binding antibodies during a short period of treatment has no clinical relevance, but a persisting high level of neutralizing antibodies leads inevitably to a complete loss of efficacy. However, the problem lies in the majority of antibody positive patients showing a response between these two extremes. In diseases like multiple sclerosis and cancer, their unpredictable clinical course and the sometimes relatively modest clinical effects of the biopharmaceuticals are additional hurdles for unambiguously showing loss of efficacy by antibodies.Antibodies directed to biopharmaceuticals have either no clinical effect, modulate efficacy, cross-neutralize endogenous proteins, or have general immune effects . InducedThere have been reports that patients making antibodies clinically respond better to therapy with biopharmaceuticals than patients without antibodies. This has been explained by the presence of low affinity antibodies during the initial antibody response extending the half-life of and by increasing the exposure to the therapeutic protein. The enhanced efficacy can also be an epiphenomena: An immunogenic response to a biopharmaceutical could also be a sign of an active immune system contributing to a better response to therapy. Also a better response to the therapeutic effects of mAbs in some cancer patients with antibodies has been reported and was explained by an anti-idiotypic response to the therapeutic monoclonal antibody directed to tumor antigens thereby enhancing the antitumor response .The most serious clinical effect of immunogenicity has been observed with biopharmaceuticals which that are homologous to unique endogenous factors. The antibodies can cross neutralize these (endogenous) factors as has happened with epoetins, which induced neutralizing antibodies neutralizedto erythropoietin, essential for red blood cell maturation, leading to Pure Red Cell Aplasia (PRCA) . AlthougThe most important clinical effects of immunogenicity of mAbs are infusion reactions (anaphylactoid) and serum sickness . There iThe standard approach for detecting antibodies induced by biopharmaceutical in sera of patients is to first screen with a highly sensitive assay for binding antibodies . This asThe preferred format for screening for binding antibodies is the bridging assay. In this type of assay the biopharmaceutical is used to capture the antibodies present in the patient sera and the captured antibodies are detected by adding labeled biopharmaceutical as a probe. Such bridging assays are independent of the type of antibodies to be detected, enabling the use of antisera induced in animals as a positive control. The same assay can be used for the determination of antibodies in treated patients, as well as in animal studies. Since the bridging assay only detects binding by proteins with double binding sites, it is more specific than the standard ELISA type of binding assay. However, the bridging immune assay may miss low affinity IgM type of immune response because of the washing steps involved. Therefore, for detection of early immune responses, biosensors applying surface plasmon resonance technology are advocated instead of ELISA type assays. In addition, it may be important to assay for the presence of neutralizing antibodies , which mAny assay for antibodies induced by biopharmaceuticals is sensitive for drug circulating at the time of sampling which may interfere with the assay. This is especially the case for therapeutic because of their relative long half-life of, the presence of natural antibodies, receptors, and immune complexes, which all may interfere with assay results and be the cause of false negative results.Over the years, many drug-tolerant assay formats have been developed to measure induced antibodies in the presence of large amounts of drug . AntibodSeveral new techniques to measure induced in the presence of drugs have been developed in the last few years. An example is the affinity capture elution ELISA (ACE) in which the induced antibodies from acidified serum samples are captured by immobilized drug and the excess of drug is washed away. In a second acidification step, the antibodies are released and absorbed onto a second carrier and detected in an electro-chemo-luminescence (ECL) bridging assay. Other examples of test formats are the biotin-drug extraction with acid dissociation (BEAD) assay the sample pre-treatment bridging ELISA, the acid dissociation radioimmunoassay, the temperature-shift radioimmunoassay, and the homogeneous mobility shift assay (HMSA).Due to the difficulties in their validation, in medical practise these assays are hardly used for clinical decision-making. As alternative with mAbs, drug trough levels are being measured as a marker for clinical activity of the drug .The potential immunogenicity of biopharmaceuticals was one the main reasons behind the dedicated regulatory biosimilar pathway for copy products after the patents and market exclusivity of the original biopharmaceuticals expire. The main difference with the generic pathway for copies of small molecules is the need for clinical trials. Biopharmaceuticals were considered too complex and heterogeneous to be completely characterized. Additionally, original products and their copies could, therefore, never be shown to be identical. To get a marketing authorization as a biosimilar, the copy needs to be similar in physical-chemical and biological characteristics and this similarity needs to be confirmed by (pre)clinical studies. In these clinical studies the immunogenicity between the original and biosimilar candidate always needs to be studied. The need for clinical to evaluate the immunogenicity is based on the notion that immunogenicity is closely linked to product characteristics as glycosylation and impurities in which the biosimilar and reference product are most likely to differ.There have been 18 biosimilar mAbs authorized in the EU by September 2018. Biosimilars and original biopharmaceuticals share the same amino acid sequence and their secondary and tertiary structure needs to be similar. So the intrinsic immunogenicity of the biosimilar will be comparable with the original product. If there is a difference between the two, it will most likely caused by differences in the extrinsic immunogenicity, like the level of impurities mainly aggregates.In


Passive acoustic target detection has been a hot research topic for a few decades. Azimuth recording diagram is one of the most promising techniques to estimate the arrival direction of the interested signal by visualizing the sound wave information. However, this method is challenged by the random ambient noise, resulting in low reliability and short effective distance. This paper presents a real-time postprocessing framework for passive acoustic target detection modalities by using a sonar array, in which image processing methods are used to automate the target detecting and tracking on the azimuth recording diagram. The simulation results demonstrate that the proposed approach can provide a higher reliability compared with the conventional ones, and is suitable for the constraints of real-time tracking. The passive sonar detection technique is important for ocean exploration. As shown in (a)Target space: this space is mainly composed of the target incident signal source and the actual environment. The DOA estimation systems capture the underwater acoustic information via some sensors, e.g., optic, pressure, or vector hydrophones.(b)Observation space: mainly refers to the use of arrays placed in space according to certain rules  in advance to obtain the array information of the target incident signal source.(c)Estimation space: the parameter information of the target signal source obtained via the sonar array is extracted by the DOA estimation algorithm.Direction of arrival (DOA) estimation is a crucial topic in the field of passive sonar information processing ,2,3. ItsThe conventional beamforming (CBF) method is recognized as one of the earliest and classical DOA estimation algorithms for sensor arrays, which is also commonly known as the Bartlett beamforming method ,5,6,7. IBased on the CBF-like techniques, azimuth recording diagram is developed to facilitate DOA estimation by visualizing the received signal information. As shown in Due to its benefits of stability and convenience, this technique is widely used. However, detecting the target on the diagram by using naked eyes is far from easy, because the received signal of a sonar array is distorted by the ambient noise, which results in a large number of random image noises, especially in a low SNR  environment ,12,13. A(a)The first step of the postprocessing framework is to find the weak trajectory inundated with the noise on the diagram quickly and accurately. This paper realizes the automatic trajectory detecting via template matching. To this end, we propose a feasible trajectory template generation method allowing users to customize the template set for different requirements.(b)Pattern enhancement is the second step. Conventional target tracking methods based on the azimuth recording diagram use the local power optima of the beams performed with different arrival directions as the patterns to track, which is easy to deviate from the trajectory due to the influences of ambient noise, so we enhance the trajectory patterns by using spatial separation methods, which significantly facilitates the tracking tasks.(c)Finally, the pattern enhancement method presented in this paper may lead to the azimuth migration if the target direction varies fast. An azimuth correction strategy is therefore conceived to improve the accuracy of the DOA estimation.Our work focuses on the explorations of robust acoustic target localization methods. This paper is an extension of our previous work presented in the ICSIP 2019 . It presThe experiment of this work is conducted by the simulated data. The proposed method is evaluated by comparing with the conventional detecting and tracking technique. The simulation results demonstrate that the proposed approach has a high stability and reliability by suppressing noise when tracking target with a strong Gaussian white noise, and its efficiency meets the real-time data processing requirements.The reminder of this paper is organized as follows. t is time, n is the additive noise. The underwater signal propagation can be modeled as. et al.  defined L dominant discrete paths. Equation  is a simEquation , we can Equation  to(3)r beamformer is a natural extension of the classical Fourier-based spectral analysis  to sonarW is constrained to To obtain a non-negative solution, the norm of i-th element of f is the frequency of the baseband signal, c is the sound velocity. Now, the array data can be visualized as the azimuth recording diagram by computing the short-time power with Equations ((a)for all the directions of arrival, compute the steer vectors Equation , then thEquation ;(b)for all the weight vectors, compute the expectations of the output power with Equation ; and(c)perform the azimuth recording diagram by establishing a time-azimuth space coordinate system, in which the image intensity is used to represent the power level of the synthetic signals over time and azimuth.quations –9). The. Thea(θ)The first step of the proposed postprocessing framework is to detect the trajectory automatically. From the view point of image pattern recognition, detecting the target via azimuth recording diagram is a pattern detection task, and the interested patterns are those trajectories performed by the power peaks. We address this problem by using the template matching technique.The preliminary preparation for template matching is to establish a suitable matching template set. To do this, some parameters of the sonar systems should be provided by the users: (a) the minimum effective distance G, which contains all two-dimensional trajectory templates. The templates D is the distance that the target moves from Next, initialize the template set t denote azimuth and time, respectively. Because the acoustic target usually moves slowly, we hypothesize that its azimuth changes linearly over time and describe the corresponding trajectory asA and B are the parameters of the linear model to be computed. As shown in The y-aixs of u and v correspond to the frequencies of the diagram within the different dimensions. With inverse Fourier transformation, the instantaneous output of the filter at We base the target trajectory detection on the two-dimensional (2-D) matched filter. Suppose that the transfer function and impulse response of the matched filter are Now we have the instantaneous output signal-to-noise ratio (SNR) of the filter asSuppose Equation  can be sThe optimal matched filter can be obtained by maximizing Equation . AccordiThe 2-D matched filter of Equation  represenM from the screen of the diagram. M is essentially a matrix that has the same row size with the template M correspond to the angle ranging from The azimuth recording diagram is updated snap by snap in real-time applications. As shown in M is spatially filtered. According to the optimal filters presented in Next, As shown in Equation  includesEquation  and θ′ iThe underwater acoustic target azimuth recording diagram is essentially a fusion of useful information and interference noise, so it can be projected into useful information and interference noise subspaces. This paper enhances the azimuth recording diagram using principal component analysis (PCA), which has been used in the sonar or radar systems ,23,24,25k singular values are kept to reconstruct As shown in s method ,27. The M into signal subspace, and the projected matrix t. The principal component map P of the diagram shown in Equation  projectsU and V of M are computed by decomposing Now, we can start to track the target trajectories. The acoustic target is used to being automatically tracked in the azimuth recording diagrams by searching for the maximum power of the received signal over the azimuths, then the corresponding azimuth is considered as the current target azimuth. Despite high stability, the peaks of PCA spectra cannot be considered as the real azimuth of the sound source, because enhancing the azimuth recording diagrams with PCA is essentially to alter the optimizing function from maximizing the power into maximizing the power dependency within a certain period, resulting in the tracking migrations. More precisely, the singular value vectors G contains 17 2-D matching templates, and each one corresponds to a change state of target azimuth in the system response time First, a template set of target azimuth trajectory is established by using the method proposed in In this subsection, we evaluate the proposed target tracking method with simulated data. Three target azimuth trajectories see  are firsM is reset as 40 s. M with red box and zoom in it in The experiment is formed within the environment of SNR = −14 dB, and the time period of the size of ROI M can be considered as the unique principal component, which corresponds to the target subspace. Next, the target tracking stability is evaluated by comparing the tracking results of the conventional and the proposed methods at different noise levels. We simulate the ambient noise with the white Gaussian noise. The variances of the noise are set as With the increasing of the noise level, the gap of the stability performance between the original and proposed methods becomes more and more significant. At SNR = −14 dB, we can see that the tracking result of the proposed method shown in Finally, the acoustic target is lost in the PCA-enhanced diagram when SNR = −28 dB see j. OveralAs discussed in We quantify the accuracy performance by measuring the mean absolute deviations of each running within different SNR environments. In order to obtain an unbiased conclusion, the measuring process is repeated three times and the average results are considered as the azimuth errors at different noise levels. Within the SNR measure scope of Acoustic target tracking is a typical real-time application, being constrained by the time interval of the data sampling. In this paper, the processing time of each snap must be shorter than the snap interval if the real-time processing capacity is desired. This subsection estimates the running time of the proposed method. We base the algorithm implementing on Matlab 2017b within 64-bit Windows-10 operation system. The processor is Inter (R) Core (TM) i7-8550U, CPU @1.80 GHz. Because the extraction process of PCA spectrum possesses high data dependency, resulting in low parallelism, we do not make any parallel optimizations on the final implementation.original” performs the target tracking directly on the original azimuth recording diagram without any enforcements. “error_correcting” optimizes the tracking results of the “original” version by using the proposed error correcting method. “pca_only” tracks the target in the PCA-enforced diagram without error correcting. Finally, “proposed” version combines the PCA enforcement and error correcting.The running time measurement includes the PCA enforcement and tracking processes of each snap. In This paper presents a post-framework for the azimuth recording diagram based acoustic target detection and tracking. The presented approach successfully realizes automatic target detections and highly robust target tracking by incorporating the image processing methods into the passive sonar information processing modalities. First, we base the automatic target detection on the 2-D template matching. A feasible target trajectory template generation method is developed, allowing for specializing the template set for different sensor array designs. Next, inspired by the idea of separating the array signal into the signal and noise subspaces, the target trajectories are significantly enhanced. Based on the separation of useful information subspace obtained by singular value decomposition, the stability of target tracking is greatly improved. Additionally, we find that the azimuth migrations constantly occur if only the PCA spectrum is used. This is because the PCA spectrum transform alters the azimuth tracking constraint from energy optima to that of the dependency of the recorded azimuths. An error-correction strategy is therefore specifically designed by combining the PCA-enhanced and original azimuth recording diagram. The simulation experiments demonstrate that the proposed method can greatly improve the stability of the azimuth tracking technique in underwater acoustic applications.In the future, improvements will be made regarding the accuracy of azimuth tracking. Additionally, the proposed method will be further evaluated in sea trials.


Ground-penetrating radar (GPR) is a kind of high-frequency electromagnetic detection technology. It is mainly used to locate targets and interfaces in underground structures. In addition to the effective signals reflected from the subsurface objects or interfaces, the GPR signals in field work also include noise and different clutters, such as antenna-coupled waves, ground clutters, and radio-frequency interference, which have similar wavelet spectral characteristics with the target signals. Clutter and noise seriously interfere with the target’s response signal. The singular value decomposition (SVD) filtering method can select appropriate singular values and characteristic components corresponding to the effective signals for signal reconstruction to filter the GPR data. However, the conventional time-domain SVD method introduces fake signals when eliminating direct waves, and does not have good suppression of random noise around non-horizontal phase axes. Here, an SVD method based on the Hankel matrix in the local frequency domain of GPR data is proposed. Different numerical models and real field GPR data were handled using the proposed method. Based on the power of fake signals introduced via different processes, qualitative and quantitative analyses were carried out. The comparison shows that the newly proposed method could improve efforts to suppress random noise around non-horizontal phase reflection events and weaken the horizontal fake signals introduced by eliminating clutter such as ground waves. Ground-penetrating radar (GPR) is a geophysical method using high-frequency electromagnetic waves to detect and locate targets and interfaces in underground structures . With thThe clutter and the target signals appear in the same time window and have the same spectral characteristics as the target signals, interlacing each other. The strong direct wave and the ground reflection signal mask the effective reflection signals of shallow targets, and reflected signals of objects on the ground and their multiple waves may also cover some effective reflection signals, affecting the detection of targets and interfaces. Random noise is generally poorly correlated, and its energy is generally weak when there is no strong electromagnetic interference from communication equipment, as the background distributed in the GPR data. The effective reflection signal is interfered with if the energy of the target reflection signal is weaker than that of the random noise. In general, the clutter and random noise in GPR data seriously affect the recognition of effective reflection signals of targets and interfaces; thus, it is necessary to adopt filter methods to eliminate these interferences after obtaining the measured GPR data. Furthermore, filtering methods cannot affect the response of the targets and must reduce the influence on effective signals as little as possible to ensure the effectiveness and accuracy of exploration using GPR.Singular value decomposition (SVD) provides a convenient way of decomposing a matrix, which perhaps contains some data we are interested in, into the multiplication of three simple matrices, and with further decomposition, these three multiplied simple matrices can be written as the addition of various components with different degrees of linear correlation weighted by singular values . GPR sigX, and there are m traces in the GPR data and n sampling points in every trace (assuming that n > m). According to the theory of SVD, the matrix X can be written asU and V are the left singular and right singular orthogonal matrices, respectively, where the size of U is n × n and the size of V is m × m; S is a diagonal matrix with a size of n × m; the elements σs (1 ≤ s ≤ m) of matrix S are the singular values of matrix X; and σ1 ≥ σ2 ≥ … ≥ σm > 0.Let us assume the two-dimensional (2D) GPR data are denoted by s-th diagnostic component of matrix X with the same size as X. In general, several front singular values contribute largely to matrix X as the decreasing order of singular values. According to the characteristics of the GPR signal, the first few singular values correspond to components denoting the direct wave, reflected signals of the horizontal interface, and their multiple waves with strong linear correlation among the traces; and the smaller singular values correspond to components denoting the random noise with almost no correlation. Thus, matrix X can be written asEquation (1) can be written ask1–k2) which denote the effective signals to reconstruct the GPR data matrix, before getting the GPR data without clutter and random noise. To eliminate clutters with strong linear correlation among the traces, we usually set k1 = 1, and, to suppress random noise, we usually delete the smaller singular values and preserve the preceding few larger singular values. It is important to note that, if there are horizontal interfaces underground, the reflected signals of these may also be eliminated when eliminating the direct wave. In this case, it may be an effective method to district the GPR profile and then use the SVD method.We can select the appropriate singular values (m traces in each frequency slice of the frequency domain denoted by t ≤ m) can be arranged in a Hankel matrix:The Hankel matrix is a matrix in which each ascending skew-diagonal from left to right is constant; thus, if the elements of the first column and last row are determined, the whole matrix can be determined. According to the characteristics of the Hankel matrix, we can arrange the GPR data in a slice of a Hankel matrix, and carry out the SVD algorithm for the Hankel matrix to denoise. This algorithm can enhance the auto-correlation of the non-horizontal phase axis and reduce the auto-correlation of the horizontal phase axis or the horizontal part on the non-horizontal phase axis (if it exists). The SVD algorithm can decompose the matrix into the addition of various components with different degrees of linear correlation weighted by singular values. Hence, the SVD method based on the Hankel matrix can improve the suppression of random noise around the non-horizontal phase axis and weaken the horizontal fake signals produced by eliminating the direct wave. The GPR data with The processes of suppressing noise with the SVD method based on the Hankel matrix in the local frequency domain are listed below.GPR data within a local window (window size = 3) sliding in the time domain are extracted and Fourier transformed.p = m/2 to ensure, as much as possible, that H is a square matrix.A frequency slice in the bandwidth is extracted to form the Hankel matrix, whereby H, and appropriate singular values are selected to reconstruct the Hankel matrix. Attention needs to be paid to the complexity of the signal data in the frequency domain; thus, transposition of the right singular vector of the SVD in the frequency domain is conjugate.SVD is applied to The Hankel matrix recovers the data in a frequency slice.The same process is repeated for every slice in the frequency domain; then, the inverse Fourier transform is used to get the noise-suppressed data in the time domain.In this paper we tested three models using a numerical simulation to compare the conventional time-domain SVD method and the SVD method based on the Hankel matrix in the local frequency domain. Then, real field data obtained from an underwater archaeological investigation and an airport runway evaluation using GPR were also handled using the two SVD methods, as well as the mean-trace-removing method.Firstly, a simple model with a horizontal interface was used to test the noise-suppressing abilities of the time-domain SVD method and the SVD method based on the Hankel matrix in the local frequency domain. y-axis), where many fake signals were introduced  and 0–1 m (x-axis) of the profile were seriously damaged because the linear correlation of these regions was enhanced using the Hankel matrix; hence, when eliminating the clutter, these regions were damaged. Nevertheless, when using the new method to suppress noise, the deep effective signal with the curved phase axis was better preserved than when using the time-domain SVD method; thus, the deeper signal was distinguished more easily.We carried out both methods to eliminate the direct wave and suppress random noise. We carried out both methods to eliminate the strong direct wave and the reflected signal of the surface, and to suppress random noise. GPR is widely used for archaeological investigation on land because it transmits non-destructive electromagnetic waves into the ground without interference on surrounding cultural relics, and it sends images of the targets in shallow subsurfaces with high lateral and vertical resolution. According to the research of Qin and Zhao et al. , GPR cant = 55 ns. We needed to eliminate the direct wave and the reflected wave of the ground surface with strong auto-correlation in the upper region of the profile using the proposed method. In the lower region, we first extracted the clutter from the hangar ceiling using the proposed method and selected the appropriate singular values, before subtracting the clutter data from the lower region. Finally, we merged the upper and lower regions to get the profile in y-axis) and 0–10 m (x-axis) of the profile in Compared with the conventional time-domain SVD method and mean-trace removing, the SVD method based on the Hankel matrix in the local frequency domain of GPR data could weaken the horizontal fake signals introduced by eliminating the direct wave, and it could improve suppression of random noise around non-horizontal phase reflection events. The re-constructed GPR profile using the new SVD method could, thus, provide more accurate results. However, the comparison of the simple-layer model experiment also revealed that the newly proposed SVD method is not effective when removing noise, and results in little damage to the effective signals. When the energy of the effective signal is not very weak, this method is acceptable to a certain degree. In some complex cases, it may be an effective method to divide the GPR data into several regions to suppress specific noise, such as interference clutter from ground objects. The elimination of clutter (ground objects) in the GPR detection of an airport runway was successfully applied.The SVD method based on the Hankel matrix in the local frequency domain needs to be optimized in future work to achieve better filtering when eliminating clutter, to improve the suppression of random noise, and to weaken the damage to effective signals.


Energy efficiency and end-to-end delay are two of the major requirements for the monitoring and detection applications based on resource-constrained wireless sensor networks (WSNs). As new advanced technologies for accurate monitoring and detection—such as device-free wireless sensing schemes for human activity and gesture recognition—have been developed, time synchronization accuracy becomes an important requirement for those WSN applications too. Message bundling is considered one of the effective methods to reduce the energy consumption for message transmissions in WSNs, but bundling more messages increases the transmission interval of bundled messages and thereby their end-to-end delays; the end-to-end delays need to be maintained within a certain value for time-sensitive applications like factory monitoring and disaster prevention, while the message transmission interval affects time synchronization accuracy when the bundling includes synchronization messages as well. Taking as an example a novel WSN time synchronization scheme recently proposed for energy efficiency, we investigate an optimal approach for message bundling to reduce the number of message transmissions while maintaining the user-defined requirements on end-to-end delay and time synchronization accuracy. Formulating the optimal message bundling problem as integer linear programming, we compute a set of optimal bundling numbers for the sensor nodes to constrain their link-level delays, thereby achieving and maintaining the required end-to-end delay and synchronization accuracy. Extensive experimental results based on a real WSN testbed using TelosB sensor nodes demonstrate that the proposed optimal bundling could reduce the number of message transmissions about 70% while simultaneously maintaining the required end-to-end delay and time synchronization accuracy. In a typical wireless sensor network (WSN) based on lots of battery-powered sensor nodes, minimizing the energy consumptions at the sensor nodes is critical to the service time of the WSN. Considering that the radio activities consume the most energy at sensor nodes, reducing the number of message transmissions is key to saving the energy ,2, and tEnergy-Efficient time synchronization scheme based on Asynchronous Source Clock Frequency Recovery—throughout the paper—leverages data bundling to further reduce the energy consumption in terms of the number of synchronization message transmissions; thanks to the reverse two-way message exchange scheme adopted in EE-ASCFR, the time synchronization is done at the head node and the corresponding synchronization data are bundled together with measurements into a bundled message at a sensor node. Consequently, the time synchronization accuracy is tied to the interval of the bundled message transmissions from the sensor node to the head node, i.e., the synchronization interval (SI). This means that the number of measurement data in a bundled message is linked to the interval of the bundled message transmissions and thereby not only affects the aforementioned E2E delay, but also the time synchronization accuracy. In such a case, we need to optimize the number of bundled messages under the constraint of E2E delay and time synchronization accuracy in achieving higher energy efficiency.Note that, for most long-term monitoring and detection applications in WSNs, energy-efficient and high-precision time synchronization is crucial to ordering and analyzing the data measured over a long period of time. For instance, in human activity and gesture recognition based on the novel device-free wireless sensing ,19, the In this paper, we formulate the aforementioned bundling optimization problem as integer linear programming (ILP), where the number of bundled messages for each sensor node is optimized while jointly satisfying the user-defined performance requirements on E2E delay and time synchronization accuracy. In this way, we can further reduce the energy consumption through data bundling while meeting the requirements.The rest of this paper is organized as follows: Most WSNs have the fundamental characteristics of limited resources, multi-hop communication, large scale and dynamic environments . To achiIn the literature, diverse methods across different layers have been proposed to improve the energy efficiency: transmission power control and multi-channel communication in the physical layer ,31,32,33The data bundling method employed in this paper belongs to the category of packet payload size adaptation since tuning the bundling number directly affects the packet payload size. Note that data bundling is a mature and effective method that has been leveraged in both the conventional optical burst switching  and the i with respect to the reference clock t of the head node. Since the hardware clocks of the sensor nodes have different clock frequency ratios and clock offsets with respect to the reference clock due to their coarse crystal oscillators, the following equation is employed in EE-ASCFR to represent the hardware clock of the sensor node i: for kth synchronization is denoted by kth synchronization are described as To fulfill the desired requirements of energy efficiency and synchronization accuracy, many schemes have been proposed such as ,24,25,26However, because the synchronization accuracy (SA) is affected by SI as illustrated in The energy consumption caused by message transmissions could be drastically reduced by the aforementioned data bundling procedure as demonstrated in m, would be relatively small  in the regular direct forwarding method. However, due to the bundling procedure in the intermediate sensor nodes, the E2E delay could be as large as multiples of measurement interval. Nonetheless, the bundling procedure is shown to be quite efficient in conserving energy by reducing the number of message transmissions as shown in Simultaneously meeting the requirements for the three performance metrics of energy efficiency, E2E delay, and synchronization accuracy is not possible due to their relationship discussed in To jointly meet the three performance requirements, comprehensive optimizations should be taken so that overall satisfactory performances among those three requirements could be achieved. In this paper, a new approach for the bundling number optimization for each sensor node is proposed to fulfill the requirement of maintaining E2E delay and synchronization accuracy while minimizing the message transmissions.N sensor nodes, the energy consumption i is modeled as follows: For i, respectively, and i. The coefficients In a WSN with If we apply data bundling, Equation  can be mWith the model for energy consumption caused by message transmissions, we can increase the network energy efficiency by minimizing the total energy consumption for message transmissions  bus loading delay Equation  could bealues in .The link delay in Equation  could beNote that the service delay i 16), the Combining the objective function Equation  and the Performance Maintainer at the head and the Parameter Adapter at each sensor node—are built to achieve the optimization target. This separation of components further releases the computational burden of the sensor node: the head is in charge of monitoring the runtime topology and computing the optimal bundling number for each sensor node dynamically; the sensor node, therefore, is relieved from the complex computation and leverages the optimal result from the head straightforwardly.MAC-Layer Time Recorder and the Time Synchronization Maintainer, the latter of which translates timestamps between the head and a sensor node. With the time synchronization component, a measurement timestamp recorded at the sensor node—i.e., Delay Calculator. Afterwards, the runtime E2E delay is monitored through the Performance Monitor.Since the time synchronization operation is centralized at the head in EE-ASCFR and AHTS, we first build the reference time synchronization system at the head as a component of the proposed system. The time synchronization is achieved through the Runtime Path Maintainer, and one set of paths is generated and delivered to the Constraint Generator. The user-defined requirements of E2E delay and synchronization accuracy are captured through the user interface of Requirement Input Interface. By combining the performance requirements and the current path information, the Constraint Generator generates a set of constraints and passes it to the Optimal Parameter Generator, where the optimal bundling number for each sensor node is obtained as a solution of the ILP model. Finally, the optimal bundling numbers from the Optimal Parameter Generator are delivered to sensor nodes by the Parameter Disseminator.Based on the topology data carried in each bundled message, the routing paths for all sensor nodes are recovered in the Of particular note is that, whenever the topology is updated or the users change their requirements dynamically, the whole process above will be operated to provide up-to-date optimal bundling numbers. In addition, since the proposed system is in a centralized manner, the major trade-off is the communication overhead for disseminating the optimal results to the sensor nodes. This overhead, by the way, would not be a major issue in practice unless topology updates and user requirements changes are too frequent.MAC-Layer Time Recorder from the time synchronization scheme) are implemented at sensor nodes. The Parameter Adapter receives the optimal bundling number and delivers it to the Data Bundler which bundles that number of measurement data temporarily stored in the Queue plus timestamps into one message. Then, the bundled message will be again timestamped for MAC-Layer Time Recorder as shown in To reduce the computational complexity required by the proposed optimal bundling on the sensor nodes, three lightweight components (including the The proposed approach is implemented on a real three-hop WSN testbed consisting of five TelosB sensor nodes as illustrated in During the experiments, each sensor node generates one measurement per second, and the E2E delays of the latest measurements in bundled messages from all sensor nodes are collected and stored in a time sequence in order of their arrivals at the head, which are shown in long-term maintenance capability.We first evaluate the E2E delay performance of the optimal bundling under static requirement setting—e.g., E2E delay requirement of 8 Equation —of 15 anThe performance of the proposed approach under the static requirement setting is explicitly exhibited through diverse experiments with different parameters and requirements. As shown in run-time maintenance capability.We also evaluate the E2E delay performance of the optimal bundling under dynamic requirement setting with the maximum bundling number of 10 and 15 to demonstrate its During the evaluation with maximum bundling number of 10, the E2E delay requirement is dynamically changed from 8 Equation . When thWith the novel time synchronization schemes of EE-ASCFR and AHTS, the synchronization accuracy could be fulfilled as far as the E2E delay of the bundled message satisfying the synchronization interval: the synchronization interval—i.e., E2E delay—exhibited in the evaluation results as exhibited in To evaluate the energy efficiency, we indirectly estimate it by comparing the number of message receptions and transmissions with and without optimal bundling. Taking the path of The number of message receptions and transmissions of each sensor node is counted every 10 As illustrated in In addition, as briefly mentioned in We have proposed an approach to optimize the number of bundled messages at sensor nodes in a WSN under the constraints of time synchronization accuracy and E2E delay. In order to solve the optimal bundling problem, we formulate it as an ILP model and employ the novel asymmetric time synchronization scheme. To the best of the authors’ knowledge, this is the first work to optimize message bundling for energy efficiency under the joint constraints of synchronization accuracy and E2E delay in the context of WSNs. The practical evaluation results on a real testbed composed of TelosB sensor nodes demonstrate the long-term and runtime maintenance capability of the proposed approach in terms of E2E delay. The energy efficiency is also illustrated through a case study, showing about 70% reduction on the overall message transmissions.Note that bundling a larger number of messages results in a longer payload, which may lead to possible link degradation such as the packet reception ratio degradation. In this regard, link quality requirements could be introduced to the optimization model as additional constraints to take into account more impacts on the overall performance by the bundling procedure. In addition, the proposed approach should be tested with a larger testbed to investigate its scalability and network-wide energy efficiency.


We study strong optical coupling of metal nanoparticle arrays with dielectric substrates. Based on the Fermi Golden Rule, the particle–substrate coupling is derived in terms of the photon absorption probability assuming a local dipole field. An increase in photocurrent gain is achieved through the optical coupling. In addition, we describe light-induced, mesoscopic electron dynamics via the nonlocal hydrodynamic theory of charges. At small nanoparticle size (<20 nm), the impact of this type of spatial dispersion becomes sizable. Both absorption and scattering cross sections of the nanoparticle are significantly increased through the contribution of additional nonlocal modes. We observe a splitting of local optical modes spanning several tenths of nanometers. This is a signature of semi-classical, strong optical coupling via the dynamic Stark effect, known as Autler–Townes splitting. The photocurrent generated in this description is increased by up to 2%, which agrees better with recent experiments than compared to identical classical setups with up to 6%. Both, the expressions derived for the particle–substrate coupling and the additional hydrodynamic equation for electrons are integrated into COMSOL for our simulations. Nanotechnologies strive for higher confinement of both photons and electrons in narrower structures, at sharper tips and in smaller gaps. Localized interactions at nanosized features can hereby strongly influence the optical properties of a large-scale structure in the interplay with long-range collective modes and retardation. Amongst the remaining challenges that computational nanophotonics faces today is the efficient introduction of quantum effects into classical electrodynamics methods, maintaining the advantages of existing numerical schemes while bridging the gap between classical and quantum theory.One crucial parameter affecting the efficiency of solar cells is the absorption rate of the solar spectrum impinging on their surface. It was shown experimentally that the efficiency of the photo-effect increases due to the deposition of metal nanoparticles (MNPs) on the photoactive surface ,2,3 for Three main mechanisms explaining these phenomena were proposed ,26: (i) While the observed scattering effects can be described with classical linear electrodynamic theory for most applications, the coupling between plasmon oscillations and semiconductor states, and the energy transfer related to “hot” carriers are best captured within quantum mechanics. In particular, the particle size and interaction volume in the systems under study, see In this article, we present a model of plasmon-enhanced solar cells based on the microscopic description of the interaction between plasmon excitations inside MNPs and the semiconductor states using the Fermi Golden Rule . A modifapproach ,57. BothWe find a strong increase in the photon absorption and, thus, a significant contribution of the plasmon-semiconductor coupling to the photocurrent. Furthermore, accounting for non-classical electron interaction effects in the dipole field of the metal nanoparticle, we observe a splitting of the local resonance into two sharp resonances which increase both the absorption and scattering cross section around the original local resonance. In our semi-classical treatment of the plasmon oscillation, we attribute this behaviour to the dynamical Stark effect, known as Autler–Townes splitting ,59,60, wswitches . Our finhttp://www.comsol.com) is outlined. We discuss our findings in detail in The article is organized as follows. The next section discusses the nanoparticle–substrate coupling and introduces the related analytic expressions. In Our derivation of the semi-classical coupling between a plasmonic particle on an Si substrate is based on the following assumptions. The presence of the semiconductor in the vicinity of MNPs provides an additional damping channel of the plasmon energy via coupling to the semiconductor band states. We consider a simple parabolic band semiconductor model. The plasmon coupling to the semiconductor can be described as a driven and damped oscillator, where the driving force is the electromagnetic field of the incident plane wave, and the damping force is the near-field energy transfer to the semiconductor. For this, we consider that the field generated by the plasmon oscillation is dipole radiation, i.e., we restrict ourselves to a regime where the near-field coupling is the most important, while medium- and far-field contributions are neglected. This is justified as long as the particle size is much smaller than the incident wavelength With this, we calculate the photon absorption probability W defines the coupling between the subbands. With this, we obtain the absorption coefficientW depends on the environment. Without nanoparticles, it is governed solely through the incident planar electromagnetic wave with vector potential a and bulk plasma frequency R is the distance form the dipole axis and Hereby, In our case, we calculate the plasmonic dipole amplitude For the ordinary photo-effect without nanoparticles, Equation , the aboThe probability of photon absorption by the semiconductor substrate in the vicinity of the MNP results in :(6)δw=43Both expressions reflect the semiconductor band gap The ratio of these probabilities with and without MNPs deposited on the surface of the semiconductor defines the photocurrent gainstrength . LikewisThe numerical evaluation with COMSOL uses for the photocurrent gainH is the depth of Si layer. Since we consider the near-field close to the Si surface, In the balanced state, we consider the stationary solution of a driven and damped oscillator, which yields for the second termThe nanoparticle–substrate coupling is studied in While first principle methods can accurately describe atomistic matter, they are strongly restricted in the maximum system size that can be described with available computers. Hence, the complex electromagnetic field distributions arising from functionalized surfaces cannot be captured and the light-matter interaction is simplified to single particles ,67,68,69Its central idea is to treat the conduction band electrons as a plasma with the (linearized) Navier–Stokes equation, separate their dynamics from bound valence electrons and couple the electromagnetic wave equation with the hydrodynamic equation via the induced charge current. The semi-classical corrections include Coulomb interactions and diffusion effects . This reSimple geometries, such as nanoparticles (NPs), nanoshells and clusters described with nonlocal Mie coefficients , and thieraction ,78. The eraction ,75, couperaction ,80, and eraction ,82. In thttp://www.comsol.com). In this work, we do so for 3D structures and earlier in Ref. [The hydrodynamic model can be implemented into the commercial software COMSOL Multiphysics 5.0  with the Wave Optics module implementing the finite element method (FEM) to solve Maxwell’s equations using the modified permittivity Equation (In practice, we study the influence of gold nanoparticle arrays deposited on the top of a Si substrate on the absorption in the dielectric in the framework presented above. In order to evaluate the derived equations, we use COMSOL Multiphysics 5.0 (Equation  for the The calculations are conducted in two steps. In the first step, we calculate the electromagnetic field around the substrate without nanoparticles in response to the incident light wave defined on the top boundary of the mesh as a TM plane wave. Simultaneously, on the side boundaries of the computational cell, we apply Flouquet periodic boundary conditions. In the second step, we calculate the electromagnetic field distribution with Au NPs deposited on the top of a Si substrate within the scattered field formulation using the results from the first step as a background field.The combined effect of the strong optical coupling between metal nanoparticles and the dielectric substrate together with nonlocal electron dynamics is shown in This is further investigated in terms of the photocurrent gain in the substrate region in our simplified solar cell setup in The impact of mesoscopic electron dynamics becomes significant for true nanoparticles. In We attribute the resonance mode splitting to the dynamical Stark effect, known as Autler–Townes splitting ,59,60. Wity wave ,52,76. TWe study the mode splitting in more detail in We have presented an analytical and numerical approach to the modeling of plasmon enhanced solar cells including quantum corrections arising from coupling between plasmon and semiconductor states captured within Fermi Golden Rule.There are two opposite phenomena influencing the plasmon enhancement in solar cells. The first one is connected to accounting for indirect transitions, according to Equation , preferrOur model based on the Fermi Golden Rule predicts higher light absorption enhancements than a simple scattering model, which is in agreement with experimental measurements . HoweverThe additional nonlocal effects in the electron–electron interaction modify the local dipole field used in the expressions to optically couple the nanoparticles with the substrate. This increases the overall enhancement by another few percent, depending on geometrical parameters, since such effects only play a role for very small particle sizes mportant ,75.Interestingly, an Autler–Townes splitting of modes is observed when nonlocal properties are included. We attribute this observation to the strong optical coupling with not only classical dipole modes, but additional nonlocal modes, which are longitudinal in character, since they describe pressure waves of the electron density. This allows for the dynamical Stark effect to occur and yields two distinct optical modes shifted by about We hope that this study will raise the interest of scientists in photovoltaics, catalysis, optical fibres, plasmonic sensing and further related hybrid metal-semiconductor research.


In this study, we have taken the concept of water treatment by functionalized magnetic particles one step forward by integrating the technology into a complete proof of concept, which included the preparation of surface modified beads, their use as highly selective absorbents for heavy metals ions , and their performance in terms of magnetic separation. The separation characteristics were studied both through experiments and by simulations. The data gathered from these experimental works enabled the elaboration of various scenarios for Life Cycle Analysis (LCA). The LCA showed that the environmental impact of the system is highly dependent on the recovery rate of the magnetic particles. The absolute impact on climate change varied significantly among the scenarios studied and the recovery rates. The results support the hypothesis that chelation specificity, magnetic separation and bead recovery should be optimized to specific targets and applications. In the coming decades, problems with accessing good quality water are expected to worsen. Water scarcity is predicted to occur globally, even in regions currently considered water-rich. Addressing these problems has triggered a tremendous amount of research to identify robust methods of purifying water at lower cost and with less energy, while at the same time minimizing the total impact on the environment.A growing number of contaminants are entering water supplies as a result of human activity. This includes traditional compounds such as heavy metals and emerging micropollutants such as pharmaceutical residues and endocrine disruptors. Heavy metals have been excessively released into the environment due to rapid industrialization and have become a major issue due to their persistence in the environment and toxicity to many life forms. It constitutes an immense problem to which a proper solution has not yet been found . Heavy mThe current technology for the removal of heavy metals from wastewater is inefficient. Mostly the use of polyelectrolytes that enable chemical precipitation, membrane filtration, and adsorption techniques are applied. These processes have significant disadvantages and limitations, including the incomplete removal of heavy metals, high operational cost, high-energy consumption, and a production of toxic sludge. In most of the cases, the recovery of the adsorbent is not possible or not cost effective.It is in this context that the application of magnetic nanoparticles has appeared as a promising approach about 15 years ago. Combined with proper surface modification, the magnetic nanoparticles offer the possibility of a facile separation after capturing the pollutants. Developed initially for analytical purposes, for which the facile separation was an asset to quantify pollutant levels , the con⁃They possess large surface-to-volume ratios, which enhance the efficiency in terms of the quantity used to capture a specific contaminant;⁃They may show superparamagnetic properties meaning that the particles get magnetized only in the presence of a field and have no residual magnetization after the field is removed, which prevents the clustering of particles. They also have a high magnetic saturation value and a high magnetic susceptibility that provides a high particle magnetic moment. Contaminant-loaded magnetic particles can therefore be easily separated from the solution via an external magnetic field and gradient;⁃Their surface can be modified with inorganic shells and/or organic molecules. Not only does this stabilize the particles and prevent their oxidation, but it also provides specific functionalities such as increased affinity towards target contaminants;⁃The possibility to tune the surface chemistry to condition the recyclability of the bead system. This implies enabling the release of the bound contaminant and re-use of the particles in multiple water treatment cycles, hence minimizing the environmental impact of the method;⁃Magnetic micro- and nano-meter sized particles based on iron oxides have been established in biomedical and medical applications for over two decades . Comprehensive in vitro/in vivo toxicity studies have already been carried out. Thus, an extensive database on the toxicity of magnetic particles has been developed which helps to develop a process with no environmentally harmful wastes or byproducts.Tailor-made magnetic nanoparticles are recognized due to their unique properties and potential for modification . In the Nowadays the most classical approach consists of realizing hybrid materials where a magnetic core will facilitate the separation while the rest of the composite is meant to provide specific adsorption and a high specific surface area, thus capitalizing on the above-mentioned properties .Despite several studies on the use of magnetic nanoparticles for water depollution, the concept has remained, at best, an appealing proof of concept. No global approach was taken to take into the account the potential of such technology in a real-life scenario. Therefore, our aim has been, through an inter-disciplinary approach, to combine the preparation and the study of the extraction capacity of the surface functionalized magnetic beads based on magnetic nanoparticles, with an investigation of the separation performance. The data gathered was used to develop different scenarios that served as input to a life cycle assessment study, thus allowing the identification of the key parameters in the further development and up-scaling of this technology.24 reduction of iron acetylacetonate solution. Details of the process are described elsewhere (4 with water created a reducing environment that prevents Fe(II) oxidation to Fe(III), thereby improving the air-stability of the magnetite nanoparticles during the reaction. The nanoparticles were accumulated with a magnet placed under the reaction container and the remaining solution containing the reaction by-products was drained away. The nanoparticles were then re-dispersed with deionized water. This process was done three times to ensure that all the unwanted reaction byproducts were removed.Iron oxide nanoparticles, to be incorporated into polymeric bead particles to provide magnetic functionality, were prepared via NaBHlsewhere . HydrogeThe magnetic cores were then incorporated into polymeric (polystyrene) microbeads and the magnetic particles were prepared by an emulsion solvent evaporation (ESE) process. The magnetic particles were then functionalized with divalent amino acid-based surfactants. The N-acyl surfactants were prepared by coupling aminomalonic acid, aspartic acid, and glutamic acid, three amino acids bearing two carboxylic groups, and differing solely in the size of the spacer between the carboxylic groups, with a fatty acid moiety, yielding N-acyl amino acid surfactants .The magnetic properties of the particles produced have been studied and compared with commercially available particle systems. The main property addressed is how fast the particles can be separated in a liquid (water) using an external magnetic field. How different magnetic setups affect the separation time has also been investigated both by simulations and by experiments. For this, a lab-scale separation system for testing different magnetic concepts, flow rates and different particles was used. The sample magnetic moment versus applied field over the sample up to 1 T at room temperature for each particle system was measured using a vibrating sample magnetometer (VSM) from Lakeshore Cryotronics. The measured sample magnetic moment was then normalized to the total particle mass to obtain the mass magnetization (mean particle magnetic moment per mass of particle) and to the number of particles to obtain the mean magnetic moment per particle . However, the models provided a good qualitative understanding and helped in the optimization of the separation system.Several separation concepts have been tested throughout the project to give input to the separation demonstrator . The sim3 of treated wastewater. The system boundary comprised the complete system of manufacturing of magnetic micro particles and their use for water treatment. Energy and resource use, including raw material production of used chemical intermediate products, were considered for the manufacturing of the particles’ production. The separation process includes energy use and compares different scenarios for the recovery of the micro particles. The data inventory used generic data for the raw materials of particle production. Data for the production of the particles and the separation process were specifically collected from the work in this study. Upstream data to describe the peripheral processes  were collected from relevant literature or from life-cycle inventory databases as modules from suitable databases, e.g. Ecoinvent 3.3 , methane (CH4) and nitrous oxide (N2O) was included.In this study, only an initial environmental impact assessment was performed, meaning that only the impact on climate change accounting for all direct and indirect emissions of the greenhouse gases carbon dioxide  were used to synthesize the total magnetic beads with sizes in the 1 μm–2 μm range. The cores are evenly dispersed in the particle matrix. Magnetic properties were assessed. For this, the sample magnetic moment versus field from up to 1 T at room temperature were measured for each particle system and benchmarked against commercial particle systems . The results showed that the aspartate-based surfactant was the most effective in chelating the divalent species and by taking advantage of the magnetic responsiveness of the particles, extraction levels of >90 % were reached. 2 induced partial aggregation of the beads, which resulted in an easier extraction, as the magnetic response is somewhat proportional to the size of the complexes.The aim of using magnetic beads based on magnetic nanoparticles in a polymeric matrix was to take advantage of the preparation route to introduce an ad-hoc surface functionalization in a one-step process. In a nutshell, the process of preparation is referred to as To measure the separation process (separation time), we used an optical method that measured the change in particle concentration in a sample volume by monitoring changes in light transmittance over time  as descrtsep) varies with particle magnetic properties, such as the mass saturation magnetization M0, the diameter of the magnetic particles, Dp and the particle density, ρ, is that, tsep shall linearly scale with 1/(M0ρDp2) (An approximate model on how the separation time ((M0ρDp2) . Below iAs can be seen in The experimental study was complemented with FEM modelling (in COMSOL) in order to simulate the separation process see . The res3.23) of wastewater from industrial processes. By analyzing the different processes, flows and parts of the system, it was possible to identify so-called ‘hotspots’ of environmental concern. Environmental hotspots point out processes that contribute significantly to the total environmental impact and hereby facilitate efforts to minimize the environmental impact of the whole system. The results for the study are divided into two parts: analysis of the hotspots for the manufacturing of particles and their use in the separation and results for different scenarios for the recovery of the particles (S1–S4).A life cycle assessment (LCA) investigates the environmental impact of a studied system. The analysis is based on the main function of a given system, defined as the treatment, collection and release of valuable substances or contaminants. To assess environmental impacts in this study, the function of the system was quantified to one thousand liters , where it is was assumed that all particles can be recovered and re-used after the separation process, the production of the raw materials for the production of the particles accounted for more than half of the impact. Within raw material production, one specific raw material (Tetrahydrofuran (THF)) showed a significant impact of more than 85 % of the impact from all raw materials combined. The impact of the production process of the particles contributes second most with 29 %, followed by the separation process, which accounts for 16 % of the total impact on climate change.To analyze how the recovery rate of the particles affects the total environmental impact of the system, three additional recovery scenarios were examined. Besides the analysis of full recovery (Scenario 1) and no recovery at all (Scenario 4), a specific case scenario (Scenario 2) assumed that 89 % of the particles can be re-used after their first application and a case scenario (Scenario 3) estimated that 38 % of the particles can be re-used. The results for the different scenarios for the recovery rate of the magnetic micro particles are illustrated in A comparison of the effect of a change in the recovery rate and energy use showed that improvements in the recovery rate have a higher effect on the total environmental impact than a reduced energy use. Furthermore, the results illustrate that further improvements have significantly higher relative potential at higher recovery rates.4The concept of a novel water treatment method using functionalized μm-size magnetic particles to enable a better and more selective removal of pollutants was successfully demonstrated, by developing tailor-made magnetic particles and implementing at lab-scale, to separate heavy metal ions  from aqueous solutions.The magnetic particles produced in the project worked well for magnetic separation, even if additional optimizations are possible. The possibility to recover a major part of the particles in a future up-scaled system looks promising.2eq. was chosen.The Life Cycle Assessment (LCA) showed that the environmental impact of the system is highly dependent on the recovery rate of the magnetic particles. The absolute impact on climate change varies significantly among the studied scenarios and the different recovery rates. Within the system studied, certain raw materials and production processes for the particles were identified as major contributors to the total environmental impact. The infrastructure required for the manufacturing (e.g. lab equipment) and separation (e.g. magnets) was not included in the analysis. In this study, only an initial environmental impact assessment was performed. That is, only the impact on climate change using the impact category ‘Global Warming Potential (GWP)’ with the unit kg CO⁃Enhanced recovery of functionalized particles from realistic water matrices to reduce costs and environmental impacts⁃Replacement of certain raw material for the bead production to reduce the overall environmental impact. This may also require an adaption of the production processes.⁃Upscaling of the process is needed to identify other limitations. This includes optimizing the magnetic properties of the particles for a resource efficient separation process. The magnetic force on a particle and thus the separation efficiency is dependent on both the applied magnetic field (field strength and gradient) and the magnetic response of the particle.The results of this study provide an indication that even if the proof of concepts have been successfully performed, several challenges remain to be solved before a wide implementation of this novel treatment approach can be achieved. These challenges are summarized below and are the target of ongoing work by the authors:In conclusion, the water treatment concept presented in this paper provides a novel approach that facilitates a number of possible technological developments and application fields. A successful further development and optimization of the system may not only provide a flexible and tailor-made system for the removal of specific pollutants but also for the recovery of specific resources from various wastewaters.C. Baresel, V. Schaller, C. Johansson, R. Bordes, V. Chauhan, A. Sugunan, J. Sommertune, S. Welling: Conceived and designed the experiments; Performed the experiments; Analyzed and interpreted the data; Contributed reagents, materials, analysis tools or data; Wrote the paper.VINNOVA, the Swedish Governmental Agency for Innovation, within the call Innovationer för ett hållbart samhälle: miljö och transport.This work was supported by The authors declare no conflict of interest.No additional information is available for this paper.


Fifty percent of the scores differed between both scoring tools, with mainly medial claw digits deviating, but this seemed biologically irrelevant. The MCSD seems to be an appropriate alternative for on-farm claw scoring and is distinguishable from other claw scoring techniques; however, it needs further optimisation to improve the similarity between the two techniques. Claw lesions and lameness in sows are important problems in the industry as they impair sow welfare and result in economic losses. Available scoring techniques to detect claw lesions are all limited in terms of collecting data during all reproductive phases and recording all claws. The Mobile Claw Scoring Device (MCSD) was designed to address these limitations. After considering different practical situations and a design phase, two prototypes were constructed and tested. Improvements were incorporated into a final aluminium apparatus, consisting of two cameras with light-emitting diode (LED) lights mounted in a two-segment aluminium box and covered with laminated tempered glass plates. The operating system slides underneath the claws and takes video images. This final prototype was optimised and validated in an experiment with 20 hybrid sows, comparing scores for soiled claws using the MCSD against scores for clean claws using the Feet First Claw lesions and lameness are a main reason for culling sows before they reach their full breeding potential and results in both impaired welfare and considerable economic losses ,3,4,5,6.The most frequently observed claw lesions in sows, varying in severity, are heel horn erosions, defects in the heel horn/sole junction, white line defects, horizontal and vertical wall cracks, claw and dewclaw overgrowth, ulcers, and skin lesions ,19,20. C© chute   Claw scoring in the farrowing crates when the sow is lying down; (2) scoring the hind claws with the sow standing in the crate by lifting the hind leg(s); (3) scoring the hind claws with the sow standing outside the crate, which requires snaring and lifting the hind legs; and (4) via the Feet Firstoration) . These tThese limitations call for the development of a new technique for on-farm claw scoring that is designed to reduce sow stress and enable sows to stay in their familiar surroundings. Furthermore, this new technology should be easy to handle and transport and the claw scoring should only take a few minutes. Another important specification should be that both front and hind claws can be scored. After the new technique is designed, it needs to be validated. The claw lesion scores obtained from the new scoring technique need to be compared against a gold standard with the hypothesis that the claw lesion scores for this new technique do not differ from the scores noted from the gold standard. For this experiment, we considered the manual inspection of the claws from a sow hoisted up in the Feet First© sow chute as the gold standard for assessing claws.-The sow remains in familiar surroundings without snaring, presumably reducing stress levels.-Easy to handle, disinfect, and transport.-Fast claw scoring without needing to clean the claws.-Claw scoring in either real time or afterwards based on recorded images.-Used during multiple phases of the reproductive cycle.-On-farm scoring of both front and hind claws.To develop an effective and differentiated technique for on-farm claw scoring, the following specifications were required for the Mobile Claw Scoring Device (MCSD): First, the conditions and feasibility of the MCSD were assessed by determining the minimum and maximum applicable specifications for its use in different housing systems. First common housing systems in the pig industry were evaluated and crate dimensions were measured. Based on these crate measurements, the average dimensions were 700 mm × 600 mm (length (l) × width (w)) with a maximal height of 150 mm. To fit in most conventional housing systems, the MCSD should not exceed these dimensions. To test usability at various locations on the farm and the willingness of the sows to cooperate, two wooden prototypes were empirically designed and used . These pAn aluminium MCSD prototype  because in the sow chute, the front and hind claws are fully visible and can be cleaned properly. This experiment was conducted according to the institutional and national guidelines for the care and use of animals. ILVO’s Ethics Committee for animal experiments  approved all experimental procedures. For the experimental design, the MCSD dimensions made it possible to place the MCSD in the sow chute using a wooden cover frame to prevent damage to the MCSD when sows entered the sow chute  of the residuals. All analyses were performed using SAS 9.4 .All gathered findings were integrated into the definitive design using Computer Aided Design (CAD) software and constructed using the third prototype as the basis. The definitive design was validated relative to the Feet Firstow chute . By posiow chute . Three tThe specifications of the definitive MCSD are summarised in Differences between the claw lesions scores of the cleaned claws obtained from the sow chute and the soiled claws obtained from the MCSD were found for 6 out of 12 scores ; 4 for mThe average claw lesion scores for the lateral claw digit and for the overall mean claw lesion score did not differ between the sow chute and the MCSD . The aveDifferences between observers were found for all claw lesion types on the lateral and medial claw digit of the left and right hind claw, except for separation along the white line of the medial claw digit of the left hind claw. Furthermore, differences between observers were also found for the average claw lesion scores for the lateral claw digit, medial claw digit, and for the overall mean.Fifty percent of the claw lesion scores differed between the MCSD and sow chute. In addition, the average claw lesion score for the medial claw digit differed, but did not differ for the lateral claw digit and overall mean. Although the differences reached significance, the question arises how relevant these differences are. Only two scores had a difference above 10 mm (11.85 and 14.41 mm). On the 160 mm tVAS scale, this means that the difference of the above scores is 7.4% and 9.0%, respectively. Expressed in terms of the adjusted 98 mm range, based on the minimum of 2 mm and maximum of 100 mm scores given during the experiment, the above differences were 12.1% and 14.7%. To our knowledge, 10 mm is presumably the lowest detectable distance on the tVAS to discriminate between scores, but 20 mm is probably more relevant as it is half the range between each claw lesion severity category of 40 mm. Furthermore, differences were found between the three observers, especially for lesion scores that differed between the two techniques. Therefore, the differences between scores seem not to be biologically relevant; however, the applicability of the MCSD for on-farm claw scoring still needs further optimisation. Caution is advised when assessing the medial claw digit and scoring for separations along the white line. Comparisons with the other scoring techniques indicated in The MCSD has the required specifications to differentiate from the other techniques . Using tUsing the MCSD, claws can be scored either in real time or afterwards, which would save time during farm visits. Real time claw scoring using the MCSD was not evaluated during the validation experiment of the present study; however, it is expected that it requires more time on the farm. More relevant is the use of digital recordings  versus direct manual scoring. Digital recordings were used in this validation experiment using the MCSD, while claws were directly manually scored using the sow chute. Differences, although probably biologically irrelevant, were found between the techniques; the impact of the type of scoring  could not be distinguished in this experiment. In a study in cows testing five claw conformation measurements manually (directly from the hoof) vs. a digital image, results showed a large variation in the difference between the manual and digital claw conformation measurements. They concluded that these two methods could not be used interchangeably . It appeDifferences in claw lesion scores for the medial claw digits were significant in four out of the total six instances, but it remains unclear why the medial claw digits had consistently worse scores using the MCSD. The digital recordings of the MCSD showed a full vision of both claw digits, with the lateral claw digits being further away from the centre of the camera than the medial claw digits. The sows preferred to stand close to the sides of the MCSD to have more grip, which might have changed their weight distribution. This in turn might have changed the print of the claw (darker and lighter spots), possibly changing the view. However, it is unknown to what extent this may have affected the scoring. When using the MCSD on-farm, some practical experiences need to be considered. The DVR was connected to the aluminium box of the MCSD using a cable, which sometimes obstructed the easy use of the MCSD. An electrical outlet must also be present in the stable. During the validation experiment, the observers often found it difficult to differentiate between a lesion and soiling of the claw. This applies for the MCSD and, to a lesser extent, for the sow chute. In the sow chute, claws can be manipulated, which might enable more accurate observations. Cleaning the claws with water, a brush, and a hoof knife might also improve the visibility of the claw, thus favouring the use of the sow chute. However, farmers do not have a sow chute and the claws are normally soiled during inspection. Another consideration is that the weight of the MCSD might hinder easy transportation. To address this issue, the two boxes can be dismounted after use and transported separately. The MCSD can be disinfected and, unlike the sow chute, can be used in various phases of the reproductive cycle. A farmer can also implement the MCSD in their management system by installing the MCSD in the electronic feeding station(s) during group housing. However, practical considerations and tests are needed to ensure clean glass plates. One limitation of the MSCD is that only the underside of the claws can be scored. Other claw lesion scores need to be scored manually on-farm, including skin lesions around the claw and dew claw, horizontal and vertical wall cracks, and the length of the claw and dewclaw. For these lesion scores, the cleanness of the claw is important to distinguish between a haemorrhage vs. soiling. When using software, some claw conformation measurements can be determined from the video recordings of the MCSD, including sole (base) length and claw width as described in van Riet et al. . In conclusion, the MCSD seems to be an appropriate alternative when compared with the sow chute as a gold standard, but it still needs some optimisation. The MCSD does meet the specifications to be different from other claw scoring techniques. The MCSD can be used on-farm for claw lesion scoring in pigs, but recordings are only possible for claw lesions at the heel horn, at the heel horn-sole junction, and at the white line. The latter provides less reliable scores using the MCSD in comparison to the sow chute technique. Other claw lesion types can be scored while the sow is standing on the MCSD. Future research is warranted and should address the lighting  and camera quality of the MCSD to create better lighting conditions without reflection and to test the possibilities of infrared lighting. Furthermore, when the MCSD is used, the stress response of the sows must be determined and compared with other alternatives for claw lesion scoring. Last, claw scoring of the front claws needs to be validated.