Monthly Archives: March 2012

Visualizing biology: from conception to birth, cell division, and more

Visualization helps in learning anything. In biology visualization has traditionally been done using pictures or posters (right).
From conception to birth. But that is so 1970s. In the technocratic future, where lullabies are delivered via iPod and iPads are norm in kindergarten, figures or posters wond do any good. Kids would hate to learn from static images….they need videos! And if you are making videos, you might as well use real data…and Alexander Tsiaras does exactly that. Using advanced technology on real pregnant women he captures images of life from conception to birth. Mes merizing!

Okay, let’s take it to a molecular level now. Let us look at structure of DNA, cell division, and molecular machinery of cell division:

Cant have enough? Visit Drew Berry’s page.


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Many years ago (2003), Steve Robison, then co-ordinator of the Associated Students of College of San Mateo (ASCSM) told me about his dream of establishing a free and self-sustaining university. His envisioned students practicing what they learn in classes to support the campus community thus making it sustainable. For example, culinary students will prepare meals, horticulturalists/botanists will maintain the gardens, architects will design new buildings and so on. At that time this idea of free education seemed a distant possibility.

But now, free education is the new trend. Unlike Steve’s model of a physically existing self-sustaining university, a few successful free ‘universities’ have emerged over the internet. Salman Khan’s Khan Academy definitely led the way by providing free and easy to understand tutorials over the internet. His materials were so awesome that Bill Gates announced he was a huge fan on national TV. MIT has been offering free online classes over the internet for a number of years and recently MIT has launched MITx, a program that provides students with “the opportunity to demonstrate their mastery of the material and earn a certificate from MITx” for a class titled Circuits and Electronics.

Being originally from Nepal, a country that suffers severe higher secondary education bottleneck, I became very excited when I first heard of MITx. So I tweeted it and put it as my facebook status. But I was thrilled to hear that MITx was not the first online university and two artificial intelligence professors at Standford are doing something even better!

Sebastian Thrun and Peter Norvig heard Salman Khan give a talk at TED and launched their own academy at Stanford which is now becoming Udacity, a free university to learn computer programming language and artificial intelligence. The best thing about Udacity is that if you are the top student in their classes you may have a job waiting for you in the leading industries in the world.

Salman Khan: Let's use video to reinvent education (TED talks)

What does Udacity mean to students in the US?
I think this is a revolution in education. For hundreds of years many students have tried to buy university brand names by paying thousands of dollars in tuition. The higher the brand name of an University, higher the tuition fees. Two incentives to pay such outrageous fees are: the university name and networking with the alumni. Third minor incentive is the quality of education. Ultimately, the hopes of new graduates is to land a good job in a leading company. Unfortunately, none of the Universities care if you do not get a job. Once you graduate (and pay all the fees without which you dont graduate), the only correspondence you get is from alumni association asking for donation.

The cool thing about Udacity is that instead of earning money from student tuition, they make their money by helping students get a job. According to Wired, this is how it works: large companies pay 10-30% of an engineers’ first year salary to employment agencies. Udacity may generate most of their income from such companies by helping their top student obtain jobs. So, the education is free but money to run the university comes from top multibillion dollar companies. This cannot get more sweeter.

What does Udacity mean to the world?
If the world’s smartest person was born in a remote village in the middle of a mountain, (s)he may never realize her/his potential because the opportunity to learn is so little. Even if we imagine a 100% literate world, lack of high schools and universities forces many intelligent students worldwide to choose jobs that is far below their potential. Only a few lucky ones with enough collateral get visas to come to a developed country for higher education. Thus we are wasting talent with current educational model.

In theory, universities such as Udacity revolutionize education for the brilliant students in every corner of the world. Even if you were born in Mustang, a remotest state in the Himalayas, you can be taking a class in artificial intelligence and be admired by two best AI experts in the world. If you excel companies such as Google may be vying to hire you to design a driverless car. This is not a distant possibility; this is a commonplace at Udacity. Hence, it is an educational revolution.

On the incongruence between theory and practice
Free internet education has tremendous discrepancies between its hypothesized potential and realized potential in the global sense. Yes, we in theory it has tremendous potential but in practice, very few countries in the developing world are using it. According to World Internet Stats, the use of internet is the lowest in Africa followed by Asia with only 14% and 26% of the population using internet (average world-wide internet use 33%). Furthermore, this statistic is further inflated by developed nations both Asia (China, India, Japan) and Africa (South Africa). On a country level, of the 58 African countries, only 5 countries in Africa (9% African countries) have more than 5% internet users whereas 46 countries (81% African countries) have less than 1% internet users. Similarly, of the 35 Asian countries, only 4 (11.4% Asian countries) have over 5% and 23 (66% Asian countries) have less than 1% internet users. These statistics are corroborated by statistics from Khan Academy: virtually all of Khan Academy users are in developed countries.

The lack of internet use in developing countries is because of lack of infrastructure. Most countries in Asia and Africa are devoid of DSL. Because of geography, it is difficult and expensive to build infrastructure in most developing countries; hence telephone lines are nonexistent. Without telephone and DSL, most people in developing nations are without internet.

A simple to do list
Industrial revolution wedged a huge gap between the developed and developing nations. Internet revolution will forge a bigger gap if developing nations do not act now. Those nations that have nationwide internet service will benefit by incorporating internet in economics, communication, media, and education. Merchants in the developing countries with internet will be communicating globally and trading in dollars, whereas those in countries will be wasting their goods because they cannot sell all of it locally. More importantly, students in the countries will be using internet to learn about Salman Khans and Bill Gateses and interacting with Sebastian Thruns and Peter Norvigs and aspiring to land jobs in Googles and Bidus. Those in countries without internet will be struggling to find inspirations from their corrupt local leaders. Yes building internet infrastructure is expensive but since mobile phones are becoming increasing popular, investing in broadband services to increase internet users is a must for developing nations.

I have no faith in the corrupt politicians of developing countries; hence I do not expect the narrow-minded government depleted of visionary leaders to bring any positive changes in near future. Also, most NGOs are top heavy (spending 70% of their budget paying their executive staff) and can do little. The most important constituents to bring any change will be local entrepreneurs. Providing grants or microloans to encourage educators and businessmen to incorporate internet in their daily lives may bring innovative methods of increasing internet use in developing countries. For example, Mahabir Pun, a Raymond Magsaysay awardee has incorporated internet in education, animal breeding, monitoring global warming, and tele-medecine (more on Pun’s work).

Khan Academy and Udacity are not only great resources for youth and students worldwide but Udacity’s model of harvesting talent from all corners of the world can also be beneficial for companies. Hence, large companies should explore the opportunities of investing in internet infrastructure in developing nations because it is in their interest to find hidden talents and hire them. May be there are Marc Zuckerbergs and Sergey Brins somewhere in the Sahara desert in Chad and the mountains of Nepal, with 1.8% and 7% internet users respectively.

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Another example of ERV’s role in evolution

To end a royal dynasty, one has to eliminate its generals: this was the lesson of a Chinese movie I once watched in Netflix. Similar strategy is adopted by ERVs.
In a recent Plos Biology article (click here for a good summary for general audience) the authors identify MAVS, a protein produced by mitochondria (the general) that ignites immune response to protect the human cell (the Royalty) from Hepatitis-C virus (HCV). Three unrelated primates have the exact same non-synonymous mutation in the MAVS gene that  potentially alters the protein’s structure making it untouchable by the HCV particles. Unfortunately, humans, the primary host of HCV, do not have that mutation thus are relatively easily conquered by HCV. Sucks!
VERY INTERESTING is the presence of that same mutation in three different species: the authors apparently conclude it is a convergent evolution. However, this finding is in stark contrast with studies in yeast where convergence occurred at genic and network level but not at SNP level. Also, population genetics theories also find it very unlikely. Think about it, what is the probability that exactly same mutation would occur in three species branch AND SNP gets selected in all three branches? MINISCULE.
Could it be more plausible that the particular mutation existed in low frequencies in the common ancestor of all the primates and was readily available in all three branches at the time HCV like virus was active and quickly got fixed in the population? That particular virus probably did not infect humans (and other primates that do not have them) so they lost the mutaiton due to drift. Just a thought…

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Mapping Human Brain:An awesome video at TED

This was an awesome presentation demonstrating appication of genomics to understand human biology. This would be wonderful to educate general public and high school students about the following:

  1. Biological systems are very complex: thousands of genes produce thousands of proteins at various times that mediate billions of neuronal interactions. Genomics tools (microarray: the things with green dots in this talk)
  2.  A lot of work and time is needed to learn fundamentals of biology: many scientists are needed to gather biological specimen, perform experiments, and to analyze data. In this video only 2 brains were used. Imagine using hundreds of tissues.
  3. Integration of computer programming in visualization: today, because of genomics massive amount of data can be generated in little time. However, in order to analyze and understand the data, computational tools are needed. Once the data is analyzed, computer graphics is needed to visualize the data (the brain with nice colors in this talk). Therefore, computational biologists and artists are becoming important components of the genomics community.
  4. Applications of such studies: Once we accumulate many such studies, they can be used to design drugs or to prevent a disease in general population. This takes even more time and resources.

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How Life Started 4 BILLION Years Ago:Experimental Demonstration

This was one of the most interesting TED talks in science in a while. Many of us are familiar with the Miller-Urey experiment (1952) that showed organic compounds can be formed from inorganic chemicals. Hanczyc takes it one step further by actually demonstrating tar-like chemicals can come together to form little pockets of life like creatures that are able to eat and replicate!

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Could Rautes, Kusundas, Chepangs, Rajis or Tharus be the first peoples to colonize the Himalayas 7000 years ago?

Rautes: The last nomads of Nepal

This picture belongs to Kishore K. Sharma, an awesome Nepali photographer. Please do visit his blog by clicking on this picture to view more pictures of the Rautes.

History of Nepal, as taught in academic institutions, starts with Gopalavamshis, the so-called first rulers of Nepal, followed by Mahispalavamshis, Kiratis, Licchavis, Mallas, and Shahs in that order. However it only represents the political history of Nepal at its best. To understand history of Nepal in its completeness, one must learn about the history of the peoples of Nepal.

Human inhabitation of the Himalayan foothills, known as present day Nepal, predates the dawn of civilization and the Gopalavamshis because prehistoric stone tools of “Patu industry,” a non-agricultural Mesothilic culture unique to Nepal were recovered in Central Nepal[1]. Two distinct types of tools, the Patu tools resembling the 10-12 thousand years old Hoabinhian culture and another resembling 10-30 thousand years old culture in India highlight three important points about ancient Nepali history: first, modern day Nepal has been inhabited by humans since the Pleistocene; second, Nepal has been cosmopolitan even in the Mesolithic harboring Indian and South East Asian cultures, and finally, the Patu people had an unique cultural identity by the Mesolithic.

But what happened to the Patu people? It is curious that a few nomadic hunter-gatherer tribes live/until recently lived the Mesolithic lifestyle in central Nepal, where the “Patu industry” once existed. Could they be the descendants of the Mesothilic humans that developed the first Himalayan culture?

Kusundas (aka Myahak, Ban Rajas) and Chepangs (aka Prajas) are one of the highly marginalized tribes in Nepal. Until a few decades ago both these tribes were nomadic hunter-gatherers. With forests gone, Kusundas were forced to desert their nomadic life and enter villages, which caused annihilation of their culture, traditions, and languages. Only a few Kusundas today, speak their native language. Like the Kusundas, Chepangs were also nomadic hunters and gatherers in central Nepal. Destruction of forests has forced Chepangs to adopt a semi-nomadic life in the non-yielding slopes of the Mahabharat range.

In addition to their hunter-gatherer lifestyles, linguistic and anthropological evidence suggest that Kusundas and Chepangs have been living in central Nepal since ancient times. Both the Kusundas and the Chepangs were officially first reported by B.H. Hodgson, a British naturalist and ethnologist in mid-nineteenth century, as “broken tribes” living nearly “in a state of nature” and carrying bows and arrows with no relationship with the rest of the “civilized races” of the country[2]. Later CJF Forbes found more plausible relationship between Chepangs and Khyens (Kiiyen) and Kumis of Arakan hills in Burma (Myanmar) and even concluded that Chepangs may have entered Nepal from the east [3]. Unlike Chepang, Kusunda language is difficult to classify as it similarities with various unrelated language groups such as Austro-Asiatic (Munda)[4], Tibeto-Burman, and even Indo-Pacific[5]. It is now widely recognized as a language isolate[6]: a language distinct from all other languages spoken in Nepal.

Although both Chepang and Kusunda languages seem to be unrelated to any other languages in Nepal, they appear to be linguistically closely related to each other (see Figure1). It is plausible that Chepangs and Kusundas have cohabited the Mahabharata hills and centuries of linguistic exchange may have resulted in their language similarities. Furthermore, anthropological evidence seems to corroborate the linguistic antiquity between these tribes, for example, both the Kusundas and the Chepangs have a folk legend according to which the Kusundas are the descendants of Kusa (thus the name Kusunda) and Chepangs are the descendants of Lava, both the sons of Rama and Sita of the Ramayana. Furthermore, interviews with Chepang traditional healers and medicine men revealed hundreds of plants used for diverse purposes and many of them were previously not documented.[7] The tremendous ethno-botanical knowledge of the Chepangs further substantiates their occupation of central Himalayas since ancient times for such knowledge of local flora can only be built with time. Hence, Kusundas and Chepangs, by virtue of their nomadic life styles and lack of linguistic affinities with any other languages of Nepal, may have inhabited the Himalayan foothills long before other ethnicities emigrated.

Recently, genomics has been used to infer the demographic histories of human populations throughout the world. Analysis of Kusunda genome in a recent issue of Science[8] supports some of the linguistic evidence and indicates that Kusundas are related to Tibeto-Burman speaking North East-Asian populations such as Hezhens, Oroqens and Mongolians but are not related to the Australian or Papuan Aborigines and virtually unrelated to any of the human populations from East or South Asia. Remarkably, a Kusunda specific genetic component is evident; however, without further analysis it is difficult to determine whether this component is due to long period of population isolation or due to ancient age of the population.

Genetic and linguistic evidence argues that Kusundas are possibly the most ancient of Nepali populations. They , may have come into contact with Mundas and Burmese in Eastern Himalayan foothills in ancient times. Words burrowed from these languages may have remained in Kusunda language to date. However, more work is needed to determine whether the Kusunda specific genetic components are a result of recent inbreeding due to population isolation or whether they are archaic genome components due to Kusundas’ antiquity in the Himalayan foothills.

Although it is tempting to crown Kusundas as the eldest peoples of Nepal, other nomadic/semi-nomadic tribes of central Nepal cannot be ignored. Genetic analysis of Chepangs may show that they have also cohabited the Mahabharata hills for centuries. It is also noteworthy that many other tribes along with Kusundas and Chepangs may have inhabited central Nepal since ancient times. For example, the Tharus may be descendants of inhabitants of the Terai since the Paleolithic. Tremendous ethnic and cultural diversity within Tharus that spread throughout the Terai region attest their occupation of the land for centuries. However, it is interesting that there is little linguistic similarity between the Tharus and the hunter-gatherers of central Nepal suggesting that there may have been very little interactions between the populations of the hills and that of the plains. Furthermore, Rautes that are still nomadic and Rajis that recently gave up nomadic lifestyle may have resided in central Nepal before the advent of agriculture. Many more ethnicities of Nepal may have inhabited the Himalayan foothills since ancient times but little is known about them. Hence, it is really important to investigate the history of all the peoples of Nepal for accurate presentation of Nepali history and their origins as such studies are also interesting from the perspectives of human evolution. Himalayas are believed to have acted as a barrier for gene flow between the Indian subcontinent and Central Asia. However, the fertile Himalayan foothills with diverse flora and fauna may have been a Mesolithic melting pot for migrants from both the sides of the Himalayas since Mesolithic times. Understanding the origins and demographic histories of present tribes of Nepal may reveal novel aspects of ancient human dynamics in Asia.

In summary, there is abundant evidence that present day Nepal was inhabited by humans since the Paleolithic and a culture unique to Nepal existed by Mesolithic. It is possible that hunter-gatherer populations currently residing in central Nepal, such as Kusundas, Chepangs, Rautes, and Rajis may be the descendents of the Patu people that developed the first culture of Nepal some 7000 years ago. There is a dire need for additional archeological, anthropological, linguistic, and genomic studies to understand the ancient history of Nepal accurately.

[2] Hodgson, B. H. (1848) J. Asiat. Soc. Bengal 17 , 73–78

[3] Forbes, C. J. F. (1877) Journal of the Royal Asiatic Society of Great Britain and Ireland, New Series, Vol. 9,No. 2,  pp. 421-424

[4] Reinhard, J. & Toba, T. (1970) A Preliminary Linguistic Analysis and Vocabulary of the Kusunda Language (Summer Institute of Linguistics, Kirtipur, Nepal).

[5] Whitehouse et al. (2004) Kusunda: An Indo-Pacific language in Nepal. PNAS Vol. 101,No. 15, pp. 5692-5695

[6] Watters, D. (2005) Notes on Kusunda grammar (a language isolate of Nepal). Kathmandu: National Foundation for the Development of Indigenous Nationalities.

[7] Rijal A. 2011. Surviving on knowledge: ethnobotany of Chepang community from midhills of Nepal. Ethnobotany Res Appl 9:181-215.

[8] Rasmussen, M. et al. (2011) An Aboriginal Australian Genome Reveals Separate Human Dispersals into Asia. Science Vol. 334, No. 6052, pp.94-98


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Google’s ngram reveals a few historical facts about Nepal

Nepal in English books (1500-1790AD)Google’s ngram allows anyone to mine English textbooks scanned by Google to track dynamics of words in the Western world since 1500AD. I decided to spend this Sunday afternoon to mine English textbooks to learn about history of knowledge of Nepal in the West. It is apparent that India (1520AD) and China (1570) were known to the Western world at least 200 years before Nepal (not mentioned until 1680).

Father Guillespie (Read Father Guillespie’s account of Prithvi Narayan Shah’s acquisition of Lalitpur form 1795AD), probably one of the first to write about Nepal mentions a road via Macwanpur (Makwanpur) leads to Nepal, an “ancient and independent” country, from India. In his account he mentions that Nepal has three principle cities: Cathmanda (Kathmandu) which extends to Thibet(Tibet), Lelit Pattan which borders Macwanpur, and the third city of Bhatgan (Bhaktapur) which borders Ceratas (Kirantas). He also mentions Timi (Thimi) and Cipoli (Siphal may be??) as two small towns. Father Gillespie claims to have witnessed the defeat of the king of Patan,  Gainprejas  by Gorc’ha king Prithvi Narayan Shah. Gillespie writes that Gainprejas paid his soldiers by digging the Treasures of Tolu, which was possessed by Prithvi Narayan Shah upon winning the battle. He claims he saw the treasure that Shah acquired.

Gillespies appears to exaggerate and fantasize about Nepal and portray it as a barbaric and exotic nation. For example, Father Guillespie mentions two religions practiced in Nepal (Kathmandu valley): Baryesu, a religion of Tibetan origins whose practitioners “pluck out all the hair from their heads” and Hindu religion “practiced in its greatest purity” which was adulterated by Mohammedans in India. Hence, his account should not be taken as a historical fact; however it is fascinating to read a document about Nepal in English, from 1700s.  A few memorable mentions from Gillespie are Banga, a castle 3 miles west of Lelit Pattan (not sure if this castle still exists) and the statue of Budhanilkantha. Another book from 1750, Memoir of a Map of Hindoostan also mentions Srinagar, Nepal, and Morung  as countries indepent of Tibet. Hence, these two articles from 1700s appear to corroborate at lest two facts about Nepal:  existence of Limbuwan in the east of Bhaktapur and existence of Morong as a state described by Iman Singh Chemjong in Kirantkalin Vijaypurko Sankshipta Itihaasa (1975). Awesome!!!

Currently, there is a considerable debate on whether Prithvi Narayan Shah unified Nepal or expanded Gorkha and whether he should be viewed in a positive or a negative light. In A view of the rise, progress, and present state of the English Government in Bengal (1772) a Governor of Bengal writes that Rajah of Nepal repeatedly pressed the English to send military aid. This is the time Prithvi Narayan Shah attached Kathmandu valley which again corroborates Iman Singh Chemjong‘s description of Gorkhali attacks in the Valley (Kirantkalin Vijaypurko Sankshipta Itihaasa (1975)). Furthermore, the Governor writes of an “advantageous trade” with Nepal “by which a considerable quantity of gold, and many other valuables were imported. The Rajan being now dispossessed of his country…by the Rajah of Goercullah (Gorkha) the usual channel of commerce has in consequence been obstructed.” This suggests Prithvi Narayah Shah stopped export of riches of the Kathmandu to the English; hence those who view his capture of the valley negatively should reconsider their views.

In summary ngram can be a valuable tool for scholars, both in Nepal and in the West to study history of ancient Nepal. For example, Francis Hamilton’s  An account of the Kingdom of Nepal documents the details of Kirants in 1819 which is similar to Limbuwan’s history in Iman Singh Chemjong‘s  Kirantkalin Vijaypurko Sankshipta Itihaasa (1975). Also, there may be valuable old resources that have been masked by a surge of recent documents that may shed more light on history of Nepal.


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