On Magic Blue

              

lapis lazuli rock ( Wiki)

"The most perfect of all colors", thus wrote Cennino Cennini in the 15th century,  about   azzurre oltre marine in his   handbook for artists.  This mesmerising, precious  blue popularly known as ultramarine was  worth its weight in gold.  For Renaissance painters,  there were several   blue pigments to choose from  such as azure della magna, indigo, lapis armenus etc., but ultramarine  was the most sought after blue pigment.  The mineral rock  lapis lazuli from which the blue pigment was extracted, had to be imported from  beyond the seas and hence the name ultramarine.    Ancient caves dotting the Sar-i-Sang region in  Afghanistan were and are still the sole yet rich source of   Lapis lazuli. In old latin lapis means stone  and  lazuli is a derivative of lazulum,  a word associated with colour  blue. During there medieval times, rich patrons who commissioned paintings would often specify in the contract that ultramarine pigment must be used.  Because the  blue pigment prepared  from lapis lazuli retained brightness and clarity  for ages  whereas the cheaper  lapis armenus   turned green over time. Though comparatively costlier, ultramarine had  excellent spreading quality minute amounts were enough to paint the flowing robes of Virgin Mary or royalty or the vault of the  sky.

 Virgin Mary and infant Jesus 14th century
(wiki)

Lapis lazuli was known to the ancient world and they fashioned it easily into artefacts such as jewellery and decorative pieces.  But the process of  extracting  the blue pigment from the  rocks was laborious. Cennini in his  handbook  on the  art and science of painting and paint formulations, describes the process in detail. He cautions that for high quality pigment, blue rocks with minimal grey areas  must be selected and   ground dry to as fine a  powder  as possible.  The fine powder was then intimately mixed with 3 times  its weight of melted bees wax and   plant resins such as mastic and pine. The dough so obtained was kneaded repeatedly while being left to age for several days. Later when  extracted with very dilute aqueous alkali the pigment settled as a fine colloidal  paste. 

From alchemists, at the turn of the 19th century, chemists inherited the  spell of utramarine blue. It was known by then that the lazurite component of lapis lazuli held the blue.  An intense competitive search for a synthetic substitute began in 1824 when a competition was 

announced in France  with a prize money  of 6000 francs.  French chemist Jean-Baptiste Guimet and German professor of chemistry  Christian Gemlin  at the Tubingen University succeeded in freezing the correct composition. The prize however was awarded to Guimet.  Gemlin as sorely disappointed. Guimet chose to keep his formula secret, Gemlin published his results  and paved the  way for the ultramarine pigment industry. 

ultramarine blue structure
courtesy PubChem CID71587188

  While it was known that  sulphur content was responsible for the blue colour,  it took a century and half to  conclusively prove that the blue color is due to trisulfur  radical anion. 


The cheap synthetic substitute had no business to retain the name ultramarine, but it did and  pushed out  the original from the artists' palette almost  for ever.  

Tailpiece

In 2015, an art exhibition "Lapis Lazuli: The Magic of Blue" was held in Florence.  On display were artefacts and paintings of unique beauty, spanning from antiquity to the  21st century. 
In 2018, an international highway, Lapis lazuli corridor was inaugurated connecting Afghanistan to Turkey, reminiscent of the old trade route.

REFERENCES:
1. A treatise on painting : Cennini,Cennio
2. Lapis Lazuli and the history of the "Most Perfect Color"
3. Color in Art: a brief history of blue pigment.

Demand and Supply : Dealing with aggressive customers

Bumblebee foraging on flowers
(courtesy: Wikipedia)

Bumblebees are very demanding customers; their demand is for steady supplies of pollen.   If pollen is in short supply, they register their protest, by injuring the suppliers.  A research team  led by De Moraes and Mescher  at the ETH, Zurich were surprised to find  this bizarre behaviour of the bumble bees and followed up with a systematic study. They were even more surprised to note that the damaged flora responded by flowering ahead of time.  Onset of flowering is known to be influenced by a variety of environmental factors such as sunlight, ambient temperature availability of water/nutrients etc., however direct bee intervention  is perhaps being reported for the first time.

Bumble bees are social creatures. Spring is the time  when they start new colonies. New colonies mean hive  full  of hungry larvae. Pollen is the  only food given to the larvae and that means there should be flowers in abundance. If for some ecological or anthropogenic reason flowering is delayed, then the bumble bee community  will have to starve to death. It is to avert   such circumstances that  worker bees  puncture   leaves of flowering plants with their proboscises and mandibles.  Plants and trees on their part, can't and don't blacklist these violent customers because bumble bees are the most important group of pollinators in the ecological symbiosis.  

De Moraes's team  noted that bee damaged  plants  flowered several weeks  ahead of undamaged control plants. Curious, they included another set of plants whose leaves were manually injured  with forceps and razor. Manual damage didn't accelerate flowering. The team alludes to the possibility that  bees must be lacing the wounds with a chemical cue.  Such behaviour, that of chemical signalling either within same species and/or between different species  is  well known in the realm of  symbiosis. Pheromones , allomones and kairomones  are classic examples. Aptly enough  these  are collectively called semiochemicals (semion in Greek means signal).  The Zurich team's next step will be to identify the chemical that the bumble bee leaves behind on the leaves.  And perhaps that might usher in the era of unseasonal flowers. 
  

REFERENCES:

1. The role of plant sensory perception in plant-animal interactions :  Journal of Experimental Botany 2015,  66(2) 425-33: Mescher, MC and De Moraes C 

2. Identification of an insect-produced olfactory cue that primes plant defenses. 

3. Bumble bees damage plant leaves  and accelerate flower production when pollen is scarce : Science 2020,  368, pp881-884 Pashalidou et al
4. Stress induced flowering in Pharbitis

When Enemy is Unknown

We humans have to be ever on  alert to combat  new, as yet  unknown pathogens. That is why WHO,  the World Health Organisation included Disease X in its list of most dreaded pandemics.  There was a brief explanation  along side which  read: " Disease X represents the knowledge that a serious international epidemic could be caused by a pathogen currently unknown to cause human disease, and so the R&D Blueprint explicitly seeks to enable cross-cutting R&D preparedness that is also relevant for an unknown “Disease X” as far as possible.  WHO has officially named the virus responsible for the  current viral outbreak in China  as COVID-19, (short for Corona Virus Disease 2019).  Is this the much dreaded Disease X? Opinions differ on this point.

Hemagglutin spikes on the viral particle(blue)
latching on to host  cell membrane(pink)

Forewarned is indeed good, but that doesn't make us exactly forearmed. How do we design weapons against an unknown pathogen? In an answer to this question a global collective has been formed called CEPI( Coalition of Epidemic Preparedness and Innovation).  Registered in Oslo, Norway CEPI is an independent organization which will facilitate collaboration among medical doctors and researchers.  A non-profit organization, CEPI will work closely with WHO  to speed up remedies for pandemics.  CEPI's ambitious plan is to build on the existing knowledge  and reduce the time span from gene sequencing of the virus to clinical testing of the vaccine to 16 weeks.   A tough task indeed given the fact that it usually takes years to develop vaccines. 

The genetic map of the COVID-19 virus , a single stranded  RNA of 29674 bases has been decoded. Scientists have also modelled its three dimensional folding pattern and identified possible niches where a drug molecule can bind and thus prevent the virus from replicating.  Currently several drugs  Flavipiravir, an antiviral drug proved efficient against a variety of viral infections and Remdesivir proven efficient against MERS and SARS in animals   are  in the pipeline.  In the meantime, China has adopted a multiprong approach  to fight the disease. From HIV drugs and  stem cells to ancient and  traditional Chinese medicines are being  tested as possible drugs. WHO authorities are making sure that strict protocols are followed in each trial.  Some of the results are indicative but not yet proven.   

But the gravest question is what if the virus is susceptible to frequent  mutations?  So far the virus hasn't exhibited any such tendency. But doctors and scientists are ever on the alert.
  
References:

1. Prioritizing diseases for research and development in emergency context
2.Therapeutic  options for the the 2019 novel coronavirus 
3. The road to a coronavirus vaccine runs through Oslo
4. More than 80 clinical trials launch to test coronavirus treatments
5. US begins trial of Gilead' Remdesivir in Covid-19 patients

Gene Editing Made Easy

Editing, in the digital world has become so easy.  Clicks such as  Find, delete/replace   allow us to a clean up a thousand page document in a jiffy. That the document runs a spellcheck as we write is another added advantage. Copy editors world over are  overwhelmed. Suppose we can do something similar for defective genes? Suppose we can search and find defective genes, delete them or  replace them with the correct version?  Well,  that is exactly what Anzalone and his team have  achieved recently.  The technique is called Prime Editing. 

DNA Double helix : Courtesy Wikipedia 

It was the discovery  of the   CRISPR -Cas9  enzyme system that made gene editing possible in the first place. (see The new genome editor: CRISPR- Cas9)  The original version of the gene editor just  nicked  both strands of the DNA double helix simultaneously,  removed the defective  portion and  then reckoned on the cell's natural repair mechanism to mend the helices.  However  more often than not, mending didn't happen in the desired way, leading to more complications.    The new improved version called Prime Editor, designed by Anzalone et al is  more precise and goal oriented.  Precision is built into the tool by tagging the Cas9 enzyme with a short RNA stub.  This RNA stub which  guides the tool to the exact  location for repair also carries the code for the edit.  More important Prime Editor cuts only one strand at a time, deletes the defective portion and inserts the edited version. It then goes and  nicks the complimentary strand at the appropriate site. The cell has to  now  match the edited piece while repairing. Armed with this tool, the team has performed 175 edits in human cells  including  deletions, insertions and point mutations. 

 David Liu, Professor at Harvard and also Director of the Merkin Institute of Transformative Technologies in Healthcare, and coauthor of the paper, is convinced that this is a great leap forward  for developing therapies for a host of genetic diseases. In fact the team claims that in principle could correct up to 89% of known genetic variants associated with human diseases.

But  still a long way to go before this becomes  clinically possible 

REFERENCE:

1.Search and replace genome editing without double strand breaks or donor DNA.  Anzalone, A.V., Randolph, P.B., Davis, J.R. et al.  Nature (2019) doi:10.1038/s41586-019-1711-4

Combating viruses of Body and Mind.

September 12th  Issue of Nature carries two interesting  reports. First one is a feature article  on how  Democratic Republic of Congo (DRC)  is reeling under the burden of ebola virus.  The second one is a scientific analysis of the dynamics of online hate activity. These two reports, from totally different domains  provide  valuable insights into how to contain a  mighty foe in real and virtual worlds.

Timely diagnosis and immediate medical care can contain ebola  outbreak to a very large extent;  yet the prevailing conditions in DRC posed  major obstacles.  Political instability, tribal rivalries, turf wars  and  armed uprisings  exasperated the health workers.  Illiterate communities were and still are ignorant of the danger they are in; they mistrust strangers, especially healthcare workers and the vaccines they bring along. In many cases, after first round of vaccination the recipients  can't be traced, hampering  follow up work  thus making the entire effort futile and perhaps even more dangerous. Hence the first step before the WHO

Ebola virus particle : Courtesy: wikipedia

team  towards containing Ebola virus in DRC was to earn  trust. This necessitated the creation of a network of healthcare workers partnering with   community/religious leaders, survivors etc.  UNICEF official Beigebieder observes that when survivors recount their experience, community members sit up, listen and are convinced.  Thus DRC has been successful in resisting the spread of ebola virus. According to the WHO website the 1000th survivor has safely returned home.  Indeed a success story.

Could we  similarly contain and  prevent the spread of hate in cyberspace?  Obstacles loom large even before we start. DRC is a country with well defined boundaries and government in place. The ebola virus and the victims are real, tangible, and there is a vaccine. In contrast  cyberspace is  a virtual reality without boundaries and everything that happens there shares the same characteristics.  Above all   in many countries strict privacy laws govern and protect  this virtual world.  

But that didn't deter Neil Johnson Professor of Physics at the George Washington University. He and his team set out to understand the seeding  and proliferation of hate networks in cyberspace; to be precise how clusters sprout and how they establish connectivity at multiple levels.   Banned clusters adopted multiple  mutation strategies to survive:  regroup into new avatars or migrate to new platforms  or even adopt a new language. Johnson et al cites the example of  KuKlux Klan, the White Supremacy Group generally abbreviated as KKK. When Ukrainian authorities banned the group, it reppeared elsewhere, with the name written in Cyrillic and English language detection algorithms couldn't  nab it. 

Johnson's team puts forward  different encounter methods which could be used singly or in combination without infringing upon privacy laws. Eliminate  smaller clusters totally or partially  that feed into a much larger node. With the support system wiped out the larger node will automatically shrivel away. Or set up rival groups  against hate groups so that the time and energy of the targeted hate group is wasted away.  Encourage dissent within hate groups thus disrupt their activities.  Are these doable? Well,   not everybody is in agreement with this strategy. 

TAILPIECE

And what physicians say about disease is applicable here: that at the beginning a disease is easy to cure but difficult to diagnose; but as time passes, not having been recognized or treated at the outset, it becomes easy to diagnose but difficult to cure. The same thing occurs in affairs of state; for by recognizing from afar the diseases that are spreading in the state (which is a gift given only to the prudent ruler), they can be cured quickly; but when, not having been recognized, they are not recognised and are left to grow to the extent that everyone recognizes them, there is no longer any cure.

Machiavelli: The Prince

REFERENCES:

1. The Ebola Wars : Amy Maxmen, Nature 12 Sept. 2019, vol 573, pp.178-183

2.Ebola virus disease

3. Hidden resilience and adaptive dynamics of the global online hate ecology: Johnson et al, Nature 12 Sept.2019, vol.573, pp.261-265

4. Hate  in cyberspace: Regulating hate speech on the internet
5. Researchers propose a new approach for dismantling online  hate networks
6. Researchers model hate networks in effort to battle them 

Algorithms: The New Props for Humankind

Did  our forefathers, the hunters and gatherers,  hear better and smell better? Probably yes, alludes  Yuval Harari.  Because their survival depended on being aware of strange, hidden, prowling  dangers. Later, as hunters settled down to be farmers, life styles changed, acute sense of smell and hearing was  no longer needed and hence  eventually lost.  Yuval Harari in his  voluminous books The Sapiens and the Homo Deus, cautions us that  we stand to  lose  our power of cognition, perception and  intuition because  we are steadily outsourcing  these mental exercises  to machines and trusting their decisions implicitly. 

True, but only when dealing with huge volumes of data.  Algorithmic analyses  with their powerful pattern finding and predictive ability have become  great enablers in diverse research  fields.  A computer algorithm can in a jiffy sift through  millions of details and arrive at  the most objective decision.  Elizabeth Honig, Art Historian  at the University of California, Berkeley ropes in  the help of algorithms   to identify the  original from fake among  art pieces. Specialists in Computer Vision and Machine Learning  consider this  a win-win situation because such  exercises challenge and sharpen  an algorithm's pattern matching ability thus  making AI  an enormously powerful tool.  

Tomasev et al   too followed the same path  to  develop  a clinical tool to predict impending kidney failure. Deep Learning is an algorithm commonly used  to identify patterns in huge data sets. Tomasev and team collected well over 6 billion data points  from multiple sources from   700,000 anonymised  patients spread over 5 years - 2011 to 2015.  Special programs such as   recurrent neural network and ablation analysis were incorporated in the data analysis. Tomasev and colleagues could  register a prediction  accuracy of 84% for serious damage 90% for eventual dialysis treatment . However this retrospective analysis has to be upgraded to prospective mode.  

But there has to be checks and balances cautions, Patrick Riley Principal Engineer and Senior researcher at the Google Accelerated Science team at Google. "Many algorithms are so complicated that it is impossible to inspect all the parameters or reasons about how the inputs have been manipulated.  As these  algorithms begin    to be applied ever more widely, risks of misinterpretations, erroneous conclusions and wasted scientific efforts will spiral" he says
 

Alan Turing 1951 Courtesy: Wikipedia 

TAILPIECE:
Father of modern computing science, Alan Turing will be seen in the new £50 notes to be issued by Bank of England.   Much maligned during his life time for being gay, he  died (or committed suicide, some believe) in 1954.  Six decades later in 2013,  he was exonerated  off all blemishes by the British Queen. 

References:

1. Sapiens : A Brief History of Humankind-  Yuval Noah Harari , Harvill Secker, London 2014

2. Homo Deus :A Brief History of Tomorrow-   Yuval Noah Harari, Vintage Publications 2017 
3. Art Attribution: AI enters the fra-y  David Adams,  Nature: 13 June 2019, vol.570, pp161-162

4. A clinically applicable approach to continuous prediction of future acute kidney failure :  
    Tomasev et al Nature  1 Aug. 2019, Vol.572, pp116-119
5. Three pitfalls to avoid in machine learning.: Patrick Riley, Nature, 1 Aug.2019, vol.572,  
   pp27-28.
6. Alan Turing to be the face of new £50 note

Eavesdropping 4G!

Human Activity Recognition (HAR, for short) is an  important   component of  surveillance and security programs. HAR can be  easily, directly  and effectively done through surveillance  cameras whether  indoors or outdoors.   However cameras are helpless when the space/room  to be monitored  is  dark, dim lit, hazy or  smoke filled.  What is the alternative?  That is the question  Guo et al asked themselves and sure enough  they hit upon an answer. 

They suggest using ultrasonic sensors. Their recent paper in Applied Physics Letters describes how this can be done.  Sound waves can  propagate  unhindered even if the ambience is  dark, dim lit, hazy or  smoke filled.  Guo's team  used  a two dimensional array of  acoustic receivers and  a special algorithm based on  the CNN (Convolutional Neural Network) to process the signals. CNNs have been in use for gesture recognition and body movements of humans  engaged in routine activities. CNNs have the capability to extract specific features from the  raw signals of complex body movements  and   classify  extracted features  into activities such as standing, sitting falling, walking etc. 

Guo and his team used an acoustic grid roughly 40x40 cm in size which  held 256 acoustic receivers in a 16X16 array   and  4 ultrasonic transmitters in the centre. The transmitters  emitted  high frequency sinusoidal acoustic  signals inclined at 45 deg. with  an effective reach  of 4meters.  The human volunteers selected for the experiment varied in height and weight.  They, one at a time, repeatedly performed   activities such as standing, sitting, falling and walking at a distance of 2 meters from the gadget. The ultrasonic sensors  collected  the reflected signals and the  CNN processor did the rest of the work.  Guo et al found  that the accuracy of HAR was 100% for simple static modes such as standing  and sitting  and 97.5% for others.  They also report  that higher the number of sensors and iterations,  higher the  recognition  accuracy for complex activities such as walking and falling. 

Guo and his team are of the opinion that acoustic surveillance is less intrusive of privacy than visual mode. Well, whatever that be,   Eavesdropping 4G has arrived!

REFERENCES:
1.Deep Learning Models for Human Activity Recognition
2.Deep learning for sensor -based activity recognition A survey: Pattern Recognition Letters, vol.119, pp3-11 (2019)
3. Convolutional neural networks for human activity recognition using body-worn sensors
Rueda et al Informatics: 5 (26)  pp (2018)
4. A single feature for human activity recognition using two dimensional acoustic array.
Guo et al, Applied Physics Letters  Vol.114, 214101 (2019)