Smart Economy

Nanoblasts from laser-activated nanoparticles move molecules, proteins and DNA into cells

Using chemical "nanoblasts" that punch tiny holes in the protective membranes of cells, researchers have demonstrated a new technique for getting therapeutic small molecules, proteins and DNA directly into living cells.

Carbon nanoparticles activated by bursts of laser light trigger the tiny blasts, which open holes in cell membranes just long enough to admit therapeutic agents contained in the surrounding fluid. By adjusting laser exposure, the researchers administered a small-molecule marker compound to 90 percent of
targeted cells – while keeping more than 90 percent of the cells alive.

The research was sponsored by the National Institutes of Health and the Institute of Paper Science and Technology at Georgia Tech. It will be reported in the August issue of the journal Nature Nanotechnology.

"This technique could allow us to deliver a wide variety of therapeutics that now cannot easily get into cells," said Mark Prausnitz, a professor in the School of Chemical and Biomolecular Engineering at the Georgia Institute of Technology. "One of the most significant uses for this technology could be for gene-based therapies, which offer great promise in medicine, but whose progress has been limited by the difficulty of getting DNA and RNA into cells."

The work is believed to be the first to use activation of reactive carbon nanoparticles by lasers for medical applications. Additional research and clinical trials will be needed before the technique could be used in humans.

Researchers have been trying for decades to drive DNA and RNA more efficiently into cells with a variety of methods, including using viruses to ferry genetic materials into cells, coating DNA and RNA with chemical agents or employing electric fields and ultrasound to open cell membranes. However, these previous methods have generally suffered from low efficiency or safety concerns.

 With their new technique, which was inspired by earlier work on the so-called "photoacoustic effect," Prausnitz and collaborators Prerona Chakravarty, Wei Qian and Mostafa El-Sayed hope to better localize the application of energy to cell membranes, creating a safer and more efficient approach for intracellular drug delivery.

Their technique begins with introducing particles of carbon black measuring 25 nanometers – one millionth of an inch – in diameter into the fluid surrounding the cells into which the therapeutic agents are to be introduced. Bursts of near-infrared light from a femotosecond laser are then applied to the fluid at a rate of 90 million pulses per second. The carbon nanoparticles absorb the light, which makes them hot. The hot
particles then heat the surrounding fluid to make steam. The steam reacts with the carbon nanoparticles to form hydrogen and carbon monoxide. The two gases form a bubble which grows as the laser provides energy. The bubble collapses suddenly when the laser is turned off, creating a shock wave that punches holes in the membranes of nearby cells. The openings allow therapeutic agents from the surrounding fluid to enter the cells. The holes quickly close so the cell can survive.

The researchers have demonstrated that they could get the small molecule calcein, the bovine serum albumin protein and plasmid DNA through the cell membranes of human prostate cancer cells and rat gliosarcoma cells using this technique. Calcein uptake was seen in 90 percent of the cells at laser levels that left more than 90 percent of the cells alive. "We could get almost all of the cells to take up these molecules that normally wouldn't enter the cells, and almost all of the cells remained alive," said Prerona
Chakravarty, the study's lead author. "Our laser-activated carbon nanoparticle system enables controlled bubble implosions that can disrupt the cell membranes just enough to get the molecules in without causing lasting damage."

To assess how long the holes in the cell membrane remained open, the researchers left thesimulated therapeutics out of the fluid when the cells were exposed to the laser light, then added the agents one second after turning off the laser. They saw almost no uptake of the molecules, suggesting that the cell membranes resealed themselves quickly.

To confirm that the carbon-steam reaction was a critical factor driving the nanoblasts, the researchers substituted gold nanoparticles for the carbon nanoparticles before exposure to laser light. Because they lacked the carbon needed for reaction, the gold nanoparticles produced little uptake of the molecules, Prausnitz noted.

Similarly, the researchers substituted carbon nanotubes for the carbon nanoparticles, and also measured little uptake, which they explained by noting that the nanotubes are less reactive than the carbon black particles.

Experimentation further showed that DNA introduced into cells through the laser-activated technique remained functional and capable of driving protein expression. When plasmid DNA that encoded for luciferase expression was introduced into the cancer cells, production of luciferase increased 17-fold.

For the future, the researchers plan to study use of a less expensive nanosecond laser to replace the ultrafast femtosecond instrument used in the research. They also plan to optimize the carbon nanoparticles so that nearly all of them are consumed during the exposure to laser light. Leftover carbon nanoparticles in the body should produce no harmful effects, though the body may be unable to eliminate them, Prausnitz noted.

"This is the first study showing proof of principle for laser-activation of reactive carbon nanoparticles for drug and gene delivery," he said. "There is a considerable path ahead before this can be brought into medicine, but we are optimistic that this approach can ultimately provide a new alternative for delivering therapeutic agents into cells safely and efficiently."

full story here http://www.eurekalert.org/pub_releases/2010-07/giot-nfl072710.php

Walter Derzko

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Public release date: 27-Jul-2010
Contact: John Toon
[email protected]
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Georgia Institute of Technology Research News

When will the recession end? Recovery start? Part 98 Why US business isn't hiring or spending? It doesn't need to

The New Yorker magazine makes a valid point about the reluctance of US business spending and hiring. IT DOES NOT NEED TO-plain and simple. (see below) Before the start of this recession I urged Smart Economy blog readers to follow the cartoon-osphere to spot weak signals when the US would be headed into recovery. Well it's not any time soon (see cartoon above left)

From: Blame Games by James Surowiecki in the New Yorker Magazine

Two Significant quotes


"If businesses aren’t hiring or investing, in other words, it’s because they don’t need to: they have enough workers and factories to meet the demand for their products. And there are few signs that this is going to change any time soon: consumer demand remains weak, economic indicators—inflation rates, consumer confidence, the stock market, bond rates—aren’t forecasting a quick return to boom times, and, just last week, the Fed chairman, Ben Bernanke, told Congress that the state of the U.S. economy was “unusually uncertain.” So it’s no wonder that companies are feeling cautious. The uncertainty that’s keeping businesses from spending or hiring isn’t uncertainty about what Barack Obama is doing or saying. It’s uncertainty about whether the economic recovery is going to stick."

[...]

"U.S. economy is limping along. The job market is in rotten shape, and business investment is hitting historic lows. And, if you’re looking for a culprit for this dismal state of affairs, many businesspeople would be happy to point you to the White House. Companies aren’t hiring or investing, businessmen say, because the combination of Barack Obama’s anti-corporate attitude and a blizzard of new regulations and proposed taxes has created what Ivan Seidenberg, the C.E.O. of Verizon, calls “an increasingly hostile environment for investment and job creation.” In a recent Newsweek column, Fareed Zakaria pointed to the fact that Fortune 500 companies are sitting on a cash hoard of $1.8 trillion, and suggested that a “profound sense of distrust” might be why they weren’t spending it."

Read more here
http://www.newyorker.com/talk/financial/2010/08/02/100802ta_talk_surowiecki#ixzz0utNieIt3

Even mainstream Canadian Bay Street economists are not just forcasting a slowdown in the second half of 2010, but a double dip recession or w-shaped recovery. David Rosenberg from Gluskin Sheff and Associated is warning clients that the chance of a double dip recession in the USA has jumped to 67% or 2/3 from 1/3 last month.

Walter Derzko

When will the recession end? Recovery Start? Part 97 US government comes clean on low growth /no growth economy for next few years

Existing debt crowds out new private investment

From Calculated Risk blog

Private Investment?

The WSJ is quoting Treasury Secretary Timothy Geithner as saying it is time for private investment to take over from government stimulus: "We need to make that transition now to a recovery led by private investment," Mr. Geithner said Sunday on NBC's "Meet the Press." [...]"I think the most likely thing is you'll see an economy that gradually strengthens over the next year or two, you'll see job growth start to come back, investments expanding ... but we've got a long way to go still," Mr. Geithner said.

I discussed this in my previous blog posts- in most industrial sectors of the US economy, there is over capacity or too much supply (residential housing & commercial real estate) and dwidling demand (debt-laddened consumers, cautious business owners), so there is no reason for significant new private investment--Walter Derzko

When will the recession end? Recovery start? Part 96 US economy slows in June 2010

The NBER in the US has yet to declare the US recession officially over and here is why they won't for a quite awhile longer.

The Chicago Fed National Activity Index (CFNAI) is a better predictor of US economic activity & inflation /deflation in the next 6 months and it's headed back into negative (below trend) territory--I follow this index more then I do the GDP--Walter Derzko

US Economic Activity Declined in June   

Led by deterioration in production- and employment-related indicators, the Chicago Fed National Activity Index declined to -0.63 in June, down from +0.31 in May.

Three of the four broad categories of indicators that make up the index made negative contributions in June, while the sales, orders, and inventories category made the lone positive contribution. The Chicago Fed National Activity Index (CFNAI) is a monthly index designed to better gauge overall economic activity and inflationary pressure.

Chicago Fed National Activity Index (CFNAI)
The Chicago Fed National Activity Index (CFNAI) is a monthly index designed to gauge overall economic activity and related inflationary pressure. The CFNAI is a weighted average of 85 existing monthly indicators of national economic activity. It is constructed to have an average value of zero and a standard deviation of one. Since economic activity tends toward trend growth rate over time, a positive index reading corresponds to growth above trend and a negative index reading corresponds to growth below trend.

The 85 economic indicators that are included in the CFNAI are drawn from four broad categories of data: production and income; employment, unemployment, and hours; personal consumption and housing; and sales, orders, and inventories. Each of these data series measures some aspect of overall macroeconomic activity. The derived index provides a single, summary measure of a factor common to these national economic data.

The CFNAI corresponds to the index of economic activity developed by James Stock of Harvard University and Mark Watson of Princeton University in an article, "Forecasting Inflation,"(external-pdf) published in the Journal of Monetary Economics in 1999. The idea behind their approach is that there is some factor common to all of the various inflation indicators, and it is this common factor, or index, that is useful for
predicting inflation. Research has found that the CFNAI provides a useful gauge on current and future economic activity and inflation in the United States.

Walter Derzko

Wild Card? USA endorses Israeli pre-emptive bombing of Iran

"Huffington Post" reports thar US Republicans in the House of Representatives have introduced a measure that would green-light an Israeli bombing campaign against Iran. The resolution, H.Res. 1553 (see full text here), provides explicit support for military strikes against Iran, stating that Congress supports Israel's use of "all means necessary" against Iran "including the use of military force". US military leaders have warned that strikes could be catastrophic to US national security interests and could engulf the
Middle East in a "calamitous" regional war.

Nearly a third of House Republicans have signed onto the resolution, which has been publicly discussed and circulated by its lead sponsor, Rep. Louie Gohmert (R-TX), for months.

The introduction of the measure coincides with a pattern of renewed calls for military strikes that have escalated since President Obama signed "crippling" Congressional Iran sanctions into law.Neoconservatives who were instrumental in orchestrating the Iraq War, such as Bill Kristol, and Reuel Marc Gerecht, have led the stepped up calls for military action. Hawkish former Bush Administration official John Bolton recently laid out the game plan to prod Israel into attacking Iran, arguing that outsiders can "create broad
support" for a strike by framing it as an issue of Israel's right to self defense.  Supporters for military strikes, Bolton says, should "defend the specific tactic of pre-emptive attacks" against Iran. He urges that Congress can "make it clear" that it supports such strikes and that "having visible congressional support in place at the outset will reassure the Israeli government, which is legitimately concerned about Mr.
Obama's likely negative reaction to such an attack."

In spite of enthusiasm from the neocons, top US military leaders have warned of the many dangers of military strikes against Iran.

Defense Secretary Robert Gates has argued, "Another war in the Middle East is the last thing we need. In fact, I believe it would be disastrous on a number of levels."

Admiral Mike Mullen, Chairman of the Joint Chiefs has expressed his own serious reservations about an attack, stating, "Iran getting a nuclear weapon would be incredibly destabilizing. Attacking them would also create the same kind of outcome. In an area that's so unstable right now, we just don't need more of that."

General David Petraeus has warned that a strike on Iran would be utilized by the Iranian government to unite it's otherwise divided populace.

Simulations have been conducted over the past year to assess the outcome of a preemptive military strike against Iran. One such simulation, by the Brookings Institution's Saban Center, found that strikes would draw the US into the conflict that would engulf the region into war, and would enable Iran to use the attacks as an opportunity to unite the Iranian people and dismantle its opposition. The simulation also found that the strikes could not destroy Iran's nuclear program but merely set it back a few years. An Oxford Research Group report released recently reinforced those findings and also warned that an
Israeli attack would be disastrous and would be unlikely to stop Iran's nuclear program. Instead, the report concluded attacks could convince Iran to withdraw from the international Nuclear Non-proliferation Treaty and to aggressively seek to develop nuclear weapons.

Does quantum entanglement optimise photosynthesis?

Recently, academic debate has been swirling around the existence of unusual quantum mechanical effects in the most ubiquitous of phenomena, including photosynthesis, the process by which organisms convert light into chemical energy.  In particular, physicists have suggested that entanglement (the quantum interconnection of two or more objects like photons, electrons, or atoms that are separated in physical space) could be occurring in the photosynthetic complexes of plants, particularly in the pigment molecules, or chromophores.  The quantum effects may explain why the structures are so efficient at converting light into energy -- doing so at 95 percent or more.

In a paper in The Journal of Chemical Physics, which is published by the American Institute of Physics, these ideas are put to the test in a novel computer simulation of energy transport in a photosynthetic reaction center.  Using the simulation, professor Shaul Mukamel and senior research associate Darius Abramavicius at the University of California, Irvine show that long-lived quantum coherence is an "essential ingredient for quantum information storage and manipulation," according to Mukamel.  It is possible between chromophores even at room temperature, he says, and it "can strongly affect the light-harvesting efficiency."

If the existence of such effects can be substantiated experimentally, he says, this understanding of quantum energy transfer and charge separation pathways may help the design of solar cells that take their inspiration from nature.

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The article, "Quantum oscillatory exciton migration in photosynthetic reaction centers" by Darius Abramavicius and Shaul Mukamel will appear in The Journal of Chemical Physics.  See: http://jcp.aip.org/

Improvised Explosive Devices or IEDs detonated by microwaves

New solution to IEDs: Microwaves that detonate them before the enemy does

Source:  http://homelandsecuritynewswire.com/new-solution-ieds-microwaves-detonate-them-enemy-does

Improvised Explosive Devices or IEDs are the main killer of U.S. Canadian and allied troops in Afghanistan, and the U.S. military has been trying many different methods to deal with them -- man-made lightning, bomb-handling robots, radio frequency jammers, and more; now, researchers are working on microwaves that do not just damage the weapon's circuitry, but are powerful enough actually to detonate a bomb before the enemy does

A new way to detonate IEDs before they cause harm, as in this controlled detonation // Source: flickr.com

Improvised explosive devices (IEDs) are the weapon of choice of insurgents, and the U.S. military keeps searching for ways to deal with this weapon: man-made lightning, bomb-handling robots, radio frequency jammers and electronics-frying high electromagnetic pulses.

Now, the U.S. military has gone one step further, developing explosive-killing microwaves that do not just damage the weapon’s circuitry, but are powerful enough actually to detonate a bomb before the enemy does.

Olivia Koski writes that pregnant women are often advised not to stand in front of micorwave ovens, even if the dangers to unborn fetuses are far from proven.  Likewise, there is still a lot of debate in the scientific community about whether the cell phone radiation is harmful or not.  In both cases, the radiation is non-ionizing, which means it does not damage DNA — as harmful UV rays from the sun do.  This is the nature of low energy microwave radiation — for most purposes, it is completely harmless and extremely useful.

But large dose of microwaves can make harmless radiation into a weapon.  Koski notes that at high enough powers, electronics-scrambling microwaves are not just a threat to radio, television, cell phones, GPS, and radar.  Like their high power directed energy cousins, lasers (the first laser was actually a maser), they can destroy anything given enough energy.  The edge they have over bomb-blasting lasers —like Boeing’s Laser Avenger — is that they can penetrate below the surface, where many of the IEDs reside.

There is not much information out there about this new technology, and the researchers working on it are not talking.  “Sorry, but due to the nature of the subject I cannot comment on this at all,” Dr. Michael Geisselmann, with Texas Tech University’s Center for Pulsed Power and Power Electronics, told Koski.

It does not even seem to have a name, or at least not one released to the public.  David Hamlbing reports in Popular Mechanics that the existence of it has been confirmed by the Office of Naval Research.

Http://www.popularmechanics.com/technology/military/news/navy-reveals-secret-device-to-destroy-ieds?click=pp

Such a device would no doubt require a truckload (or two) of its own electronic equipment, considering that the Active Denial System, which is a non-lethal microwave device, needs a heavy vehicle to haul it around.  “But with improvised bombs killing troops and civilians in Afghanistan in record numbers, the need for a bomb-cooker is greater than ever,” Koski writes.

Http://homelandsecuritynewswire.com/new-solution-ieds-microwaves-detonate-them-enemy-does

Women's figure-type can raise dementia risk, say scientists

How brain function can go pear-shaped; Women's figure-type can raise dementia risk, say scientists Hannah Devlin.  The Times.  London (UK): Jul 15, 2010.  Pg.  17

Pear-shaped women may be at greater risk of developing dementia in old age than women with rounder, apple-like figures, research suggests.

The large-scale study is the first to show that obesity has a direct impact on cognitive and memory decline.  It also unexpectedly revealed, however, that shape as well as size appeared to be a risk factor.

"Obesity is bad, but its effects are worse depending on where the fat is located," said the study leader, Diana Kerwin, of Northwestern University, Chicago.

Pear-shaped women are defined as those with high hip-to-waist ratios, such as the actress Jennifer Lopez and the singer Beyonce.  In apple-shaped women the waist and hip measurements are much closer, as with the actress Catherine Zeta-Jones and Judy Finnigan, the television presenter.

"Pears" tend to gain most weight on the hips and bottom, while "apples" accumulate a tyre around the middle.

Dr Kerwin and colleagues assessed 8,745 women aged between 65 and 79 on the basis of a standard memory test that is typically used to screen for dementia.  About 70 per cent of the women were overweight or obese.

Although all the women were classified as "cognitively normal", the results revealed differences linked to weight and body shape.  Test scores out of 100 dropped by a point for every one-point increase in body mass index.  Being overweight was generally associated with reduced memory and brain function, but overweight pear-shaped women were more affected than the "apples" with thick waists.

Rebecca Wood, chief executive of the Alzheimer's Research Trust, remained sceptical.  "The pear shape is incredibly common, and this study doesn't explain fully the link between body shape and brain function," she said.

She added, however, that the findings strengthened the case for maintaining a healthy weight.  "There is little we can do about our natural body shape, but a lot we can do about our weight," she said.

Fat cells release immune system signalling molecules, called cytokines, that may affect the brain, scientists believe.  Different kinds of fat are known to release different cytokines that have various effects on blood fats, blood pressure and the way the body responds to insulin.

Another possible factor is that fat around the waist produces the female hormone oestrogen, which naturally dips after the menopause and which is thought to help to protect the brain from cognitive decline.

"We need to find out if one kind of fat is more detrimental than the other and how it affects brain function," Dr Kerwin said.

"The fat may contribute to the formation of plaques [brain deposits] associated with Alzheimer's or a restricted blood flow to the brain."  The findings could help to guide treatment of obese patients and ultimately help to develop drugs to protect against cognitive decline with age, she added.

Walter Derzko

More than half the world's population gets insufficient vitamin D-2000 international units per day recommended for most adults

More than half the world's population gets insufficient vitamin D, says UCR biochemist Vitamin D expert Anthony Norman recommends a daily intake of 2000 international units for most adults

RIVERSIDE, Calif.  – Vitamin D surfaces as a news topic every few months.  How much daily vitamin D should a person get?  Is it possible to have too much of it?  Is exposure to the sun, which is the body's natural way of producing vitamin D, the best option?  Or do supplements suffice?

In the July 2010 issue of Endocrine Today, a monthly newspaper published by SLACK, Inc., to disseminate information about diabetes and endocrine disorders, Anthony Norman, a distinguished professor emeritus of biochemistry and biomedical sciences and an international expert on vitamin D, notes that half the people in North America and Western Europe get insufficient amounts of vitamin D.

"Elsewhere, it is worse," he says, "given that two-thirds of the people are vitamin D-insufficient or deficient.  It is clear that merely eating vitamin D-rich foods is not adequate to solve the problem for most adults."

Currently, the recommended daily intake of vitamin D is 200 international units (IU) for people up to 50 years old; 400 IU for people 51 to 70 years old; and 600 IU for people over 70 years old.

"There is a wide consensus among scientists that the relative daily intake of vitamin D should be increased to 2,000 to 4,000 IU for most adults," Norman says.  "A 2000 IU daily intake can be achieved by a combination of sunshine, food, supplements, and possibly even limited tanning exposure."

While there is now abundant data on vitamin D and its benefits, Norman believes there is room for more study.

"The benefits of more research on the topic justifies why this field of research deserves additional governmental funding," he says.  "Already, several studies have reported substantial reductions in incidence of breast cancer, colon cancer and type 1 diabetes in association with adequate intake of vitamin D, the positive effect generally occurring within five years of initiation of adequate vitamin D intake."

Because vitamin D is found in very few foods naturally (e.g. fish, eggs and cod liver oil) other foods such as milk, orange juice, some yogurts and some breakfast foods are fortified with it.  The fortification levels aim at about 400 IU per day.

Norman, who holds the title of Presidential Chair in Biochemistry-Emeritus, has been researching vitamin D for nearly 50 years.  In 1967, his laboratory discovered that the vitamin is converted into a steroid hormone by the body.  Two years later, his laboratory discovered the vitamin D receptor (or VDR), an essential receptor for the steroid hormone form of vitamin D that is present in more than 37 target organs of the body that respond biologically to the vitamin.

"There is now irrevocable evidence that receptors in the immune, pancreas, heart-cardiovascular, muscle and brain systems in the body generate biological responses to the steroid hormone form of vitamin D," he says.

Study: Skilled immigrants boost US innovation

A study published in the latest issue of the Journal of Labor Economics finds that highly skilled temporary immigrants boost technological innovation in the U.S. without displacing U.S.-born workers in the process.

The study, by William Kerr of the Harvard Business School and William Lincoln of the University of Michigan, looked at fluctuations over the last 15 years in the number of immigrants admitted to the U.S. under the H-1B visa program, which governs immigration of highly skilled temporary workers. The researchers found that when more H-1B visas are granted, the number of U.S. patent applications filed by people with Chinese and Indian names increased substantially in cities and firms dependent upon the program. Much of that increase can be attributed to H-1B immigrants.

Meanwhile, the number of applications filed by people with Anglo-Saxon names—a proxy for U.S.-born workers—did not vary with fluctuations in H-1B admissions.

"We conclude that total invention increased with higher [H-1B] admissions primarily through the direct contributions of immigrant inventors," the authors write. "We are also able to rule out displacement [of native workers]."

The study used data gathered from 1995 to 2008. Patent applications do not record inventors' nationalities, so the researchers used an algorithm to determine probable nationalities based on the inventors' names. They then compared those data with the number of H-1B visas granted in a given year. The number of visas fluctuated widely over the study period, due to changes in a government-mandated cap on the program. At its lowest, visas were capped at 65,000 per year, and peaked at 195,000.

"This study quantifies the impact of changes in H-1B admission levels on the pace and character of U.S. invention …," the authors write. "We hope that this assessment aids policy makers in their current decisions about appropriate admission rates in the future."

Source: William R. Kerr and William F. Lincoln, "The Supply Side of Innovation: H‐1B Visa Reforms and U.S. Ethnic Invention." Journal of Labor Economics 28:3 (July 2010).

Walter Derzko; The Opportunity Clinic, Smart Economy, Toronto