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Food was good, not great, a little overpriced. My biggest complaint is that they tried to charge me an extra 50 cents on my bill, I asked them what this was for, and the waitress said it was a charge for the use of a credit or debit card. The problem was, i hadn't given them my card yet, i hadn't chosen my method of payment yet, but it was just on the bill. So, had I happened to pay cash, they would have still charged me that extra 50 cents. 50 cents is not much money, but i consider what they did an unscrupulous, shady and under-handed business practice; one that I will remember and as a result, will never go to this place again. The waitress also tried to charge me extra for the spicy vegetable side dishes, something that never happens at any of the other Korean restaurants I've ever been to.
Whoever owns the place must be incredibly stingy, petty and cheap, I would hate to be an employee there.
My husband and I have been watching Kitchen Nightmares recently and I felt it was our responsibility to let the public know about this place.
He worked there for a few weeks a couple years ago. He quit because he said the place was filthy. He previously worked at Olive Garden for 3 years which has is immaculate I might add. He ended going back to Olive Garden.
When they were showing him around they went inside the walkin in cooler. On the floor was a bin...like a Sterilite bin. Inside this bin was their main sauce that they use. It was not covered at all, just sitting on the floor open to let stuff fly in it. They told him to step over so they could show him stuff. He lost balance while doing so (those things are pretty large) and his foot went in the sauce. He immediately apologized and they were like "Don't worry about it" and continued to use it. His nasty dirty shoe WENT IN THE SAUCE and they STILL USED IT!!!! EW. He also said the kitchen was disgusting. He actually took it upon himself and tried to clean it.
He and the other line cooks would smoke in the walk in cooler. The managers/owners did know about this because he said one time they walked in when they were smoking. The guy was like "Hurry up" He also said they would sometimes join.
Before I even met my husband and knew about this place, many of my friends had gotten food poisoning from this place as well.
I beg of you, please please do not go to this restaurant. I've never eaten there myself and now I never will.
This is NOT a brewpub but a motel restaurant/bar. Old folks from Green Valley. Worse now with the Snow Vultures back.
Not sure what Mo is trying to pass off as veal but it looked and tasted like deli turkey. It should be illegal to fradulently advertise and serve something that isnt.
Look forward to this place closing.
Will never patronize this restaurant ever again!. They wouldn't accept a $100 gift certificate. We received it as a gift from some grateful friends, but management wouldn't honor it. WHY NOT? It's equivalent to us having paid for our meal in advance. Definitely not a sound business approach for endearing themselves to their customers.
This place sucks. Horrible service, poor food. They give hamburgers cutesy 50's names and charge 8 bucks for a basic fast food ho-hum burger that's nothing special. Our waitress forgot about us for 40 minutes after we ordered and brought us cold food, I complained to the manager the next day and never heard back. Avoid this place
Terrible food and the owner is incredibly rude. I've seen him harass cyclists and customers. Perhaps if he spent as much time working on his business as he does bothering customers it'd be worth eating here. As it stands, better to run the other way.
I could cry. Yes its that bad, the service, is deplorable, small portions, of not very good food, horrible chairs,
and the only thing that i can say was good, was the nice waiter, the bus boy, ect. I have never seen anything like this. the only good thing was the refried beans. Go to Mi Nidito (520) 622-5081 - 1813 S 4th Ave, Tucson, AZ , that is where I am going to from now on. Trust me this place is a disaster , and even with a reservation you are greeted with the most unfriendly hostess.
Not only is the strip mall dumpy, its also a hangout for those who have trouble coping with the law of gravity, and its surrounded by one of the worst slumlord neighborhoods in the city. TPD should just open a satellite office here as they are in they parking lot most of the time anyway. Last time I ate there the coffee was truly awful, more like colored water. Eggs sunny side up were served up almost raw and the hash browns barely touched the stove. Serving up undercooked food can be a health hazard. Yes it might be cheap, but its also really bad. There might be a chef on the business card, but there certainly is not one in the kitchen. People who like the food served up there must be desperate, because frankly, in this neighborhood there is no other place you can go to.
Time Market has entered into a serious period of decline. This Tucson Weekly review has become dated. Time no longer has a deli. They primarily serve pizza slices, beer, and wine. Although they close at 10pm, do not expect to be served if you arrive after 9pm (youll be told nothing is available except the last few leftover cheese slices). They turn off their coffee machine at 7pm because they want to start breaking down three hours before closing. Don't turn to management for any help, even the owner will attempt to insult you with smug remarks when given reasonable feedback.
Mosaic is not the same restaurant I remember. Went there for New Year Eve lunch 12/31/14. Asked for a window seat,(there were plenty) and got seated in a plastic bush in the center of the room. Across the way,a tablecloth was draped over a table that had the top glass over its contents broken,that was left there next a to the window....where some of us would have liked to sit.The waitress warned us about the new waiter that would be taking our order,and mentioned that she would make sure he got it right.Which he did,but then we never were checked on after that,until he brought the check.Our table had only forks on a napkin,as did most of the tables with diners and without. As I pondered whether it was a new Mexican tradition to eat with only forks,I noticed that 4 recently seated diners had knives and forks. Okay....dishwasher problem,not enough utensils,who knows....But I will not be returning to Mosaic any time soon.Shoddy shoddy shoddy without the dialed down drink or menu prices.
We ordered the cheese crisp. We forgot to order chiles on it. When she brought it back it had green peppers on it. I said these are green peppers, and she told the cook and he said no, those are green chiles. Ok. Bottom line is I was born in Tucson and raised on sonoran style Mexican food. I KNOW the difference between the two. Don't insult me by telling me different. And, and, the beans I ordered maybe were four tablespoons full. If the young man who came to the table to sooth us is the owner, oh, my, god. Good luck in the future little boy, were gone and won't be back. Barry A Malone
Used to like it but it has gone down hill over the last few years. Poor quality pizza and horrible service. I have had multiple deliveries where the pizza arrives 30 or 40 minutes later than they say it will and when it gets there it is burnt on the bottom and cold. It takes a lot of effort to screw up that bad. Not to mention EVERY time I have added a six pack to my order the driver "forgets it in the cooler" and has to go back to his car for it. Hmmmmm. Im guessing they hope you forget so they get free beer.
The crust use to be excellent. Just a few weeks ago, had it delivered to my house....so disappointed! The crust tasted like it had been frozen for a long time. Low Quality Pizza.
There is something 'off 'about the food here. I think the ingredients are not of high quality and it sure shows. It's always packed because there isn't any competition in that particular area.
I had got married on the 29th of March and had a little less than 200 people or at least 200 people. we were supposed to get food at 5:00pm for all of our guest Marys lucky dollar didn't come until 7:00pm. My guest where upset hungry and some even left because they couldn't wait any longer to eat due to them being elderly and needing to take medicine. Mary's lucky dollar decided to give my Mother in Law their pots and pans and said to give it to Gabby at Balloon Land that they didn't have enough room and didn't want to wait to finish serving everyone till the food was completely gone. They had called my phone asking for their pots and pans I informed them my mother in law has them. she then stated can you call her and have her drop them off at the balloon land. I did do this and informed my mother in law they needed them that night for a job the following day as soon as they called me. I tried talking to them about them being two hrs late and they just pretended they didn't know what I said and said we just need our stuff you talk to gabby then hung up. The lady didn't call back nor gave me her name when I asked so I assumed it was taken care of. Two weeks later she calls back again stating we haven't given them their stuff back. So I responded and said Why was the stuff given to my mother in law in the first place it's not our responsibility to have your stuff that is your guys job to have all of your stuff and be responsible for it at all times. And another thing I would like to know who I speak to about the dinner service you guys where 2 hrs. late and I had guest who had left because of this. She immediately said YOUR A LIAR!!! WE WHERE A COUPLE OF MINS LATE AND THATS IT. You owe us money if anything because we made food for 275 people. I said excuse me???? Did you just call me a liar??? this is how you treat your customers ??? First of all I paid a good amount of money for Gabby to pay you to feed for 200 people and that was at an all you can eat expense as well so that's not my problem you made more then you were supposed to. What is your name? she said why do you need to know my name you just call gabby and take it up with her!! I said because I need to know who I am speaking to! So may I have your name please? she said Rosa I said ok Rosa and what is your last name? she said why do you need to know this information I said so I can report you for the bad service you did you were 2 hrs. late then you give my mother in law stuff that wasn't hers to make it her responsibility and now you are calling me a liar and saying I owe you money when i paid 5500 for all of this to be perfect and it wasn't!!!! well Roberto said it was good service and yes and who is Roberto was he my husband ?? was he the one who paid for all of this to happen???? No it was me and my husband and I'm telling you it was not a good service because you were 2 hrs. late may I speak to your manager. She then just stuttered um um um I said Rosa are you the manager or owner? she said no I said ok I need to speak to someone above your head please put your manager on the phone but she can't speak to you because she doesn't know. She doesn't know what? She doesn't know English so you need to take it up with gabby if you have a problem. I said oh I will and may I have your last name please or do I need to record this call? And she hung up. How rude of this place to one call me a liar when i have 200 witness stating when the food came and when it should have been then and two giving other people their stuff that she should be responsible for so now im getting harassed. This was suppose to go perfect considering it was my wedding day and it didn't but i was willing to talk bout it until i was called a LIAR and now im going to make sure this get's handled properly i don't care what it takes! NO ONE SHOULD GET TREATED THIS WAY AND I SURE WOULDN'T WANT IT TO BE THE NEXT COUPLES WEDDING TO GET SCREWED OVER AS WELL!
This place is terrible. overpriced food and obnoxious bands. it was empty when i went there and the staff didnt seem to care. good luck surviving the summer
Worst food EVER!! Cole slaw was smothered in mayo only! French fries were no longer than an inch and a half----what? The end of the bag? Mashed potatoes stale and cold.
Fried fish was covered in a leathery weirdness that is indescribable. Only thing good was the beer and Cosmo but then again, it took forever to get refills. Place should have been packed given the number of TVs and that it was Final Four weekend but apparently previous guests had tasted the truly awful food and decided never to come back. Lord knows, won't be either!!!
Went to the restaurant on Thorneydale today, worst waitress I ever had at a restaurant. Turned out she was the manager. I ask the other waitress, who she ask to finish with us why she was so nasty, she said she works a lot. No excuse for me, I went there to have a nice lunch, not so nice!
This place is disgusting. I see roaches came out from the kitchen. Where's the inspector?..


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Tell Us and Enter for a Chance to Win a $250 Best Western Travel Card!
Whether it was a family vacation, a business trip or a solo adventure tell us about your favorite road trip and you will be automatically entered for a chance to win a $250 Best Western Travel Card!
Limit one entry per person. Must be 18 years of age or older and a resident of the US or Canada to be eligible to win. Winner will be randomly selected from all entries posted in the comments below. Winner will be announced via comment post on youmustbetrippin.com and via Facebook/Twitter posts after winner is verified. Contest begins Mar. 1st and ends Mar. 31st.

subset: commoncrawl


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Archaeus Six
Archaeus Six Poems
- Vespertine Quickened by wonder, my mind asunder, The ...
- Living Silver Move along, with the descending silver ...
- Pendulum Have you ever been surrounded, by the sweetest of ...
- Now I am still, now, Admits my endless turning. There is ...
- Copper Voice, Golden Heart Bliss we are in your arrival, ...
- Elusive So this, is the elusive. The cause, the goal. It ...
- Midnight Take my hand, You beautiful and crippled ...
I live, and write to share. more »
Click here to add this poet to your My Favorite Poets.
Comments about Archaeus Six
Quickened by wonder, my mind asunder,
The empyrean speaks to me.
Alas the frightful, yet, calming insightful,
A disposition, free from apathy.
Why always in twilight, the gentle encroaching night,
Do blights of torment, find sympathy.
To emancipation, by an act of aberration,
For a moment, my sins are free.
Perhaps Selene, in her smile so serene,
Pardons the fool, with amnesty.
To be silent and embrace, what leaves no trace,
Disturbs not, this rapture in me.
In the midst of alone, forthcoming I condone,
What the day would not let me ...
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text:
DUQUESNE (AP) — A pregnant 15-year-old girl who was shot after opening the door of her family's home and lost her fetus is expected to survive, her mother said Tuesday.
DaRae Delgado, who was seven months pregnant, was shot Monday by someone who knocked on the door of the Duquesne home, covered the door's peephole and then opened fire when she answered, police said.
Delgado's twin brother, Darrell Delgado, was in the house, in western Pennsylvania near Pittsburgh, at the time of the shooting.
"I heard the door, and I came to the top of the steps," he said. "She opened the door, and I saw the sparks and gunshots go off."
Delgado's mother, Deanna Weams, said doctors told her the fetus apparently bore the brunt of the gunfire. She said Delgado remained hospitalized Tuesday.
Allegheny County police haven't identified any suspects or made any arrests.
"Absent a motive, we are moving in several different directions," Lt. Andrew Schurman said.
Investigators said the person or people who fired the shots fled the scene on foot. Police said they believe three people may have been involved in the shooting but did not disclose additional details.
Pregnant girl, 15, expected to survive doorway shooting
May 27, 2014 at 9:06 PM
May 27, 2014 at 9:08 PM


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Ashchi Heart and Vascular Center
Jacksonville, FL 32216
About Majdi Ashchi
A graduate of The College of Osteopathic Medicine at Nova-Southeastern University of The Health Sciences, and The University of South Florida, he was recruited to The prestigious Cleveland Clinic Foundation for his Internal Medicine residency. He then undertook his Cardiology Fellowship at Case Western Reserve University program at MetroHealth/Mount Sinai Medical Centers in Cleveland, Ohio. He then advanced to The University of Connecticut, Hartford Hospital where he underwent a year of dedicated training in Interventional Cardiology. He has attended numerous courses in the Endovascular treatment of peripheral vascular disease, and has been a real pioneer in the field in the First Coast region, having accumulated the largest experience in the evolving field of carotid artery stenting. He has proven himself to be a very aggressive cardiologist with the greatest compassion to his patients and an unparalleled devotion to their well being. Whether it is Saturday morning or Tuesday after midnight he has always been readily available to attend to his patient's cardiovascular emergencies.
Dr. Ashchi has a vision of putting the patient first, and he is always striving for excellence. Dr. Majdi Ashchi shares a strong commitment to quality and doing whatever it takes to improve the patient symptoms and prognosis. Dr. Ashchi has been selected as the primary investigator in the CAPTURE, SAPPHIRE and EXACT trials for carotid artery stenting and many other vascular trials. This honor goes to the few physicians that meet strict criteria of performing these procedures.
Internal Medicine – Cleveland Clinic Foundation
Cardiology Fellowship – Case Western Reserve University, Interventional Cardiology Fellowship – University of CT
Certifications & Memberships
Licensure & Board Certifications
American Board of Internal Medicine, Cardiovascular Disease
American Board of Internal Medicine, Interventional Cardiology
American Board of Vascular Medicine, Vascular Medicine
American Board of Vascular Medicine, Endovascular Medicine
American College of Cardiology
American College of Chest Physicians
Society for Cardiovascular Angiography and Interventions
Languages Spoken
English, Arabic, Persian, Hebrew
Procedures & Conditions
Specialties: Clinical & interventional cardiology, Cardiovascular disease, Internal medicine, Endovascular specialist, Vascular medicine
Cardiovascular Disease
Vascular Medicine
Endovascular Specialist
Interventional Cardiology
Office Locations
Ashchi Heart and Vascular Center
3900 University Blvd S Suite A
Jacksonville, FL 32216
Phone: (904) 222-6656
Fax: (904) 222-6657
Accepted Insurance
We accept ALL insurances with the exception of Humana HMO Gold plans


text:
Active Tags
Click tags to the right to narrow your search. Unclick tags to remove.
Family Affairs Ch. 21
— Mary & her son are devastated by the news.Please, separate your tags with comma: anal orgasm, oral sex.
Read the Literotica Story Tag FAQ for more information on these tags.


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WATSEKA (AP) — A northeastern Illinois lawmaker is announcing plans to remove himself from the November ballot.
State Rep. Josh Harms is a Watseka Republican and a longtime teacher at Watseka Community High School. He released a statement this week citing a desire to return to teaching and be closer to his family.
Harms was first elected to represent the 106th District in 2012. It includes the eastern portion of Woodford County, including Eureka and part of Roanoke.
He calls his experience as a legislator "a tremendous experience" that he appreciates greatly.
Republican party officials are now tasked with choosing a replacement for Harms on the November ballot.
Harms says he's confident the area will be well represented moving forward.


text:
ASP.NET Web API Gets OData v4.0 Support, WCF Will Not
ASP.NET Web API 2.2 for OData v4.0 are now available as nightly builds. The team also released OData core libraries version 6.1 on nuget with several bug fixes and new features, especially increased support for OData v4 spec. However, the MS team suggested that WCF will not get OData v4 specific features.
WCF Data Services 5.6.0 Adds Entity Framework 6 Support
The recently released WCF Data Services 5.6.0 provides support for Entity Framework 6 and provides an option either to upgrade or create nww OData services to target EF 6.
ODataUriParser Now Supports $select and $expand
The ODataUriParser, part of WCF Data Services, can now parse $select and $expand expressions and produce matching abstract syntax trees.
WCF Data Services 5.4.0 Released with Client Hooks and Instance Annotations on Atom Payloads
Microsoft has announced the availability of WCF Data Services 5.4.0 release candidate with new features and several bug fixes.
WCF Data Services 5.3.0 with Instance Annotations and request URL
Microsoft has released WCF Data Services 5.3.0 with support for instance annotations in JSON payloads, modifying request URL in the OnStartProcessingRequest method including few bug fixes.
Getting Started with OData v3 and WCF Data Services 5.x
If you are building new web services with .NET then OData should be high on your list of frameworks to investigate, especially if you need to support unknown third parties. The technology inherently supports both SOAP and REST style messages with the latter offering ATOM (XML) and JSON representations. This means consumers can pretty much request whatever format is best for them.
WCF Data Services 5.2.0 with UriParser Support
Microsoft has announced the availability of WCF Data Services 5.2.0 with support for UriParser and fixes to several bugs.
Enums, Entity Framework And WCF Data Services
Enumerations have been supported in Entity Framework 5 – however Enums are not yet supported in WCF Data Services, which means you still need to handle them explicitly when writing OData services.


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Friday, February 15, 2013
Vitesse Debuts New Gigabit Ethernet Cores
Camarillo-based Vitesse Semiconductor, the developer of packet processing and networking chips, said this week that it has debuted a new set of Gigabit Ethernet (GE) IP cores. The firm said the cores allow customers to integrate Gigabit switch functionality into Ethernet ICs. The company said it is aiming at consumer electronics, gaming, printers, smart grid, industrial and other applications with the new cores. Semiconductor cores can be incorporated into other chip designs by companies, and are typically used so that those firms do not have to develop their designs for including functionality in ASICs, FPGA, and other designs. Vitesse said the chips are available in two versions, one with GE switch functionality only, and the other also supporting Audio Video Bridging (AVB) including the IEEE 802.1AS-2011 timing and synchronization protocol.


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Chana Masala
Prep time
15 mins
Cook time
20 mins
Total time
35 mins
Chana Masala
Holy Cow! Vegan Recipes
Recipe type:
1 cup garbanzo beans or chickpeas, soaked overnight if possible, the cooked until tender. If using canned, use about 3 cups of the beans
1 tbsp vegetable or canola oil
1 large red onion, diced
4 cloves of garlic, minced
1 tbsp grated ginger
2 canned whole tomatoes with juice, diced
1 chipotle chili pepper in adobo sauce, minced
½ tsp red chilli powder or cayenne pepper
½ tsp turmeric
Salt to taste
Grind to a powder in a coffee grinder and set aside:
1 tbsp coriander seeds
1 tsp cumin seeds
1 tsp black peppercorns
1 dried bay leaf
2 cloves
2 cardamom pods
½-inch piece of cinnamon
Heat the oil in a saucepan. Add the onions and cook, stirring, until browned
Add the ginger and garlic and saute for a minute.
Add the ground spices, turmeric, chili powder and the chipotle chili pepper and stir for a minute until the spices are well-coated with the oil and lightly toasted.
Add the tomatoes and cook until they break down and express the oil.
Add the garbanzo beans, enough liquid to make a thick gravy, and stir together. Add salt to taste.
Bring to a boil, turn heat to low, and simmer about 10 minutes so all the flavors can merge.
Turn off the heat and garnish with coriander leaves.
Serve hot with a splash of lemon juice. You can also add a garnish of minced onions which would be delicious.
Recipe by
Holy Cow! Vegan Recipes
at http://holycowvegan.net/chana-bhatura-trip-down-memory-lane/


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The Centre for Sustainable Chemical Processes
Centre for Sustainable Chemical Processes
"World-class Research for Innovation"
Welcome to Durham University's Centre for Sustainable Chemical Processes
- The Centre for Sustainable Chemical Processes (CSCP) was founded in 2009 to address the need to integrate a resource-sustainable ethos into chemical research and development – both at the academic and industrial levels.
- The Centre's members have collectively a wide range of unique synthetic expertise and know-how spanning organic, inorganic and process chemistry and catalysis.
- CSCP brings together academic and industrial synthetic chemists from Durham University and the surrounding region under a single umbrella.
- The Centre seeks actively to enable and support innovative new collaborations, information sharing, and to provide expertise in synthetic chemistry, hence opening new, exciting research opportunities
- CSCP acts as a conduit facilitating and providing access to its unique specialist equipment and research facilities and those of its members.
- The Centre aims to catalyse the long term development of new strategically important research initiatives via multidisciplinary projects.
CSCP Integrated Chemical Reaction Facility Launch
Durham University
Wednesday 24 September 2014
Durham University is announcing the launch of its £1.1M dedicated, state-of-the-art Integrated Chemical Reaction Facility (ICRF), a part of the Department of Chemistry's Centre for Sustainable Chemical Processes (CSCP). The ICRF laboratory is custom-designed to support academic and industrial researchers by providing access to complex chemical process reactor systems and associated analytical instruments and facilities, enabling unique high pressure, high hazard, flow and parallel reactions to be undertaken in a controlled and safe environment. The ICRF provides not only access to world-class equipment, but also to expertise, advice and training from dedicated support staff, complemented by full access to the Department's analytical facilities.
ICRF Research Manager - Dr Li Li
Contact Details
Department of Chemistry
Durham University
South Road


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Dimag ho to
Dimag ho tu jawab doo…
Din say roshan hai,,Raat say seyah hai"
Khao tu haram hai"peo tu Hilal hai
Aurt sari zindagi mein ek bar use karti hai
mard din mein 3 br use karta hai
QURAN mein 5 martba zikar hai
MEEM say start hota hai5 harrof ka lafaz hai
Here is Some Related SMS Messages
- ajib cheez
Woh Kon Si Cheez Hai? Jo 2012 K Saal Main 1 Baar Aai, Aur Har Mahine Main 2 Baar Hafte Main 4 Baar Aur Din Main 6 Bar Aai Thi? Reply Must Plz. Related posts:mohabbat Kya cheez hoti hy Rehne walon se nhijane walon se Pucho K zindgi Kya… Baar baar … - without taking
A____ is something u cannot give without taking and take without giving. Related posts:Your validity for taking a Your validity for taking a bath expires on this 14th… If CARE is a WAVE, I give u sea If CARE is a WAVE, i give u SEA. - Take the number
You will need a calculator for this: Take the number of the month you were born, multiply by 4, add 13, multiply by 25, subtract 200, add the day of the month on which you were born, multiply by 2, subtract 40, multiply by 50, add the last two digits of the year in which you were born, subtract 10,500. Notice anything funny - Two question
Related posts:Could u pls give me an answer for two question Could u pls give me an answer for two question… Life gives answer in 3 ways Life gives answer in 3 ways… It says Yes &… Related posts:Could u pls give me an answer for two question. - wish kya hogi
Wish 1 Wish 2 Wish 3 Wish 4 Wish 5 Wish 6 Wish 7 Wish 8 Wish 9 Wish 10 Wish 11 Wish 12. In Ma Sy Koi 1no Choz Kro. Den I Will Tell U K Ap Ki Wish Kya Hogi.


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"The Best of Being Catholic" a good gift for discouraged members at Christmas
Review: "The Best of Being Catholic," by Kathy Coffey (Orbis Press, August 2012).
OK, so I know the author, co-taught freshman writing classes with her back when, and for 20-some years co-edited Leaven, a small magazine for "Vatican II Catholics."
I knew she was working on this book (latest of 14 since mid-1990s). But I suddenly find that it's out and that I very much want to recommend it – perhaps as a gift for some discouraged Catholics you may know (even yourself), or for young folks who've just drifted away.
I admit when I heard she was working on this topic I hesitated. She says she did as well when an editor asked her to write it. So much bad news these days about Catholicism. Was it to be just another counterbalancing catalog, some long list of "good things?" Another report on "why I stay Catholic [nonetheless]"? Another theological argument about why we "should stay"?
Actually, none of the above – or some of all that, but in a refreshingly affirmative and very readable format. It's realistic, critical at times, reflective, suggestive – with the good poet's eye for endless detail and concreteness, but the good writer's ability to move things even while reaching deep and wide.
Reading made me think of a group of friends meeting over wine or beer, telling stories, sharing memories (quirky and even strange), yet all in atmosphere of deep affection for things really good.
At one point Coffey quotes her pastor (Father Pat Dolan at Most Precious Blood) urging people at Christmas "to let the child in the manger overshadow the elephant in the living room." He meant by "the elephant," I take it, all the problems and woes of our burdened lives.
But I thought it a good image for Catholics today and for this book – letting the many "beautiful children" and stories and practices of the Catholic life – starting with that Child in that manger but "through, with and in Him," developing into the immensely creative and living culture that, in all its global variants, still keeps (or makes) so many people Catholic.
Yes, problems enough in the Church and in our lives. But much more that holds and roots and feeds.
And Coffey has the touch for the telling – such rich observations and reflections, so much affection expressed and love evoked and recommended, but with such an intelligent and artfully adult pen.
It is a gift of many good things that need remembrance and retelling. Once you're into it, you can pick it up at any place and be nourished.
(More at 'Kathy's blog": http://kathyjcoffey.wordpress.com/.)


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Article Dated: 9/24/2013
New Bedford - Governor Deval Patrick will today join MassDOT Secretary and CEO Richard A. Davey to announce that the U.S. Army Corps of Engineers has released the Final Environmental Impact Statement (FEIS) for the South Coast Rail project, and MassDOT has adopted the Corps' document as the state-required Final Environmental Impact Report (FEIR). MassDOT has identified the Stoughton rail alternative as its preferred route for providing the best transportation, environmental and smart growth benefits.
The FEIS/FEIR released today is the culmination of more than five years of coordination among the Patrick Administration, the Corps and 17 other state and federal agencies.
"Residents of the South Coast have been waiting for 20 years for a reliable transit system that connects conveniently to Boston and everything in between," said Governor Patrick. "We are making it happen, and we thank the Army Corps of Engineers and MassDOT for moving us so far forward."
"South Coast Rail will reconnect the cities of Taunton, New Bedford and Fall River to Boston and position the South Coast region for smart growth and sustainability," said Secretary Davey. "Completing the final environmental document is a critical step forward in obtaining the environmental clearances MassDOT and the MBTA need to bring long-awaited commuter rail service to the South Coast."
The FEIS/FEIR outlines the Corps' conclusion that there is no practicable alternative to the Stoughton Electric Alternative with less environmental impact, and notes that MassDOT has complied with the requirements of a Certificate issued by the Secretary of Energy and Environmental Affairs on the draft document and confirms the agency's choice of the Stoughton route.
As part of the environmental review process, the Massachusetts Environmental Policy Act office (MEPA) will accept public comments on the FEIS/FEIR until October 26, 2013. MassDOT is sponsoring two public Open Houses to provide information on the FEIR. The MEPA review process will end once the Secretary of Environmental Affairs issues a Final Certificate, which will include any additional requirements for mitigation or avoidance of impacts. The federal NEPA process will conclude with the issuance of a Record of Decision (ROD) by the Corps.
Governor Patrick has remained committed to expanding transportation options on the South Coast in order to grow jobs and economic opportunity in the region.
Investments supporting South Coast Rail to date include the completed rebuilding of three New Bedford rail bridges, funded by a $20 million federal TIGER grant that enhances current freight rail and will serve commuter rail, along with the completion of a historic agreement with CSX Transportation to purchase 30 miles of track from Taunton to Fall River and New Bedford necessary for South Coast Rail.
The South Coast Rail Economic Development and Land Use Corridor Plan, developed in 2009, has made strategic investments to assist the 31 corridor communities in preparing for passenger rail through sustainable development and appropriate land use. The Plan identifies areas that are appropriate for new development near proposed South Coast Rail transit stations. The fifth round of technical assistance announced in October 2012 provided grants to 15 Corridor communities of $5,000 - $25,000 to plan for sustainable, smart growth; a sixth round will be announced shortly.
The Patrick Administration has continuously supported the transportation infrastructure on the South Coast including the Accelerated Bridge Program "mega" project to rebuild the I-195, Route 79 and Route 138 interchange in Fall River along with improvements to Route 18 and other state roadways, and local road and bridge projects funded by Chapter 90. The Patrick Administration has made 245 investments totaling $939 million in the region, including $11.7 million in 2011 and 2012 MassWorks infrastructure program grants to five communities in the region, among them a grant of $3.25 million to New Bedford for improvements in the city's Acushnet Avenue International Marketplace area.
The FEIS/FEIR details the transportation benefits of the Stoughton Alternative and its potential impacts on noise, visual, wetlands, environmental justice, air quality and other social, historic and environmental resources. It advances designs of the tracks, stations and layover facilities over the draft document, and estimates wetland impacts and describes measures to avoid, minimize or mitigate such impacts. MassDOT has proposed a plan and monitoring component to assess smart growth implementation.
Once the state environmental review process is completed, MassDOT can invest in developing the final design plans for the project and can begin to obtain all of the required permits. The MBTA will assume a primary role in final design.
The FEIS/FEIR is available at local libraries throughout the South Coast region and by request from MassDOT. There is a link to the electronic version of the report, an Executive Summary, Guide to the FEIS/FEIR and a project fact sheet at www.mass.gov/southcoastrail. Information on the Open Houses and how to comment on the FEIS/FEIR is also posted on the website.
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Gene therapy can be broadly defined as the transfer of defined genetic material to specific target cells of a patient for the ultimate purpose of preventing or altering a particular disease state. Genes and DNA are now being introduced without the use of vectors and various techniques are being used to modify the function of genes in vivo without gene transfer. If one adds to this the cell therapy particularly with use of genetically modified cells, the scope of gene therapy becomes much broader. Gene therapy can now combined with antisense techniques such as RNA interference (RNAi), further increasing the therapeutic applications. This report takes broad overview of gene therapy and is the most up-to-date presentation from the author on this topic built-up from a series of gene therapy report written by him during the past decade including a textbook of gene therapy and a book on gene therapy companies. This report describes the setbacks of gene therapy and renewed interest in the topic
Gene therapy technologies are described in detail including viral vectors, nonviral vectors and cell therapy with genetically modified vectors. Gene therapy is an excellent method of drug delivery and various routes of administration as well as targeted gene therapy are described. There is an introduction to technologies for gene suppression as well as molecular diagnostics to detect and monitor gene expression.
Clinical applications of gene therapy are extensive and cover most systems and their disorders. Full chapters are devoted to genetic syndromes, cancer, cardiovascular diseases, neurological disorders and viral infections with emphasis on AIDS. Applications of gene therapy in veterinary medicine, particularly for treating cats and dogs, are included.
Research and development is in progress in both the academic and the industrial sectors. The National Institutes of Health (NIH) of the US is playing an important part. As of 2015, over 2050 clinical trials have been completed, are ongoing or have been approved worldwide.A breakdown of these trials is shown according to the geographical areas and applications.
Since the death of Jesse Gelsinger in the US following a gene therapy treatment, the FDA has further tightened the regulatory control on gene therapy. A further setback was the reports of leukemia following use of retroviral vectors in successful gene therapy for adenosine deaminase deficiency. Several clinical trials were put on hold and many have resumed now. The report also discusses the adverse effects of various vectors, safety regulations and ethical aspects of gene therapy including gene editing and germline gene therapy.
The markets for gene therapy are difficult to estimate as there is only one approved gene therapy product and it is marketed in China since 2004. Gene therapy markets are estimated for the years 2016-2026. The estimates are based on epidemiology of diseases to be treated with gene therapy, the portion of those who will be eligible for these treatments, competing technologies and the technical developments anticipated in the next decades. In spite of some setbacks, the future for gene therapy is bright.The markets for DNA vaccines are calculated separately as only genetically modified vaccines and those using viral vectors are included in the gene therapy markets
The voluminous literature on gene therapy was reviewed and selected 750 references are appended in the bibliography.The references are constantly updated. The text is supplemented with 75 tables and 19 figures.
Profiles of 188 companies involved in developing gene therapy are presented along with 233 collaborations. There were only 44 companies involved in this area in 1995. In spite of some failures and mergers, the number of companies has increased more than 4-fold within a decade. These companies have been followed up since they were the topic of a book on gene therapy companies by the author of this report. John Wiley & Sons published the book in 2000 and from 2001 to 2003, updated versions of these companies (approximately 160 at mid-2003) were available on Wiley's web site. Since that free service was discontinued and the rights reverted to the author, this report remains the only authorized continuously updated version on gene therapy companies.
Benefits of this report:
- Up-to-date on-stop information on gene therapy with 75 tables and 19 figures
- Evaluation of gene therapy technologies
- 750 selected references from the literature
- Estimates of gene therapy markets from 2016-2026
- Profiles of 188 companies involved and collaborations in this area
Who should read this report?
- Biotechnology companies developing gene therapy
- Academic institutions doing research in gene therapy
- Drug delivery companies
- Pharmaceutical companies interested in gene therapy
- Gene therapy companies
- Venture capital and investment companies
Part I: Technologies & Markets
0. Executive Summary
1. Introduction
Historical evolution of gene therapy
Relation of gene therapy to other biotechnologies
Molecular biological basics for gene therapy
Alternative RNA splicing
Silent gene mutations
Gene regulation
Gene expression
2. Gene Therapy Technologies
Classification of gene therapy techniques
Ex vivo and in vivo gene therapy
Ex vivo gene therapy
In vivo gene therapy
Physical methods of gene transfer
Applications of electroporation
Clinical applications of electroporation
Advantages of electroporation
Limitations of electroporation
Particle bombardment
Ultrasound-mediated transfection
Molecular vibration
Application of pulsed magnetic field and superparamagnetic nanoparticles
Gene transfection using laser irradiation
Photochemical transfection
Chemical methods of gene transfer
Gene repair and replacement
Gene repair by single-stranded oligonucleotides
History and current status of chimeraplasty
Genome editing
Gene editing by use of short synthetic oligonucleotides
Genome engineering by using TALENs
Targeted genome editing by artificial nucleases
Clinical applications of gene editing
Genome editing by using CRISPR system
A method for generating genome-wide gRNA libraries for CRISPR
CRISPER system for creating animal models of human diseases
CRISPR/Cas9 technology for drug discovery
Expanding the range of Cas9s
Inducible CRISPR/Cas9 for multiple gene targeting
Photoactivatable CRISPR-Cas
Protein delivery and genome editing
Potential clinical applications of CRISPR systems
PERV blockage by CRISPR to facilitate xenotransplantation
RNA alteration by CRISPR
Clinical trial of CRISPR in human cancer
Complications and limitations of CRISPR/Cas9 technology
mRNA gene therapy
Spliceosome mediated RNA trans-splicing
Vectors for gene therapy
Basic considerations
Use of genes as pharmaceuticals
The ideal vector for gene therapy
Viral vectors
Adenovirus vectors
Adeno-associated virus vectors
Alphavirus vectors
Baculovirus vectors
Foamy virus vectors
Herpes simplex virus vectors
Lentiviral vectors
Multicistronic retroviral vectors
Retroviral vectors
Oncogenic potential of retroviral vectors
Quantification of viral vectors
Future prospects of viral vectors
Companies using viral vectors
Nonviral vectors for gene therapy
Anionic lipid-DNA complexes
Cationic lipid-DNA complexes
Effects of shape of DNA molecules on delivery with nonviral vectors
Electrostatic modifications of surface to improve gene delivery
Liposomes for gene therapy
Liposome-nucleic acid complexes
Liposome-HVJ complex
Transposons DNA vectors
Polycation-DNA complexes (polyplexes)
Plasmid DNA vs minicircle DNA
Polymer vectors for gene therapy
Synthetic biology and DNA vectors
Synthetic peptide complexes
Future prospects of nonviral vs viral vectors
Nanobiotechnology for gene therapy
Antisense nanoparticles
Calcium phosphate nanoparticles as nonviral vectors
DNA nanoparticles as nonviral vectors
Gelatin nanoparticles for gene delivery
Lipid nanoparticles for nucleic acid delivery
Lipid nanoparticles for delivery of genome-editing proteins
Nanoparticles as nonviral vectors for gene therapy
Nanoparticles with virus-like function as gene therapy vectors
Nanobiolistics for nucleic acid delivery
Nonionic polymeric micelles for oral gene delivery
Silica nanoparticles as a nonviral vector for gene delivery
Virus-like particles as nonviral vector
Receptor-mediated endocytosis
Artificial viral vectors
Directed evolution of AAV to create efficient gene delivery vectors
Bacterial ghosts as DNA delivery systems
Bacteria plus nanoparticles for gene delivery into cells
Chromosome-based vectors for gene therapy
Mammalian artificial chromosomes (MACs)
Human artificial chromosomes (HACs)
FC31 integrase system
Companies using nonviral vectors
Concluding remarks about vectors
Cell-mediated gene therapy
Skeletal muscle cells
Vascular smooth muscle cells
Regulating protein delivery by genetically encoded lymphocytes
Implantation of microencapulated genetically modified cells
Stem cell gene therapy
Therapeutic applications for hematopoietic stem cell gene transfer
Improving delivery of genes to stem cells
Lentiviral vectors for gene transfer to marrow stem cells
Use of mesenchymal stem cells for gene therapy
Microporation for transfection of MSCs
In utero gene therapy using stem cells
Gene delivery to stem cells by artificial chromosome expression
Linker based sperm-mediated gene transfer technology
Combination of gene therapy with therapeutic cloning
Expansion of transduced HSCs in vivo
The future of hematopoietic stem cell gene therapy
Role of genetically modified bacteria in gene therapy
Routes of administration for gene therapy
Direct injection of naked DNA
Intramuscular injection
Intravenous DNA injection
Intraarterial delivery
Companies with gene delivery devices/technologies
Targeted gene therapy
Targeted integration
Bacteriophage integrase system for site-specific gene delivery
Controlled-release delivery of DNA
Controlled gene therapy
Controlled delivery of genetic material
Controlled induction of gene expression
Drug-inducible systems for control of gene expression
Timed activation of gene therapy by a circuit based on signaling network
Small molecules for post-transcriptional regulation of gene expression
Engineered zinc finger DNA binding proteins for gene correction
Light Activated Gene Therapy
Spatial control of gene expression via local hyperthermia
Companies with regulated /targeted gene therapy
Gene marking
Germline gene therapy
Potential applications of human germline genome modification
Pros and cons of human germline genome modification
Role of gene transfer in antibody therapy
Genetically engineered vaccines
DNA vaccines
DNA inoculation technology
Methods for enhancing the potency of DNA vaccines
Advantages of DNA vaccines
Vaccine vectors
Challenges and limitations of genetically engineered vaccines
RNA vaccines
Nonviral delivery of self-amplifying RNA vaccine
Vaccines based on reverse genetics
Technologies for gene suppression
Antisense oligonucleotides
Transcription factor decoys
Peptide nucleic acid
Intracellular delivery of PNAs
Locked nucleic acid
Gene silencing
Post-transcriptional gene silencing
Definitions and terminology of RNAi
RNAi mechanisms
Inhibition of gene expression by antigene RNA
RNAi gene therapy
microRNA gene therapy
Application of molecular diagnostic methods in gene therapy
Use of PCR to study biodistribution of gene therapy vector
PCR for verification of the transcription of DNA
In situ PCR for direct quantification of gene transfer into cells
Detection of retroviruses by reverse transcriptase (RT)-PCR
Confirmation of viral vector integration
Monitoring of gene expression
Monitoring of gene expression by green fluorescent protein
Monitoring in vivo gene expression by molecular imaging
Advantages of gene therapy compared with protein therapy
Formulation, transport and storage of materials for gene therapy
3. Clinical Applications of Gene Therapy
Aging research
Bone and joint disorders
Bone fractures
Gene therapy for intervertebral disc degeneration
Spinal fusion
Osteogenesis imperfecta
Rheumatoid arthritis
Local or systemic treatment
In vivo or ex vivo gene therapy of RA
Clinical trials of gene therapy for rheumatoid arthritis
Gene therapy for osteoarthritis
Sports injuries
Repair of articular cartilage defects
Regeneration and replacement of bone by gene therapy
Bacterial infections
Antisense approach to bacterial infections
Tissue engineering in dental implant defects
Endocrine and metabolic disorders
Gene therapy of obesity
AAV vector-mediated delivery of GDNF for obesity
Oligopeptide for targeted nonviral gene delivery to adipocytes
Viral vector-mediated leptin gene therapy
Diabetes mellitus
Methods of gene therapy of diabetes mellitus
Viral vector-mediated gene transfer in diabetes
Gene delivery with ultrasonic microbubble destruction technology
Genetically engineered cells for diabetes mellitus
Genetically altered liver cells
Genetically modified stem cells
Genetically engineered dendritic cells
Glucokinase and insulin co-expression
Leptin gene therapy
Concluding remarks about cell and gene therapy of diabetes
Gene therapy of growth-hormone deficiency
Gastrointestinal disorders
Methods of gene transfer to the gastrointestinal tract
Direct delivery of genes
Naked plasmid DNA into the submucosa
Viral vectors
Receptor-mediated endocytosis
Indications for gastrointestinal gene therapy
Gene therapy for inflammatory disorders of the bowel
Gene transfer to the salivary glands
Potential clinical applications of salivary gene therapy
Gene therapy of hemophilia
Hemophilia A
Hemophilia B
Concluding remarks about gene therapy of hemophilias
Stem cell-based gene therapy and RNAi for sickle cell disease
Gene editing in sickle cell disease
Gene therapy for ß-thalassemia
Gene editing using ZFN as treatment for both SCD and ß-thalassemia
Gene therapy of Fanconi's anemia
Acquired hematopoietic disorders
Chronic acquired anemias
Concluding remarks about gene therapy of hemoglobinopathies
Companies involved in gene thery of hematological disorders
In utero/fetal gene therapy
Fetal gene transfer techniques
Animal models of fetal gene therapy
Potential applications of fetal gene therapy
Fetal gene therapy for cystic fibrosis
Fetal intestinal gene therapy
Gene therapy for fetal growth restriction
Hearing disorders
Potential of gene therapy
Vectors for gene therapy of hearing disorders
Auditory hair cell replacement and hearing improvement by gene therapy
Kidney diseases
End-stage renal disease
Methods of gene delivery to the kidney
Gene transfer into kidney by adenoviral vectors
Non-viral gene transfer to the kidneys
Gene transfer into the glomerulus by HVJ-liposome
Bone marrow stem cells for renal disease
Mesangial cell therapy
Liposome-mediated gene transfer into the tubules
Gene transfer to tubules with cationic polymer polyethylenimine
Gene therapy in animal experimental models of renal disease
Genetic manipulations of the embryonic kidney
Antisense intervention in glomerulonephritis
Gene therapy for renal fibrosis
Use of genetically engineered cells for uremia due to renal failure
Concluding remarks
Liver disorders
Techniques of gene delivery to liver
Direct injection of DNA into liver
Local gene delivery by isolated organ perfusion
Liposome-mediated direct gene transfer
Retroviral vector for gene transfer to liver
Adenoviral vectors for gene transfer to liver
Receptor-mediated approach
Cell therapy for liver disorders
Transplantation of genetically modified hepatocytes
Genetically modified hematopoietic stem cells
Gene therapy by ex vivo transduced liver progenitor cells
Gene therapy of genetic diseases affecting the liver
Crigler-Najjar syndrome
Hereditary tyrosinemia type I (HT1)
Hereditary tyrosinemia type
Gene therapy of acquired diseases affecting the liver
Cirrhosis of liver
Ophthalmic disorders
Introduction to gene therapy of ophthalmic disorders
Methods of gene therapy for ophthalmic disorders
Delivery of gene therapy by intravitreal injection
DNA nanoparticles for nonviral gene transfer to the eye
Optogenetic gene therapy for blindness due to retinal degeneration
Age-related macular degeneration
Inherited disorders of optic nerve affecting vision
Leber hereditary optic neuropathy
Inherited retinal degenerations
Leber congenital amaurosis
Retinitis pigmentosa
Stargardt disease
Other inherited disorders affecting vision
Color blindness
Usher syndrome
X-linked retinoschisis
Diabetic retinopathy
Future prospects of gene therapy of inherited retinal degenerations
Combining cell and gene therapies for retinal disorders
Prevention of complications associated with eye surgery
Prevention of proliferative retinopathy by gene therapy
Posterior capsule opacification after cataract surgery
Autoimmune uveitis
Retinal ischemic injury
Corneal disorders
Corneal scarring
Companies developing gene therapy for eye disorders
Organ transplantation
DNA vaccines for transplantation
Gene therapy for prolonging allograft survival
Genetically modified Tregs expressing CAR for preventing GVHD
Gene therapy in lung transplantation
Role of gene therapy in liver transplantation
Gene therapy in kidney transplantation
Veto cells and transplant tolerance
Pulmonary disorders
Techniques of gene delivery to the lungs
Adenoviral vectors
Nonviral vectors
Aerosolization as an aid to gene transfer to lungs.
Cystic fibrosis
Genetics and clinical features
Gene therapy for CF
CFTR gene transfer in CF
Concluding remarks about gene therapy of CF
Miscellaneous pulmonary disorders
Gene therapy for pulmonary arterial hypertension
Gene therapy for bleomycin-induced pulmonary fibrosis
Gene therapy of emphysema due to a1-antitrypsin deficiency
Gene therapy for asthma
Gene therapy for adult respiratory distress syndrome
Gene therapy for lung injury
Gene therapy for bronchopulmonary dysplasia
Concluding remarks about gene therapy of lungs
Companies involved in pulmonary gene therapy
Skin and soft tissue disorders
Gene transfer to the skin
Electroporation for transdermal delivery of plasmid DNA
Electroporation for transdermal delivery of DNA vaccines
Liposomes for transdermal gene delivery
Ultrasound and topical gene therapy
Gene therapy in skin disorders
Gene therapy of hair loss
Gene therapy for epidermolysis bullosa
Gene therapy for xeroderma pigmentosa
Gene therapy for lamellar ichthyosis
Gene therapy for epidermolysis bullosa
Gene transfer techniques for wound healing
Urogenital disorders
Gene therapy for urinary tract dysfunction
Gene therapy for erectile dysfunction
NOS gene transfer for erectile dysfunction
Clinical trial of hMaxi-K Gene transfer in erectile dysfunction
Gene therapy for erectile dysfunction due to nerve injury
Concluding remarks on gene therapy for erectile dysfunction
Veterinary gene therapy
Gene therapy for mucopolysaccharidosis VII in dogs
Gene therapy to increase disease resistance
Gene therapy for infections
Gene therapy for chronic anemia
Gene therapy for endocrine disorders
Gene therapy for arthritis
Cancer gene therapy
Brain tumors in cats and dogs
Breast cancer in dogs
Canine hemangiosarcoma
Canine melanoma
Canine soft tissue sarcoma
Melanoma in horses
4. Gene Therapy of Genetic Disorders
Primary immunodeficiency disorders
Severe combined immune deficiency
Chronic granulomatous disease
Wiskott-Aldrich syndrome
Purine nucleoside phosphorylase deficiency
Major histocompatibility class II deficiency
Future prospects of gene therapy of inherited immunodeficiencies
Metabolic disorders
Alpha1-antitrypsin deficiency
AAV mediated gene therapy for a1-antitrypsin deficiency
iPSCs for targeted gene correction of a1-antitrypsin deficiency
Canavan disease
Lesch-Nyhan syndrome
Lipoprotein lipase deficiency
Alipogene tiparvovec
Ornithine transcarbamylase deficiency
Gene therapy for OTCD
AAV-mediated gene editing for OTCD using CRISPR-Cas
Tetrahydrobiopterin deficiency
Lysosomal storage disorders.
Batten disease
Fabry's disease
Farber's disease
Gaucher disease
Animals models of Gaucher's disease
Gene therapy of Gaucher's disease
Hunter syndrome
Krabbe's disease
Metachromatic leukodystrophy
Mucopolysaccharidosis type 1 (Hurler syndrome)
Niemann-Pick type A disease
Pompe disease
Sanfilippo A syndrome
Sly syndrome
Tay-Sachs disease
Future prospects of gene therapy of lysosomal storage disorders
Trinucleotide repeat disorders
Muscular dystrophies
Duchenne muscular dystrophy (DMD)
Animal models for gene therapy of DMD
Antisense approaches to DMD
Exon-skipping for DMD
Galgt2 gene therapy
Liposome-mediated gene transfer
Microdystrophin gene therapy
Myoblast-based gene transfer in DMD
Plasmid-mediated gene therapy
Purinoreceptor P2RX7 ablation
Post-transcriptional modulation of gene expression in DMD
Repair/Editing of dystrophin gene
Routes of administration of gene therapy in DMD
Types of dystrophin constructs
Viral vectors for DMD
Conclusions and future of gene therapy of DMD
Limb-girdle muscular dystrophy
Myotonic dystrophy
Spinal muscular atrophy
Gene therapy for SMA
Antisense therapy of SMA
X-linked myotubular myopathy (XLMTM)
Hereditary neuropathies
Charcot-Marie-Tooth disease
Hereditary axonal neuropathies of the peripheral nerves
Gene therapy of mitochondrial disorders
Techniques for mitochondrial replacement therapy
Status of mitochondrial replacement and transfer therapies
Companies involved in gene therapy of genetic disorders
5. Gene Therapy of Cancer
Strategies for cancer gene therapy
Direct gene delivery to the tumor
Injection into tumor
Direct injection of adenoviral vectors
Direct injection of a plasmid DNA-liposome complex
A polymer approach to local gene therapy for cancer
Electroporation for cancer gene therapy
Control of gene expression in tumor by local heat
Radiation-guided gene therapy of cancer
Radioprotective gene therapy
Nanoparticles to facilitate combination of hyperthermia and gene therapy
Cell-based cancer gene therapy
Adoptive cell therapy
Cytokine gene therapy
Genetic modification of human hematopoietic stem cells
Immunogene therapy
Cancer vaccines
Genetically modified cancer cell vaccines
GVAX cancer vaccines
Genetically modified dendritic cells
Nucleic acid-based cancer vaccines
DNA cancer vaccines
RNA vaccines
Viral vector-based cancer vaccines
Intradermal delivery of cancer vaccines by Ad vectors
Future prospects of cancer vaccines
Companies involved in nucleic acid-based cancer vaccines
Monoclonal antibody gene transfer for cancer
Transfer and expression of intracellular adhesion-1 molecules
Other gene-based techniques of immunotherapy of cancer
CRISPR for immunogene therapy
Fas (Apo-1)
Major Histocompatibility Complex (MHC) Class I
IGF (Insulin-Like Growth Factor)
Inhibition of immunosuppressive function in cancer
Delivery of toxic genes to tumor cells for eradication
Gene-directed enzyme prodrug therapy
Combination of gene therapy with radiotherapy
Correction of genetic defects in cancer cells
Targeted gene therapy for cancer
Antiangiogenic therapy for cancer
Bacteria as novel anticancer gene vectors
Cancer-specific gene expression
Cancer-specific transcription
Delivery of retroviral particles hitchhiking on T cells
Electrogene and electrochemotherapy
Epidermal growth factor-mediated DNA delivery
Gene-based targeted drug delivery to tumors
Gene expression in hypoxic tumor cells
Genetically modified T cells for targeting tumors
Chimeric antigen receptor T cells
Genetically engineered stem cells for targeting tumors
Hematopoietic stem cells for targeted cancer gene therapy
Immunolipoplex for delivery of p53 gene
Nanomagnets for targeted cell-based cancer gene therapy
Nanoparticles for targeted site-specific delivery of anticancer genes
Targeted cancer therapy using a dendrimer-based synthetic vector
Tumor-targeted gene therapy by receptor-mediated endocytosis
Virus-mediated oncolysis
Cytokine-induced killer cells for delivery of an oncolytic virus
Monitoring of viral-mediated oncolysis by PET
Oncolytic adenoviruses
Oncolytic HSV
Oncolytic measles viruses
Oncolytic vaccinia virus
Oncolytic vesicular stomatitis virus
Targeted cancer treatments based on oncolytic viruses
Concluding remarks on oncolytic gene therapy
Companies developing oncolytic viruses
Apoptotic approach to improve cancer gene therapy
Tumor suppressor gene therapy
P53 gene therapy
BRIT1 gene therapy
Nitric oxide-based cancer gene therapy
Anticancer effect of nitric oxide synthase
Gene therapy for radiosensitization of cancer
Gene therapy of cancer of selected organs
Gene therapy for bladder cancer
Gene therapy for glioblastoma multiforme.
Adenoviral vectors for treatment of brain tumors
Antiangiogenic gene therapy
Autophagy induced by conditionally replicating adenoviruses
Baculovirus vector for diphtheria toxin gene therapy
Cerepro® (sitimagene ceradenovec)
Gene therapy targeting hepatocyte growth factor
Genetically engineered MSCs for gene delivery to intracranial gliomas
Intravenous gene delivery with nanoparticles into brain tumors
Ligand-directed delivery of dsRNA molecules targeted to EGFR
Olig2 targeting to hinder growth of treatment-resistant glioblastomas
RNAi gene therapy of brain cancer
Targeting normal brain cells with an AAV vector encoding interferon-ß
Viral oncolysis of glioblastoma multiforme
Gene therapy for breast cancer
Gene vaccine for breast cancer
Recombinant adenoviral ErbB-2/neu vaccine
Gene Therapy for ovarian cancer
Gene therapy for malignant melanoma
Immunogene therapy
Nonviral immunogene therapy for malignant melanoma
Oncogene targeted therapy
Targeted gene therapy for malignant melanoma
Gene therapy of lung cancer
Intravenous nanoparticle formulation for delivery of FUS1 gene
Aerosol gene delivery for lung cancer
Gene therapy for cancer of prostate
Experimental studies
Nanoparticle-based gene therapy for prostate cancer
Tumor suppressor gene therapy in prostate cancer
Vaccines for prostate cancer
Viral oncolysis for prostate cancer
Clinical trials of gene therapy for prostate cancer
Gene therapy of head and neck cancer
Adenoviral vector based P53 gene therapy
Gene therapy as adjunct to 5-FU for nasopharangeal carcinoma
Gene therapy of pancreatic tumors
Pancreatic neuroendocrine tumors
Pancreatic ductal adenocarcinoma
Correction of altered genes
Targeted gene therapy
Targeting in pancreatic adenocarcinoma with cell surface antigens
Targeted Expression of BikDD gene
Viral oncolysis in pancreatic cancer
Concluding remarks on gene therapy of pancreatic cancer
Gene therapy of renal cancer
Viral onclolytic therapy for renal cancer
Gene therapy of hematological malignancies
Genetically engineered T lymphocytes
Cancer gene therapy companies
6. Gene Therapy of Neurological Disorders
Gene transfer techniques for the nervous system
Methods of gene transfer to the nervous system
Ideal vector for gene therapy of neurological disorders
Promoters of gene transfer
Lentivirus-mediated gene transfer to the CNS
AAV vector mediated gene therapy for neurogenetic disorders
Gene transfer to the CNS using recombinant SV40-derived vectors
Routes of delivery of genes to the CNS
Direct injection into CNS
Introduction of the genes into cerebral circulation
Introduction of genes into cerebrospinal fluid
Intravenous administration of vectors
Delivery of gene therapy to the peripheral nervous system
Cell-mediated gene therapy of neurological disorders
Neuronal cells
Neural stem cells and progenitor cells
Cerebral endothelial cells
Implantation of genetically modified encapsulated cells into the brain
Gene transfer for neuromodulation
Gene therapy of neurodegenerative disorders
Gene therapy for Parkinson disease
Techniques of gene therapy for PD
Augmenting CNS glucocerebrosidase activity
Delivery of neurotrophic factors by gene therapy
Delivery of parkin gene
Introduction of functional genes into the brain of patients with PD
Nanoparticle-based gene therapy for PD
Mitochondrial gene therapy for PD
RNAi approach to PD
Prospects of gene therapy for PD
Concluding remarks about gene therapy of PD
Companies developing gene therapy for PD
Gene therapy for Alzheimer disease
NGF gene therapy for AD
FGF2 gene transfer in AD
Neprilysin gene therapy
Targeting plasminogen activator inhibitor type-1 gene
Viral gene transfer of APPsa for rescuing synaptic failure in AD
Gene vaccination
Combination of gene therapy with other treatments for AD
Gene therapy of Huntington disease
Encapsulated genetically engineered cellular implants
Viral vector mediated administration of neurotrophic factors
RNAi gene therapy
Gene therapy of amyotrophic lateral sclerosis
Technique of gene therapy of ALS
Other approaches to gene therapy of ALS
Gene therapy of cerebrovascular diseases
Preclinical research in gene therapy for cerebrovascular disease
Animal models of stroke relevant to gene therapy
Transgenic mice as models for stroke
Animal models for gene therapy of arteriovenous malformations
Gene transfer to cerebral blood vessels
Gene therapy for vasospasm following subarachnoid hemorrhage
NOS gene therapy for cerebral vasospasm
Gene therapy for stroke
Gene therapy for stroke using neurotrophic factors
Gene therapy of strokes with a genetic component
Gene therapy for intracranial aneurysms
RNAi-based gene silencing for neuroprotection in cerebral ischemia
Concluding remarks about gene therapy for stroke
Gene therapy of injuries to the nervous system
Traumatic brain injury
Spinal cord injury
Peripheral nerve injuries
Gene therapy of epilepsy
Gene therapy for control of seizures
Gene therapy for neuroprotection in epilepsy
Gene therapy for genetic forms of epilepsy
Gene therapy for multiple sclerosis
Gene therapy for impairment of special senses
Gene therapy for hearing loss
Gene therapy for olfactory impairment
Gene therapy for relief of pain
Rationale of gene therapy for pain
Vectors for gene therapy of pain
Methods of gene delivery for pain
Endogenous analgesic production for cranial neuralgias
Gene delivery by intrathecal route
Gene transfer for delivery of analgesics to the spinal nerve roots
Gene therapy of peripheral neuropathic pain
Gene transfer by injections into the brain substance
Targets for gene therapy of pain
Zinc finger DNA-binding protein therapeutic for chronic pain
Gene therapy for producing enkephalin to block pain signals
Targeting nuclear factor-?B
Gene therapy targeted to neuroimmune component of chronic pain
Potential applications of gene therapy for management of pain
Concluding remarks on gene therapy for pain
Gene therapy for psychiatric disorders
Gene therapy for depression
Gene therapy for enhancing cognition after stress
Gene therapy against fear disorders
Companies involved in gene therapy of neurological disorders
7. Gene Therapy of Cardiovascular Disorders
Techniques of gene transfer to the cardiovascular system
Direct plasmid injection into the myocardium
Catheter-based systems for vector delivery
Ultrasound microbubbles for cardiovascular gene delivery
Vectors for cardiovascular gene therapy
AAV vectors for therapeutic delivery to the heart
Adenoviral vectors for cardiovascular diseases
Molecular cardiac surgery with recirculating delivery of AAV vectors
Plasmid DNA-based delivery in cardiovascular disorders
Gene therapy for counteracting hypoxia in myocardial ischemia
Therapeutic angiogenesis vs vascular growth factor therapy
Gene painting for delivery of targeted gene therapy to the heart
Gene delivery to vascular endothelium
Targeted plasmid DNA delivery to the cardiovascular system with nanoparticles
Vascular stents for gene delivery
Gene therapy for genetic cardiovascular disorders
Genetic disorders predisposing to atherosclerosis
Familial hypercholesterolemia
Apolipoprotein E deficiency
Genetic factors for myocardial infarction
Acquired cardiovascular diseases
Coronary artery disease with angina pectoris
Gene therapy for improving long-term CABG patency rates
Ischemic heart disease with myocardial infarction
Gene therapy and angiogenesis in ischemic heart disease
Induction of angiogenesis in myocardium by HEXIM1 re-expression
Myocardial repair with IGF-1 therapy
Metalloproteinase-2 inhibitor gene therapy
miRNA gene therapy for ischemic heart disease
Congestive heart failure
Rationale of gene therapy in CHF
AAV-mediated gene transfer for CHF
AngioCell gene therapy for CHF
ß-ARKct gene therapy
Elevating cardiac dATP by gene therapy to improve cardiac function
Elevating cardiac adenyl cylase type 6 to improve cardiac function
Intracoronary adenovirus-mediated gene therapy for CHF
nNOS gene transfer in CHF
Cardiac conduction disturbances
Gene transfer approaches for biological pacemakers
Genetically engineered biological pacemakers
Gene therapy and heart transplantation
Hyperlipidemia and hypercholesterolemia
Antisense approach to hypertriglyceridemia
Cholesterol reduction by genetic engineering of PCSK9 gene
Inactivating variants in ANGPTL4 for lowering circulating triglycerides
Peripheral arterial disease
Incidence and clinical features
Current management
Gene therapy for peripheral arterial disease
Angiogenesis by gene therapy
HIF-1? gene therapy for peripheral arterial disease
HGF gene therapy for peripheral arterial disease
Prevention of restenosis after angioplasty
Antisense approaches
Gene therapy to prevent restenosis after angioplasty
hTIMP-1 gene therapy to prevent intimal hyperplasia
miRNA-based gene therapy for restenosis
NOS gene therapy for restenosis
Techniques of gene therapy for restenosis
Maintaining vascular patency after surgery
Companies involved in gene therapy of cardiovascular diseases
Future prospects of gene therapy of cardiovascular disorders
8. Gene therapy of viral infections
Acquired Immunodeficiency Syndrome (AIDS)
Current management of AIDS
Gene therapy strategies in HIV/AIDS
HIV/AIDS vaccines
Insertion of protective genes into target cells.
Cell/gene therapies for HIV/AIDS
Transplantation of genetically modified T cells
Transplantation of genetically modified hematopoietic cells
Anti-HIV ribozyme delivered in hematopoietic progenitor cells
Inhibition of HIV-1 replication by lentiviral vectors
Intracellular immunization
Engineered cellular proteins such as soluble CD4s
Intracellular antibodies
Anti-rev single chain antibody fragment
Use of genes to chemosensitize HIV-1 infected cells
Autocrine interferon (INF)-? production by somatic cell gene therapy
Antisense approaches to AIDS
RNA decoys
Antisense oligodeoxynucleotides
RNA decoys
RNAi applications in HIV/AIDS
siRNA-directed inhibition of HIV-1 infection
Role of the nef gene during HIV-1 infection and RNAi
Bispecific siRNA constructs
Targeting CXCR4 with siRNAs
Targeting CCR5 with siRNAs
Companies involved in developing gene therapy for HIV/AIDS
Conclusions regarding gene therapy of HIV/AIDS
Genetic vaccines for other viral infections
Cytomegalic virus infections
Viral hepatitis
Vaccine for hepatitis B
Vaccine for hepatitis C
Gene therapy for hepatitis C
Vaccine for herpes simplex virus
DNA vaccine against rabies
DNA vaccine for Ebola
Vaccines for avian influenza
Future prospects of DNA vaccines for avian influenza
Human trial of a DNA vaccine for avian influenza
Companies developing genetic vaccines for infections other than AIDS
9. Research, Development and Future of Gene Therapy
Basic research in gene therapy
R & D in gene therapy
Animal models of human diseases for gene therapy research
Lentiviral transgenesis
Financing research and development
Role of the NIH in gene therapy research
National Gene Vector Laboratories
Funding of gene therapy research in Europe
Gene therapy funding in Horizon 2020 of European Commission
Financing by the industry
Clinical trials in gene therapy
Clinical trials worldwide
Clinical trials in cancer gene therapy
Trials of gene therapy for neurological disorders
Clinical trials for genetic disorders
Clinical trials in cardiovascular gene therapy
Clinical trials for infectious diseases
Gene therapy for other disorders
Clinical trials in the US
Vectors used in gene therapy clinical trials
Vector analytics for clinical trials using rAAV vectors
Future prospects for the gene therapy
How to improve gene therapy
International Gene Therapy Consortium
Future opportunities and challenges for gene therapy
Promising areas of application of gene therapy
Neurological disorders
Gene therapy of cardiovascular disorders
Cancer gene therapy
Personalized gene therapy
10. Regulatory, Safety, Ethical Patent Issues of Gene Therapy
Regulation of gene therapy in the United States
US Federal guidelines for research involving recombinant DNA molecules
Regulation of gene therapy in US
Implantation of genetically manipulated cells
Modification of oocytes for use in IVF
Clinical trials in gene therapy
Cell and gene therapy INDs placed on hold by the FDA
Regulation of gene therapy in Europe
European Union
Regulation of gene therapy in Germany
Preclinical research
Clinical Trials
Marketing authorization
Regulation of gene therapy in the United Kingdom
Regulation of gene therapy in France
Regulation of gene therapy in Italy
Regulation of gene therapy in the Netherlands
Gene therapy regulation in Switzerland
Regulation of gene therapy in Australia
Regulation of gene therapy in Japan
Regulation of gene therapy in China
Safety issues of gene transfer
Adverse effects of retroviral vectors
Insertional mutagenesis
Adverse effects of HSV vectors
Neurotoxicity of HSV vectors
Hepatotoxicity of HSV-tk/ganciclovir approach
Adverse effects of adenoviral vectors
Inflammatory effects of adenoviruses in lungs
Inflammatory effects involving the liver
Induction of immune response by adenoviral vectors
Impairment of adrenocortical steroidogenesis
Adverse effects of AAV vectors
Toxicity associated with cationic lipid-mediated gene transfer
Toxicity of lipopolysaccharides
Potential side effects of RNAi gene therapy
Role of molecular diagnostics in safety of gene therapy
Quality control of vectors
Testing for retroviruses
Adenoviral vectors
Replication competent viruses
Genetic characteristics of viral vectors
Concluding remarks about safety of viral vectors
Ethical aspects of gene therapy
The lay consumer's view of somatic gene therapy ethics
Ethical aspects of clinical trials
Regulatory and ethical issues for in utero gene therapy
Ethical aspects of germline gene therapy
Ethical aspects of mitochondrial replacement therapy
Ethical aspects of gene editing
Germline gene therapy for genetic enhancement
Athletic enhancement by genetic engineering
Gene doping in sports
Gene transfer methods used for enhancing physical performance
Adverse effect of genetic engineering
Problems in detecting genetic manipulations in athletes
Ethical dilemma
Gene therapy patents
CRISP/Cas9 patents
11. Markets for Gene Therapy
Gene therapy markets in various regions of the world
Gene therapy markets according to therapeutic areas
Cancer gene therapy market
Markets for gene therapy of genetic disorders
Markets for DNA vaccines
DNA vaccines markets according to technologies
DNA vaccines markets according to therapeutic indications
DNA vaccines markets according to geographical areas
Competing treatments
Cell therapy
Strategies for developing gene therapy markets
Collaboration with pharmaceutical companies
Collaboration with companies developing cell-based therapies
Collaboration with academic gene therapy centers
Developing safer and cost-effective gene medicines
Intellectual property and commercialization of gene therapy
Overcoming obstructions to the development of gene therapy
Unmet needs in gene therapy
Promises and challenges for the development of gene therapy
Development of gene therapy market in China
Challenges of developing gene therapy in the USA
Challenges of developing gene therapy in the European Union
12. References
List of Tables
Table 1-1: Landmarks in development of gene therapy
Table 2-1: Classification of methods of gene therapy
Table 2-2: A comparison of various physical methods of gene transfer
Table 2-3: Experimental applications of gene transfer by electroporation
Table 2-4: An overview of characteristics of commonly used viral vectors
Table 2-5: Companies using viral vectors
Table 2-6: Companies using nonviral vectors
Table 2-7: Target organs for non-viral gene therapy methods.
Table 2-8: Potential routes for administration of DNA
Table 2-9: Companies with gene delivery devices/ technologies
Table 2-10: Strategies for targeted gene therapy
Table 2-11: Animal experimental studies of in vivo gene delivery with polymer systems
Table 2-12: Approaches to controlling gene expression in gene therapy
Table 2-13: Companies with regulated/targeted gene therapy and special techniques
Table 2-14: Potential applications of human germline genome modification
Table 2-15: Applications of molecular diagnostics in gene therapy
Table 2-16: Advantages of gene therapy compared with protein therapy
Table 3-1: Experimental approaches to gene therapy of rheumatoid arthritis
Table 3-2: Gene therapy strategies for osteoarthritis
Table 3-3: Cell and gene therapy approaches for type 1 diabetes mellitus
Table 3-4: Indications for gastrointestinal gene therapy
Table 3-5: Hematological disorders that can be potentially treated by gene therapy.
Table 3-6: Companies involved in gene therapy of hematological disorders
Table 3-7: Techniques of gene transfer to the kidneys
Table 3-8: Gene therapy in animal experimental models of renal disease.
Table 3-9: Applications of gene therapy in ophthalmological disorders
Table 3-10: Companies developing gene therapy for eye disorders
Table 3-11: Strategies for gene delivery to the lungs
Table 3-12: Companies developing gene therapy for pulmonary disorders
Table 4-1: Genetic disorders that are being investigated for gene therapy
Table 4-2: X-linked immunodeficiency disorders
Table 4-3: Examples of inherited metabolic disorders amenable to gene therapy
Table 4-4: Gene therapy approaches to Duchenne muscular dystrophy
Table 4-5: Companies involved in gene therapy of genetic/metabolic disorders
Table 5-1: Strategies for cancer gene therapy
Table 5-2: Cell-based gene therapy for cancer
Table 5-3: Companies with nucleic acids/genetically modified cell cancer vaccines
Table 5-4: Enzyme/prodrug combinations employed in suicide gene therapy
Table 5-5: Mutation compensation strategies used clinically
Table 5-6: Companies developing oncolytic viruses
Table 5-7: Strategies for gene therapy of malignant brain tumors
Table 5-8: Clinical trials of oncolytic virotherapy against glioblastoma multiforme
Table 5-9: Clinical trials of gene therapy in ovarian cancer
Table 5-10: Gene therapy for malignant melanoma
Table 5-11: Clinical trials of gene therapy for prostate cancer
Table 5-12: Companies involved in cancer gene therapy
Table 6-1: Example of potential indications for gene therapy of neurologic disorder
Table 6-2: Methods of gene transfer as applied to neurologic disorders
Table 6-3: Gene therapy techniques applicable to Parkinson disease
Table 6-4: Companies developing gene therapy for Parkinson's disease
Table 6-5: Gene transfer in animal models of carotid artery restenosis
Table 6-6: Gene therapy strategies for vasospasm
Table 6-7: Neuroprotective gene therapy in animal stroke models
Table 6-8: Experimental gene therapy approaches for relief of pain
Table 6-9: Companies involved in gene therapy of neurological disorders
Table 7-1: Cardiovascular disorders that are potential indications for gene therapy
Table 7-2: Catheter-based systems for vector delivery to the cardiovascular system
Table 7-3: Companies involved in gene therapy of cardiovascular diseases
Table 8-1: Strategies for gene therapy of AIDS
Table 8-2: Companies involved in developing gene therapy for HIV/AIDS
Table 8-3: Companies developing genetic vaccines for infections other than AIDS
Table 9-1: Geographical distribution of gene therapy clinical trials
Table 9-2: Opportunities and challenges for gene therapy and resources needed
Table 9-3: Potential applications of gene therapy in disorders of the nervous system
Table 10-1: Genes that may be used for performance enhancement
Table 11-1: Gene therapy market according to regions/countries ? 2016 to 2
Table 11-2: Gene therapy markets according to therapeutic areas ? 2016 to 2
Table 11-3: Cancer gene therapy market according to type of cancer - 2016 to 2
Table 11-4: Gene therapy market for selected genetic disorders - 2016 to 2
Table 11-5: DNA vaccines markets according to technologies - 2016 to 2
Table 11-6: DNA vaccines markets according to therapeutic indications - 2016 to 2
Table 11-7: DNA vaccines markets according to geographical areas - 2016 to 2
List of Figures
Figure 1-1: Relation of gene therapy to other biotechnologies
Figure 1-2: Relationship of DNA, RNA and protein in the cell
Figure 2-1: Ex vivo and in vivo techniques of gene therapy
Figure 2-2: Structure of the Helios gene gun
Figure 2-3: A scheme of CRISPR/Cas9 gene editing
Figure 2-4: Bacteria plus nanoparticles for drug delivery into cells
Figure 2-5: Schematic of suppression of gene expression by RNAi
Figure 3-1: Retina and routes of administration of gene therapy for retinal disorders
Figure 4-1: Targeted gene correction of a1-antitrypsin deficiency by iPSCs
Figure 4-2: Application of CRISPR-Cas9 in a mouse model of DMD
Figure 4-4: Techniques for mitochondrial nuclear transfer
Figure 5-1: Gene therapy approaches for pancreatic cancer
Figure 6-1: Effect of tyrosine hydroxylase gene delivery on dopamine levels
Figure 6-2: Role of cell and gene therapy in stroke according to pathology and stage
Figure 9-1: Product development cycle in gene therapy
Figure 9-2: Proportions of therapeutic areas in clinical trials of gene therapy in the US
Figure 9-3: Proportions of various vectors used in gene therapy trials
Figure 10-1: Evaluation system of gene therapy clinical studies in Japan
Figure 11-1: Unmet needs in gene therapy
Part II: Companies
13. Companies involved in Gene Therapy
History of commercial development of gene therapy
Selection of companies and information
Supporting services for gene therapy
Profiles of Companies
List of Tables
Table 13-1: Major players in gene therapy
Table 13-2: Companies with supporting services for gene therapy
Table 13-3: Product pipeline of Medegene AG
Table 13-4: Product pipeline of Valentis
Table 13-5: Collaborations of gene therapy companies


text: Super Mario Galaxy 2 Forecast Cloudy With A Chance Of PlumbersMike Fahey4/16/10 1:30pmFiled to: NintendoSuper Mario Galaxy 2WiiCloud MarioPower-up299EditPromoteShare to KinjaToggle Conversation toolsGo to permalink The latest new power-up reveled for Super Mario Galaxy 2 shows how light on his feet everyone's favorite plumber can be as he takes on the powers of Cloud Mario. Along with dressing our hero up in white overalls, puffing up his hat, and giving him attractive neck ruffles, the Cloud power-up also lets our hero create cloud steps, which he can then walk on them to reach out of the way places. It's also a nice counterpoint to the recently-revealed Rock Mario, showing us the plumber's softer side. New Mario Galaxy 2 Power-Up revealed! [Official Nintendo Magazine UK - Thanks Fernando!]Reply299 repliesLeave a reply


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International News Latest Attempt to Block HIV: Stronger Vaginal GelsMay 21, 2010 Researchers gathering for the 2010 International Microbicides Conference in Pittsburgh, May 22-25, are cautiously optimistic about new approaches to prevent HIV infection in spite of two decades of failed attempts. "Frankly, blocking transmission of the virus appears to be a lot harder than anyone understood it would be at the beginning,' said Dr. Sharon Hillier of the University of Pittsburgh, who is the meeting's co-chair and a principal investigator of the Microbicide Trials Network. "The reason we're not depressed in the microbicide world? We actually have learned a lot and moved on to think about potent drugs and really cool delivery methods." Researchers have discovered that cells on the vaginal surface are not large targets of HIV, yet the virus somehow manages to quickly penetrate to a much more susceptible second layer. Primate studies indicate a small population of "founder" cells apparently reproduce in that area for a few days before HIV is ready to spread, said Hillier. Karim is leading the first study to see if this new strategy works. Nine hundred HIV-negative, heterosexual South African women are taking part to see whether the tenofovir gel, applied up to 12 hours prior to intercourse and again within 12 hours following sex, lowers the risk of infection. The study's results are due in July. Meanwhile, the National Institutes of Health is funding the first study to compare the effect of taking tenofovir daily via a vaginal gel -- rather than timed around intercourse -- versus daily oral tenofovir. Up to 5,000 healthy women in several African countries will take part in that study. For more information about the conference, visit www.microbicides2010.org. Associated Press 05.18.2010; Lauran Neergaard This article was provided by CDC National Prevention Information Network. It is a part of the publication CDC HIV/Hepatitis/STD/TB Prevention News Update.
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Our growing portfolio of beautifully designed mounting and mobility products for computer systems, displays, laptops, TVs, tablets & mobile devices has empowered Ergotron to lead and innovate in each of these markets while continuing to provide a number of solutions for nearly every niche.
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St. Paul, MN, US
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Purchases of WorkFit or Lift35 help provide classrooms with complimentary LearnFit student desks, bringing the benefits of moving more.
Press Release | FitForward™ Program
Ergotron's second JustStand Index outlines the survey results and the business implications of sedentary workstyles as well as the promising news that public awareness of sitting disease is shifting.
Press Release | JustStand Index
The successful reduction of sedentary behaviours in young people is pertinent for the prevention of diseases. These studies add to the limited evidence base on the efficacy of sit-to-stand desks on objectively measured sitting time.
Press Release | Research in Wellness
Introducing the newest member of our LX family of products: the LX Desk Dual Direct Arm allows businesses to create a fully adjustable side–by–side monitor configuration.
Our new sleek and stylish HX Arms are ideal for businesses seeking flexible and efficient options for multiple screen configurations, with weight capacity to allow for up to three monitors.
Thank you to those who joined us for the recent live Standing Desks: How and Why Educators Are Using Them webinar about how standing desks create a healthy, flexible, and personalized learning...


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Hostelworld Tavsiyeleri
Bu hostele bayılıyoruz! Tutarlı bir şekilde yüksek müşteri puanları ve üstün kalite notlarıyla beğenimizi kazandı.
Sonuçları Karşılaştır
- Albufeira şehrinde ne zaman kalmak istiyorsunuz?
- Fiyat
- Oy
- Uzaklık
- Adı
Orange Terrace is a charming and fun Hostel located right in the city centre just 200 metres to the beautiful beach of Albufeira and Restaurants, Shops, Supermarkets, Bars and Clubs.
The hostel ha... Daha fazla...
- Fiyat Oda Tipi
Our house, belonging to one of the oldest families in Albufeira, is located in the heart of the old town "Baixa" and was completely remodeled in order to offer our guests the highest stand... Daha fazla...
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This small Hostel situated in a privileged area of Albufeira, only 2 km from the city centre and 1 km away of several beautiful beaches which have been awarded, such as the beach of S. Rafael, Evarist... Daha fazla...
- Fiyat Oda Tipi
Portekiz olarak sunmak için tüm muhteşem deniz ürünleri ile çok iyi bir restoran ile çevresinde, muhteşem plajları ile , Albufeira, Algarve , Portekiz güney ke... Daha fazla...
- Fiyat Oda Tipi
Welcome to Ale-Hop Albufeira Hostel!
In the heart of Albufeira's historical center, the Ale-Hop Albufeira Hostel is within very easy access to all tourist attractions, while featuring very affordab... Daha fazla...
- Fiyat Oda Tipi
Hostel DP – Albufeira is a beautiful and comfortable hostel, ideally located in Albufeira, Algarve. For your comfort and make your stay unforgettable, the property offers many different faciliti... Daha fazla...
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Apartamentos Turísticos Regina*** Policies and Conditions:
Confirmation and Deposit
To confirm and guarantee your booking is necessary a deposit of the amount of the first night from Octobe... Daha fazla...
- Fiyat Oda Tipi
Du4arte hostel has the privilege of being born in a traditional town with an amazing cuisine and enviable beaches.
A building whose construction dates back to 1969, our facilities were completely r... Daha fazla...
- Fiyat Oda Tipi
Soldoiro Apartments are located in Praia da Oura, Albufeira, 130 m from the beach, 150 m from the most busy night life street in the area.
There are apartments for 2 to 6 persons, all with WC, kit... Daha fazla...
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... Daha fazla...
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Hotel da Galé** is a small beach hotel, located in Cerro da Piedade, at the town center a few minutes walk from the historical Moorish castle, and just 100m of the new Albufeira marina. Its pr... Daha fazla...
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The Hotel Topázio is a three star hotel implemented in the tourist area of Albufeira, just 200 from the Aveiros beach. The center of Albufeira (oldest part) is only approximately 2 km.
Albuf... Daha fazla...
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The house is in the centre of Albufeira, in the old part of the city. Located about 100 meters from Peneco Beach, allows beach without having to think about travelling, especially in high season. In l... Daha fazla...
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This apartment complex is situated in Olhos de Agua, just 170 meters from the beach.
There are small shops restaurants, bars, pubs and public transport links, about 800m from the hotel.... Daha fazla...
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Lyme disease can cause memory loss & brain fog. Now there's compelling evidence it might cause Alzheimer's too. Learn about the connection.
Deer ticks. Lyme disease. Those words might be enough to keep you indoors this summer.
First discovered in Lyme, Connecticut, this disease is now found in all 50 US states and on every continent except Antarctica.
In 2013, the Centers for Disease Control announced that the current rate of Lyme disease was found to be ten times higher than was previously believed, with 300,000 new cases each year. (1)
It's growing in numbers and spreading geographically, yet some medical professionals don't acknowledge that its chronic form even exists!
Lyme Disease Basics
This disease is a hard nut to crack on just about every level.
- Lyme disease is transmitted through a bite from an infected deer tick the size of a poppy seed. Deer have gotten the blame as tick carriers but most people are bit by ticks from mice, not deer.
Most people who are bitten by a tick never even know it. Fewer than half of people infected get the telltale bull's eye rash, the first obvious sign of the disease.
- There is no accurate diagnostic test for Lyme. Current tests have about 50% false negative results. You'd do just as well flipping a coin.
- Lyme disease is caused by Borrelia burgdorferi, a bacteria that can lie dormant for months or years, making diagnosis even more difficult.
- Lyme disease is called the "great imitator" because symptoms can mimic many other diseases — fibromyalgia, arthritis, chronic fatigue syndrome, multiple sclerosis, and lupus.
- Even if you receive an accurate diagnosis, it is persistent and difficult to treat. The bacteria form "biofilms," a slimy protective coating that keep the bacteria safe from detection and antibiotics. (2)
The most common symptoms of Lyme disease are fatigue, muscle and joint pain, joint inflammation, memory loss, mental confusion, brain fog, vision problems, digestive issues, and headaches.
If undiagnosed or untreated, it can lead to encephalitis, a potentially fatal inflammation of the brain. (3)
The Lyme-Alzheimer's Connection
There is reason to believe that the Borrelia bacteria might be a cause of Alzheimer's.
Alan MacDonald, MD has been studying Lyme disease for 30 years and came across an amazing discovery while analyzing brain specimens of Alzheimer's victims: 70% of these Alzheimer's-riddled brains contained the Lyme bacteria Borrelia. (4)
Dr. Dietrich Klinghardt, another Lyme specialist, states he's never had a single patient with Alzheimer's, ALS, Parkinson's disease or multiple sclerosis who did not test positive for Borrelia.
These are all diseases with no known cause and he suspects that Lyme disease might be the common link.
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Both Dr. MacDonald and Dr. Klinghardt are among the many forward-thinking health care professionals interviewed in the award-winning documentary Under Our Skin.
In this movie, you'll be exposed to a very ugly chapter in modern medicine.
You'll learn how official Lyme disease policy is dictated by insurance companies who don't want to pay for treatment.
You'll see special interests putting profits above the lives of thousands, including children.
You'll witness doctors losing their licenses for treating chronic patients, including the doctor who is considered the top pediatric Lyme's specialist in the country.
Watch the movie trailer:
If you have an Amazon Prime account you can watch it for free.
It's also available for viewing on Netflix. Or you can buy the DVD on the movie's website.
If You Think You Have Lyme Disease
If you suspect you have Lyme disease, visit the International Lyme And Associated Diseases Society.
This organization is an excellent place to start for unbiased, evidence-based information on this disease.
Chris Kresser, one of my favorite nutrition experts, interviewed Dr. Sunjya Schweig, a functional medicine physician who specializes in tick-borne illness in a recent podcast.
Topics covered include:
- Promising new testing solutions
- What to do if you think you have Lyme disease
- Steps for prevention
- Effective treatment options
Podcast: Diagnosing and Treating Lyme Disease
Listen here.
Lastly, there is an excellent book, Cure Unknown: Inside the Lyme Epidemic by Pamela Weintraub, a science journalist whose oldest son had Lyme disease.
This books gets five stars from both the public and health care professionals.
I expect we'll be hearing a lot more about Lyme disease and the connection with Alzheimer's and other neurological diseases in the future.