Tag Archives: RET

ARIAD Presents New Preclinical Data Showing Ponatinib is a Potent Inhibitor of RET and FGFR, Two Onc

By Business Wirevia The Motley Fool

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ARIAD Presents New Preclinical Data Showing Ponatinib is a Potent Inhibitor of RET and FGFR, Two Oncogenic Drivers of Non-Small Cell Lung Cancer

CAMBRIDGE, Mass. & WASHINGTON–(BUSINESS WIRE)– ARIAD Pharmaceuticals, Inc. (NAS: ARIA) today announced the presentation of preclinical data on ponatinib (Iclusig™) , at the American Association for Cancer Research (AACR) Annual Meeting 2013, in Washington. In separate studies, ponatinib is shown to potently inhibit RET, a clinically proven oncogenic driver of medullary thyroid cancer (MTC) and non-small cell lung cancer (NSCLC), and FGFR, which is commonly mutated in endometrial, lung and other cancers.

The first preclinical study, “Ponatinib is a highly-potent inhibitor of activated variants of RET found in MTC and NSCLC,” shows that ponatinib inhibits naturally occurring activating mutants of RET found in MTC and NSCLC at clinically achievable plasma concentrations. The potency of ponatinib was found to substantially exceed that of other approved tyrosine kinase inhibitors with RET activity. These results provide strong support for the clinical evaluation of ponatinib in patients with RET-driven cancers.

“The unique design features that allow ponatinib to overcome mutation-based resistance in CML, including the gatekeeper mutation, also apply to its activity against its other tyrosine kinase targets including RET, FGFR and KIT,” stated Timothy P. Clackson, Ph.D., president of research and development and chief scientific officer at ARIAD. “These preclinical data strongly support moving forward with evaluating ponatinib in RET-positive cancers, and we look forward to the start of a Phase 2 investigator-sponsored trial in patients with RET-positive NSCLC in this second quarter of 2013.”

In the second preclinical study, “Ponatinib potently inhibits the activity of mutant variants of FGFR commonly found in endometrial, lung and other cancers,” the ability of ponatinib to inhibit a broad panel of naturally occurring mutant variants of FGFR1, 2, 3, and 4 was evaluated. Ponatinib potently blocked a variety of mutant variants of FGFR, with particularly promising activity against mutant variants of FGFR2 that have been observed in endometrial and squamous cell carcinomas (SCCs) of the lung. Specifically, ponatinib inhibits the eight mutants that make up more than 90 percent of the mutations observed in endometrial cancer patients, and six mutants observed in SCC at clinically achievable plasma concentrations. Ponatinib also shows encouraging activity against FGFR1/3 fusion proteins found in glioblastoma multiforme. These data support clinical evaluation of ponatinib in FGFR-driven cancers, including a Phase 2 investigator-sponsored trial of ponatinib in patients with SCCs that is currently underway and enrolling patients.

About ARIAD
…read more

Source: FULL ARTICLE at DailyFinance

ARIAD Announces Presentations of Preclinical Data at American Association for Cancer Research Annual

By Business Wirevia The Motley Fool

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ARIAD Announces Presentations of Preclinical Data at American Association for Cancer Research Annual Meeting

CAMBRIDGE, Mass.–(BUSINESS WIRE)– ARIAD Pharmaceuticals, Inc. (NAS: ARIA) today announced its schedule of preclinical data presentations to be made at the American Association for Cancer Research (AACR) Annual Meeting 2013, taking place Saturday, April 6 through Wednesday, April 10, 2013, in Washington.

Listed below are the details of presentations at AACR that describe ARIAD’s product candidates. There will be four presentations of data on ARIAD‘s targeted therapies, Iclusig™ (ponatinib) and AP26113; and one invited talk:

Title: Ponatinib is a highly potent inhibitor of activated variants of RET found in MTC and NSCLC
Date & Time: Monday, April 8, 1:00-5:00 p.m. (Poster)
Abstract: #2084
Location: Hall A-C, Poster Section 38

Title: Ponatinib potently inhibits the activity of mutant variants of FGFR commonly found in endometrial, lung and other cancers
Date & Time: Monday, April 8, 1:00-5:00 p.m. (Poster)
Abstract: #2083
Location: Hall A-C, Poster Section 38

Title: Ponatinib, a pan-BCR-ABL inhibitor, potently inhibits key activating and drug-resistant KIT mutants found in GIST
Date & Time: Tuesday, April 9, 8:00 a.m.-12:00 p.m. (Poster)
Abstract: #3394
Location: Hall A-C, Poster Section 42

Title: Design and development of ponatinib, a pan-BCR-ABL inhibitor for CML
Date & Time: Tuesday, April 9, 9:30-10:00 a.m. (Major symposium)
Presentation: #SY19-04
Location: Salon A-B, East Hall

Title: AP26113 possesses pan-inhibitory activity versus crizotinib-resistant ALK mutants and oncogenic ROS1 fusions
Date & Time: Wednesday, April 10, 8:00 a.m.-12:00 p.m. (Poster)
Abstract: #5655
Location: Hall A-C, Poster Section 42

About ARIAD

ARIAD Pharmaceuticals, Inc., headquartered in Cambridge, Massachusetts and Lausanne, Switzerland, is an integrated global oncology company focused on transforming the lives of cancer patients with breakthrough medicines. ARIAD is working on new medicines to advance the treatment of various forms of chronic and acute leukemia, lung cancer and other difficult-to-treat cancers. ARIAD utilizes computational and structural approaches to design small-molecule drugs that overcome resistance to existing cancer medicines. For additional information, visit http://www.ariad.com or follow ARIAD on Twitter (@ARIADPharm).

ARIAD
For Investors<br …read more
Source: FULL ARTICLE at DailyFinance

Mario Limonciello: Multi-homed MythTV backend

This is the first of my non OpenWRT related posts.

I have a peculiar situation.  I have two houses that I split my life between.  I don’t want to pay for cable in both houses, but I also want access to some of the TV shows that you only get newer episodes on cable and not via Netflix/Hulu/Amazon.

So to solve this, I have set up MythTV in both houses.  Both setups run Mythbuntu 12.04.1 (www.mythbuntu.org).  In the house without cable I have a Silicondust HD Homerun.

The HD Homerun is set to record OTA content exclusively.  I get all the basic TV networks this way in that house.

In the second house I have a Silicondust HD Homerun Prime.  I’m fortunate that in that house I have Comcast, which is one of the more friendly companies with regard to copy protection.  I’m able to record pretty much everything except the premium networks like HBO and Showtime.
 

In the second house I duplicate all the OTA recording schedules but also schedule things on the other stations I care about.

Secondary House

Now to get the recordings from the second house to the first house, I had to setup a collection of scripts that run in staggered cron jobs.  The first one is on the secondary house.  I first determined which channel ID’s I needed to export from.  This can be found by looking through mythweb or by examining the database with a tool like phpmyadmin.  Look for ‘chanid’ in the ‘channels’ table.

Once I had those channels figured out I created this script.  On each daily run it will find all the recordings who’s starttime happened to be “today”.  It exports all relevant SQL data about that recording into a flat SQL file that can be imported on the primary house.

Next it creates a list of recordings that will need to be synced over to the primary house.  This list is based upon the last successful sync date from the primary house.  It only syncs all recordings between the lastrun date and “tomorrow”.  This sets it up so that if for some reason the primary backend doesn’t sync a day it will still work.  Also it’s important to sync only a handful of days because the autoexpire will be happening at different rates on the two backends.

I store all this content in the directory /var/lib/mythtv/exported-sql

sudo mkdir -p /var/lib/mythtv/exported-sql 

sudo chown mythtv:mythtv /var/lib/mythtv/exported-sql

/home/mythtv/export.sh 

#!/bin/sh

#export SQL
chanid=”2657 2659 2622″
DIRECTORY=/var/lib/mythtv/exported-sql/
BIGGEST_DATE=`find $DIRECTORY -maxdepth 1 -name ‘*.sql’ | sort -r | head -1 | sed ‘s,.*exported-,,; s,.sql,,’`
for chan in $chanid;
do
[ -n “$where” ] && where=”$where or”
[ -n “$BIGGEST_DATE” ] && date=” and starttime > ‘$BIGGEST_DATE 00:00:00′”
where=”$where (chanid=’$chan’$date)”
done
CONFIG=$HOME/.mythtv/config.xml
DATE=`date ‘+%F’`
if [ “$DATE” = “$BIGGEST_DATE” ]; then
echo “Already ran today, not running SQL generation again”
else
db=`xpath  -q -e ‘string(//DatabaseName)’ $CONFIG 2>/dev/null`
user=`xpath  -q -e ‘string(//UserName)’ $CONFIG 2>/dev/null`
pass=`xpath  -q -e ‘string(//Password)’ $CONFIG 2>/dev/null`
host=`xpath  -q -e ‘string(//Host)’ $CONFIG 2>/dev/null`
fname=/var/lib/mythtv/exported-sql/exported-$DATE.sql
mysqldump -h$host -u$user -p$pass $db recorded recordedseek recordedrating recordedprogram recordedmarkup recordedcredits –where=”$where” –no-create-db –no-create-info > $fname
fi


#generate a recordings list
lastrun=/home/mythtv/lastrun
tomorrow=$(date –date=”tomorrow” ‘+%Y%m%d’)
if [ -f $lastrun ]; then
        tmp=$(cat $lastrun)
else
        tmp=$tomorrow
fi
while [ “$tmp” != “$tomorrow” ]
do
        test_dates=”$test_dates $tmp”
        tmp=$(date –date=”1 day $tmp” ‘+%Y%m%d’)
done
test_dates=”$test_dates $tomorrow”
for date in $test_dates;
do
        for chan in $chanid;
        do
                from=”$from /var/lib/mythtv/recordings/${chan}_${date}*”
        done
done
ls $from 2>/dev/null | tee /var/lib/mythtv/exported-sql/recordings-list
Next I set up rsync to export my /var/lib/mythtv directory (read only) and my lastrun successful (write only).

/etc/rsyncd.conf

max connections = 2
log file = /var/log/rsync.log
timeout = 300

[mythtv]
comment = mythtv
path = /var/lib/mythtv
read only = yes
list = yes
uid = nobody
gid = nogroup
auth users = rsync
secrets file = /etc/rsyncd.secrets

[lastrun]
comment = last rsync run
path = /home/mythtv/
write only = yes
read only = no
list = no
uid = mythtv
gid = mythtv
auth users = rsync
secrets file = /etc/rsyncd.secrets
Last thing to do on the secondary house is to set up the crontab to run at night.  I set it for 11:05 PM every day.  It should only take a 10-15 seconds to run.
5 23 * * * /home/mythtv/export.sh
Because of the way this all works, I decide to leave my secondary house backend on all the time.  

Primary House

Now in my primary house I need to sync recordings, SQL data, and then update the last successful run at the secondary house.

/home/mythtv/import.sh

#!/bin/sh

domain=rsync@address
sql_directory=/home/mythtv/sql
recordings_directory=/var/lib/mythtv/recordings
password_file=/home/mythtv/password-file
lastrun=/home/mythtv/lastrun

sync_recordings()
{
today=$(date ‘+%Y%m%d’)
from=$(cat $sql_directory/recordings-list | sed “s,/var/lib/mythtv,$domain::mythtv,”)
RET=30
while [ $RET -eq 30 ]; do
#rsync -avz –partial –timeout 120 –progress $from –password-file=password-file $recordings_directory
rsync -av –partial –timeout 120 –progress $from –password-file=$password_file $recordings_directory
RET=$?
done
echo “rsync return code: $?”
[ $RET -ne 0 ] && exit 1
echo “$today” > lastrun
rsync -avz –password-file=password-file lastrun $domain::lastrun/
}

sync_sql()
{
rsync -avz $domain::mythtv/exported-sql/* –password-file=$password_file $sql_directory
}

insert_sql()
{
CONFIG=$HOME/.mythtv/config.xml
db=`xpath  -q -e ‘string(//DatabaseName)’ $CONFIG 2>/dev/null`
user=`xpath  -q -e ‘string(//UserName)’ $CONFIG 2>/dev/null`
pass=`xpath  -q -e ‘string(//Password)’ $CONFIG 2>/dev/null`
host=`xpath  -q -e ‘string(//Host)’ $CONFIG 2>/dev/null`
old_host=supermario
new_host=kingkoopa
for fname in $(find $sql_directory -maxdepth 1 -name ‘*.sql’);
do
if [ ! -f ${fname}.imported ]; then
cat $fname | sed “s,${old_host},${new_host},g; s,INSERT INTO, INSERT IGNORE INTO,g” > ${fname}.imported
mysql –host=$host –user=$user -p$pass $db < ${fname}.imported
fi
done
}

suspend()
{
sudo /usr/local/bin/setwakeup.sh $(date –date=’18:00′ ‘+%s’)
sudo pm-suspend
}

mythfilldatabase
sync_sql
sync_recordings
insert_sql
#suspend
I’m careful about the order I do things.  The SQL has to get inserted last in case for some reason the recordings fail to sync or don’t all sync while i’m watching.
I currently don’t suspend afterwards due to some instability on my system, but I have been experimenting with that too.  If S3 is reliable you can configure the setup to suspend after the sync is done and wake up next time you need to use it or record from it.
I set the cronjob to run at midnight every day on the primary backend.
0 0 * * * /home/mythtv/import.sh

Source: FULL ARTICLE at Planet Ubuntu

Reitmans About To Put More Money In Your Pocket

By DividendChannel.com On 1/15/13, Reitmans, Ltd. (Toronto: RET) will trade ex-dividend, for its quarterly dividend of $0.20, payable on 1/31/13. As a percentage of RET‘s recent stock price of $11.90, this dividend works out to approximately 1.68%, so look for shares of Reitmans, Ltd. to trade 1.68% lower ? all else being equal ? when RET shares open for trading on 1/15/13.
Click here to find out which 9 other Canadian stocks going ex-dividend you should know about, at DividendChannel.com »
Source: FULL ARTICLE at Forbes Markets