The puzzle called Universe.

Our romantic relationship with the Cosmos  will continue.   The more it reveals  the less we recognise.  Primitive man looked at the lustrous objects in the sky with awe. The Unknown  elicited fear and suspicion. He feared and  suspected it affected him, his health, his family his crops...... Bewilderment launched  imagination to the utmost bounds. He built an unattainable heaven in the skies and spun tales of myriad hues  to appease his troubled heart.   But his  yearning to know all, continued.

Time went by.  Man made rapid progress in path of knowledge.   In 400 BC Aristotle  came up with the geocentric model of the Cosmos in his book De Caelo( On the Heavens). Though in 300 BC Aristarchus murmured the cosmos is heliocentric, no one took him seriously. Aristotle's model continued o hold good without  being questioned for almost   thousand years.  Then came Copernicus, who in his books substantiated the concept of heliocentric universe. So did Giordino Bruno and later Galileo. But alas, Copernicus had to keep his writing hidden from Church, Bruno was burnt at stakes and Galileo was made to apologise. For it was unbiblical to negate geocentric universe.  Nevertheless, even as he apologised,  Galileo muttered eppur si muove ( still it moves)

A year after Galileo died, Newton was born. Alexander Pope, the English poet puts it emphatically: 

Nature and Naure's laws lay hid in night; 

God Said let Newton be! and all was light 

Newton brought about a paradigm shift in many areas of science. Most important being in recognising  Gravity as the  fundamental natural force.  He described a static, steady state infinite Universe. But this model was rather unstable because the gravitational  pull would have caused the universe to collapse into itself. Notwithstanding this, our repertory  was  getting crammed  with information on stars, planets, comets, nebulae, galaxies.......

Introducing  Λ  the Cosmological constant ,an equivalent repulsive force to balance the  gravitational pull, Einstein steadied Newton's model. Before we could  get settle down with that model,   Edwin Hubble's  observations and calculations showed that  galaxies are receding and that meant  the universe is expanding.  But that didn't  in anyway hinder our space projects, we sent Man to the Moon, probed Venus and Mars for possible life, built space stations.......Figured out the necessity of black holes and wormholes  to explain the unexplainable. 

Artist's concept of the Cosmic explorer to be launched in 2020

Scientists  built more and more sophisticated instruments to peer into the darkness.  And based on what they saw  were forced to revise their stand:  No,  the universe was not just expanding at a slow monotonous rate, but rather   expanding at an accelerated rate. They needed   Dark Matter  and Dark Energy to  explain the unexplainable.  


We practically know nothing about Dark Matter and Dark Energy except that  the material Universe that   we know including all the far and near galaxies, black holes and other cosmic matter  account for  only roughly 5% of the normal matter, the rest is divided between dark matter  (~27%) and dark energy (~68%). 

Euclid is getting ready to probe the Darkness  around us. The launch is scheduled for 2020. 

REFERENCES:
1. De Caelo by Aristotle
2. Aristarchus of Samos- The Ancient Copernicus by Thomas Heath Oxford @ Clarendon Press 1913
3. On the Shoulders of Giants: Stephen Hawking. Viva Books Private Ltd. New Delhi ISBN 8176494518
4. Dark Energy, Dark Matter
5. Euclid 

Let's thumb our nose at the superbug

Yes, indeed at the  superbug, the  multi drug resistant   Staphylococcus aureus.  Generally referred to as Methicillin resistant Staphylococcus aureus (MRSA for short) this strain is not only resistant to the beta lactam antibiotic methicillin(production and use of which have since been discontinued) but also to subsequent generations of more potent versions of such as oxacillin, nafcillin, cloxacillin,  flucloxacillin, dicloxacillin etc.  Indiscriminate use of  antibiotics   has given rise to multi drug resistant bacteria. Sturdier strains  evolve naturally as part of survival strategy. Currently methicillin resistant  S. aureus, vancomycin resistant enterococci, and third generation cephalosporin resistant gram negative bacteria all have become a reality.  For quite sometime now the last remaining weapon  in our armoury has been carbapenem, and suspicions abound that  carbapenem resistant varieties too have made their appearance. According to WHO report (2014) in  a couple of decades   antimicrobial resistance will pose more dangers to mankind than perhaps even cancer.

Multi drug resistant Staphylococcus aureus is the root cause of alarmingly high percentages of hospital associated infections (HA-MRSA) and community associated infections (CA-MRSA).  It is known that one of the niche sites where S.aureus sets up colonies in human body   is the nasal passage.  But amazingly,  only  30% of the human population permit S.aureus to colonize in their the nasal passage.  So how does  the rest 70%  prevent  S.aureus  colonisation? What is the barrier?  An interdisciplinary research team at  Tubingen University (Germany) sought answers to this key question.  Samples of nasal microbiota were collected, screened and analysed which revealed that  in presence of  Staphylococcus  lugdunensis,   S. aureus just couldn't survive. The team then conducted experiments on cotton rats, the well established model for studying infectious diseases because they are vulnerable to various human pathogens.  Focused studies revealed that S. lugdunensis secretes a compound which proves lethal to S. aureus. The compound has been named lugdunin.

Lugdunin (courtesy:wikipedia)  

Zipperer et al tested the efficacy of lugdunin against several other pathogenic bacteria and found the results extremely encouraging.  The team feels  that lugdunin could open up a new class of antibiotics: Macrocyclic thiazolidine peptide antibiotics. This might prove to be a paradigm shift  from the  beta lactam family of antibiotics which bacteria have learned to counter. 

But again we need to tread  cautiously, because S.lugdunensis is neither benign nor innocuous; it is pathogenic and can  cause cardio-vascular and soft tissue infections. Indiscriminate use of lugdunin shouldn't create another Frankenstein. 

Tailpiece: 

References:

1. WHO on Antimicrobial resistance:Global report on surveillance(2014)

2. Carbapenems: Past, present and future:   Antimicrobial agents and Chemotherapy   Papp-Wallace et al 55(11) 4943-4960, 2011

3. The role of nasal carriage in Staphylococcus aureus infections: Lancet Infectious 
     diseases5 751-762 (2005)

4. Human commensals producing a novel antibiotic impair pathogen colonization:            Zipperer  et al Nature(28 July 2016)  vol.535, pp511-516. 

Pain Management: Should it be Gender Specific?

From the time when  the blame was squarely put on the shoulders of  spirits, demons, ghosts and wrath of gods,  we have come a long way in understanding and managing pain.  Sure,  we still don't have the complete picture , but what we know  enable us to manage pain to a great extent.  For example  we know that  the bundle of nerves inside the  dorsal horn of  spinal chord  processes somatosensory information, nociceptive terminals  relay signals to several domains in the brain,  that   body secretes its own brand of analgesics called  endorphins and enkephalins, that these bind to opioid receptors and block pain signals ,  that modern day painkillers act the same way,   so on and so forth..... .

We also know that physiological and psychological factors can modulate the intensity of pain. Gonadal hormones are known to influence the  behaviour of one set of opioid receptors called mu receptors.   Naturally the question arises-   is there a significant gender difference  in the  sensation and perception of pain? Do  male and female species respond differently to  pain  and its management?. In general  experimental data  indicate that women have a lesser threshold for pain than men. Male rats injected with the female hormone oestrogen  showed lower threshold and female rats injected with testosterone the male hormone registered elevated tolerance. Certain classes of painkillers give better relief for females.  Jeffrey S. Mogil,  a neuroscientist with both the Dept of Psychology and the Alan Edwards Centre for Research on Pain,  at the McGill University, Montreal, Canada   is very clear on this topic. He states that " sex differences in pain and analgesia are real and robust."  Mogil and his research team are convinced that these differences go beyond what  hormones can account for.   They have detected that  pain pathway itself is different - in male rodents microglial  cells  and  in female rodents  T cells process pain. (By the way  microglial cells are  immune cells of the central nervous system  and T cells are a subgroup of white blood cells.)

Preclinical research is routinely conducted  using male rats only. Female rats are not included for the simple reason that their fluctuating hormonal levels might introduce unwanted variability. Perhaps it will be practical  to include a set of male rats injected with prescribed levels of female hormones.   Or include  a parallel set of female rats. 

However  given that Pain is forever  accompanied by patient specific  emotional baggage of  the past, the present and the future,   the need of the hour is  an analytical tool for objective and unbiased measurement. Several groups are at work to realise this goal. Well, the ultimate device won't be as simple as  a thermometer, but more like a brain scan. Current focus is on  brain imaging using functional MRI.  But  it would indeed be a painstaking exercise to sift the actual pain signal  from its  virtual components. 

Tailpiece:

According to Roman mythology, Doloros (Algea in Greek mythology) is the goddess of anguish and pain.  In 1945 Dr LJB Gluzek claimed to have designed a device called Dolorimeter  which could measure pain with 97% accuracy.  Time magazine dated Jan 1945 published  an interesting commentary on it. 

References:

1. Pain : Nature Outlook -Nature 14 July 2016,  Vol.535, issue 7611, S1-S19

2.Sex differences in pain and pain inhibition: multiple explanations of a controversial phenomenon.  Mogil, J.S, Nature Reviews Neuroscience, 13:pp859-866, (2012.)

3. Sex differences in pain and analgesia :Mogil, J.S et al Progress in Brain Research 186, pp141-57 (2010)

4. Sex differences in pain: A brief review of clinical and experimental findings: Bartley et al British Journal of Anaesthesia vol. 111(1),pp52-58(2013)  

5. Sex, Gender and Pain : A review of recent Clinical and Experimental Findings,
Fillingim et al, J. Pain  10(5) pp 447-485(2009)

Sneezing: A study in fluid dynamics

Sneezing is an explosive event. There are some who can sneeze unobtrusively into their handkerchief  but more often than not it is an involuntary, uncontrollable  reaction of the body to  tinkling in the nostrils. Why would anybody want to analyse sneezing?

Lydia Bourouiba's area of research is the interface of  Fluid Dynamics and Epidemiology.  A faculty at the MIT, Cambridge, USA,  she with her research team is in the process of understanding the fluid dynamics of sneezing.  It is a well accepted fact that  fluids expelled by an infected person during a sneeze or a cough have the potential to infect those who are nearby. If this violent expiratory event, as Bourouiba describes sneezing, could be well understood in terms of  how far the pathogens could be propelled, then public health officials could put in place appropriate programs for the containment of contagious diseases.

A sneeze in progress: courtesy wikipedia 
For videos taken by Bourouiba's group visit Video Gallery

A " let go " sneeze has been vividly captured in the picture shown. Aerogel particles spewed out by the sneezer (if I may use the term)  spread  and eventually disappear into the air. Bourouiba and her team are  concerned about   how fast and how far the aerosol particles can travel.   Healthy volunteers  were invited to participate in a study and their nostrils were tingled in the old fashioned way to induce sneeze. The research team then  captured the entire event using ultra high speed cameras.  
Violent expulsion of air -saliva mixture formed an elongated   cone of  turbulent cloud which expanded and  spread around.  (The dynamics has marked differences  from the focussed high pressure spray from an aerosol can).   The team was surprised to find that aerosol droplets could reach  as high as the ceiling and as far as the end of he room. They also observed that the droplets could persist in the air  for almost 10 minutes. In a follow up study  the team  took 8000 frames per second to film  the entire process of sneezing.  Replaying it later in slow motion, they saw  that  fluid mixture is expelled as a sheet which breaks up into rings as air pokes holes in the sheet, the rings   then elongated into filaments and ultimately formed droplets. Droplets  are then transported through the air  by diffusion. The diffusion controlled movement of aerosol droplets in  confined spaces such as inside a cinema hall or an aeroplane is what interests Bourouiba and her team. They want to understand how  the logistics of airflow within the confined space,  ambient temperature,  humidity, etc. will influence  aerosol size  and transport. 

References
1. Where sneezes go- Corie Lok,  Nature pages 24-26 vol. 534, 2 June 2016. 
2. Bourouiba Group

Urgently Needed: Smarter Ways of Separation

Stages of Crude oil refining Courtesy Wikipedia


 . 

Chemical industries  not only  top the list of environmental polluters but also  energy guzzlers. According to the US Dept. of Energy,  petroleum, paper and other chemical industries together consume 32% of the total national energy. Of  this 45-55% energy is spent just to separate chemical mixtures.  Separation and refinement of components  are absolutely unavoidable steps in chemical industry. If so could we have more energy efficient separation processes, please?

A report  analysing the energy expenditure  in the US Petroleum Industry,  hints that if we could cut down the energy incurred  for chemical  separations,   possible  saving of 420 TBtu per year could be achieved. Fractionation of crude oil, separation of alkenes and alkanes, separation of isomers of  benzene derivatives - all these  are essential yet  tricky downstream operations Because the components are so similar in their chemical and physical properties, as  of now fractional distillation is the only effective answer. Professors David Sholl and Ryan Lively   (School of Chemical and Biomolecular Engg, Georgia Institute of Technology, Atlanta Georgia, USA)    reiterate  that " Purifying mixtures without using heat would lower global energy use, emissions and pollution and open up new routes to resources."  
   
Sholl and Lively suggest that we re-evaluate  alternate  technologies such as adsorption, crystallisation and membrane separation. Of course they  are aware that thermal processes can't be avoided altogether but even a partial substitution can cut down  the energy cost and reduce  pollution substantially.  For example petroleum cracking  yields a mixture of paraffins. Ethylene, a gaseous olefin  which polymerises to yield polyethylene, (or polythene as it is  commonly called )  must be isolated from this mixture. The current process of separating  the components  of the   paraffin gas mixture involves first liquifying the gaseous mixture   then subjecting the liquid  to cryogenic distillation under high pressure at ultra low temperatures. Could we avoid  this intermediate liquefaction/distillation step?  If so a lot of energy can be saved.  Perhaps a two step process could be adopted: in the first step carbon membranes  separate the hydrocarbon mixture into individual streams of 99.9% purity at ambient temperature and moderate pressure and the second step adopts cryogenic distillation to achieve higher purity.  
Sholl and Lively list seven processes which would  yield huge energy savings if alternate smarter methods can be devised. 

1. Hydrocarbons from crude oil
2. Uranium from seawater
3. Alkenes from alkanes
4. Greenhouse gases from dilute emissions
5. Rare-earth metals from ores
6. Benzene derivatives from each other
7. Trace contaminants from water  

Scientists and engineers need to think out of the box

Tailpiece:

Folklore tells the story of a little princess who was harassed by the wicked queen, her stepmother. The little girl had to sort out a hillock high mixture of grains into separate heaps, that too before sunset.  An army of ants came to her rescue and finished the job neat and clean before the timeline ended. 

If only life were a fairy tale!


REFERENCES

1. Seven chemical separations to change the world: Sholl and Lively,  Nature 28 April 2016, vol. 532, pages  435-7 

2. Bandwidth study on energy use and potential energy saving opportunities in US petroleum refining

3. Bandwidth study on energy use and potential energy saving opportunities in US pulp-paper Manufacturing

TRUST and FAITH: On Breaching the Barrier

"How could you, a mathematician, a man devoted to reason and logical proof....how could you believe that extraterrestrials are sending you messages? How could you believe that you are being recruited by aliens from outer space to save this world? How could you......?

.........................

 " Because" Nash  said slowly in his soft  reasonable, southern  drawl as if talking to himself, "the ideas I had about supernatural beings came to me the same way that mathematical ideas did. So I took them seriously." 

That was  from A Beautiful Mind : a biography of the  Nobel laureate and mathematical genius John Forbes Nash Jr. by Sylvia Nasar.

Almost half a century earlier Srinivasan Ramanujan had put it  slightly differently  "An equation for me has no meaning unless it expresses a thought of God". He was  certain that   it was goddess Namagiri, to whom he owed his mathematical gifts. Namagiri would write the equations on his tongue, Namagiri  would bestow mathematical insights in his dreams.  (The Man who knew Infinity  a   biography of Srinivasan Ramanujan by  Robert Kanigel 

Their respective colleagues   would state categorically that it was as if  Ramanujan and Nash knew the final answers before they even saw the problem. How do such brilliant  minds work?  Is it intuition?  The Oxford dictionary defines intuition as immediate apprehension or insight  without reasoning. 

Scientists are forever  curious to know.  Google's   AlphaGO , an  algorithm   programmed to play the board game GO, is the latest attempt to mimic this elusive human trait.   Located on networked computers (technical term distributed computing) the AlphaGO algorithm enables  

A GO game in progress(courtesy en:wikipedia)
Played with white and black chips, it is basically  a "surround and eliminate"  game

not only programmed moves but also  intuitive decisions, its creators claim.  With a computing power amounting to 1202 CPUs and 172 GPUs,   AlphaGO  demonstrated its capability  when it won 4-1  against the world champion Lee Sedol, recently.  

Tailpiece:

"Proof and Verification"  are the mainstays of Science.  In a recent editorial Nature cautions: Intuitive machines will need more than trust; they will demand Faith. 

A Beautiful Mind, biography of the Nobel laureate John Forbes Nash Jr. by  Sylvia Nasar  was made into a film in 2001 with the same title.    "The Man who knew Infinity"  a film based on Kanigel's book  has just been released. 

References:
1. The man who knew Infinity : Robert Kanigel,  Scriber 1991;Abacus 1999
2. A Beautiful Mind : Sylvia Nasar, Faber& Faber 1998
3. A Mathematician's Apology : G.H. Hardy , Cambridge University Press, 1967
4. AlphaGO 
4. How Google's AlphaGO Beat Lee Sedol
5. In two moves AlphaGO and Lee Sedol Redefined the future
5. Digital Intuition Nature, 529, 437 (28 January 2016)

On being environmentally conscious

Biologist and conservationist Edward O Wilson strongly feels that half of earth's surface must be set aside just for Mother Nature.  Its feasibility is debatable, but then we can't close our eyes to the hard facts that  a variety of human activities continuously pollute air and water  two precious components for the sustenance of life on this planet. This great threat to our ecosystem need remedies in real time.    

14 January issue of Nature carries a report by Alsbaiee et al from Cornell University on the use of beta cyclodextrin polymers as molecular filters for the instant removal of organic micro pollutants from water.  This could indeed  revolutionise water purification.  Molecular pockets of cyclodextrin(CD) can trap organic molecules. If you  string together thousands of  CD molecules and  knit them into a three dimensional polymeric network, then such a network  can be used as a membrane or mat  to  filter off toxic solutes from water. This has been tried earlier but  the performance was not upto the mark. In this context the standard is activated charcoal. The low efficiencies of CD polymers were  mainly because  of their very low surface area.  Now Alsbaiee et al  report the use of   rigid aromatic groups to tie up chains of CD polymers to  enhance the  porosity and  the surface area of the final product.    The new improved version registered performance efficiencies several fold higher than activated carbon.  Moreover the soiled filter could be easily regenerated by mild washing and reused.  

Alsbaiee et al demonstrated that 85% of toxic molecules such as   Bisphenol A  and S, 2,4- dichlorophenol, 2-naphthol, 1-naphthyl amine, metolachlor, propranolol, ethyl oestradiol were removed within minutes. The process holds enormous promise and could revolutionise the way we currently purify polluted water.  

Aanindeeta Banerjee et al from Dept. of Chemistry, Stanford University , California USA report their efforts to utilise atmospheric carbon dioxide through an environmentally friendly route. They steer clear of conventional chemical pathway, as that would involve high energy processes. Taking a clue from  the Calvin biochemical cycle, where carbon centred nucleophile reacts with CO2 to from  carboxylate anion,  Banerjee et al achieved the following transformations using moderate conditions: 200-350 deg.C and molten salts as catalysts. 

~~~C-H + CO2 ----------> ~~C-CO2H

~~~C-H +CO2 +ROH ---------->  ~~C-CO2R + H2O

Keeping in mind the abundance of lignocellulose (inedible biomass),  Banerjee et al demonstrate the conversion of   2-furoic acid  into furan 2,5 dicarboxylic acid, which  is an industrially important feedstock.  

Tailpiece:

If we surrendered
To  earth's intelligence, 
We could rise up rooted, like trees
Rilke in Rilke's Book of Hours: Love Poems to God 

References:
1. Half Earth:Our Planet's fight for Life: Edward O Wilson  Publisher Liveright 2016, iSBN-13:978-1631490828

2. Rapid removal of organic micro pollutants from water by a porous beta cyclodextrin polymer.   Alsbaiee et al Nature Vo. 529 14 January 2016, pp 190-194

3. Carbon dioxide utilization via carbonate -promoted C-H carboxylation. Banerjee et al Nature Vol.531 , 10 March 2016, pp 215-219