Saturday, January 3, 2015

Say that again, FRACKING ?

FRACKING  and Shale gas are  going to be increasingly in the News from now on. Shale is already present in the Oxford dictionary, but FRACKING  is yet to gain reputation to be admitted into the elite club.   In any case Fracking has gained popularity and assumed global importance because  that is how we  mine natural gas from shale deposits.   Obama has already declared that for the next 100 years America doesn't have to worry because "we have an abundance of natural gas". It is estimated that by 2040, about 50% of America's natural gas will be from Shale. 
  
Shale Gas Mining- Courtsey Wikipedia
Naturally then one asks  what is Shale?   It is a slate-like mineral deposit of limestone rich in sulfides  and carbonates of iron. Geologists call it Marcellus shale  (Utica or Upper Devonian shale also belong to this family).  These mineral deposits    hold large quantities of natural gas,in their pores and crevices.  in other words, natural gas is entrapped in  shale rock. It is not easy to pump out the gas. One needs to dig more than a kilometer  to reach the shale structure, and then  the structure tends to crack horizontally into layers making drilling difficult. Hydraulic  fracturing is  a specialized technique which uses a pressurized liquid to crack open the rock horizontally. A variety of fracturing liquids and gels  to suit the chemistry of the  rock type are used. Fracking is  an easier and more popular term  for hydraulic fracturing. Shale gas mining involves two steps:  first  step is to  drill straight down to reach the shale structure and then  drill  horizontally,  to take advantage of the layered structure of shale. One end of the well is sealed off and water (or any other fluid) is pumped under very high pressure to fracture the  rock.  This allows the interconnection of crevices spread over a large area. The gas is then mined out. 

In the US  West Virginia, Pennsylvania, New York, Texas, Arkansas  have already highly developed shale plays, (Plays mean fields). These plays collectively   " now supplies 385 million cubic metres of gas per day, more than  enough to supply half of the gas currently burned in US power plants.   And the US Energy Information Administration appears very confident  in its Annual Energy Outlook 2014.  The dream of cheap and abundant energy could soon come true. But as always there are skeptics. In a recent article in Nature says this could be just a wishful thinking. However  US dept. of Energy was quick to respond and allay the misgivings. 

Will shale gas remain a pipe dream? Let us wait and watch. 

References:
2. The Gas Surge : Science 27 June 2014 (vo.344, Issue 6191, page 1464-1475
3. The Fracking Fallacy - M.Inman, Nature 4 Dec. 2014 (Vol.516, page 28-30)




. 

Friday, December 12, 2014

On how plants keep Time.

Sun is THE MASTER CLOCK  for all  earthly beings, no doubt about that. (Of course having a clock and being punctual are two entirely different stories, we won't get into that now). We take a brief look at how living beings carry out their cellular functions punctually.  Mammals have a built-in super synchronizer  suprachiasmatic nucleus, (SCN) which coordinates and maintains a standard time for all cellular functions and set in motion the circadian rhythmHow do plants keep time? They directly receive their daily bread (via photosynsthesis) from the sun. But  apart from that   plants also have  short term and long term ( daily and seasonal ) rhythms. Some  flowers bloom with the early rays of Sun while others are literally  late bloomers; there are even those which spread their fragrance exclusively during the night. Mangoes and litchies arrive only in summer, while ripe oranges flood the markets  winter . So the question is do plants have a synchronizer? Or in other words, what is the SCN equivalent  in plants.?  Till now the general assumption has been that plants do have several built in  clocks but they all keep their own local time and are not exactly   synchronized. Sounds  a bit chaotic, but then there were no evidence to prove otherwise. And without proof scientists don't take decide one way or the other. 

20th November issue of Nature carries an interesting report by Endo et al  on the circadian clocks operative in plants. Endo and team proceeded to take a closer look at the  plant Arabidopsis thaliana. With short life span and  a  small genome (135mbp), arabidopsis thaliana is roughly  the vegetarian  equivalent of the guinea pig  in the lab. 
  

Endo et al sought answers at  molecular and genetic level on the circadian rhythms in arabidopsis thaliana.   The team  separately analysed three main cell lines in the leaf:  the epidermal cells on the surface ,  the   mesophyll cells underneath , which run  the photosynthesis factory and then the   vasculature cells  responsible for the plumbing system. This is important because, even when the solar factory is closed for the day, the plumbing system continues to do the logistics work  Endo and team  monitored the gene expression and  level of specific marker proteins  in vivo and also   in vitro for  these three types of tissues. It was  found that the mesophyll and vasculature clocks function independently but are not altogether uncoupled. Plants have two loops of cellular activity, the day loop and the night loop. The genes responsible for rhythmic behaviour in the mesophyll tissue are active during day time and those in the vasculature  tissues  report for duty during the evening hours. The day partollers must be leaving telltale signs for the night patrollers. The team also found that the vasculature clock has the upper hand and controls the physiological responses of the  plant as a whole. They suggest that the vasculature and mesophyll clocks are akin to the central and peripheral clocks in mammals  or evening and morning cells in drosophila
Tailpiece  
Acharya Jagadish Chandra Bose was one of the first to suggest  that plants have life and that they responded to various stimuli including light and dark cycles through  electrical impulses. In 1902  Bose compiled his  experiments, observations and conclusions   and published   Response in the living and non-living . This book  (currently  available  an e-book  in public domain, thanks to the Project Gutenberg),  carries complete details of the simple,  elegant and extensive  studies.
 References:

1. Response in the Living and the non-Living : J.C. Bose
2. Time specific clocks in Arabidopsis show assymmetric coupling.  Endo et al Nature,       20th Nov. 2014 p419-422.
3. Spontaneous spaciotemporal waves of gene expression from biological clocks in the leaf : Wenden B et al  Proc. Natl. Acad. Sci.(USA),109, 6757-6762 (2012)
4. The circadian clock in Arabidopsis is a simplified slave version of the clock in shoots.James, A.B. et al  Science 322, 1832-1835(2008)

Wednesday, November 12, 2014

Science and the Society : The TWAS-Lenovo Science Prize 2014

Sultanate of Oman hosted the 25th  annual meeting of The World Academy of Sciences (TWAS) at the capital city of Muscat from 26 till 28th of October. The venue was  one of the most scenic locations of Muscat, the Barr Al Jissa resort


 Quarraisha Abdool Karim 

This year, epidemiologist  Dr Quarraisha  Abdool Karim  was awarded   the  most prestigious TWAS-Lenovo Science Prize  for her relentless work in the area of HIV/AIDS prevention. Her research work  which  has few parrallels in terms of the socio-medical strategies and human impact has  helped set guidelines for patients infected with HIV  and doctors treating them.  It was in 1989 that Ms Karim joined  Aids Research Program of South African Medical Research Council' after obtaining a post graduate degree in Public Health  from Columbia University, USA. She soon realized that sociology is an integral part of epidemiology. She says "AIDS brought together two separate things for me; I saw the convergence between advocacy work and science ". The  extensive surveys she conducted in sub-Saharan Africa  brought to light not only the alarming statistics  but also  the plight of helpless and ignorant  adolescent girls    in a male dominated society.  Public health data showed that in South Africa alone an estimated 6.1 million people suffer from HIV infection, more than any other nation in the world. Women who are younger than 24 years are at  a greater risk than men in the same age group. Could there be a way to protect the women from HIV infection that didn't call for cooperation from their male partners? That is the question Karim and her team asked aloud. 


Tenofovir :courtsey Wikipedia
The team took a relook at   tenofovir an antiretroviral   drug used in HIV treatment   and developed it into a topical gel to be applied to genital areas.  In a study  spread over 3 years,  Karim and her team demonstrated that application of 1% tenofovir  gel  reduced infection in women by ~40%.   Follow up studies and mathematical modelling have indicated that tenofovir gel has the potential to  prevent millions of new infections. Currently  the gel is undergoing rigorous clinical trials. By the end of  2015  it would  move into licensing, manufacturing and distribution stage. 

Dr Karim is an associate professor of epidemiology at the Columbia University medical Center  and associate director of CAPRISA ( short for Centre for the AIDS program Research in South Africa).  The TWAS-Lenovo prize comes with a an award of 100,000 US$ provided by Lenovo.
Tailpiece: 
TWAS delegates were pleasantly surprised to  receive  a small (4cm long) Omani Khanjar  as memento . While fiddling with it,  it suddenly unleashed  a pendrive!

References: 
  • Simon V, Ho DD, Abdool Karim Q HIV/AIDS epidemiology, pathogenesis, prevention, and treatment Lancet. 368 489-504 2006
  • Woodsong C, Abdool Karim Q    A model to enhance informed consent: experiences from the HIV Prevention Trials Network American Journal of Public Health 95 412-419 2005
  • Q.A Karim et al Effeciveness and Tenofovir Gel an antiretroviral microbicide for the prevention of HIV infection in Women Science 3 September 2010:1168-1174


Thursday, October 9, 2014

Now you see it; Now you don't


Hiding in plain sight is a common theme  in sci-fi or horror movies. Sci-fis show some respect for the rules of physics, or hypothesize  new ones ; but ghosts spurn  all laws and do as they please. And  Man? Man definitely knows ways and means to play with the laws, bend them, hoodwink them, and even  find loopholes. Light is an electromagnetic radiation(EMR) and hence one way to hide from light will be  to design a cloak using a special fabric with unique electrical  and magnetic characteristics (electrical permittivity and magnetic permeability to be precise).  Such a fabric will be able to bend and curve light  in every which way we want.  Not that we haven't been successful in this attempt; lo and behold! we have created metamaterialsThese man-made materials, by virtue of their patterned structure can manipulate light very effectively. Thus metamaterial cloaking could  bestow invisibility on an object.  Yes cloaking indeed; precisely and literally covering up. The wrapper will gently and smoothly guide light that falls on it as if there is no solid object underneath.Though as of now a definite possibility, metamaterial cloaking  is not yet  a reality but  a field of intense research activity.  Inspired by the powerful and versatile attributes of the  binary system (0,1) of digital electronics, Giovampaola and Egheta have suggested the  concept of  Digital metamaterials  using just two elements of unique permittivity  as bits  to design a series of unique and versatile  metamaterial bytes  to suit any application. Still have miles to go in that direction. 

Peacock in the woods,
Painting by Thayer  Courtsey wikipedi
a
Bradypodion taeniabronchum
Courtsey : Wikipedia
We need to pause here and ask an important question: what exactly do we mean by being invisible? Please ignore the philosophical tone in the question and consider it  purely in the  practical context. Invisibility is neither abstract nor absolute in practical terms,  it is  always relative- relative to the ambiance, or the background. For example chameleons change color and merge with the ambiance and go undetected; Abralia, a variety of   mid-water squid, uses counter illumination to camouflage itself against the ocean glow. Likewise  Thayer with deft strokes of  brush  concealed his peacock in the woods.

Since light can't be fooled in a straight fight,  Schittny et al  decided to try   concealing objects in  in diffused  ambience such as mist, smoke, fog or  turbid liquids(1). In a murky medium photons gets tossed around, scatter and diffuse.  Hence its behavior is  best described by Fick's Law  of diffusion  and not by Maxwell's equations. The diffusivity of the ambience (D0), the object (D1) and  the wrapper(D2) assume significance.  Schittny et al caught on this point. How about negating the diffusivity  of the object to be hidden   with an equal but opposite diffusivity of a wrapper? 
  
In the July issue of Science Schittny et al demonstrate how an object can  be effectively hidden  in diffused light. They chose  hollow stainless steel cylinder and sphere as test objects to be concealed.  Since light doesn't  pass through steel these objects have zero diffusivity (that is D1=0). Based on the mathematical relationship that  linked  the dimensions of the object and  thickness of the  wrapper to D0 and D2 they could  formulate the conditions for perfect concealment (2).  Armed with these results they first coated the object with a very thin layer of white acrylic paint to ensure efficient diffusive reflection. For wrapper they chose polydimethylsiloxane (more popularly known as PDMS) doped with 10 micron size melamine resin particles.  To give a feel for the sizes involved : the cylinder (and the sphere) had a diameter of little more than 3 cm,  and in each case  the wrapper  thickness was less than 4mm. The objects were immersed in a rectangular transparent plastic  tank filled with deionized water containing  a small amount of white dispersion paint. The paint particles imparted the required turbidity to the medium. One side of the tank was illuminated by the glow from a computer screen. The monitor provided the flexibility of adjusting the incident light.  Images were captured using a digital camera positioned on the opposite side. Experiments were carried out with the cylinder as well as the sphere,  both  could be completely hidden from view.  The results are highly significant on two counts:  The omni-directionality of the phenomenon  and validity throughout the visible spectrum.

Schittney et al  conclude their paper with the suggestion " one could insert metal bars which are almost as thick as glass into bathroom frosted-glass window to prevent burglary. Usually these bars would be visible via the diffusive  shadow they cast. By adding thin diffusive cloaking shells around the metal bars, the window would again appear as a homogeneously bright milky glass".  

Tailpiece:
What does invisibility portend for Man? 

Almost 2400 years ago Plato cautioned  that invisibility will completely shatter   man's fragile morality mask;  he gave the parable of   Gyges of Lydia (The Republic  Plato -Book 2 : Story of Ring of Gyges). 

Nor did   Griffin  have a happy ending. For him invisiblity was a power tool to usher in reign of terror.( Invisible Man - 1897 novel by H.G Wells )

References:

1.Invisibility cloaking in diffusive light scattering medium Schittny et al Science 25th July 2014 Vol 345, pp 427-429
.
2. Fick's second Law  transformed: One path to cloaking in mass diffusion  Guenneau  and Puvirajasinghe,   J. Royal Society Interface 10 20130106 (2013) 



Sunday, September 7, 2014

Revolutions : Of the Biomedical Type

Ambitious research programs in the bio-medical field are set to bring in revolutions: not imminent  but sure enough.


DARPA (Defense Advanced Research Projects Agency, U.S.A)  is asking a  rebellious question  about RAM; no it is not about  the familiar Random Access Memory, but Restoring Active Memory.  Or in simpler terms the question is can we reverse memory lapse? In soap operas sudden memory loss of a key character  is a trick  to raise TRP when the story reaches a cul-de-sac.  But DARPA has more serious concerns. Its focus is on soldiers who have suffered severe traumatic brain damage and as consequence lost memory. Many in the scientific fraternity are skeptical but a  few are optimistic and would like to give it a try. Research teams at University of Pennsylvania and University of California @ Los Angeles have decided to jump in. The first step of course will be neuronal mapping of the brain and both teams  feel it will be advantageous to start with epileptic patients.  Ultimately  DARPA  wants tiny implantable devices that can RAM. 

In matters of heart the attempt is to get away from the implantables and  substitutes. Could we browse around in body's own toolkit and come up with mix and match tricks? Cardiomyocytes are heart muscle cells.  It is known that the human development Factor T-box-18, (a gene necessary for the development of pacemaker cells in the heart)  has the power to reprogram ventricular cardiomyocytes to pacemaker cells. Hu et al  are exploiting this possibility, a biological alternative for an implantable pacemaker. In a recent report they indicate that this indeed is possible. Hu and team have conducted experiments on pigs with induced cardiac block.  Using   a specially designed   catheter they directly delivered the gene concoction via an intravenous injection to the left ventricle. Though the test animals registered improved performance, a lot more follow up studies are pending. 

On a parrallel highway, as a part of stem cell therapy,  Organoid technologies are being actively pursued. Organoid means organ-like . Pluripotent sem cells can turn into any cell line, liver cells or spleen cells, kidney cells, intestinal cells ....etc.  And the amazing thing is when coaxed into such specialized  cell lines, the cells organize themselves exactly  as in that tissue. And if we can let them grow on appropriate   Extra cellular matrix (ECM)    then   we would  have a great organ model  to study the progress of  and possible remedies  for   diseases. The significance and value of such studies multiply infinitely if the patient's stem cells are used.

Tailpiece
Birbal was going ga-ga about the advantages of having a flying horse.  Finally Akbar relented and agreed to fund the project. But  on one condition: if  the flying horse doesn't become a reality in 25 years, Birbal will be executed.  Birbal agreed; his well wishers chided him. But Birbal was undaunted: he said "In 25 years a lot of things can happen. For example the emperor might die, I might die . And who knows even the horse might fly" 

Of course, it took centuries,but  it did fly , didn't it? And how elegantly! 
  
Pegasus in Greek Mythology



Concorde Supersonic
Albatross II 1868




2.Y.F.Hu et al: Sci.Transl.Med. 6, 245ra94(2014)
3.Organogenesis in a dish: Modeling development and disease using organoid technologies
  M.A. Lancaster & J.A. Knoblich   Science: 345, 1247125(2014)

Friday, August 8, 2014

Water Stories

Any discussion on water slips into the domain of philosophy. Most mundane at  the same time most sublime, scientific aspects of water are equally fascinating. Chemically water is an innocuous molecule, with the simple formula H2O. Alas! don't be fooled by the simple formula, because it conceals incredulous  complexities that made Life itself possible on this planet. The chemical formula shows one oxygen atom linked two hydrogen atoms, but in reality  there is extensive  sharing of hydrogen atoms. Hydrogen bonding. is the term chemists would prefer. Hydrogen bonding is a very fast  dynamic process,  breaking and making  happens in a jiffy,  in picoseconds (10 -12 second).  Almost all  the unusual properties that water exhibits, have been be linked to hydrogen bonding. For decades Ander Nilsson and his team  have been investigating the weirdness of water. In his opinion Water is the strangest liquid known. His .Public Lecture Water The Strangest Liquid  is a nice refresher on the uniqueness of water. 

273K (more popularly known as  0 degree Celsius), is  the melting point of ice or freezing point of water. But under certain circumstances water can be cooled to well below 273K without ice formation. In other words water can be coaxed into a supercooled liquid state.  Here is the only catch : water should be  ultrapure,  and shoulld very carefully cooled. Till about 232K (-41 degree C)  water  remains a liquid and then homogeneous crystallization sets in.  This temperature referred to as TH, is the lowest temperature at which rate of crystallization of ice can be measured reliably. Below TH,  ice crystallizes in microseconds.  It must be mentioned that  experimental variations do affect TH by a unit or  two.  The pertinent question is what is the structure of  water below TH?.  

A very difficult question indeed. Because of experimental limitations  the domain   below TH  has so far remained a blackbox and is generally  referred to as No Man's landThere are indications that below TH   heat capacity and compressibility of water increase abnormally and several  structural models have been proposed to account for  these phenomenal changes. In the recent issue of Nature magazine(1) Nilsson's team at the SLAC National Accelerator Laboratory, Menlo Park, California report an  an elegant experimental platform with ultrafast X-rays as the probing eye which can  blink in femtoseconds, (Femtosecond= 10 -15 of a second) . Water droplets of diameters ranging from 9 to 37 microns  were cooled rapidly by evaporation as they  were propelled through vacuum.The team could detect liquid water  even at temperature as low as 229K  but noticed that  a crop of  ice crystals too appeared very quickly. The X-ray pattern suggested tetrahedrally coordinated liquid phase. which could  the trigger   homogeneous nucleation. 

When  experimental hurdles  block your way , the next best thing is   to resort to simulation and modeling.  In the same issue of Nature a group from  Princeton University, headed by Pablo Debenedetti report (2) Monte Carlo simulations of deeply supercooled water. They performed calculations on ST2 model of water  with  temperature fixed at 228.6K and pressure at 2.4kbar .  Profile of   the energy surface was monitored as a function of density and a structural parameter called Q6 . They propose that  the system oscillates between two liquid forms, High Density Liquid (HDL) and (LDL) with no inclination to crystallize, though a crystalline phase too is present.  

The same issue of Nature  carries a write-up on the scarcity of drinking water and unconventional methods  being used to address this challenge, such as construction of qanats as practised by  ancient Persians  and   the modern fog harvesting technique.



1.Ultrafast X-rayprobing of water structure below the homogeneous ice nucleation temperature : Sellberg et al: Nature 19 June 2014( Vol. 510, pp381-384)

2.Metastable liquid-liquid transition in a molecular model of water,  Palmer etal: Nature 19th June 2014 ( Vol. 510, pp385-388)

3.Water on Tap , Schiermeier:  Nature 19th June 2014 ( Vol.510 pp 326-328 )

Tuesday, July 15, 2014

Genetic Matchmakers?


Matchmaker, Matchmaker,Make me a match,
Find me a find, catch me a catch
Matchmaker, Matchmaker
Look through your book,
And make me a perfect match 
(Film :Fiddler on the Roof (1971))



Perfect 46 is a recent science fiction movie  by Brett Ryan Bonowicz,  centered around a personal genomics  company  named  Perfect 46. Perfect 46  symbolizes 23 pairs of  perfectly matching genes in a progeny. The Company counsels couple planning parenting hood and based on a unique algorithm suggest  a perfect match between a donor and a receiver. 

 Well, there indeed is an element of truth in the story;  given that the United States Patent Office has granted patents to this effect to two companies  GenePeeks  and  23andMe.     The GenePeeks patent lists 14 claims  and states  that  it addresses the   need for methods of assessing  the inheritance of such complex attributes prior to, or in place of, conception. and provides a pre-conception method for  predicting the likelihood that a hypothetical child of any two persons, of opposite sex,or same sex, who may or may not be fertile , will express any trait or disease that is subject of genetic influences that have been previously characterized , completely or partially.  This patent is the foundation of GenePeeks' Matchright™   Program. Perhaps 23andMe took a few more hasty steps  towards what looked like eugenics and designer babies,   but beat a quick  retreat when   USFDA  imposed certain restrictions.  

GenePeeks claims that its  services are limited to identifying the probability of inherited diseases;  as a screening tool to select suitable donor for a given receiver or vice versa . The CEO of the company Anne Morriss had to endure anxious moments   because her baby was born with a rare genetic disorder called the MCADD ( medium chain acyl CoA dehydrogenase deficiency) which meant the baby's enzymatic apparatus  couldn't digest fat.  It was only later that she found that she as well as the sperm donor she had chosen, both carried this rare genetic trait. There are several hundred inheritable diseases but the probability  of someone receiving defective genes from  both parents is rather low. The question Anne asked was could this have been avoided?  Sure, if she had prior knowledge of the genetic makeup of herself and the donor. That was the motivation for Anne Morriss and soon the company GenePeeks and the program Matchright™   became a reality   with the active participation of molecular biologist Lee Silver.  Matchright™   aims to completely eliminate the possibility of the Mendelian diseases in  assisted reproduction technology  by thorough genetic screening of the prospective donor/recipient pair for recessive genes.   For the time being the capability of Matchright™   is limited to single gene defects but  they hope to be able to confront in future more complex diseases such as diabetes, cancer, stroke etc.  where multiple genes are implicated.


References:

Gamete donor selection based on genetic calculations 
Method and system for generating a virtual progeny genome