A humble tavern for all travellers

Strategies in fighting AIDS

2008-11-18T06:08:00.001-08:00

Few days ago, I blogged about how Perez et al made use of zinc finger nucleases as DNA scissors to get rid of the CCR5 allele within the CD4 T cell, which would confer resistance to the HIV virus. Yet another method exists, which allows gene editing to be made to the CCR5 gene. This is achieved using single-stranded oligonucleotides. These single-stranded oligonucleotides were shown to induce site-specific alterations by activation of DNA repair pathways.

Oligonucleotide-based gene editing has been suggested as an approach to correct genes resulting in neuro-muscular disorders (Bertoni, 2005). Other than single stranded DNA oligonucleotides, DNA/RNA hybrid molecules and double stranded DNA molecules of 100 - 1000 base pairs can be used. The use of microinjection technology allow for the introduction of these genome-altering molecules into the stem cell (Davis).

Unlike current therapeutic approach to correct the defective gene, the trick is to make the CCR5 gene defective which is the opposite, and in doing so, generate a population of HIV-resistant CD4 T cells.

Citations
1) Bertoni C. Oligonucleotide-mediated gene editing for neuromuscular disorders. Acta Myol. 2005 Dec;24(3):194-201.

2) David BR. Genome editing - Its promise and limitations for gene therap. At: http://www.pasteur.fr/applications/euroconf/geneandcelltherapy/22_Davis_abstract.pdf

Cure for AIDS

2008-11-15T10:22:00.000-08:00

The successful transplant of bone marrow by Dr Gero Huetter and followed by the patient's showing no signs of HIV infection might provide some insights into the road to eradicating HIV.

In 2002, it was reported that the Great Ormond Street Hospital successfully attempted gene therapy of a 'bubble' child, who is obviously suffering from SCID. Earlier in June this year, Perez et al demonstrated HIV resistance in CD4 T cells by transciently expressing CCR5 zinc finger nuclease to induce genetic disruption of the CCR5, which provides stable and heritable resistance to HIV virus (Perez et al, 2008). CCR5 is known to be a mediator in the entry of a HIV virus to a T cell. Those with a mutation in the CCR5 are known to be resistant to HIV. The CCR5 zinc finger nuclease provides permanent disruption of the CCR5 allele. Advances have also been made in "gene editing" techniques, which uses zinc finger nucleases.

Perhaps, a possible approach to curing AIDS would be to introduce the zinc finger nucleases to bone marrow cells via gene therapy techniques, transciently expressing these nucleases in order to disrupt the CCR5 alleles. Without the functional CCR5, these altered cells which will be transplanted back into the bone marrow would generate new generations of HIV resistant CD4 T cells.

Citations

1) Perez EE, Wang J, Miller JC, Jouvenot Y, Kim KA, Liu O, Wang N, Lee G, Bartsevich VV, Lee YL, Guschin DY, Rupniewski I, Waite AJ, Carpenito C, Carroll RG, Orange JS, Urnov FD, Rebar EJ, Ando D, Gregory PD, Riley JL, Holmes MC, June CH. Establishment of HIV-1 resistance in CD4+ T cells by genome editing using zinc-finger nucleases. Nat Biotechnol. 2008 Jul;26(7):808-16. Epub 2008 Jun 29

Benefits of cooperate charity

2008-10-02T08:03:00.000-07:00

In a bid to promote industrialization, tax benefits, discounted operating costs and freely available land are being dangled as carrots to entice companies. Companies also participate in charity drives, which provide them with a form of tax relief.

From a public policy planning perspective, it might be worthwhile to consider the benefits of attacting the cooperate sector to partake in charity drives or relief programs through tax reliefs and forms of benefits. Thus, the policy planner can identify a particular area which requires monetary resources, and solicit for the participation of various companies. Monetary resources are not required all the time. Even donated office space, land, equipment, stores and other peripherals can be done in the name of charity towards the community.

The companies will naturally benefit from tax relief and other benefits in exchange for their charity. They will also benefit from the positive image the community has of them, which itself is a form of advertorial.

In the past, charity organisations have always borne the mantle of charitable or relief works. Perhaps, the cooperate segments of the society should also be roped as well.

A possible cancer immunotherapy approach - Inducing the formation of granulomas

2008-09-27T06:09:00.000-07:00

Granulomas are formed when the immune system encounters an antigen it cannot destroy, and as a result, it attempts to isolate the antigen, leading to the formation of a granuloma. A granuloma consists of macrophages, immune cells and a extracellular matrix. T cells are the perpetuator of granuloma formation, secreting cytokines and expressing adhesion molecules.

Non-resectable tumours have always posed problems for cancer patients. Standard treatment of non-resectable tumours include radiotherapy and chemotherapy. Perhaps, it is possible if the immune system can be tweaked to form a granuloma around the tumour mass, isolating it from the rest of the body. More work into the cellular processes of granuloma formation will give us an idea of the physiological mechanisms behind it. A greater understanding behind the mechanisms will perhaps allow us to consider this part of our immune process a weapon in the fight against cancer.

Citations
Sacco RE, Jensen RJ, Thoen CO, Sandor M, Weinstock J, Lynch RG, Dailey MO. Cytokine secretion and adhesion molecule expression by granuloma T lymphocytes in Mycobacterium avium infection. Am J Pathol. 1996 Jun;148(6):1935-48.

Alternative approach to tackling cancer: B cell therapy

2008-03-27T18:17:00.000-07:00

The work of Brendjens et al in retrovirally infecting peripheral T cells thereby transforming them into 19z1+ cells (capable of targeting CD19+ Burkitt lymphoma cell line) marked another approach in cancer therapy. This work demonstrates the possibility of genetically engineering large populations of patient T cells with reactivity towards tumour antigens. Some of the challenges to these approach are the long-term survivalability of the genetically engineered T cells, their ability to home in on tumour sites and establishing a tumour-specific immune response.

Another approach will be to harness the potential of B cells. Like what Brendjens et al did with T cells, the B cells can be virally infected and transformed into cells that are capable of expressing the tumour specific antibodies. Biologics have become notably used in the war against cancer, with avastin, an anti-VEGF antibody, making the headlines in recent times. Thus, the ability to produce anti-cancer antibodies, our body's natural biologics seem to be an attractive proposition. What is so attractive about the use of B cell therapy comes from another intrinsic property of B cells - their ability to present antigens, i.e. they are antigen presenting cells. This means that the B cells are able to augment the adaptive arm of immune response, presenting antigens and co-stimulating T cells in order to direct immune response against the cancer cells. Thus, the possible approach maybe to genetically-engineer the B cells and expose them to tumour antigens. Some of the challenges may be similar to that experienced in T cells, i.e. the ability of the populations of B cells to survive in the body.

Citations

1) Brian Becknell & Michael A. Caligiuri. Cancer T cell therapy expands. Nature Medicine 9, 257 - 258 (2003)

2) Brentjens, R. et al. Eradication of systemic B cell tumors by genetically targeted human T lymphocytes co-stimulated by CD80 and interleukin-15. Nat. Med. 9, 279–286 (2003).

3) Maher, J., Brentjens, R.J., Gunset, G., Riviere, I. & Sadelain, M. Human T-lymphocyte cytotoxicity and proliferation directed by a single chimeric TCR /CD28 receptor. Nat. Biotechnol. 20, 70–75 (2002).

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

2007-11-17T21:46:00.000-08:00

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.

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

2007-11-07T10:36:00.000-08:00

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/

The craving for a refuge

2007-11-02T11:16:00.000-07:00

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)

Dollars and sense

2007-10-06T23:35:00.000-07:00

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.

What was Martin Jol thinking of?

2007-09-28T22:27:00.000-07:00

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.

Spoofed interview with Celine Dion by Weird Al Yankovic

2007-09-25T08:59:00.001-07:00

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

2007-09-25T07:16:00.000-07:00

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.

The eldest child is the smartest!

2007-09-24T08:35:00.000-07:00

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

2007-09-24T08:31:00.000-07:00

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

2007-09-24T07:31:00.000-07:00

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.

Really stranger than friction

2007-09-17T06:58:00.000-07:00

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

The driving force of morality

2007-09-16T06:05:00.001-07:00

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

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

2007-09-07T08:09:00.000-07:00

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

The dream of robotic science

2007-06-26T23:28:00.000-07:00

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.

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

2007-06-11T08:02:00.001-07:00

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!

Anticancer peptides

2007-05-26T13:31:00.001-07:00

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.

Of fullerenes and viruses

2007-05-11T23:44:00.000-07:00

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

2007-05-11T22:51:00.000-07:00

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.

Designing the potent cocktail

2007-05-04T23:29:00.000-07:00

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?

2007-05-04T10:54:00.000-07:00

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.