Digital game-based learning (DGBL) makes use of the entertaining power of digital games for educational purposes. Effectiveness assessment of DGBL programs has been underexplored and no attempt has been made to simultaneously model both important components of DGBL: learning attainment  and engagement of users  in evaluating program effectiveness.Professor Gooley and the Flame of Mind, which promotes mental health to adolescents in a positive youth development approach. In particular, we investigated whether user engagement in the DGBL program could enhance their attainment on each of the learning constructs per DGBL module and subsequently enhance their mental health as measured by psychological well-being.This study aimed to describe and evaluate an Internet-based DGBL program, Users were assessed on their attainment on each learning construct, psychological well-being, and engagement in each of the modules. One structural equation model was constructed for each DGBL module to model the effect of users' engagement and attainment on the learning construct on their psychological well-being.Of the 498 secondary school students that registered and participated from the first module of the DGBL program, 192 completed all 8 modules of the program. Results from structural equation modeling suggested that a higher extent of engagement in the program activities facilitated users’ attainment on the learning constructs on most of the modules and in turn enhanced their psychological well-being after controlling for users’ initial psychological well-being and initial attainment on the constructs.This study provided evidence that Internet intervention for mental health, implemented with the technologies and digital innovations of DGBL, could enhance youth mental health. Structural equation modeling is a promising approach in evaluating the effectiveness of DGBL programs. Problems with mental health are common in adolescents. Review studies have consistently shown that the prevalence of youth mental illnesses has been increasing and the onset age of developing mental illnesses has been decreasing . For insEffective psychotherapies for treating mental illnesses exist -12, withWhereas CBT works toward risk prevention for mental health, positive psychology takes a more positive development orientation to mental health. Positive psychology is an approach which encompasses psychological theories that focus on individual traits or character strengths . As poinOver the past two decades, major advances have been made in intervention programs designed to promote or enhance youth mental health . TraditiWith the evolution and advancement of the Internet in the past decade, intervention programs could be delivered through that medium to more beneficiaries with nearly no marginal cost for each additional participant . The easbeyondblue  1.2) years. There were attritions after the first module at a cumulative rate of 37% (Module 2), 47% (Module 3), 50% (Module 4), 53% (Module 5), 56% (Module 6), 59% (Module 7), and 61% (Module 8). Specifically, the number of completers across modules is 498 (Module 1), 312 (Module 2), 265 (Module 3), 249 (Module 4), 235 (Module 5), 221 (Module 6), 202 (Module 7), and 192 (Module 8). The user data of completers was included in the statistical analysis on evaluation outcomes.Confirmatory factor analyses suggested that the outcome variable , module constructs , and predictor variable  followed the 1-factor model with good fit: all CFIs above .90 and RMSEAs below .08. Thus, the 1-factor model could be identified for each of the constructs of interest and this also supported the reliability of all the scales adapted in the study.P<.05).One SEM was used for each module to test the extent to which users’ psychological well-being could be predicted by their engagement and whether this relationship was mediated by their learning on the module construct. Based on the criteria of good fit previously mentioned, the model fit was regarded as good . The overall pattern of results showed that the extent of engagement in the module activities positively predicted user attainment on the psychological constructs and that higher attainment on the psychological constructs would predict higher psychological well-being after controlling for users’ initial psychological well-being and initial attainment on the psychological constructs. As expected, an opposite direction was found in modules using negative constructs as measures. In other words, there is an indirect effect of user engagement on psychological well-being through learning on the psychological constructs. Apart from the indirect effect, the direct effect of user engagement on psychological well-being was also present in some of the modules, meaning that engagement in the module activities alone had an impact on psychological well-being regardless of the learning attainment on psychological constructs.Specifically, a significant indirect effect was found in five modules  and a significant direct effect was found in three modules . For modules not having a significant indirect effect , there is a need to review the role of the corresponding psychological constructs in enhancing psychological well-being and/or review the design of the module activities in facilitating attainment on the psychological constructs.Professor Gooley and the Flame of Mind, was effective in enhancing the mental health of adolescents. The program was evaluated using SEM based on a DGBL effectiveness model. Specifically, the structural relationship between engagement in the program activities and psychological well-being was examined as well as the potential mediating effect of the attainment on each of the psychological constructs in each of the DGBL modules, controlling for users’ initial psychological well-being and initial attainment on the psychological constructs. The results generally supported the program effectiveness by demonstrating that users’ extent of engagement in the module activities positively predicted their psychological well-being, users’ extent of engagement in the module activities positively predicted their attainment on the psychological constructs, and users’ attainment on the psychological constructs positively predicted their psychological well-being.The Internet-based DGBL program, The findings of this study added support to findings in previous research and theory. The learning constructs underlying the DGBL modules in this program pertain to positive psychology , cognitive behavioral modification (automatic thoughts and procrastination), and interpersonal skill training (communication and problem-solving skills). Since no substantial difference was observed in the learning of these constructs and its effect on the program outcome on psychological well-being, this study provides theoretical support to the use of positive psychology, cognitive-behavioral modification, and interpersonal skill training for mental health promotion. Specifically, our findings advocated acting on human strengths  for enhancement of well-being, which is in line with the movement for positive psychology called upon by Seligman and colleagues to complement the risk prevention approaches in mental health programs -22. SecoFurthermore, the results of this study have been impressive when it is considered that all the users are undergoing self-learning on Internet-based learning modules. Evidence was observed from our study on the feasibility and effectiveness of Internet-based intervention programs as an alternative approach to traditional classroom-based intervention sessions. Taken together with the review findings of other studies concerning the potential feasibility and effectiveness of the Internet-based intervention ,26, it iProfessor Gooley and the Flame of Mind is a bridge between our prior work on The Little Prince is Depressed, a classroom-based program enhanced with audio-visual materials [Professor Gooley and the Flame of Mind is an evolution of the delivery mode of our project along with the shift of focus from the risk prevention approach in The Little Prince is Depressed to the positive development approach in Professor Gooley and the Flame of Mind. A typical example is that while the former focused on reducing depressive symptoms, the latter focused on enhancing psychological well-being. From the evaluation outcomes, Professor Gooley and the Flame of Mind as a DGBL program has the potential to facilitate learning and engagement/motivation of adolescents in the program which in turn enhancing their psychological well-being as expected.t videos),35. DGBLbeyondblue [MoodGYM [SPARX [WalkAlong [MyHealth Interactive Magazine [Professor Gooley and the Flame of Mind was designed for enhancing the mental health of the youngsters in the general population with a more structured program in a series of learning modules tied with storyline and DGBL pedagogy. Furthermore, the use of SEM and the DGBL effectiveness model for understanding DGBL and evaluating DGBL program outcomes is a novel approach which can make a significant contribution to the field of Internet interventions.Most of the existing Internet interventions for mental health  were usalkAlong  and MyHeMagazine  were useProfessor Gooley and the Flame of Mind encountered about the same attrition rate as other Internet-based educational programs or Internet-based intervention programs . In a systematic review and meta-analysis of 40 eTherapy programs [The present study has a major limitation of the attrition of users across modules. In particular, out of the 498 completers of Module 1, the cumulative numbers of attrition (cumulative attrition rate) from Module 2 to 8 were 186 (37%), 233 (47%), 249 (50%), 263 (53%), 277 (56%), 296 (59%), and 306 61%), respectively. Despite the innovative design, interesting story, and incentive that had been introduced to motivate the students to complete the whole program, %, respecOne speculated reason for the high attrition rate in our program was that users could only proceed to the next module after they had completed all the module activities in the active module. If they were stuck at the certain point of a module activity or if the play time expired, respondents could not proceed further in the DGBL. Further, students could only complete one module every 7 days; therefore, they might need to wait for a few days in order to start the next module. The time lag or waiting time may have resulted in the low completion rate or, in other words, the high attrition rate. As improvement measures to manage or reduce the attrition rate, email reminders to attempt the next module were sent to users who completed the previous module. Also, users whose play time had expired were allowed to restart the program from the last checkpoint after the expiration date. The system also made changes to shorten the waiting time so that users who have completed all the module activities in an active module were allowed to go to the next module in 1 day. However, these improvement measures can only apply to new users, and therefore the impact can only be observed and studied in future implementation.Learning from the experience of other Internet-based programs with below average attrition rates , a blendFuture research may address other psychological constructs not covered in this program that contribute to the enhancement of psychological well-being or mental health. Also, future research may study the generalizability of program outcomes to users of other age groups or sociodemographic groups. Although the educational content and learning platform developed in this DGBL program was tailor-made for adolescents, it may be adapted to promote the psychological well-being of various age groups  and sociodemographic groups  in the community. The DGBL effectiveness model developed in this study may guide similar evaluation studies of the DGBL in other contexts. Also, a blended approach of program delivery could be explored to reduce the attrition rate.Professor Gooley and the Flame of Mind, which intervened on a range of key psychological constructs of mental health under a positive development approach, adopted a well-structured DGBL pedagogy, and evaluated the effectiveness of the program based on rigorous outcome measurement methodology. The findings of the study support the effectiveness of promoting youth mental health through DGBL which combines education and entertainment to equip youngsters with the knowledge and skills of the psychological constructs. The SEM approach and the DGBL effectiveness model used in this evaluation study could be applied to evaluate the effectiveness of other DGBL programs.This study describes an Internet-based program,


The emergence of influenza drug resistance has become of particular interest as current planning for an influenza pandemic involves using massive amounts of antiviral drugs. We use semi-stochastic simulations to examine the emergence of drug resistant mutants during the course of a single infection within a patient in the presence and absence of antiviral therapy. We specifically examine three factors and their effect on the emergence of drug-resistant mutants: antiviral mechanism, the immune response, and surface proteins. We find that adamantanes, because they act at the start of the replication cycle to prevent infection, are less likely to produce drug-resistant mutants than NAIs, which act at the end of the replication cycle. A mismatch between surface proteins and internal RNA results in drug-resistant mutants being less likely to emerge, and emerging later in the infection because the mismatch gives antivirals a second chance to prevent propagation of the mutation. The immune response subdues slow growing infections, further reducing the probability that a drug resistant mutant will emerge and yield a drug-resistant infection. These findings improve our understanding of the factors that contribute to the emergence of drug resistance during the course of a single influenza infection. The annual cost of influenza illness and the ongoing threat of emergence of a pandemic strain make it all the more necessary to revisit the treatment options currently available. Two classes of drugs, adamantanes and neuraminidase inhibitors (NAIs), are currently available for treatment of influenza, although resistance to both classes of drugs threatens our ability to effectively treat influenza . Better The adamantanes and NAIs exert their antiviral effects by blocking different phases of the viral replication cycle. Adamantanes, such as rimantadine and amantadine, act at the start of the replication cycle by blocking the ion channel activity of the matrix M2 protein and preventing viral uncoating, and thus viral replication , and theResistance to adamantanes emerges rapidly during treatment –12 and ePrevious work on the emergence of drug-resistance in influenza A has focussed largely on epidemiological models –37 whichIn this paper, the effect of treatment with adamantanes or NAIs on the emergence of drug resistant mutants is explored using several within-host mathematical models. The models contain several novel features; they allow for the possibility of back mutation (a mutant strain reverting back to its wild-type form) and they consider the effect of a mismatch between the viral surface proteins and the RNA contained within the virus. These models will be used to determine whether internal/external mismatch, antiviral mechanism, or the immune response affect how quickly drug resistance emerges during the course of a single infection.μnt = 7.3 × 10−5 per nucleotide per replication ) is this conversion factor. α gives the number of infectious virus particles in one TCID50/mL. This rescaling requires that we also adjust the virus production rate (p) and infection rate per virion (β) which both carry units of virus, such that β → β/α and p → pα , the value at which the fraction of breakthrough infections has reached its asymptotic value and consistent with an estimate of this conversion factor used in , on the order of 1012 virions, consistent with the previous estimate. For low relative fitness, our models predict 108–109 drug-resistant mutants. This is lower than the previous estimate since they estimated the number of virions with a single nucleotide mutation at any location, whereas our work counts the number of virions with a single nucleotide mutation at a specific location. Since the number of nucleotides in the influenza genome is 1.4 × 104, the previous estimate suggests that there should be on the order of 106 mutants with mutations at a specific location, which is lower than our estimate. The main reason for the difference between these two estimates is due to the assumed nucleotide mutation rate , so we Beyond these general findings for the emergence of drug-resistant mutants, our model has helped elucidate differences between the emergence of adamantane-resistant mutants and NAI-resistant mutants. In the presence of drug treatment, NAI-resistant mutants emerge faster and at lower relative fitness than adamantane-resistant mutants. The dynamical differences we see are because the two drugs act at different points in the replication cycle. NAIs act at the end of the replication cycle, they prevent the production and release of susceptible virions , 6, but Our model also considered the effect of virion external packing on the emergence of drug resistant mutants. The internal mutation model, which assumes that there is a mismatch between the viral surface proteins and the RNA contained within for newly mutated strains, essentially gives drugs a second chance to prevent the drug-resistant mutant from spreading. When the drug-resistant mutant is initially created, its RNA is packed in a capsid that contains the wild-type surface proteins which are sensitive to the drug and will prevent spread of the mutant. The wild-type exterior, then, acts as a further hindrance to the emergence of drug resistance in the presence of drug treatment. Dynamical differences between IM and CM models are evident even in the absence of drugs, although it tends to be less dramatic here. In this case, the differences are due to the decrease (or increase) of fitness of the surface proteins. In reality, there is likely to be a mix of surface proteins on the surface of virions created from a new mutation, although this has not been experimentally examined. Many parts of the viral replication cycle are still not clearly understood , with buWhile there are other modeling studies of the emergence of drug resistance in the literature, this study does provide new insights. A study by Canini et al. canini14 uses viral kinetic modeling to examine emergence of drug resistance during oseltamivir treatment in both immunocompetent and immunocompromised patients. Studies by Loverdo et al. , 82 do nSince most of our results examine emergence as a function of viral fitness, it is rather difficult to experimentally verify some of the specific model predictions. First, while our model assumptions allow for a simple definition of relative fitness, in practice there are several quantities that can be used to characterize viral fitness , 54. If Even though we included several biological processes not included in previous mathematical models of drug resistance, our models are still simplified representations of the infection process. Our inclusion of an immune response was simplistic, including only antibodies, even though other components such as interferons and cytotoxic T-lymphocytes will also help to clear the infection . InterfeOur models present a simplified version of viral dynamics which help to elucidate some of the mechanisms driving the emergence of drug-resistant mutants during the course of a single infection. Our models show that the mechanism of drug action as well as the surface proteins present on the surface of the mutant virus both play a role in how quickly drug-resistant mutants will emerge and how many mutants will be produced over the course of the infection.


Concrete is prone to crack formation in the tensile zone, which is why steel reinforcement is introduced in these zones. However, small cracks could still arise, which give liquids and gasses access to the reinforcement causing it to corrode. Self-healing concrete repairs and seals these small (300 µm) cracks, preventing the development of corrosion. In this study, a vascular system, carrying the healing agent, is developed. It consists of tubes connected to a 3D printed distribution piece. This distribution piece has four outlets that are connected to the tubes and has one inlet, which is accessible from outside. Several materials were considered for the tubes, i.e., polymethylmethacrylate, starch, inorganic phosphate cement and alumina. Three-point-bending and four-point-bending tests proved that self-healing and multiple self-healing is possible with this developed vascular system. Cracks are the initial symptoms of damage on concrete. Concrete is prone to cracking due to its limited tensile resistance. These cracks can be a gateway for liquids and gasses to the steel reinforcement, causing it to corrode . TraditiIn the case of autonomous self-healing, the recovery process is due to engineered additions. The repair agent is a polymer-based or bacterial agent embedded in protective capsules ,6,7. TheEmbedding glass into concrete has two main drawbacks: glass induces alkali–silica reactions and may not survive in the long-term aggressive chemical environment of concrete . AdditioTo overcome the drawbacks of autonomous healing with multiple short capsules, i.e., cost-ineffectiveness, difficulty to place in concrete, current inability to survive the mixing process, uncertainty of enough capsules breaking and no multiple self-healing possiblilty, the vascular system provides the answer. Vascular self-healing is inspired by the blood-vessel system. The advantages are that bigger volumes of healing agent are available and that such a system can be connected to the outside, allowing (re)filling or replacing the healing agent and so taking the lifetime of the healing agent out of the equation. The design of vascular networks was successfully introduced in polymer matrix composites and remains a hot topic of research in material science . Joseph In this study, the commonly used encapsulation material glass is replaced with alternative brittle materials: poly methyl methacrylate (PMMA), starch, alumina or inorganic phosphate cement (IPC). First, the performance of the new encapsulation materials is evaluated by testing small-scale concrete beams, carrying short tubular capsules, under repeatable bending load. Next, a vascular network is accomplished by adding a distribution piece on both sides of long tubular capsules, which connects the system to the outside.For the first time in the literature, the vascular network idea with an internal distribution piece is applied to design concrete with self-healing properties and the limitations of glass capsules are overcome. This new design aims to provide repeatable repair of different cracks formed in concrete. The assessment of several cracks that interact, close and reopen simultaneously is successfully done by using an integrated monitoring system: an optical method that visualizes cracking stages  is combined with the acoustic emission technique that accurately locates in space and in time the damage in concrete. Both techniques are commonly applied for fracture mechanics studies of construction materials and have shown great monitoring performance in previous autonomous healing studies ,20,21,22It is found that the PMMA capsules are not brittle enough to break when cracking occurs. Additionally, after testing, the beams were cut using a diamond cutter and it was visually observed that the PU-based agent polymerized inside the capsules. Moisture was able to get inside the capsule, causing the healing agent to react. Similarly, after testing the beams carrying starch capsules, they are split in two pieces at the cracked section and the fracture surface is visually inspected. It is noted that the capsules, despite the presence of a waterproof coating, have attracted water from the concrete mixture. A circle around the capsules is observed, as shown in In contrast to starch and PMMA, the inorganic phosphate cementitious (covered by PEEK plasticizer) and the alumina ceramic capsules have shown to be compatible with the PU-based healing agent.Under three-point-bending, a macro-crack initiates from the notch and propagates along the height of the beam. The crack propagation along the capsules successfully leads to their rupture. The moment at which the capsules break is detected based on the AE hits energy analysis previously presented in . In FiguIt is shown that both alumina and IPC capsules rupture only in the presence of macro-cracks wider than 80 μm. More ceramic capsules break in comparison to the cementitious ones. The fact that the capsules rupture energy is greater in the case of ceramic capsules may indicate significant resistance of alumina to damage. The excess resistance of alumina to damage can introduce local stress concentrations and interfacial detachment at the capsules’ zone and modify the concrete mechanical damage. This is not the case for the IPC capsules that break and only emit relatively low energy. The high bond strength between IPC and concrete can be the reason for the latter observation. However, few IPC capsule breakages are detected (one or two for each beam). In both cases, the agent is released in time into the crack void and the healing process is successfully activated.The efficiency is measured considering the strength and stiffness regain. In this way, the beams are reloaded up to two times after the initial damage and their mechanical response is summarized in The specimen with alumina capsules achieve significant stiffness recovery but limited strength restoration. At the third loading, i.e., the second reloading, the alumina specimen show a regain in stiffness of 104%, based on Equation (3). This can be explained by a very efficient healing the second time, a lot more healing agent was able to flow into the crack. The DIC deformation (U) map at the end of the second reloading cycle shows that the crack reopens only at the bottom of the sample and does not propagate higher than the capsules level d. The la-Three-point-bending (notched beams) simulates the guided unique cracking.-Four-point-bending, where multiple cracking occurs, simulates more realistic loading conditions.In this section, specimens with IPC or alumina long capsules, connected to a 3D printed distribution piece  are tested. The mechanical performance of the concrete beams after healing is evaluated for two cases:The addition of capsules in the tensile zones of the concrete specimen has a reinforcing effect. This is due to their superior tensile properties with respect to concrete. Depending on the capsule’s material, the reinforcing effect can be bigger. As a result, the ultimate strength of the beam carrying ceramic capsules is greater than there reference one and the one carrying cementitious capsules. The capsules resist cracking formation and enhance the fracture toughness, but as soon as the ultimate strength of the sample is reached, the crack propagates and the capsules instantly fail.In It is shown that several alumina capsules break at the post-peak stage of loading a. The AEThe difference in the emitted energy between ceramic and cementitious capsules can be attributed to two parameters: firstly, the AE hits energy is relevant to the mechanical properties of the capsule material  and the interfacial bonding developed between the concrete matrix and the capsule. Secondly, the AE energy emission depends on the fracture process that occurs locally: the local stress field is limited at the early loading stage before the crack formation and for this reason the cementitious capsule breaks “softly” emitting lower AE energy. At the ceramic capsules case, the local stress field is significant at the zone of the macro-crack that continuously widens at the post-peak stage. Therefore the capsule that resists this stress accumulates strain and as it breaks emits greater fracture energy. In any case, it is shown that the failure process of short capsules is repeated in the case of the piping system.As capsules break, the healing activation process is initiated since the healing agent is released into the crack void. The concrete beams are left at their neutral, unloaded position and the agent polymerizes. Repeatable and efficient healing can be noted for the IPC vascular system, since for the first and second reloading cycle the mechanical features are restored up to 126% and 96%, respectively.On the contrary, the ceramic piping network achieves significant stiffness recovery but limited strength regain after healing (less than 40%). The result is in agreement with the previous findings regarding the alumina short capsules see . The parxx) maps of the IPC piping network concrete beam at the end of the first and second loading cycle is presented in DIC strain (εxx) maps of the ceramic piping network series show that the crack that forms at the first loading cycle is not located at the middle section of the beam  and the VASC IPC (n = 3) a statistical analysis could be performed.Due to the small amount of specimen that survived the production process, only for the reference  piping networks were tested under four-point-bending. The test aims at evaluating the mechanical response of the embedded piping system in the presence of multiple cracks.Following the testing protocol discussed in previous paragraphs, the concrete beams are loaded up to overall deflection equal to 1 mm. DIC-strain profiles shown in The damage propagation is monitored by DIC and AE techniques for both alumina and IPC piping systems and is presented in This is not the case for the cementitious piping system. Once again, embedding the rigid 3D printed distribution piece controls the crack distribution leading to a unique macro-crack shown at the DIC deformation (U) maps in The AE hits and energy remain low for both cementitious and ceramic vascular systems as the load linearly increases at the beginning of the reloading stage b. When tThe AE location analysis confirms the DIC findings. In the graphs of X-Y coordinates c, the evIn Concrete beams are designed to be tested under four-point-bending. Normal strength concrete beams are prepared with the composition presented in The healing agent (MEYCO MP355 1K) is provided by BASF. This agent is a polyurethane pre-polymer, consisting of two components with, respectively, viscosities of 600 mPa·s and 70 mPa·s at 23 °C, which start to foam in moist surroundings. The expanding foaming reaction of this healing agent may lead to an increase in volume .The capsules are manually filled with the agent and immediately sealed by using X60 adhesive. First a layer of concrete is put into the mold. Then three capsules are carefully placed on this concrete layer, parallel to each other and held into place by a fabric wire anchored at the mold’s sides, the distance between the capsules is around 20 mm. This process is illustrated in A layer of concrete is put on top of these capsules and then a new set of three parallel capsules is put into place at a height of 45 mm from the bottom of the beam. Six capsules are used. The rest of the mold is then carefully filled with concrete.The three-point-bending load induces stresses and forms a unique crack that initiates at the pre-crack and propagates across the beam’s height. The loading stops when the crack opening at the section above the pre-crack is equal to 300 µm considering the serviceability stress limitation (EC 2). During loading, the crack widens and the capsules standing on the crack propagation track break due to tension. The healing agent is released from the capsules and fills the crack void.After loading until a crack width of 300 µm, the specimen is left in unloaded condition for 24 h so that the healing agent has sufficient time to polymerize. Two loading cycles, with a 24 h healing period in between, follow the initial bending and subsequently the initial crack repeatedly reopens as shown in Different alternatives to glass are considered for the design of the agent carriers. Their physical and mechanical properties are briefly described in the following paragraphs. The dimensions of the capsules strongly depend on the availability at the manufacturer and the production process. The presence of the capsules slightly affects the ultimate strength with respect to a normal concrete beam. The amount of healing agent in each capsule is sufficient to fill the formed crack void.Polymethylmethacrylate (PMMA) is a thermoplastic material that is able to resist the aggressive chemical environment of concrete, it has a density that is only half of glass and has a higher strength see , therefoStarch-based materials are brittle when dry, and flexible when exposed to humidity or increased temperatures. In a humid environment, the alpha-bonds that are encountered in starch are gradually destroyed and the material becomes flexible. Starch macaroni tubes were bought from the brand Soubry. The short (around 33 mm long) starch-based capsules used have an outer diameter of around 8 mm and an inner diameter of 2.5 mm. A water-repellent wax coating both on the inside and outside of the starch-based capsules was applied a to avoiInorganic Phosphate Cement (IPC) is an inorganic non-alkaline ceramic material developed at the Vrije Universiteit Brussel (VUB) and has comparable properties to cement-based materials see . It has Ceramics are favorable due to their brittle behavior, their great strength and stiffness see  and greaFrom the design perspective, the innovation of this study is the introduction of a vascular system that can repeatedly provide sufficient healing agent at any damage location. The tubes discussed in the previous section are elongated (100 mm) and placed at the same height covering the tensile loaded section of the beam (across the beam’s length). In a first stage these beams are tested under three-point-bending and the performance of the vascular system is evaluated in the case of a unique guided crack. In a second stage, new beams with a vascular system are tested under four-point-bending simulating the realistic loading conditions. For both three-point and four-point-bending, the imposed speed was 0.04 mm/min. In the case of three-point-bending, the crack width is measured by a crack mouth opening displacement (CMOD) sensor and loading is performed until 300 µm. In the case of four-point-bending, the distance between the upper supports is 180 mm.At the first step, it should be verified that the healing agent can efficiently travel through the capsule using capillary forces and potential energy caused by a height difference. It should be highlighted that the healing agent used is the one with the optimal rheological features: the viscosity of the two components of the polyurethane agent is low enough to flow through the vascular network and is high enough so that the healing agent does not flow out of the crack and is not absorbed too much by the matrix.The flowing of the polyurethane-based healing agent was tested in a simple setup as shown in In the next step, a more complex system is designed: the inlet and outlet tubes are replaced by a distribution piece that guides the agent into the capsules, positioned at the damaged zone of the beam—note that healing is limited to the zone within the distribution pieces. This way, a reservoir system of agent is placed out of the area of damage and fills the tubes with agent only if required. This design allows repeatable self-healing capability. The concept is presented in A channel brings the liquid to the bottom where it is distributed over up to four tubes which can be attached to the 3D printed piece. In F is the applied force, and δ is the associated displacement.The strength and stiffness are chosen as the mechanical features that quantify the material’s cracking resistance. Both features can be accurately calculated considering the mechanical performance of a healed concrete beam that is tested before and after the healing agent is released and polymerizes into the crack void. Note that this can be different depending on the used encapsulation material. The stiffness is calculated with the following formula for the elastic  region of the specimens:maxF is the ultimate load, L is the length between the supports, b is the width, and d is the height of the specimen.The strength is determined using the formula below:The self-healing efficiency is defined as the ratio between a property, i.e., strength or stiffness, at reloading  and at initial loading . Note that this definition includes the effect of the remaining strength/stiffness of a specimen.xx, εyy, and εxy) are obtained from the deformation derivatives.Acoustic emission (AE) and digital image correlation (DIC) are used for inspection during the experiments. As can be seen in The AE resonant sensors (resonant frequency 150 kHz) are attached by means of magnetic holders at the concrete surface at all sides of the concrete beam. The signal is received by the sensors and is amplified by 40 dB before reaching the digital storing system (8-channel AE software provided by Mistras). The received hits are filtered considering a magnitude threshold equal to 40 dB. The AE events are located in the three dimensions using the triangulation technique and considering the P-wave velocity on concrete equal to 4000 m/s. Each plastic deformation, i.e., cracking emits an elastic wave, captured by the sensors. The energy of this waveform can be quantified. Depending on the cracked material, the emitted energy is different. In the case of a heterogeneous material, such as a concrete beam with embedded capsules or vascular system, the differentiation in energy can be used to find out which material is cracking, i.e., the cementitious matrix or the capsules or tubes from the vascular system.In In this study, several alternatives  to glass material are studied to develop the optimal encapsulation system for autonomous healing applications. Both ceramic  and cementitious (IPC) were successful in this study. Additionally, inspired by vascular blood vessels in nature, a vascular network system was developed, by implementing multiple vanes  inside the beam, in order to provide repeatable autonomous healing in concrete. The polymer-based healing agent is automatically released into the concrete as soon as cracking occurs through the vascular network. The agent is delivered from a reservoir station at any location between the reservoirs into the concrete. It aims to fill and mechanically restore the damage the same way as the injection technique does traditionally on concrete repair works. It was found that the fracture toughness under bending load of concrete beams carrying ceramic tubes is significantly modified. The presence of ceramic tubes provides local strain concentration zones at the tensile section of the concrete beams and the ultimate load is increased compared to the reference case (no tubes). On the other hand, the presence of inorganic phosphate cement tubes into concrete does not affect the mechanical properties of the concrete beams and permits stable strain-softening phenomena on concrete. For this latter reason the IPC piping system appears the most viable option. In all cases, the tubes break in the presence of a macro-crack. It was proven by means of Acoustic Emission wave energy analysis that the tubes break as the crack forms and widens. The healing activation by means of tubes rupture is successfully done in all cases. At the next step, the well-studied piping system of healing agent carriers is connected with a reservoir station that stands at the beam’s vicinity and carries the polymer agent. The agent was successfully imported into the piping system through a distribution piece (accessible from outside the beam) as soon as the cracks break the capsules. The mechanical repair was observed at the second and third loading cycle proving that healing can be repeatedly achieved. Multiple self-healing phenomena are observed under four-point-bending tests at which several cracks form and propagate simultaneously. The four-point-bending test set-up on small scale concrete beams provides realistic crack patters and simulates the loading response of real-scale concrete beams under continuous load. The main contribution of this study is the design and manufacturing of the piping system by introducing innovative 3D printed agent suppliers and alternative and more efficient tubes.In future research, the distribution piece should be adapted so that it does not cause crack formation at its position. The integrated self-healing system should be implemented in real concrete applications. In this case, the healing design should face two challenges: repair should be provided in complex micro- to macro-scale cracks and the agent should be delivered at different sections of the concrete structure. Concrete beams or slabs should be constructed and evaluated under realistic loading conditions .Monitoring techniques should also be implemented for the self-healing concrete of the future. A sensing system that provides information on crack formation and propagation can be built using optical fibers or piezoelectric transducers. The sensing system should be embedded into the structure, have no impact on the mechanical and physical features of the concrete and be robust and accurate enough to detect cracks in order to activate in time the healing agent release from the reservoir station. The design of effective vascular healing networks and their application on real concrete structures will be the focus of our future research.


This work focuses on the experimental data analysis of electroencephalography (EEG) data, in which multiple sensors are recording oscillatory voltage time series. The EEG data analyzed in this manuscript has been acquired using a low-cost commercial headset, the Emotiv EPOC+. Our goal is to compare different techniques for the optimal estimation of collective rhythms from EEG data. To this end, a traditional method such as the principal component analysis (PCA) is compared to more recent approaches to extract a collective rhythm from phase-synchronized data. Here, we extend the work by Schwabedal and Kantz ) evaluating the performance of the Kosambi-Hilbert torsion (KHT) method to extract a collective rhythm from multivariate oscillatory time series and compare it to results obtained from PCA. The KHT method takes advantage of the singular value decomposition algorithm and accounts for possible phase lags among different time series and allows to focus the analysis on a specific spectral band, optimally amplifying the signal-to-noise ratio of a common rhythm. We evaluate the performance of these methods for two particular sets of data: EEG data recorded with closed eyes and EEG data recorded while observing a screen flickering at 15 Hz. We found an improvement in the signal-to-noise ratio of the collective signal for the KHT over the PCA, particularly when random temporal shifts are added to the channels. Non-invasive techniques such as electroencephalography (EEG), functional magnetic resonance imaging (fMRI) or magnetoencephalography (MEG) are widely used to study the brain activity –3. SinceConsumer EEG headsets are typically used for gaming and simple brain-computer interface (BCI) tasks. However, these consumer devices are being used more and more in research –11. Low-The raw data measured in EEG is oscillatory, and it is common to examine the data for different frequency bands . A commoThe brain activity may exhibit characteristic frequencies for certain tasks, e.g. memory retrieval or sustained attention . In thisOur work focuses on the analysis and comparison of different techniques for the estimation of collective rhythms from EEG data measured using a consumer EEG device. More specifically, we choose the Emotiv EPOC+ for our measurements as it is a user-friendly, comfortable and non-invasive EEG headset with 14 channels. In what follows, we describe the different phase extraction methods and compare their benefits. We show that the Kosambi-Hilbert Torsion (KHT) method  is extre® headset as the EEG recording device. For the extraction of a collective phase, we describe the methods of principal component analysis (PCA) .Compute the signal variance at the given center frequency, x(t) − xf(t)].Compute the noise variance at the given center frequency as Compute the SNR, see A high SNR indicates high precision data. The noise variance depends on the definition of noise, which in our case and for an arbitrary signal we define using bandpass filters at different frequencies and a given bandwidth. The level of noise then corresponds to the out-of-band variance, following the recommendations in . The proSNR(fc).Here, everything that is not the signal within a given frequency range is considered to be noise. This procedure can be repeated for several center frequencies in the desired range to obtain the spectrum ya(t) = y(t) + iH(y(t)), where H(y(t)) is the Hilbert transform of y(t). This analytic signal can also be written as ya(t) = A(t)exp(iϕ(t)), where A(t) is the amplitude envelope and ϕ(t) = arg[ya(t)] is the instantaneous phase  for j = 1, 2, …, 14. The horizontal axis in Figs Figs One can observe in Figs One could expect a priori that the SNR of the KHT remains approximately constant when the time shift between the data channels is changed, however the SNR actually increases. Our interpretation of these results rely on the fact that the KHT method aims at correcting phase lags between a reference channel and the rest of the channels. In this manner, the rest of the channels are phase-shifted in order to obtain in-phase oscillations. This shift is typically restricted to be smaller than half a period of the main oscillating signal. The correcting shift applied by the KHT aims at keeping the phases aligned. This procedure does not necessarily align the amplitudes when going back to the original signal space. For increasing time shifts, we have checked that the variance of the out-of-band signal decreases since the amplitudes lose correlation. At the same time the variance of the in-band signal increases, leading to the observed increase in the SNR.In the bottom signal of Here, we compare the standard PCA to more recent approaches to extract a collective rhythm from phase-synchronized data. We observe that the KHT method improves the SNR of a collective EEG signal over the standard PCA. More specifically, we find this clear improvement when we add random phase lags  among time series before using the KHT.For the experimental data recorded with the eyes closed condition and using the KHT method, the quality of the extracted collective rhythm keeps improving as more channels are added to the analysis, even if the added channels have a lower SNR. In contrast, we find that using the PCA the best result is typically obtained by selecting only a few channels with the highest SNR.For the experimental data recorded watching a flickering screen, the quality of the extracted collective rhythm using the KHT improves when channels with a lower SNR are added to the analysis. In contrast, we found that using only a few channels is the best choice when using the PCA. In the latter case, adding more channels with lower SNR typically makes the quality of the collective rhythm to start decreasing significantly.Comparing all subjects and the two experimental conditions, we find a larger SNR for the KHT than for the PCA. The overall SNR enhancement when using all channels is larger in the case of the eyes closed experiment than in the flickering screen one. This is due to the fact that the signal is more distributed along the channels in the former case.Here, we recorded EEG data for two experimental conditions in order to characterize the signal quality of a commercial “low-cost” headset (Emotiv EPOC). We show that the KHT method provides an improvement in the quality of the extracted collective rhythm. We argue that similar qualitative results are to be expected, in terms of the SNR improvement of a collective signal, using other EEG devices and in the presence of phase lags. This is a major advantage of the KHT over the PCA by the very own definition of the methods, independent of the EEG recording device. In this context, we also show that the introduction of an additional time-shift (or phase lag) to the original time series can enhance the extracted signal quality when using the KHT method. This finding applies to signals whose main frequency content is sustained over time.As future work, we intend to test the performance of the KHT outcome for BCI tasks  , 45. The


The evolution of language correlates with distinct changes in the primate brain. The present article compares language-related brain regions and their white matter connectivity in the developing and mature human brain with the respective structures in the nonhuman primate brain. We will see that the functional specificity of the posterior portion of Broca’s area (Brodmann area [BA 44]) and its dorsal fiber connection to the temporal cortex, shown to support the processing of structural hierarchy in humans, makes a crucial neural difference between the species. This neural circuit may thus be fundamental for the human syntactic capacity as the core of language. The Descent of Man in The evolution of language has been discussed since Darwin’s One possibility to approach this issue is comparative: to identify the brain structures that subserve language, and particularly syntactic abilities, in the human brain and to compare these to homologous structures in the nonhuman primate brain. Structural and functional neuroanatomical differences may provide relevant information on the neural basis of the evolution of language. In addition, a comparison between the phylogenesis and ontogenesis of language-relevant brain structures may help to enrich the picture to be drawn on the biological foundation of the language faculty. Here, I will follow this line of examination. I will focus on syntactic structure, because it is a well-defined area that clearly differentiates humans from other animals; however, this is not to suggest that other components of language  are not interesting or important, because these guarantee the communication of meaning.type of sequences and structures can be learned  phrase structure grammars (PSG) following an AnBn rule , at least as long as no build-up of a minimal hierarchy is required. Third, the build-up of hierarchies, however, is required in natural grammars, for example, between a determiner (the) and a noun (man) when building a determiner phrase. This build-up of a phrasal hierarchy is implemented through the computation “Merge” that binds two elements into a minimal hierarchical structure  study in human adults using the same type of grammars was conducted. The data revealed different activation patterns for the processing of (AB)The specific function of BA 44 and the frontal operculum for the computation Merge has been investigated in a series of fMRI studies  via a dorsal white matter pathway  activate the ventral frontal opercular cortex bilaterally when processing a simple forward-branching grammar . The ability to learn such nonadjacent dependencies is taken to be a precursor to learn syntactic dependencies in a natural language. An electrophysiological (EEG) study with 3-month-old infants revealed that violations in AxB sequences were reflected in a mismatch negativity (Mueller et al., Infants have been shown to learn rule-based sequences (Saffran, Aslin, & Newport, To see to what extent human infants and nonhuman primates show similar sequence processing abilities, a recent EEG study with macaques (Milne et al., The data discussed lead to the tentative conclusion that the neural circuit, consisting of BA 44 and the posterior superior temporal cortex connected via a dorsally located fiber tract, may be seen as a crucial evolutionary advancement toward the unique human faculty of language.


In the present work, an elaborate one-dimensional thermofluid model for a human body is presented. By contrast to the existing pure conduction-/perfusion-based models, the proposed methodology couples the arterial fluid dynamics of a human body with a multi-segmental bioheat model of surrounding solid tissues. In the present configuration, arterial flow is included through a network of elastic vessels. More than a dozen solid segments are employed to represent the heat conduction in the surrounding tissues, and each segment is constituted by a multilayered circular cylinder. Such multi-layers allow flexible delineation of the geometry and incorporation of properties of different tissue types. The coupling of solid tissue and fluid models requires subdivision of the arterial circulation into large and small arteries. The heat exchange between tissues and arterial wall occurs by convection in large vessels and by perfusion in small arteries. The core region, including the heart, provides the inlet conditions for the fluid equations. In the proposed model, shivering, sweating, and perfusion changes constitute the basis of the thermoregulatory system. The equations governing flow and heat transfer in the circulatory system are solved using a locally conservative Galerkin approach, and the heat conduction in the surrounding tissues is solved using a standard implicit backward Euler method. To investigate the effectiveness of the proposed model, temperature field evolutions are monitored at different points of the arterial tree and in the surrounding tissue layers. To study the differences due to flow-induced convection effects on thermal balance, the results of the current model are compared against those of the widely used modelling methodologies. The results show that the convection significantly influences the temperature distribution of the solid tissues in the vicinity of the arteries. Thus, the inner convection has a more predominant role in the human body heat balance than previously thought. To demonstrate its capabilities, the proposed new model is used to study different scenarios, including thermoregulation inactivity and variation in surrounding atmospheric conditions. A fundamental understanding of heat transport in a human body is important for studying a broad range of situations, such as the effect of temperature controlled surgeries and the impact of dramatic change in atmospheric or surrounding temperature. The thermal manipulation of body temperature has been used for a long time in cryosurgery and cancer treatment (hyperthermia)    (Nithiarasu A), the average values of velocity (u) and temperature (T) over the artery cross section. Fluid pressure (p) is linked to area via the following nonlinear relation  of the blood are also assumed to be constant. Following some relevant works , left external carotid , right external iliac , and right radial , are selected  are shut down. All other parameters are assumed to be the same as the previous subsections.Figure A novel, next-generation bioheat model for the human body has been developed and tested. The systemic circulation embedded human body model is more comprehensive than existing models. Further improvements are nevertheless possible by including more arteries and veins. The proposed model in its present form can test various parameters including artery stiffness, blood pressure, various dimensions, tissue properties, surrounding conditions and many more. The results produced very clearly highlight the effect of arterial heat convection on the surrounding tissues. The heat convection and perfusion enhances the energy exchange between the blood and surrounding tissues. As expected surrounding temperature changes significantly affect the skin temperature; however, the control system limits the rapid variation of temperature whenever outside temperature is far from thermally neutral conditions.There are numerous potential applications of the proposed model, such as better understanding of hyperthermia/hypothermia and the detailed study of resulting temperature transport and distribution. Besides these applications, the proposed model can study the influence of disease conditions such as hypertension and arterial dysfunction and also ageing on energy exchange. The model can also be used to study changing environments as a condition for enhanced quality of life.


Molecular fingerprints are widely used in several areas of chemoinformatics including diversity analysis and similarity searching. The fingerprint-based analysis of chemical libraries, in particular of large collections, usually requires the molecular representation of each compound in the library that may lead to issues of storage space and redundant calculations. In fact, information redundancy is inherent to the data, resulting on binary digit positions in the fingerprint without significant information.Herein is proposed a general approach to represent an entire compound library with a single binary fingerprint. The development of the database fingerprint (DFP) is illustrated first using a short fingerprint (MACCS keys) for 10 data sets of general interest in chemistry. The application of the DFP is further shown with PubChem fingerprints for the data sets used in the primary example but with a larger number of compounds, up to 25,000 molecules. The performance of DFP were studied through differential Shannon entropy, k-mean clustering, and DFP/Tanimoto similarity.The DFP is designed to capture key information of the compound collection and can be used to compare and assess the diversity of molecular libraries. This Preliminary Communication shows the potential of the novel fingerprint to conduct inter-library relationships. A major future goal is to apply the DFP for virtual screening and developing DFP for other data sets based on several different type of fingerprints.The online version of this article (doi:10.1186/s13321-017-0195-1) contains supplementary material, which is available to authorized users. The concept of molecular similarity is commonly used in different areas of chemistry including drug discovery. This is because one of the core paradigms in drug design is that similar compounds share similar properties. A number of molecular representations and similarity coefficients have been proposed  to quantIn chemoinformatics, molecular fingerprints are one of the most common representations of chemical structures. Representations of this type are simplifications of the chemical information contained in any chemical entity through binary vectors. Figure The goal of this work was to introduce a new binary fingerprint that encodes the main features of a compound data set. The herein called database fingerprint (DFP) is schematically illustrated in Fig. www.random.org (that uses atmospheric noise to generate random numbers). Since the focus of this work was the generation of a novel fingerprint representation that includes the main features (bit positions) of the compounds in a molecular library, the following approach, inspired on the concept and applications of SE  is clear that DFP saves time because they are pre-calculated and stored for later applications.


As Global Navigation Satellite System (GNSS) signals travel through the troposphere, a tropospheric delay occurs due to a change in the refractive index of the medium. The Precise Point Positioning (PPP) technique can achieve centimeter/millimeter positioning accuracy with only one GNSS receiver. The Zenith Tropospheric Delay (ZTD) is estimated alongside with the position unknowns in PPP. Estimated ZTD can be very useful for meteorological applications, an example is the estimation of water vapor content in the atmosphere from the estimated ZTD. PPP is implemented with different algorithms and models in online services and software packages. In this study, a performance assessment with analysis of ZTD estimates from three PPP online services and three software packages is presented. The main contribution of this paper is to show the accuracy of ZTD estimation achievable in PPP. The analysis also provides the GNSS users and researchers the insight of the processing algorithm dependence and impact on PPP ZTD estimation. Observation data of eight whole days from a total of nine International GNSS Service (IGS) tracking stations spread in the northern hemisphere, the equatorial region and the southern hemisphere is used in this analysis. The PPP ZTD estimates are compared with the ZTD obtained from the IGS tropospheric product of the same days. The estimates of two of the three online PPP services show good agreement (<1 cm) with the IGS ZTD values at the northern and southern hemisphere stations. The results also show that the online PPP services perform better than the selected PPP software packages at all stations. GNSS data is widely used for positioning and navigation in mass-market and engineering applications  and for The ZWD and the Zenith Hydrostatic Delay (ZHD) comprise the total Zenith Tropospheric Delay (ZTD) that can be estimated with the Precise Point Positioning (PPP) technique. PPP estimates the tropospheric delay, the position and clock offsets using precise ephemeris and the ionospheric-free combinations of dual-frequency GPS pseudorange and carrier-phase observations .2 of precipitable water.Given the increasing attention of PPP among the GNSS community, different software packages have been developed. The precision of the positioning results can be assessed, for example, the online PPP solution by the University Of New Brunswick (GAPS) has been evaluated in terms of its achievable accuracy . An overStudies about estimated ZTD with PPP are scarce, the results of estimated ZTD with the Automatic Precise Positioning Service (APPS), the GPS Analysis and Positioning Software, Canadian Spatial Reference System precise point positioning service (CSRS-PPP), and the Magic-PPP online PPP software have been compared to assess the quality of positioning estimation . The suiHowever, there has been no assessment on the quality of ZTD-estimates using data from stations in different latitudes and in the four seasons using both, online and post-processing PPP software packages. Also, the quality of ZTD-estimates obtained with the software developed by the University of Nottingham (POINT) has not yet been assessed.This paper presents a comparative analysis of ZTD-estimates obtained with six different software packages using eight days of data from nine IGS stations. The ZTD estimated with JPL’s APPS, CSRS-PPP, MagicGNSS, European Space Agency and Barcelona’s tech GNSSLab Tool (gLAB), the open source RTKLIB and the University of Nottingham’s POINT using eight days  of observation data from nine IGS stations around the world are compared with the ZTD-estimates obtained from the IGS tropospheric product of the same day epoch by epoch in order to assess the quality of the estimation by comparing which estimated ZTD is closer to the value provided by the IGS Tropospheric Product using the Root Square Mean Error of the differences. The results of the comparison are grouped depending on the station’s latitude in order to investigate if the quality of the estimates depend on the latitude of the station, this analysis helps users to select the most appropriate PPP software for regional ZTD determination in the user latitude. Then, the results are grouped by season of the year when the data was collected, in order to evaluate the effect of the weather. Finally, all the results obtained with the same software are grouped in order to compare the quality of estimations with each of the software packages. The days chosen for this assessment are days 027,118,208 and 300 of year 2016 and days 027,117,207 and 299 of year 2017, covering different meteorological conditions during different seasons. This assessment is relevant for GNSS meteorology applications such as water vapor calculation using ZWD and Numeric Weather Prediction models where a precise tropospheric delay is needed.n or the total refractivity N of the troposphere is described by:GNSS signals propagating through the atmosphere are delayed due to the free electron content in the ionosphere and by the air density in the electrically neutral atmosphere also called troposphere. The refractive index p, temperature T and water vapor partial pressure e [k1 = 77.689 K·h·Pa−1, k2 = 71.295 K·h·Pa−1 and k3 = 375,463 K2·h·Pa−1 are empirically determined coefficients [N along the propagation path s from receiver r to the satellite w:The total refractivity of the troposphere can be separated into two main components, the hydrostatic or dry (ectively  and it cessure e : (2)N=Ndficients . The troThe tropospheric delay can also be separated in the hydrostatic and the wet component. Therefore, Equation (3) can be written as:N in the zenith direction [The total tropospheric delay in slant path delay can be mapped to the zenith direction, yielding the Zenith Tropospheric Delay (ZTD) using a mapping function depending on the elevation angle of the satellite. The ZTD is defined as the addition of the Zenith Hydrostatic Delay (ZHD) and the Zenith Wet Delay (ZHD) which are the left and the right side of Equation (4): irection : (7)ZTD=Equation (7) indicates that the Zenith Tropospheric Delay and the refractivity of the troposphere are related. Since the refractivity depends on meteorological conditions along the signal path, the ZTD can be related to these conditions. The ZTD is a parameter estimated in the Precise Point Positioning technique.a priori information such as satellites orbits and clock errors from different sources like the International GNSS Service (IGS) [Undifferenced pseudorange and carrier phase observations from a single GPS receiver are processed in the PPP technique . The tecce (IGS) , the Jetce (IGS)  are usedce (IGS) ) and thace (IGS) . Moreovedt is the receiver’s clock offset from GPS time, dT is the satellite clock offset from GPS time, Tr is the signal path delay due to the neutral-atmosphere (primarily the troposphere), λ is the carrier wavelength, B is the ambiguity of the carrier-phase ionosphere-free combination, and Xs,Ys,Zs) and station coordinates  defined as:The ionosphere causes a delay to the GNSS signal propagating through the atmosphere which can be reduced greatly with dual-frequency data. The ionosphere-free combinations of dual-frequency GPS pseudoranges (P) and carrier-phase observations (ϕ) are related to user position, clock, troposphere and ambiguity parameters according to the following simplified observation equations : (8)lp=ρThe PPP technique has been implemented by different software packages which follow different estimation strategies or use precise ephemeris from different sources. There are online services accessible through the Internet and software packages that have to be installed and run locally in a computer. For this study, six PPP post-processing software packages were used in total, three of them are online services, APPS, CSRS-PPP and MagicGNSS and three stand-alone post-processing software packages gLAB, POINT and RTKLIB. A summary of the characteristics of the online-services and the software used for this study can be found in The Automatic Precise Positioning Service (APPS) is an online service by the Jet Propulsion Lab which can estimate position coordinates as a single set in Static Mode or a time series in Kinematic Mode. In APPS the receiver clock states are estimated as white noise with updates every measurement epoch and the Zenith Wet delay (ZWD) is estimated as a random walk with variance of 3  numbers . a priori hydrostatic delay of h is the station height above the ellipsoid in meters and a priori wet delay of 0.1 m. The wet delay is estimated together with positioning unknowns.APPS can take only dual-frequency GPS observations. The service allows the user to decide whether to use Final, Rapid and Ultra-rapid type products from the Jet Propulsion Lab (JPL) for corrections of obits and clocks of satellites. The ZTD is estimated applying the Global Mapping Function troposphere mapping function with an The Canadian Spatial Reference System (CSRS-PPP service) by Natural Resources Canada uses a dynamic filter to estimate the station position in static or kinematic mode, the station-clock states, the local tropospheric zenith delays and the carrier-phase ambiguities. The approach used in CSRS-PPP for ZTD estimation is to smooth the estimates by a backward substitution with the final converged satellite ambiguity parameters held fixed for all epochs.This approach is implemented to obtain optimal station Zenith Path Delay time series based on all observations within the observation session . PreciseThe service of MagicGNSS operated by the company GMV Aerospace and Defense is made available through their website where the user can process data in static and kinematic mode at two frequencies. The user can choose to use final and rapid products for corrections of orbits and clocks of satellites made accessible by the IGS or GMV, the user can choose either rapid or final products. The current version can process data from constellations, GPS, GLONASS, Galileo, BeiDou. Coordinates of the calculated position can be determined in two frames of reference ITRF2008 or ETRS89. MagicGNSS does not take into account in calculation parameters of the phase center antenna.The following three software packages had to be installed in the computer and had to be run locally in the processing computer. For all of them, it is necessary to load the observation file, the navigation file and for PPP, the precise ephemeris are also needed. Additionally, other corrections such as Ocean Tide Loading or the parameters of the phase center antenna can be included. Since the user has to load all the files, there is flexibility to use corrections from different sources. For this study, all the final products from the IGS were used.H is the height above sea level, in meters. gLAB is an advanced interactive educational multipurpose package to process and analyze GNSS data  developerameters ,26,27. OdryM and wetM are the dry and wet mapping function (Neill mapping function) which does not require any meteorological data. The multiplication of the mapping function and the slant delay yield the Zenith Troposheric Delay.POINT is a software package developed by the University of Nottingham. It is capable of processing L1 and L2 GPS data. It implements an Extended Kalman Filter for positioning employing double differences observables . The hydz = 0 and relative humidity hrel = 0. RTKLIB is an open source positioning software developed by Takatsu. It can implement different positioning techniques, among them, PPP which can be computed in static or kinematic mode. All the corrections are input to the software via its Graphic User Interface. The effect of the troposphere is modelled using a mapping function and zenith tropospheric delays. The mapping function in terms of the elevation angle  computed by the Institute of Geodesy and Geophysics of the Chinese Academy of Sciences was used. The Ocean Tide Loading (OTL) file obtained with the GOT00.2 model was also included and the same ANTEX file as for gLAB was used as well. The Saastamoinen model is used to compute the hydrostatic component of the tropospheric delay and the wet component is estimated as an unknown in the Extended Kalman Filter. RTKLIB had as input the same ephemeris file  and the same corrections as POINT, the same DCB, OTL and ANTEX files were used, it was run in PPP kinematic mode, the elevation mask was set to 10 degrees. The tropospheric effect was calculated as an unknown in the Extended Kalman Filter.The data used in this experiment was collected from the IGS which operates over 400 GNSS stations across the world, it provides daily and hourly observation and navigation files for each station. Furthermore, the IGS provides other products, such as satellite ephemeris, earth rotation parameters and tropospheric delay with different latencies. The tropospheric delay product is generated from ground-based GNSS data with the Bernese GPS Software version 5.0, a cut-off angle of 7, IGS final satellite, orbit and EOP products are used for the computation . Therefon is the total number of ZTD estimates available. The RMSE was computed for each station and each software per day using Equation (17). All estimates available were used. The results are shown in In order to assess the quality of the ZTD estimates of the 6 PPP software previously described, observation data from the 9 IGS stations were processed with each of the software packages and the ZTD was estimated in kinematic mode. The Root Mean Square Error (RMSE) is used as the quality indicator in this performance assessment, which is computed as:April 27th 2016 and 2017 are days 118 2016 and 117 2017 respectively. This is a day in spring in the northern hemisphere or autumn in the southern hemisphere. Therefore, mild changes of temperature are expected. The RMSE values of the differences between the estimated ZTD and the IGS tropospheric product’s value are depicted in Day 209 2016 and 208 2017 correspond to 27 July 2016 and 2017 respectively which is a day in summer in the northern hemisphere with high temperatures expected or winter in the southern hemisphere with low temperatures expected. According to the results shown in In order to evaluate the quality of ZTD estimates of each software, the RMSE of all the differences  was calculated. Its results are shown in Every software used for the analysis presented in this study uses a similar strategy to estimate the Zenith Tropospheric Delay, which is using a model to estimate the hydrostatic slant delay, use a mapping function to estimate the delay in the zenith direction and estimate the wet delay as an unknown in the parameter estimation process typically done with an Extended Kalman Filter. The online PPP software use the Global Mapping Function based on numerical weather model data while the locally run PPP processing software implement the Niell Mapping Function which depends only on the site coordinates and day of the year. Because the GMF involves the use of weather model data, it models better the delay caused by the troposphere which as seen in Equation (2) is affected by the meteorological variables near the receiver such as temperature, pressure, and partial water vapor pressure. The use of the GMF is one of the reasons why online services obtain an estimation closer to the IGS tropospheric product.The effect of the ionosphere is another reason why the estimated value and the value of ZTD from the IGS tropospheric product are different. The model used to correct the ionosphere effect used by the online PPP services is not stated, for the other three locally-run software no ionosphere model is used, only the carrier phase and code combinations is done to obtain ionosphere-free pseudoranges, this combination only eliminates the first order ionosphere effect but residual effects are not eliminated and they can cause an effect on to the signal.A third reason for the discrepancies between estimated ZTD and the values in the IGS tropospheric product is the different cut-off angle set up in the software. The IGS tropospheric product has a cut-off angle of 7. All the software packages and online PPP services used for this study allow to set the cut-off angle. However, the RTKLIB version used for this study allows to use only angles multiple of 5, therefore, 10 was used as the closest option. Also, in the other software the cut-off angle was set to 10 degrees. It is possible that this 3 degrees difference has an effect on the ZTD estimation because some satellites might be discarded for the solution. Furthermore, multipath affects the signal as well.According to the results presented in this study, POINT and RTKLIB had very high RMSE values for stations near the equator which means that the model currently used does not clearly represent the tropospheric effect at these latitudes, possible reasons is that the thickness of the troposphere on the equatorial region is higher than in the polar region and different weather conditions near the equator. Also, APPS and MAGIC obtained the highest RMSE values for stations in the center for days 27 2016 and 2017, 118 2016, 117 2017 and 209 2016, however for the other days the highest values were found for the southern and northern hemisphere respectively which confirms that the equatorial region has specific atmospheric conditions that are not properly accounted for with models and the parameters used for the estimation. CSRS-PPP and GLAB obtained high RMSE values with data from different latitudes at different days. However, the results with CSRS-PPP were always less than 1 cm (except for day 27 2017) and in the case of GLAB the results were in the range of 2 and 6 cm always which means that both software obtained estimates very close to the IGS tropospheric value with all data. The solution with GLAB takes one epoch to converge, so the first epoch is not considered in the RMSE analysis.This study only included eight days of data, however the same days in different years were chosen, also, the stations chosen are distributed throughout the globe. It is expected to find similar weather conditions the same days of two different years, therefore a trend can be found of how close the estimations are to the IGS tropospheric product. The stations are located in different latitudes which allows to study how the different models used for the tropospheric model are influenced by the latitude of the station.In this paper, a comparison analysis of the estimated Zenith Tropospheric Delay (ZTD) obtained with 6 Precise Point Positioning (PPP) post-processing software and the International GNSS Service (IGS) tropospheric product is presented. The estimated ZTD obtained with APPS, CSRS-PPP, MagicGNSS, POINT, RTKLIB and gLAB were compared with the ZTD provided by IGS. The Root Mean Square Error (RMSE) was used as the indicator of accuracy of the estimation because it indicates how different the estimated value is from the ground truth.Three trends were found in this study, first, it was found that CSRS-PPP obtains ZTD estimates very close to the value from the IGS Tropospheric product. Second, it was found that the tropospheric models currently implemented in RTKLIB and POINT do not account properly to the weather and atmospheric conditions in the equatorial region. The corrections used by CSRS-PPP and MAGIC are very precise so estimates closer to the truth value were found. The third trend found was that GLAB also estimates the ZTD to a value very close to the IGS Troposheric product.The season change did not have a big impact on the ZTD estimation by PPP software. With the selected data sets. If precise ZTD estimates are needed for GNSS meteorology or numeric weather models, CSRS-PPP can provide very accurate estimates followed by MagicGNSS and gLAB.