Thursday 29 January 2015

Diaper Absorbant Enhances Resolution Capacity of Ordinary Microscope


Some of the fantastic innovations of science which brought about a tremendous change are often outcomes of ingenuity and out of box of thinking. Here is one such classical example which opened up new vistas of microscopy. Edward Boyden a neuroengineer of Massachusetts Institute of Technology (MIT) in Cambridge with his colleagues developed a novel and subtle way of observing living tissues. The technique called as expansion microscopy uses the material used in baby diapers to observe the living tissues.

Conventional Optical microscope suffers from the major impediment of distinguishing the objects which are closer together than about 200 nanometres or roughly half the wavelength of visible light. These objects appear blurred or as a blob. This resolution limit is referred to as Abbe’s diffraction limit after the scientist Ernst Abbe who first identified it in 1873. Hence the optical microscope which is otherwise desirable for identifying the cell organelles is not suitable for observing structural details. Microscopes which use electron beams instead of light have finer resolution but they can be used in vacuum hence dead tissues alone can be used. Abbe’s limit couldn’t be overcome according to laws of physics. But scientists using fluorophores or fluorescent molecules and hitting them with lasers of specific wavelength engineered new ways to resolve proteins as close as 20 nanometres in living cells. These techniques developed by three scientists independently- Stephan Hell, William Moerner and Eric Betzig were awarded the Nobel Prize in Chemistry in 2014 for the pioneering work on super-resolution microscopy. These techniques are very useful in observing the vesicle moments across the nerve synapses, cell protein complexes and spaces between rows of skeletal microtube filaments etc but these cumbersome techniques demand expertise in handling expensive and specialised equipment.

In contrast to the super-resolution microscopy, Boyden employed the super absorbent material acrylate used in diapers for resolving the structural details of the brain tissues. Acrylate has two advantages. It is capable of forming a dense mesh capable of holding the proteins in place and it swells in presence of water. Acrylate salts form water lock and gives the diapers sponginess. They have a capacity to expand four and half times the original size. In order to locate the proteins which are closely packed, the living tissues before swelling are soaked in a chemical cocktail which makes them transparent and then infused with fluorescent molecules that anchor specific proteins to acrylate. Upon adding water, the acrylate would cause the living tissues to swell uniformly in all directions. In their experiment with brain tissues of mice, Boyden and his colleagues demonstrated that proteins which were too close and probably difficult to distinguish could be identified under visual-light microscope. With this technique proteins as close as 60nm were resolved. In future with further fine tuning of the techniques the resolution can be improved.

In this new technique of expansion microscopy the original living tissues are increased in size upon absorption of water. Crucially it also maintains the relative orientation and interconnections of the proteins and other cellular structures intact. But the position of position is shifted by 1-4%. The results of the expansion microscopy were comparable to super-resolution microscopy techniques.

This novel technique was feted by scientists all around who commended its ingenuity. These kinds of unique scientific feats would lay foundation for a genre of science which circumvents the use of highly sophisticated and complicated equipment. It also opens new frontiers in science where a judicious combination of the ingenious techniques with the hardwired innovative equipment could unravel the mysteries of life. 
 
 
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Friday 23 January 2015

NASA’s DSCOVR Probe Resurrected to Monitor Space Weather


I was thoroughly amused when I first read about a satellite launch that was postponed for incredible 14 years in the US due to frivolous political reasons. Here is the story of the DSCOVR probe brain child of former US Vice-president Al Gore. He hypothesised about a probe in space capable of streaming live images of illuminated side of the Earth that could be available online. He believed that such advanced images would be a great learning opportunity and would inspire enthusiastic youngsters. But the idea was scorned by Republicans who ridiculed it as “multi-million dollar screen saver”. NASA meanwhile formulated a complementary mission by soliciting expert recommendations. Accordingly, it designed a mission which besides acting as educational tool could carry bunch of sophisticated instruments which can measure the radiations reflected by the Earth back into space.

Initial proposal was to include two earth science instruments: EPIC and NISTAR. EPIC is the Earth Polychromatic Imaging Camera for capture the images of the sun-lit side of the earth. The images will allow the determination of physical quantities like ozone, aerosols, dust, volcanic ash, cloud height and vegetation cover. NISTAR (National Institute of Standards and Technology Advanced Radiometer) will audit the atmospheric pollution by measuring the amount of the radiations emitted and retained by the Earth. Emitted radiations lower the temperature while retaining more emissions would make Earth warm.

Thus, NASA constructed the satellite (also called as Triana) by 2000 and was readied for launch. During the Presidential elections in 2001, George W Bush defeated Al Gore as a result the project shelved in NASA’s rooster. While politics has been one of the reasons for halting this project, NASA head argued that space shuttle’s crowded launch calendar as the major stumbling block. In November 2001, the satellite was sent to storage at Goddard Space Flight Centre. It would have remained indefinitely lost if not for the interest of the space-weather forecasters of NOAA (National Oceanic Atmospheric Administration) and USAF (United States Air Force). In 2008 Congress approved the revival of the satellite and then further tests were carried out to refurbish it. During its resurrection, scientists identified a serious anomaly in the functioning of the EPIC instrument. Most of them were glad that the satellite wasn’t flown into space as it would have revealed the defect which would be more embarrassing.

After 14 years of prolonged delay, Earth Monitoring Satellite DSCOVR (Deep Space Climate Observatory) of NASA scheduled for launch on January 29th was deferred to February 18th. The project is a joint collaboration between the NASA, NOAA and USAF. The satellite will be put in the L1 (Lagrange Point 1), the neutral gravity point between Earth and Sun, approximately 1 million miles from Earth by the launch vehicle Space X Falcon V 1.1. Satellite will weigh 570 kg at the time of launch and has mission life of 5 years. L1 is a good point to monitor the Sun because constant stream of particles or the solar storms reached L1 about an hour before reaching Earth. DSCOVR can thus send warning signals to Earth 15 to 60 minutes ahead of surge of particles and magnetic field termed as Coronal Mass Ejection (CME) associated with geomagnetic storm of Sun. These solar storms have severely impact on the public transport system by disabling the power grids, telecommunications, GPS-positioning systems etc. The collateral damages in event of a severe solar storm might run into $2 trillion and its full recovery can take 4 to 10 years. Moreover bursts of ionised particles and radiations pose severe threat to astronauts and other orbiting satellites in the space. This aspect has been the special interest for the USAF which is funding its launch.

The satellite has five instruments on board. Besides NISTAR and EPIC, it has Electron Spectrometer, Pulse Height Analyser (PHA) and Solar Wind Plasma Sensor (Faraday Cup) and Magnetometer (MAG) to measure solar wind velocity, its magnitude and direction of solar wind magnetic field and sends the warning signal.

Till now estimates about the Earth’s radiations were arrived at by stitching up the data obtained by various satellites orbiting it. DSCOVR will observe the entire sunlit side of Earth and hence the estimates would be more accurate. It will thus help in making climate simulations. It is expected to succeed NASA’s ACE (Advanced Composition Explorer) satellite launched in 1997 which has worked well beyond its expected life period. At present ACE is the only satellite providing real time information about solar radiations and winds from the L1 orbit. To sum up, DSCOVR will measure magnetic field intensity, direction and distribution of incoming ions and electrons in the solar wind plasma according to their energies which enables scientists to determine solar wind plasma velocity, density and temperatures.

No country is immune to the cascading effects of politics- be it a developed country like India or the most powerful nation of the World, the US.
 
 
 
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Friday 9 January 2015

New Antibiotic Teixobactin Knocks Down Drug Resistant Bacteria


Antibiotic resistance has become the most insurmountable problem in recent years. The situation is particularly worse in India as antibiotics can be purchased over the counter without an authorised prescription. The issue is further aggravated due to the prevalent practice of personal medication. As a result even the most efficacious antibiotics are rendered incapable of fighting common hospital bound infections too. Disease resistant pathogens have become invincible. The fragile medical infrastructure in developing countries like India is unable to mitigate the burgeoning cases of antibiotic resistance.

According to Centre for Disease Control and Prevention nearly two million people are infected by bacteria, resistant to antibiotics and of those at least 23,000 people die. A new review on the antimicrobial review indicated that at the pace with which the resistant bacteria are multiplying, by 2050 it is estimated that 10 million people will die of otherwise curable diseases.  Several World leaders expressed anguish that antibiotic resistance might cause damage to a tune of $10 trillion for the global economy

Antibiotic resistance is a natural part of evolution. As humans discover new drugs to combat the infections, bacteria are acquiring resistance. Previously, by the time bacteria had evolved resistance man would have developed a new form of drug. Of late, due to human-influenced factors bacteria are acquiring resistance towards the existing drugs so quickly that Pharmacists are unable to create a new drug. As a result this crisis has turned out to be a man-made global threat and thousands of people are succumbing to diseases which are otherwise completely curable. To combat this problem most medical practitioners strictly warn against extensive usage of antibiotics.

In the latest break through scientists reported discovery of an antibiotic from an uncultivatable soil bacterium which shows no evidence of inducing the evolution of spontaneous resistance in its bacterial targets. The first set of the most successful antibiotics mined during early twentieth century are microbial natural products or their derivatives of soil bacteria and fungi. The golden age of antibiotics between 1940 and 1960 is marked by extensive use of these compounds for treating curable diseases.  Extensive mining of the soil bacteria resulted in obtaining compounds which are more or less chemically similar. Hence most of the antibiotics developed during that time had almost chemical configuration with minor variations. By 1980’s pharmaceutical companies turned their attention towards synthetic compounds which resulted in developing drugs for other diseases but failed to generate new set of antibiotics. Meanwhile, Actinomycetes, spore forming, soil bacteria has become favourite organism for antibiotic production as it is easily cultured in lab. Scientists have for long time ignored other rare taxa of soil bacteria which had unique chemical properties as they cannot be easily cultured. Due to the inability of culturing soil bacteria only 1% of them are studied so far for their antibiotic properties. Realising the grave folly, scientists developed new culturing techniques to cultivate rare taxa including insitu growth in natural environments.

Ling et al in their Nature paper which heralded the development of the new antibiotic, described a novel approach which revolutionised the culturing of soil bacteria which were difficult to grow in laboratory conditions. The new technique termed as iChip technology is a multichannel, miniature device used for high throughput production of rare cells directly in their source environment. Thus these species which replicate in the natural environment and fail to survive under the traditional lab methods are cultivated.

Using this technology the lab isolated 10,000 soil bacterial strains from which they prepared extracts and tested them for their ability to inhibit the growth of Staphylococcus aureus (a gram-positive bacterium that causes respiratory tract infections. The extracts of the bacterium that could kill the pathogenic bacterium are identified. The extract after the activity-guided purification is fractionated using several techniques and its antibiotic activity is again after every step. The new bacterium identified as Eleptheria terrae is the producer of the new generation antibiotic teixobactin.

Teixobactin basically inhibits cell wall synthesis by binding to the highly conserved motif of lipid II (precursor of peptidoglycan) and lipid III (precursor of teichoic acid). It is proved to be a potent chemical that can kill wide spectrum of disease-causing bacteria including Clostridium difficle (causes diarrhoea) and those which are resistant to vancomycin, pencillin and methicillin. The drug exhibited selective killing of bacteria even at very high doses and most importantly labs failed to generate Gram positive bacteria that is resistant to killing of teixobactin. Unfortunately, it is ineffective against gram negative bacteria which have developed a multi-drug resistance like Klebsiella pneumonia, pathogenic versions of E.coil, Neisseria gonorrhoeae, Pseudomonas aeruginosa.

Unlike the earlier antibiotics which targeted the bacterial enzymes involved in cell wall formation, teixobactin launches a double attack by blocking the building blocks of cell wall. Consequently the newly replicating bacteria will die. Hence bacteria evolving resistance against this drug would be unlikely or may be it might take several years. Human trials might begin two years from now. But for now teixobactin seems to offer a great promise against the Gram positive bacteria.
 
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Thursday 8 January 2015

Planet-hunting NASA’s Space Craft Kepler


Ever since man stepped on moon, there has been tremendous interest and excitement among the scientific community to explore the vast space in pursuit of other worlds like our earth. Already the existence of three types of exoplanets- hot super Earths, gas giants and ice giants was established. Now there is renewed enthusiasm towards quest for terrestrial planets (those one half to twice the size of earth) those in habitable zone of their stars where liquid water and possibly life might exist. Kepler Mission was thus designed to survey our region of the Milky Way galaxy to discover Earth-like or other smaller planets in or near habitable zone and to determine the fraction of hundreds of billions of stars in our galaxy which might have such planets.

Mission Launch and Objectives

The Kepler Space craft was launched by the United Launch Delta II vehicle from the Cape Canaveral Air Force Station in Florida on March 6th 2009. It was the first planet-hunting space craft sent into space on three and half year mission. The region in the Cygnus and Lyra constellations of our galaxy containing around 150,000 stars is watched by the Kepler space craft. The main objective of the mission is to monitor all stars continuously and measure their brightness at least once in every few hours. To ensure that Kepler telescope’s field of view (FOV) is never blocked at any time of the year by Sun it must be above the elliptic plane. The Spacecraft is placed in an Earth- trailing heliocentric orbit with a period of 372.5 days and it drifts away slowly from Earth in this orbit. By the end of four years, space craft is at distance of 0.5 astronomical units. This orbit is not subjected to earth torques due to gravity gradients, magnetic moments or atmospheric drag and helps in maintaining stable pointing altitude.

Instruments

The Space craft has a specially designed Kepler photometer with 0.95 meter aperture and 105 square degree FOV astronomical telescope. It is pointed at and records the data from just a single group of stars throughout the duration of its mission. Spacecraft provides power, pointing and telemetry to the photometer. Apart from the four small reaction wheels used for maintaining pointing and an ejectable cover no other movable parts were deployed. The data stored will be transmitted to the Earth once in a month.
 

Mode of detection of Extra Solar Planets:

When a planet passes in front of a star as viewed from earth it is called transit.  During the occasions of Mercury or Venus transit we observe a small dot creeping across the Sun and transiting planet would block the sunlight to the Earth. Similarly, Kepler finds new planets by looking for tiny dips in the brightness of the star when the planet crosses the star.  Subsequently the planet’s orbital size would be calculated based on the time taken by the planet to orbit once around the star and the mass by the Kepler’s third law of planetary motion. The size of the planet is found from the depth of the transit (amount of dip in the brightness of the star). From the Orbital size and temperature of the planet, its characteristics can be determined and its habitability will be estimated.

For the first four years after its commissioning, Kepler has successfully identified several planet candidates until it encountered a technical glitch in May 2013 where it lost two of the four reaction wheels that helped in fixing the star field it was staring. But the planet- hunting space craft received a new lease for life when a graduate student with his innovative idea of using pressure from the sunlight as virtual reaction wheel, stabilised the spacecraft. By June 2014, K2mission has become fully operational with expanded search for planets orbiting bright stars nearby. The spacecraft made a comeback with the discovery of a new exoplanet, HIP 116454b using its new mission K2. The newly confirmed planet announced on December 18th is 2.5 times diameter of earth and follows 9-day orbit around the star which is smaller and cooler than Sun and is 180 light years away from Earth.

Till now the Kepler Space telescope has identified an overwhelming 4175 candidate planets for study and 1000th planet has been recently verified. Scientists have now verified eight more new planets, six of which are near Earth size and orbit in habitable zone of stars similar to our Sun. This is the region where temperatures are just right for supporting liquid water on the planet’s surface or the Goldilocks Zone. Two of the newly validated planets Kepler-438b and Kepler-442b are less than 1.5 times the diameter of Earth and are supposed to be rocky like Earth. Kepler-438b is 475 light years away, 12% bigger than Earth and orbits its star once in 35.2 days. Kepler-442b is 1,100 light years away, 33% bigger than Earth and orbits its star in 112 days. Both of these planets orbit around stars which are smaller and cooler than our Sun, making the habitable zone to its parent star, in the direction of constellation Lyra. With the treasure trove of the planets discovered by Kepler, planets identified by other telescopes astronomers now have 1800 planets outside our solar system.

One major limitation with K2 mission is that it has to change its FOV after every 80 days. This will help the mission to observe not only on the Earth- sized planets but also at celestial bodies especially cluster of newly-formed stars. Accordingly it will turn its gaze to clusters Pleiades and Hyades followed by Beehive and M67 clusters in April. During the initial stages of the mission, it discovered that Neptune sized cold giants are most common in the Galaxy and that Jupiter-sized planets outnumber stars in the Galaxy. By April 2016 Kepler mission was planned to observe the centre of Milky Way in search of mysterious bodies termed as free-floating planets. By 2018, the mission would be taken over by NASA James Webbs Space Telescope, another exoplanet-hunting spacecraft.
 
With this tantalizing new information, scientists are really excited about the possibility of finding another Earth in space and brimming with hope that we are not alone in this Universe.
 
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Wednesday 7 January 2015

ISRO to test Reusable Launch Vehicle in March


In a major leap towards affordable launching of payloads into space ISRO is all set for a test demonstration of reusable space vehicle in March. A reusable vehicle system (RLV) is designed to carry a launch vehicle into space more than once. In contrast to the expendable satellite launch vehicles that are launched once and discarded as different stages burn off and separate from the vehicle. Space exploration and space utilisation is often deterred by huge expenses incurred in building instruments for space access. The cost of delivering 1 kilogram of payloads into designated orbit using conventional rockets is $5000. India currently spends Rs 300 Crores annually on satellite launches. Scientists has hit upon the promising idea of using Reusable Launch Vehicle- Technology Demonstration Program (RLV-TD) to cut down the expenses by 10 times. Also, a manned reusable space vehicle if developed can boost the lucrative business of space tourism as well. Along these lines, AVATAR (Aerobic Vehicle for Trans Atmospheric hypersonic Aerospace Transportation) was aimed at developing a single- stage reusable space vehicle capable of horizontal takeoff and landing by DRDO, ISRO and other institutions way back in May 1998 at the Aero 98 exhibition at Bangalore. Accordingly, it was approved in January 2012 to build and test a prototype RLV-TD by 2015 and the first manned AVATAR flight is proposed for 2025.

A winged RLV-TD has been configured to test various technologies like the hypersonic flight, autonomous landing, powered cruise flight and hypersonic flight using air-breathing propulsion. RLV-TD is aimed at realising the Two Stage To Orbit (TSTO) fully reusable launch vehicle. These technologies will be developed in phases through a series of experimental flights. The first in the series is the hypersonic flight experiment (HEX) followed by the landing experiment (LEX), return flight experiment (REX) and scram jet propulsion experiment (SPEX). The aerodynamics characterisation of RLV-TD was carried out by the National Aerospace Laboratories. The unmanned-prototype will weigh 12 tonnes at take-off and has a diameter of 0.56mt and length of 10 mts. RLV-TD will be mounted on the top of the rocket and would be launched beyond the atmosphere. After separation from the rocket, it will re-enter following the hypersonic regime.

The initial ground tests on the vehicle were completed by ISRO. It is now getting ready for the hypersonic flight and landing on water. It is actually a winged vehicle which will take off vertically and land horizontally like an aircraft. It is fitted with solid strap on thrusters similar to those used in PSLV’s. It will reach a speed of five times the sound (mach 5) to reach an altitude of 100 mts in five minutes. After ascent the vehicle will take a 180 degree turn and activates its control system for eventual re-entry and splashing into Bay of Bengal 20 minutes after takeoff. Water landing has been planned as India doesn’t have a run way of 5 km. In the subsequent steps attempts would be made to land the vehicle on the runway by releasing it from an aircraft from a height of about 5 km. The third attempt would be to take it to a higher altitude and prepare for ground landing. The concept of reusable space vehicle is much popular among the private companies in the US and currently Space X a private company is developing reusable vehicles.

Scientists at Vikram Sarabhai Space Centre (VSSC) opined that if rocket structure is made of 98% of propellant and 2% of the structure then reusability is possible. But rocket structure doesn’t give such a lee way and usually rocket structure accounts for 5-10% and 90% of propellant. Propellant is not costly but the hardware is very sophisticated and expensive. It needs to be reused to make space travel affordable.

Attempts at developing a reusable vehicle haven’t been successful so far. Only two space shuttles have come closer the reusable vehicles. The US Space Shuttle developed by NASA and the Buran launch vehicles developed by Russia were only partially reusable. Some components were expendable.

The US Space Shuttle first launched in 1981 carried out 135 missions till July 2011 when it was finally decommissioned. It had a fleet of five orbiter space planes: Atlantis, Challenger, Columbia, Discovery and Endeavour. Columbia and Challenger were destroyed following tragic accidents. These were developed to deploy satellites into orbits, carry scientific experiments, used to service and repair International Space Station and orbiting satellites and to carry out military operations. These constituted the Space Transportation System (STS) and they had orbiter, propulsion systems-two solid rocket boosters (SRB), three main engines and an external fuel tank. Buran completed one unmanned space flight in 1988 but the programme was cancelled in 1993 following the dissolution of Soviet Union.
 
 
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