More and more often these days, authors are considered responsible for their own success—and those who were once responsible for promoting them now tout the glories of self-promotion. Or, as a cheery New York literary agent recently put it, “You, the author, have an unprecedented amount of control over the way people discover you and your work, and how your ‘presence’ is presented to the world.”
Here’s what an author’s guide to stardom might look like in the near future.
My new “throne”. I went all over town looking at computer chairs and finally decided on the Realspace Pro 15000 from Office Depot, even though it was a little over my budget. I was able to use a Staples coupon for 20% after talking to a manger so I got $80 off.
I justified the expense that on average the cheaper chairs last me 1.5-2 years and this one has a 3 year warranty on the padding (which goes flat for me a lot) and 10 years on parts.
Putting it together was a bit of a pain and it is extremely heavy, 80+ lbs, and I made the mistake on assembling it downstairs and then fighting to get it upstairs only to have it be too wide to get through my doorway so I had to remove an arm to make it fit.
Researchers have pinpointed a catalytic trigger for the onset of Alzheimer’s disease – when the fundamental structure of a protein molecule changes to cause a chain reaction that leads to the death of neurons in the brain.
For the first time, scientists at Cambridge’s Department of Chemistry, led by Dr Tuomas Knowles, Professor Michele Vendruscolo and Professor Chris Dobson working with Professor Sara Linse and colleagues at Lund University in Sweden have been able to map in detail the pathway that generates “aberrant” forms of proteins which are at the root of neurodegenerative conditions such as Alzheimer’s.
They believe the breakthrough is a vital step closer to increased capabilities for earlier diagnosis of neurological disorders such as Alzheimer’s and Parkinson’s, and opens up possibilities for a new generation of targeted drugs, as scientists say they have uncovered the earliest stages of the development of Alzheimer’s that drugs could possibly target.
The study, published today in the Proceedings of the US National Academy of Sciences, is a milestone in the long-term research established in Cambridge by Professor Christopher Dobson and his colleagues, following the realisation by Dobson of the underlying nature of protein ‘misfolding’ and its connection with disease over 15 years ago.
The research is likely to have a central role to play in diagnostic and drug development for dementia-related diseases, which are increasingly prevalent and damaging as populations live longer.
In 2010, the Alzheimer’s Research UK showed that dementia costs the UK economy over £23 billion, more than cancer and heart disease combined. Just last week, PM David Cameron urged scientists and clinicians to work together to “improve treatments and find scientific breakthroughs” to address “one of the biggest social and healthcare challenges we face.”
The neurodegenerative process giving rise to diseases such as Alzheimer’s is triggered when the normal structures of protein molecules within cells become corrupted.
Protein molecules are made in cellular ‘assembly lines’ that join together chemical building blocks called amino acids in an order encoded in our DNA. New proteins emerge as long, thin chains that normally need to be folded into compact and intricate structures to carry out their biological function.
Under some conditions, however, proteins can ‘misfold’ and snag surrounding normal proteins, which then tangle and stick together in clumps which build to masses, frequently millions, of malfunctioning molecules that shape themselves into unwieldy protein tendrils.
The abnormal tendril structures, called ‘amyloid fibrils’, grow outwards around the location where the focal point, or ‘nucleation’ of these abnormal “species” occurs.
Amyloid fibrils can form the foundations of huge protein deposits – or plaques – long-seen in the brains of Alzheimer’s sufferers, and once believed to be the cause of the disease, before the discovery of ‘toxic oligomers’ by Dobson and others a decade or so ago.
A plaque’s size and density renders it insoluble, and consequently unable to move. Whereas the oligomers, which give rise to Alzheimer’s disease, are small enough to spread easily around the brain - killing neurons and interacting harmfully with other molecules - but how they were formed was until now a mystery.
The new work, in large part carried out by researcher Samuel Cohen, shows that once a small but critical level of malfunctioning protein ‘clumps’ have formed, a runaway chain reaction is triggered that multiplies exponentially the number of these protein composites, activating new focal points through ‘nucleation’.
It is this secondary nucleation process that forges juvenile tendrils, initially consisting of clusters that contain just a few protein molecules. Small and highly diffusible, these are the ‘toxic oligomers’ that careen dangerously around the brain cells, killing neurons and ultimately causing loss of memory and other symptoms of dementia.
“There are no disease modifying therapies for Alzheimer’s and dementia at the moment, only limited treatment for symptoms. We have to solve what happens at the molecular level before we can progress and have real impact,” said Dr Tuomas Knowles from Cambridge’s Department of Chemistry, lead author of the study and long-time collaborator of Professor Dobson and Professor Michele Vendruscolo.
“We’ve now established the pathway that shows how the toxic species that cause cell death, the oligomers, are formed. This is the key pathway to detect, target and intervene – the molecular catalyst that underlies the pathology.”
The researchers brought together kinetic experiments with a theoretical framework based on master equations, tools commonly used in other areas of chemistry and physics but had not been exploited to their full potential in the study of protein malfunction before.
The latest research follows hard on the heels of another ground breaking study, published in April of this year again in PNAS, in which the Cambridge group, in Collaboration with Colleagues in London and at MIT, worked out the first atomic structure of one of the damaging amyloid fibril protein tendrils. They say the years spent developing research techniques are really paying off now, and they are starting to solve “some of the key mysteries” of these neurodegenerative diseases.
“We are essentially using a physical and chemical methods to address a biomolecular problem, mapping out the networks of processes and dominant mechanisms to ‘recreate the crime scene’ at the molecular root of Alzheimer’s disease,” explained Knowles.
“Increasingly, using quantitative experimental tools and rigorous theoretical analysis to understand complex biological processes are leading to exciting and game-changing results. With a disease like Alzheimer’s, you have to intervene in a highly specific manner to prevent the formation of the toxic agents. Now we’ve found how the oligomers are created, we know what process we need to turn off.”
Clever and surprising urban transport solution.
Again. From an engineering point of view, there is a reason why this didn’t catch on, or at least why no one is using it.
A design like this requires the entire weight of the train to be spread over the two very thin sides. This makes it very difficult to design, and would probably result in either thicker sides which makes it incredibly heavy and also renders the whole idea pointless leaving no room in between, or the train has to use lightweight composites which makes it either incredibly expensive or the load has to be reduced significantly.
You will be much better off if you bulid elevated tracks. But elevated tracks are also very expensive.
And that’s why no one does it.
Clever and surprising urban transport solution.
Conceptually elegant, but logistically awkward… I can’t imagine this working in any city that already has an established road transit network
so… I’m guessing the height of the bottom of the train would be at least 25 ft high because of trucks and when there’s a car accident, you leave all of your passengers who-knows-how-many miles away from their final destination stranded in the middle of a congested freeway.
A different red, the same Robin van Persie finally conquers England
Everything turned to gold for Manchester United the moment Alex Ferguson completed one of the finest signings of his career. A historic coup d’etat. On the 15th of August 2012, Robin Van Persie joined the club for £24m and a masterplan to retake the Premier League crown from local rivals was set in place.
They had already tasted success as Ferguson triumphed before the start of another season, jousting Roberto Mancini in a transfer market where he’d previously been so active and dominant. Van Persie wanted one club, the red one, as he clearly stated during his unveiling: “Manchester United breathes football. If you look at all the players from Manchester United, the stadium, the manager - my choice was made very soon in my mind.”
Originally, this was set to be posted yesterday morning as a commemoration of sorts to the victims of the 1989 Hillsborough Tragedy. While polishing the post and gathering a few accompanying photos, I received a text message alerting me to the fact that something terrible had occurred near the finish line of the Boston Marathon.
Like with most instances of breaking news, I scanned my Twitter feed, looking for any bit of information that might confirm the horrible event that my friend had alluded to, and then, seeing a few photos tumble down my timeline, the day changed.
Everything else seemed inconsequential; the workday effectively over. How could one dedicate themselves to their own interests when such an event had happened? How could we obsess over something as insignificant as football when people were still missing, families separated and victims in the midst of emergency operations?
A misery overtook me, and the rest of the day was spent sitting in front of a television screen, fervently searching for any update.
Today, while stories of the strength and resiliency of the people of Boston give us a sense of optimism and confidence, the pit remains in my stomach. But while I had initially thought to scrap this post, I realized that much of it applies to yesterday’s events. We cannot push away tragedy because it is too painful, and we cannot simply overlook the past, no matter how heartbreaking it may be. We must not allow tragedies to fade, but rather, keep them in mind, as we honor the victims by remembering them not as statistics, but as they were, people, with their own hopes, dreams and families.
Whether Hillsborough or yesterday’s events in Boston, we must honor their legacy by remembering them as they would have wanted, and never ending our search for justice.
Busy Is The New Lazy
If you’re telling everybody that you’re busy all the time, it’s time to rethink your ideas about productivity.
So why do we keep doing all this humblebragging about how busy we are? It’s a question Choi investigates thoughtfully: She observes that people who are “legitimately occupied” with work or family rarely play the “too busy” card (clearly, we don’t know the same people)—or, may even go out of their way to make a connectionbecause they’ve been so swamped.
To Choi, when we say “busy,” we’re really trying to say something else—although what exactly that might be depends on the harried soul that’s complaining.
She supplies some translations:
I’m busy = I’m important.
Being busy gives people a sense they’re needed and significant, Choi says. It’s also a sign saying that you’re about to be on-ramped into somebody’s misguided ego trip.
I’m busy = I’m giving you an excuse.
Saying that you’re busy is a handy way to outsource your responsibility to your irresponsibility. Since you’re always distracted, you don’t have to do anything for anybody.
I’m busy = I’m afraid.
Look above at the “I’m important” part. Whether the speaker knows it or not, complaining of busyness is a subtle cry for help, one that reassures us that yes, we are in demand.
In this way, busyness functions as a kind of laziness. When we fill our schedules with appointments and hands with phones, we divest ourselves of downtime. When we’re endlessly doing, it’s hard to be mindful of what we’re doing.
Of course, it’s a interdependent issue. It’s hard to have downtime if your bosses subscribe to what Anne Marie Slaughter calls our time macho culture, “a relentless competition to work harder, stay later, pull more all-nighters, travel around the world and bill the extra hours that the international date line affords you.”
But don’t let that excuse suffice. You can convince your bosses—if you know how to approach the conversation.
Forget GDP: The Social Progress Index Measures National Well-Being
This new index tracks everything from opportunity to health to sustainability.
For many years, the powers that be thought that economic indicators were the ultimate measure of a country’s wellbeing. That’s starting to change. As we have discussed before, the general happiness of a country doesn’t always correlate with its wealth.
In fact, economic indicators don’t match up with a number of important indicators about well-being.
Hence the Social Progress Index, an initiative from The Social Progress Imperative and Harvard Business School Professor Michael Porter that examines how 50 countries perform on 52 indicators related to basic human needs, the foundations of well-being, and opportunity.
The top country: Sweden. The U.S. doesn’t even rank in the top five…