This same phenomena can occur on the molecular level. It’s possible to make two proteins that are exact mirror images, or “reflections,” of each other. In nature, proteins are made of L-amino acids. However, if you make proteins using the mirror image D-amino acids you can make the exact mirror image of a protein. These mirror image proteins aren’t recognized by the enzymes that naturally degrade proteins or by the immune system, so they can hang around longer in the body, potentially making them more effective as drugs.

Professor Sachdev “Dev” Sidhu of molecular biology has started a company, appropriately named Reflexion Pharmaceuticals, to make an entirely new class of drug molecules in mirror image form. In addition to evading the body’s usual ways of eliminating drugs, Reflexion’s drugs are made chemically at a fraction of the cost of making traditional biologic drugs.

The core technology, which the company licensed from the Whitehead Institute, involves first making a mirror image of the protein to which the drug will bind (the target protein). Dr. Sidhu then uses his expertise in molecular and phage library design to find a protein that can bind to and inhibit the activity of the target protein. By then making the mirror image of the protein he’s discovered, he can inhibit the original, non-mirror, target protein. Dr. Sidhu, together with U of T postdoctoral fellow Maruti Uppalapati, has successfully used this technique to discover a novel mirror image inhibitor of vascular endothelial growth factor (VEGF), a protein which stimulates new blood vessel growth.

There are several approved drugs that inhibit VEGF and are used to treat a variety of serious diseases, including colon, kidney, lung and breast cancers and the eye disease, including wet age-related macular degeneration, the leading cause of blindness in the developed world. The currently marketed VEGF-inhibiting drugs generate over $10 billion in annual revenues.

The first step in Reflexion’s drug discovery process is to make the target protein in mirror image form, something that can only be done chemically. For this, Dr. Sidhu teamed up with Reflexion co-founder and U of Chicago professor, Stephen Kent.

Dr. Dana Ault-Riché, Reflexion’s CEO says, “Steve is the best person in the world at making proteins using chemistry and Dev is the best phage library designer, so Reflexion has the two best people it could possibly have joining forces to make its technology work.”

In addition to cancer and eye diseases, Reflexion has plans to use its technology to make drugs for a variety of other conditions including inflammatory diseases like arthritis and osteoporosis, infectious diseases and chronic pain.

What made you decide to write this book?

It’s a mainstream book but it arises directly from my academic work. After finishing my PhD at Harvard in 2000, I spent four years there as assistant director of the Program for the Study of Women, Gender and Sexuality. I taught a course on romantic love and after many years of thinking about it I decided I wanted to put those ideas into a book that would be accessible to mainstream readers.

Do you consider it a self-help book?

I consider it an anti-self-help book! It’s a hard-hitting critique of contemporary self-help culture. I really take on the whole “Men are from mars, women are from Venus” mentality.

What’s the message?

The main argument is that the image of romantic love that the self-help industry tries to sell is based on a few misconceptions. The first is the idea that love is a game with winners and losers. The second is the idea that men and women are inherently different so that to make romance work, women need to learn to read the so-called male psyche.

I argue that there is no such thing as the male psyche and I also argue that the more we try to manipulate our romantic lives, the more we think of love as a game, the less authentically we are able to love. So basically, whoever came up with the idea that love is a game destroyed its soul.

How did we get to the point where we think that love is a game to be won and that men and women are opponents?

There was a trend toward turning love into a game via a series of books. It began in the 1980s with The Rules. And John Gray came up with his “Mars-Venus” franchise in the 1990s—he’s written 15 books now. By now it’s so ingrained in our psyches, particularly female psyches, that it’s hard to banish.

One of the things that drives me crazy about the self-help industry is that the books that women read are trying to drag us back into the 1950s, into gender roles that are not applicable today in terms of how contemporary men and women behave.

Right. You argue in the book that there is some hope in that young people are thinking differently about love and about gender roles. Can you tell us some more about this?

Yes, this is one of the reasons I wrote the book. As a university professor, I teach 18- to 22-year-olds. I know from experience that their understanding of gender is a lot more fluid than what these self-help books portray.

As research for my book I read 20 to 25 self-help books. Their portrait of men in particular is really strange. Book after book tells us that men are these cave men who are wired to hunt women. They’re wired to cheat on you. They don’t understand emotions. They will forget your birthday. They’re commitment phobic. The young women I teach don’t think of men in these terms and the young men I teach don’t think of women as prey to be conquered. There’s a lot more fluidity and there’s a lot more mutual respect than these authors are suggesting. When you look at younger people you see this clearly.

There’s a whole chapter in my book on how television shows and movies that are aimed at young audiences—teen shows—often actually have amazingly progressive gender configurations. They do not perpetuate gender stereotypes, which is one reason I’m so intrigued by the fact that self-help authors are so gung ho about dragging us back into the 1950s. Why? What is their agenda? A lot of these books are aimed at young women. Why are they trying to convince young women to go back to the 1950s when the rest of the culture is moving forward? Why are television shows more progressive than self-help books? What’s in it for the self-help industry?

Do you know the answers to these questions?

In my more paranoid moments, I think that they’re quasi-intentionally trying to set women’s liberation back by a few decades. In my less paranoid moments, I realize that the self-help industry is probably caught up in the cultural machinery that it is perpetuating. They don’t necessarily realize the impact of what they’re doing.

But even so, my argument is that if you’re going to position yourself as a cultural gatekeeper, if you’re going to start telling other people what to do, then you should be aware of the implications of what you’re saying. I’m pretty hard on self-help authors.

I suppose it’s easier to write a book that offers a simple formula than to write a book that says that life is not necessarily programmable or predictable.

Yes. We live in such a pragmatic culture that we are trained to think that everything is controllable. Romantic love is not controllable. The whole point of love is to overflow all of our systems of control. It’s not meant to be manipulated.

Why are we so focused on falling in love?

I talk a lot more about this in my most recent book, an academic book called The Summons of Love. I think that there’s something about the experience of romantic love that gives us access to frequencies of our own being that we can’t access any other way. These are sublime feelings—that sensation of blissful happiness and all the problems of the world dissolving. There are very few other things in our lives that allow us to access those kinds of feelings.

Of course this only applies to new, fresh love. But I think we covet that experience so strongly because that’s the one of the few ways way we can get it. We know that. If we’ve had it before, we know that it’s the only way we can get it again.

It sounds like a drug.

Absolutely!

So what should women—or men—do if they’re looking for some advice about love?

One of the main points of this book is that love’s failures are not life failures. I think that the self-help industry teaches women to think that when love goes wrong, when their relationships fail, it’s because they did something wrong. I’m saying that most times when love fails it’s not because you’ve done something wrong. It’s because love is inherently fickle and capricious. Most of our relationships are not meant to last. Most people who get married and stay married had many other relationships before that did not last. That’s the whole point.

Often it’s the failed affairs that teach us the most, so thinking about love’s failures as life failures is not productive because a lot of time it’s the failure that teaches us something really important.

Maybe failure isn’t even the right word.

Exactly. Love’s mission is in some way much more expansive or much more panoramic than what we are trained to think. It may not be that love’s mission is to make us happy in the conventional sense. It may be that love’s mission is to refine our character or to help us grow. If you think of it that way, suddenly the failures don’t seem like failures.

The experience of love as you describe it almost sounds like it’s outside the norms of our culture, which trains us to believe that everything is controllable. It’s almost as if being in love is a different way of being.

People do experience love in a transcendent way. What happens is that when it fails we flock to Chapters or Amazon in search of these books because we want answers and we want those answers to be simple. It’s comforting to get some sort of formula because this leads us to think that the next time we’ll be able to control things so we won’t get hurt. I think there is this tension in that, yes, we experience love in this more expansive, panoramic sense, but when it fails we want it to be simple. Of course it’s never going to be simple. We do everything in our power to make it simple but that’s completely artificial.

• read more

Professor Baird is giving a public reading of Dickens’s The Pickwick Papers on Feb. 7 at the Jackman Humanities Institute on U of T’s St. George campus.  Details can be found here. 

Why is the work of Charles Dickens still so important 200 years after his birth?

We’re still reading Charles Dickens. He continues to be taught in courses on Victorian literature, but he also continues to be read by people who are just looking for an interesting read. This is really a continuation of the success he enjoyed in his own time.  He was a hugely popular author, read by everybody from Queen Victoria down throughout English society. He found this audience early in his career with his first novel, The Pickwick Papers, when he was 25 years old, and he never lost that grip on his public.

His popularity has survived a variety of shifts in critical opinion. Fifty years after his death in 1870, he was looked down upon by sophisticates like Oscar Wilde who felt Dickens was a rather artless writer whose work was full of sentimental passages one could only laugh at, someone too simple-minded to be a great artist. But people continued to read his work.

Do you think he was a great artist?

Undoubtedly. He wrote 12 major novels, and each one is an imaginative world of its own. He was a writer who ceaselessly reinvented himself as times changed. He was also an important person in the history of fiction. He wasn’t the first person to write novels with complicated plots, but Dickens, in Bleak House in particular, was really a pioneer of the detective novel. It was his assistant editor in the weekly magazine he put out, Household Words, a man named Wilkie Collins, who went on to write a number of novels which are now regarded as the prototypical detective novels. Collins and others were following in a direction where Dickens had set the standard.

The other striking thing about Dickens is his use of language. His writing comes alive. These aren’t just words strung together into sentences. When you read the sentences they have a dynamic kind of relationship with each other, which makes reading Dickens a lively experience. Dickens’s language has a poetic quality, which is in keeping with the kinds of stories that he tells.

Dickens seems to be a novelist who succeeds as both a literary artist and a popular writer.   

Dickens was exceptional in the social range of his readership. His contemporary William Makepeace Thackeray wrote much more for a well-heeled, educated audience. Dickens wrote for everybody, and in that respect he’s like Shakespeare in his plays for the Globe Theatre, where the audience ranges from the nobility in the boxes to the groundlings standing in front of the stage — and Shakespeare is speaking to all of them.  Dickens was that kind of writer and exceptional in that respect.

He was also quite a celebrity, wasn’t he? He did lecture tours that were quite popular. I believe he lectured in Toronto at one point, didn’t he?

Yes, he visited Toronto first at the end of his first North American tour in 1842 and was very pleased to get out of the United States and find himself in Queen Victoria’s empire once again. The public readings were enormously successful but also quite demanding on him and in the end his doctors urged him to stop. He finally did not long before his death. His audiences kept demanding — and he was drawn to it — his version of the end of Oliver Twist where Bill Sykes kills his girlfriend Nancy. It’s a very melodramatic episode and Dickens was physically exhausted by it.

The other aspect of Dickens’s work is that it has an almost journalist aspect to it. In Oliver Twist, for example, he exposed the poverty in London at the time to readers.

That was a very important part of his writing. He began life as a journalist. He became a highly esteemed shorthand reporter around 1830 before he started writing himself. He became a parliamentary reporter. This was just before the reform bill of 1832 and there was a tremendous amount of speechmaking in parliament and elsewhere, and Dickens was very much in demand as a reporter because he was so good at it.

His work as a parliamentary shorthand reporter gave him a lifelong distaste for parliament, which he once called the “national ash heap”. It started him on a career in journalism that in a sense never ended. He became a successful writer of fiction with The Pickwick Papers when he was about 25, but he also edited a daily newspaper for a time. Later for many years he published his own magazines, in which novels were serialized, his own and those of other authors. And his novels are full of reflections of the issues of his day.

He was quite pointed in his social commentary, wasn’t he?

Yes, he touched on many subjects, but three run through all of his novels.

The first was public health, which was very important from the 1830s to the 1860s. Issues like drainage, sewage, provision of clean water, the problems of congested urban areas and the way that disease proliferated in such districts. He not only wrote about public health in his novels, he also campaigned for it — he became president of a society devoted to improving public health.

Another theme is crime, also an issue of continuing concern in the England of his day. How do you catch criminals? And once you’ve caught them,  then what do you do?  He was involved in debates about the function of  prisons — are they places where you take people who have done wrong out of circulation for a while, or are they places where people can be reformed and rehabilitated?

And the most important was education, a crucial issue throughout Dickens’s lifetime.  Education was a battleground between various religious organizations, which argued that education had always historically been a function of the church and ought to remain so, and others contending that in the modern world, education was the responsibility of the state to see that everybody had basic literacy.

These debates were raging throughout Dickens’s life and he goes back again and again in his novels to question how you get education to people, especially to the poor. How do you rescue children from a life of crime or from child labour, how do you get them educated, what are the schools to be like?

Nicholas Nickleby starts out with scenes in Yorkshire schools, which were notorious in the 1830s as places where parents could send children who they had no interest in. Dickens went to Yorkshire and looked into these schools and had his hero, Nicholas Nickleby, look for work as a schoolmaster in a Yorkshire school. This is a good example of the way Dickens used his fiction to expose a social problem. It’s also a good example of his campaigning against the mistreatment of children.

Is there one novel that can be called his best?

That’s a hard question. I usually think that Dickens’s best novel is the one I happen to be reading at the time.

Perhaps the easiest novel to read for somebody who’s never read Dickens is David Copperfield, which is partly autobiographical, the story of a boy who has a difficult childhood, rather like Dickens’s, and who goes on to become a successful parliamentary reporter and novelist.

But the novel he wrote after that, Bleak House, to me is the novel that conveys more of Dickens’s qualities. Its two stories — one is a retrospective account and one in the present tense. The two stories alternate throughout the novel. They seem to be disconnected, but eventually converge in the same spot and the same moment in time. This shows Dickens’s powers of construction in fiction extremely well, and it’s an exciting read.

You’re reading from The Pickwick Papers.  Why?

My bicentennial project is to read all the novels in chronological order and I like to re-read The Pickwick Papers, which is the first one, at Christmas every year. Also, the trial scene that I’m reading was one of Dickens’s favourite readings.

Pickwick was hugely important for him because he came to write it almost by accident. He was asked to take on this job of writing monthly installments to provide an opportunity for a popular artist to draw pictures and the idea was that readers would pay a shilling a month to get four pictures and 24 pages of prose narrative.  He took this on because they were offering him 14 pounds a month and that would enable him to get married.

After two months the original artist died and Dickens got more control over the project. The monthly installment went up to 32 pages of narrative and he found an illustrator who would follow his wishes. Gradually he developed the monthly episodes into something quite different. Within a year the print run went from 400 copies a month to 40,000 a month. This was a runaway bestseller and it set Dickens up as the most popular writer of his time, and he never lost that position in later years.

NSERC’s Strategic Project Grants (SPG) Program aims to increase research and training that will enhance Canada’s economy, society, and/or the environment over the next 10 years in the following target areas:

• Information and Communications Technologies
• Environmental Science and Technologies
• Manufacturing
• Natural Resources and Energy

Key Requirements:

• Have well-defined objectives, scope and duration   (1-3 years)
• Have one or more supporting organizations that are actively involved in all stages of the project and can apply the results

Funding:

• No Limit (Note: Average yearly request is ~$45,000)

The 2012 competition is now open.

Learn more about this program at an Information Session featuring an NSERC Representative who will discuss the program and changes for 2012, and a successful applicant at UofT.  The Session details are as follows:

Thursday, February 9, 2012, 2-4 pm
Michael E. Charles Council Chambers,
GB202, Galbraith Building, 35 St. George Street.

Please RSVP by February 7th, by sending an email to:  Martina Simmonds

More Information:  details about this year’s competition, including new features of the SPG program, and deadlines for those wishing to apply are available on our website at:  NSERC Strategic Project Grant Program 2012.

• read more

“Understanding and accurately predicting the response of physicians to incentives is essential if governments wish to increase the supply of physician services,” says Prof. Brian Golden, who holds the Sandra Rotman Chair in Health Sector Strategy at the University of Toronto’s Rotman School of Management, who wrote the article with Rotman Prof. Doug Hyatt and Rosemary Hannam of the Rotman School’s Centre for Health Sector Strategy.

Access to health care in Canada is a challenge in many regions, and while there has been an oversupply of physicians in the past, many people currently have problems getting care. “Central to the issue of access is the adequacy of the supply of physicians — specifically, whether the number of physicians and their work effort sufficiently addresses the health care needs of the population,” write the authors. “Supply is appropriately managed when there is neither a shortage nor surplus of services.”

Provincial and territorial governments can help increase access to care by setting policies that influence physicians to increase their working hours and thereby affect the supply of services they provide. Ironically, by having such a strong impact on hours worked, the authors report that increased pay to attract more physicians can also have the unintended consequence of reducing the hours physicians choose to work.

Governments may provide nonwage compensation such as recruitment or retention bonuses, repayment of tuition fees, relocation support or staffing costs. However, nonwage rewards not linked to hours worked “also reduce the fixed costs of a practice and create a pure income effect, thereby inducing fewer hours of work and fewer services provided.”

“Linking compensation to time worked or services provided, as opposed to forms of pay that are unrelated to time worked, will better ensure the goal of increased work hours,” the authors conclude. “Policy-makers should recognize that policies for compensation may result in just what we hope for — or just the opposite.”

CMAJ showcases innovative research and ideas aimed at improving health for people in Canada and globally. It publishes original clinical research, analyses and reviews, news, practice updates and thought-provoking editorials. In 2011, the journal celebrates 100 years of publishing medical knowledge in print and now online at cmaj.ca.

For the latest thinking on business, management and economics from the Rotman School of Management, visit http://www.rotman.utoronto.ca/NewThinking .

A new article by researchers at the Rotman School of Management at the University of Toronto and the Kellogg School of Management at Northwestern University presents a new model that explains how the diverse domains of power, intoxication, and anonymity produce similarly paradoxical social behaviors – for better or worse.

According to the researchers, all three states work to break down inhibitions in a person, thus triggering the most prominent response in any given situation regardless of the consequences. As a result, alcohol, power, and anonymity can all inspire heroism and hedonism in the same person depending on the context.

The paper, by Rotman Profs. Jacob Hirsh and Chen-Bo Zhong and the Kellogg School’s Adam Galinsky appears in the current issue of Perspectives on Psychological Science.

“Disinhibition occurs when the forces that normally constrain behaviour are temporarily removed, allowing a person’s initial impulses to be expressed without hesitation, regardless of the consequence,” says Prof. Hirsh.

The authors argue that disinhibition can lead behavior to be more consistent with one’s true underlying motives or dispositions. However, if strong external cues are present, disinhibition can also result in greater situational influences on behavior. Whether the resulting behavioral outcomes are pro-social or anti-social depends upon the nature of the dispositional or situational cue.

“This is why intoxicated individuals can be aggressive in one instant and altruistic in another, for example, or why anonymity can at once increase selfishness and cheating while also promoting helping behavior,” said Prof. Hirsh.

The new paper presents a general model of and three pathways to disinhibition:

•    Social Power: Powerful people are used to relative abundance and have an increased inclination to pursue potential rewards. Because the experience of power increases a “goal and reward focus,” individuals feel less restrained in expressing their current motives – regardless of the social implications.

•    Intoxication: Consuming too much alcohol decreases cognitive resources, and only the most prominent cues will guide behavior in this state. Thus, pre-existing attitudes and personality traits may be expressed more freely, such as aggressive tendencies or risky sexual decision-making. At the same time, however, inebriated individuals tend to be more helpful than sober counterparts when the situation calls for heroism.

•    Anonymity: A cloaked identity serves to reduce social desirability concerns and external constraints on action. As such, an individual may be less inclined to maintain usual levels of social acceptance. This could result in higher levels of honesty and self-disclosure – or heightened aggression and verbal abuse – in an anonymous chatroom.

Each of these processes – a reward focus, cognitive exhaustion, and lack of social concerns –block the same neurological system – the Behavioral Inhibition System – that regulates behavior. The combination of these forces (e.g., a powerful person who has been imbibing all night and then goes into an anonymous chat room) is likely to produce the most disinhibition.

“Although these pathways appear to be unrelated on the surface, they all lead to disinhibited states through a common psychological mechanism,” said Prof. Hirsh.

In conclusion, Prof. Hirsh said a joint understanding of an individual’s motivations and the situational context in which they find themselves allows for a better understanding of how to manage the impact of disinhibition.

“Disinhibition can bring out the best or worst in people, depending on the most salient cues for action. Bars and boardrooms alike should be designed to encourage the desired responses from their disinhibited occupants,” said Prof. Hirsh.

For the latest thinking on business, management and economics from the Rotman School of Management, visit http://www.rotman.utoronto.ca/NewThinking .

Khan, a master’s degree student in applied computing, used the course Topics in Human-Computer Interaction (HCI) to explore the ways Kinect might be used in elementary school classrooms for gesture and speech recognition.

The course focused on user experiences with next-generation input and output technologies. Students read and discussed papers from leading researchers around the world, and had the opportunity to apply their teachings to building their own interactive system using exciting new technologies. Khan decided to use the Microsoft Kinect as new hardware.

Khan enjoyed developing some ways that the Kinect might be used for pedagogical purposes. She explained: “While we discussed various HCI papers in class, I constantly found myself applying the research ideas and techniques specifically to the user group of children… I thought that applications of these techniques could help tremendously in early childhood education.”

Inspired by course readings, Khan developed prototypes in which the user participates in activities by using voice commands and gestures – “pointing to objects on screen and using voice commands to select them.” In her research examples, the voice command could be a simple “this” or “that”, or be a more specific naming activity (e.g., “horse”), based on the activity. (Watch a related video.)

Khan said, “The power of using gesture and speech-based systems in classrooms could not only make an interactive and fun experience, but could also simplify a lot of complex learning.”

Khan tested out her prototypes on her daughters, ages four and seven, and found the use of the Kinect made the activities, such as counting, classification, patterning, and identification, very effective and entertaining for her “usability testers.” She was also able to test her work in her daughter’s Junior Kindergarten classroom.

“As a mother involved in [my daughters’] early years learning development,” Khan noted, “I definitely see the potential use of this technology in education.”

When asked about future plans for research in this area, the graduate student said, “I plan to continue developing more simple prototypes, demonstrating my ideas that can be adapted to classroom education. I also hope to explore this space in the development of assistive and rehabilitative technologies.”

Work with next-generation technologies offers a whole host of life-changing possibilities.