text:
Hi Jasmine,
My case was both peripheral neuropathy and the central form, Subacute combined degeneration. I have regained a lot of neurological function, can feel most of my feet, have decent balance. At one point I was falling and close to a wheel chair. That is why tjhe BRANDs mentioned are so critical. They are the only ones that so far are predictable at this present time. Good luck. You may have to order from the USA.
You sound like you have paradoxical folate deficiency. Perhaps there is folic acid or folinic acid in the bioplex b-complex or some other supplement(s). You need to be on the 5 star MeCbl, Enzymatic Therapy B12 infusion. and hold it for 2 hours under your lip. You need as much absorbtion as possible. 10mg of ENZY could produce 3mg absorbed in 2 hours, having a superior effect to most injections of that size. Also, you may need to titrate the L-methylfolate until the folate deficiency symptoms go away. Also, for full effectivenss you will need AdoCbl (the mitochondria b12 , allows tissues to be made and makes ATP for energy) and L-carntine fumarate, with microtitration if you have anxiety. Those 4, the Deadlock Quartet, turn on multiple levels of healing with very great success. Potassium needs to be titrated by effect and it may trade back and forth between potassium and l-methylfolate until an equilibrium is reached with all the needs for bboth satisfied. The combination of the 5 star AdoCbl and MeCbl, the other two of the Quartet, potassium, zinc, D etc, also needs 2000mg of active components Omega3 oils.
Also, folic acid, folinic acid, glutathione, NAC and Whey need to be avoided. They can cause problems such that the nerves will be further damaged instead of healing.
Hi Fred !! i have been following your protocol and so far i'm waiting for my Adb12 and Potassium package to arrive. I would however like to ask you some things that has made me confused.
-so far i was taking 10mg of Jarrow just because i couldn't return them but now that i am switching to Enzymatic Therapy B12 do i still need to go up to 50 mg per day? -how do you know that you have reached equilibrium? is it when you don't have any unpleasant symptoms anymore? -is there a limit for both Potassium and Metafolin that would make it dangerous (i'm assuming it's the same as l-methylfolat?) ?
Thank you so much…all this info means a world to me
Hi Jasmine,
Unfortunately the Jarrow ceased being effective at some batch change point about a year ago. Unfortunately for me it wasn't fully apparant till I had a relapse in August. At 5mg a day after you add the AdoCbl and titrate the potassium as needed with the Metafolin, and sometims the potassium and Metafolin alternate for a few rounds of adjustments. Then the l-carnitine fumarate needs to be added in. With Omega3 oils etc a lot of healing can happen on 5 levels and maybe 6. The 6th is the CSF/CNS level and if there is a problem getting enough into your CNS for healing, then a 50mg continuous dose of ENZY over 4 hours or so will be a real eye-opener. Each time you notice an effect in the CNS from that you are not yet at equilibrium. A 50mg dose of AdoCbl can also be tried. Because that lasts ever so much longer in the mitochondria you may find that you only need to repeat that one once a month to maintain CNS AdoCbl equilibrium. As long as a 50mg does causes a noticable change, you are not maintaining equilibrium. Some people need that dose once and some need it 3 times a day for healing, less for maitenance. Typical levels of Metafolin for adequacy (no folate insufficiency symptoms) are 800-2400mcg for those with no paradoxical folate deficiency, 6000-8000mcg for folic acid only paradoxical folate deficiency, and 12,000-30,000 mcg of Metafolin (Deplin at 15mg) for folinic acid-vegetable folate paradoxical folate deficiency. The ammount of supplemental potassium is achieved by titrating to effect, usually 2000-3000mg above dietary intake daily for somebody with widespread healing. Equilibrium is reached when the 50mg doses doesn'ty repeat immediate effects and the nerves heal 24 hrs per day. Body equilibrium is reached when a 5mg larger dose makes no noticable difference. MeCbl and HyCbl each have their own body equilibrium and their own CNS equilibrium, 4 possibilities in all.
Stol K, Diavatopoulos DA, Graamans K, Engel JA, Melchers WJ, Savelkoul HF, et al. Inflammation in the Middle Ear of Children with Recurrent or Chronic Otitis Media is Associated with Bacterial Load. . 2012 Jun 4. .
Marom T, Nokso-Koivisto J, Chonmaitree T. Viral-Bacterial Interactions in Acute Otitis Media. . 2012 Sep 12. .
Danishyar A, Ashurst JV. Otitis, Media, Acute. 2018 Jan. . .
Seo Y, Nonaka M, Yamamura Y, Pawankar R, Tagaya E. Optimal control of asthma improved eosinophilic otitis media. . 2018 Jan. 8 (1):e5. . .
Iino Y, Nagamine H, Kakizaki K, et al. Effectiveness of instillation of triamcinolone acetonide into the middle ear for eosinophilic otitis media associated with bronchial asthma. . 2006 Dec. 97(6):761-6. .
Hurst DS. The role of allergy in otitis media with effusion. . 2011 Jun. 44(3):637-54, viii-ix. .
Coughlin L. AHRQ data on antibiotic use in children with otitis media. . June 2005.
Tong S, Amand C, Kieffer A, Kyaw MH. Trends in healthcare utilization and costs associated with acute otitis media in the United States during 2008-2014. . 2018 May 2. 18 (1):318. . .
King LM, Bartoces M, Hersh AL, Hicks LA, Fleming-Dutra KE. National Incidence of Pediatric Mastoiditis in the United States, 2000-2012: Creating a Baseline for Public Health Surveillance. . 2018 Mar 27. .
Vayisoglu Y, Gorur K, Ozcan C, Korlu S. Unusual complication of otitis media with effusion: facial nerve paralysis. . 2011 Jul. 22(4):1525-7. .
Browning GC. Medical management of chronic mucosal otitis media. . 1984 Jun. 9(3):141-4. .
Dubey SP, Larawin V, Molumi CP. Intracranial spread of chronic middle ear suppuration. . 2009 Mar 31. .
McCormick DP, Jennings K, Ede LC, Alvarez-Fernandez P, Patel J, Chonmaitree T. Use of symptoms and risk factors to predict acute otitis media in infants. . 2016 Feb. 81:55-9. .
Miura T, Matsubara A, Kudo N, Hara R, Takahata J, Sasaki A. The expression of thymic stromal lymphopoietin in patients and animal models with eosinophilic otitis media. . 2018 May. 138 (5):447-51. .
Sakulchit T, Goldman RD. Antibiotic therapy for children with acute otitis media. . 2017 Sep. 63 (9):685-687. . .
Rosenfeld RM, Shin JJ, Schwartz SR, et al. Clinical Practice Guideline: Otitis Media with Effusion (Update). . 2016 Feb. 154 (1 Suppl):S1-S41. . .
Frellick M. Otitis Media: New Guideline Includes Screening At-Risk Kids. . 2016 Feb 4. .
Barclay L. Postop Tympanostomy Tube Obstruction Common. . Jul 2014. .
Conrad DE, Levi JR, Theroux ZA, et al. Risk factors associated with postoperative tympanostomy tube obstruction. . 2014 Aug 1. 140(8):727-30. .
Balbani AP, Montovani JC. [Impact of otitis media on language acquisition in children]. . 2003 Sep-Oct. 79(5):391-6. .
Diego A Preciado, MD, PhD, FAAP
Assistant Professor, Department of Otolaryngology, Division of Pediatric Otolaryngology, George Washington University School of Medicine, Children's National Medical Center Diego A Preciado, MD, PhD, FAAP is a member of the following medical societies:
Iro Woman Scalloped Broderie Anglaise Cotton Mini Dress Black Size 40 Iro DEwrrS8n
, American Academy of Pediatrics , Sneakers 360 Flexy Walk grey Loro Piana FNRrJgQX
, American Society of Pediatric Otolaryngology , Unisex Adults 410 Trainers New Balance YahFWIb
Disclosure: Nothing to disclose.


text:
(Sorry about the horrible YouTube compression!)
Experience Renegade Kid's award-winning first-person shooter, remastered in glorious 3D. Moon Chronicles delivers an atmospheric sci-fi adventure with enhanced graphics and intuitive touch screen controls for a truly unique experience – all running at a silky smooth 60 frames per second.
Join Major Kane on a mysterious mission to Earth's moon to investigate a unique hatch of unknown origin. With each new episode you are brought one step closer to understanding the secrets that lie beneath the surface of the moon.
• Immerse yourself in the gripping story-driven episodic action adventure.
• Equip a variety of guns, including powerful alien weaponry.
• Utilize Remote Access Droid (RAD) to navigate tunnels and unlock secret pathways.
• Explore the moon's surface with the LOLA-RR10 buggy, armed with a plasma turret.
• Choose from a wide selection of control schemes, including Circle Pad Pro support.
About Renegade Kid
For more information on Moon Chronicles, visit http://www.moonchronicles.com.

subset: commoncrawl


text:
Dale Marvin Stevenson
Dale Marvin Stevenson, age 82, of Miles City, MT, went to be with his Lord and Savior on Monday, Dec. 9, 2013 at Saint Vincent Health Care in Billings after complications from surgery with his family by his side.
Dale was born in Merrill on Aug. 15, 1931, the son of Hjalmer and Alma (Duranceau) Stevenson. Dale attended local schools and graduated from Merrill High School. He was very active playing football in high school for the Merrill Blue Jays and continued playing semi-pro football for the Merrill Foxes. In January of 1952, Dale enlisted in the United States Air Force, serving during the Korean Conflict. Following his honorable discharge, he returned to the family farm and cattle business in partnership with his father. Dale was married to his beloved wife and best friend Marlene Joan Van Der Geest on Feb. 23, 1957. Following their marriage he attended School of Mortuary Science in Cincinnati, Ohio. Following his graduation in 1958, they moved to Miles City. In 1958, he went to work for J.E. Graves Funeral Home until 1962 when he purchased Hinther-Jensen Funeral Home and later changed the name to Stevenson Funeral Home which is now Stevenson & Sons Funeral Home. He was very proud of the fact that his three sons and now four grandsons are in the family business. Throughout the years he expanded the business to serve throughout Montana and North Dakota. Dale truly loved the people he served in this community. He instilled this great love for community in the next generation and generations to come to continue this great love for community. He was always grateful to the community.
Dale was a charter member of Grace Bible Church, Commander of the American Legion, Montana State Board of Morticians and a member of many community organizations. Dale's true love was his wife and family. His biggest hobbies were his Clydesdale horses, making trips to the Van Der Geest Dairy Farms in Wisconsin, and working on his son Joe's farm feeding and preparing horses, riding on his 4-wheeler, taking trips with Marlene and seeing his daughters in Branson and Orlando. One of his greatest accomplishments was the joy of reading the bible with Marlene every morning.
Dale is survived by his loving wife of 56 years Marlene Stevenson of Miles City, MT; three sons: Joseph Dale and his wife Patricia of Miles City; Jonathan Lee and his wife Marlys of Dickinson, ND; Todd Floyd and his wife Terri of Miles City; two daughters: Mary Ann Treat and her husband Tom of Branson, MO and Cathy Alma Hill and her husband Mark of Orlando, FL; his sister Joan (Roger) Gutknecht of Merrill; 12 grandchildren: Jason Riley, Scott Joseph (Andrea), Mikel Dale and David Leroy (Suella) Stevenson; Nicholas Jon (Terri) and Brandon Dale (Wendy); Tiffany Lynn (Ren) Gardner and Todd John "TJ" Stevenson; Lucas Thomas William and Anna Marie Marlene Treat; and Tori Ann and Brittany Nicole Hill; eight great grandchildren: Carson Dale, Cooper Douglas, Colton Todd Gardner and one due in January; Joseph Patrick Stevenson; Sadie Marie, Nathan Jon, Ali Ann and Patrick James Stevenson and numerous nieces and nephews. He was preceded in death by his two brothers: Floyd Stevenson and Lee Stevenson, two sisters: Lola Waid and Vera Sutton and three nephews: Keith Sutton, Gary Van Der Geest and Dean Waid.
A special thanks to Pastor Jerry and Becky Coon, Saint Vincent Health Center and Dr. KayCee Gardner for being by our side with dad.
Funeral services were held on Monday, Dec. 16, at Grace Bible Church. Interment followed in the Custer County Cemetery with full military honors. Condolences may be sent to the family by visiting: www.stevensonandsons.com.
Should friends desire, memorials may be made in memory of Dale to Grace Bible Church.


text:
Children's Center
Our Mission
The Children's Center at Bowdoin College strives to provide an excellent standard of care that intentionally nurtures and supports all children, families and educators.
Our Philosophy
The educators at the Bowdoin College Children's Center welcome children and their families appreciating the diversity that forms our classroom communities. We celebrate a joyful, warm, and nurturing atmosphere throughout the center where educators and children create strong foundational relationships through vibrant experiences and reflective practice. The center embodies commitment for our young children through our responsiveness to the interests of children and families and our partnership in their lives.
Our Community
The Children's Center places itself in the context of community within and between classrooms, as an integral part of Bowdoin College and in the Brunswick neighborhood. We identify ourselves as community members through our professional interactions, support for educators, and partnerships with families. By designing our curriculum to use the offerings of the college we establish a strong relationship with this immediate community and its members helping children see themselves as part of a larger group. The diversity of our community rich with skills, interests, and abilities is enhanced as we draw on all of these parts. At times the Center is a continuing resource to the academic life at Bowdoin by opening our doors to students and faculty as they build understandings of young children or offering employment to students throughout the year.


text:
1 deal available
Save 28%
Sterling Silver 9.5mm Hammered Mens Cuff Bracelet
True Life Fly Company
$136.18 $189.99 (-28%)
Did you know that Shopcade is available in 3 countries? You can pick between UK, US and FR to check out unique content and sales.
Plus when you start shopping everything is tailored to your location, so all details automatically update! We'll race you to the checkout…


text:
Nneka Ogwumike scored 16 points, Candace Parker and Kristi Toliver added 13 points and six assists apiece, and the Sparks routed the San Antonio Silver Stars 84-48 Saturday night at Staples Center.
Jantel Lavender scored 14 points in a reserve role and Ogwumike also had seven rebounds for the Sparks (3-2), who bounced back from a 16-point loss Friday night in Phoenix.
The Sparks allowed 49 second-half points in that game but held San Antonio to 20 after the break one night later.
Danielle Adams had 12 points and Shenise Johnson added 11 for the Silver Stars (2-4), who are seeking their first road victory after going winless on a three-game trip.
San Antonio played without leading rebounder Jayne Appel. The Silver Stars are also without Becky Hammon until July because of a broken finger and Sophia Young was lost for the year because of an ACL tear during the offseason.
The Sparks blew open the game in the third quarter, outscoring San Antonio 26-8.
Parker scored nine in the third, including consecutive baskets on a 3-pointer and a runner in the paint while being fouled.
She converted a finger roll for a 55-34 lead and Toliver sank a jumper to push it to 61-36 entering the fourth.
The Sparks ended up shooting 59 percent from the field, making 39 of 61 shots. The Silver Stars made just 16 of 53 shots for 30.2 percent.


text:
Beginning January 12, 2016, outdated versions of Internet Explorer will no longer be supported and your browsing security may be compromised. For more information click here
CI Logo Library
CI Investments terms of usage agreement
Welcome to the CI Investments Corporate logo library site. This
Usage Agreement represents a binding agreement between you and CI Investments. If you are entering into this Agreement on your employer's
behalf, this Agreement applies to both you and your employer. The
following terms and conditions govern your access and use of images
from the CI Investments site. CI Investments reserves the right to change the
Terms of Use and other guidelines or rules posted on the website
from time to time at its sole discretion. By clicking "Accept" and
using this site to download any images, you agree to be bound by
the most current version of this Agreement.
If you do not agree to the following terms, please do not click
"Accept" and you will not be able to download or use any of the
images from this website.
In agreeing to abide by the terms of the Usage Agreement, you are
free to download the images posted on this website. You may not
distribute copies of any material containing the CI Investments logo for
any purpose or utilize the logo in any website you create or operate
unless you do so with the approval of CI Investments. Permission for use
of the CI Investments logo for any printed or online material can be requested
through the Marketing Department at CI Investments, 1-800-268-9374.
Please read the CI Graphic Standard before downloading.
Any unauthorized usage or modification of the logos posted on this
website may result in legal action.


text:
Alabama quarterback AJ McCarron may have led his team to victory over Notre Dame in Monday night's BCS National Championship but it was his girlfriend Katherine Webb, the reigning Miss Alabama, who emerged as the star of the game.
ESPN cameras couldn't stay away from Webb, obsessively showing her in the stands watching the game at Sun Life Stadium with Dee Dee Bonner, her boyfriend's mother.
Webb has not acknowledged her sudden fame but her Twitter following and Google ranking have skyrocketed. Since Monday, she has only retweeted a Sports Centre comment about the game, as well as this, on Monday night: " So extremely blessed ... @10AJMcCarron. Congrats to Alabama and making history! #BCSChamps."
Click here to see photos of Katherine Webb.
Webb's cover girl looks prompted ESPN commentator Brent Musburger to provide everyone with an ewwwww moment when he commented: "You see that lovely lady there, she does go to Auburn, but she's also Miss Alabama and that's AJ McCarron's girlfriend. You quarterbacks, you get all the good looking women. What a beautiful woman. Wow. If you're a youngster in Alabama, start getting the football out and throw it around the back yard with pops!"
In turn, Musburger's comment prompted Yahoo! Sports columnist Jeff Passan to tweet: "Sources: A.J. McCarron's girlfriend to seek restraining order from Brent Musburger at halftime."
Webb also made an impression on NFL player Darnell Dockett, who asked Webb out to the Miami nightclub King of Diamonds via Twitter.
"@_KatherineWebb hit me (XXX) XXX-XXXX when game over, lets go to wing stop then King of diamond," tweeted the Arizona Cardinals defensive end. Needless to say, he was horrified to realize he'd tweeted his phone number to his 130,000 followers instead of in a private message as he'd intended. He deleted the tweet, explaining: "(Expletive) that was suppose to be DM!"
And oh, the game? Alabama routed Notre Dame 42-14 for its second consecutive national title and its third in four years.


text:
Each Thanksgiving, we read about new ways to cook the big bird. And we all know what happens. We chicken out.
Each Thanksgiving, we read about new ways to cook the big bird. There are only 1.9 billion Google hits on "How to cook a turkey." That's billion, folks.
And we all know what happens. We chicken out. We return to the same turkey recipe our mother used, and her mother, and her mother's mother. We know that to change, we're asking for a table-side riot.
We stand together in fear. I served a curried turkey. It's amazing watching an 18-pound bird just sitting there, congealing.
Still, we learn we can make changes if they are subtle and not bragged upon beforehand. Still, we know the ultimate reward: "This tastes just like mom's." And mom's mom, and all the way back to the Pilgrims.
Every Thanksgiving spawns a trendy way to cook a turkey. It's what keeps food writers busy, if not our readers. I've tried everything, including nearly cremating the garage, and me, with a deep fryer. So here you go, the five most popular ways (plus a bonus) to cook a turkey. May the turkey gods be with us. We'll need them Nov. 28.
Slow roast the turkey, basting every 25 minutes with butter and drippings until the skin is crackling brown and the meat is bursting with juices. It's simple and direct, no messing around, and by far the most popular method. Follow the label cooking charts to avert disaster (usually an undercooked bird). Fresh turkeys, ordered ahead at the store, are the modern roasting vogue. Just remember: Butterball does not contain butter. The recipes on wrappers always are the basic one. The most basic of the basic birds can be found at www.butterball.com.
Aluminum foil was invented in 1910. Manufacturers still are trying to convince cooks it is a necessity for improving roasted turkey. Line your roasting pan with foil twice the size of the pan. Place bird skin side up. Bring the excess foil together and seal. Poke a few holes in top. This requires removing the foil and upping the heat by 20 degrees to brown the skin, about 15 minutes before it's done. It promises no more basting, and the wet heat inside tenderizes the bird. Big plus: It's almost impossible to overcook. Don't forget the browning. It looks a little sick without it. This is also called steaming the turkey. http://urbanext.illinois.edu/turkey/foil.cfm
A variation is the plastic oven bag developed in the 1980s: www.reynoldskitchens.com.
One of the oldest methods to tenderize a bird is to brine it, meaning soak in salt water. One cup of kosher or sea salt (no iodine) per gallon of water will do it. Pour into a crock or heavy-duty food bag. Add washed and cleaned turkey and refrigerate overnight, turning occasionally. Then rinse the bird again, pat dry and roast via your favorite method.
Citrus marinades are perfect for turkeys, but the easiest marinade is milk or buttermilk. It relaxes the toughest bird. http://www.recipe.com
Dried herbs make a good turkey rub, but don't overdo it. Some herbs such as oregano and basil can overpower the turkey taste. Most rubs contain salt and pepper. Good candidates are savory, nutmeg, sweet paprika and garlic powder. Chili powder will it spice up. http://lookbook.mccormick.com
You'll need one of those massive needle syringes to reach deep into the meat. One-half pound of melted butter mixed with a half can of beer works well with most herbs or pepper sauce such as Tabasco or Sriracha. http://bbq.about.com/od/turkeyinjectionrecipes
You'll need a turkey deep fryer, heat source, an injection marinade and about two gallons of peanut oil for a 15-pound bird. That's at least a $100 investment. What can we say about it: Very expensive, somewhat dangerous, adds fat, tastes exceptional. http://www.foodnetwork.com
Reach Jim at 330-580-8324.
On Twitter: @jhillibishREP


text:
This week the erotic "Fifty Shades of Grey" trilogy reached a huge milestone: It sold more than 100 million copies worldwide. Forty-five million of those books were bought by readers in the U.S.
The 100-million mark puts E.L. James' bestselling series on par with Ian Fleming's James Bond series. But the first Bond book, "Casino Royale," was published more than 50 years ago; "Fifty Shades of Grey" debuted in 2011.
Originally self-published, "Fifty Shades of Grey" gained even wider reach after being picked up by Vintage, an imprint of Random House, in 2012.
In a release, Vintage notes that two copies of the trilogy sold every...


text: Handling Specialty was approached by the technical director of the Pacific Repertory Theater in Carmel, CA, to engineer and manufacture a rotating circular stage (double revolving stage) that included both an inner and an outer ring. Both rings rotate clockwise and counter-clockwise, and can move together or separately, to meet show cues. The rings are also capable of stopping and reversing motion independently of each other, with minimal acceleration and deceleration time.


text:
Santosh D'Mello, PhD
B.S., University of Bombay
M.S., University of Bombay
Ph.D., University of Pittsburgh
Postdoctoral Training, Boston University Medical School
Postdoctoral Training, Institute of Neurobiology, Rome
Research in the lab is centered on understanding the molecular mechanisms regulating neurodegeneration. Specifically, primary cultures of neurons, transgenic and knockout mice, and animal models of neurological disease are used to study genes, proteins, and signal transduction pathways regulating neuronal cell death. We are also interested in identifying chemical compounds that protect the brain from neurodegeneration. The long-term objective of the laboratory's research is to develop strategies to prevent, treat, or cure degenerative diseases of the brain. Recently, we have expanded our interests to investigate neurodevelopmental disorders also.
Research interests
Our ongoing research on neurodegeneration and neurodevelopmental disorders is described below.
Neurodegenerative disorders
Neurodegenerative diseases such as AD, PD and HD are progressive and fatal disorders affect millions of individuals in the U.S. alone costing the economy over $100 billion annually. While there are drugs that can reduce the symptoms associated with some of these diseases (for example, Parkinson's disease), these do not slow down the relentless loss of neurons and therefore the disease progresses. Our lab is interested in understanding the molecular mechanisms underlying neurodegeneration. We hope that our efforts will lead to the identification of molecules that are important in the control of neuronal survival and death and whose altered function contributes to neurodegenerative disorders. Such molecules can then be targeted in the development of effective therapeutic strategies for these disorders. Much of our focus has been on histone deacetylases (HDACs) a family of 18 proteins initially identified based on their ability to repress gene expression through the deacetylation of histones, but which are now known to have a variety of other functions mediated through the deacteylation of non-histone proteins residing in the nucleus, cytoplasm or mitochondria. Chemical inhibitors of HDACs protect neurons from death in animal models of neurodegenerative diseases. Because the chemical inhibitors used so far inhibit all HDAC proteins, however, the identity of the specific HDAC(s) responsible for promoting neurodegeneration has remained unclear. We recently discovered that activation of HDAC3 has a neurotoxic effect and hence this protein is the likely target of the HDAC inhibitors in their neuroprotective effect. In ongoing studies funded by the NIH, we are investigating the role of HDAC3 in the pathogenesis of Huntington's disease. Surprisingly, while HDAC3 can be neurotoxic, we have found that some of the other HDAC proteins, including HDAC4, HDAC7, and HDAC9, promote the survival of neurons and protect them form degenerative stimuli.
Another protein of interest to the lab is FoxG1, a transcription factor that is critical for proper brain development where it controls the production of neurons by regulating proliferation of neural progenitor cells. Mice that lack FoxG1 have a severely underdeveloped brain and die early during gestation. But FoxG1 is highly expressed in the adult brain where its function had not been studied. We recently found that FoxG1 maintains the survival of mature neurons. We have been investigating the molecular mechanism through which the activity of FoxG1 is regulated and the mechanism by which FoxG1 affects other molecules to maintain the survival of neurons. As part of an NIH-funded project, we are currently generating transgenic mice that express elevated levels of FoxG1. These mice will be used to test whether elevated FoxG1 can protect mice against neurodegenerative diseases such as Huntington's disease. Among other proteins that are being currently studied in the lab are the transcription factors c-Fos, FoxP1, HSF1 and Jaz, the chaperone protein DNAJB6, and a protein that resides in the nucleolus called nucleophosmin-1.
In addition to understanding the molecular biology of neurodegeneration the lab has been identifying chemical compounds that protect neurons from death. This drug discovery effort has led to the identification of several indolone and benzoxazine compounds that are highly protective in cell culture models and animal models of neurodegenerative diseases. Exactly how these neuroprotective compounds act is an area of interest. Some of the benzoxazine compounds have been licensed to EnCephRx, a biotechnology company dedicated to finding a treatment for Huntington's disease.
Neurodevelopmental disorders
Several years ago we reported the identification of a novel rat mutant that displayed abnormal brain development. This mutant, which we called Flathead, was microcephalic (small brain), suffered severe seizures, and had progressive ataxia and paralysis of the hindlimbs. We found that the neurological abnormalities in Flathead were caused by the death of late developing neural progenitor cells which resulted from a defect in cytokinesis. We discovered that the mutation in Flathead is in the gene encoding a protein called citron kinase which regulates cyokinesis.
Recently, we have been interested in MeCP2, a gene that can repress gene transcription globally as well as locally. Mutations in the MeCP2 gene cause Rett syndrome, a neurodevelopmental disorder characterized by normal early growth and development followed by a slowing of development, loss of purposeful use of the hands, distinctive hand movements, slowed brain and head growth, problems with walking, seizures, and intellectual disability. While reduced MeCP2 activity causes Rett syndrome, elevated activity of this protein as a result of duplication or triplication of the MeCP2 gene causes a disorder called MeCP2 duplication syndrome. Patients with this disorder are born normal but then display progressive mental retardation, spasticity, epilepsy, and die at adulthood. We are studying MeCP2 duplication syndrome using transgenic mice that make 3-4 times more MeCP2 than normal. Like patients, these mice display neurological deficiencies and die early in adulthood. We find that MeCP2 transgenic mice display neuronal loss in certain brain regions just before they die. We are characterizing other abnormalities in the MeCP2 transgenic brain with the goal of getting a better understanding of why human patients with MeCP2 duplication syndrome suffer the neurological phenotype that they do. A recent discovery that we have made is that astrocytes within certain brain regions of the MeCP2 transgenic mice have high levels of a protein called GFAP. Interestingly, increased GFAP production is the primary cause of another neurological brain disorder called Alexander disease, which is characterized by spasticity, mental retardation, and seizures. We are exploring whether MeCP2 duplication syndrome and Alexander disease share mechanistic commonalities.
Recent publications (Last 5 years only)
Chen H-M, Wang L, D'Mello SR. (2008) Inhibition of ATF-3 expression by B-Raf mediates the neuroprotective action of GW5074.J. Neurochem. 105:1300-1132
Zhang X, Jaramillo E, Wang L, D'Mello SR. (2008) Histone deacetylase-related protein inhibits AES-mediated neuronal cell death by direct interaction J. Neurosci. Res. 86:2423-2431. (Cover article)
Majdzadeh N, Morrison BE, Wang L, D'Mello SR. (2008) HDAC4 inhibits cell cycle progression and protects neurons from cell death. Dev. Neurobiol. 68:1076-1092
Morrison BE and D'Mello SR. (2008) Polydactyly in mice lacking HDAC9/HDRP. Experimental Biology and Medicine 233:980-988.
Chen HM, Wang L, D'Mello SR. (2008) A chemical compound commonly used to inhibit PKR, {8-(imidazol-4-ylmethylene)-6H-azolidino[5,4-g] benzothiazol-7-one}, protects neurons by inhibiting cyclin-dependent kinase. Eur J Neurosci. 28:2003-2016.
Balderamos M, Ankati H, Akubathini SK, Patel AV, Kamila S, Mukherjee C, Wang L, Biehl ER, D'Mello SR. (2008) Synthesis and Structure-Activity Relationship Studies of 3-Substituted Indolin-2-ones as Effective Neuroprotective Agents. Exp Biol Med 233:1395-1402.
Pfister JA, Ma C, Morrison BE, D'Mello SR. (2008) Opposing effects of sirtuins on neuronal survival: SIRT1-mediated neuroprotection is independent of its deacetylase activity. PLos One 3(12):e4090.
Ankanti H, Akubathini SK, Kamila S, Mukherjee C, D'Mello SR, Biehl ER (2008). Synthesis of 3-benzylidene, 5-substituted 3-bennzylidene, 3-hetarylmethylene and 5-substituted hetarylmethylene derivatives of indolin-2-ones. Organic Chemistry Journal 2: 138-147.
Wang L, Ankati H, Akubathini S, Balderamos M, Storey C, Patel AV, Kretzschmar D, Biehl ER, D'Mello SR. (2010) 1, 4- benzoxazine compounds as novel neuroprotective agents. J. Neurosci. Res. 88: 1970-1984.
Ankanti H, Akubathini SK, D'Mello SR., Biehl ER (2010) Synthesis of 2-Benzylidene and 2-Hetarylmethyl Derivatives of 2H-1,4-Benzoxazin-3-(4H)-ones as Neuroprotective Agents" Synth. Communications 40: 2364–2376
Zhao K, Ippolito G, Wang L, Price V, Kim MH, Cornwell G, Fulenchek S, Breen GA, Goux WJ, D'Mello SR. (2010) Neuron-selective toxicity of tau peptide in a cell culture model of neurodegenerative tauopathy: essential role for aggregation in neurotoxicity. J Neurosci Res. 88:3399-3413.
Chen HL, D'Mello SR. (2010) Induction of neuronal cell death by paraneoplastic Ma1 antigen. J Neurosci Res. 88:3508-3519.
Dastidar SG, Landrieu PM, D'Mello SR. (2011) FoxG1 Promotes the Survival of Postmitotic Neurons. J Neurosci. 31:402-413.
Ma C, D'Mello SR. (2011) Neuroprotection by histone deacetylase-7 (HDAC7) occurs by inhibition of c-jun expression through a deacetylase-independent mechanism. J. Biol. Chem. 286:4819-4828.
Bardai FH, D'Mello SR. (2011) Selective toxicity by HDAC3 in neurons: Regulation by Akt and GSK3b. J. Neurosci. 31:1746-51. (In the list of 50 most downloaded Journal of Neuroscience papers, March 2011)
Garcia-Oscos F, Salgado H, Hall S, Thomas F, Farmer GE, Bermeo J, Galindo LC, Ramirez RD, D'Mello S, Rose-John S, Atzori M. (2011) The stress-induced cytokine interleukin-6 decreases the inhibition/excitation ratio in the rat temporal cortex via trans-signaling. Biol Psychiatry. 71:574-582.
Ghosh Dastidar S, Bardai F, Ma C, Price V, Rawat V, Verma P, Narayanan V, D'Mello SR. (2012) Isoform-specific toxicity of Mecp2 in postmitotic neurons: Suppression of neurotoxicity by FoxG1. J. Neurosci. 32:2846-2855.
Ghosh Dastidar S, Narayanan S, Stifani S, D'Mello SR. (2012) Transducin-like enhancer of Split-1 (TLE1) combines with Forkhead box protein G1 (FoxG1) to promote neuronal survival. J Biol Chem. 287:14749-14759.
Bardai FH, Price V, Zaayman M, Wang L, D'Mello SR. (2012) Histone deacetylase (HDAC1) is a molecular switch between neuronal survival and death. J Biol Chem. 287:35444-35453. (Paper of the week - Oct 12, 2012); Best neuroscience paper in 2012)
Price V, Wang L, D'Mello SR (2013). Conditional deletion of HDAC4 in the CNS has no major effect on brain architecture or neuronal viability. J. Neurosci. Res. 91:407-15.
Bardai FH, Verma P, Smith C, Rawat V, Wang L, D'Mello SR. Disassociation of HDAC3 from normal huntingtin underlies mutant huntingtin neurotoxicity. J. Neurosci. (in press).
- Updated: February 6, 2006


text:
October 23, 2012
Why do so many lawyers dislike networking events? Usually it comes down to these three dreaded moments: walking up to a stranger, explaining what you do while you introduce yourself, and then forcing yourself to make small talk. However, if you can master these three key moments, you can make networking events much more productive—and a productive networking event is one that leads to referrals.
Moment Number One: Hello, Stranger
Whether it is an alumni association gathering or an event specifically geared to making business contacts, networking events have a way of reminding us of all the most socially awkward moments of our lives. We stand against the wall trying not to appear inept while looking sheepishly for someone we know, or someone to wave us over to their group.
But there is an important distinction between a networking event and that awkward first high school dance—everybody is at the networking event, whether reluctantly or not, to advance a business development agenda. Whether it's an agenda to directly get new clients or to more indirectly make contacts that could lead to clients, everyone at the event represents an opportunity for everyone else there. So, fundamentally, everyone there is looking to meet you because to them you represent the same potential opportunity that they represent to you. Given that, you truly have nothing to be anxious about, so put a drink in your hand, turn to the person standing closest to you and just say hello! Frankly, it is amazing how open everyone is to meeting others at a networking event.
Moment Number Two: Make Your Introduction Memorable to the Listener
When it comes to introducing ourselves, it's important to remember that we typically network with different constituencies and we should vary our introductions based on the given constituencies at the event. For example, you would introduce yourself differently if you were meeting a new person in your firm versus if you were meeting another lawyer outside your firm versus if you were meeting a prospective client and so on.
Of course, you should always clearly state your name, say where you work and briefly explain what you do. The key to successful introductions, though, is to say what you do in a way that's both understandable and memorable to the particular listener. For example, saying that you practice complex civil litigation is straightforward enough to another lawyer, but it's not necessarily understandable or memorable to a "civilian" who might very well be a potential client.
So how do you make it memorable? When you tell people what you do, you should also tell them how you saved the day, solved the problem or served the client so that they have examples they can relate to and understand. For example, if you're a civil litigator being introduced to a nonlawyer, you might introduce yourself this way:
"I'm a civil litigator who helps companies get what they deserve in legal disputes. For example, I just helped a small manufacturing company in Des Moines collect $250,000 from one of the big three automakers for a contract dispute."
This introduction describes the practice area in basic terms and provides a concrete example that enables a real understanding of how you might be helpful to the person you are meeting.
Similarly, when being introduced to another lawyer, you want to give that lawyer a good sense of what makes you different and why he or she might refer a client to you. You need to be succinct but specific—for example:
"I'm a civil litigator and I specialize in defending insurance companies in property and casualty matters."
Of course, there are those who believe it's best to introduce themselves as generalists because it doesn't exclude any opportunities. However, here is a caution to heed: That strategy might impress the most naïve of potential clients, but most people would no more engage a lawyer who says she is the best "at everything" than they would ask a generalist doctor to perform knee surgery.
What if you work in a firm that truly can provide a wide range of specialized legal services? In this case, you want to introduce the firm as broadly as possible to potentially originate cases outside your specialty for other departments, while at the same time highlighting your own expertise. For example, you might say this:
"I'm a lawyer with Smith and Jones. I specialize in trust and estates law, but my firm has specialized capability in all areas of the law, from patents to matrimonial law and everything in between. As a trust and estates lawyer, I just helped an Internet entrepreneur set up a trust structure so that he can pass his estate to his children tax free, regardless of what they end up doing in Washington."
Moment Number Three: Go Deep, Not Wide When Making Small Talk
I like to think of the act of making conversation as more than simply talking. Rather, it is, or should be, an act of teaching and learning. When we're networking, we want to teach other people about us, what we're competent at and what our personal character is like, and we want to learn these same things about the people we meet. Remember, ultimately you are looking to build a network of allies with whom you can share opportunities, so you are looking for a network of people who are both competent and have character so you can trust them—and these are the very same characteristics other people are looking for in you.
To accomplish this, you need to "go deep," not "wide," when making conversation at networking events. In other words, spend the time needed to really learn about people and to teach people about you. Show them that you are as good of a listener (learning) as you are a talker (teaching), that you are not dominating the conversation, and that you are well mannered and professional to a T. They will quickly see you want to build meaningful relationships, not simply a network of nodding acquaintances.
You will certainly meet people who are "takers," but you will also meet those willing to be "investors" in relationships—people who understand that every referral given is a reflection of the person giving the referral and that referrals should never be given casually. The individuals referring you must trust the good job you will do for their contacts, and gaining that trust requires that you invest time and effort in building the relationship—an investment that only starts at the networking event.
That's why you will need to follow up with the people you believe may be valuable to you within a reasonable time after the event. Send them a personal note with a copy of an interesting article that might tie to the conversation you had. Invite them to lunch, coffee or another event. Keep working to build a meaningful, trusting relationship with them.
etworking events can be a great way to meet referral sources as well as prospective clients, but it's rarely as simple as just showing up and pressing a business card into someone's hand. Mastering some simple relationship-building skills, however, will serve you well at events and make your business development efforts far more productive.
About the Author
Steven J. Shaer is a principal of Shaer Associates, a management consulting and training firm that specializes in teaching clients how to build referral business.


text:
In other words, is Y up, or is Z up? It's a loaded question. My little lesson (YouTube) from the course is here, in case you don't know the issue. What's more entertaining, and the point of this post, are the answers I got back from the people I asked. I've asked this question before in this blog.
Speaking of cameras, is there nothing that three.js cannot do? Check out this incredible piece of wonderfulness and have a webcam ready. Or go right to the demo, and then the other demo. It's one of those "of course we should be able to do that" kinds of things, but to have it just one mouse click away (assuming you're set up to run WebGL; if not, go here).


text:
$750,000 United Way Advance Helps Homeless Agencies
At least a half dozen homeless agencies in Central Florida will keep providing services this summer- thanks to a funding advance by the Heart of Florida United Way. The agencies were supposed to receive federal grant money that hasn't come through yet.
[U.S. Housing and Urban Development logo]
One of the programs run by the Rescue Outreach Mission of Central Florida is transitional housing. It's specifically for families that are on a path to self-sufficiency. The agency was approved to receive a U-S Department of Housing and Urban Development grant to support the program, but the money is delayed by several months. Executive Director Andrew Powell said that put 17 families with a total of 30 children at risk. "It was a major concern for us, the cost impact is somewhere between 16-18 thousand dollars per month," he said.
The short fall is now being offset by the Heart of Florida United Way, which is giving 15 area agencies an advance on funding it would normally have given them in the next 6 months. The advance area-wide totals 750-thousand dollars. United Way CEO Bob Brown said it's a really bad time for the HUD grant hold up because people are still struggling- despite the improving economy. Last year the United Way received 165-thousand calls for help.
"We're almost on the same plane this year, people who don't know what to do, 50-percent of them are unemployed, so the homeless service providers are running at full in almost all cases," he said.
HUD said administrative changes are behind the funding delays, but it expects to pay the grant money within the next few weeks.