Activity 45.1 how can you identify

For more information, see "Actions". You can define your own actions, for WebCenter or for other applications, by exporting the Activity Graph metadata definitions to an XML file, editing the file, and then importing the metadata back into WebCenter. For example, if you want to integrate your CRM application with Activity Graph, you could define new actions for opening a service request, assigning a service request to a customer service representative, and closing a service request.

URN —An attribute of the action element, this is a string that uniquely identifies the action. Simple —These actions are useful for counting. They have no other metadata besides the source, the target, and the occurred time. For example, WebCenter comes with a preregistered view-count simple action whose associated relation value increases each time the person clicks on the same item, but also decays over time.

Boolean —These actions are useful when you just want to know whether something has happened or not, but not how many times it has happened. Boolean actions have one additional Boolean as metadata. For example, WebCenter comes with a Boolean view action whose associated relation value doesn't increase each time the person clicks on the same item.

It just records whether a person has clicked on a specific item or not. Non-negative Integer —Actions that have one additional integer as metadata, where the integer cannot be negative. Rating assigning a number of stars is the typical example. Integer —Actions that have one additional integer as metadata. This can be used for ratings that allow negative values. An example of a symmetric action is the connect action, which occurs when two users connect in the People Connections service.

Valid values are User or Item. Valid values are Sum or LastAssigned. Sum actions increment each time they occur, for example the edit-count action.

LastAssigned actions keep whatever value was passed in the most recent occurrence of the action. Non-counting simple actions like create and edit are LastAssigned. An example of a LastAssigned Integer action would be a rating action. When computing the relation value, the value of each action is multiplied by the decay factor every decay period following the occurrence of the action. Activity Graph includes metadata definitions for the similarity calculations that are used by WebCenter.

For more information, see "Similarity Calculations". You can define your own similarity calculations, for WebCenter or for other applications, by exporting the Activity Graph metadata definitions to an XML file, editing the file, and then importing the metadata back into WebCenter. For example, if you want to integrate your CRM application with Activity Graph, you could define an item-assign similarity calculations for to help recommend other service requests that were assigned to the same person.

Edit the XML file to define the new similarity calculation. For each similarity calculation, you must specify:. URN —An attribute of the similarityCalculation element that is a string that uniquely identifies the similarity calculation. There is currently only one supported similarity function: Tanimoto.

This function measures similarity between two items as the ratio of the number of common actions to the total number of actions on those items.

These are the targets of the actions represented in the similarity calculation's relation combination. Boolean OR is used by all WebCenter out-of-the-box similarity calculations and it simply states that the resulting relation combination has a value of 1 if an only if any of the constituent relations have a positive value.

A Weighted Sum relation combination is a linear combination of relation values, where the coefficients have to be specified as part of the combination. In the out-of-the-box metadata definitions, Weighted Sum relation combinations are used in rank calculations. Activity Graph includes metadata definitions for the rank calculations that are used by the Activity Graph Rank Engine to calculate the importance of nodes in the activity graph.

You can define your own rank calculations, for WebCenter or for other applications, by exporting the Activity Graph metadata definitions to an XML file, editing the file, and then importing the metadata back into WebCenter. Edit the XML file to define the new rank calculation. For each rank calculation, you must specify:. URN —An attribute of the rankCalculation element, this is a string that uniquely identifies the rank calculation. This class receives a set of object rankings from the Rank Engine and stores them in a search engine where they can later be used to influence search query ranking.

WebCenter includes one rank acceptor out of the box, which will persist ranks to Oracle Secure Enterprise Search. Activity providers are used by the Activity Graph engine during the gathering process to generate activities from recorded occurrences of actions. For example, the Analytics Activity Provider reads actions from the Analytics event tables and uses a registered set of mappings to generate activities.

These activities are then used to determine relations, which are used in turn to determine recommendations and search ranks. If you want to integrate other applications with the Activity Graph engine, you can create your own activity providers to generate activities from those applications. To make a custom activity provider available to the Activity Graph engine, you must register it by adding an activity provider assignment to the Activity Graph metadata definitions. An activity provider assignment maps the triple of the action , srcClass , and trgClass to the Java class that implements the activity provider.

Edit the XML file to define the new activity provider assignment. For each activity provider assignment, you must specify:. Specify one registered action.

Specify one registered node class. You can create your own QRPPs to further filter recommendation results or to provide display metadata for recommendations when you are integrating the Activity Graph engine with other applications. This section provides information to assist you in troubleshooting problems you may encounter while using the Activity Graph service. Check whether the events are being captured by the Analytics Event Collector.

You can verify this by checking the collector logs. If the logs do not show the events being captured, the problem is with the Analytics Event Collector. The Analytics Event Collector logs show that events are being captured but recommendations are not shown in the task flows.

You may need to adjust the schedule or launch an immediate run in order to gather and analyze recent events. Verify the relation tables in the Activities database ActivitiesDS for the presence of any data. If the Activity Graph engines are working correctly, these relation tables should have some data in them. If data is present in the tables and there are still no recommendations in the task flows, then the task flows might be broken.

In this case, users who are not present in the OID to which the services are wired will not be suggested recommendation connections. A Space is not suggested in the Similar Spaces task flow even after a successful user interaction. Check to see that the logged in user has permissions to access the Space by finding the Space in the Browse Spaces task flow.

For recommended items to be displayed in the Similar Items task flow, the item for which the recommended items are to be displayed should be selected in another task flow on the page for example, the Document Manager task flow.

This could be because the current user does not have view privileges on the item. This is the correct behavior. Users should not see recommendations for items on which they do not have sufficient privileges.

If the user should be able to see the item, grant the user sufficient privileges. Specific types of items are not being displayed for example, documents, wikis, and blogs are seen in the task flow, but not discussions. Check the status of the specific service. If the service is unavailable items from that service will not be displayed in the Similar Items task flow.

Items are suggested only for some users; other users do not get any suggested items in the Similar Items task flow. In this case, users who not present in the OID to which the services are wired will not see suggested items from that service.

Skip Headers. This chapter includes the following sections: Section It includes the following subsections: Section For the Similar Spaces task flow, the context is the current Space. Test that activity graph data is available in the WebCenter Portal application 6. Note: While you can set up the connections to back-end servers at design time in JDeveloper, you can later add, delete, or modify connections in your deployed environment using Enterprise Manager Fusion Middleware Control.

Table lists the task flows provided by the Activity Graph service. The Recommended Connections task flow is available by default on each user's Profile page. Items of interest may include a wiki page, a blog post, a document, or a discussion topic. To add the Recommended Connections task flow to your WebCenter Portal application: Prepare your application as described in Section Select Region from the resulting context menu.

In the Edit Task Flow Binding dialog, enter values for the parameters, or accept the defaults. Save and run your page. Under Executables , you'll see the task flow you added. For items, the value is derived from the selection event. By default the information is derived from the selection event.

The WebCenter default actions are listed in Table The default value is false. Note: For convenience, the getSimilarObjects method takes string arguments instead of the list and map arguments used at the lower levels of the APIs, since that is typically how you would configure them as task flow input parameters.

To find the entry point for the Activity Graph service, find the link element with a resourceType of: urn:oracle:webcenter:activitygraph:recommendations urn:oracle:webcenter:activitygraph:items The corresponding href or template element provides the URI entry point.

Navigation Paths to recommendations This section shows how the client can navigate through the hypermedia to access this resource: resourceIndex recommendations Supported Methods for recommendations The following methods are supported by this resource: GET request - Parameters: startIndex , itemsPerPage , utoken For information about these common parameters, see "Common Request Query Parameters".

The following additional parameters are available: classURN —the node class URN that identifies the type of the object for which you are requesting recommendations.

For example, gs-edit;gs-all:1 classURNRestrictions —a comma-separated list of types of objects, identified by node class URN, to exclude from the recommendations excludeObjectActions —a comma-separated list of actions, identified by action URN, to exclude from the recommendations. Table Related Resource Types for recommendations rel resourceType self urn:oracle:webcenter:activitygraph:recommendations.

Navigation Paths to recommendation This section shows how the client can navigate through the hypermedia to access the recommendation resource: resourceIndex recommendations recommendation Read-only Elements for recommendation Table lists the read-only elements for the recommendations resource.

Navigation Paths to items This section shows how the client can navigate through the hypermedia to access this resource: resourceIndex items Supported Methods for items The following methods are supported by this resource: GET request - Parameters: startIndex , itemsPerPage , utoken For information about these common parameters, see "Common Request Query Parameters".

The following additional parameters are available: similarityURN —the URN of the similarity calculation to be used determine which objects to return. For example item-tag , gs-edit , user-connect srcClassURN —the node class URN that identifies the type of the object for which you are requesting recommendations. Table Related Resource Types for items rel resourceType self urn:oracle:webcenter:activitygraph:items.

Navigation Paths to item This section shows how the client can navigate through the hypermedia to access the item resource: resourceIndex recommendations recommendation item resourceIndex items item Supported Methods for item The following method is supported by this resource type: PUT Request—Body: item Response—Body: item Writable Elements for item Table lists the writable elements for this resource type.

Table Related Resource Types for item rel resourceType self urn:oracle:webcenter:activitygraph:items:item. This section includes the following subsections: Section Edit the XML file to define the new node class. For each custom node class, you must specify: URN —An attribute of the nodeClass element, this is a string that uniquely identifies the node class nodeType —A sub-element that indicates whether objects defined by the node class are items or users.

Edit the XML file to define the new action. For each custom action, you must specify: URN —An attribute of the action element, this is a string that uniquely identifies the action actionType —A sub-element. Valid values are: Simple —These actions are useful for counting. For each similarity calculation, you must specify: URN —An attribute of the similarityCalculation element that is a string that uniquely identifies the similarity calculation. For each rank calculation, you must specify: URN —An attribute of the rankCalculation element, this is a string that uniquely identifies the rank calculation.

You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser or turn off compatibility mode in Internet Explorer. In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. Malaria parasite transmission to mosquitoes relies on the uptake of sexual stage parasites during a blood meal and subsequent formation of oocysts on the mosquito midgut wall.

Transmission-blocking vaccines TBVs and monoclonal antibodies mAbs target sexual stage antigens to interrupt human-to-mosquito transmission and may form important tools for malaria elimination.

Although most epitopes of these antigens are considered highly conserved, little is known about the impact of natural genetic diversity on the functional activity of transmission-blocking antibodies. Transmission-reducing activity TRA was measured as reduction in mean oocyst intensity.

Sequencing of oocysts that survived high mAb concentrations did not suggest enrichment of escape genotypes. Using six laboratory-adapted strains, we revealed that mutations in one Pfs domain correlate with mAb gamete surface binding and functional TRA.

Our findings demonstrate that, despite the conserved nature of sexual stage antigens, minor sequence variation can significantly impact the efficacy of transmission-blocking mAbs. Since mAb Malaria, caused by the unicellular parasite Plasmodium spp.

Current tools, while demonstrating great impact, are considered insufficient to eliminate malaria from most African regions 2. One tremendous challenge for malaria control and elimination is the efficient spread of malaria to mosquitoes that starts with the uptake of circulating sexual stage parasites, gametocytes, by the mosquito vector during a blood meal on an infected individual.

In the mosquito midgut, gametocytes egress from the host red blood cells and develop into gametes. Male gametocytes produce up to eight motile microgametes upon exflagellation and female gametocytes develop into one immotile macrogamete.

Zygotes are formed upon fertilization of a macrogamete by a microgamete 3 , 4. The zygote develops into a motile ookinete that is able to traverse the midgut wall to establish an oocyst 5. After differentiation and replication inside the oocyst, parasites are released as sporozoites that migrate to the salivary glands and render the mosquito infectious.

Transmission-blocking vaccines TBVs aim to induce antibodies that are taken up by the mosquito vector together with the infectious blood meal containing gametocytes. In the mosquito midgut, these antibodies bind to surface antigens on sexual stage parasites and thereby interfere with sexual development. Antibodies against Pfs25 target zygotes and ookinetes and prevent oocyst formation 6 , 8 , 9. Development of these vaccine candidates has been hampered by challenges with recombinant protein expression and replication of pre-clinical successes.

The first versions of Pfsbased vaccines have been tested in both naive healthy adults and in malaria-exposed individuals 10 , 11 , 12 , Recently, Pfsbased vaccines have also entered phase I studies ref. While the development of a highly effective TBV formulation is still challenging, a panel of potent monoclonal antibodies mAbs targeting these antigens is readily available. These have been isolated from immunized rodents and block development of cultured parasites in in vitro standard membrane feeding assays SMFAs These mAbs provide insight into protective epitopes and as such may inform vaccine design and development In addition, passive immunization with mAbs can form an alternative immunization strategy that conveys predictable high-level protection.

Fc modifications that extend the serum half-life of immunoglobulin IgGs 17 make it conceivable that efficacious concentrations of mAbs can be sustained for periods that are sufficiently long to support malaria elimination initiatives, contain outbreaks or span seasonal peaks of transmission. Given the genetic diversity of parasites in endemic settings, cross-strain protection is crucial for the efficacy of both active and passive immunization strategies.

Asexual stage antigens in particular are highly polymorphic and vaccines targeting these antigens face challenges to induce cross-strain protection The general consensus is that sexual stage antigens are well conserved Supplementary Fig.

Nevertheless, genetic variation has been observed, especially in Pfs Given their increasing prominence in malaria vaccine development, it is both timely and important to assess whether active and passive immunization strategies are likely to encounter challenges due to genetic diversity.

All mAbs were raised against Plasmodium falciparum NF Cultured NF54 parasites were mixed with serial dilutions of mAbs and fed to Anopheles stephensi mosquitoes. Oocysts were counted and TRA was calculated as the mean decrease in the number of oocysts per mosquito compared to negative controls from the same experiment In SMFA experiments, reductions in oocyst intensity rather than prevalence are the most robust and informative read-out Monoclonal antibodies mAbs 4B7 Pfs25, a , Thin grey lines connect observations from individual feeding experiments with multiple mAb concentrations.

Thin grey lines connect observations from individual patients. The mAb concentration is shown on the x -axis square root-transformed. The ratio of oocyst intensity in control conditions over antibody test conditions is shown on the left y -axis and corresponding transmission-reducing activity TRA on the right y -axis. Note that transmission in some conditions was higher compared to controls, i. It is currently unclear whether this is a methodological artefact or real biological phenomenon related to low antibody density We then tested the efficacy of mAbs in direct membrane feeding assay DMFA experiments with blood from naturally infected gametocyte carriers in Cameroon and Burkina Faso.

Compared to SMFA, these DMFA experiments more closely resemble natural transmission conditions as they cover variation in gametocyte densities, genetically diverse strains and potentially multiclonal infections.

Sequencing of parasite clones was not performed for blood isolates due to complexity of associating genotypes present in the bloodstream in relation to transmission potential Naturally acquired antibodies were removed by serum replacement and mAbs were added in European control serum at various concentrations before feeding to Anopheles coluzzii mosquitoes. Oocyst prevalence i. We therefore suspected that many patient-derived blood samples contained parasite strains that were not sensitive to mAb 2A2.

The concentration of a monoclonal antibody mAb 4B7 Pfs25 , b mAb Transmission-reducing activity TRA was quantified as the reduction in mean oocyst intensity between antibody control and mAb condition for each donor. DMFA direct membrane feeding assays.

To further investigate the impact of genetic variation on the efficacy of mAb 2A2, SMFA experiments with several laboratory-adapted parasite strains were performed. SMFAs with six P. White arrows in bright field images indicate activated female gametes. Non-synonymous single-nucleotide polymorphism SNP -encoded amino acids are specified and invariant amino acids are shown as dots. Histidine H is mutated to aspartate in all strains that are not sensitive to mAb 2A2 and is highlighted in red.

Other amino acid variants are shown in blue. Histidine H is located in a non-structured loop, which is presented as a dashed line. Binding experiments in which female gametes were incubated with mAb 2A2 demonstrated a similar heterogeneity in antibody binding to parasite strains Fig.

Strong reactivity of the mAb with native protein on the gamete surface of NF54 parasites was observed, even at a low concentration of 0. For the strains that showed binding with mAb 2A2 at all tested concentrations, we did not detect any non-specific signal with the secondary antibody Supplementary Fig. The observed differences in antibody binding were not the result of variation in Pfs antigen abundance as demonstrated by binding experiments with polyclonal anti-Pfs mice serum Fig.

The Pfs domain that is targeted by mAb 2A2 is currently unknown. In western blots, mAb 2A2 did not recognize recombinantly expressed fusion of pro-domain and domain I, while it did recognize Pfs in gametocyte extract Supplementary Fig.

We explored Pfs sequence data to identify the antibody-binding site. We had full genome sequences available for three of the strains and full-length Pfs gene sequences revealed five domains that contain unique non-synonymous single-nucleotide polymorphisms SNPs for NF that are not present in NF54 and NF Supplementary Fig.

Sequencing of these five domains in the other three strains suggested that domain IV contains the presumed binding site of mAb 2A2, since this is the only domain that contains non-synonymous SNPs in all three non-sensitive strains NF, NF and NF that are absent in the sensitive strains Fig. One non-synonymous SNP, resulting in an HD mutation, is unique to non-sensitive strains, suggesting that this residue could be critical for antibody binding.

A three-dimensional 3D model of domain IV revealed that most of these non-synonymous SNP-encoded amino acids are in close proximity to each other, and it is therefore plausible that several are located in the mAb 2A2-binding site Fig.

The amino acid variations that we find in Pfs domain IV in the laboratory strains are also observed in parasite strains from most geographical regions 28 indicating that there is no geographical fixation Supplementary Fig. Altogether, our data strongly suggest that domain IV is the binding domain of mAb 2A2 and that amino acid mutations affect antibody binding and thereby efficacy. To test this hypothesis, we extracted DNA from single oocysts that formed in mosquitoes that fed on gametocytes in the presence of high mAb concentrations and sequenced the targeted domains.

These data were available for donors from Burkina Faso only, where single oocyst dissections were performed. Oocyst DNA was also sequenced from control samples without test antibodies. We did not find non-synonymous SNPs in Pfs25 in oocysts from both the antibody and control condition Fig. Oocyst genotypes from direct membrane feeding experiments with high concentrations of mAb 4B7 Pfs25 , mAb The sequences were compared to the NF54 reference strain to identify non-synonymous single-nucleotide polymorphisms SNPs.

Only oocysts from Burkina Faso were available and included in this analysis. The raw data of this figure can be found in the Supplementary Material Supplementary Tables 2 — 4. We detected three of these among the sequenced oocysts Fig.

All three non-synonymous SNPs are distal to the previously characterized binding site of mAb For some donors, we sequenced multiple oocysts and obtained more than one unique sequence, as could be expected from multiclonal infections.

For Pfs, we examined the sequence of domain IV, which we identified as the likely target of mAb 2A2. No exact NF54 reference sequence was observed. At three positions amino acid mutations HY, YS and QK , NF54 carries the minor allele while most oocysts and all five analyzed laboratory-adapted strains carry the major allele Fig. The eight non-synonymous SNPs observed in the oocysts were reported before and exact combinations of these SNPs for each oocyst are diverse Supplementary Table 3.

Five oocysts were identical to the NF genotype, but none of the other 31 oocysts matched with any of our laboratory strains. No clear difference was observed in the number or combination of non-synonymous SNPs in oocysts that appeared at high mAb 2A2 concentration compared to control condition. One of the major hurdles in malaria vaccine and antibody development is genetic variation across Plasmodium strains. Since mAbs target single epitopes, they are particularly vulnerable to polymorphisms.

Although sexual stage antigens are more conserved than asexual stage antigens, it is unknown whether transmission-blocking antibodies indeed provide cross-strain protection. In in vitro experiments with P. We evaluated the potency of three established transmission-blocking mAbs against naturally acquired P. While the overall potency of mAb Since many of our donors carried multiclonal P. In total, we identified three previously described SNPs 33 , all of which are outside the mAb Moreover, at high mAb Taken together, it seems unlikely that parasites escape antibody pressure due to polymorphisms in the 6C domain.

Small differences in achieving full transmission blockade between DMFA and SMFA while having highly comparable IC 80 estimates have to be interpreted with caution and may be a chance finding in the limited number of individual experiments. The current data do not indicate substantial heterogeneity in mAb efficacy. Similar findings were obtained for mAb 4B7. In contrast, the Pfs targeting mAb 2A2 failed to block transmission of gametocytes from most gametocyte donors tested.

While this was based on a limited number of experiments and it is not possible to estimate what fraction of naturally acquired infections was not blocked by 2A2, the limited mAb efficacy is striking. This contrasts with its potency in the SMFA and findings with polyclonal antibodies 34 , 36 and strongly suggests that genetic variation in the Pfs locus of circulating gametocytes affects the efficacy of this mAb.

Using six laboratory-adapted strains from geographically distinct locations, we demonstrated that mAb 2A2 did not bind to the gamete surface of certain strains and that binding was in line with functional TRA. The target epitope of mAb 2A2 is currently unknown. Importantly, many immunogenicity studies with recombinant Pfs fragments have demonstrated that only antibodies induced against the pro-domain and domain I of Pfs, which together encompass the leading vaccine construct D1M 37 , block transmission.

Our data strongly suggest that another domain of Pfs can also be the target of potent transmission-blocking antibodies. Recombinant fragments covering domains outside the pro-domain and domain I may have failed to induce efficacious antibodies in previous studies due to improper folding of recombinant immunogens. Our data support renewed efforts to produce properly folded Pfs fragments, which could lead to the discovery of potent novel Pfsbased vaccine candidates.

In conclusion, we demonstrate that evaluating potency of transmission-blocking mAbs against field strains is important in the pre- clinical development process and for identification of potent and conserved epitopes to inform vaccine design and development.

We tested three different mAbs against three leading TB vaccine candidates and found that the potency of one of these was affected by genetic diversity in contrast to the other two mAbs. Increased oocyst densities were sporadically observed in experiments with low mAb concentrations. Whether this is explained by biologically relevant transmission enhancement or methodological issues is currently unknown 38 and requires dedicated studies. Our data are not predictive for cross-strain efficacy of other mAbs and polyclonal antibodies to these targets as other antibodies may target different epitopes.

The pro-domain and domain I contained in the leading Pfs vaccine construct D1M are more conserved and mAbs and polyclonal antibodies against this target are therefore more likely to provide cross-strain protection. Setting: New Haven, Connecticut. Participants: nondisabled members of a large health plan, 70 years of age or older, who were categorized according to their risk for disability low, intermediate, or high. Measurements: Occurrence of restricted activity defined as having stayed in bed for at least half a day or having cut down on one's usual activities because of an illness, injury, or another problem , problems leading to restricted activity, and health care utilization were ascertained during monthly telephone interviews for up to 2 years.

Results: In median follow-up of 15 months, The rates of restricted activity per person-months were Of the 24 prespecified health-related and non-health-related problems, the rates per person-months of restricted activity ranged from 0.