Saturday, November 17, 2007

Top civil servant versus private sector executive - an argument from the standpoint of competitivieness


Earlier on, the Singapore government tabled a motion to peg the salaries of ministers and civil servants to that of the private sector. To peg the salaries against earners in the private sector, there must be some basis to show that a civil servant is indeed comparable to someone who is employed in the private sector.

One of the questions that arises is if there is any basis of comparison in the first place. If there is no basis of comparison, the argument for the need to raise salaries of civil servants and ministers by pegging them to the salaries of executives in the private sector is untenable. This is simply because there is little basis for comparison with their counterparts in the private sector.

In fact, in reality, there is little basis of comparison between someone working in the private sector and a civil servant. In the private sector, the raison d'etre for an employee or executive is simply to generate revenue or profits for the firms they are working for. A top executive in a firm is ultimately answerable to the shareholders, in as far as profits are concerned. Thus, more often than not, the worth of an employee or executive for that matter in the private sector is based on his ability to generate revenue. Therefore, his salary is justified by his ability to generate revenue or level of competitiveness, one way or another. (in the context of this article, competitiveness means the ability to generate profits or revenue in the financial sense).

How about a civil servant or even a top grade civil servant for that matter? His raison d'etre is public administration. Barring exceptions of civil servants occupying certain positions in the Economic Development Board or the Ministry of Trade and Industry, majority of civil servants are not in the position to generate revenue, so to speak. It follows that the working philosophy is not competitive in the sense. This can be illustrated with a simple comparative example. A superscale civil servant working at the headquarters of the Education Ministry makes decisions on the education system in Singapore in a public administrative capacity. However, a top executive in an educational provider company would be tasked with steering the company with the goal of generating more profits in mind. There is a world of difference between the two and the nature and aims of their work. It follows that the argument of using the private sector as a basis to justify the revisions in salary is not tenable.

There is another argument from the basis of lost opportunities, i.e. what talents in the civil service would have gained if they worked in the private sector instead. I am not denying that there are people formerly in the civil service who will eventually do well in the private sector, BUT again, to assert that a top executive within a civil service would go on to be a high flyer in the private sector may not sound convincing. The reason is the argument that I highlight earlier. The civil servant may have been brilliant at public administration, but we do not know if he is brilliant at generating revenue. An extrapolation of such a nature would be problematic.

The main thrust of my argument is that if one wants to peg salaries against a benchmark, there must be some basis of comparison with the benchmark. Thus, it is important to compare a civil servant with a someone working in the private sector. If there is no basis of comparison, then it follows that there is no basis for pegging salaries against that certain benchmark.

Wednesday, November 7, 2007

A critical look at the current electoral system's problem and a possible solution


Abstract
The current system of elections in Singapore has this unique feature - the Group Representation Constituency (GRC), whose purported existence is to allow minority representation. That aside, parliamentary elections have seen large percentages in walkovers , i.e. in more than 40% of the seats especially in the years after the GRC was introduced . In the event of a walkover, the political party facing a no-contest automatically gains seat (s) in the parliament. Walkovers occur due to the fact that the current opposition could not field that many candidates to contest all the seats. This paper critically examines the current electoral system's ruling of a walkover, and suggests a possible solution.

The problem with the current electoral system's ruling of a walkover is based on the flawed assumption that the party with the default victory has the mandate of the people living in the ward. This may not necessarily be the case. It could be possible that majority of the people in the uncontested ward desire another political party to represent them. Thus, from the representative democrat viewpoint, the current system is problematic since the wishes of the majority in the ward may not be reflected in the outcome of the elections.

Thus, the solution is to subject the entire "uncontested ward" to a vote. The residents will vote on whether they want the uncontested party to represent them in parliament. If it turns out that majority of the residents wants the uncontested party to represent them, the uncontested party candidates will naturally win their parliamentary seats. If it turns out that the majority of the residents do not want the uncontested party to represent them, the party is out of the running. A subsequent poll will be designated for a later date. In this subsequent poll, the uncontested party is excluded from contesting, given the fact that the majority of the residents do not desire their representation in an earlier vote. The seats at the constituency will then be contested by the other remaining parties. Candidates of other political parties who were unsuccessful in their wards may also contest in this subsequent poll.

Introduction
The parliamentary General Elections is held once every five years. On polling day, voters will vote for their desired representatives, who upon winning the contest in the ward, will serve as Members of Parliament. In the 1991 General Elections, the People's Action Party was returned to power on nomination day, as a result of 10 walkovers in 15 GRCs, and 1 walkover in a Single Member Constituency (SMC), gaining a total of 41 seats out of 81 seats. During the 1997 General Elections, the number of seats in some of the GRCs was increased to 5 seats in some and 6 seats in the others. The People's Action Party was returned to power on nomination day as a result of walkovers in 9 out of 15 GRCs, gaining a total of 47 out of 83 seats. During the 2001 General Elections, the People's Action Party was returned to power on nomination day as a result of walkovers in 10 out of 14 GRCs, gaining a total of 55 out of 84 seats. During the 2006 General Elections, the People's Action Party was not returned to power on nomination day, but it had walkover victories in 7 out of 14 GRCs, gaining a total of 37 out of 84 seats (Singapore Elections). Thus, an interesting observation is that most of the walkovers take place in the GRCs. In the current electoral system, the uncontested party automatically gains the seats in parliament. The question arises whether the residents of the walkover ward supports the uncontested party. From the democratic viewpoint, the current electoral system fails to address the voices of residents in the walkover ward as victory is given to the uncontested party by default, with the possibility that the uncontested party never had the residents' support (majority support) in the first place.

What then are the suggested changes to the current system of electoral contest to address the voices of the residents in the uncontested ward? A two-phase electoral contest is suggested herein as a possible solution. The first phase is known as the "Gatekeeping" phase, which ensures that the uncontested party has the mandate of the people living in the ward. In this "gatekeeping" phase, people will vote on whether or not they want the uncontested party to represent them. If the uncontested party has the approval of the majority in the ward, the "gate" is opened for its entry into parliament. However, if majority votes against the uncontested party, then it is out of the running of the elections. A subsequent poll is carried out at a later date involving the other political parties to determine the representatives of the ward. If the other political parties have enough candidates, they can take part in this subsequent poll. Candidates of the other political parties who are unsuccessful in their contested wards during the earlier election may participate in this subsequent poll too.

Discussion
The suggested approach has its strengths and weak points. Touching on the weak points, one of its criticisms will be from the standpoint of proportional representation (Proportional Representation Library). For example, if in a particular ward, 30,000 voters support the uncontested party, and they are likely to vote for the uncontested party at the "Gatekeeper" polls. However, 20,000 voters support a second political party, while 20,000 voters support a third political party. Thus, the end result is that the 30,000 "majority" out of this 70,000 do not "have their voices heard". In the winner-takes-all nature of the "First Past The Post" system, the uncontested party rightly deserves victory since it has the 30,000 majority. If you have 40,000 voters voting against the uncontested party, will it even be democratic to suggest that the uncontested party deserves to represent the entire ward (Ace Project)? In any sense, current polls at every single ward under the current system is based on the majority-wins-all First Past the Post system. The same criticism of proportional representation can be leveled at the current First Past the Post system. The nature of the contest in each ward under the current electoral system is that of majority is the winner-takes-all, and is by no means based on proportional representation.

Another weak point is perhaps the longer than usual polling period in the event that the "Gatekeeper" poll has eliminated the uncontested party. A later date for the poll has to be set aside for the residents of the uncontested ward to determine their representatives. The drawback is that the formation of the parliament is being delayed.

Moving on to the strength of this approach, first and foremost, it addresses the question of whether or not the uncontested party has the mandate of the people in the ward. It goes that if majority of the people do not desire its representation as reflected in the polls, it's only right that the "gate" to its entry into parliament is closed.

Another strength of this approach is that it preserves the fundamental values of meritocracy. Suppose in a situation whereby the other parties encounter mishaps, be it administrative mishaps or otherwise, and a group of individuals or a single individual apply to contest in this ward. It follows that this group of individuals or individual for that matter are applying for the sake of contesting per se, and are not interested in representing the interests of the voters. Will it wise to give this group of individuals or individual a walkover victory? The answer is an obvious no. The "gatekeeper" poll will be able to easily eliminate such individuals from the contest. In essence, candidates who merit the voter's support will be rewarded accordingly and those who do not deserve the support will be eliminated.

Yet another strength of this approach is that it will further encourage more pro-active participation from the political parties in improving the lives of the voters. Under the current system, the uncontested party is automatically given default victory. If the uncontested party has to win the approval of the voters at the "Gatekeeper" polls, it will have greater impetus to be more pro-active in winning the hearts and minds of voters. All the more the voters will benefit.

The thrust of this paper is to critically examine the current drawbacks of electoral contests in the event of a walkover. There is not much literature out there addressing the event of a walkover, especially from the standpoint of the voters' desires in a walkover ward. Although, it is not without its drawbacks, the benefits outweighs the drawbacks. Thus, it will be a positive move from a democratic perspective that the relevant authorities do try to take steps to allow voters in "walkover wards" to decide who should represent them, either through wholesale changes or revision in the current electoral system.

Citations
1) Ace Project. Electing a President using FPTP. accessible at http://www.aceproject.org/ace-en/topics/es/ese/ese01/ese01a/

2) Proportional Representation Library. Mount Holyoke College accessible at http://www.mtholyoke.edu/acad/polit/damy/prlib.htm

3) Singapore Elections Results accessible at http://www.singapore-elections.com/


Friday, November 2, 2007

The craving for a refuge


I have just made inroads as I contemplated further on the philosophy of LIFE. It was an unusual event that has "enlightened" me.

A ex-classmate cum project mate of mine was a committed Christian. She was into church activities, helps out in bible studies and plays in a church band. I was more or less aware of her beliefs during the days when we worked together on group projects. I graduated before her, but we still keep in contact, but curiously our topic always veer towards Christianity. It's also a curious position for me, because I consider myself a staunch critic of Christianity. I am a self-confessed avid reader of Bertrand Russell and Friedrich Nietzsche, the former who gave an exhaustive explanation why he isn't a Christian and the latter, known for launching a series of philosophical diatribes on Christianity.

Thus, it's inevitable that in one of the conversations that I launched into a rebuttal of Christianity. Admittedly, I also mentioned things to her like why Christianity is the second most disliked religion here. I also spoke of my cheeky pun at a pastor who conducted services at my grandfather's funeral. I actually asked the pastor,"hey, don't you think the use of sheeps as a description in Christianity is little inappropriate, because sheeps will eventually be fleeced and be sent to a slaughterhouse? Okay, I know I stepped outside the boundaries for once. I also told this classmate of mine that I could not really tolerate Christian groups launching agendas against sexual minorities like gays and lesbians. Don't mistake me for a homosexual, I am a straight, but I feel that everyone deserves a breathing space, a right to employment into the Singapore civil service, irregardless of sexual orientation.

Later on, I thought through my experiences philosophically especially why I seem to observe that some people follow their beliefs in a steadfast fashion. A realization soon struck me. Each and everyone of us craves for a refuge. Some refuges are permanent, whilst others are temporary. A non-performing ex-champion seeks refuge in the memories of his past victories as a source of solace for his current defeats. A practising Buddhist seeks refuge in the Buddha, Dharma and Sangha, and like-wise, a Christian seeks refuge in the arms of the Lord. It is inevitable at various times of our lives, we need shelter from the storms we face, and a refuge is a necessity. I for one admittedly seek refuge in my philosophical imagination, a mental getaway from all the strife out there. It's where my mind leaves my body and I float around in some noumenal realm (not in specific reference to Kant's noumenal realm). Thus, it can be said that the craving for a refuge is a primal urge. There is no denying the importance of a refuge, as it not only allows a person to be temporarily free from the storms, it is also a place of recovery for a person, mentally and to a certain, physically (placebo effect).

Perhaps, it is destiny, Christians call it God's will, Muslims refer to it as Allah's will, Buddhists call it Karma, etc, that I met this classmate of mine. And that my meeting and discussions with her gave me important philosophical insights. I am still what I am, just that I learn to appreciate the why my fellow homo sapiens chose to harbor certain beliefs. Religionwise, I am still at the same station as I was, no I am still not a Christian. (Sorry for the anti-climax)

Saturday, October 6, 2007

Dollars and sense


I may have been a little late in my posting regarding this issue, but I simply couldn't hold my horses with my fingers itching to hit the keyboard. Of late, the media was abuzz with a plethora of response to recent changes to the CPF policy. One of the changes is that the CPF minimum sum will be raised gradually from SGD$80,000 to SGD$120,000 in 2013. The other ubiquitous change is the introduction of compulsory annuities. For those who cannot afford to purchase annuities, they may use their minimum sum for the annuity. In addition, the age for CPF withdrawal has been raised from 55 to 65. Of late, the government is finding ways and means to help our senior brethren to seek employment. One could be forgiven for having the impression that the government is making it more difficult for one to withdraw his CPF.

With the mechanics of the CPF changes in place, one also cannot ignore the costs of living. The passing years have seen rises in costs of necessities such as healthcare, transport and utilities. One would dare to make a safe bet that even beyond 2010, the inflation in costs of the aforementioned necessities will continue.

Of late, the government was alarmed by the fact that a number of Singaporeans are uprooting themselves and planting their roots else where. The thrust of this discussion is not so much the social basis and implication for migration, but rather the "dollars and sense" of migration. The rising costs of necessities is already a push factor for many a retiree. A welfare state that takes care of senior citizens or one with a lower cost of living would be more attractive to a retiree. It doesn't come as a surprise that Singaporeans have settled down in neighboring countries like Thailand, Malaysia and China, other than the popular destinations of US, UK and Canada.

Migration is also the key to the lock of the CPF safe. If one renounces his Singapore citizenship and has become the citizen of another country, he will be entitled to withdraw his CPF savings. The choice of withdrawing CPF monies and settling down in a destination with a lower cost of living would seem like an attractive option. I would surmise in the foreseeable future migration figures will sky-rocket despite the recent changes to the CPF policy. This could be a worrying sign for the investment arm of the Singapore government who use the CPF monies for investments.

Friday, September 28, 2007

What was Martin Jol thinking of?


Beleaguered Tottenham manager Martin Jol claims that only Arsenal come close to matching his record for introducing talented youngsters onto the first-team stage since he took over at White Hart Lane.

Of course Jol, who succeeded Jacques Santini as Spurs manager three years ago, has spent heavily in the transfer market i that time. But he says his biggest kick is watching Tottenham's youngsters into stars.

And he believes that the young players who have taken Arsenal to the top of the Premier League are no better than his own crop of young players, even though Spurs are currently in the bottom three.

Quoted in The Sun, Jol said: “I feel we have more talented players at Tottenham than any other club. Maybe only Arsenal have the same but their approach is different to mine.

“If you were fickle you would say it is the same for both clubs, but it isn’t. It’s totally different.

“Gael Clichy has been playing at Arsenal for years, getting used to his role behind Ashley Cole before he moved on. Then he comes into the team after a couple of years of preparation.

“Cesc Fabregas was there for three or four years. They were all on the bench and came on when things were going well.

“If your team is in a position where you are playing well and then you bring on, for example, Kevin-Prince Boateng or Adel Taarabt, it’s an easy decision to make.

“Sometimes you have to play them no matter what.

"I felt I had to play Gareth Bale because he is a good option. The same goes for Younes Kaboul. Against Middlesbrough I played Michael Dawson, 22, Kaboul, 20, Bale, 18. That is probably the difference with the big clubs.

“Kaboul, Boateng and Bale didn’t play in the Premier League until this season. Hopefully they will develop into very good players.”

Having been criticised for Tottenham's early-season results, which have pushed the tarhget of Champions League football some way into the distance, Jol said defensively: “It’s not always about the scoreboard. It’s about the development of players like Kaboul, Bale and Aaron Lennon.

“It’s been a bad start, but it’s not as bad as it seems. Nothing is as it seems in football.

“I have to combine the results with the development. Even at Arsenal that is not the case.

“I can mention five or six players who chose to come to Tottenham ahead of other clubs.

“When you buy players, especially young players, you’ve got to play them.

“Look at my team and you will see examples of young players getting the right opportunity here.

“If they see Tom Huddlestone, Lennon and Dawson playing, it is a good example for what someone new can achieve.

“How many years will it take them to develop? What are you on about — we finished fifth last year.

“My philosophy is to get players young, get them used to Spurs and the Premier League.”

No doubt Arsene Wenger would query Jol's assertion that Arsenal do not have to combine results with development.

Critics would also point out that while Tottenham do indeed have some talented young players - though many of them such as Bale, Kaboul, Lennon, Dawson and Huddlestone were bought expensively rather than scouted as unknown youngsters and nurtured through the academy - they do not yet play together as a successful team unit, as the league table confirms. That is a key difference between Tottenham and Arsenal at the moment.

Jermain Defoe might also be surprised by Jol's comment that, if you buy young players, you have got to play them - Source: Goal.com accessible at http://www.goal.com/en/Articolo.aspx?ContenutoId=428607


Perhaps, this is one of the more mundane posts, and it is about most guys' favorite topic - soccer. Apparently, I read during the wee hours of the morning that Monsieur Jol of Tottenham Hotspurs had seemingly claimed that Spurs' youngsters are as good as Arsenal's youngsters. I don't know how will Monsieur Wenger reply to Jol's remarks, but I figure Jol's words will be like a red cloth teasing the most bullish of supporters from both the white and red side of North London.

First and foremost, I would like to qualify myself as a neutral fan, who supports good attacking soccer. Maybe, I may sound biased towards Arsenal, but this is justified based on the free flowing football that Arsenal produces week in week out. If I was born earlier, I might have loved the generation of Spurs players spearheaded by the likes of Oswaldo Ardiles in the 1980s.

One of my initial impression of Jol's remarks is that he has to get a grip of things, and be able to segregate his vision from reality. Jol has done a whole world of good during the time he has been in charge, transforming Spurs from a mid-table team to one that finishes within the top 5 of the English Premier League. From the aforementioned excerpts, I believe Jol has a vision of watching his youngsters develop into future stars. However, realistically speaking, the youngsters at Arsenal are operating at a different plateau as compared to the ones at Spurs.

Firstly, Jol has erroneously pointed out that Arsenal bloods her youngsters when things are going well. That is not really true exactly. The Carling Cup has always been the platform used by Wenger to springboard the progress of his youngsters, and he has never shied away from fielding his fledglings against Premier League sides in the Carling Cup, even more during last season's amazing run to the Carling Cup final, when he stuck by his youngsters against the megastars of Chelsea. Even the neutrals were won over by the fact that the Wengerboys played the diamond-studded stars of Chelsea off the park during certain spells of the match. The Wengerboys had a measure of success of their own, claiming scalps against Premier League sides like Liverpool, Tottenham, and just this week, Newcastle.

Secondly, Jol has to realise the crucial factor of success building on success during the development of youngsters. The Arsenal team has successfully qualified for the UEFA Champions league every season. I would argue that participation in the UEFA Champions League will steepen the learning curve of many a youngster, a luxury that Wenger's youngsters enjoy. Indeed, for a youngster to test himself against Europe's elites, his exposure to the brand of soccer played by the other top sides in Europe and in facing world class players will surely broaden his horizon. I believe players like Gael Clichy, Cesc Fabregas, Theo Walcott, etc have been put through a steep learning curve on European nights. The burgeoning maturity of Wenger's youngsters culminated in their run to the UEFA Champions league final in 2005, with Cesc Fabregas stepping ably into Patrick Viera's shoes. This is why I believe that Arsenal's youngsters operate on a different plateau from Spur's youngsters.

Perhaps, Martin Jol needs a bit more time at Spurs in order to see his vision come into fruition. Wenger has been at Arsenal for more than 10 years and the entire club echoes his brand of footballing ethos from the boardroom to the football pitch. Arsenal's senior team, composed of a group of youngsters plays a triangular form of short passing game that is attractive to watch. The reserve team composed of another group of youngsters plays similarly. The youngsters could fit into the game that the senior team plays. The Arsenal forward, Nicklaus Bendtner, gave an apt epitomy of the Arsenal game - it's about passing and moving. This is not true in the case of Spurs whereby Bale, Kaboul, Dawson, Huddlestone and Lennon who have yet to show that they can click as a successful team unit. Wenger also had the support of the Arsenal boardroom, and his influence of "buying a player and moulding him the Arsenal way" is rather infectious. It is quite obvious that Wenger buys and selects players according to the system that he believes in, which is one of the reasons why his youngsters do not have much of a problem fitting into his team.

Another aspect of Wenger is his proven reputation in youth development. The work of Wenger's talent scouts such as Gilles Grimandi cannot be underestimated. George Weah, Thierry Henry, Patrick Viera and now Cesc Fabregas are among the products of Wenger's development. Young footballers cite Wenger as being the magnet behind their desire to move to Emirates.

It appears that Jol needs more time and other ingredients for his remarks to turn into reality.


Tuesday, September 25, 2007

Spoofed interview with Celine Dion by Weird Al Yankovic

Weird Al Yankovic is an immensely talented musician, a one of a kind, whom in my honest opinion really owns the domain of song parody. Who would have forgotten his parody song of Michael Jackson's Bad - Fat, or his comical rapping to the tunes of Gangster's Paradise in Amish Paradise?

Notwithstanding his singing talents, he is also known for conducting spoofed interviews in his very own Al TV. Contemporary artistes alike are being projected in an awkward fashion, through their past recorded responses which were superimposed onto Al's hilarious jibes and queries. He claimed a "victim" in Celine Dion. Enjoy his "interview" with Celine Dion.

Changing the template of my blog

I have just received feedback from my students that my blog looked rather bland. Hence, I adjusted the background of my blog using a downloaded image of the Aurora Borealis (the Northern Lights), a beautiful and captivating natural phenomenon. Hopefully, it gives my blog a more colourful, albeit mystifying feel.

Monday, September 24, 2007

The eldest child is the smartest!

I found an interesting article in the International Herald Tribune, and it was found that the eldest child score on average three points higher than his/her other siblings in IQ tests. The reason is due to family dynamics rather than biological factors, e.g. changes in gestation processes. I guess the pressure is on the eldest to learn as much as possible about life in general, in order to guide his/her younger siblings. For those who are the eldest, do rejoice over the fact that you may be more intelligent. For those whom are not the eldest, you can always seek the counsel of your eldest sibling! Be comforted that you have your eldest sibling around to hold your hands and guide you through obstacles when you need him/her the most!


Citations

Benedict Carey. Family dynamics, not biology, behind higher IQ. International Herald Tribune accessible at http://www.iht.com/articles/2007/06/21/africa/siblings.php

Life Science queries

Students in my lessons, feel free to voice whatever queries, thoughts or views you may have during your course. I will try to respond ASAP. Remember no vulgarities, personal attacks, flaming or anything that is detrimental to the discussion.

Cancer, metastasis and the entire business of vesicle trafficking


Vesicle trafficking plays a part in cellular processes. Vesicles are formed, undergo expansion and completion, and finally participating in lysosomal degradation. Vesicles are involved in this process known as autophagy. Autophagosomes are double-membrane vesicles. In a paper published by Takahashi et al in Nature Cell Biology, it was found that Bif-1 interacts with Beclin-1, and together with ATG-5, is involved in the formation of autophagosomes. Loss of Bif-1 led to abrogation of autophagy, and the arising of spontaneous tumours in mice (Takahashi et al, 2007). It was also found that during the process of carcinogenesis in mice, there was reduced autophagic activity (Schwarze and Seglen, 1985). Indeed, it's interesting to note the part played by vesicle trafficking pathways in tumorigenesis. Vesicle trafficking pathways may play a part in metastasis. Jiang et al has found that the regulation of matrix metalloproteinase-1 activity was achieved by dynamin-mediated endocytosis (Jiang et al, 2001). The study of vesicle trafficking pathways in cancer and metastatic cells will gives us insights into how they actually assist in the latter's functions.


Citations

1) Yoshinori Takahashi, Domenico Coppola, Norimasa Matsushita, Hernani D. Cualing, Mei Sun, Yuya Sato, Chengyu Liang, Jae U. Jung, Jin Q. Cheng, James J. Mul, W. Jack Pledger & Hong-Gang Wang. Bif-1 interacts with Beclin 1 through UVRAG and regulates autophagy and tumorigenesis. Nature Cell Biology, 23 Septemter 2007

2) Schwarze, P. E. & Seglen, P. O. Reduced autophagic activity, improved protein balance and enhanced in vitro survival of hepatocytes isolated from carcinogen-treated rats. Exp. Cell Res. 157, 15–28 (1985)

3) Jiang A, Lehti K, Wang X, Weiss SJ, Keski-Oja J, Pei D. Regulation of membrane-type matrix metalloproteinase 1 activity by dynamin-mediated endocytosis. Proc Natl Acad Sci U S A. 2001 Nov 20;98(24):13693-8.

Monday, September 17, 2007

Really stranger than friction


Read an article in Times about the trial of Krystian Bala, a novelist of a macabre best seller, containing a story of a murder of which he was responsible for three years ago. He murdered a lover of his former wife. Apparently, the murder victim was tortured to death, presumably by asphyxiation and drowning, whereby a noose was tied around his neck and he was being thrown into a river. A similar account of the murder was written in a book published by Bala titled Amok.

Yet, this account of a crime involving a jealous lover was a poignant reminder to me. During my college days, I was mistaken by a jealous fellow as a boyfriend of a female friend who was my orientation group mate. Yes, I treated her as a friend, but no more than that. This guy actually claimed that I looked like a playboy and told a martial arts-trained friend of his to fix me. It happened that this martial arts trained friend of his was also my friend too. It was from the latter that I found out what happened.

Guess when one is in the deeper throes of passion does he lose his rationality.

Citations
Jail for author of ‘a perfect crime’

http://www.timesonline.co.uk/tol/news/world/europe/article2395523.ece

Sunday, September 16, 2007

The driving force of morality


It has been put forth by Creationists that one of the driving force for the existence of a god is the existence and nature of morality. My first response to this line of arguement is to re-examine the driving force of morality, as in why the need for morality arises?

However, let's begin with this important question - What is morality? Referring to the Stanford Encyclopedia of Philosophy, it refers to a code of conduct put forth by a society or a religious group or normatively refer to a code of conduct would be put forward by rational persons under specific conditions.

The agglomeration of individuals in societies can be argued as the driving force for the need for morality. Simply put, in order for society to function and for its members to thrive, there is a need for the latter to abide by a certain code of conduct so that his/her fellow members will benefit or will be free from harm. Take for instance the traffic code of conduct whereby drivers are exhorted to drive safely by keeping within speed limits. Clearly, the safety of the other members of the society is likely to be preserved if such a code of conduct is in place.

The arising of civil societies is seen as the apex in evolution of a society. There is a paradigm shift away from a more individualistic outlook to a more socially conscious perspective in as far as members are concerned. Thus, going by the London School of Economics definition of civil societies, a civil society is one which revolves around shared interests and values, whereby collective action is taken.

In essence, the society is seen as the driving force of morality for the simple reason that morality is seen as the means to the society's end (good).

Citations
1) The Definition of Morality. Stanford Encyclopedia of Philosophy http://plato.stanford.edu/entries/morality-definition/

2) Definition of Civil Society. London School of Economics
http://www.lse.ac.uk/collections/CCS/what_is_civil_society.htm

Friday, September 7, 2007

Concepts in peer to peer computing: A hierarchical model of file distribution in peer to peer networks through designation of sub-hubs



Abstract

The use of an algorithm to designate sub-hubs within a peer to peer network will help to lessen some of the problems that networks face i.e. excessive traffic within the network leading to situations such as upstream congestion, which results in the deterioration in performance of other softwares that upload information into the Internet. Besides, the sub-hubs will ensure that the file is being distributed throughout the network as the latter will be relatively free from the constraints of congestion. The algorithm is as follows:

1) Status of user node is determined in terms of percentage of file downloaded;
2) Scan the network for other nodes whose download status is of a certain percentage e.g. 10% greater than the user;
3) Generate a distribution curve of the other nodes over this percentage range;
4) Determine the highest frequency of nodes over the range (if the frequency of nodes over the range is determined to be too low, steps 2 to 4 is repeated, but the network is scanned for nodes whose download status range is greater than the current one e.g. 20% > 10%);
5) Designate these nodes as sub-hubs;
6) User will download from these sub-hubs;
7) else (download from any user irregardless of download status with the part of the file in demand)

Introduction

Peer to peer networks are a popular way to transfer files, and is quite likely, they will be here to stay for quite a long time. They are different from the traditional client-server system, adopting a more decentralised mode of file distribution whereby peers act as equal, merging the roles of server and clients. A number of peer to peer software are in popular usage, e.g. Bittorrent, Emule and many others. This is not to say that peer to peer file transfer is free of any problems of its own. The growth in peer to peer traffic results in network congestion. Upstream traffic congestion can occur in circumstances when a particular user within the network is uploading the file to a large number of peers. This results in a large upstream to downstream ratio. This will likely result in congestion in the upstream link. Interestingly, it has also been shown that 60% of all Internet traffic is being driven by peer to peer traffic (Briere and Hurley, 2007).

A hypothetical scenario and the solution

Consider the network in Figure A. One seed (red node) with 100% of the file is being swarmed by downloaders. The seed is swarmed by 2 downloaders (green nodes) with 90% of the file, 3 downloaders with 70% of the file (blue nodes), 4 downloaders with 20% of the file (brown nodes) and 5 downloaders with 10% (magenta nodes) of the file. There is high likelihood that the seed will experience upstream congestion with dire consequences in their respective networks. The aforementioned algorithm serves to reduce the likelihood of congestion through designation of sub-hubs. In figure B, you can see the frequency distribution of the nodes in terms of percentage of file downloaded. In Figure C, you will be able to see what the algorithm does, i.e. to designate sub-hubs in a hierarchical fashion. You will notice that instead of the seed supplying the file to everyone, it will instead supply the file to the 90% completed downloaders, and the latter will supply the file to the 70% completed downloaders, who will supply the file to the 20% completed downloaders, who will lastly supply the file to the 10% completed downloaders. It can be seen in a hierarchical sense, nodes with a certain percentage of file downloaded that are at the lower echelons of the hierarchy will act as sub-hubs, which can relieve upload traffic from the main hub (the seed or those who have nearly completed downloading the file). It should be noted that the nodes can progress through the hierarchy as a greater percentage of file is being downloaded with time.

Discussion

This algorithm, which can be adopted in peer to peer softwares, is suggested as one of the possible solutions to ease some of the problems inherent in networks with heavy peer to peer traffic. However, it is not really known at this point of time the speed of file download relative to the current peer to peer softwares in use. However, prediction is that the speed of download should be comparable vis-a-vis current peer to peer softwares. Firstly, it will be relatively freer from congestion problems as which is the case with current peer to peer software. Secondly, at each step of progression of download, a source of sub-hubs will increase the speed of file download. It has also been pointed out that one of the main concerns on peer to peer networks is that the speed of download slows down towards the end. However, it's still not known whether this algorithm will be able to address this problem. Finally, it can be seen that this algorithm retains the essential features of the mainstream peer to peer software, i.e. users upload and download files simultaneously, whereby they function as downloaders from sub-hubs above them in the hierarchy (in terms of percentage of file completed), whilst they themselves act as uploaders to users below them in the hierarchy.

Citations
Briere, D and Hurley, P. The Bleeding Edge. Networkworld.com









Tuesday, June 26, 2007

The dream of robotic science

As time passes, the size of the microchip becomes more and more miniature. Now, they are talking about creating robotic insects. Perhaps, a more exciting field will see the fusion of nanotechnology with robotic technology, where we create robotic micro-organisms. Imagine a robotic immune cell that is intelligent enough to sniff out cancer cells, virus-infected cells and other pathogen and then get rid of them. Alternatively, we can have a robotic friendly "micro-organism" that targets a tumour mass and gets rid of it. Pretty exciting for the field of medical robotics huh? Okay back to work. I have fantasized enough.

Monday, June 11, 2007

The metastatic stem cell/cancer cell - the inspiration for drug delivery?

Stem cells and metastatic cancer cell-lines have been known to be able to colonize other tissues. Perhaps, this property might be worth considering in drug delivery, especially for biologic agents. It is possible to use one of these cells, and diminish any potential tumorigenic properties at the same time, introduce the gene to produce the biologic agent. The cell will then be able to metastasize to the target organ to produce its therapeutic effect. Okay, this sounds a little crazy. Back to daydream time!

Saturday, May 26, 2007

Anticancer peptides

There is a series of cationic peptides that are capable of altering the electrical environment of the cell, disrupting it physiologically and causing the death of the cell as a result of affecting the pathways within the cells. The mechanisms of these peptides in altering the cell membrane are two fold. The first mechanism can may involve the peptide's interaction with the ion transport proteins of the cell. The second mechanism involves formation of ion channels per se (Kourie and Shorthouse, 2000). These peptides are available in nature and come from exotic creatures such as scorpions to bees and amphibians like frogs. I figure that targeting the electrical environment of cancer cells that result in their death might be one of the strategies in developing therapeutics against cancer.

Citations
Kourie, J.I. & Shorthouse, A.A. Properties of cytotoxic peptide-formed ion channels. Am J Cell Physio 2000 Jun; 278(6): C1063 - 87.

Friday, May 11, 2007

Of fullerenes and viruses

I chanced upon an article by RSC Publishing on the use of fullerenes conjugated to antibodies in anticancer therapies(RSC publishing, Ashcroft et al, 2006). Fullerenes are hollow buckyballs, which can be used to carry an assortment of anticancer drugs. The investigators made the fullerene more specific to target cancer cells by conjugating it to antibodies that recognize cancer. With anti-cancer viral therapy now in vogue and nanotechnology progressing, it would even be possible to produce a fullerene conjugated with viral coat proteins for specific targeting of cancer cells.

Citation
1) Fullerene promise in anti-cancer therapy accessible at http://www.rsc.org/Publishing/Journals/cb/Volume/2006/8/Fullerene_anticancer_therapy.asp

2) JM Ashcroft, DA Tsyboulski, KB Hartman, TY Zakharian, JW Marks, RB Weisman, MG Rosenblum and LJ Wilson, Chem. Commun., 2006

The cancer killing virus

In recent years, the use of virus to eradicate cancer have received a certain measure of success. The use of attenuated viruses with reduced virulence have been shown to be efficacious in certain form of cancers. The concept is simple. Allow the virus to reach the tumors, and the former will replicate within the latter, killing it. I have given this topic a long thought and I thought if it would be possible to infect the cancer cells, and then bring in the immune system to deal with the cancer cells, which were our normal cells gone awry, as though they were infected cells. It would be a combination of two hits on the cancer cells, with the viruses killing and lysing them, and the immune cells killing them too. Such recombinant viruses would have to express genes that are able to mobilize the immune system like the Monocyte Chemotactic Protein-1(MCP-1) and Interleukin-12 (IL-12), which can recruit and activate cellular components of our immune system like Natural Killer Cells, CD8 T cells, etc (Allavena et al, 1994). Under these inflammatory conditions, the Treg cells functions which downregulates immune response will be over-written. Thus, the first steps would be to sneak the virus into the tumour mass and infect the tumour cells, and subsequently, the tumour cells would be lysed by the viruses themselves and the chemokines and cytokines expressed by the tumours would recruit the immune system to kill the tumour mass. The immune system is seen something as a clean-up agent, which also wipes out any trace of the virus, which may persist in the body. However, in scenarios where the tumour cells express pro-apoptotic proteins like the FAS ligands in a mechanism known as the FAS counterattack, which induces apoptosis of immune cells, the efficacy of such a using such a recombinant virus might be reduced, and the reliance would be on the virus to replicate and kill off the tumour cells. However, in certain types of cancer like brain tumour and colorectal carcinoma, there is over-expression of the CD155 (Masson et al, 2001). CD155 can ligate the activating receptor of Natural Killer Cells and induce killing by the latter (Castriconi et al, 2004). Such a proposition makes the idea of recruiting our immune system to target the cancer cells' weakness(overexpressing CD 155) attractive.

Citations
1) Allavena P,Bianchi G,Zhou D,van Damme J,Jilek P,Sozzani S,Mantovani A. Induction of natural killer cell migration by monocyte chemotactic protein-1, -2 and -3.Eur J Immunol. 1994 Dec;24(12):3233-6.

2) Mavoungou E. Interactions between natural killer cells, cortisol and prolactin in malaria during pregnancy. Clin Med Res. 2006 Mar;4(1):33-41

3) Masson D, Jarry A, Baury B, Blanchardie P, Laboisse C, Lustenberger P, Denis MG. Overexpression of the CD155 in human colorectal carcinoma. Gut. 2001 Aug;49(2):236-40.

4) Castriconi R, Dondero A, Corrias MV, Lanino E, Pende D, Moretta L, Bottino C, Moretta A. Natural killer cell-mediated killing of freshly isolated neuroblastoma cells: critical role of DNAX accessory molecule-1-poliovirus receptor interaction. Cancer Res. 2004 Dec 15;64(24):9180-4.

Friday, May 4, 2007

Designing the potent cocktail

Multidrug resistance is a barrier to the treatment of cancer with chemotherapeutic strategies (Gottesman et al, 2002). P-glycoprotein transporters are responsible for the efflux of drugs from the cancer cells. A number of inhibitors have been designed for the multidrug resistance protein, for instance, the MDR-1 P-glycoprotein. These inhibitors will be added into the cocktail containing an arsenal anti-cancer drug to ensure a move effective treatment. However, side effects should be anticipated considering the fact that MDR drug pumps have a physiological role in our livers and kidneys.

Citations
1) Gottesman MM, Fojo T, Bates SE. Multidrug resistance in cancer: role of ATP-dependent transporters. Nat Rev Cancer. 2002 Jan;2(1):48-58.

Using hepatitis virus to fight liver cancer?

As my title suggests, it's one big irony considering the fact that hepatoma or hepatocellular carcinoma which involves transformation of hepatocytes is a consequence of viral hepatitis. Liver cancer has a high occurance amongst Asians. In recent days, anti-cancer viral therapy offers a great promise in the fight against cancer, which is why I was wondering if we could use an attenuated hepatitis virus to infect and kill the hepatoma cells. The Hepatitis B virus for instance targets hepatocytes. My suggestion was inspired by this experiment on a rat hepatoma cell-line, whereby scientists demonstrated the propagation of the human Heptitis B virus in vitro (Shih et al, 1989).
Citations
Shih CH, Li LS, Roychoudhury S, Ho MH. In vitro propagation of human hepatitis B virus in a rat hepatoma cell line. Proc Natl Acad Sci U S A. 1989 Aug;86(16):6323-7.

Saturday, April 28, 2007

An alternative speculation to the origin of Life?

The endosymbiosis theory postulates that the mitochondria of eukaryotes evolve from an aerobic bacteria. In recent times, the discovery of the Mimivirus was hailed as a missing link between a virus and a bacteria. However, it is also a fact that the Mimivirus possesses a genome of a size that is comparable to the other bacteria. The mimivirus also possesses genes that are involved in nucleotide and amino acid synthesis, which some bacteria lacked. It also possesses an inner lipid membrane. I was speculating on a model of endosymbiosis whereby the ancestral virion particle like the mimvirus enters a prokaryotic cell. This virus may have accumulated mutations resulting in a defect in assembly of viral coat. As it may have coded for genes that may be beneficial to the prokaryote, it forms a symbiotic relationship with the host. It may be possible that the virus is the ancestor of the nucleus in a modern day eukaryotic cell. Like a nucleus, it can take over the role in controlling the cells.

Sunday, April 22, 2007

Mimivirus, the hope for medicine?

The Mimivirus is the largest known virus known to mankind. It has a size of up to 600 nm. Another amazing thing about this virus is that it harbors a level of complexity which brings it closer in relation to our modern cells, with 911 genes (Prescott, 1993) encoding proteins like the amino - acyl tRNA synthetases, DNA polymerases and other metabolic enzymes. The size of its genome is 1.2 megabase (La Scola et al, 2003). Perhaps the size of the Mimivirus virion is large enough to deliver a human minichromosome into the cell. However, the capsid needs to be engineered in such a way that it can bind to receptors of specific cells. Another challenge would be to package the minichromosome into the viral capsid. If the artificial chromosome is going to be the next thing in gene therapy, the search for a nanoparticle that can act as its carrier continues.

Citations
1) Prescott, L. (1993). Microbiology, Wm. C. Brown Publishers

2) La Scola B, Audic S, Robert C, Jungang L, de Lamballerie X, Drancourt M, Birtles R, Claverie JM, Raoult D. A giant virus in amoebae. Science. 2003 Mar 28;299

Saturday, April 21, 2007

Study of the effects of trans-acting factors encoded by viruses

The proteins encoded by viruses can affect the cell in more ways than one. Thus, it would be interesting to study the long term effects of trans-acting factors encoded by the viruses on cells. One approach may be to integrate the virus's genome into that of the cell's like how a normal virus would infect a cell. The problem is that the virus may integrate in a location within genome whereby the integrated viral DNA element may affect the function and expression of neighbouring genes. In the end, our observations may be affected. I was wondering if it is possible to introduce an artifical chromosome with an integrated viral element instead. It would allow us to study the effects of trans-acting elements encoded by the virus on cells' functions and the long term effect on the cell.

Friday, April 20, 2007

New drug delivery methods delivered at delivering artificial chromosomes aimed at gene therapy

The use of viral vectors in gene therapy has a severe setback - the risk of cancer. Understandably, viruses have potent promoters and if integrated into a region where an oncogene is found, there is a possibility that cancer can arise. The use of artificial chromosome is attractive as it doesn't disrupt the original genome of the cell and is also capable of replicating. However, it's may be too big to be packaged into viral particles. The advantage of having a viral nanoparticle is its target specificity. However, research on nanoparticles is currently ongoing and before long, we may have a nanoparticle large enough, but having the properties of viral protein coats for target specificity in order to deliver the artificial chromosomes into mammalian cells. I think the artificial chromosome is the future direction of gene therapy but "drug" delivery methods have to be worked on.

Citations
1) New cancer case halts US gene therapy trials. http://www.newscientist.com/article.ns?id=dn3271

2) Human minichromosomes. http://bric.postech.ac.kr/science/97now/01_5now/010504c.html

Artificial chromosomes and their promise in research

Genetics research has come a long way since the discovery of the DNA double helix by Watson and Crick. It's now possible to construct mammalian artificial chromosomes. Ways have been discovered to induce stable gene expression from a mammalian artifical chromosome (Grimes et al, 2001). There have also been improved methods in delivery of artificial chromosomes to mammalian cells (Chen et al, 1997). Indeed, it's a great way to study trans-acting factors being expressed on a long term basis WITHOUT disrupting the original genome in cell-lines.

Citations
1) Grimes BR, Schindelhauer D, McGill NI, Ross A, Ebersole TA, Cooke HJ. Stable gene expression from a mammalian artificial chromosome. EMBO Rep. 2001 Oct;2(10):910-4.

2) Chen M, Compton ST, Coviello VF, Green ED, Ashlock MA. Transient gene expression from yeast artificial chromosome DNA in mammalian cells is enhanced by adenovirus. Nucleic Acids Res. 1997 Nov 1;25(21):4416-8.

Saturday, April 14, 2007

The Civil Servant in the Emperor's court

I was inspired to write this post when I came across this piece of writing on Du Fu the poet on answers.com. http://www.answers.com/topic/du-fu

(born 712, Xiangyang, China — died 770, Hunan) Chinese poet, often considered the greatest of all time. After a traditional Confucian education, he failed the important civil service examinations and consequently spent much of his life wandering, repeatedly attempting to gain court positions, with mixed success. His early poetry, which celebrates the natural world and bemoans the passage of time, garnered him renown. He suffered periods of extreme personal hardship, and as he matured his verse began to express profound compassion for humanity. An expert in all the poetic genres of his day, he is renowned for his superb classicism and skill in prosody, though many of the subtleties of his art do not survive translation.
A renowned poet, yet I found it surprising that his ambition was to be a civil servant in the emperor's courts, hence my musings on the mind of a civil servant in the emperor's court as shown below:
I, as a civil servant in the Emperor's court acknowledge that:
1) The Emperor is the dragon and he is my overlord.
2) I am also subserviant to the empress dowager.
3) The emperor's son will be the next in line to the throne.
4) If I am under a minister, I have to serve him with unquestioning loyalty.
5) I am prepared to be punished for violating any part of the system that was put into place.
6) I have to pass important examinations if I want to be appointed in leadership roles.
7) Scholars who did better than me in the important examinations would be appointed as officials holding positions that are higher than mine.
8) A degree holder will not necessary be appointed to a civil service position.
9) Someone with a higher classification of degree will stand a better chance at appointment in the civil service than me.
10) This examination system is meritocratic.
11) The values of Confucianism in running the country.

Virology and oncology

It is known that viruses produce potent activators as well as repressors. An example of a potent transactivator is Tat, in the case of HIV viruses. These transactivators are known to increase the expression of viral genes. However, if such activators are integrated in the vicinity of an oncogene like Ras or Myc, there lies a possibility of transformation. Tat itself has a repressive function on p53, a tumor suppressor (Harrod et al, 2003). Thus, investigating the implications of viral activators and repressors on tumorigenesis is an interesting field. Using a viral vector, a gene encoding an oncogene can be joined TOGETHER with the attenuated viral genome (can synthesize activator proteins, but not others like the viral protein coat) to investigate the effects of the virus' activator function on the oncogene's expression. To investigate the effects on tumor suppressor, the gene encoding the tumor suppressor should be joined together with the attenuated viral genome (can synthesize repressor proteins, but not others like the viral protein coat) and homologous recombination with the wild type tumor suppressor within the genome should be carried out. This is to simulate the event in which the virus integrates itself in the vicinity of the tumour suppressor.
Citations
1) Harrod R, Nacsa J, Van Lint C, Hansen J, Karpova T, McNally J, Franchini G. Human immunodeficiency virus type-1 Tat/co-activator acetyltransferase interactions inhibit p53Lys-320 acetylation and p53-responsive transcription. J Biol Chem. 2003 Apr 4;278(14):12310-8.

A "BAD" day for HIV?


When the HIV virus infects a cell, usually a CD4 T cell, the reverse transcriptase generates the DNA strand from the RNA, which is then integrated into the host cell's genome. In order for the virus to activate transcription of its genes, it must be able to activate transciption in the chromatin context. Tat, a potent trans-activator was shown to associate with p300 and P/CAF in order to activate transcription (Benkirane, 1998). Tat was also shown to bind to a RNA stem loop structure known as TAR, activating HIV gene transcription (Braddock, 1993). I was wondering if a potential mode of viral therapy could take advantage of a predominance of pro-apoptotic factors over anti-apoptotic factors in inducing the cells to undergo apoptosis.


Genetic engineering can allow us to manufacture a mutant HIV virus. This mutant HIV virus should have Bad and Bax downstream of TAR. It can be generated in caspase 9 knockout cells with the help of a helper virus that allows packaging of the recombinant genome. If introduced into a HIV infected cell, the Tat encoded by HIV within the infected cell can transactivate the expression of Bad and Bax, allowing for the predomination of pro-apoptotic factors and leading to the apoptosis of the infected cell (Gavrilescu and Denkers, 2003). A "Bad" day for HIV indeed.


Citations

1) Benkirane M, Chun RF, Xiao H, Ogryzko VV, Howard BH, Nakatani Y, Jeang KT. Activation of integrated provirus requires histone acetyltransferase. p300 and P/CAF are coactivators for HIV-1 Tat. J Biol Chem. 1998 Sep 18;273(38):24898-905.


2) Braddock M, Powell R, Blanchard AD, Kingsman AJ, Kingsman SM. HIV-1 TAR RNA-binding proteins control TAT activation of translation in Xenopus oocytes. FASEB J. 1993 Jan;7(1):214-22.


3) Gavrilescu LC, Denkers EY. Apoptosis and the balance of homeostatic and pathologic responses to protozoan infection. Infect Immun. 2003 Nov;71(11):6109-15.

Wednesday, April 11, 2007

Zoonotic viruses: The jump from animals to humans and a possible mechanism for RNA editing?

Zoonosis is any infectious disease that may be transmitted from animals to human. Some may wonder what are the exact mechanisms that made the virus jump from infecting animals to infecting humans.
There are a number of studies directed at elucidating the role of RNA editing of viral genes. It was found that RNA editing at the amber/W site plays a central role in the replication scheme of the Hepatitis Delta Virus (Casey, 2002). RNA editing was also found to have downregulated the cytotoxicity of Ebola (Volchkov, 2001). In fact, RNA editing was proposed to have occurred in the case of HIV, where there are changes in the viral proteins but no changes in the RNA viral genome that is packaged within the viral particles (Berkhout, 2001 and Bourara, 2000). Thus, the question that remains could be if RNA editing in an animal host results in the synthesis of viral proteins and structurally different viral particles that makes the virus capable of being pathogens in humans and a similar RNA editing mechanism in infected humans lead to other humans being infected too?
Citations
1) Casey JL. RNA editing in hepatitis delta virus genotype III requires a branched double-hairpin RNA structure. J Virol. 2002 Aug;76(15):7385-97.
2) Volchkov VE, Volchkova VA, Muhlberger E, Kolesnikova LV, Weik M, Dolnik O, Klenk HD. Recovery of infectious Ebola virus from complementary DNA: RNA editing of the GP gene and viral cytotoxicity. Science. 2001 Mar 9;291(5510):1965-9.
3) Berkhout B, Das AT, Beerens N. HIV-1 RNA editing, hypermutation, and error-prone reverse transcription. Science. 2001 Apr 6;292(5514):7.
4) Bourara K, Litvak S, Araya A. Generation of G-to-A and C-to-U changes in HIV-1 transcripts by RNA editing. Science. 2000 Sep 1;289(5484):1564-6.

Monday, April 9, 2007

Anti-cancer bacteria?

I came across an interesting article describing the genetic engineering of myxobacterium in producing an anti-tumor compound (Heim). I worked on colorectal cancer, and I thought it will be interesting to be able to genetically engineer bacteria that is capable of colonizing the colon of colorectal cancer patients and produce the anti-tumor compound through fermentation of raw materials. These bacteria can also be engineered to produce anti-cancer biologics. A good example of a useful bacteria would be Lactobacillus casei Shirota strain, which we can find in Yakult.
Administering these genetically engineered bacteria will be as easy as administering Yakult.
Citations

Saturday, April 7, 2007

My exchange with NMP Siew Kum Tong on the NS issue

Disclaimer: The contents of my post were SOLELY BASED on MY EXPERIENCE. This is NOT to say that a thorough study was done. Lastly, my experiences DO NOT necessarily reflect the realities on the ground in the absence of a thorough study being conducted.
I happened to chance on NMP Siew Kum Tong's blog, and the pertinent issue of NS men was raised. The crux of the issue was based on comments raised on National Service liabilities handicapping male Singaporean's career.
I did have my fair share of job interviews, and as regards to National Service liabilities (reservist), only one raised the issue. Coincidentally, the interviewer was a Caucasian foreigner, the only foreign interviewer I had. The rest of the interviewers for my other jobs were all Singaporeans. However, I would like to qualify that this is only based on my experience and impressions of Singaporeans and foreigners shouldn't be judged on the basis of my post.
I happened to have an interview for a certain job, although I had another dream job in mind. I wasn't particularly keen on this job, but nonetheless, I attended the interview to satisfy my curiosity and also, as a learning experience. The interview went on okay until the end when the Caucasian interviewer questioned me about my National Service committments. I reassured him that if my services were very urgent to the company, there is an avenue for me to seek a deferment. I also told him that I wasn't a key appointment holder in my National Service unit.
Needless to say, I didn't get the job in the end although I landed my dream job. This is NOT TO say that I was discriminated based on National Service liability. It could also be that I wasn't too particularly keen and treated the interview as some sort of excursion trip to open my eyes. Secondly, I landed my dream job.
Speaking of my dream job, my interviewer who was to become my direct superior was a Singaporean lady. We spent most of our interview discussing the company's vision and other things relevant to my job scope. Nothing was raised about National Service issues. At the end of the day, I was thoroughly satisfied as I managed to land my dream job.

The A*STAR scholar cum Financial Analyst

I had an interesting exchange with Mr Philip Yeo about biomedical researchers equipping themselves with financial know-hows. I would think that is possible. I knew a friend who was a Ph.D. candidate and passed his Chartered Financial Analyst stage 1 and 2 examinations. His story was a little different because he subsequently grew disillusioned with his life in the laboratory and gave up his Ph.D. studies altogether. He told me that he wanted to move on to finance as a career option.
However, I think being a financial analyst is more than just "knowing the know-hows". Looking at balance sheets for the P/E ratios, liquidity numbers or studying stock market activity by looking at level II quotes, past trends, etc, aren't enough. More research has to be done on the stock option, futures, equities, bonds, etc. The typical financial analyst has to be in the know of the events concerning a company. For instance, news on a particular company buying over another company whose products can boost the current technology of the former's products, thereby increasing sales, is valuable. It doesn't come as a surprise that a typical financial analyst working for a top financial firm spends a substantial amount on his image. These typical analysts are also social animals, and having established a wide network of contacts, they are able to make informed decisions on their choice of investments.
To conclude, it's possible to do biomedical science and KNOW HOW to read financial statements. However, being a financial analyst involves more than just reading financial statements. To be a financial analyst, the proverbial scientist has to swap his lab coat for his business suit!

Story of stem cell transformation continues


I found an interesting paper describing the formation of DNA adducts in quiescent cells arrested for DNA synthesis and the necessity for the cell to enter the cell proliferation stage for DNA synthesis to occur, resulting in the repair of DNA adducts (O'Neill, 2000). However, it is also during this DNA synthesis stage that the DNA adducts are processed into cellular mutations. Thus, cell proliferation results in both repair of potentially mutagenic adducts and the processing of mutations in the remainder of the DNA adducts (Bielas and Heddle, 2000).


It is known that adult stem cells can be quiescent for a number of years. Thus, there lies the possibility that the adult stem cells could be exposed to mutagens or electrophilic agents capable of forming adducts with DNA. A portion of them can be processed into mutations when the adult stem cells start proliferating. It has also been found that oxidative stress can induce hematopoietic stem cells to proliferate (Liu and Finkel, 2006, Ito et al, 2006). The question that remains is when the adult stem cell is exposed to mutagen and stresses to the cell from reactive oxygen species, are we witnessing its transformation?



Citations

1) J. Patrick O'Neill. DNA damage, DNA repair, cell proliferation, and DNA replication: How do gene mutations result? Proc Natl Acad Sci U S A. 2000 October 10; 97(21): 11137–11139.


2) Bielas JH, Heddle JA. Proliferation is necessary for both repair and mutation in transgenic mouse cells. Proc Natl Acad Sci U S A. 2000 Oct 10;97(21):11391-6.


3) Liu J, Finkel T. Stem cell aging: what bleach can teach. Nat Med. 2006 Apr;12(4):383-4.


4) Ito K, Hirao A, Arai F, Takubo K, Matsuoka S, Miyamoto K, Ohmura M, Naka K, Hosokawa K, Ikeda Y, Suda T. Reactive oxygen species act through p38 MAPK to limit the lifespan of hematopoietic stem cells. Nat Med. 2006 Apr;12(4):446-51.

Friday, April 6, 2007

The loose cannons of stemness

It has been found that during early metastasis in breast cancer, the early disseminated cancer cells in the bone marrow of breast cancer patients have a breast cancer stem cell phenotype (Balic et al, 2006). Another group have found that mesenchymal stem cells can undergo spontaneous transformation after four to five months in culture (Rubio et al, 2005). Thus, it is likely that during early metastasis of breast cancer, transformation of adult stem cells could have occured. Therefore, it can be seen that tumors arising out of stems cells undergoing neoplastic transformation will lead to a poorer prognosis. These cancer stem cells are capable of limitless proliferation and metastasizing to the other parts of the body. I thought that knowing the type of genetic hits and the steps of progression of a normal stem cell to a cancer stem cell will allow researchers to understand the biology behind early metastasis of cancer cells with stem cell properties.
Lastly, it will be interesting to know how adult stem cells respond to factors resulting in genetic insults. Elucidating how the adult stem cells respond to oxidative stress or electrophilic direct-acting and indirect-acting compounds will allow us to evaluate the degree of susceptility of the stem cell to such insults.
Citations
1) Balic M, Lin H, Young L, Hawes D, Giuliano A, McNamara G, Datar RH, Cote RJ. Most early disseminated cancer cells detected in bone marrow of breast cancer patients have a putative breast cancer stem cell phenotype. Clin Cancer Res. 2006 Oct 1;12(19):5615-21.
2) Rubio D, Garcia-Castro J, Martin MC, de la Fuente R, Cigudosa JC, Lloyd AC, Bernad A. Spontaneous human adult stem cell transformation. Cancer Res. 2005 Apr 15;65(8):3035-9.