Archive for the ‘Brad’s Sci-Tech Blog’ Category

IPS-Like Stem Cells Made From Fibroblasts Reprogrammed Via mRNA, Sans Viruses Or Genes

By: Bradley Fikes —  July 23rd, 2010

Proteins necessary for reprogramming human fibroblasts into induced pluripotent stem (IPS) cells have been produced in the fibroblasts via introducing protein-coding messenger RNA (mRNA), MIT researchers say today in the open access journal PLoS One. Click here for the article in PDF.

The cells produced seem like induced pluripotent stem cells; however, they have yet to be differentiated into other cells types to prove their pluripotency. That work is ongoing, say the MIT researchers, Mehmet Fatih Yanik, an associate professor of electrical and biological engineering and Matthew Angel, an electrical engineering graduate student.

The study’s key accomplishment is to show that mRNA can be efficiently delivered into cells and produce the reprogramming proteins. Another significant benefit is that the technology eliminates the need to inhibit p53, a major tumor-suppressing gene.

Yanik and Angel said they overcame the immune response to introduced mRNA, or “long RNA,” by using a method patterned on how RNA viruses inhibit the immune response in the cells they infect. Their paper is titled: “Innate Immune Suppression Enables Frequent Transfection with RNA Encoding Reprogramming Proteins.”

MIT researchers used RNA to induce these fibroblast cells to express four genes necessary to reprogram cells to an immature state.  Credit: Yanik Laboratory, MIT

MIT researchers used RNA to induce these fibroblast cells to express four genes necessary to reprogram cells to an immature state. Credit: Yanik Laboratory, MIT

They wrote in the article:

“Although the innate immune response to exogenous RNA is initiated and regulated by intra- and extracellular signaling networks containing a great deal of redundancy, RNA viruses have evolved methods of disrupting these pathways by destroying or inhibiting specific immune-related proteins to enable persistent infection. We hypothesized that mimicking viral immunoinhibition by co-transfecting cells with an siRNA cocktail designed to directly knock down expression of immune-related proteins could desensitize cells to exogenous RNA, and thus enable repeated long-RNA transfection. . . ”

“Here we have shown that combined knockdown of Ifnb1, Eif2ak2, and Stat2 rescues human fibroblasts from the innate immune response triggered by frequent transfection with protein-encoding RNA, and enables sustained, high-level expression of active proteins.”

The RNA world has been abuzz over siRNA, or Short Interfering RNA, for the last several years. These short RNA snippets have the ability to silence specific genes, and are being researched by various biotech companies for their therapeutic potential. Antisense pioneer Isis Pharmaceuticals Inc. is among those working with siRNA technology.

On July 14, Silence Therapeutics and AstraZeneca extended their siRNA drug development partnership.

Safer approach
IPS cells are typically produced by using a viral vector to introduce genes that produce reprogramming proteins. However, this can disrupt the genome’s integrity, so it’s undesirable for producing cells for transplantation into humans. So researchers are trying to find other methods to induce pluripotency, such as by using plasmids.

IPS cells have previously been made by protein transduction, or transferring the reprogramming proteins into the cell through the cell membrane. But that method is inefficient, the researchers said. By placing the mRNA that codes for the reprogramming proteins inside the cells, Yanik and Angel say they’ve caused the proteins to be made efficiently.

The mRNA for the proteins can be introduced multiple times, which would kill non-immunosuppressed fibroblasts, the researchers wrote.

As another benefit of their approach, Yanik and Angel write that their method of knocking down the immune-related proteins eliminates the need to knock down p53, a tumor-suppressor gene. The authors wrote that this “may facilitate the use of long-RNA transfection in therapeutic applications as p53 is crucial for the maintenance of genomic integrity.”

Poseidon Desalination Term Sheet OK’d By San Diego County Water Authority Board: UPDATED

By: Bradley Fikes —  July 22nd, 2010

UPDATE: This is an early version of my story on the Water Authority’s approval of a term sheet to guide negotiating a water purchase agreement with Poseidon Resources. The final version will be in the news section of the North County Times’ Web site, and in the print edition.

The San Diego County Water Authority approved Thursday a set of basic conditions to be used in drawing up an agreement to buy desalinated ocean water from Poseidon Resources Corp.
The board of directors endorsed a term sheet that lists key points for drawing up a contract with Poseidon, which plans to build a desalination plant near the Encina Power Station in coastal Carlsbad. Stamford, Conn.-based Poseidon must still arrange financing before a binding deal can be reached.
Poseidon will be in a position to sign such a binding deal by the end of the year, said Peter MacLaggan, a Poseidon senior vice president. The deal would supersede an earlier agreement with local agencies that has failed to get the required financial backing.
As with the earlier deal, Poseidon says the desalination plant will have the capacity to make 56,000 acre-feet of fresh water per year, enough for 300,000 residents of San Diego County. That amounts to 50 million gallons per day. One acre-foot is about 326,000 gallons, or enough water annually for two average families of four.
Supporters of the desalination plant say it adds a valuable new water source to arid San Diego County, which is also suffering along with the rest of California in a drought.
Board members approved the term sheet with almost no discussion; it had been discussed extensively earlier that afternoon by the board’s water planning committee.
The term sheet places nearly all the risk on Poseidon, Ken Weinberg, the authority’s director of water resources, told the water planning committee.
“This is a 30-year agreement and we are buying water: That is the extent of our role,” Weinberg said.
Poseidon will take all the risks of raising money and building and operating the plant, Weinberg said. The main risk to the Water Authority is that Poseidon might not be able to deliver the water, Weinberg said.
Under the term sheet, the authority will only pay for the water it receives from Poseidon, and it must meet the authority’s quality requirements. If Poseidon delivers less water than it’s required to, it could be required to pay damages, Weinberg said.
Mark Watton, a board member and general manager of Otay Water District, cautioned the authority staff against using the earlier agreement with Poseidon as a financial baseline for any potential contract.
Watton said the desalination project may not have been financially feasible, even if the project had been given a promised $250 per acre-foot subsidy from Metropolitan Water District, Southern California’s main water wholesaler.
That subsidy was called into question after the Water Authority filed suit against Metropolitan over supposedly excessive water costs Any suit gives Metropolitan authority under its contracts to cancel subsidies and incentives given to its customers.
“Even with the $250, I don’t think we had a viable model,” Watton said. “I think we may be kidding ourselves a little bit.”
The subsidy would have defrayed the cost to the purchasers, a coalition consisting of the cities of Carlsbad and Oceanside, along with seven local water districts. Without a guaranteed subsidy, Poseidon has said the original deal could not be financed
The agencies are: Valley Center Municipal Water District, Rincon del Diablo Municipal Water District, Sweetwater Authority, Rainbow Municipal Water District, Vallecitos Water District, Santa Fe Irrigation District and the Olivenhain Municipal Water District.
Poseidon and the nine partners agreed to let the Water Authority try its hand at doing a deal.

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The San Diego County Water Authority’s board of directors voted today to authorize staff to use a term sheet submitted by staff to start drawing up a water purchase contract with Poseidon Resources Corp. There are lots of steps that must be taken, mostly by Poseidon, for a binding deal to be reached.

Poseidon will provide the water from a desalination plant to be built in coastal Carlsbad by the Encina Power station. Peter MacLaggan, a Poseidon senior vice president, said after the board meeting that he expects Poseidon will have finished arranging financing and other requirements for a contract by the end of the year. At that point, the Water Authority plans to enter into a binding deal, barring any unexpected setbacks.

For more information, see my previous blog post.

I’ll update this post later in the day with more details.

SDCWA Water Planning Committee OKs Poseidon Carlsbad Desal Term Sheet: UPDATED

By: Bradley Fikes —  July 22nd, 2010

UPDATE: 3:45 p.m. The term sheet for drawing up a water purchase agreement with Poseidon Resources was approved by the San Diego County Water Authority’s water planning committee.

The item now goes to the full Water Authority board, which is about to meet.

If the full board approves, Water Authority staff will then prepare a draft water purchase agreement, based on the key conditions in the term sheet.

———————————————-

“This is a 30-year agreement and we are buying water: That is the extent of our role.”
– Ken Weinberg, Director of Water Resources, San Diego County Water Authority, on proposed desalinated seawater purchase agreement between the authority and Poseidon Resources Corp.

Weinberg is now (starting around 1:30 p.m. today) discussing the term sheet for the agreement at the water planning committee meeting. The full board is scheduled to meet at 3 p.m. today.

The “avoided costs” model is not used, he said, a big difference with the previous agreement between Poseidon and the nine local water agencies. Poseidon wasn’t able to finance the Carlsbad desalination plant under that agreement, which is why the Water Authority stepped in.

Allocation of major risks between Poseidon and Water Authority. Source: Water Authority presentation to Water Planning Committee

Allocation of major risks between Poseidon and Water Authority. Source: Water Authority presentation to Water Planning Committee.

“Avoided costs” means that the agencies would pay no more for Poseidon’s water than if they had to get the water from another source. This has been ditched in favor of a formula intended to give Poseidon a profit but also give the Water Authority a good price.

Poseidon will take all the risks of raising money and building and operating the plant, Weinberg said. The main risk to the Water Authority is that Poseidon won’t be able to deliver the water, Weinberg said.

If and when a term sheet can be agreed on, Water Authority staff will then work with Poseidon to draw up a contract.

Mark Watton, a board member and general manager of Otay Water District, cautioned the authority staff against using the defunct nine-agency agreement with Poseidon as a financial baseline for any potential contract.

Watton said the desalination project may not have been financially feasible, even if the project were given the $250 per acre-foot subsidy promised from Metropolitan Water District. That subsidy was called into question after the Water Authority filed suit against Metropolitan over supposedly excessive water costs Any suit gives Metropolitan authority under its contracts to cancel subsidies and incentives given to its customers.

“Even with the $250, I don’t think we had a viable model,” Watton said. “I think we may be kidding ourselves a little bit.”

Draft Poseidon Desalination Contract Goes To San Diego County Water Authority — UPDATED 2X

By: Bradley Fikes —  July 21st, 2010

UPDATE: The proposal before the County Water Authority is a “term sheet,” and not a draft contract, said Bob Yamada, the authority’s water resources manager. The difference is that a term sheet is an outline of basic conditions, and a contract spells out all the details, Yamada said. So if the term sheet is approved, that will set the conditions for drawing up a contract.
————————————————————————–
The San Diego County Water Authority is scheduled Thursday to consider a draft contract to buy water from Poseidon Resource Corp.’s proposed seawater desalination plant in coastal Carlsbad. Here’s the agenda.

The cost of the plant is estimated at $690 million, according to a report by authority officials that accompanied the nonbinding draft contract. Of the total financing, 82.5 percent, or $569 million, would come through the sale of tax-exempt private activity bonds authorized by the state, with the rest, 17.5 percent, or $121 million, consisting of cash equity from investors.

Last fall, Poseidon raised its request for the private activity bonds by $50 million, from $480 million to $530 million. That request was granted in January. by the California Debt Limitation Allocation Committee (CDLAC).

Five years ago, the plant’s cost was estimated at $230 million by Poseidon.

Poseidon Resources

The project’s cost figure isn’t final, according to the report.

“Because Poseidon is still negotiating agreements for construction and operation and has not yet prepared final draft financing documents, their financial projections for the project are still changing significantly,” the report said.

Term sheet for proposed water purchase agreement - Click for full report

Term sheet for proposed water purchase agreement - Click for full report

Click here for the report, which begins on page 39 of the 1.4 megabyte PDF. The draft contract, or “term sheet,” follows on page 46.

Draft contract provisions specify that if a binding deal is reached:
- Poseidon must complete financing by July 1, 2011, or the deal may be canceled.
- Poseidon is solely responsible for financing the plant.
- The Water Authority can review the plant design to ensure it complies with contract requirements.

However, a final agreement can’t be negotiated with Poseidon until it gets a commitment from investors, the report said.

UPDATE: From page 42 of the agenda linked above, here’s a description of the intricate negotiation and approval process. I’ve broken up the single paragraph into multiple ones to make it easier to understand:

“As a condition precedent to the Water Authority negotiating and finalizing a water purchase agreement with Poseidon, it will be necessary for Poseidon to receive a definitive executed commitment from construction equity investors sufficient to meet requirements to fully finance the project. Because it is a private project, the amount of the project cost not funded by bonded indebtedness will be cash equity put up by private investors interested in infrastructure investments.”

“Currently, Poseidon is proposing the financing of the $690 million project to be 82.5% debt through tax exempt Private Activity Bonds and 17.5% cash equity. It is not until Poseidon has a commitment from the construction equity investors that the project can be considered financeable and the Water Authority has a bona fide counter party with which to negotiate an agreement.”

“In addition to the Equity Commitment, conditions precedent to negotiating and finalizing an agreement include: the termination of all existing confidentiality agreements between the Water Authority and Poseidon and a waiver and release from any claims related to those agreements; execution of an acknowledgement by Poseidon and the nine Desal Partner member agencies requesting the Water Authority enter into negotiations and a waiver of all claims related to their existing agreements; and authorization by the Water Authority Board to commence negotiations of a final agreement. If the Board were to approve the staff recommendation, that final condition would be met.”

The nine Desal Partner agencies are the cities of Carlsbad and Oceanside, along with Valley Center Municipal Water District; Rincon del Diablo Municipal Water District; Sweetwater Authority; Rainbow Municipal Water District; Vallecitos Water District; Santa Fe Irrigation District; and Olivenhain Municipal Water District. These agencies have an existing deal with Poseidon; however, it has foundered on the lack of a financial guarantee for the water purchase. They have agreed to let the County Water Authority negotiate its own purchase agreement. Under that deal, the San Diego County Water Authority would provide that guarantee.

The authority’s Water Planning Committee is scheduled to consider the draft contract at its 1 p.m. meeting Thursday. The full board is scheduled to consider the deal at its meeting beginning at 3.p.m. The meetings will take place at authority headquarters, 4677 Overland Ave. in San Diego.

The desalination plant will have the capacity to make 56,000 acre-feet of fresh water per year, Poseidon says, enough for 300,000 residents of San Diego County. That amounts to 50 million gallons per day. One acre-foot is about 326,000 gallons, or enough water annually for two average families of four.

San Diego’s SkinIt Raises $60 Million Venture Capital Round

By: Bradley Fikes —  July 21st, 2010

SkinIt Inc, a provider of personalization products for tech devices, said Tuesday it has raised $60 million in a round led by the venture firm ABS Capital Partners.

SkinIt sells customizable skins to protect and decorate laptops, cell phones, gaming devices and other electronic gadgets.

Political Letter On AB 32 Global Warming Law From Union Of Concerned Scientists

By: Bradley Fikes —  July 19th, 2010

The Union of Concerned Scientists, a left-leaning environmentalist group, has ginned up a letter endorsed by 118 people representing themselves as economists urging California voters not to suspend AB 32. That’s the global warming law requiring drastic cutbacks in greenhouse gas emissions to stop putative CAGW, or catastrophic anthropogenic global warming.

An initiative is on the ballot to suspend AB 32 while California struggles with a crushing recession. But the economists say AB 32 will create new jobs in a green economy. And they also say the law will prevent degradation of California’s climate through putative global warming.

Both of these claims are groundless. While some green jobs will be created, many other jobs will be destroyed, such as in construction-related industries, especially cement production. And the entire state will be hit with higher energy costs. Those factors aren’t mentioned in the UCS letter. But that’s to be expected. This isn’t a balanced scientific study. It’s a political press release. The point of such polemical letters is to impress with numbers, not with facts.

The letter doesn’t even include any scientific references or economic studies to back up its claims. It is entirely opinion. And not all of the signers are economists. In a quick check, I found that one signer, James Barsimantov, has no degree in economics – he’s trained as an environmental activist. Here’s his CV.

The CV lists James Barsimantov’s current job as founding principal of EcoShift Consulting, an environmental consulting firm that provides “carbon accounting, climate action plans, lifecycle assessment, energy planning, corporate greening, and GIS and remote sensing.” Presumably, legislation like AB 32 is driving some of his company’s business. When groups like UCS point out that money from Texas-based Valero was used to put the initiative to suspend AB 32 on the ballot, this is worth keeping in mind. These eco-activists have political and financial interests at stake too.

And the predictably leftist media stenographers who publish worshipful articles about UCS as if it’s actually about science instead of political propaganda should wake up.

The claim that AB 32 will enhance California’s climate by retarding global warming is very dubious, and that’s being kind. Even assuming that CAGW is true, California is far from the largest emitter of carbon dioxide in the country. And companies that are effectively banned from California, such as cement producers, will simply relocate out of state — taking their emissions — and jobs — with them.

Moreover, China is now the biggest CO2 emitter.

Since CO2 doesn’t magically stay where it’s produced, it’s scientifically impossible for AB 32 to have any effect on climate, even if CAGW were true. But like virtually everything else from UCS, it’s about left-wing politics, not science. Of course, that won’t stop the press stenographers as hyping this as news. It’s not.

Encinitas To Hold Hearing On WiMax Plans

By: Bradley Fikes —  July 19th, 2010

On Wednesday at 6 p.m., the Encinitas City Council is scheduled to hear an appeal (PDF) of plans by Sprint and Clearwire to add WiMax antennas on top of the existing facility at Davina’s Cabo Grill, at La Costa Avenue and North Coast Highway.

Opponents say the WiMax installation is a health hazard, citing reports by various scientists, and a peer-reviewed meta-study.

The meta-study looked at 10 studies of the possible effects of living near mobile phone base stations, and found that 8 of them said there was a greater incidence of “adverse neurobehavioral symptoms or cancer in populations living at distances < 500 meters from base stations."

I personally doubt there’s a link between garden-variety wireless exposure and health problems and I take a skeptical view of reports from groups with an agenda. Still, I’m willing to look at peer-reviewed evidence. However, the full paper is behind a paywall, so I couldn’t read it. One question I have about the meta-study is what wireless technologies it looked at, as there are several (GSM, CDMA, etc). So from the information provided, I can’t determine how pertinent the findings are to the particular technologies used by Sprint and Clearwire.

If anyone will send me the full paper, I’ll read it and report back here.

Here’s a couple other reports about the opposition. One, from the San Diego Reader, and another one from Leucadia Blog.

Vista’s Auspex Raises $12 Million

By: Bradley Fikes —  July 19th, 2010

Auspex Pharmaceuticals has raised $12 million, according to a filing by the Vista-based company with the SEC.

Auspex is developing varieties of existing drugs using deuterium to make them act longer and more safely.

Here’s a link to an article I wrote about Auspex in March of 2009.

I’m checking with the company for more details of the funding.

H/t to SoCalTech.com for noticing this filing.

Tom Daschle Keynotes Venture Capital Summit in San Diego

By: Bradley Fikes —  July 16th, 2010

Former Senator Tom Daschle delivered the keynote address at the 8th annual venture summit held Friday morning by the San Diego Venture Group.

I’ve included audio of the South Dakota Democrat’s speech in MP3 format. I have broken it up into four parts for convenience of downloading — they are 2 to 3 megabytes each. There is at times some of the inevitable clatter of cutlery at the table, but other than that it is a fairly clear recording.

Life Technologies CEO Greg Lucier, left, asks a question of former senator Tom Daschle (D-South Dakota).

Life Technologies CEO Greg Lucier, left, asks a question of former senator Tom Daschle (D-South Dakota).

Here are Part 1, and Part 2, which mainly focus on the health care overhaul and Daschle’s views as why it was necessary.

Here are Part 3, and Part 4, which mainly concern Daschle’s views on venture capital, life sciences and innovation.

The former Senate majority leader has a new book coming out on health care. Daschle was hired last November as a senior policy advisor to DLA Piper, a legal services provider.

Daschle was President Barack Obama’s first choice to be Secretary of Health and Human Services. He withdrew after admitting he had failed to pay about $140,000 in taxes.

After the address, Greg Lucier, CEO of Life Technologies, interviewed Daschle, and Daschle held a Q and A with the audience of several hundred, at the Omni Hotel in downtown San Diego.

I’ll add more to this post over the weekend.

New Plate Tectonics Theory Proposed By UCSD, Monash Scientists

By: Bradley Fikes —  July 15th, 2010

This just in from UCSD’s Scripps Institution of Oceanography:

A research team including Scripps Institution of Oceanography geophysicist Dave Stegman has proposed a new theory to explain the motion of tectonic plates.

The theory, published in the July 16 issue of Science, explains the differences in movements of the various plates. It combines observation and new computer models to show that the plates’ velocities are a factor of how big the subduction zones are and subduction zone edges. It bears the title, “Cenozoic Tectonics of Western North America Controlled by Evolving Width of Farallon Slab.”

Plate Tectonics

Stegman likens the sinking of subducted plates to how a penny falls through honey — the “honey” in this case being the hot, plastic rock beneath the earth’s surface.