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1. Happy Saturday Everyone….. You know what time it is! It's time for name that OG strain! Its a goodie and worth checking out. Click to see more images.
2. Yes, this is an OG strain! Super green in color with its dark and light hues! And it's not lacking any trichomes, that's for sure. There are a few burnt orange hairs popping their heads out but overall, it's all green frosty nugs!
3. Rocking a spicy but hint of sweet smell once you open the container and start breaking it up! Becomes a little more pungent as you get to the core of the flower!
4. This is an Indica dominant flower and you will feel it's power after treating yourself to a nice fat bowl! Doesn't take long for the meds to kick in!
5. This OG will leave you pie eyed and heavy on the lids! Giving you a feeling of relaxation and calmness from your head to your toes!
6. Super nice for night time if you have problems sleeping or anxiety… this will do the trick! It's dank!
7. What's your guess? Leave me a comment and let's see who is right. And who is guessing wrong! Cheers to a great day. One Love.

subset: commoncrawl


text:
The Small Files Problem
- by Tom White
- February 02, 2009
- 32 comments
Small files are a big problem in Hadoop — or, at least, they are if the number of questions on the user list on this topic is anything to go by. In this post I'll look at the problem, and examine some common solutions.
Problems with small files and HDFS
A small file is one which is significantly smaller than the HDFS block size (default 64MB). If you're storing small files, then you probably have lots of them (otherwise you wouldn't turn to Hadoop), and the problem is that HDFS can't handle lots of files.
Every file, directory and block in HDFS is represented as an object in the namenode's memory, each of which occupies 150 bytes, as a rule of thumb. So 10 million files, each using a block, would use about 3 gigabytes of memory. Scaling up much beyond this level is a problem with current hardware. Certainly a billion files is not feasible.
Furthermore, HDFS is not geared up to efficiently accessing small files: it is primarily designed for streaming access of large files. Reading through small files normally causes lots of seeks and lots of hopping from datanode to datanode to retrieve each small file, all of which is an inefficient data access pattern.
Problems with small files and MapReduce
Map tasks usually process a block of input at a time (using the default
FileInputFormat). If the file is very small and there are a lot of them, then each map task processes very little input, and there are a lot more map tasks, each of which imposes extra bookkeeping overhead. Compare a 1GB file broken into 16 64MB blocks, and 10,000 or so 100KB files. The 10,000 files use one map each, and the job time can be tens or hundreds of times slower than the equivalent one with a single input file.
There are a couple of features to help alleviate the bookkeeping overhead: task JVM reuse for running multiple map tasks in one JVM, thereby avoiding some JVM startup overhead (see the
mapred.job.reuse.jvm.num.tasks property), and
MultiFileInputSplit which can run more than one split per map.
Why are small files produced?
There are at least two cases
- The files are pieces of a larger logical file. Since HDFS has only recently supported appends, a very common pattern for saving unbounded files (e.g. log files) is to write them in chunks into HDFS.
- The files are inherently small. Imagine a large corpus of images. Each image is a distinct file, and there is no natural way to combine them into one larger file.
These two cases require different solutions. For the first case, where the file is made up of records, the problem may be avoided by calling HDFS's
sync() method (which came with appends, although see this discussion) every so often to continuously write large files. Alternatively, it's possible to write a program to concatenate the small files together (see Nathan Marz's post about a tool called the Consolidator which does exactly this).
For the second case, some kind of container is needed to group the files in some way. Hadoop offers a few options here.
HAR files
Hadoop Archives (HAR files) were introduced to HDFS in 0.18.0 to alleviate the problem of lots of files putting pressure on the namenode's memory. HAR files work by building a layered filesystem on top of HDFS. A HAR file is created using the
hadoop archive command, which runs a MapReduce job to pack the files being archived into a small number of HDFS files. To a client using the HAR filesystem nothing has changed: all of the original files are visible and accessible (albeit using a har:// URL). However, the number of files in HDFS has been reduced.
Reading through files in a HAR is no more efficient than reading through files in HDFS, and in fact may be slower since each HAR file access requires two index file reads as well as the data file read (see diagram). And although HAR files can be used as input to MapReduce, there is no special magic that allows maps to operate over all the files in the HAR co-resident on a HDFS block. It should be possible to built an input format that can take advantage of the improved locality of files in HARs, but it doesn't exist yet. Note that MultiFileInputSplit, even with the improvements in HADOOP-4565 to choose files in a split that are node local, will need a seek per small file. It would be interesting to see the performance of this compared to a SequenceFile, say. At the current time HARs are probably best used purely for archival purposes.
Sequence Files
The usual response to questions about "the small files problem" is: use a SequenceFile. The idea here is that you use the filename as the key and the file contents as the value. This works very well in practice. Going back to the 10,000 100KB files, you can write a program to put them into a single SequenceFile, and then you can process them in a streaming fashion (directly or using MapReduce) operating on the SequenceFile. There are a couple of bonuses too. SequenceFiles are splittable, so MapReduce can break them into chunks and operate on each chunk independently. They support compression as well, unlike HARs. Block compression is the best option in most cases, since it compresses blocks of several records (rather than per record).
It can be slow to convert existing data into SequenceFiles. However, it is perfectly possible to create a collection of SequenceFiles in parallel. (Stuart Sierra has written a very useful post about converting a tar file into a SequenceFile — tools like this are very useful, and it would be good to see more of them). Going forward it's best to design your data pipeline to write the data at source direct into a SequenceFile, if possible, rather than writing to small files as an intermediate step.
Unlike HAR files there is no way to list all the keys in a SequenceFile, short of reading through the whole file. (MapFiles, which are like SequenceFiles with sorted keys, maintain a partial index, so they can't list all their keys either — see diagram.)
SequenceFile is rather Java-centric. TFile is designed to be cross-platform, and be a replacement for SequenceFile, but it's not available yet.
If you are producing lots of small files, then, depending on the access pattern, a different type of storage might be more appropriate. HBase stores data in MapFiles (indexed SequenceFiles), and is a good choice if you need to do MapReduce style streaming analyses with the occasional random look up. If latency is an issue, then there are lots of other choices — see Richard Jones' excellent survey of key-value stores.
Jean-Daniel Cryans /
February 02, 2009 / 4:43 PM
Nice post Tom. Just to add some info with regards to HBase, we are currently integrating TFile in HBase for 0.20 which will hopefully reduce the latency to a reasonable level (looking good). We are also in the process of adding a new cache (HBASE-80).
ryan /
February 18, 2009 / 3:38 AM
Hi Tom,
We are making substantial changes to HBase for 0.20 to improve all manners of performance. Random reads, large scans, etc, etc are all anticipated to be faster.
The new file-format, HFile (hbase-file! get it?) is behind these changes. Check out this for a history of how it came to be:
Mark Schnitzius /
March 30, 2009 / 5:52 PM
Great article – we are going through many of the same issues. I'm curious to hear how others are dealing with concurrency issues, i.e. external processes adding new data while consolidation of smaller files is taking place.
Tongjie Chen /
May 21, 2009 / 2:58 PM
Each day we have to deal with around 20,000 gzip files, each gzip file is around 25M(not sure whether 25M falls into *small file* category or not :-) ).
Hadoop tasktracker has memory leaking bug prior to 0.19(http://issues.apache.org/jira/browse/HADOOP-4906), which basically disallows us to run job with 20k+ mappers.
We found that MultiFileSplit is very good fit for this problem:
1. convert the whole gzip file to bytes and wrap it with BytesWritable; and wrap multiple BytesWritables into one ArrayWritable
2. Write a CustomMultiFileInputFormat and CustomMultiFileRecordReader where record key is NullWritable, and record value is ArrayWritable.
3 In the map task, for each value(ArrayWritable), We can restore the original bytes from BytesWritable (element of array) and process.
I have used this approach to process around 1.5 millions gzip files (each with 25M in size) in one job and use only 10000 mapper (our cluster size is 61 machines, each 16G memory).
One important thing is that We have to increase the child jvm's -Xmx to big enough to hold ArrayWritable.
Konstantin Shvachko /
July 13, 2009 / 5:57 PM
This might be also useful in the context of this discussion.
HADOOP-1687. Name-node memory size estimates…
Name-node object (file or block) size is less than 200 bytes. This is more conservative than 150 bytes, but more practical in my experience.
So the rule of thumb would be: 10 million files require 4 GB of memory.
Eko Kurniawan Khannedy /
April 28, 2010 / 4:25 AM
anyone can tell me, why hadoop default block size is 64MB? why not larger?
Prabhu /
July 28, 2010 / 9:06 AM
Great exposition, thanks a lot !
I am faced with a somewhat related problem. Initially I obtained a directory containing a lot of files from the customer. Hadoop was ideal for this, I used the older api for random sampling and totalOrderSort partitioning. Now they are feeding one small file at 6 hour intervals and want it to be processed at the same rate. Now, when I try to run my job, I am getting an ArrayIndexOutOfBoundsException while it tries to write the partition file. I suspect it is because I don't have as many splits as I specify in new RandomSampler(0.1,10,1000). Any help resolving this would be greatly appreciated.
Thanks very much !
Prabhu /
July 28, 2010 / 11:48 AM
I solved th eproblem by determining the block size. If it is less than 256 MB, set number of reduce tasks to 1. Else, use random sampler, total order sort partitioner etc.,
Adolf /
October 01, 2010 / 3:58 AM
TO solve small files problem in HDFS , DO you know What can be done?
Q Ethan /
February 10, 2011 / 2:21 PM
If SequenceFiles are your way to address the small files problem, you may be interested in forqlift:
forqlift is a commandline tool that makes it easy to import/export small files to/from SequenceFiles. (It's also free and open-source.)
Jeans zhong /
March 08, 2011 / 10:17 AM
Hii ,Tom, can you explain the following sentence more detailedly ?or give me some reference information?
this sentence:
Reading through small files normally causes lots of seeks and lots of hopping from datanode to datanode to retrieve each small file, all of which is an inefficient data access pattern.
why cause seeks and hopping? I think it only need to read block of small file at the best datanode.why did you say like that.what 's your reason?
please help me .
TreeMan /
March 19, 2012 / 4:30 AM
begin to understand this,a good document !
Viraj Paropkari /
November 05, 2012 / 10:42 AM
Hi Tom,
I think there is miscalculation in the sentence.
"So 10 million files, each using a block, would use about 3 gigabytes of memory. "
It should be 1 million instead of 10 million.
Andrew /
November 06, 2012 / 2:02 AM
I have found using SequenceFile.Reader via a direct DFSClient to be very slow at around 4.5MB/s.
Compared to using FSDataInputStream and reading blocks of bytes directly we get 76MB/s.
Is the SequenceFile reader expected to be this slow?


text:
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It wasn't long until tourists started to flow into this magic land, after opening its borders to the outsiders, 60 years ago, tiny mountain nation, trekkers, hikers and legions, curious and extreme ones, incredibly friendly people and irresistible warm apple pie...not only the adrenaline seekers head to Nepal, also Buddhist pilgrims finding their ways on a spiritual stroll, centuries old temples will leave you speechless. It's not a secret that Nepal is home to some of the bets will and woody national parks with excotic birds, Indian elephants and scarry jungle with tigers.
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City: Kathmandu
Country: Nepal
By: Infohostels.com staff
Published on 22-Gen-2014
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Genre: Pop
Total Tracks: 91
Duration: 10 hours, 41 minutes
Total plays0,000,167
Listen to this playlist for FREE on Spotify!
Playlist Description:
Music to party to if you have an eclectic taste in music and youre 41.5 yrs old.
Spotify playlist:
Eels – Novocaine for the Soul
Eminem – The Way I Am
Prodigy – Firestarter
Skunk Anansie – Weak
...show more
Music to party to if you have an eclectic taste in music and youre 41.5 yrs old.
Spotify playlist:
Eels – Novocaine for the Soul
Eminem – The Way I Am
Prodigy – Firestarter
Skunk Anansie – Weak
Eminem – The Real Slim Shady
Grandmaster Flash – White Lines (Long Version) (Re-Recorded / Remastered)
Guns N' Roses – Dead Horse
The Jam – Going Underground
Queen – Don't Stop Me Now
Skunk Anansie – Twisted 'Everyday Hurts'
Nickelback – Rockstar
Prodigy – Smack My Bitch Up
Massive Attack – Teardrop
Guns N' Roses – Bad Obsession
Madness – Wings Of A Dove
Moloko – Sing It Back
System Of A Down – Chop Suey!
Nirvana – Lithium
System Of A Down – B.Y.O.B.
Nickelback – Never Again
Grandmaster Flash – The Message (Re-Recorded / Remastered)
Nirvana – Smells Like Teen Spirit
Prodigy – Breathe
Puddle Of Mudd – She Hates Me
The Doors – Break on Through (to the Other Side)
The Specials – Ghost Town
Puddle Of Mudd – Blurry
Queen – Under Pressure
Nirvana – Come as You Are
Puddle Of Mudd – Control
Guns N' Roses – Don't Damn Me
The Cult – She Sells Sanctuary
Olive – You're Not Alone
The Doors – Light My Fire
The Jam – Town Called Malice
Madness – One Step Beyond
Portishead – Glory Box
Electric Six – Gay Bar
Lou Reed – Perfect Day
Lou Reed – Walk On The Wild Side - 2003 Remaster
The Proclaimers – I'm Gonna Be (500 Miles)
The Proclaimers – I'm on My Way
The Proclaimers – Letter From America
The Proclaimers – Let's Get Married
Creedence Clearwater Revival – Bad Moon Rising
Marilyn Manson – Rock Is Dead
Marilyn Manson – The Beautiful People
Marilyn Manson – Tourniquet
Slipknot – Wait And Bleed
Stealers Wheel – Stuck In The Middle With You
Chuck Berry – You Never Can Tell
R.E.M. – Losing My Religion
Radiohead – Karma Police
Radiohead – My Iron Lung
Blur – Parklife
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Pulp – Common People
Suede – Animal Nitrate
Kula Shaker – Hey Dude
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Inspiral Carpets – This Is How It Feels
Happy Mondays – Step On
EMF – Unbelievable
The Shamen – Ebeneezer Goode
Nik Kershaw – The Riddle
Tears For Fears – Shout
Depeche Mode – Personal Jesus (Single Version)
Ultravox – Dancing With Tears in My Eyes
Wang Chung – Dance Hall Days
The Police – Roxanne
U2 – Pride (In The Name Of Love)
U2 – With Or Without You
U2 – Where The Streets Have No Name - Single Edit
The Waterboys – The Whole of the Moon
The Specials – Too Much Too Young
The Killers – Mr. Brightside
The Killers – Somebody Told Me
Razorlight – Golden Touch
The Libertines – Can't Stand Me Now
The Libertines – Don't Look Back Into the Sun
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Alex Vakakis is Professor in the Department of Mechanical Science and Engineering of the University of Illinois at Urbana - Champaign
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Alex Vakakis is Professor in the Department of Mechanical Science and Engineering of the University of Illinois at Urbana - Champaign
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John Judge
John Judge is an Associate Professor of Mechanical Engineering at The Catholic University of America in Washington, DC. He earned his B.S. at Cornell University in 1996 and his Ph.D. at the University of Michigan in 2002, where he conducted an experimental investigation of vibration localization in turbomachinery. Prior to joining the faculty at CUA, he spent two years as a postdoctoral researcher in the Physical Acoustics branch at the Naval Research Laboratory. His research areas include vibration and dynamics of complex structures, dynamics of micro- and nano-mechanical systems (MEMS/NEMS), laser vibrometry and experimental characterisation of systems using vibration and acoustics, and seismic/acoustic detection of landmines and improvised explosive devices.
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Andrew Dick is an assistant professor of mechanical engineering in the Department of Mechanical Engineering and Materials Science at Rice University in Houston, Texas. He received a Ph.D. in mechanical engineering from the University of Maryland in 2007.
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Lawrie Virgin is Professor of Mechanical Engineering and Materials Science at Duke University in North Carolina. He is a former Chair of the Department of Civil and Environmental Engineering and has been a faculty member at Duke since 1988. Prior to that he received his education in the United Kingdom culminating in a PhD from the University of London. His research interests are centered on nonlinear mechanics especially buckling, nonlinear vibration and their interaction. Applications of his research include ship capsize, aeroelasticity, marine risers, rocking blocks, control, sonic fatigue, solar sails and the dynamics of very slender structures. He has written more than a hundred journal papers and two books: Introduction to Experimental Nonlinear Dynamics" (2000) and "Vibration of Axially Loaded Structures" (2007) both published by Cambridge University Press.
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Dr. Balachandran is a Professor of Mechanical Engineering at the University of Maryland, College Park. His research interests include nonlinear phenomena, dynamics and vibrations, and control.
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Matt Allen joined the faculty of the Engineering Mechanics program in the department of Engineering Physics at the University of Wisconsin-Madison in 2007. He was previously employed as a post-doctoral researcher at Sandia National Laboratories and received Doctoral and M. S. degrees from the Georgia Institute of Technology in 2005 and 2004 and a B.S. in Mechanical Engineering from Brigham Young University in 2001. His current interests include: modal parameter identification, micro- and nano- scale systems, uncertainty in dynamic systems, nonlinear dynamic systems, force reconstruction, admittance (impedance) coupling techniques, time-periodic systems, rotating machinery, and controls. Matt's Doctoral thesis was concerned with Multi-Input-Multi-Output modal parameter identification algorithms. As an undergraduate, he worked in testing and developing carbon fiber materials with a unique viscoelastic damping treatment. He also enjoys downhill skiing, tennis, mountain biking, Spanish language and spending time with his wife and two kids.
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Brian Feeny
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Mohammed F. Daqaq
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Christopher D. Rahn graduated from the University of Michigan with a Bachelors degree in mechanical engineering in 1985. He then obtained a Masters degree from the University of California, Berkeley in 1986. After three years as a Research and Development Engineer at Space Systems/LORAL, he returned to Berkeley to pursue a Ph.D. After graduating from Berkeley in 1992, Dr. Rahn joined the Department of Mechanical Engineering at Clemson University. In 2000, Dr. Rahn moved to the Pennsylvania State University where he is now a Professor of Mechanical Engineering. His research interests include dynamic modeling, design, and control of distributed nonlinear systems with application to robotics, mechatronics, and MEMS.
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Presentation: Machining dynamics, smart fluids, energy harvesting, and uncertainty propagation
Dane Quinn
D. Dane Quinn was awarded the B.M.E. degree from Georgia Tech in 1991 and, in 1995, a Ph.D. from Cornell University in the Department of Theoretical and Applied Mechanics. He is currently a Professor on the faculty of The University of Akron in the Department of Mechanical Engineering. His research interests lie in the areas of applied dynamical systems and mechanics. Finally, he serves as an Associate Editor for the ASME Journal of Vibration and Acoustics, Mathematical Problems in Engineering, and on the editorial board of Nonlinear Dynamics.
Presentation: Nonlinear Energy Harvesting
Patricia Davies
Patricia Davies received her B.Sc. in Mathematics from the University of Bristol in 1977, and her M.Sc. and Ph.D. in Sound and Vibration from the University of Southampton in 1981 and 1985, respectively. Her Ph.D. research was focused on time-domain modeling applied to acoustics and vibrations problems. She stayed at the Institute of Sound and Vibration Research (ISVR) until December 1986 doing postdoctoral research on statistical modeling of shock propagation through structures. She is currently a Professor of Mechanical Engineering at Purdue and teaches courses in measurements, controls, signal processing and mechanics. Dr. Davies is also the Director of the Ray W. Herrick Laboratories, where she conducts research in the areas of sound perception, signal processing, and nonlinear system identification. Her research has been funded by government and by industry. She has applied her research to modeling of human response to machinery and transportation noise; modeling the dynamics of viscoelastic materials and seat-occupant systems; visualization of automobile noise sources during pass-by tests; predicting machinery failure; and developing automatic analysis tools for classification of infant and mother laughter. She co-founded a Perception-based Engineering research Center which was formed from the collaborative research of a group of engineering and psychology professors at Purdue. Dr. Davies has just completed a two-year term as President of the Institute of Noise Control Engineering.
Presentation: Seat-Occupant & Polyurethane Foam Modeling; Aircraft Noise & Sleep Disturbance Modeling
David Chelidze
David Chelidze is a Professor of Mechanical Engineering at the University of Rhode Island. His expertise is in experimental nonlinear dynamics and data-driven system health monitoring. His current research (sponsored by NSF, NIH, US Army and AFRL) focuses on nonlinear dynamics of structures, structural damage identification and prediction, and identifying fatigue related changes in human coordination. He obtained his PhD in Engineering Science and Mechanics from the Pennsylvania State University, and is a recipient of the NSF CAREER award, and Edmund and Dorothy Marshall Award for Faculty Excellence in Research.
Presentation: Multivariate Analysis for Characterizing Multiscale Dynamical Systems
Phil Bayly
Phil received his BS from Dartmouth College, his MS from Brown University, and his PhD in Mechanical Engineering from Duke University in 1993. Since then he has been at Washington University in St. Louis, where he is currently Professor and Chair of Mechanical, Aerospace and Structural Engineering. His research interests involve nonlinear dynamics, vibrations and waves in mechanical and biomedical systems.
Presentation: Mechanics and coordination of cilia and flagella
Earl Dowell
Dr. Dowell is an elected member of the National Academy of Engineering, an Honorary Fellow the American Institute of Aeronautics and Astronautics (AIAA) and a Fellow of the American Academy of Mechanics and the American Society of Mechanical Engineers. He has also served as Vice President for Publications and member of the Executive Committee of the Board of Directors of the AIAA, as a member of the United States Air Force Scientific Advisory Board, the Air Force Studies Board, the AGARD (NATO) advisory panel for aerospace engineering, as President of the American Academy of Mechanics, Chair of the US National Committee on Theoretical and Applied Mechanics and as Chairman of the National Council of Deans of Engineering. He is a recipient of the the AIAA Structure, Structural Dynamics and Materials Award, the Von Karman Lectureship and the Crichlow Prize as well as the ASME Spirit of St. Louis Medal and Den Hartog Award as well as the Guggenheim Medal awarded jointly by the AIAA, ASME, AHS and SAE.
Presentation: Nonlinear Aeroelasticity Energy Harvesting
Raymond Plaut
Raymond Plaut is an emeritus professor in the college of engineering at Virgnia Tech. He was the Dan H. Pletta Professor of Engineering in the department of Civil & Environmental Engineering. He has published many papers on various aspects of structural behavior and dynamics. He has won many awards for his work. He obtained his undergraduate education at Cal Tech, and did his graduate work at UC-Berkeley.
Presentation: Rocking instability of a two-wheeled suitcase
Eric Butcher
Eric Butcher is an Associate Professor of Mechanical and Aerospace Engineering and is the inaugural holder of the Dwight and Aubrey Chapman Endowed Professorship. His research interests in Mechanical Engineering are in the areas of nonlinear dynamics and vibrations (with a focus on time-varying, time-delayed, and stochastic systems) and mechanisms (using graph-theoretic methods in type synthesis). In Aerospace Engineering he teaches classes and performs research in controls and astrodynamics, including both orbital mechanics and satellite attitude dynamics. He has been at NMSU since Jan. 2007, during which time he has been a PI or co-PI on grants from NASA, Air Force, Los Alamos National Labs, Department of Education, and NSF. Dr. Butcher has 71 refereed publications and has taught 11 different classes at the undergraduate and graduate levels (with 2 new courses planned for 2010-11). He is a member of AIAA, SIAM, ASEE, the Planetary Society, and serves on the Technical Committee for Multibody Systems and Nonlinear Dynamics of ASME. Previously he was an assistant and associate professor at the University of Alaska Fairbanks and a postdoctoral researcher at Sandia National Laboratories. His M.S. and Ph.D. degrees are both from Auburn University , where he was a student of Prof. S. C. Sinha. He has a B.S. in engineering physics as well as a Bachelor of Musical Arts degree from the University of Oklahoma. His current hobbies include music (drumming and DJing electronic club music), outdoor activities (backpacking and mountain biking), and anything to do with space exploration. While living in Alaska he raced sled dog teams, and completed both the Iditarod and Yukon Quest sled dog races. He has plans to learn to skydive and get a motorcycle.
Presentation: Three Current Research Interests
Shane Ross
Ross is the author of several publications in the areas of mechanics and nonlinear dynamics, related to areas such as vehicle control, transport and mixing in fluids, bio-locomotion, and chemical physics. His work has been featured in Science, New Scientist, American Scientist, and the Times of London. He has Ph.D. from Caltech in control and dynamical systems and has been at Virginia Tech in the department of Engineering Science and Mechanics since 2006.
Presentation: Geometric and statistical tools for state space analysis
Giuseppe Rega
Professor of Solid and Structural Mechanics at Sapienza University of Rome, Italy, where is Chairman of Ph. D. Program in Structural Engineering and Director of Doctoral School in Civil Engineering and Architecture. Past President of Italian Association of Theoretical and Applied Mechanics (AIMETA). Member of EUROMECH Nonlinear Oscillations Conference Committee. Chairman of Euromech Colloquia and IUTAM Symposia, he will chair next ENOC 2011 in Rome. Associate Editor, Guest Editor, Editorial Board Member of several International Journals. Research interests in cable dynamics, nonlinear vibrations in applied mechanics and structural dynamics, bifurcation and chaos, control of oscillations and chaos, reduced-order modeling, dynamic integrity, wave propagation, smart materials.
Presentation: Dynamic Integrity and Control of Nonlinear Mechanical/Structural Systems
Sophia Santillan
I earned my MS and PhD in Mechanical Engineering from Duke University, studying with Lawrie Virgin. I also earned a certificate in Nonlinear and Complex Systems. I'm currently an Assistant Professor at the US Naval Academy in the Mechanical Engineering Department.
Presentation: Highly Deformed Slender Structures
Harry Dankowicz
Harry Dankowicz is Associate Professor in the Department of Mechanical Science and Engineering at the University of Illinois at Urbana-Champaign and has held faculty positions in the Department of Engineering Science and Mechanics at Virginia Polytechnic Institute and State University and in the Department of Mechanics at the Royal Institute of Technology (KTH) in Stockholm, Sweden. He received his M.S. degree (1991) in Engineering Physics from KTH; and his Ph.D. degree (1995) in Theoretical and Applied Mechanics with minors in Mathematics and Astronomy from Cornell University. Prof.
Presentation: A lumped-parameter model of tire-terrain interactions for off-road vehicles
Stephen Rizzi
Stephen Rizzi is a Senior Research Engineer in the Structural Acoustics Branch at the NASA Langley Research Center. His two primary areas of research are thermal-acoustic fatigue and aircraft flyover noise simulation. Within the area of thermal-acoustic fatigue, he has focused his research efforts on nonlinear dynamic response simulation, high-cycle fatigue, and high-intensity thermal-acoustic testing. He is an associate fellow of the American Institute of Aeronautics and Astronautics, and longtime member of the Acoustical Society of America and the Society for Experimental Mechanics.
Presentation: Nonlinear Reduced-Order Analysis
Hartmut Hetzler
2003: Dipl.-Ing. in MechEng., University of Karlsruhe
Presentation: Research on Nonlinear Dynamics at ITM / Karlsruhe Institute of Technology
Steven Shaw
Steve Shaw is a Professor of Mechanical Engineering at Michigan State University. He work in applications of nonlinear dynamics to vibration absorbers and micro- and nano-scale sensors.
Presentation: Noise and Nonlinearity in Nanoresonators
Horst Ecker
Assoc. Prof. at Technical University of Vienna. Sabbaticals at Duke University in 1995 and 2005. Interested in all kinds of vibrations.
Presentation: Unstable Torsional Vibrations of Centrifuges
Tamás Kalmár-Nagy
Currently, I am an Assistant Professor of Aerospace Engineering at Texas A&M University. Within the broader field of Aerospace Engineering, my specialty areas are robotics, dynamics and control of autonomous vehicles, and nonlinear vibrations. I received my M.S. degree in Engineering Mathematics from the Technical University of Budapest and my Ph.D. degree in Theoretical and Applied Mechanics from Cornell University in 1995 and 2002, respectively. During 2002-2005 I was a Research Engineer at the United Technologies Research Center.
Presentation: Sliding Mode
Ilinca Stanciulescu
Dr. Stanciulescu's research focuses on computational mechanics (non-linear finite elements), constitutive modelling of materials, multiscale and multiphysics formulations, non-linear dynamics and stability of complex systems. Ilinca Stanciulescu holds a B.Eng (1995) and a M.A.Sc (1996) from the Technical University of Civil Engineering Bucharest, a B.S. in Applied Mathematics (2000) from Bucharest University and a Ph.D. in Civil Engineering (2005) from Duke University. Before joining the Ph.D. Program at Duke University, she served as a junior lecturer (1996-2000) in the Department of Strength of Materials of the Technical University of Civil Engineering (T.U.C.E.) in Bucharest, Romania. She has also worked as a structural design engineer (full-time in 1995 before joining the faculty at T.U.C.E., and part-time thereafter). Prior to joining Rice University as Assistant Professor in July 2009 she served as Assistant Professor in the Civil and Environmental Engineering Department at the University of Illinois, Urbana-Champaign (2006-2009) and as Postdoctoral Research Associate in the Duke University Computational Mechanics Laboratory (2005-2006).
Presentation: When algorithms create chaos
Tom Burton
Currently Department Head and Professor, Department of Mechanical and Aerospace Engineering, New Mexico State University.
Presentation: Nonlinear Vibrations and Structural Health Monitoring - Ongoing Work
Jeff Rhoads
Jeffrey F. Rhoads is an Assistant Professor in the School of Mechanical Engineering at Purdue University and is affiliated with both the Birck Nanotechnology Center and Ray W. Herrick Laboratories at the same institution. He received his B.S., M.S., and Ph.D. degrees, each in mechanical engineering, from Michigan State University in 2002, 2004, and 2007, respectively. Dr. Rhoads' current research interests include the predictive design, analysis, and implementation of resonant micro/nanoelectromechanical systems (MEMS/NEMS) for use in chemical and biological sensing, signal filtering, and inertial sensing systems, the behavior of nonlinear, parametrically-excited systems and coupled oscillators, and the behavior of mechanical and/or electromechanical parametric amplifiers. Dr. Rhoads is a member of the American Society for Engineering Education (ASEE) and the American Society of Mechanical Engineers (ASME), where he serves on both the Student Design Committee and the Design Engineering Division's Technical Committee on Micro/Nanosystems. Dr. Rhoads is a 2009 recipient of the National Science Foundation's Faculty Early Career Development (CAREER) Award and the Purdue University School Mechanical Engineering's Harry L. Solberg Best Teacher Award.
Presentation: Parametric Amplification: Macro to Nano


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23Rylie Chappell
2013 (Freshman): Played in nine games, making six starts as a freshman ... had four hits in 21 at bats, one RBI and one stolen base.
High School: A four-year starter and letter winner at Forney High School ... played outfield under coach Eric Montegomery ... helped lead her team to Class 4A state finalists as a junior and senior ... was named second-team all-district 15-4A as a freshman ... first-team all-district 15-4A as a sophomore, junior and senior ... named to the all-state tournament as a senior ... played club softball for the Texas Glory.
Personal: Daughter of Greg and Kimberly Chappell ... majoring in kinesiology.


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Robert Novy-Marx is an assistant professor of finance at the University of Rochester's Simon Graduate School of Business. Joshua Rauh is a professor of finance at the Stanford Graduate School of Business and a senior fellow at the Hoover Institution.
How much will the underfunded pension benefits of government employees cost taxpayers? The answer is usually given in trillions of dollars, and the implications of such figures are difficult for most people to comprehend. These calculations also generally reflect only legacy liabilities — what would be owed if pensions were frozen today. Yet with each passing day, the problem grows as states fail to set aside sufficient funds to cover the benefits public employees are earning.
In a recent paper, we bring the problem closer to home. We studied how much additional money would have to be devoted annually to state and local pension systems to achieve full funding in 30 years, a standard period over which governments target fully funded pensions. Or, to put a finer point on it, we researched: How much will your taxes have to increase?


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The National Institute of Child Health and Human Development has selected 15 outstanding scientists for its Hall of Honor, which recognizes scientists supported by the Institute for exceptional contributions to advancing knowledge and improving maternal and child health.
The scientists are being honored today in a ceremony on the NIH campus that commemorates the Institute's 40th anniversary. After the ceremony, the scientists' portraits and brief descriptions of their research contributions will hang in the halls of the Institute.
"The NICHD Hall of Honor scientists exemplify the scientific achievement for which they are honored, as well as the common humanity that motivates us all to serve others," said Duane Alexander, M.D., Director, NICHD. "We honor them for who they are, as much as for what they have done."
Listed below are the 15 Hall of Honor scientists and their award citations:
Since its creation by Congress in 1962, NICHD's mission has encompassed research across the life span. This includes development before and after birth; maternal, child, and family health; reproductive biology and population issues; and medical rehabilitation. NICHD research over the past forty years has led to advances enabling millions of people in this country and around the world to lead healthier lives. For example:
The NICHD is part of the National Institutes of Health (NIH), the biomedical research arm of the federal government. NIH is an agency of the U.S. Department of Health and Human Services. The NICHD sponsors research on development, before and after birth; maternal, child, and family health; reproductive biology and population issues; and medical rehabilitation. NICHD publications, as well as information about the Institute, are available from the NICHD Web site, http://www.nichd.nih.gov, or from the NICHD Information Resource Center, 1-800-370-2943; e-mail email@example.com.


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Hey Mother Nature: Was It Something We Said?
I would like to ask Mother Nature a question. Was it something we said? This is New Jersey, after all, and I know we sometimes say things we probably shouldn't, but Sandy, then a below freezing night with so many without power, and now a Nor'easter? Really?


text: (Photo by Rick Diamond/Getty Images) The Duck Dynasty Bowl? By Results Radio Townsquare Media March 11, 2014 They've got one of the most popular shows on cable TV and now they're name will be on a college football Bowl game for the next five years. Read More|Comment Category: Sports Tags: College Football, Duck Dynasty, Independence Bowl Send to a friend! Share on Facebook Share on Twitter Pin it! Reddit This! Share on Tumblr!


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Social media is an excellent way to communicate. Among the different types of social media Linkedin stands as the most appropriate for growing someone's professional network.
Tag Archives: interview
Behind The Scenes Interview: How A Clinical Research Organization Functions
I was able to interview Prasad Sristi, CEO of Mindprint Solutions. Mindprint helps CRO's efficiently run their businesses by integrating various layers of software in order to allow the CRO's to focus on their core competency: drug discovery, development and clinical trial management. Prasad shares some of the insider knowledge with regards to how CRO's negotiate their budgets with Sites, what business activities generate the most profit for them and we even get into the topic of remote monitoring. This was one of the better interviews I have conducted in some time as the behind the scenes insight into how a cro operates was valuable. I hope you find some of the findings helpful from this interview!
Interview With A Future CRA and Former Study Coordinator In Clinical Research
Below is the video where I interview a future hopeful clinical research associate (CRA). We get into some of her background as a study coordinator for oncology trials at a Southern California University. Mya also shares a bit of her personal story with respect to clinical trials and what they mean to her personally.
In this video below, Mya is actually interviewing me for a PhD program thesis that she is writing on the business of clinical trials and government funding.
Thanks for watching and as always, let me know if you have any questions regarding CRA's, funding, or careers in research!
How Technology Will Change Clinical Trials and More Random Talk With Barbara Duck
I finally got the chance to interview the one and only Barbara Duck also known as "The Medical Quack" which is the name of her world famous blog where she discusses many issues related to healthcare, privacy, data, technology and more. This conversation is extremely casual, but we discuss a few trends that we see taking form when it comes to clinical trials, particularly the use of electronic health records and health data storage websites such as mediguard that could be used to recruit study participants in the future. Many CRO's have entered this space, most notably Quintiles, and we discuss whether this is a good recruitment method or not. Let us know what you think about this rather controversial issue.
How Pharma MegaMergers Will Affect Clinical Research, Remote Monitoring, Investigator Initiated Trials and More!
In today's video, regular guest guru and producer of the show, Darshan Kulkarni stopped by to char regarding Investigator Initiated Studies, PDUFA, how mergers and acquisitions in the industry will affect us research clinics, remote monitoring and a whole lot more. We hope you enjoy and learn something new here!
Get An Insider's Perspective On How Biotechs Function!
Listen to this episode
I interview Barry Werth, author of The Antidote and Billion Dollar Molecule. I am currently reading his latest book, The Antidote, and I describe it as the Moneyball for Biotechs. In this interview, Barry and I discuss his two books, as well as the entire drug development process and even get into some of the guerilla marketing tactics that Vertex biotech, the star of the books, used in order to raise awareness about itself and some of the medical conditions that their researchers were working on.


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April 19, 2007 12:33 PM
One or two majors out of... hundreds?
How do you pick just one or two majors? When first coming to college, it may seem very overwhelming since at UC Berkeley there are hundreds of different majors, so one may feel as if they don't know where to start. However, I believe that the most important part about picking a major is chosing something that you have an interest in. Do not chose something because your parents, your boyfriends, or your family want you to do. Do something that YOU want to do. I know, this may sound trite and obvious, but you know, there are pressures out there from our loved ones telling us that they want us to do this, but really, who are you living for? You are living for you and only you.
How I went about chosing my major is similar to my why CNR blog on how I became to be in the college of natural resources. I chose it because I did not know that it was in CNR or a different college from L&S. However, I realized how interesting the biology majors in CNR are. The one I chose, Microbial Biology interests me because it is about the study of viruses and bacteria and how they may affect us. Since I have an interest in becoming a pediatrician and going into medicine, I figured that this major would perfectly suit my interests.
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David Leppard / London Times | August 20 2006
THE French authorities have reopened their inquiry into the circumstances behind the car crash that killed Diana, Princess of Wales after fresh doubts emerged over scientific tests that stated her chauffeur was drunk.
The French director of public prosecutions has authorised a judge to reexamine two forensics experts whose evidence was central to the finding that the 1997 crash in Paris was a simple road accident caused by a drunk driver.
The move will excite Diana conspiracy theorists and could lead to further delays in the UK authorities closing the case.
French investigators found in 2002 that Henri Paul, the chauffeur, was to blame for the accident. Their conclusion relied on blood tests showing that Paul was more than three times over the alcohol limit when the Mercedes he was driving crashed, killing himself, Diana and Dodi Fayed, her lover.
Doubts over the blood tests are also delaying the submission of a lengthy report into Diana's death by Lord Stevens, the former Metropolitan police commissioner.
Thierry Betancourt, the deputy chief judge at Versailles, last week ordered fresh depositions to be taken from Professor Dominique Lecomte, the pathologist who conducted Paul's post-mortem, and Dr Gilbert Pepin, who tested his blood.
The judge appears to have accepted claims that there are serious inconsistencies and omissions in the scientific paper trail that led French police to conclude in 2002 that the crash was caused by Paul's drink-driving. The new documents show that:
While Lecomte testified on oath that she had taken just three blood samples from Paul, a log book shows five samples were taken, suggesting the extra samples may have been wrongly attributed to Paul.
Pepin said one sample he tested showed Paul had 1.74 grams per litre of alcohol in his blood. But his finding is not supported by paperwork.
Paperwork relating to a second blood test by Pepin gives two widely differing readings for the amount of alcohol in Paul's blood.
There is no suggestion that either expert acted improperly. But failure to lay to rest the lingering doubts over the blood tests will make it impossible for any court to rule conclusively that Diana's death was a simple accident caused by Paul.
Betancourt's inquiry followed complaints from lawyers acting for Paul's parents and for Dodi's father, Mohamed al-Fayed, the owner of Harrods, the London store.
Fayed has claimed that Diana was murdered by MI6 on the orders of the Duek of Edinburgh and the blood tests were tampered with to cover up the murder plot. The duke, MI6 and Diana's friends reject the allegation.
INFOWARS.net Copyright © 2001-2006 Alex Jones All rights reserved.


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Al HeldAmerican (Brooklyn, New York, 1928 - 2005, Todi, Italy)
House of Cards
1960painting | acrylic on canvas
Not on view at this time; find out where you can see works from our collection at locations around the Bay Area while our building is closed for expansion
114 in. x 252 1/2 in. x 2 in. (289.56 cm x 641.35 cm x 5.08 cm)
Acquired 1969
Collection SFMOMA
Gift of Mr. and Mrs. George Poindexter
© Al Held Foundation, Inc. / Licensed by VAGA, New York


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It would not surprise me if Pakistan were to win the upcoming four-Test series against England. And that's not just trying to be sensationalist; I think there are very sound cricketing reasons for saying it.
England, for a start, have not played any five-day Test cricket against a leading nation until the trip to South Africa last winter. That's quite a time ago now.
Since then there have been four Tests against Bangladesh, two away in March and then two at home earlier this summer. But the last of those games was in the first week of June.
It is now the end of July, and England's players will need to get attuned to the demands of Test cricket very quickly. Pakistan, of course, have had two Test matches against Australia to get themselves attuned.
A number of England players have also not played very much cricket in the past month or so. Some have played a lot of Twenty20 but not much else. Kevin Pietersen has played no cricket at all since injuring himself during the one-day series win against Australia.
To me, at the start of the England-Pakistan series, there are some quite large question marks hovering over the heads of a good number of England players: Cook, Pietersen, Trott, Morgan, Prior, Anderson, Finn.
They all have question marks for different reasons – lack of cricket, fitness, technical questions, the need to pin down a Test place are some of them – but question marks they still are.
Most of all, though, there is the Pakistan bowling attack. That is the main reason why I have made the statement I have at the top of this column.
The Pakistan bowling attack is very, very good. Mohammad Aamer, Mohammad Asif, Umar Gul and Danish Kaneria represent one of the best bowling attacks in world cricket. They all offer something different, and they are all world-class performers.
The way their seamers bowled when Australia were shot out for just 88 at the start of the second Test at Headingley, for instance, was truly superb.
To my mind, these four bowlers – with someone like Shoaib Malik to act as a fifth bowler and second spinner – are good enough to operate in all conditions and to pose batsmen problems with both the new ball and the older ball. Between them, there is swing, seam, spin, pace – and control.
If they bowl to their potential in the four Tests at Trent Bridge, Edgbaston, The Oval and Lord's, I can see Pakistan causing England's batsmen a lot of problems. They certainly offer a bowling attack that will be a major challenge.
This series has been billed all summer as the perfect preparation for the Ashes series in Australia this winter, but I think England need to concentrate fully on these four games and forget anything to do with 'preparing' for the Ashes.
Mohammad Aamer is clearly a great bowler in the making – if he's not one already, at 18 – and he has real pace to go with his ability to swing the ball back into the right-handers. Mohammad Asif swings it both ways with wonderful control and Umar Gul is just a very good bowler who knows what he is doing. Add Kaneria's leg spin and googlies – yes, it is very special.
Pakistan's weakness, clearly, is their batting, but they still have some very fine players in Salman Butt, Shoiab Malik, Umar Akmal and Kamran Akmal. If, as rumoured, Mohammad Yousuf and even Younis Khan come back into the picture then they will have a very solid-looking batting unit, too.
England, then, have to attack the Pakistani batting and need to bowl very tightly and yet aggressively themselves. Ravi Bopara might be coming back into the picture on the batting front, but with Ian Bell injured the first opportunity looks like it will go to Jonathan Trott and Eoin Morgan amongst the less established batsmen – assuming Andrew Strauss, Cook, Pietersen and Paul Collingwood are all fit and firing.
The month of August promises a genuinely fascinating Test series, and don't be surprised if the outcome is not the one England's team and their supporters might expect.
Pakistan may be like a wandering side these days, due to the unfortunate situation they have at home, but they are hugely talented and they will also not want for support here in this country.


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April 25, 2012
Anthony Dasher
If there's one thing Ben Jones has learned throughout the weeks and months leading up to the NFL Draft, it's to enjoy the process.
That includes the countless workouts, interviews with scouts and coaches, pretty much the entire gamut.
"You just try to be yourself," Jones said Wednesday in a telephone interview with UGASports. "Everybody's going to ask you specific questions. You've just got to go out, stay focused and have a good time with it. Try to have a little sense of humor. Don't bore them to sleep; make yourself a little different."
Jones certainly didn't have a problem with that during his four-year career with the Bulldogs.
Whether it's eating crickets, chomping on a piece of sod from Bobby Dodd Stadium or going through pre-game walkthroughs barefoot, Jones admits he's always been a little different than most of his colleagues on the football field.
But when it comes to his dream of playing football in the NFL, it's no joking matter.
"I've always dreamed of getting to play in the NFL, and it's finally coming true," Jones said. "I'm just really trying to take it in and soak up this moment."
Jones won't be the only one.
The three-day NFL Draft (Thursday-Saturday) should be a very profitable one for former Bulldogs, as offensive tackle Cordy Glenn, tight end Orson Charles, defensive lineman DeAngelo Tyson, cornerback Brandon Boykin, punter Drew Butler and placekicker Blair Walsh have each been projected by different draft experts to hear their names called.
Tight end Aron White, offensive lineman Justin Anderson and fullback/tight end Bruce Figgins will also get their shot, either in the draft or as a free agent.
"I feel my chances now are better than before the combine, I can tell you that," Anderson said. "It's all in God's hands. The book is already written for our lives. What God has for us is going to be for us, so regardless of what happens, I've done all I can do."
The draft begins with the first round Thursday at Radio City Music Hall in New York starting at 8 p.m., followed on Friday at 7 p.m. by rounds 2-3 and Saturday with rounds 4-7 beginning at noon.
"I'm going to be sitting here watching it with my family," Jones said. "I think they're just as excited as I am. We're just looking forward to seeing where I'll wind up."
Most experts project Jones to be selected somewhere in the third or fourth round.
The Philadelphia Eagles are conceivably a team who could call Jones' name.
Jones recently travelled to Philadelphia for a private workout and said that "seven or eight" other teams held workouts for him in Athens.
But impressing the experts isn't always easy.
According to the NFL draft website sidelinescouting.com, one of the negatives evaluators use to describe Jones states that he "is not an overly impressive player by any right, doesn't really stand out or do anything particularly well... Not as big as you would like him to be, shorter than ideal arms and small hands, doesn't have elite size or overall athleticism."
However, Jones doesn't take such criticism in a negative light. In fact, in recent weeks, Jones said he's tried to read up on just as many opinions as he can.
"I definitely look at it, just to see what they're saying and try to pick out any little thing I can improve on," he said. "If they're saying I need to work on my feet, I'll definitely try to do that."
That said, if scouts want a true view of his ability on the field, Jones said all they've got to do is look at the film.
"I know I might not be as good in some things," he said. "But you can put on the tape and see whether you can play football or not."
Scouts obviously feel that way about Glenn.
Measured at 6-foot-5 ¾, and 345 pounds at the NFL Combine last February, Glenn is projected to go somewhere in the latter half of Thursday's first round.
Having played both guard and tackle for the Bulldogs, Glenn feels his versatility is what's helped put him in the position he is. Either way, he's confident he'll be a success.
"That's always my mindset," Glenn said. It's all about being confident and trusting yourself."
That's exactly what Boykin is doing, too.
Described by sidelinescouting.com as a "feisty player who loves to compete," is projected to go as high as the second round, despite the leg injury he suffered in the Senior Bowl that kept him from competing in the NFL Combine and limited his participation during Georgia's Pro-Day.
"People show out at the Combine, have a great showing and people think their stock is rising so much, but end all to beat all is that film and I think I put a lot of film, a lot of good film in people's hands," said Boykin, who was given a clean bill of health during a re-check by league doctors recently in Indianapolis. "They know I'm a great player."
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Thank you to Dyke Hendrickson for this wonderful story featuring Greta in the Newburyport News!
Lucky 7
If seven is a lucky number, Greta Reineke was a lucky young woman when she migrated from Austria. "We came on 7-7-77," Reineke said recently. "July 7, 1977. I will always remember that."
Reineke is the owner of Greta's Great Grains, a popular bakery and pastry shop on Pleasant Street. She is a fixture in the community today, but it has been a long vocational journey that actually started with her being one of the first physical-fitness mentors in this area.
"My husband, John, was from Germany, and I was from the Kitzbuhl area in Austria," Reineke said, whose age she ascribed to be "of retirement age."
"We had been children during the war, and when we started a family, we were still concerned about the security of the area, since the Soviet Union was so near and the Cold War was very much on people's minds. We wanted our children to be safe."
John was able to land a job on the North Shore, and Greta started her life in this area as a housewife taking care of the children. She soon was giving exercise classes at The Tannery. As a hobby, she did baking at a shop close by in the complex.
"My fitness students smelled my bread and pastries and started buying them," Greta said with a smile. "Soon, I started looking for space to open a store. But I didn't want to do wholesale. I wanted to meet and talk with customers. There was a storefront on Pleasant Street that was empty; I rented it, just about 16 years ago, and I started the business of selling breads, pastries and pies. No sugar, no fat. Just basic foods."
Greta was a tennis player in those days, and one of here teammates lightheartedly made her an apron that said Greta's Great Grains. "She gave it to me as a surprise, and I ended up using it as the name of the shop."
The store, which employs five, has been a major success, even as competitors move in each year. On one wall is a large framed photo taken years ago of a woman baking bread in a huge outdoor oven in Austria.
"I love that photo because it reminds me of my old country and the people there. My mother ran a small country store and worked all the time. If I wanted to visit with her, I'd go to the store. So, I grew up behind a counter. Now, with Thanksgiving, this is a very busy time of year for me.
"I'm pleased we came to America — my children did well, and we were able to make good lives here. I have warm memories of both places — my early life in Europe and then settling here, starting the store and raising a family. But I do go back to Austria regularly to see family and friends. I want to keep ties there."


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Situated in Lincoln, this hotel is 3.5 mi (5.6 km) from International Motorsports Hall of Fame and within 12 mi (20 km) of Talladega Superspeedway and Heritage Hall. Bingham Park and Pines Park are also within 12 mi (20 km).
Hotel Features
Along with coffee/tea in the lobby, this hotel has a seasonal outdoor pool and laundry facilities. Free continental breakfast and free self parking are also provided. Other amenities include a 24-hour front desk, free newspapers, and a front-desk safe.
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Guests can enjoy a complimentary breakfast each morning. This Lincoln hotel also offers a seasonal outdoor pool, coffee/tea in the lobby, and complimentary newspapers in the lobby. Complimentary self parking is available on site.
- 24-hour front desk
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Guests are offered a complimentary continental breakfast each morning.
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Implementation Guide
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Postinstallation phase
If you encounter issues either during the installation of the BlackBerry Mobile Voice System or after you have installed the BlackBerry MVS, you can engage BlackBerry Technical Support in one of the following ways:
- Visit the BlackBerry Expert Support Center at www.blackberry.com/besc
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When you are talking with BlackBerry Technical Support Services you must provide your subscriber code to gain access to technical support. The support analyst will request the data that you gathered in the preinstallation checklist topic and the site survey checklist topic, so be sure to have the information available.
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« Fakery And Its Ends |
| Hits, Misses, and Some More Misses »
Posted by Derek
Hang around any drug discovery organization and you'll hear complaints about how the drug candidates don't dissolve well. The people who test the compounds on cells and proteins complain a bit about this, and the ones who test on mice and rats complain even more. Traditionally, the problem eventually lands on the lab benches of the people who work out formulations, who complain that by the time it gets to them that there's only so much than can be done. So over the years, it's become more of a concern for the chemists who make the things in the first place, as I guess it should.
Solubility isn't the single most important factor in making drug candidates, but you can't ignore it, either. Having a drug that dissolves well frees you up during development. Whenever you get low or variable blood levels while testing a new compound in animals, you always wonder if the compound was dissolving in the gut properly. If the answer is already known to be "Yes", then you can concentrate on the other potential problems. (That said, solubility doesn't correlate with good blood levels as well as you might imagine, because of those other factors. Awful solubility correlates pretty well with awful blood levels, though).
There are other virtues: a soluble compound is also a lot easier to dose i.v., which is a valuable stage in figuring out how it's being distributed in whole animals. And getting into the clinic is hard enough without having to worry about how you're going to dose the first human volunteers, and whether a temporary fix for the problem (a "service formulation") will provide relevant data or hold up at all as you go on into Phase II. There are, to be sure, some valuable drugs with absolutely horrible solubility problems (taxol comes immediately to mind), but you'd rather not find yourself competing with it for the title.
But solubility, as a word, conceals several different behaviors. It comes down to how much the compound likes to associate with itself versus how much it likes to associate with solvent. Those two values can vary pretty independently, and you get different situations as they slide up and down. In the case of a drug formulation, that solvent is going to be as watery as feasible, so here's how things break down:
Low self-affinity and low aqueous affinity: the first value will give you an oil or a low-melting solid, and the second will give you trouble going into solution. We try to avoid this category if possible, although you can always formuate as some sort of oil-filled gel cap if you're really up for it, as with Vitamin E.
Lower self-affinity and higher aqueous affinity: Depending on the absolute values here, this could be low-melting again. But this time it'll hop right into water, because it's actually happier there than it is in its own crystal form. Formulation should be a breeze, but the problem with these guys is that they'll soak water right out of the air and turn into goo if you don't watch out.
High self-affinity and lower aqueous affinity: here's where you run into trouble, and here, unfortunately, is where a lot of med-chem drug candidates land. The first value will give you a high melting point – the crystal's very happy the way it is, thanks, and would rather not give up its structure. And water has a hard time competing. This is where the formulations people really get a workout – in a future post we'll talk about some of the tricks used in this situation. Sometimes the chemists can fix things by making one part of the molecule lumpier – literally – so that the structure doesn't pack so well into a crystal form.
High self-affinity and high aqueous affinity: depending on the absolute values again, this could be tricky. There are some high-melting solids that dissolve in water just fine: ionic substances like table salt make great crystals, but their interactions with water are even more favorable. But you can also end up with a compound that will stay in water, but has trouble going into water. Once the molecules are surrounded by water, they're happy, but those first few water molecules have a tough time pulling each drug molecule out of the crystal surface. If you grind one of these guys up really fine and stir it for three days, you'll probably get a reasonable solution, but at first glance you'd take it for a compound from the previous class. All the more reason to make sure you're at equilibrium before drawing any conclusions.
So that's a quick look at solubility, and a quick look at the range that a medicinal chemist has to think about: from picturing molecules stacking one by one into a crystal, to picturing a drug candidate gumming up a syringe held by a muttering, red-faced pharmacologist.
Comments (17)
+ TrackBacks (0) | Category: Drug Development
1. John Johnson on March 7, 2008 10:33 AM writes...
The moral of the story: drug discovery is tricky no matter what solution you come up with.
2. Analytical Scientist on March 7, 2008 10:38 AM writes...
If you can get solubility without compromising intestinal permeability, though, that's really the brass ring. BCS class I compounds tend to be a joy to develop and their success rates through to market are markedly higher than for other compounds according to retrospective analyses done at several big pharma companies.
The flip side of this is that high intestinal permeability is often the saving grace of some of those marginal solubility compounds that you mention above. If the compound is a greaseball or brick dust without the corresponding virtue of permeability...well, hope is dim for these compounds.
3. Formulation Sci on March 7, 2008 11:32 AM writes...
A lot of the solubility or lack of solubility of drug molecules may begin with HTS methods used to identify these molecules.
I do not have any concrete evidence for this except some anecdotal ones. Would like comments on this?
4. Anonymous on March 7, 2008 11:49 AM writes...
Can the soluility issues be solved for ever by using nano technology to deliver the drugs right to the target? Ex: Taxol
5. CMC guy on March 7, 2008 12:19 PM writes...
I know (and applaud) a number of examples where Formulations groups have successfully overcome difficulties in dissolution or other poor properties for candidates from their bag of tricks/expertise. That said it is so much better to build in molecule up front however functionality that helps solubility can hurt activity, stability or synthesis so most candidates end up compromising factors. Taxol may be example of ultimate compromise because it works and readily sourced but use of (very) undesirable cremophor tolerated.
#3 Form Sci may have a point in that HTS often uses DMSO or DMF that can negate poor solubility and thus hits are not best drugs. In most circumstances med chemists do not have time to make adjustments of leads to more viable molecules because of pressures to progress or cancel project so HTS hit is chosen little or no modification- if additional research done can sometimes result in back ups that are more suitable.
6. CMC guy on March 7, 2008 12:27 PM writes...
Meant to ask if most people include Log P (or D) either meassured or calculated as part of the selection process? This info can provide much guidance on potential problems but often seen as post evelauate of candidate rather than screen or selection tool.
7. Enoch on March 7, 2008 2:13 PM writes...
#3 Form Sci -
Chris Lipinski has published and given several talks on the subject. You can Google to your heart's content, but here's one published reference to this work;
8. Polymer Bound on March 7, 2008 7:19 PM writes...
#3: The source of the lead could influence solubility but, oddly enough, I think the nature of the target tends to cause these problems. I lack experience in these areas, but most gripes about solubility I've heard come from people working on proteases and kinases. It might just have to do with the nature of their active sites.
9. NJBiologist on March 7, 2008 9:32 PM writes...
Derek (or anyone else)--Are self-affinity and aqueous affinity essentially the parameters that govern kinetic and equilibrium solubility? How do you predict this sort of thing?
--the guy sitting at his desk, swearing in anticipation of the vial of brick dust which arrives Monday
10. Morten on March 8, 2008 4:29 AM writes...
Guys remember that taxol is actively transported into the body from the intestine. It's not a good model for anything.
I've heard of using sonication to reach solubility equilibrium faster but does anyone have any other tricks?
11. weirdo on March 8, 2008 12:05 PM writes...
HTS: HTS is the problem only in that allowing biologists near screening data should never be allowed. They always like the most potent molecule. Seldom, in my experience, are the most potent hits the best starting points for lead optimization. (That's not really fair to biologists, there are plenty of chemists who like to start with good potency, too!). I even know some chemists who complain when they make molecules that have too much water solubility, because they're "hard to isolate". Yikes.
Pressures of short lead times: I hear this all the time, and it's a cop-out. Who forces those short lead times? Managers who were once (at many companies) or still are (at my company) drug discovery scientists? I think it's the teams themselves that make bad decisions, rather than so-called "managers". But it's a lot easier to blame your boss for doing a poor job, than admitting something could have been done differently earlier in the project. If you find yourself at a company that forces bad scientific decisions to meet artificial timelines, go to another one. There are plenty of pharma companies, big and small, that don't reward bad decisions.
Philosophy of drug design: Clearly an important factor, as Lipinski's article elegantly shows. Overreliance on potency leads to low solubility, if one does not analyze HOW that potency is achieved. Take a look at how the appropriate placement of an adamantyl group can lead to a log-improvement in "affinity". Duh, make a molecule with good affinity want to get out of water and into grease as quickly as possible, and all of a sudden you have great affinity. Not exactly the path to happiness, however.
PolymerBound: I think you're absolutely correct. But this only points out how project teams need to do a better job at selecting targets!
12. milkshake on March 9, 2008 4:37 AM writes...
Weirdo: It is pretty easy to grab a HTS hit and run with it. You optimise the hell out of it and within a year you get a low-nanomolar undruggable compound. But the management flowchart checkpoints are met and the pencil-pushers look more dynamic as they seriously chew around on their endless project meetings
I have been on a project that suffered an embarassment of riches. First the people working on this target re-synthesized couple of literature compounds, made hybrids and came up with two patentable leads - one ho-hum, one pretty decent one. Meanwhile our HTS group kicked in and we got at least five more dissimilar very promising-looking drug-like hit classes. (Each structural class showed in screening several times, you could almost build a SAR starting point from the HTS data alone). Now with a small academic group - with only few people in chemistry and biology - how do you work on seven dissimilar molecules all at the same time? It took us quite some time to narrow it down to only two or three most promissing leads that we pursue full time - but after a year you suddenly reach the stage in SAR where the each class diverges into two so you have again four lead substructures... It has been a strange situation, but comparing different kinds of molecules for the same target lets us to appreciate the different properties of these leads (and rather tired when thinking how much work remains to be done, to get a good PK and cell potency and selectivity, all at the same time). We are lucky to have a grant so that we can go on like this for couple of years. Our top management are scientists so no-one is forcing us to pick one particular lead and "make a candidate from it by the end of year"
13. Great Molecular Crapshoot on March 9, 2008 4:45 PM writes...
A quick comment because the last one I made didn't get thru. Nobody seems to have said much about ionisation (apart from CMC Guy's query about logD) and this is a very important determinant of solubility. Here's a review article that may be of interest:
14. weirdo on March 10, 2008 10:44 AM writes...
milkshake: It is also pretty easy to blame bad decisions on "management pressure". Too easy, unfortunately.
15. Kay on March 10, 2008 1:08 PM writes...
Morten: since taxol is not oral, I am confused by your comment.
16. Morten on March 10, 2008 6:33 PM writes...
Freg... what drug was I thinking of then... I'm blank.
17. markm on March 18, 2008 8:12 AM writes...
A discussion of solubility reminds me of the sulfa drugs discoverd by Bayer (IIRC) in the 1920's (the first effective antibiotics, based on sulfonamide). Sulfonamide was soluble enough to be readily absorbed in therapeutic concentrations from a pill, but often patients with sore throats and children had difficulty swallowing the pills, so oral liquid and injectable formulations were greatly desired - and it simply would not dissolve in high enough concentrations for these purposes.
In the 1930's one small American drug company finally found a solvent - ethylene glycol. Somehow they didn't do any toxicity testing, and marketed the sweet-tasting solution primarily as a children's medicine. To their credit, they reacted to the first reports of poisonings by immediately doing all they could to recall the drug, including publicity and asking the FDA to get their entire (rather small) staff out to help track down every bottle, but there were over 100 fatalities before all the shipments were accounted for. It was after this incident that Congress gave the FDA the powers to require drug testing, approve drugs before they were marketed, and to order recalls.
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This item is currently backordered. We will ship it to you as soon as we receive it.
Power up to a better clean with the Braun Oral-B Battery Powered Toothbrush! Your teeth and gums will feel pampered because you're removing more plaque than an ordinary manual toothbrush every time you brush.


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25th Anniversary of VA Wine Month Celebrated
Oct 01
On Monday Sept. 30th, Gov. Baliles, who launched the first October Virginia Wine Month in 1988, joined Gov. Bob McDonnell and Sec. Todd Haymore to celebrate the 25th Anniversary of October Virginia Wine Month. All living former Governors of the Commonwealth of Virginia were invited to attend this special event, which was held at the Library of Virginia and will highlight red and white wine samplings from 25 award winning wineries including library wines dating back to the much earlier vintages. In addition, an archival exhibit of historical Virginia wine artifacts, including a signed letter from Thomas Jefferson was displayed. The exhibit, which showcases the past and present of the Virginia Wine industry, also included library wines from earlier vintages. The event took place at the Library of Virginia in Richmond.
Virginia celebrates Virginia Wine Month each October with an array of unique wine experiences, wine festivals, winery tours, travel packages and more. First celebrated in 1988, Virginia Wine Month has grown to highlight Virginia's wine production as it has grown to be ranked fifth in the nation.


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Ayariga rubbishes doubts over FIFA letter to Ghana over interference
Ghana's sports minister Mahama Ayariga has rubbished reports by a section of the Ghana media that FIFA's recent letter over potential government interference is fake.
A section of the Ghana media cast doubt over the legitimacy of the FIFA letter to the GFA seeking clarification of the setting up of a commission of enquiry on the Black Stars World Cup failure.
Government set up a commission of enquiry to investigate Ghana's participation but the terms of reference of the enquiry raised eyebrows over possible government interference in the sport.
Media reports prompted FIFA to write to the Ghana FA to seek clarification over the issue but some have called the authenticity of the letter into question saying it was cooked by the GFA.
But sports minister Mahama Ayariga, who has confirmed receiving a copy of the letter, says he has no doubts about the authenticity of the FIFA missive.
"FIFA is legitimate to write to the local G.F.A requesting to be briefed on events in Ghana," Ayariga said.
"We are in a digital world so it's easier to have information by so doing they want concrete evidence from the source and I think it's legitimate. There is nothing wrong with that,'' he stated.
The three-man commission set up by the Ghana government is yet to start its work.


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Vero Beach Yacht Club plans Silent Auction for March 17
VERO BEACH - The Vero Beach Yacht Club will have its first Silent Auction fundraiser that will benefit The Source.
The auction will be from 4 to 8 p.m. March 17 at 3601 Rio Vista Blvd., Vero Beach. The evening will include heavy hors d'oeuvres, cocktails, and a live performance by the Vero Beach High School String Quartet. Ticket price is $75.
The Source is a Christian outreach ministry serving those less fortunate in Indian River County.
For information on donating cash or new items for the auction, call Woody and Karen Boarman at 772-770-0028. To RSVP, contact Jack and Mary Berrigan at 772-234-5286 by March 12, as seating is limited.
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- Product measurements were taken using size 9, width M. Please note that measurements may vary by size.


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Hotsos Symposium Speaker – Kellyn Pot'Vin
Kellyn Pot'Vin is a new Hotsos Symposium presenter.
Kellyn Pot'Vin has more than fifteen years of experience in information technology and more than twelve years with Oracle, SQL Server and numerous years with the MySQL database platforms. She specializes in database performance tuning and the glories of simplifying database management.
In recent years, she's been working with large SSD databases and Exadata, taking advantage of the newest technology and performance tuning features. Kellyn is known for her technical blog, dbakevlar.com, numerous technical sites, including a main contributer at OraDBPedia.com.
She is on the board of directors for RMOUG and the database track for ODTUG's KSCOPE 2012-13. She's performed numerous presentations, including RMOUG, KSCOPE, MOW, OOW and SQL Saturday. Kellyn is an Oracle ACE .
Kellyn lives with her partner, Tim, and her three children in Broomfield, CO. She is currently honing her technical skills at Enkitec, an Oracle-centric consulting partner (www.Enkitec.com).
Presentation Title
EM12c: Metric Extensions — Designing, Deploying and Dynamic Success
Oracle Enterprise Manager 12c has introduced adaptable and fluid new monitoring concepts, including "metric extensions," which all DBAs who manage their environment with Oracle Enterprise Manager 12c should understand how to use. Attendees will leave this session with a clear understanding of how to plan, develop, and deploy metric extensions to ensure dynamic and full monitoring of any Oracle environment.
The session discusses monitoring templates, the metric extension library, and the full suite of metric and collection capabilities. It also includes demonstrations showing how to utilize the features and a full Q&A period to ensure that everyone grasps the full potential of Oracle Enterprise Manager 12c in this arena.
Presentation Materials
Presentation materials are available online to attendees only.
The speaker schedule is as follows:


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The Immokalee Foundation serving kids
The Immokalee Foundation, with a mission to inspire the underserved youth of Immokalee through education, recently hosted a tennis clinic featuring the Gwynedd-Mercy College women's tennis head coach and players at Immokalee High School.
Assisting coach Jim Holt Jr. and his players were the Center Court Athletics, members of the Pelican Marsh Tennis Club including member Jim Holt Sr. who is also assistant coach of the Gwynedd-Mercy College women's tennis team in Gwynedd Valley, Penn. Along with providing lessons to The Immokalee Foundation youth, the Center Court tennis players secured donations of rackets, balls and miscellaneous equipment with the hope that the students will continue to play with family members or friends.
Holt Jr., was the recipient of the U.S. Tennis Association's 2011 Adaptive Tennis Community Service Award. He, along with his players and Center Court athletes, spent an afternoon teaching tennis fundamentals and running drills with students from Immokalee Middle School, RCMA Charter School and Immokalee High School.
The Immokalee Foundation has a range of programs that focus on building pathways to success through college and vocational school, mentoring and tutoring, and opportunities for broadening experiences and life skills development. To learn more about TIF, volunteering as a mentor or for additional information, call 239-430-9122 or visit www.immokaleefoundation.org.
This story is contributed by a member of the community and is neither endorsed nor affiliated with Naples Daily News.
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