Car chemistry insert

Car chemistry insert DEFAULT

Four Success Stories in Gene Therapy

After numerous setbacks at the turn of the century, gene therapy is treating diseases ranging from neuromuscular disorders to cancer to blindness. The success is often qualified, however. Some of these therapies have proved effective at alleviating disease but come with a high price tag and other accessibility issues: Even when people know that a protocol exists for their disease and even if they can afford it or have an insurance company that will cover the cost—which can range from $400,000 to $2 million—they may not be able to travel to the few academic centers that offer it. Other therapies alleviate symptoms but don’t eliminate the underlying cause.

“Completely curing patients is obviously going to be a huge success, but it’s not [yet] an achievable aim in a lot of situations,” says Julie Crudele, a neurologist and gene therapy researcher at the University of Washington. Still, even limited advances pave the way for ongoing progress, she adds, pointing to research in her patients who have Duchenne muscular dystrophy: “In most of these clinical trials, we learn important things.”

Thanks to that new knowledge and steadfast investigations, gene therapy researchers can now point to a growing list of successful gene therapies. Here are four of the most promising.

Gene Swaps to Prevent Vision Loss

Some babies are born with severe vision loss caused by retinal diseases that once led inevitably to total blindness. Today some of them can benefit from a gene therapy created by wife-and-husband team Jean Bennett and Albert Maguire, who are now ophthalmologists at the University of Pennsylvania.

When the pair first began researching retinal disease in 1991, none of the genes now known to cause vision loss and blindness had been identified. In 1993 researchers identified one potential target gene, RPE65. Seven years later Bennett and Maguire tested a therapy targeting that gene in three dogs with severe vision loss—it restored vision for all three.

In humans, the inherited condition that best corresponds with the dogs’ vision loss is Leber congenital amaurosis (LCA). LCA prevents the retina, a layer of light-sensitive cells at the back of the eye, from properly reacting or sending signals to the brain when a photon strikes it. The condition can cause uncontrolled shaking of the eye (nystagmus), prevents pupils from responding to light and typically results in total blindness by age 40. Researchers have linked the disease to mutations or deletions in any one of 27 genes associated with retinal development and function. Until gene therapy, there was no cure.

Mutations in RPE65 are just one cause of inherited retinal dystrophy, but it was a cause that Bennett and Maguire could act on. The researchers used a harmless adeno-associated virus (AAV), which they programmed to find retinal cells and insert a healthy version of the gene, and injected it into a patient’s eye directly underneath the retina. In 2017, after a series of clinical trials, the Food and Drug Administration approved voretigene neparvovecrzyl (marketed as Luxturna) for the treatment of any heritable retinal dystrophy caused by the mutated RPE65 gene, including LCA type 2 and retinitis pigmentosa, another congenital eye disease that affects photoreceptors in the retina. Luxturna was the first FDA-approved in vivo gene therapy, which is delivered to target cells inside the body (previously approved ex vivo therapies deliver the genetic material to target cells in samples collected from the body, which are then reinjected).

Spark Therapeutics, the company that makes Luxturna, estimates that about 6,000 people worldwide and between 1,000 and 2,000 in the U.S. may be eligible for its treatment—few enough that Luxturna was granted “orphan drug” status, a designation that the FDA uses to incentivize development of treatments for rare diseases. That wasn’t enough to bring the cost down. The therapy is priced at about $425,000 per injection, or nearly $1 million for both eyes. Despite the cost, Maguire says, “I have not yet seen anybody in the U.S. who hasn’t gotten access based on inability to pay.”

Those treated show significant improvement: Patients who were once unable to see clearly had their vision restored, often very quickly. Some reported that, after the injections, they could see stars for the first time.

While it is unclear how long the effects will last, follow-up data published in 2017 showed that all 20 patients treated with Luxturna in a phase 3 trial had retained their improved vision three years later. Bennett says five-year follow-up with 29 patients, which is currently undergoing peer review, showed similarly successful results. “These people can now do things they never could have dreamed of doing, and they’re more independent and enjoying life.”

Training the Immune System to Fight Cancer

Gene therapy has made inroads against cancer, too. An approach known as chimeric antigen receptor (CAR) T cell therapy works by programming a patient’s immune cells to recognize and target cells with cancerous mutations. Steven Rosenberg, chief of surgery at the National Cancer Institute, helped to develop the therapy and published the first successful results in a 2010 study for the treatment of lymphoma.

“That patient had massive amounts of disease in his chest and his belly, and he underwent a complete regression,” Rosenberg says—a regression that has now lasted 11 years and counting.

CAR T cell therapy takes advantage of white blood cells, called T cells, that serve as the first line of defense against pathogens. The approach uses a patient’s own T cells, which are removed and genetically altered so they can build receptors specific to cancer cells. Once infused back into the patient, the modified T cells, which now have the ability to recognize and attack cancerous cells, reproduce and remain on alert for future encounters.

In 2016 researchers at the University of Pennsylvania reported results from a CAR T cell treatment, called tisagenlecleucel, for acute lymphoblastic leukemia (ALL), one of the most common childhood cancers. In patients with ALL, mutations in the DNA of bone marrow cells cause them to produce massive quantities of lymphoblasts, or undeveloped white blood cells, which accumulate in the bloodstream. The disease progresses rapidly: adults face a low likelihood of cure, and fewer than half survive more than five years after diagnosis.

When directed against ALL, CAR T cells are ruthlessly efficient—a single modified T cell can kill as many as 100,000 lymphoblasts. In the University of Pennsylvania study, 29 out of 52 ALL patients treated with tisagenlecleucel went into sustained remission. Based on that study’s results, the FDA approved the therapy (produced by Novartis as Kymriah) for treating ALL, and the following year the agency approved it for use against diffuse large B cell lymphoma. The one-time procedure costs upward of $475,000.

CAR T cell therapy is not without risk. It can cause severe side effects, including cytokine release syndrome (CRS), a dangerous inflammatory response that ranges from mild flulike symptoms in less severe cases to multiorgan failure and even death. CRS isn’t specific to CAR T therapy: Researchers first observed it in the 1990s as a side effect of antibody therapies used in organ transplants. Today, with a combination of newer drugs and vigilance, doctors better understand how far they can push treatment without triggering CRS. Rosenberg says that “we know how to deal with side effects as soon as they occur, and serious illness and death from cytokine release syndrome have dropped drastically from the earliest days.”

Through 2020, the remission rate among ALL patients treated with Kymriah was about 85 percent. More than half had no relapses after a year. Novartis plans to track outcomes of all patients who received the therapy for 15 years to better understand how long it remains effective.

Precision Editing for Blood Disorders

One new arrival to the gene therapy scene is being watched particularly closely: in vivo gene editing using a system called CRISPR, which has become one of the most promising gene therapies since Jennifer Doudna and Emmanuelle Charpentier discovered it in 2012—a feat for which they shared the 2020 Nobel Prize in Chemistry. The first results from a small clinical trial aimed at treating sickle cell disease and a closely related disorder, called beta thalassemia, were published this past June.

Sickle cell disease affects millions of people worldwide and causes the production of crescent-shaped red blood cells that are stickier and more rigid than healthy cells, which can lead to anemia and life-threatening health crises. Beta thalassemia, which affects millions more, occurs when a different mutation causes someone’s body to produce less hemoglobin, the iron-rich protein that allows red blood cells to carry oxygen. Bone marrow transplants may offer a cure for those who can find matching donors, but otherwise treatments for both consist primarily of blood transfusions and medications to treat associated complications.

Both sickle cell disease and beta thalassemia are caused by heritable, single-gene mutations, making them good candidates for gene-editing therapy. The method, CRISPR-Cas9, uses DNA sequences from bacteria (clustered regularly interspaced short palindromic repeats, or CRISPR) and a CRISPR-associated enzyme (Cas for short) to edit the patient’s genome. The CRISPR sequences are transcribed onto RNA that locates and identifies DNA sequences to blame for a particular condition. When packaged together with Cas9, transcribed RNA locates the target sequence, and Cas9 snips it out of the DNA, thereby repairing or deactivating the problematic gene.

At a conference this past June, Vertex Pharmaceuticals and CRISPR Therapeutics announced unpublished results from a clinical trial of beta thalassemia and sickle cell patients treated with CTX001, a CRISPR-Cas9-based therapy. In both cases, the therapy does not shut off a target gene but instead delivers a gene that boosts production of healthy fetal hemoglobin—a gene normally turned off shortly after birth. Fifteen people with beta thalassemia were treated with CTX001; after three months or more, all 15 showed rapidly improved hemoglobin levels and no longer required blood transfusions. Seven people with severe sickle cell disease received the same treatment, all of whom showed increased levels of hemoglobin and reported at least three months without severe pain. More than a year later those improvements persisted in five subjects with beta thalassemia and two with sickle cell. The trial is ongoing, and patients are still being enrolled. A Vertex spokesperson says it hopes to enroll 45 patients in all and file for U.S. approval as early as 2022.

Derailing a Potentially Lethal Illness

Spinal muscular atrophy (SMA) is a neurodegenerative disease in which motor neurons—the nerves that control muscle movement and that connect the spinal cord to muscles and organs—degrade, malfunction and die. It is typically diagnosed in infants and toddlers. The underlying cause is a genetic mutation that inhibits production of a protein involved in building and maintaining those motor neurons.

The four types of SMA are ranked by severity and related to how much motor neuron protein a person’s cells can still produce. In the most severe or type I cases, even the most basic functions, such as breathing, sitting and swallowing, prove extremely challenging. Infants diagnosed with type I SMA have historically had a 90 percent mortality rate by one year.

Adrian Krainer, a biochemist at Cold Spring Harbor Laboratory, first grew interested in SMA when he attended a National Institutes of Health workshop in 1999. At the time, Krainer was investigating how RNA mutations cause cancer and genetic diseases when they disrupt a process called splicing, and researchers suspected that a defect in the process might be at the root of SMA. When RNA is transcribed from the DNA template, it needs to be edited or “spliced” into messenger RNA (mRNA) before it can guide protein production. During that editing process, some sequences are cut out (introns), and those that remain (exons) are strung together.

Krainer realized that there were similarities between the defects associated with SMA and one of the mechanisms he had been studying—namely, a mistake that occurs when an important exon is inadvertently lost during RNA splicing. People with SMA were missing one of these crucial gene sequences, called SMN1.

“If we could figure out why this exon was being skipped and if we could find a solution for that, then presumably this could help all the [SMA] patients,” Krainer says. The solution he and his colleagues hit on, antisense therapy, employs single strands of synthetic nucleotides to deliver genetic instructions directly to cells in the body [see “The Gene Fix”]. In SMA’s case, the instructions induce a different motor neuron gene, SMN2, which normally produces small amounts of the missing motor neuron protein, to produce much more of it and effectively fill in for SMN1. The first clinical trial to test the approach began in 2010, and by 2016 the FDA approved nusinersen (marketed as Spinraza). Because the therapy does not incorporate itself into the genome, it must be administered every four months to maintain protein production. And it is staggeringly expensive: a single Spinraza treatment costs as much as $750,000 in the first year and $375,000 annually thereafter.

Since 2016, more than 10,000 people have been treated with it worldwide. Although Spinraza can’t restore completely normal motor function (a single motor neuron gene just can’t produce enough protein for that), it can help children with any of the four types of SMA live longer and more active lives. In many cases, Spinraza has improved patients’ motor function, allowing even those with more severe cases to breathe, swallow and sit upright on their own. “The most striking results are in patients who are being treated very shortly after birth, when they have a genetic diagnosis through newborn screening,” Krainer says. “Then, you can actually prevent the onset of the disease—for several years and hopefully forever.”

This article is part of “Innovations In: Gene Therapy,” an editorially independent special report that was produced with financial support from Pfizer.

Sours: https://www.scientificamerican.com/article/four-success-stories-in-gene-therapy/
Anyone played with Car Chemistry Header Inserts????#758530
07/26/1003:38 PM07/26/1003:38 PM
Joined: Jan 2003
Posts: 430
Saint John

C

CanuckOfflineOP
super gas
 OfflineOP
super gas

C


Joined: Jan 2003
Posts: 430
Saint John

Looking for an easy way to quiet the race car down in the driveway so I don't get thrown out of my subdivision when i want to set the timing. These look to be a cost effective way of doing it. Just wondering if anyone around Moparts has actually tried them


http://www.jegs.com/i/Car+Chemistry/176/3DI35L/10002/-1


Re: Anyone played with Car Chemistry Header Inserts???? [Re: Canuck] #758531
07/26/1003:56 PM07/26/1003:56 PM
Joined: Oct 2003
Posts: 7,506
Az
CrizilaOffline
master
 Offline
master

Joined: Oct 2003
Posts: 7,506
Az

I tried them and didn't have much luck - still loud. Put the washers in and that helped a little - still too loud. Also tried the perferated cones. Also didn't help much. I have had the best luck with a pair of Summit race mufflers #638230 - under $30 each. Short piece of 3" pipe clamped to my headers ( stainless exhaust clamp ), those muffs, and down spouts dumping in front of the axle and angled towards the center of the car. Quiet enough not to PO the neighbors too much and easy to remove for the track. I also use them for any T&T on the street that I might do.



Fastest 300

Re: Anyone played with Car Chemistry Header Inserts???? [Re: fbernard] #758533
07/27/1007:14 AM07/27/1007:14 AM
Joined: Jan 2003
Posts: 430
Saint John

C

CanuckOfflineOP
super gas
 OfflineOP
super gas

C


Joined: Jan 2003
Posts: 430
Saint John

Thanks Guys, I might head to Carquest and see if they have anything similar....or call Summit

You saved me $100.00 today


Re: Anyone played with Car Chemistry Header Inserts???? [Re: Canuck] #758534
07/27/1012:22 PM07/27/1012:22 PM
Joined: Aug 2009
Posts: 456
corpus christi tex

C

CheathamOffline
mopar
 Offline
mopar

C


Joined: Aug 2009
Posts: 456
corpus christi tex

i bought the collector inserts (bolt on) they were quieter at an idle compared to open headers but were just as loud driving, i took them off and went with a flow master mufflers 2 chmber


Re: Anyone played with Car Chemistry Header Inserts???? [Re: Cheatham] #758535
07/28/1008:43 AM07/28/1008:43 AM
Joined: Jan 2003
Posts: 4,448
Phoenix, AZ

M

MoparBillyOffline
master
 Offline
master

M


Joined: Jan 2003
Posts: 4,448
Phoenix, AZ

Stay away from those, waste of money! Unless you are looking for a way to slow the car down by a tenth or 2.

Tommy Johnsons motorsports warehouse sells some collector insert mufflers that basically look like a mini glass pack...they are more effective at sound cancellation, and slow you down less. But in the end, a good race muffler is usually cheaper and more effective.


6109479-IMAGE0006.JPG(190 downloads)


"Livin' in a powder keg and givin' off sparks" 4 Street cars, 5 Race engines

Re: Anyone played with Car Chemistry Header Inserts???? [Re: MoparBilly] #758536
07/28/1003:51 PM07/28/1003:51 PM
Joined: Jan 2003
Posts: 1,311
Johnstown
69dartOffline
pro stock
 Offline
pro stock

Joined: Jan 2003
Posts: 1,311
Johnstown

I agree they are terrible. I tried them years ago and they added so much back pressure it blew the dipstick out and oil went everywhere. O and slowed the car about 3 tenths.

The dynatech splitfow mufflers are very good. I saw no ET loss with them. The only problem I had with them was it was difficult to hear my car start in the lanes with all the open header cars...lol.



33 Plymouth Roadster - 383 - 5.90 1/8th 9.58 1/4
68 Dart 340


Moderated by  Al_Alguire, Hotwheelsjr, McLovin, moparts, not_a_charger, tboomer 


Sours: https://board.moparts.org/ubbthreads/ubbthreads.php/topics/758530/anyone-played-with-car-chemistry-header-inserts.html
  1. Complete home candles reviews
  2. 2014 pistons
  3. Fashion week gucci
  4. Shippo webhooks
  5. Vitamix legacy

How To Winterize A Pool

Unless you live in a region where it’s sunny and warm all year round, there will come a day when it’s time to close up the pool for the season. To ensure that your pool is secure in the off-season, you must know how to winterize your pool properly. Just as your home needs to be winterized, it’s important to know the proper steps to winterizing your full property correctly.

Compare Quotes From Top-rated Local Pool Contractors

Select a State To Get Started With Your No Commitment, Free Estimate

Get Free Estimates

When To Winterize A Pool

It’s important to have a plan in place for how to close a pool as early as the beginning of pool season. You want to get the most use of your pool during the hot weather, of course, but you also want to leave ample time for the winterizing process so that you can reopen the pool next season with little hassle.

If you plan to close up your pool after the summer on your own, then you can allow the weather, and your own schedule, to dictate when to complete the work. Typically, the end of pool season comes when the outside temperature consistently falls below 65 degrees Fahrenheit. If you are hiring a pool professional to do the work, be sure to book the appointment sooner rather than later.

The beginning and end of each pool season are typically very busy times of year for technicians in the pool industry, and you don’t want the health of your pool to suffer if you are unable to hire an available pool professional to close your pool until the fall is underway.

Tools

Materials

  • Additives/chemicals needed to stabilize the water’s chemistry, depending on the type of pool you have

Instructions

1. Remove All Pool Accessories From the Water

After you have taken your final swim for the season, it’s time to deflate that swan float, remove the ladder (if you are winterizing an above-ground pool) and take away any other objects that are on or near the surface of your pool. Hose everything off to get rid of dirt, algae or other residue, then let it all dry in the sun. Store them in a garage, shed or pool house until they are needed again next season. Now is also the time to capitalize on any end-of-season sales so that you can stock up on fun pool toys and accessories for next season.

2. Give the Pool a Deep Clean

This step is easier if you’d kept on top of skimming the surface and vacuuming the bottom of your pool throughout the season. However, now is your chance to give it a deep clean. Skim the surface well and give the pool’s bottom a thorough vacuuming so that every last blade of grass and leaf are removed for the winter.

If you see dirt stains on the sides of the pool or the bottom, use a chlorine-based cleaner and a scrub brush to gently remove it from the pool liner or the tiles. If you have concrete in your pool that needs to be cleaned, use a pumice stone to remove any remaining dirt.

3. Balance the Chemistry of the Water

Ideally, you want the alkalinity to be between 80 and 150ppm with a pH level between 7.2 and 7.6. Calcium hardness should be in the range of 175 to 225ppm. If you use chlorine to sanitize your pool, that level should be between 1ppm and 3ppm.

Call a professional as soon as possible if you have any difficulty adjusting the chemistry of your pool. Pool water that does not have the proper chemistry balance is not ready for swimming, and it could turn into a bigger problem next season if left unchecked.

4. Reduce the Water Level

The amount of water that remains in the pool during the off-season depends on the type of cover you’re using. If you use a solid cover, the water should be six inches below it. If you use a mesh cover, the water should be about a foot below. Allow at least a day or two for draining of your pool to the appropriate water level.

5. Drain the Equipment

If water freezes in any of the equipment used to clean and sanitize your pool, it will cause a headache—possibly an expensive one—at the start of next season. Use a blower to dry out the pool lines and then insert expansion plugs to avoid breakage when the temperature drops during the winter. Empty the water pump and heater and remove the filter for cleaning. Examine all of these components to see if there is any maintenance or replacement that is required and make plans to get it done during the office season. If possible, bring the filter and pump indoors where it’s warmer for the off-season. Add antifreeze to the water if you live in a region where the water could freeze.

6. Give It a Dose of Shock and Algaecide

Your pool water is a breeding ground for bacteria and algae if it goes untreated at any time, but particularly in the winter. You’ll need a few days for this step, so get your last swim in before you start. Be sure to follow all manufacturer guidelines for the chemicals you use, including whether or not you should use additives at the same time. If the algae in your pool have grown to where the algaecide isn’t getting rid of it, call in a pool cleaning company to get it taken care of immediately.

Otherwise, the problem will only be compounded when you go to open the pool next season.

7. Install the Pool Cover

The final step to closing up your pool is to install a snug-fitting cover that will protect your investment from autumn leaves, winter snowfall and other off-season elements. If you need to purchase a new cover, make sure you measure your pool carefully so that you choose the right size.

While the installation of your pool cover will depend on whether you have an above-ground or in-ground pool, you must ensure that it is secured well with cover clips. In a milder climate, you might be able to make cover adjustments as needed during the offseason, but if you live where snow is the other covering on your pool, it will be difficult to fix during the winter.

When to Call a Pro

Your pool is a major investment for your home, and it is one that will require ongoing maintenance so you can enjoy it for years to come. While winterizing a swimming pool can be accomplished on your own, it pays to hire a professional to do it for peace of mind.

Like many technicians, an experienced pool professional will have done the work of closing a pool many times over. They will be able to recognize any issues that need to be taken care of prior to reopening the pool next season. To avoid the disappointment of delaying that first swim next season, you may want to hire a pool pro to winterize your pool properly during the last days of the swim season.

Proper pool maintenance all season long can make it easier to winterize a swimming pool yourself. However, if you do not close it up properly, you could be in for a hefty repair bill next pool season. Be sure to call a pro for advice if you need any assistance in winterizing your pool for the off-season.

Compare Quotes From Top-rated Pool Contractors

Free, No-commitment Estimates

Find a Contractor

Was this article helpful?

Thank You for your feedback!

Something went wrong. Please try again later.

Sours: https://www.forbes.com/advisor/home-improvement/how-to-winterize-a-pool/
Interview with Ken from Car Chemistry

.

Chemistry insert car

.

Car Chemistry insert with restrictor welded on

.

You will also like:

.



1117 1118 1119 1120 1121