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Two! New videos released on the GOTO YouTube Channel. Watch:
AngularJS (4 days) - March 24 - 27
Core Spring (4 days) - April 7 - 10
Introduction to Docker (2 days) - April 29 & 30 in Eindhoven
This two day training is a solid introduction to the Docker platform. In this training you will investigate the "why" of Docker and through a series of exercises learn it's most important commands and capabilities. After this workshop, you will have a basic understanding of Docker and you will be able to comfortably integrate it in your working environment For more info or please contact us or visit the Academy.
Enterprise Integration with Spring (4 days) - May 18 - 21
Axon Immersion (2 days) - October 8 & 9 -
A 2-day immersion training, the ideal way to learn how to apply CQRS using the Axon Framework, an open source Java framework that helps developers create scalable and extensible applications by providing the building blocks that CQRS based infrastructures typically require. The training will be led by our CQRS expert, Allard Buijze, who has been investigating and applying CQRS to a number of projects. As a result, Allard created the Axon Framework. For more info or please contact us or visit the Academy.
|Trainings A'dam 2015
|March 24 - 27
|Andreas Frisch
|April 7 - 10
|Core Spring
|Joris Kuipers
|April 14 - 17
|Andreas Frisch
|May 18 - 21
|Enterprise Integration
|Joris Kuipers
|June 9 - 12
|Core Spring
|Joris Kuipers
|June 23 - 26
|Andreas Frisch
|September 1 - 4
|Core Spring
|Joris Kuipers
|September 1 - 4
|Andreas Frisch
|October 6 - 9
|Spring Web
|Joris Kuipers
|October 8 - 9
|Axon Immersion
|Allard Buijze
|November 10 -13
|Andreas Frisch
|November 17 - 20
|Core Spring
|Joris Kuipers
But wouldn't it be great if there was only one Elasticsearch cluster and every departments could manage their own Kibana dashboards? And still have the security in place to prevent leaking of private data?
With Elasticsearch Shield, you can create a configurable layer of security on top of your Elasticsearch cluster. In this article, we will explore a small example setup with Shield and Kibana.
In this article, we'll use Elasticsearch 1.4.4, Shield 1.0.1 and Kibana 4.0.0. These are at the time of writing the most-recent versions. Beginner knowledge of Elasticsearch is expected.
Suppose we want to keep our patient's names private. An index of patients will be available only for one department. An index of cases will be available to all departments.
First, we'll add some test data to the cluster. Create a file
hospital.jsonwith the following content:
{ "index" : { "_index" : "cases", "_type" : "case", "_id" : "101" } } { "admission" : "2015-01-03", "discharge" : "2015-01-04", "injury" : "broken arm" } { "index" : { "_index" : "cases", "_type" : "case", "_id" : "102" } } { "admission" : "2015-01-03", "discharge" : "2015-01-06", "injury" : "broken leg" } { "index" : { "_index" : "cases", "_type" : "case", "_id" : "103" } } { "admission" : "2015-01-06", "discharge" : "2015-01-07", "injury" : "broken nose" } { "index" : { "_index" : "cases", "_type" : "case", "_id" : "104" } } { "admission" : "2015-01-07", "discharge" : "2015-01-07", "injury" : "bruised arm" } { "index" : { "_index" : "cases", "_type" : "case", "_id" : "105" } } { "admission" : "2015-01-08", "discharge" : "2015-01-10", "injury" : "broken arm" } { "index" : { "_index" : "patients", "_type" : "patient", "_id" : "101" } } { "name" : "Adam", "age" : 28 } { "index" : { "_index" : "patients", "_type" : "patient", "_id" : "102" } } { "name" : "Bob", "age" : 45 } { "index" : { "_index" : "patients", "_type" : "patient", "_id" : "103" } } { "name" : "Carol", "age" : 34 } { "index" : { "_index" : "patients", "_type" : "patient", "_id" : "104" } } { "name" : "David", "age" : 14 } { "index" : { "_index" : "patients", "_type" : "patient", "_id" : "105" } } { "name" : "Eddie", "age" : 72 }
Then bulk index these documents in the cluster:
$ curl -X POST 'http://localhost:9200/_bulk' --data-binary @./hospital.json
Without security, every user can access all documents. Let's install Shield to add security.
Directions on how to install Shield can be found at the Elasticsearch website. We will do this step by step.
Shield is a commercial product, so first we need to install the license manager:
$ elasticsearch/bin/plugin -i elasticsearch/license/latest -> Installing elasticsearch/license/latest... Trying http://download.elasticsearch.org/elasticsearch/license/license-latest.zip... Downloading .....................................DONE Installed elasticsearch/license/latest into /home/patrick/blog/elasticsearch/plugins/license
Now install Shield itself in the same manner:
$ elasticsearch/bin/plugin -i elasticsearch/shield/latest -> Installing elasticsearch/shield/latest... Trying http://download.elasticsearch.org/elasticsearch/shield/shield-latest.zip... Downloading .....................................DONE Installed elasticsearch/shield/latest into /home/patrick/blog/elasticsearch/plugins/shield
You will need to restart the nodes of your cluster to activate the plugins.
In the logs of Elasticsearch you'll see some messages from the new plugins:
[2015-02-12 08:18:01,347][INFO ][shield.license ] [node0] enabling license for [shield] [2015-02-12 08:18:01,347][INFO ][license.plugin.core ] [node0] license for [shield] - valid [2015-02-12 08:18:01,355][ERROR][shield.license ] [node0] # # Shield license will expire on [Saturday, March 14, 2015]. Cluster health, cluster stats and indices stats operations are # blocked on Shield license expiration. All data operations (read and write) continue to work. If you # have a new license, please update it. Otherwise, please reach out to your support contact. #
Notice that you will get a 30-day trial period to experiment with Shield.
Now all our data is protected. See what happens when we try to get a document:
$ curl localhost:9200/cases/case/101?pretty=true { "error" : "AuthenticationException[missing authentication token for REST request [/cases/case/1]]", "status" : 401 }
We need to add some roles and users to configure the role-based access control of Shield. First we define the roles and their privileges. The definition of these are found in the
elasticsearch/config/shield/roles.yml file. Some roles, like admin and user are predefined:
# All cluster rights # All operations on all indices admin: cluster: all indices: '*': all # Read-only operations on indices user: indices: '*': read
Let's edit this
roles.yml file to describe our needs. We do not want for every user to access all indices, so we'll change
user.indices. We'll add the two roles needed for our organization: doctor and nurse. A doctor has more privileges than a nurse. Doctors can access all indices. Nurses can only access the cases index:
# Read-only operations on indices #user: # indices: # '*': read # Doctors can access all indices doctor: indices: '*': read # Nurses can only access the cases index nurse: indices: 'cases': read
Now that the roles are defined, we can create users that have these roles. Shield provides three realms to store the users: an internal realm, LDAP or Active Directory. For now, we use the internal realm. The realm is configured in
elasticsearch/config/elasticsearch.yml. If nothing is explicitly configured, the internal realm is used.
To add users the esusers command line tool can be used. Let's create two users (both with abc123 as password), one for each role:
$ elasticsearch/bin/shield/esusers useradd alice -r nurse $ elasticsearch/bin/shield/esusers useradd bob -r doctor
Just to check if the security works:
$ curl --user alice:abc123 localhost:9200/_count?pretty=true { "count" : 5, "_shards" : { "total" : 1, "successful" : 1, "failed" : 0 } } $ curl --user bob:abc123 localhost:9200/_count?pretty=true { "count" : 10, "_shards" : { "total" : 2, "successful" : 2, "failed" : 0 } }
Alice can see the 5 cases in our cases index. Bob can see those 5 cases plus the 5 patients in the patients index.
Now it's time to add Kibana in the mix. Instructions to download and install Kibana 4 can be found on the Elasticsearch website.
When we start the Kibana server we notice that Kibana is not allowed access to the Elasticsearch cluster:
$ kibana/bin/kibana {"@timestamp":"2015-02-26T08:24:48.958Z","level":"fatal","message":"AuthenticationException[missing authentication token for REST request [/.kibana/config/_search]]","node_env":"production","error":{"message":"AuthenticationException[missing authentication token for REST request [/.kibana/config/_search]]","name":"Error","stack":"Error: AuthenticationException[missing authentication token for REST request [/.kibana/config/_search]]\n at respond (/home/patrick/kibana/src/node_modules/elasticsearch/src/lib/transport.js:235:15)\n at checkRespForFailure (/home/patrick/kibana/src/node_modules/elasticsearch/src/lib/transport.js:203:7)\n at HttpConnector. (/home/patrick/kibana/src/node_modules/elasticsearch/src/lib/connectors/http.js:156:7)\n at IncomingMessage.bound (/home/patrick/kibana/src/node_modules/elasticsearch/node_modules/lodash-node/modern/internals/baseBind.js:56:17)\n at IncomingMessage.emit (events.js:117:20)\n at _stream_readable.js:944:16\n at process._tickCallback (node.js:442:13)\n"}}
We need to tell Shield that Kibana is allowed to access our cluster. Extra information of how to let Kibana work with Shield can be found in the Elasticsearch guide.
Shield is shipped with a default configuration for Kibana 4. We find the following role definition in
# The required role for kibana 4 users kibana4: cluster: cluster:monitor/nodes/info indices: '*': - indices:admin/mappings/fields/get - indices:admin/validate/query - indices:data/read/search - indices:data/read/msearch - indices:admin/get '.kibana': - indices:admin/exists - indices:admin/mapping/put - indices:admin/mappings/fields/get - indices:admin/refresh - indices:admin/validate/query - indices:data/read/get - indices:data/read/mget - indices:data/read/search - indices:data/write/delete - indices:data/write/index - indices:data/write/update
When the Kibana Server starts it needs to access the .kibana index. So we need to create a user in Shield for Kibana to connect with:
$ elasticsearch/bin/shield/esusers useradd kibana -r kibana4
This account must be configured in Kibana. Modify
# If your Elasticsearch is protected with basic auth, this is the user credentials # used by the Kibana server to perform maintence on the kibana_index at statup. Your Kibana # users will still need to authenticate with Elasticsearch (which is proxied thorugh # the Kibana server) kibana_elasticsearch_username: kibana kibana_elasticsearch_password: abc123
The Kibana users must have the kibana4 role to be able to work with Kibana. They must be able to store their visualizations and dashboards in the .kibana index:
$ elasticsearch/bin/shield/esusers roles alice -a kibana4 $ elasticsearch/bin/shield/esusers roles bob -a kibana4
Since the default kibana4 role has read access on all indices, alice and bob will be granted all access on all indices. Therefore the role permissions must be modified:
# Doctors can access all indices doctor: indices: 'cases,patients': - indices:admin/mappings/fields/get - indices:admin/validate/query - indices:data/read/search - indices:data/read/msearch - indices:admin/get # Nurses can only access the cases index nurse: indices: 'cases': - indices:admin/mappings/fields/get - indices:admin/validate/query - indices:data/read/search - indices:data/read/msearch - indices:admin/get # The required role for kibana 4 users kibana4: cluster: - cluster:monitor/nodes/info - cluster:monitor/health indices: '.kibana': - indices:admin/exists - indices:admin/mapping/put - indices:admin/mappings/fields/get - indices:admin/refresh - indices:admin/validate/query - indices:data/read/get - indices:data/read/mget - indices:data/read/search - indices:data/write/delete - indices:data/write/index - indices:data/write/update - indices:admin/create
With this configuration any user with the kibana4 role is able to use Kibana but only sees data that he or she has the proper clearance for.
We can now start the Kibana Server and see that it runs as it should:
$ kibana/bin/kibana {"@timestamp":"2015-02-26T08:53:18.961Z","level":"info","message":"Listening on 0.0.0.0:5601","node_env":"production"}
We can open a browser and head to localhost:5601 to open the Kibana web interface. Log in as Alice:
After logging in, Kibana will ask for the index pattern. We'll keep it simple:
Then in the discover tab you can add fields to your view. Notice that Alice only sees cases:
When we log in as Bob our discover tab shows both cases and patients:
To summarize: we added security to Elasticsearch with Shield and configured some users and roles. There's nothing more to it!]]>
Join us at our FREE GOTO Night on the 16th April
"An Introduction to Docker" with Adrian Mouat
Host: Adrian Mouat, Allard Buijze & Marc te Vruchte
When: 16. Apr 2015 at 17:30 - 20:30
Where:Trifork B.V in Eindhoven Register today!
In this talk, Adrian Mouat will look at how Docker can be used to provide specialized environments, catering to niche requirements by wrapping applications along with their dependencies and configuration. For example, imagine starting on a new software-development project and being given a container holding an IDE configured with the coding standards, plug-ins and repositories used by the project rather than spending days getting a working environment up and running.
The talk will explore this technique and its potential benefits and applications, centering on a demonstration of using Docker and a customized version of Vim to provide a "writeroom" like writing environment. This will then be followed by hands-on session so bring your laptop! Register today!
All Android UI are based on XML files describing the desired design. Developers are easily carried away by nesting several instances of different elements like <LinearLayout> or <RelativeLayout> to solve a layout puzzle. This can be a potential performance problem, since each elements require initialization, layout and drawing. We are talking milliseconds here, but with several layouts on-screen using, for example a <ListView>, these milliseconds get multiplied and noticeable delay could occur.
The golden rule when constructing Android layouts is to make the layout shallow and wide rather than narrow and deep. This can often be achieved by using <RelativeLayout>. A good indication of bad layout design is when nested <LinearLayout> is used. This often calls for a different approach to solving the design problem.
Below is a very simple example of layout nesting. The two <LinearLayout> are redundant and can easily be removed.
The Android SDK ships with a tool to help you with tracking down these layout issues. In the "<sdk>/tools/ folder" locate hierarchyviewer. This tool will give you a visual representation of the view hierarchy as a tree graph. More importantly, it makes it possible to inspect each individual view element and get metrics about the measure, layout, and draw times of the rendering. Color coding for each metric makes it easy to identify the slowest parts of your view. By finding the nodes with red and yellow performance indicators, you can identify the problems you should address first.
For more information of the Hierarchy Viewer, visit the Google developer page here
One of the metrics mentioned as part of the layout performance in the previous sections is drawing. Drawing performance issues can have many causes, but a common one is overdraw. Overdraw happens in all apps, but the important part is to keep it at a minimum. At its core, overdraw simply denotes the concept of the system drawing something on the screen on top of something else. If a blue rectangle is placed on a white background, the rectangle would create overdraw.
The easiest way to test an app for overdraw problem is to enable "Show GPU overdraw" in the Developer Settings of the phone or emulator. This will color the entire screen based on the amount of overdraw.
Simply put, red is bad, blue and green is good. No color at all implies no overdraw - the pixels were only painted a single time. Blue means 1x overdraw and green means 2x overdraw. Light and dark red means 3x overdraw and 4x overdraw, respectively. All red areas should be optimized. Minor light read areas are acceptable, but larger areas of red and even green should be examined further.
A common cause for overdraw is often the use of several full-screen backgrounds. If the view have several layers of overdraw even before the content is drawn, overdraw is inevitable. It is easy to fix this by simply removing the extraneous layers - again optimizing the layout hierarchies.
Android Lint is a great tool which scans the project for bugs and performance issues. Lint will find much more than just UI issues but focusing on the UI related findings it will help developers with common errors in the XML structure. It will recommend the use of compound drawables where possible and recommend removal or merge of layouts if possible to reduce nesting.
Running an Android Lint scan is simple and is a great source of potential performance gains. The tool is constantly under development and new checks are added. Another good reason to run a new scan regularly.
These simple UI performance hints are just scratching the surface of good practice when creating Android apps. One common pitfall when developing for the mobile devices: Remember the limited resources. An Android app does not have the same amount of resources as a server application even if they are both written in Java. While this post has been focusing on Android UI, several other aspects affect the performance of an app. These are out of scope of this post, but have a look at Google's own performance page for further details.
A couple of general points regarding Android app performance:
And for a quick update...
In February we ran 3 courses: the AngularJS, Core Spring and the UX Course and they all turned out to be a big hit and they were all sold out. For March we've planned the following courses, AngularJS, Axon Immersion, Intro to Docker and What's New in Spring. Usually we organize 2 trainings a month, and with 3 trainings in February and 4 in March, we are excited to see that the GOTO Academy is growing.
NEW! Introduction to Docker (2 days) - March 11 & 12 -
This two day training is a solid introduction to the Docker platform. In this training you will investigate the "why" of Docker and through a series of exercises learn it's most important commands and capabilities, including.. After this workshop, you will have a basic understanding of Docker and you will be able to comfortably integrate it in your working environment. The trainer, Quinten Krijger, is one of the earliest adopters of Docker. Shortly after its conception, Quinten co-founded Container Solutions and he is eager to share his new founded passion with others. For more info or please contact us or visit the Academy.
Axon Immersion (2 days) - March 12 & 13
A 2-day immersion training, the ideal way to learn how to apply CQRS using the Axon Framework, an open source Java framework that helps developers create scalable and extensible applications by providing the building blocks that CQRS based infrastructures typically require. The training will be led by our CQRS expert, Allard Buijze, who has been investigating and applying CQRS to a number of projects. As a result, Allard created the Axon Framework. For more info or please contact us or visit the Academy.
NEW! What's New in Spring (3 days) - March 18 - 20
This comprehensive three day course will give you an update on the new features introduced in the Spring Framework 3.x versions. In addition, you will get an overview of the latest changes in some of the other Spring projects and a quick look at the Spring Framework 4 including the Java 8 support. This training will be led by Joris Kuipers, a former SpringSource Consultant. For more info or please contact us or visit the Academy.
AngularJS (4 days) - March 24 - 27
Core Spring (4 days) - April 7 -10
|Trainings A'dam 2015
|March 11 - 12
|Intro to Docker
|Quinten Krijger
|March 12 - 13
|Axon Immersion
|Allard Buijze
|March 18 - 20
|What's New in Spring
|Joris Kuipers
|March 24 - 27
|Andreas Frisch
|April 7 - 10
|Core Spring
|Joris Kuipers
|April 14 - 17
|Andreas Frisch
|May 18 - 21
|Enterprise Integration
|Joris Kuipers
|June 9 - 12
|Core Spring
|Joris Kuipers
|June 23 - 26
|Andreas Frisch
|September 1 - 4
|Core Spring
|Joris Kuipers
|September 1 - 4
|Andreas Frisch
|October 6 - 9
|Spring Web
|Joris Kuipers
|October 8 - 9
|Axon Immersion
|Allard Buijze
|November 10 -13
|Andreas Frisch
|November 17 - 20
|Core Spring
|Joris Kuipers
The Chicago tech community has hit Meetup.com with full force and it seems that the lead players in the programming arena are attempting to bridge the gap between a multitude of diverse languages to create a cohesive Chicago programming family. Some of the faces behind these Meetups are Bob Paulin and Freddy Guime of Chicago Java User Group (CJUG); Mike Hall of UGtastic; Jerry Cattell of Chicago DevOps; and Dean Wampler of Chicago Area Scala-Enthusiasts. Earlier this month, we hosted a Meta GOTO Night with the leaders of the Chicago tech community in the hopes of learning about what was needed to improve an already thriving developer community. What we came away with was a sense that there was a lot of optimism for the future and also a consensus that in order for Chicago's blossoming tech community to thrive, there needs to be more communication across the lines of languages and companies. We think that this is where GOTO Chicago comes in to play.
Not only do developers need to get out of the office and gather with developers from other companies, an opinion held by Dean Wampler, they need to do so in a supportive environment: "There is also less of a community spirit, in the sense that relatively few developers see the need to meet regularly with their peers outside their jobs, to learn from each other... I would like to see these barriers go away." But what seems to be truly lacking in Chicago at this moment is what Mike Hall calls "cross-pollination" of communities. It seems that, thus far, individual languages have been working to strengthen their own user group without looking outside of their community. Mike Hall notes that he'd "like to see the Chicago community turn into one big amorphous blob of tech where there isn't any 'I'm a Ruby developer' ... or 'I'm a Java developer' ... No, let's simplify the equation and just say 'I'm a developer'." Now is the time to reach out and connect the dots between Java, Scala, Agile, DevOps, and so many more and to start the discussion of what exactly they want Chicago tech to look like. The more communication there is, the better chance they have on selling Chicago as a place where people to stay for jobs, rather than leave for cities like San Francisco or New York. Freddy Guime said it best, "the end-game is to help/consolidate and nurture the different user groups to make for a great ecosystem."
The consensus is pretty clear: that in order for this ecosystem to grow, there needs to be nurturing, diversity, communication and development. There need to be opportunities for everyone to gather together and really talk about what's happening and what's lacking in Chicago tech and then from there take collective actions to make those changes happen. Because, as Bob notes, "a thriving community benefits everyone: employers, staffing companies, students, and of course developers at all stages of their career… the more we can help our developers learn and grow the better the projects they can create."
With GOTO Chicago, our goal is to offer a space where this is possible: we've asked for recommendations for speakers and topics from user-groups, and are trying to make our program tailored to those needs. We offer opportunities for local tech students to participate as crew, where, in exchange for a days worth of work, they get a free registration to the conference. We also aim to highlight the benefits of all languages and platforms, and not sell anyone on one specific product. It is through conferences like GOTO that developers can learn, connect and grow to make Chicago a better environment for tech.
The obvious question here is why would you want to develop .NET software on Linux or for Linux? At the risk of sounding like throwing buzzwords around, I will say it is because Linux dominates the cloud completely. Many cloud-related technologies such as Docker, Mesos, and others build on Linux as a base. Sure, it is possible to run Windows in the cloud one way or another, but it is really hard to match the flexibility of Linux, especially when running more than just a few instances.
Quite recently Microsoft announced open-sourcing of .NET Core paving new grounds for a truly cross-platform .NET implementation. It has already been possible to run a lot of .NET software on Linux and OSX for quite some time on an independent .NET implementation called Mono, and now Microsoft is saying that they will work with the Mono project on a common code base that will eventually become the .NET core. In fact, Microsoft has been close to Xamarin, a company behind Mono, for a while now, so this step is not that surprising.
But how usable is Mono right now? That is what I set out to find out in my little experiment.
In a few words Mono is a
cross platform, open source .NET framework which supports
everything in .NET 4.5 except WPF, WWF, and with limited WCF and limited ASP.NET 4.5 async stack. It is important to note that Mono version numbers do not reflect Microsoft .NET versions in any way, so it is a good idea to take a look at the compatibility notes before starting.
Installing Mono on a modern Linux system is just a matter of typing a few commands and waiting for a few packages to download. On Debian, running the following command will give you the runtime, development toolchain, an embedded ASP.NET-compatible web server, and an IDE with a few useful plugins. This will get you started, although for a more permanent replacement for IIS, you will want to look into mod_mono for the popular Apache HTTP server.
sudo aptitude install mono-devel mono-xsp4 monodevelop monodevelop-nunit monodevelop-versioncontrol nuget
On my machine it installed Mono version 3.2.8. The latest release at the time of writing is 3.12.0. Meh, close enough. Although if you want the latest and greatest, convenient packages are available.
Now that we are setup and good to go, we needed something to tinker with. I decided to dive into Triforks source code repository and fetch the first .NET project that crossed my mind. It can be opened directly inside MonoDevelop, which is the official IDE for the Mono project, and supports C#, F#, Visual Basic .NET, C/C++, and Vala. It can natively open SLN and CSProj files.
A small complaint I have is that MonoDevelop tends to reformat and rearrange the project files. Not a big deal, but it does make it harder to compare the files with the originals.
When opening a new project, MonoDevelop will attempt to download the required assemblies using the NuGet package manager. It may complain about an invalid certificate, because none are trusted in Mono by default. Certificates can be imported by running the following command:
mozroots --sync --import
After that it worked as expected for the most part. Although it did fail to download some of the packages because for some reason it could not resolve some transitive dependencies. If that happens, you will want run it manually. Telling it to download the transitive dependency explicitly with a specific version number did the trick:
nuget install jQuery -Version 2.1.3
And after a few hours your workspace may look something like this.
Now that the assemblies are in place, clicking on Build, Build All in MonoDevelop yields the first interesting error:
The type or namespace name `AccountManagement' does not exist in the namespace `System.DirectoryServices'. Are you missing an assembly reference?
Am I? No, it does not seem to be implemented in Mono. This is an example of Windows-specific functionality, and it would need to be rewritten. A quick look at the project code reveals that it is used for managing user groups. In my case this was not a crucial functionality, so I was able to replace the code with a simple mock.
Identifying such platform-specific functionality and listing possible solutions is a good starting point in considering if moving to another platform is at all worthwhile. The exact amount of work may vary greatly depending on alternatives available, how tightly it is integrated into the project, etc.
Luckily that was the only build error, and I could attempt to run the project. But before doing that, an essential difference in how Windows and Linux systems handle file systems has to be considered. If the software was developed on Windows, it is very likely to use Windows paths such as
C:\Directory\File.txt as opposed to what is expected on Linux such as
/directory/file.txt. This and case-sensitivity is the most common source of headache. Mono does have a work-around, which can be enabled by setting the environment variable MONO_IOMAP like this:
MONO_IOMAP=all mono myapp.exe
Although first make sure that it is really needed, because such magic solutions may cause problems as much as solve them, and you may end up with a confusing error message. Fixing the core of the problem inside the source code is often the more reliable and permanent solution. Do not rely on absolute paths, but rather use paths relative to where your application is deployed, whenever possible.
Other useful parameters are MONO_LOG_LEVEL=debug and MONO_LOG_MASK=asm, which will make Mono output detailed information about assemblies being loaded. It will come in handy when there is something wrong with the project dependencies. In my case it was a .NET 4.0 project trying to load a library built for .NET 4.5.
These can also be set up from within MonoDevelop inside Project Options.
One more important thing I will only mention briefly is a database (or data storage in general). If your project uses Microsoft SQL Server, get ready to get your hands dirty migrating your data elsewhere. Case-sensitivity will probably be your enemy number one once again. In addition to SQL statements, watch out for C# code like
something.ToUpper().Equals(somethingElse), which may potentially be a problem if
somethingElse is read from a database. You may want to do something like
something.ToUpper().Equals(somethingElse.ToUpper()) to make it consistent.
So is it realistic to deploy your .NET applications on Linux? I would say yes. Even though you have to be aware of the platform you are targeting, and some compatibility problems are to be expected. But with Microsoft backing Mono, it will only become easier and more reliable to run .NET software on alternative platforms. When the platform is no longer dictated by the implementation technology, it becomes a question of what serves the interest of the involved parties best? It becomes a motivated choice.
Dear Reader,
It's been an exciting start to 2015. We have several news items that we would like to share with you. Our new launch of our new global website and we have plenty of meetup activities and GOTO nights planned for the agenda that you don't want to miss. We are thrilled to announce the new Docker training's are now available through our Trifork GOTO academy .We are creating momentum in the education market with our Brightcenter proposition and an introduction to our Eindhoven team who are actively involved in driving successful client engagements supporting our core customer needs in the the Southern part of Holland. Read on to learn more about all of this!
We are delighted to reveal our newly designed website for The Trifork Group, feel free to Take a Peek!
We encourage you to visit and explore the site so we can introduce you to our full suite of global product offering and solutions. Our new website, aside from being aesthetically pleasing, is more agile, interactive, and is easier to scan, read and navigate, enabling you our customers to find what you may need quickly. Just as importantly, our key messages and value propositions are evident and clear.
One of our main goals we wanted to achieve when designing the new site was to help you our clients get to know us better and get a feel for who we are as a company. We are now using a responsive design, which means that you'll see essentially the same design optimized for your smart phone, tablet and desktop.
We hope you will visit the new website at our new address, www.trifork.com and acquaint yourself with the new design and product offerings. We're quite proud of it, but we know there's still work to do. In the coming months, we hope to continue improving the site so that it best serves how we communicate with you. We always welcome feedback so let us know what you think by sending your comments to Global Marketing Tanya McCabe.
Thanks for being part of The Trifork Group.
We aim to empower our customers by providing expert advice on the optimization of business critical IT systems and cutting-edge technology. Enabling our customers to seamlessly integrate and use these technologies – bringing immediate value to our customers' business and its customers.
We are thrilled to have a clear value proposition to the market with our full suite of global product offerings and there will be more to come in the future. Explore more here
Interested in a 60-minute consulting session with a senior Elasticsearch specialist. We call these Brown Bag sessions. The aim is to educate and demonstrate, using best practices gleaned from thousands of deployments, how Elasticsearch can be used to architect a solution. You will soon see how easy and quick it is to get started.Request a brown bag session today!
BRIGHTCENTER: Education is rapidly taking a monumental shift from print to digital and personalized learning materials. We are delighted to announce our collaboration with ParnasSys one of the largest electronic student learning and development institutes. We are working closely with them to further develop the Master Dashboard ParnasSys giving teachers insight into the learning's of students in real–time.
The Master Dashboard retrieves the progress and results from the various content sources and matches it to the personal learning goals of students and tick off or tracks if applicable. Both the teacher and the student gain an oversight in the Master Dashboard insight into his or her development in real-time. You can view the goal of our collaboration in the following video: Master Dashboard ParnasSys . If you would like to know more round this solution or Brightcenter , please contact Peter Meijer
We are thrilled to be now creating momentum at our new Trifork Eindhoven offices. We have two new members Marc te Vruchte and Adriaan Wisse on board our team! They both bring a huge amount of industry knowledge and know-how to enable Trifork drive successful client engagements and projects across the southern part of Holland. We will soon be launching our GOTO Academy trainings in the Eindhoven area. If you are interested in any of the current training's schedules our customized workshops please feel free to contact Marc te Vruchte direct!
The energy and buzz around the Eindhoven area inspired us to join Wonderlab, and set up office in Videolab at Strijp-S. We wholeheartedly believe in the way that technology and business is combined in this region. It's our ambition to be part of this community and help local businesses in delivering high quality products through excellent technology and expertise. Read more
We love to talk with you about anything digital! So if you want to discuss technical challenges or validate the technical feasibility of your concept; feel free to contact Marc te Vruchte direct !
For the 5-year anniversary of GOTO Amsterdam, we will open the stage to YOU. The submission phase is open and we invite you to enter your talk proposal for our new 10-minute Lightning Talks track.Call for papers submit your entry here.
The International Software Development Conference designed for software developers, IT architects and project managers is back in June 2015 at the Beurs van Berlage, Amsterdam.The program is complete with impressive speakers and key not tracks you won't want to miss with key industry leaders such as Jeff Sutherland, Prag. Dave Thomas, Mary Shaw, Prof. Dr. Gunter Dueck.
Core Tracks at this year's event.
AngularJS: Take a deep dive into the latest innovations with AngularJS.
Disruption: How to change the World.
Docker: Getting from development to production hassle free, on time, every time.
Drones: Programming Drones are a Lot of Fun.
Elasticsearch: All about real-time search & analytics.
Hadoop: Getting the most value out of your data.
Micro services: A deep dive into Microservices.
Scrum: The Art of Doing Twice the Work in Half the Time.
Solutions Tracks: The talks in this track are kindly provided by our sponsors.
We are delighted to be able to be part industry events and Meetups happening in our offices! If you are interested to host your own developer Meetup, in our offices please contact us email@example.com.
This year we have a fantastic schedule outlined for keeping you up-to-date with the latest technologies and training's. The GOTO Academy is very proud to share with you that we have started to organize Docker trainings! And these will soon be available in Eindhoven !
We've published some great blogs, the newest ones.
Do you wake up in the middle of the night for the latest technologies, developments and Java updates? Or do you aspire to be part of the next generation of software gurus? Then there's only one thing to do….Join our team today!
Imagine being able to say… "I am part of the next generation!"
Think doing cool stuff! Think having fun doing it! Think of telling the world about it!
Check out our openings below :
Software Enthusiast Noord Holland
Software Enthusiast Zuid-Oost Nederland
Javascript / Front-End Developer – Amsterdam
Senior Sales Manager Nederland – Amsterdam
Senior Sales Manager Nederland – Eindhoven
We just finished building the new website for a well-known Dutch newspaper. The old website had a 15 minute TTL cache and we knew that wasn't going to cut it in the new website. Visitors want to see new articles and updates to articles the minute they're published, not 15 minutes later. Therefore, we developed a scalable caching mechanism with active, fine-grained cache invalidation using just EhCache along with Java and Spring concepts you're probably already familiar with. The solution we developed works in a distributed environment without the need for expensive distributed cache solutions.
In this blog post I'll describe how we did it.
Our website shows lists of articles. Only the title and a summary are shown. Clicking on the article will retrieve and display the full article. Articles can contain pictures. The first picture is used as the headline picture, and is shown with the article summary in article lists.
|Blog: Active cache eviction with Ehcache and Spring Framework
|Triforker Frans shows you how to do active cache eviction with Ehcache and Spring Framework.
|Spring Framework 4.1.3 released
|Spring has released a new update of its core framework today. Besides bug fixes, it contains many user-suggested and user-contributed features. It also fixes some security issues.
|Apple announces iOS 9
|Apple has announced that the new version of its mobile operating system iOS, iOS 9 version 9, will be released in the spring of 2015. To make sure everyone buys a new iPhone, it will not work on older iPhones.
A simple data model:
Articles are imported from a CMS and inserted into the database by an importer application. The articles are read from the database and presented by multiple redundant presentation applications:
The presentation nodes do caching of pretty much everything, including the article lists and the articles, in the service layer. We use the Spring declarative caching by means of the @Cacheable annotation:
public class ArticleServiceImpl { @Cacheable(value = CacheConstants.ARTICLE) public List<ArticleImpl> getArticleById(long id) { // ... } @Cacheable(value = CacheConstants.ARTICLE_LIST, key = "#listName + '-' + #numArticles") public List<ArticleImpl> findArticlesForList(String listName, int numArticles) { // ... } } public abstract class CacheConstants { public static String ARTICLE = "article"; public static String ARTICLE_LIST = "articleList"; }
Nothing too special here:
Declarative caching is enabled by an
@EnableCaching(proxyTargetClass = true) on our JavaConfig configuration class:
@Configuration @EnableCaching(proxyTargetClass = true) public class CacheConfig { @Bean public CacheManager cacheManager() { net.sf.ehcache.CacheManager ehcacheCacheManager = ehCacheManagerFactoryBean().getObject(); return new EhCacheCacheManager(ehcacheCacheManager); } @Bean public EhCacheManagerFactoryBean ehCacheManagerFactoryBean() { EhCacheManagerFactoryBean cacheMgrFB = new EhCacheManagerFactoryBean(); // setting shared to true allows to use the same manager for e.g. Hibernate 2nd level cache cacheMgrFB.setShared(true); cacheMgrFB.setCacheManagerName("cacheManager"); cacheMgrFB.setConfigLocation(ehCacheConfigResource); return cacheMgrFB; } }
Finally, we have an
ehcache.xml that defines our caches:
<?xml version="1.0" encoding="UTF-8"?> <ehcache xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xsi:noNamespaceSchemaLocation="ehcache.xsd" updateCheck="false" name="ehcache" maxBytesLocalHeap="25%"> <sizeOfPolicy maxDepth="2000" maxDepthExceededBehavior="abort"/> <defaultCache eternal="true" overflowToDisk="false"/> <!-- Since we use active cache invalidation these caches can be eternal --> <cache name="article" eternal="true" statistics="true"> <searchable> <searchAttribute name="pictureIds" class="nl.trifork.cache.ArticleAttributeExtractor" /> </searchable> </cache> <cache name="articleList" eternal="true" statistics="true"> <searchable> <searchAttribute name="articleIds" class="nl.trifork.cache.ArticleListAttributeExtractor" /> <searchAttribute name="pictureIds" class="nl.trifork.cache.ArticleListAttributeExtractor" /> </searchable> </cache> </ehcache>
A few things to take note of here:
@Cacheable annotation.
eternal="true". We're going to remove entries from the cache exactly when we need to, so there's no reason to have entries expire automatically after a period of time!
<searchable> before in your Ehcache configuration. We need these to do fine-grained cache eviction. We'll get to this when we discuss the cache eviction. For now, see them as extra columns in your cache table next to the key and value
So our application is running. We've imported some articles that are now in the database. Our visitors have viewed some articles and article lists and these are now cached, eternally, on both presentation nodes. Now an editor changes the title of one of the articles that are already cached. This means we need to evict this article from the "article" cache as the new version needs to be read from the database. Additionally, because we show article titles when we display an article list on our website, we also need to evict any article lists containing this article.
Spring offers a
@CacheEvict annotation for declarative cache eviction, but this only works if the caching and updating of the data happens in the same JVM. In our case, data is written in one JVM -- the one running our importer -- and read in several others -- the presentation nodes. Additionally, only very simple logic can be handled in
@CacheEvict, and as we'll see later, we have more complex requirements that need some handwork.
As I pictured above, we have one node writing data - the importer - and several nodes reading and caching the data - the presentation nodes. Whenever an importer imports something, it should notify the presentation nodes so they can evict the relevant entries from the cache.
This is simple:
public void evictArticle(long id) { Ehcache ehcache = cacheManager.getEhcache(CacheConstants.ARTICLE); ehcache.remove(id); }
We could even have done this with a
@CacheEvict-annotated method:
@CacheEvict(value = CacheConstants.ARTICLE) public void evictArticle(long id) { // NOOP }
However, when an article changes, so might its representation in an article list - as seen above, we show a title, a summary, and a picture. However, when an article changes, we only have its id, not the ids of the article lists it appears in. This is where the
searchAttributes in our
ehcache.xml come in: we want to search for all article lists containing the article.
In our
ehcache.xml, we defined a
searchAttribute in the articleList cache called
articleIds. Part of the search attribute definition was a class attribute pointing to an attribute extractor. This is what it looks like (I've removed some
null and type checks for legibility) :
import net.sf.ehcache.Element; import net.sf.ehcache.search.attribute.AttributeExtractor; public class ArticleListAttributeExtractor implements AttributeExtractor { @Override public Object attributeFor(Element element, String attributeName) { List<?> articleList = (List<?>) element.getObjectValue(); StringBuilder attribute = new StringBuilder(); for (Object el : articleList) { Article article = (Article) el; attribute.append(' ').append(article.getId()).append(' '); } return attribute.toString(); } }
As you can see we concatenate the IDs of all articles in the article list separated by white space. EhCache only offers basic types for search attributes and a List or Set type is not available, so this is our way of using a String to represent a List.
This attribute extractor will be called when EhCache needs to know the value of the search attribute for a specific cache entry. When does this happen? When an EhCache query using the search attribute is performed!
So now that we have a search attribute, we can use it to search.
public void evictArticleListsForArticle(long id) { Ehcache articleListCache = cacheManager.getEhcache(CacheConstants.ARTICLE_LIST); Query query = allArticlesInListCache.createQuery(); query.addCriteria(Query.VALUE.ilike("* " + articleId + " *")); query.includeKeys(); Results results = query.execute(); for (Result result : results.all()) { String key = (String) result.getKey(); articleListCache.remove(key); } results.discard(); }
In our case, we expanded this even more. When a picture is changed, we need to evict:
The basic technique used is still the same as the one I showed above, though.
By default when
@Cacheable returns a cached value you get a pointer to the object in the cache. This means that if you change that object (by calling setters or other state-changing methods on the object), you are actually changing the object in the cache! Usually that is not what you want. There are three ways around this:
clone()) and work with it
As we recently discovered, there is a possible concurrency issue here. The
@Cacheable annotation along with the Spring directive to enable them, creates an aspect that surrounds the caching method. Before method invocation, the cache is checked. In case of a cache hit, the cached method return value is returned and the method is not executed at all. In case of a cache miss, the method is executed, and after method invocation, Spring adds an entry to the cache: the key is determined by the method parameters, the value is the result of the method call.
However, what happens if halfway during method invocation, a cache evict is done in another thread? We could get this sequence of events:
We now have old data in the cache! And it won't be evicted until version X+2 of the article is saved and another cache evict is requested.
This is actually very similar to Spring Framework issue SPR-9304, which is currently unresolved. We are looking at possible solutions here. The easiest, of course, is to synchronize the evict and
@Cacheable so that they can never execute at the same time. But this would create a bottleneck and really harm performance. Something more along the lines of optimistic locking might work better. To be continued...
We've presented a simple way to use Spring declarative caching to cache the results of a service method invocation and to also selectively evict cache entries when the data is changed from an outside source, in this case an import application. This way long-lived caches can be used to cache data while also reflecting changes in the data immediately.
I hope this will be of use to you. Do share your questions, comments, and experiences in the comments box below!]]>
This data comes from many different sources and is available as open data. Wouldn't it be great if the ANWB could use this open data to provide more accurate traffic information, either in real-time or as a prediction for a certain period? In a proof of concept we have collected and analysed the real-time traffic information to calculate the traffic intensity on the roads using elasticsearch. We also used weather information to see if the weather has influence on the need of roadside assistance.
The data is available as XML files on a FTP server and is refreshed every minute. We are processing two files, one with measurements and one with traffic speed information. The file with measurements contains 25494 records and the file with traffic speed information contains 15767 records. The traffic speed records are combined with the measurements. So this means that we index 25494 documents every minute.
Because the data consists a lot of different measure points (like cameras or lasers) we only used the measure points that are bedded in the tarmac. A road can be divided in multiple lanes and each of those lanes can have a measure point. This image displays the different measure points that are available.
Each measure point contains a lot of information such as the location, type of vehicle that passed, type of carriage way, direction but also how many vehicles passed that point. In our proof of concept we have used the measured speed and vehicle flow rate for a specific location or route to display the data for a given period. If a road contains a measure location with multiple measure points on different lanes, we summed the values of all lanes to keep the data a little bit simple.
In the image above you see a graph that displays two road directions (blue and green lines) and their corresponding traffic speed (orange and red lines). On the map you can see all the measure points that have been used to calculate the data. With this data you could possibly get a real-time overview of routes where the traffic speed becomes less and the number of cars passing a measure point will decrease. These locations could be an indication that something is happening and could be the start of a traffic jam.
The number of cars that need to be available for roadside assistance are predicted each year based on historic information. On a regular base the ANWB checks if the predictions needs to be adapted by checking a number of different possible causes that could increase the traffic like events or sudden weather changes. To make this forecast even better we have added the daily temperature (which is also available as open data provided by KNMI). With the temperature and maybe the precipitation in the future they might be able to see if there is a correlation between the numbers of assistance cars that were needed and the weather.
Here you can see the number of cases that needed assistance (green bar), long term forecast (orange bar), short term forecast (purple bar) and the temperature (blue line).
In the image above you see a list of regions and areas. Because we want to be able to filter the data on a specific region, we needed a way to store the region and area with the measurement document. Elasticsearch provides a way to match an document (which is a measurement in our case) against stored queries. This is called the percolator.
As said before, each measure point contains the location. The location consists of a latitude and longitude. We created a separate percolator type that contains all regions and areas.
So before we index a measurement document we percolate the index with the location to see which region and area matches and store these values with the measurement document. This allows us to execute a query that filters on a region and provides us correct data.
This project was only a proof of concept, but provided the ANWB enough input to talk about. With open data and the power of elasticsearch to search in near real-time we created a simple application, but this could lead to something very useful. Hopefully this project will continue and gives us better traffic information in the future!]]>


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Getting Down to the Wire
Planned departure day, barring any problems is Friday Jan. 2, 2015; which will soon be upon us. Up till now just making lists in my head, now time to do the actual packing. Am a little nervous as to how the dogs will react. It will be an adventure. Home for the next 3 months will be our 2010 Keystone Outback Sydney Edition in a small family owned campground ...
Day 1 and day 2 - Flight from JFK to Mumbai
... it. It didn't even move. See picture below. You'll know what I mean :) Our next flight from Abu Dhabi to Mumbai was shorter, about 3 hours long. Finally, we reached Mumbai at 4 in the morning and the date had changed again 12/14/14. I've been waiting for so long! I'm super excited to be in India and looking forward to our trip! Stay tuned... See you ...
Rocks & Wolves
... t bother getting up. Sandy's favorite wolf was Winston, an older wolf who lived in this pack. Denny said he had to specially give Winston his food as the others sometimes bullied him. At one point, Denny made howling sounds. Soon, one wolf joined in howling, then a couple more, and pretty soon, just about all the wolves were howling! It was a beautiful sound. We had a really good time ...
The pretty hills of Pennsylvania
... it was a problem for us as we had to push the van back up the road and into the driveway before we went out for the evening to a barbecue put on by some friends.
All went well there, I was able to source a bolt from the garage and I knew I'd be able to get another nut somewhere in the morning. The job ahead of me now was to get all the way down the East Coast to Florida without wasting too much time.
Amish Country
... much respect for their belongings. Their properties are perfectly manicured, their children are dressed immaculately and their live stock healthy and stronge. Bike riding was the perfect way to see the Amish communities, and they are so friendly. It was also a great way to show respect for their culture. When biking the country roads we had Amish people wave and greet us, we passed woman working in the gardens, men ploughing the fields, children ...

subset: commoncrawl


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The Mariah at Windswept, 2-BR Oceanfront, Clean!!
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- 2 bedrooms
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Bedrooms: 2
Bathrooms: 2
Sleeps: 6
Type: VillaThe Mariah at Windswept, 2-BR Oceanfront, Clean!!
Description from the owner
The Mariah at Windswept, located just 14 miles from historic downtown Charleston, on Kiawah's East Beach, is just steps away from the Atlantic Ocean (you can hear the surf from your bedroom), and within a short walking distance to the Night Heron Park, The Sanctuary hotel, shopping and restaurants.
Our premier end unit Windswept offers ocean views throughout the villa - with a real emphasis on luxurious comfort... professionally decorated with custom drapery, designer furniture and colors, original artwork and granite countertops throughout. Step out onto the living room balcony and enjoy the ocean view and refreshing sea breezes.
Upstairs, ...Read more
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The Mariah at Windswept, 2-BR Oceanfront, Clean!!
Kiawah Island, South Carolina
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This property is located inside a 4/5 story building that has approximately 20 villas in it. Oceanfront, oceanview, easy beach access. THIS is the SPOT for a GREAT summer vacation!!
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It appears about half of yesterday's volume happened after 3:30 pm. Maybe an attempt to keep the stock above $9.00 on a post-adjusted reverse split?
it appears revlon has fallen victim to to obamas reagon 101 romneys in jail so don't worry they have to keep outsiders out of the balance sheets for a correct turnaround 10-1 splits have never been successful they consider the pink sheets like siri stock did for a turnaround
You really have no idea what your talking about. Just because the board voted for a reverse split doesn't mean they will do one, and if they go through with it's great for REV. It's a lot easy-er to make earnings on less shares. The funds will show up, and the debt refided.
Maybe short covering because the funds are coming!


text:
Latest Constitutional monarchies Stories
By Emma Ross-Thomas MELILLA, Spain (Reuters) - It's Ramadan in Spain's North African enclave of Melilla and as tempers fray, a group of shopkeepers argue about how Spanish they are. "I am a Spanish Berber," one fasting shopkeeper shouts in Spanish, repeating it in the Berber language Tamazight.
By Emma Ross-Thomas MELILLA (Reuters) - African migrants in Spain's North African enclaves said on Friday they feared for their lives if Madrid sent them back under a plan to end attempts by hundreds to storm border fences into Spanish territory.
By Lamine Ghanmi and Emma Ross-Thomas RABAT/MELILLA (Reuters) - Moroccan troops, attempting to prevent illegal immigrants from reaching a Spanish enclave, killed six Africans in clashes in northern Morocco on Wednesday night, a local government official said on Thursday.
MADRID (Reuters) - An internal investigation has concluded that Spanish police did not fire shots that killed five migrants trying to enter Spain's North African enclave of Ceuta last week, Spain's interior minister said on Thursday. "It can be confirmed that Civil Guard (police) forces ...
By Emma Ross-Thomas MELILLA, Spain (Reuters) - Spain said on Wednesday it planned extraordinary measures to deter African migrants from storming the borders of its North African outposts after 500 people tried to burst through.
By Emma Ross-Thomas MELILLA, Spain (Reuters) - Some 500 African migrants charged the razor-wire border at Spain's north African enclave of Melilla on Wednesday, and many of the 65 who got through were injured, the government said.
By Ed Cropley BAN MUANG MANG, Thailand (Reuters) - Treading in the footsteps of her father and grandfather, Tawin Suanchatree makes the pre-dawn rounds of her rubber grove in southern Thailand armed only with a headlamp and curved knife.
By Carsten Lietz LUXEMBOURG (Reuters) - Luxembourg approved the European Union's troubled constitution by a solid majority in a referendum on Sunday, averting a threat by Prime Minister Jean-Claude Juncker to resign.
- Forsooth! indeed! originally a parenthetical phrase used in repeating the words of another with more or less contempt or disdain.


text:
Quotations About / On: CAR
Page :
Billboards, billboards, drink this, eat that, use all manner of things, everyone, the best, the cheapest, the purest and most satisfying of all their available counterparts. Red lights flicker on every horizon, airplanes beware; cars flash by, more lights. Workers repair the gas main. Signs, signs, lights, lights, streets, streets.(Neal Cassady (1926-1968), U.S. beat hero. "Leaving LA by Train at Night, High ...," The First Third and Other Writings (1971).)More quotations from: Neal Cassady, red
It all began so beautifully. After a drizzle in the morning, the sun came out bright and clear. We were driving into Dallas. In the lead car were President and Mrs. Kennedy.(Lady Bird Johnson (b. 1912), U.S. first lady. A White House Diary, first entry, Nov. 22, 1963 (1970).)More quotations from: Lady Bird Johnson, car, sun
Between here and that old car outside there are twenty-five paces. Make them. Now.(Vladimir Nabokov (1899-1977), Russian. Humbert Humbert (James Mason), Lolita, urging Lolita to leave her husband and run away with Humbert (1962).)More quotations from: Vladimir Nabokov, car
Space isn't remote at all. It's only an hour's drive away if your car could go straight upwards.(Fred, Sir Hoyle (b. 1915), British astronomer. Observer (London, Sept. 9, 1979).)More quotations from: Sir Hoyle, Fred, car
It's like driving a car at night. You never see further than your headlights, but you can make the whole trip that way.(E.L. (Edgar Lawrence) Doctorow (b. 1931), U.S. novelist. Interview in Writers at Work, Eighth Series, ed. George Plimpton (1988). Said of his writing technique.)More quotations from: E.L. (Edgar Lawrence) Doctorow, car, night
The will is never freeit is always attached to an object, a purpose. It is simply the engine in the carit can't steer.(Joyce Cary (1888-1957), British author. Interview in Writers at Work, First Series, ed. Malcolm Cowley (1958).)More quotations from: Joyce Cary, car
What our children have to fear is not the cars on the highways of tomorrow but our own pleasure in calculating the most elegant parameters of their deaths.(J.G. (James Graham) Ballard (b. 1930), British novelist. The Atrocity Exhibition, ch. 8 (1970).)
No illusion is more crucial than the illusion that great success and huge money buy you immunity from the common ills of mankind, such as cars that won't start.(Larry McMurtry (b. 1936), U.S. screenwriter, novelist, essayist. Danny Deck, in Some Can Whistle, pt. 1, ch. 11 (1989).)More quotations from: Larry McMurtry, success, money
The American Dream has run out of gas. The car has stopped. It no longer supplies the world with its images, its dreams, its fantasies. No more. It's over. It supplies the world with its nightmares now: the Kennedy assassination, Watergate, Vietnam.(J.G. (James Graham) Ballard (b. 1930), British author. repr. in Re/Search, no. 8/9, San Francisco (1984). interview in Métaphors, no. 7 (1983).)
Freedom is not an ideal, it is not even a protection, if it means nothing more than freedom to stagnate, to live without dreams, to have no greater aim than a second car and another television set.(Adlai Stevenson (1900-1965), U.S. Democratic politician. "Putting First Things First," Foreign Affairs (New York, Jan. 1960).)More quotations from: Adlai Stevenson, freedom, car, television
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Read Quotations On / About:
- alone
- america
- angel
- anger
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- believe
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- courage
- crazy
- dance
- daughter
- death
- depression
- dream
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- fire
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- future
- girl
- god
- greed
- happiness
- happy
- heaven
- hero
- home
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- june
- kiss
- laughter
- life
- lonely
- loss
- lost
- love
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- memory
- mirror
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- night
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- rain
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Capital Markets
Company Overview of Greene Holcomb & Fisher LLC
Company Overview
90 South 7th Street
Wells Fargo Center
54th Floor
Minneapolis, MN 55402
United States
Founded in 1995
Key Executives for Greene Holcomb & Fisher LLC
Greene Holcomb & Fisher LLC Key Developments
Greene Holcomb & Fisher LLC Presents at SBIA's National Summit for Middle Market Funds, Oct-21-2014 09:55 AM. Venue: The Breakers, One South County Rd, Palm Beach, FL 33480, United States. Speakers: Philip I. Smith, Managing Director and Senior Member of Healthcare Team.
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Family Values Andy Garcia & Dominik Garcia-Lorido
He Was a Strict Cuban Dad, but He's Proud of His Daughter's Turn as a Stripper in the New Film City Island
DOMINIK: My dad was the disciplinarian for sure. I'm the oldest of four, and I wasn't even allowed to have my own house key in high school.
And when you brought guys home?
DOMINIK: I didn't.
ANDY: Yeah. They were in fear.
Has your dad ever embarrassed you?
ANDY: How much time do we have?
DOMINIK: Oh yeah. When I played junior high basketball, he would run up and down the court yelling, "Keep the pressure!" in all the girls' faces. My coach ended up quitting.
ANDY: I was emotionally involved.
Same question, Andy.
ANDY: No. I'm very proud of all my kids. My girls have been great examples for what a young girl should be.
DOMINIK: Maybe when my bathing suits are too small. Those one-pieces that the Olympic swimmers wear? My dad thinks that's sexy.
ANDY: To me that's the way to go. You leave it up to the imagination.
So how did you handle Dominik playing a stripper in City Island? DOMINIK: I tip my hat to pole dancers. It's superhard!
ANDY: I was barred from set that day.
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The present invention relates to prodrug compounds of inhibitors of dipeptidyl peptidase IV (DP IV), which prodrug compounds have the general formula A-B-C, wherein
A is an amino acid,
B is a chemical bond between A and C or is an amino acid, and
C is a stable inhibitor of DP IV.
Such prodrug compounds are used in the treatment of impaired glucose tolerance, glucosuria, hyperlipidaemia, metabolic acidoses, diabetes mellitus, diabetic neuropathy and nephropathy and of sequelae of diabetes mellitus in mammals.
1. Prodrug compounds of inhibitors of dipeptidyl peptidase IV (DP IV), which prodrug compounds have the general formula A-B-C, wherein
A is an amino acid,
B is a chemical bond between A and C or is an amino acid, and
C is a stable inhibitor of DP IV.
2. Prodrug compounds according to
3. Prodrug compounds according to
4. Prodrug compounds according to one of the preceding claims, characterised in that C is an aminoacylpyrrolidide, aminoacylthiazolidide or N-dipeptidyl, O-acyl hydroxylamine.
5. Prodrug compounds according to one of the preceding claims, characterised in that the inhibitors are present in salt form.
6. Prodrug compounds according to one of the preceding claims, characterised in that A-B is a dipeptide of formula Ile-Pro or Gly-Pro.
7. Pharmaceutical composition, especially for oral administration, characterised in that it comprises at least one prodrug compound according to one of the preceding claims optionally in combination with customary carriers or excipients.
8. Use of prodrug compounds or pharmaceutical compositions according to one of the preceding claims in the preparation of a medicament for the temporally controlled in vivo inhibition of DP IV.
9. Use of prodrug compounds or pharmaceutical compositions according to one of
10. Use of prodrug compounds or pharmaceutical compositions according to one of
11. Use according to
12. Use according to
[0001] According to the invention there are provided prodrug compounds of inhibitors of dipeptidyl peptidase (DP IV), which prodrug compounds have the general formula A-B-C, wherein
[0002] A is an amino acid,
[0003] B is a chemical bond between A and C or is an amino acid, and
[0004] C is a stable inhibitor of DP IV.
[0005] It has been found that administering inhibitors (effectors) of DP IV or DP IV-analogous enzyme activity in the blood of a mammal causes, because of the associated temporary reduction in enzyme activity, reduced breakdown of the endogenous (and also exogenously administered) insulino-tropic peptides Gastric Inhibitory Polypeptides 1-42 (GIP1-42) and Glucagon-Like Peptide Amides-1 7-36 (GLP-17-36) (or also GLP-17-37 or analogues thereof) by DP IV and DP IV-like enzymes and, accordingly, the fall in concentration of those peptide hormones, or analogues thereof, is reduced or delayed. The greater stability of (endogenously present or exogenously introduced) incretins or analogues thereof, which results from the action of DP IV-effectors, increases their availability for insulinotropic stimulation of the incretin receptors of the Langerhans cells in the pancreas and alters, inter alia, the effectiveness of the body's own insulin, resulting in stimulation of carbohydrate metabolism in the treated organism. As a result, in the serum of the treated organism, the blood sugar level drops below the glucose concentration that is characteristic of hyperglycaemia. Consequently, by means of DP IV-inhibitors it is possible to prevent or to mitigate metabolic anomalies such as excess weight, glucosuria, hyperlipidaemia and also possible serious metabolic acidoses and diabetes mellitus, which are a consequence of prolonged elevated glucose concentrations in the blood [see DE 196 16 486].
[0006] With the aid of DP IV-inhibitors, it is also possible, experimentally, to prevent the penetration of CD 26 (DP IV) positive cells by HIV [see WAKSELMAN, M., NGUYEN, C., MAZALEYRAT, J.-P., CALLEBAUT, C., KRUST, B., HOVANESSIAN, A. G., Inhibition of HIV-1 infection of CD 26+ but not CD 26-cells by a potent cyclopeptidic inhibitor of the DPP IV activity of CD 26. Abstract P 44 of the 24th European Peptide Symposium 1996].
[0007] It has also been found that DP IV can modulate the activity of neuroactive peptides, such as neuropeptide Y and CLIP [see MENTLEIN, R., DAHMS, P., GRANDT, D., KRUGER, R., Proteolytic processing of neuropeptide Y and peptide YY by dipeptidyl peptidase IV. Regul. Pept. 49, 133 (1993); WETZEL, W., WAGNER, T., VOGEL, D., DEMUTH, H.-U., BALSCHUN, D., Effects of the CLIP fragment ACTH 20-24 on the duration of REM sleep episodes. Neuropeptides, 31, 41 (1997)].
[0008] The problem of the present invention is to provide effectors of DP IV which have an increased action compared with known inhibitors and which have a temporally defined onset of action.
[0009] The problem is solved by providing prodrug compounds of inhibitors of dipeptidyl peptidase IV (DP IV), which prodrug compounds have the general formula A-B-C, wherein
[0010] A is an amino acid,
[0011] B is a chemical bond between A and C or is an amino acid, and
[0012] C is a stable inhibitor of DP IV.
[0013] Surprisingly, inhibitors of that kind which are masked as prodrugs have significantly increased activity compared with non-masked inhibitors: When identical amounts of non-masked DP IV-inhibitors and of prodrug compounds according to the invention are used, an improvement in glucose tolerance of up to 75% is obtained in Wistar rats; see also Table 4.
[0014] That improvement is all the more astonishing in view of the fact that it has been found that 100% of non-masked inhibitors of DP IV are absorbed from the gastrointestinal tract of mammals and enter the vascular compartment of the body. It might, therefore, have been expected that prodrug compounds, which normally are intended only to prevent degradation of orally administered compounds in the gastrointestinal tract, would not lead to an increase in the activity of the inhibitors. Furthermore, it should be mentioned just in passing that there was no cause whatever for a person skilled in the art, on the basis of those facts, to look for modified inhibitors, even though prodrug compounds were known per se; see e.g. PCT/US 97/09421.
[0015] According to a preferred embodiment of the present invention, prodrug compounds are used in which B is proline, hydroxyproline, thiazolidinecarboxylic acid, dehydroproline, pipecolic acid, azetidinecarboxylic acid or aziridine-carboxylic acid, with proline and hydroxyproline being especially preferred. B preferably represents a peptide bond between A and C or is linked to A and C via peptide bonds.
[0016] The compounds according to the invention also have the advantage especially that the inhibitors of DP IV are released according to individual patient needs:
[0017] When a prodrug compound according to the invention interacts with a DP IV molecule, it is cleaved by the enzyme into the groups A-B and the inhibitor C. The inhibitor C will inhibit the DP IV molecule so that the latter cannot cleave any further prodrug compounds. When further DP IV molecules are present, prodrug compounds will be cleaved (if a sufficient amount of prodrug compounds has been administered) until the last DP IV molecule has been inhibited. The remaining prodrug compounds are not degraded and thus constitute an inhibitor reservoir until the concentration of DP IV molecules increases again or inhibitor molecules are displaced by DP IV or inhibitor molecules are eliminated, and the prodrug compounds are cleaved again, thus releasing inhibitors.
[0018] The invention therefore has the further advantage that each organism will release precisely the amount of inhibitor that is necessary to inhibit DP IV, which is present in different amounts in individual cases. If, for example, a patient has a high concentration of DP IV, a large amount of inhibitor will be released; if there is only a slightly elevated concentration of DP IV, only a small amount of inhibitor will be released.
[0019] Furthermore, preference is given, according to the invention, to prodrug compounds wherein C is an amino-acylpyrrolidide, aminoacylthiazolidide or N-dipeptidyl, O-acyl hydroxylamine. Such inhibitors have shown themselves to be especially active DP IV-inhibitors. As examples of such inhibitors there may be mentioned, for example, Ile-Thia, Ile-Pyr, Val-Thia and Val-Pyr.
[0020] The inhibitors (component C) can, according to the invention, also be present in salt form, with organic salts such as acetates, succinates, tartrates or fumarates or inorganic acid radicals such as phosphates or sulphates being preferred. Fumarates are especially preferred.
[0021] Special preference is given to compounds wherein A-B is a dipeptide of formula Ile-Pro or Gly-Pro.
[0022] The present invention therefore relates to novel prodrug compounds of inhibitors of the serine peptidase dipeptidyl peptidase IV, which prodrug compounds can be used in the treatment of various disorders, especially metabolic disorders associated with diabetes mellitus.
[0023] A further advantage of the prodrug compounds according to the invention lies in the fact that it is possible for the onset of action and also the duration of action of the DP IV-inhibitors to be temporally controlled by suitable selection of the groups A-B. In particular, the release of the groups A-B from the prodrug compounds according to the invention depends upon the nature of the amino acid radical of A: In respect of the definition of group A, the following sequence has been found, in particular, for the rate at which the radicals A-B are released from the prodrug compounds A-B-C by DP IV: Ile<Val<Phe<Pro<Ala<Gly. The rate constants of the corresponding DP IV-catalysed release reactions are between 1 s−1 and 100 s−1. A means is thus available for releasing the DP IV-inhibitors in a precisely temporally defined manner: When the enzymes are to have an immediate onset of action, for example upon ingestion of glucose-rich nutrient, a compound A-B-C will be selected that has, for example, the amino acid Gly as group A; when the onset of action of the inhibitor is to be delayed, the amino acid Ile, for example, can be selected as group A. By means of the prodrug compounds according to the invention, therefore, it is possible for DP IV-inhibitors to be transported through the mucosa of the small intestine especially almost without a delay, for example almost simultaneously with ingested nutrients.
[0024] When B represents a bond, it is especially a peptide bond; when B represents an amino acid, it is linked to A and C preferably via peptide bonds.
[0025] On analysis of the dose-effect relationships of the DP IV-inhibitor isoleucyl thiazolidide as a modulator of the blood glucose concentration in the mammalian organism, a difference can be found between oral and parenteral administration of the active substance to Wistar rats: On oral administration, saturation was observed in the uptake of the active substance (measured on the basis of inhibition of the serum enzyme), whereas on parenteral administration of the inhibitor complete inhibition of the enzyme was observed. That is demonstrated, by way of example, in Table 1:
[0026] In view of the fact that in the intestine there are also present enzymes, especially high concentrations of DP IV, that are capable of cleaving the cleavable groups of prodrugs and consequently of releasing the medicament and also�as already mentioned�it has been found that DP IV-inhibitors are absorbed quantitatively from the gastrointestinal tract, it was to be expected that the use of prodrug compounds of DP IV-inhibitors would not bring about any improvement in that situation.
[0027] It was, therefore, extremely surprising to find that the prodrugs of DP IV-inhibitors according to the invention bring about clearly enhanced glucose tolerance in the glucose tolerance test compared with the corresponding non-masked DP IV-inhibitors. That behaviour was especially surprising because�as mentioned hereinbefore�it is possible for the prodrugs to be cleaved already in the intestine by enzymes present therein such as dipeptidyl peptidase and therefore, exactly like the non-masked inhibitors, ought no longer to be available for transport to the target site:
[0028] As soon as the prodrug compounds are cleaved by DP IV or other enzymes present in the intestine, the inhibitors according to the invention are released, which causes inhibition of DP IV in exactly the same manner as when non-masked inhibitors are used. Consequently, no further breakdown of the prodrug compounds by DP IV takes place; all prodrug compounds that are still undegraded or additionally introduced, as well as excess (that is to say, not bound to DP IV) non-masked inhibitors, can pass undegraded from the gastrointestinal tract into the vascular compartment of a body. There they can then be used as DP IV-inhibitors according to individual needs, as mentioned hereinbefore. However, after a certain time, the inhibitors bound to DP IV in the intestine are released again and enter the vascular compartment.
[0029] With the aid of the prodrug compounds according to the invention, it is therefore also possible to obtain a desired increase in action in vivo.
[0030] Moreover, it is possible to control the site of release and action of the DP IV-inhibitors by means of the nature of the radicals A-B:
[0031] Various other aminopeptidases such as, for example, pyroglutamyl aminopeptidase and prolyl aminopeptidase are present in the blood of mammals, in addition to dipeptidyl peptidase IV. By suitable selection of the radicals A-B, it is possible according to the invention to predetermine which aminopeptidase is to release the DP inhibitor and so to determine where the action of the inhibitor is to occur. The prodrug compounds according to the invention or corresponding pharmaceutical compositions can therefore be used in cell-, tissue- or organ-specific inhibition of DP IV. It is also possible to select the groups A-B so that only those enzymes that are present in the vascular compartment and that release the inhibitors at a sufficiently fast rate are targeted.
[0032] To summarise, it may be stated that, by means of the prodrug compounds of DP IV-inhibitors according to the invention, it is possible, in an entirely surprising manner:
[0033] 1. to achieve increased action of the inhibitors;
[0034] 2. for the inhibitors to be released according to patient needs;
[0035] 3. for the inhibitors to be released from the prodrug compounds in a temporally controlled manner;
[0036] 4. for the site at which the inhibitors are released from the prodrug compounds to be controlled; and
[0037] 5. for a reservoir of DP IV-inhibitors to be provided.
[0038] According to the invention, pharmaceutical compositions, especially for oral administration, are also provided, which are characterised in that they comprise at least one prodrug compound according to the invention optionally in combination with customary carriers or excipients.
[0039] The prodrug compounds or pharmaceutical compositions comprising them in accordance with the invention can be used in the treatment or prophylaxis of disorders in mammals that can be treated by modulating the DP IV activity of a mammal, such as, for example, metabolic disorders in humans.
[0040] In particular, they can be used in the treatment of impaired glucose tolerance, glucosuria, hyperlipidaemia, metabolic acidoses, diabetes mellitus, diabetic neuropathy and nephropathy and of sequelae of diabetes mellitus in mammals.
[0041] 1. Synthesis of Prodrug Compounds According to the Invention
[0042] 1.1. Synthesis of H-Pro-Ile-Thia/HCl
[0043] 6.5 mM Boc-Pro-Ile-OH (one equivalent=1 eq.) is suspended, together with N-hydroxybenzotriazole (1 eq.) and thiazolidine (1 eq.), in 30 ml of dichloromethane (DCM). The equivalent amount of 1 M dicyclohexylcarbodiimide solution is added dropwise, at −10� C., with stirring. Stirring is carried out at −10� C. and overnight at room temperature. For the purpose of working-up, the solution is thoroughly filtered off from the dicyclohexylurea that is precipitated out, DCM is drawn off in vacuo and the residue obtained is taken up in ethyl acetate. The ethyl acetate solution is washed at least three times with saturated bicarbonate solution, once with saturated NaCl solution, three times with dilute KHSO4 solution and again with NaCl solution. The ethyl acetate phase is dried over Na2SO4 and concentrated using a rotary evaporator, and the remaining crude product is re-crystallised using ethyl acetate/pentane. Boc-Pro-Ile-Thia crystallises after 1-2 days at 4� C. (yield 80%). 1.1N HCl/glacial acetic acid solution is added to Boc-Pro-Ile-Thia (3 ml per mmol of peptide). Stirring is carried out for two hours at RT, absolute ether is added and excess removal solution is evaporated off using a rotary evaporator. The hydrochloride crystallises quantitatively under absolute ether overnight at 4� C. The crystals are quickly separated off by suction filtration, washed several times with absolute ether, and the product is stored in a desiccator over KOH or phosphorus pentoxide.
[0044] 1.2. Synthesis of H-Gly-Pro-Ile-Thia/HCl
[0045] Boc-Gly-OH (1 eq.) is dissolved in 20 ml of tetrahydrofuran (THF), cooled to −10� C. and, with stirring, N-methyl-morpholine (1 eq.) and chloroformic acid isobutyl ester (1 eq.) are added in succession. Activation is carried out for about 20 min. In parallel, Pro-Ile-Thia.HCl (1 eq.) is suspended in 10 ml of THF, equilibrated to −10� C., and N-methylmorpholine (1 eq.) is added for the purpose of neutralisation. After completion of the activation time, both solutions are mixed together and, after one to two hours, heated to room temperature and stirred overnight. A small amount of water is then added to the reaction mixture and the THF is distilled off in vacuo. The remaining residue is taken up in ethyl acetate and washed at least three times with saturated sodium bicarbonate solution, once with saturated NaCl solution, three times with dilute KHSO4 and again with saturated NaCl solution. The ethyl acetate phase is dried over Na2SO4, concentrated using a rotary evaporator and the product Boc-Gly-Pro-Ile-Thiazolidide is re-crystallised using ethyl acetate/pentane (yield 85%). The removal of Boc is carried out analogously to the synthesis of H-Pro-Ile-Thia/HCl (yield>95%).
[0046] 2. Affinity and Transport of Various Peptides, DP IV-inhibitors and Prodrugs to the Peptide Transporter PepT1
[0047] The affinity of various peptides, DP IV-inhibitors and prodrugs of inhibitors of DP IV to the peptide transporter PepT1 were analysed by displacement of the radioactively labelled substrate D-Phe-Ala (AMASHEH, S., WENZEL, U., WEBER, W. M., CLAUSS, W., DANIEL, H., Electrophysiological analysis of the function of the mammalian renal peptide transporter expressed in Xenopus laevis oocytes. J. Physiol. 504, 169-174 (1997)]. It is shown that, for example, the tetrapeptide derivative Ile-Pro-Ile-Thia becomes bound to the transporter protein PepT1 in a comparable manner to, or better than, selected amino acid derivatives and, in comparison with selected amino acid and peptide analogues, is transported in a similar or better manner (Table 3).
[0048] Release of the active DP IV-inhibitor Ile-Thia from prodrugs according to the invention in human whole blood.
[0049] According to an embodiment of prodrugs of DP IV-inhibitors according to the invention, retarded release of DP IV-inhibitors in the target compartment, for example, in the blood circulation, is also possible.
[0050]FIG. 1 shows, by way of example, the inhibition of human blood-DP IV resulting from release of the inhibitor isoleucyl thiazolidide from prodrug compounds according to the invention, the inhibition following different courses as a function of time. Release of the masked DP IV-inhibitor in the blood can be carried out, in the case of the examples selected, by DP IV itself (Pro-Pro-Ile-Thia=PPIThia, Gly-Pro-Ile-Thia=GPIThia) or by aminopeptidases (pGlu-Ile-Thia=pEIThia, Pro-Ile-Thia=PIThia) (FIG. 1). When the same concentration of prodrug compound is used, there is a difference in the efficiency with which the DP IV-inhibitor isoleucyl thiazolidide is released from the prodrug compounds in the blood, a more marked delay in the release of active substance being shown in the case of Pro-Pro-Ile-Thia (PPI Thia) and pGlu-Ile-Thia (pEI Thia) compared with Pro-Ile-Thia (PI Thia) and Gly-Pro-Ile-Thia (GPI thia).
[0051] 3. Enhancement of DP IV-inhibitor-imparted Glucose Tolerance Resulting from the Use of Prodrugs
[0052] As a result of converting the active substance isoleucyl thiazolidide into prodrugs according to the invention, a markedly improved profile of action is observed in the Wistar rat following oral administration (FIG. 2). The desired reduction in the level of blood glucose caused by DP IV-inhibitors in the time period examined is enhanced by about 30% by using the prodrug compounds according to the invention as opposed to the non-masked active substance Ile-Thia (Table 4):
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Bagged leaves
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I have been offered about a dozen bags of leaves that I thought would be good mixed with manure and soil but on opening a couple of them I found ants and lots of tiny (1/4 inch) never seen before, black worm like insects. I have no idea what they are or if they are harmless to my garden. The bagged leaves are from the NW Austin area. When I opened the bags they got busy moving, maybe they are larva I don't know but do I want the bags of leaves?
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Pretty Much Every U.S. Demographic Group Believes Torture Is Justified
The good news: For those who are worried that the nation is more divided than ever, there's finally one contentious issue that a majority of Americans agree upon. The bad news: Most people are okay with the CIA torturing suspected terrorists. »