text:
Chapter 17. Learning and Memory
Follow us on Facebook and Twitter, or subscribe to our mailing list, to receive news updates. Learn more.
By Emily Underwood We've all heard how rats will abandon a sinking ship. But will the rodents attempt to save their companions in the process? A new study shows that rats will, indeed, rescue their distressed pals from the drink—even when they're offered chocolate instead. They're also more likely to help when they've had an unpleasant swimming experience of their own, adding to growing evidence that the rodents feel empathy. Previous studies have shown that rats will lend distressed companions a helping paw, says Peggy Mason, a neurobiologist at the University of Chicago in Illinois who was not involved in the work. In a 2011 study, for example, Mason and colleagues showed that if a rat is trapped in a narrow plastic tube, its unrestrained cagemate will work on the latch until it figures out how to spring the trap. Skeptics, however, have suggested that the rodents help because they crave companionship—not because their fellow rodents were suffering. The new study, by researchers at the Kwansei Gakuin University in Japan, puts those doubts to rest, Mason says. For their test of altruistic behavior, the team devised an experimental box with two compartments divided by a transparent partition. On one side of the box, a rat was forced to swim in a pool of water, which it strongly disliked. Although not at risk of drowning—the animal could cling to a ledge—it did have to tread water for up to 5 minutes. The only way the rodent could escape its watery predicament was if a second rat—sitting safe and dry on a platform—pushed open a small round door separating the two sides, letting it climb onto dry land. © 2015 American Association for the Advancement of Science
Keyword: Emotions; Learning & Memory
Link ID: 20923 - Posted: 05.13.2015
By Gareth Cook Much has been written on the wonders of human memory: the astounding feats of recall, the way memories shape our identity and are shaped by them, memory as a literary theme and a historical one. But what of forgetting? This is the topic of a new book by Douwe Draaisma, author of The Nostalgia Factory and a professor of the history of psychology at the University of Groningen. In Forgetting, Draaisma considers dreaming, amnesia, dementia and all of the ways that our minds — and lives — are shaped by memory's opposite. He answered questions from Mind Matters editor Gareth Cook. What is your earliest memory and why, do you suppose, have you not forgotten it? Quite a few early memories in the Netherlands involve bicycles, and mine is no exception. I was two-and-a-half years old when my aunts walked my mother to the train station. They had taken a bike along to transport her bags. I was sitting on the back of the bike. Suddenly the whole procession came to a halt when my foot got caught between the spokes. I'm pretty sure this memory is accurate, since I had to see a doctor and there is a dated medical record. It's a brief, snapshot-like memory, black-and-white. I don't remember any pain, but I do remember the consternation among my mom and her sisters. Looking back on this memory from a professional perspective, I would say that it has the flash-like character typical for first memories from before age 3; 'later' first memories are usually a bit longer and more elaborate. It also fits the pattern of being about pain and danger. Roughly three in four first memories are associated with negative emotions. This may have an evolutionary origin: I never again had my foot between the spokes. And neither have any of my children. © 2015 Scientific American
Keyword: Learning & Memory
Link ID: 20918 - Posted: 05.13.2015
By Simon Makin After wandering around an unfamiliar part of town, can you sense which direction to travel to get back to the subway or your car? If so, you can thank your entorhinal cortex, a brain area recently identified as being responsible for our sense of direction. Variation in the signals in this area might even explain why some people are better navigators than others. The new work adds to a growing understanding of how our brain knows where we are. Groundbreaking discoveries in this field won last year's Nobel Prize in Physiology or Medicine for John O'Keefe, a neuroscientist at University College London, who discovered "place cells" in the hippocampus, a brain region most associated with memory. These cells activate when we move into a specific location, so that groups of them form a map of the environment. O'Keefe shared the prize with his former students Edvard Moser and May-Britt Moser, both now at the Kavli Institute for Systems Neuroscience in Norway, who discovered "grid cells" in the entorhinal cortex, a region adjacent to the hippocampus. Grid cells have been called the brain's GPS system. They are thought to tell us where we are relative to where we started. A third type—head-direction cells, also found in the entorhinal region—fires when we face a certain direction (such as "toward the mountain"). Together these specialized neurons appear to enable navigation, but precisely how is still unclear. For instance, in addition to knowing which direction we are facing, we need to know which direction to travel. Little was known about how or where such a goal-direction signal might be generated in the brain until the new study. © 2015 Scientific American
Keyword: Learning & Memory
Link ID: 20915 - Posted: 05.13.2015
Jane Brody With people worldwide living longer, marketers are seizing on every opportunity to sell remedies and devices that they claim can enhance memory and other cognitive functions and perhaps stave off dementia as people age. Among them are "all-natural" herbal supplements like Luminene, with ingredients that include the antioxidant alpha lipoic acid, the purported brain stimulant ginkgo biloba, and huperzine A, said to increase levels of the neurotransmitter acetylcholine; brain-training games on computers and smartphones; and all manner of puzzles, including crosswords, sudoku and jigsaw, that give the brain a workout, albeit a sedentary one. Unfortunately, few such potions and gizmos have been proven to have a meaningful, sustainable benefit beyond lining the pockets of their sellers. Before you invest in them, you'd be wise to look for well-designed, placebo-controlled studies that attest to their ability to promote a youthful memory and other cognitive functions. Even the widely acclaimed value of doing crossword puzzles has been called into question, beyond its unmistakable benefit to one's font of miscellaneous knowledge. Although there is some evidence that doing crosswords may help to delay memory decline, Molly Wagster, a neuroscientist at the National Institute on Aging, said they are best done for personal pleasure, not brain health. "People who have done puzzles all their lives have no particular cognitive advantage over anyone else," she said. The institute is one of several scientific organizations sponsoring rigorous trials of ways to cash in on the brain's lifelong ability to generate new cells and connections. One such trial, Advanced Cognitive Training for Independent and Vital Elderly, or Active, was a 10-year follow-up study of 2,832 cognitively healthy community-dwelling adults 65 and older. © 2015 The New York Times Company
Keyword: Learning & Memory; Alzheimers
Link ID: 20910 - Posted: 05.12.2015
Andrew Griffin Scientists have created an electronic memory cell that mimics the way that human brains work, potentially unlocking the possibility of the making bionic brains. The cell can process and store multiple bits of information, like the human brain. Scientists hope that developing it could make for artificial cells that simulate the brain's processes, leading to treatments for neurological conditions and for replica brains that scientists can experiment on. The new cells have been likened to the difference between having an on-off light switch and a dimmer, or the difference between black and white pictures or those with full colour, including shade light and texture. While traditional memory cells for computers can only process one binary thing at a time, the new discovery allows for much more complex memory processes like those found in the brain. They are also able to retain previous information, allowing for artificial systems that have the extraordinary memory powers found in human beings. While the new discovery is a long way from leading to a bionic brain, the discovery is an important step towards the dense and fast memory cells that will be needed to imitate the human brain's processes. "This is the closest we have come to creating a brain-like system with memory that learns and stores analog information and is quick at retrieving this stored information," Sharath Sriram, who led the project, said.
Keyword: Learning & Memory; Robotics
Link ID: 20909 - Posted: 05.12.2015
Douwe Draaisma When we sleep, wrote English psychiatrist Havelock Ellis over a hundred years ago, we enter a 'dim and ancient house of shadow'. We wander through its rooms, climb staircases, linger on a landing. Towards morning we leave the house again. In the doorway we look over our shoulders briefly and with the morning light flooding in we can still catch a glimpse of the rooms where we spent the night. Then the door closes behind us and a few hours later even those fragmentary memories we had when we woke have been wiped away. That is how it feels. You wake up and still have access to bits of the dream. But as you try to bring the dream more clearly to mind, you notice that even those few fragments are already starting to fade. Sometimes there is even less. On waking you are unable to shake off the impression that you have been dreaming; the mood of the dream is still there, but you no longer know what it was about. Sometimes you are unable to remember anything at all in the morning, not a dream, not a feeling, but later in the day you experience something that causes a fragment of the apparently forgotten dream to pop into your mind. No matter what we may see as we look back through the doorway, most of our dreams slip away and the obvious question is: why? Why is it so hard to hold on to dreams? Why do we have such a poor memory for them? In 1893, American psychologist Mary Calkins published her 'Statistics of Dreams', a numerical analysis of what she and her husband dreamed about over a period of roughly six weeks. They both kept candles, matches, pencil and paper in readiness on the bedside table. But dreams are so fleeting, Calkins wrote, that even reaching out for matches was enough to make them disappear. Still with an arm outstretched, she was forced to conclude that the dream had gone. © 2015 Salon Media Group, Inc
Keyword: Sleep; Learning & Memory
Link ID: 20894 - Posted: 05.06.2015
|By Michele Solis An individual with obsessive-compulsive disorder (OCD) is overcome with an urge to engage in unproductive habits, such as excessive hand washing or lock checking. Though recognizing these behaviors as irrational, the person remains trapped in a cycle of life-disrupting compulsions. Previous studies found that OCD patients have abnormalities in two different brain systems—one that creates habits and one that plays a supervisory role. Yet whether the anomalies drive habit formation or are instead a consequence of doing an action over and over remained unclear. To resolve this question, a team at the University of Cambridge monitored brain activity while people were actually forming new habits. Lapses in supervision are to blame, the researchers reported in a study published online in December 2014 in the American Journal of Psychiatry. They scanned 37 people with OCD and 33 healthy control subjects while they learned to avoid a mild shock by pressing on a foot pedal. Pressing the pedal became a habit for everyone, but people with OCD continued to press even when the threat of shock was over. Those with OCD showed abnormal activity in the supervisory regions important for goal-directed behavior but not in those responsible for habit formation. The finding suggests that shoring up the goal-directed systems through cognitive training might help people with OCD. The growing understanding of OCD's roots in the brain may also help convince individuals to engage in standard habit-breaking treatments, which expose a person to a trigger but prevent his or her typical response. "It's hard for people to not perform an action that their whole body is telling them to do," says first author Claire Gillan, now at New York University. "So if you have an awareness that the habit is just a biological slip, then it makes OCD a lot less scary and something you can eventually control." © 2015 Scientific American
Keyword: OCD - Obsessive Compulsive Disorder; Learning & Memory
Link ID: 20880 - Posted: 05.04.2015
Neuroscientists have discovered brain circuitry for encoding positive and negative learned associations in mice. After finding that two circuits showed opposite activity following fear and reward learning, the researchers proved that this divergent activity causes either avoidance or reward-driven behaviors. Funded by the National Institutes of Health, they used cutting-edge optical-genetic tools to pinpoint these mechanisms critical to survival, which are also implicated in mental illness. "This study exemplifies the power of new molecular tools that can push and pull on the same circuit to see what drives behavior," explained Thomas R. Insel, M.D., director of NIH's National Institute of Mental Health (NIMH). "Improved understanding of how such emotional memory works holds promise for solving mysteries of brain circuit disorders in which these mechanisms are disrupted." NIMH grantee Kay Tye, Ph.D. External Web Site Policy, Praneeth Namburi and Anna Beyeler, Ph.D., of the Massachusetts Institute of Technology (MIT), Cambridge, and colleagues, report their findings April 29, 2015 in the journal Nature. Prior to the new study, scientists suspected involvement of the circuits ultimately implicated, but were stumped by a seeming paradox. A crossroads of convergent circuits in an emotion hub deep in the brain, thebasolateral amygdala, seem to be involved in both fear and reward learning, but how one brain region could orchestrate such opposing behaviors – approach and avoidance – remained an enigma. How might signals find the appropriate path to follow at this fork in the road?
Keyword: Learning & Memory; Emotions
Link ID: 20866 - Posted: 04.30.2015
Pete Etchells Over the past few years, there seems to have been a insidious pandemic of nonsense neuroscientific claims creeping into the education system. In 2013, the Wellcome Trust commissioned a series of surveys of parents and teachers, asking about various types of educational tools or teaching methods, and the extent to which they believe they have a basis in neuroscience. Worryingly, 76% of teachers responded that they used learning styles in their teaching, and a further 19% responded that they either use, or intend to use, left brain/right brain distinctions to help inform learning methods. Both of these approaches have been thoroughly debunked, and have no place in either neuroscience or education. In October last year, I reported on another study that showed that in the intervening time, things hadn't really improved – 91% of UK teachers in that survey believed that there were differences in the way that students think and learn, depending on which hemisphere of the brain is 'dominant'. And despite lots of great attempts to debunk myths about the brain, they still seem to persist and take up residence as 'commonplace' knowledge, being passed onto children as if they are fact. When I wrote about an ATL proposal to train teachers in neuroscience – a well-intended idea, but ultimately grounded in nonsense about left brain/right brain myths – I commented at the end that we need to do more to bring teachers and neuroscientists together, to discuss whether neuroscience has a relevant role in informing the way we teach students. Now, a new initiative funded by the Wellcome Trust is aiming to just that. © 2015 Guardian News and Media Limited
Keyword: Learning & Memory; Development of the Brain
Link ID: 20845 - Posted: 04.25.2015
By Felicity Muth One of the first things I get asked when I tell people that I work on bee cognition (apart from 'do you get stung a lot?') is 'bees have cognition?'. I usually assume that this question shouldn't be taken literally otherwise it would mean that whoever was asking me this thought that there was a possibility that bees didn't have cognition and I had just been making a terrible mistake for the past two years. Instead I guess this question actually means 'please tell me more about the kind of cognitive abilities bees have, as I am very much surprised to hear that bees can do more than just mindlessly sting people'. So, here it is: a summary of some of the more remarkable things that bees can do with their little brains. In the first part of two articles on this topic, I introduce the history and basics of bee learning. In the second article, I go on to discuss the more advanced cognitive abilities of bees. The study of bee cognition isn't a new thing. Back in the early 1900s the Austrian scientist Karl von Frisch won the Nobel Prize for his work with honeybees (Apis mellifera). He is perhaps most famous for his research on their remarkable ability to communicate through the waggle dance but he also showed for the first time that honeybees have colour vision and learn the colours of the flowers they visit. Appreciating how he did this is perhaps the first step to understanding everything we know about bee cognition today. Before delving into the cognitive abilities of bees it's important to think about what kinds of abilities a bee might need, given the environment she lives in (all foraging worker bees are female). Bees are generalists, meaning that they don't have to just visit one particular flower type for food (nectar and pollen), but can instead visit hundreds of different types. However, not all flowers are the same. © 2015 Scientific American,
Keyword: Learning & Memory; Evolution
Link ID: 20831 - Posted: 04.22.2015
By Alix Spiegel In 1979, when Jim Stigler was still a graduate student at the University of Michigan, he went to Japan to research teaching methods and found himself sitting in the back row of a crowded fourth-grade math class. "The teacher was trying to teach the class how to draw three-dimensional cubes on paper," Stigler explains, "and one kid was just totally having trouble with it. His cube looked all cockeyed, so the teacher said to him, 'Why don't you go put yours on the board?' So right there I thought, 'That's interesting! He took the one who can't do it and told him to go and put it on the board.' " Stigler knew that in American classrooms, it was usually the best kid in the class who was invited to the board. And so he watched with interest as the Japanese student dutifully came to the board and started drawing, but still couldn't complete the cube. Every few minutes, the teacher would ask the rest of the class whether the kid had gotten it right, and the class would look up from their work, and shake their heads no. And as the period progressed, Stigler noticed that he — Stigler — was getting more and more anxious. In Japanese classrooms, teachers consciously design tasks that are slightly beyond the capabilities of the students they teach, so the students can actually experience struggling with something just outside their reach. "I realized that I was sitting there starting to perspire," he says, "because I was really empathizing with this kid. I thought, 'This kid is going to break into tears!' " © 2015 KQED Inc.
Keyword: Learning & Memory
Link ID: 20820 - Posted: 04.20.2015
By Nicholas Bakalar Breathing problems during sleep may be linked to early mental decline and Alzheimer's disease, a new study suggests. But treating apnea with a continuous positive airway pressure machine can significantly delay the onset of cognitive problems. In a group of 2,470 people, average age 73, researchers gathered information on the incidence of sleep apnea, a breathing disorder marked by interrupted breathing and snoring, and the incidence of mild cognitive impairment and Alzheimer's disease. After adjusting for a range of variables, they found that people with disordered breathing during sleep became cognitively impaired an average of about 10 years sooner than those without the disorder. But compared with those whose sleep disorder was untreated, those using C.P.A.P. machines delayed the appearance of cognitive impairment by an average of 10 years — making their age of onset almost identical to those who had no sleep disorder at all. The lead author, Dr. Ricardo S. Osorio, a research professor of psychiatry at New York University, said the analysis, published online in Neurology, is an observational study that does not prove cause and effect. "But," he added, "we need to increase the awareness that sleep disorders can increase the risk for cognitive impairment and possibly for Alzheimer's. Whether treating sleep disorders truly slows the decline is still not known, but there is some evidence that it might." © 2015 The New York Times Company
Keyword: Sleep; Learning & Memory
Link ID: 20806 - Posted: 04.16.2015
Jon Hamilton There's new evidence that the brain's activity during sleep isn't random. And the findings could help explain why the brain consumes so much energy even when it appears to be resting. "There is something that's going on in a very structured manner during rest and during sleep," says Stanford neurologist Dr. Josef Parvizi, "and that will, of course, require energy consumption." For a long time, scientists dismissed the brain's electrical activity during rest and sleep as meaningless "noise." But then studies using fMRI began to reveal patterns suggesting coordinated activity. To take a closer look, Parvizi and a team of researchers studied three people awaiting surgery for epilepsy. These people spent several days with electrodes in their brains to help locate the source of their seizures. And that meant Parvizi's team was able to monitor the activity of small groups of brain cells in real time. "We wanted to know exactly what's going on during rest," Parvizi says, "and whether or not it reflects what went on during the daytime when the subject was not resting." In the study published online earlier this month in Neuron, the team first studied the volunteers while they were awake and answering simple questions like: Did you drive to work last week? "In order to answer yes or no, you retrieve a lot of facts; you retrieve a lot of visualized memories," Parvizi says. © 2015 NPR
Keyword: Sleep; Learning & Memory
Link ID: 20801 - Posted: 04.15.2015
By Megan Griffith-Greene The idea of playing a game to make you sharper seems like a no-brainer. That's the thinking behind a billion-dollar industry selling brain training games and programs designed to boost cognitive ability. But an investigation by CBC's Marketplace reveals that brain training games such as Lumosity may not make your brain perform better in everyday life. Lumosity Brain training games, such as Lumosity, are a billion-dollar industry. Many people are worried about maintaining their brain health and want to prevent a decline in their mental abilities. (CBC) Almost 15 per cent of Canadians over the age of 65 are affected by some kind of dementia. And many people of all ages are worried about maintaining their brain health and possibly preventing a decline in their mental abilities. "I don't think there's anything to say that you can train your brain to be cognitively better in the way that we know that we can train our bodies to be physically better," neuroscientist Adrian Owen told Marketplace co-host Tom Harrington. To test how effective the games are at improving cognitive function, Marketplace partnered with Owen, who holds the Canada Excellence Research Chair in Cognitive Neuroscience and Imaging at the Brain and Mind Institute at Western University. A group of 54 adults, including Harrington, did the brain training at least three times per week for 15 minutes or more over a period of between two and a half and four weeks. The group underwent a complete cognitive assessment at the beginning and end of the training to see if there had been any change as the result of the training program. ©2015 CBC/Radio-Canada.
Keyword: Learning & Memory; Alzheimers
Link ID: 20774 - Posted: 04.10.2015
Cari Romm "As humans, we can identify galaxies light-years away. We can study particles smaller than an atom," President Barack Obama said in April 2013, "But we still haven't unlocked the mystery of the three pounds of matter that sits between our ears." The observation was part of the president's announcement of the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative, an effort to fast-track the development of new technology that will help scientists understand the workings of the human brain and its diseases. With progress, though, comes a whole new set of ethical questions. Can drugs used to treat conditions like ADHD, for example, also be used to make healthy people into sharper, more focused versions of themselves—and should they? Can a person with Alzheimer's truly consent to testing that may help scientists better understand their disease? Can brain scans submitted as courtroom evidence reveal anything about a defendant's intent? Can a person with Alzheimer's truly consent to testing that may help scientists better understand their disease? To address these questions, the Presidential Commission for the Study of Bioethical Issues, an independent advisory group, recently released the second volume of a report examining the issues that may arise as neuroscience advances. The commission outlined three areas it deemed particularly fraught: cognitive enhancement, consent, and the use of neuroscience in the legal system. © 2015 by The Atlantic Monthly Group
Keyword: Drug Abuse; Learning & Memory
Link ID: 20771 - Posted: 04.08.2015
Alison Abbott Historian of psychology Douwe Draaisma knows well how to weave science, history and literature into irresistible tales. Forgetting, his latest collection of essays around the theme of memory, is — like his successful Nostalgia Factory (Yale University Press, 2013) — hard to put down. His vivid tour through the history of memory-repression theories brings home how dangerous and wrong, yet persistent, were the ideas of Sigmund Freud and his intellectual heirs. Freud thought that traumatic memories and shameful thoughts could be driven from the consciousness, but not forgotten. They would simmer in the unconscious, influencing behaviour. He maintained that forcing them out with psychoanalysis, and confronting patients with them, would be curative. Draaisma relates the case of an 18-year-old whom Freud dubbed Dora, diagnosed in 1900 with 'hysteria'. Dora's family refused to believe that the husband of her father's mistress had made sexual advances to her. Among other absurdities, Freud told Dora that her nervous cough reflected her repressed desire to fellate the man. Dora broke off the therapy, which Freud saw as proof of his theory. He thought that patients will naturally resist reawakening painful thoughts. What Dora did not buy, plenty of others did. Psychoanalysis boomed, becoming lucrative. Its principles were adopted in the 1990s by an unlikely alliance of lawyers and some feminists, who argued that repressed memories of childhood abuse could be recovered with techniques such as hypnosis, and used as evidence in court. Many judges went along with it; the rush of claims cast a shadow over genuine cases of abuse, Draaisma points out. We now know from studies of post-traumatic stress disorder that traumatic memories are impossible to repress. They flood into the conscious mind in horrifying flashbacks. © 2015 Macmillan Publishers Limited
Keyword: Learning & Memory
Link ID: 20747 - Posted: 04.02.2015
|By Dwayne Godwin and Jorge Cham Our minds are veritable memory machines. © 2015 Scientific American
Keyword: Learning & Memory
Link ID: 20734 - Posted: 03.31.2015
|By Roni Jacobson As intangible as they may seem, memories have a firm biological basis. According to textbook neuroscience, they form when neighboring brain cells send chemical communications across the synapses, or junctions, that connect them. Each time a memory is recalled, the connection is reactivated and strengthened. The idea that synapses store memories has dominated neuroscience for more than a century, but a new study by scientists at the University of California, Los Angeles, may fundamentally upend it: instead memories may reside inside brain cells. If supported, the work could have major implications for the treatment of post-traumatic stress disorder (PTSD), a condition marked by painfully vivid and intrusive memories. More than a decade ago scientists began investigating the drug propranolol for the treatment of PTSD. Propranolol was thought to prevent memories from forming by blocking production of proteins required for long-term storage. Unfortunately, the research quickly hit a snag. Unless administered immediately after the traumatic event, the treatment was ineffective. Lately researchers have been crafting a work-around: evidence suggests that when someone recalls a memory, the reactivated connection is not only strengthened but becomes temporarily susceptible to change, a process called memory reconsolidation. Administering propranolol (and perhaps also therapy, electrical stimulation and certain other drugs) during this window can enable scientists to block reconsolidation, wiping out the synapse on the spot. The possibility of purging recollections caught the eye of David Glanzman, a neurobiologist at U.C.L.A., who set out to study the process in Aplysia, a sluglike mollusk commonly used in neuroscience research. Glanzman and his team zapped Aplysia with mild electric shocks, creating a memory of the event expressed as new synapses in the brain. The scientists then transferred neurons from the mollusk into a petri dish and chemically triggered the memory of the shocks in them, quickly followed by a dose of propranolol. © 2015 Scientific American
Keyword: Learning & Memory; Stress
Link ID: 20732 - Posted: 03.30.2015
by Michael Slezak What were we talking about? Oh yes, brain-training programmes may be useful for helping inattentive people focus on tasks in their daily life. At least, that's the implication of an analysis looking at one particular programme. It's the latest salvo in a field that has seen the battles lines drawn between those who believe there is no compelling scientific evidence that training the brain to do a specific task better can offer wider cognitive improvements, and those that think it can work in some cases. The party line is that brain training improves only that which it exercises, says Jared Horvath from the University of Melbourne in Australia. "What this means is, if the training programme uses a working memory game, you get better at working memory games and little else." But an analysis by Megan Spencer-Smith of Monash University in Melbourne, Australia, and Torkel Klingberg at the Karolinska Institute in Stockholm, Sweden, claims to show that there are benefits for daily life – at least for people with attention deficit hyperactivity disorder or other problems related to attentiveness. They focused on a programme called Cogmed, which Klingberg has helped develop, and combined the results of several smaller studies. Cogmed is designed to improve how much verbal or visual information you can temporarily remember and work with. © Copyright Reed Business Information Ltd.
By PAM BELLUCK What happens to forgotten memories — old computer passwords, friends' previous phone numbers? Scientists have long held two different theories. One is that memories do not diminish but simply get overshadowed by new memories. The other is that older memories become weaker, that pulling to mind new passwords or phone numbers degrades old recollections so they do not interfere. The difference could be significant. If old memories stay strong and are merely papered over by new ones, they may be easier to recover. That could be positive for someone trying to remember an acquaintance's name, but difficult for someone trying to lessen memories of abuse. It could suggest different strategies for easing traumatic memories, evaluating witness testimony about crimes, or helping students study for tests. Now, a study claims to provide evidence of memory's weakening by showing that people's ability to remember something and the pattern of brain activity that thing generates both appear to diminish when a competing memory gets stronger. Demonstrating sophisticated use of brain scans in memory research, authors of the study, published Monday in the journal Nature Neuroscience, appear to have identified neural fingerprints of specific memories, distinguishing brain activity patterns produced when viewing a picture of a necklace, say, from a picture of binoculars or other objects. The experiment, conducted by scientists in Birmingham and Cambridge, England, involved several stages with 24 participants first trained to associate words to two unrelated black and white pictures from lists of famous people, ordinary objects or scenes. © 2015 The New York Times Company
Keyword: Learning & Memory
Link ID: 20695 - Posted: 03.17.2015


text:
Officials with the U.S. Department of Agriculture have been quietly assuring illegal immigrants that taking food stamps and other government assistance won't slow their paths toward citizenship.
The agency's Supplemental Nutrition Assistance Program addresses the point: The brochure asks, "If I get on SNAP benefits, will I be a 'public charge?'"
The brochure then answers: "No. You and your family can apply for and receive SNAP benefits without hurting your chance of becoming U.S. citizens."
The Daily Caller reported on the brochure, which was part of a packet the USDA gives Mexican consulates for distribution among various Mexican communities in the United States.
The Census Breau reports that heads of households born in Mexico are more likely than any other nationality to take some form of government food assistance.
More than 45 percent are on food assistance, according to March 2011 Census figures, The Daily Caller reports. By way of comparison, just under 14 percent of native-born Americans use food stamps, the report continued.
© Copyright 2015 The Washington Times, LLC. Click here for reprint permission.

subset: commoncrawl


text:
|Reviews for Coffee, coffee and even more love
| Just Another Hawk chapter 1 . 6/17/2012
Great job! I love the book and your story is written great! :)
| confusednikki24-7 chapter 1 . 6/2/2012
awww cute story! i loved it!
| Tripple J chapter 1 . 5/11/2012
I loved your story. Love the moviee, too. It's sad that there are only a few stories in this novel.
| PrincessBella15 chapter 1 . 12/22/2011
it's a cute story
| XxxpokeyxxX chapter 1 . 1/25/2011
it's awesome you are a great writer
| InspyreLove chapter 1 . 1/14/2011
Awww! Very sweet!
I'm about to start a chapter length story with Jane and Michael, so maybe you would like to read it? :D
| Arctic Symmetry chapter 1 . 1/11/2011
Just finished the book seconds ago, it was so sweet and wonderful that i had to look up if it was here. I loved your fic, it was just like the book. Just one question that i cant help but ask, what about jake? Maybe he wil be the second kid they are planning? How about a sequel, eh?
| gabelle chapter 1 . 12/22/2010
so sweet...I loved this book!
| hopewithgraywings chapter 1 . 9/15/2010
Have you read j p's seires Maximum ride? Best seires ever!
| MyelleWhite chapter 1 . 6/7/2010
Beautifully written. I wondered if there were going to be any stories about the novel and I found yours and nearly fell out of my chair! I was so happy! I desperately hoped your story wouldn't be dumb but my worries for for nothing and your story was amazing! Thanks for writing it! I'm soooo glad you did!
| Nana Rae chapter 1 . 6/3/2010
fantastic! very cute ) I'm glad someone finally wrote something for this book, its one of my favorites.


text:
I'm thinking about containers and contents lately. We all love great containers. Last year, I went to a local shop and purchased a new hummingbird feeder crafted by an artist somewhere near Asheville. Instead of the plastic parts found on a standard retail feeder, this one has a very unique red bottle as a container. It is decorated with copper tubing from which the hummingbird drinks and metal flowers are soldered onto the copper. It is a real work of art, and I enjoy it tremendously.
I'm pretty sure the hummingbirds, however, care more about the content in the bottle. If I put something less to their liking in the bottle, it doesn't matter how attractive the container. Not only will they not drink from it, they will eventually quit coming to that particular bottle. Birds are quick learners. Read the rest of this entry »
This past Wednesday, I disembarked Seabourn Sojourn along with my son and cinematographer Chris Stanley. We were on board shooting a new show featuring "Adventures Ashore" throughout Europe. During our ten days on Seabourn Sojourn (and in the ports where she called), we saw the sights, met the locals, and had some fun in the sun-splashed Mediterranean. Read the rest of this entry »
I can't believe it was 26 years ago that I got my first job in the travel industry. My parents had just returned from a big trip overseas booked through Austravel and noticed they were advertising for an administrative assistant in their Bristol, UK office. We always traveled a lot as a family and it seemed like a good fit for a young 18 year old just starting out in her career. I applied, got the job, and never looked back! I quickly moved into their ticketing department and spent a year there, but always yearned to be more involved with the customers and the process of planning their holidays. I moved into sales and was hooked. I enjoyed sharing my experiences with potential travelers and also loved the travel that we got to experience. Read the rest of this entry »
"I have a Facebook page, but I can't get anyone to like or comment on anything!" is something I hear often from travel professionals. They know that social media can help build their business, but they can't quite seem to get things moving on their page. I can relate. I spent YEARS with a Facebook page that might as well have had crickets chirping in the background. Fast forward to today, and we have an active and engaged community of over 22,000 fans on our page and Facebook drives a lot of traffic (and bookings) for the agency. Read the rest of this entry »
I have often said that the industry has changed. One of the biggest changes, if not the biggest change, is that today's customers quite likely know more than you do. There is a world of information at their fingertips and we are no longer their "google." Customers come to us based on our relationships, or because they need someone to wade through the muck of booking travel, or because of some access to travel that is not necessarily available elsewhere. They no longer come to us for information about destinations. Sure, they will ask our opinions and thoughts and take them under consideration, but if you think your customers are coming to you with a blank slate, you are sorely mistaken. Read the rest of this entry »
In addition to being a business owner and a luxury travel advisor, many of my friends and followers on social media have come to know me as a self-motivator who often shares daily messages of encouragement. Typically, these posts are along the lines of not being afraid to go after what you really want, dream big, and of course, do bigger. While at times the messages might sound a bit cliché, they are often the extra little push to get me through a current challenge or to have the strength to both deal with a difficult client and complete a punishing spin class in the same hour. I love when I get a message from someone else telling me they "needed that today", as it's clear I'm not the only one who needs constant reminders that I really can do whatever I decide to do. Read the rest of this entry »
If you could double your cruise commission, would you do what was necessary? If you're not already selling cruise tours in eligible destinations, you are definitely leaving serious money on the table. One simple example: a 7-night Alaska sailing southbound from Seward to Vancouver with two passengers in a balcony stateroom. Cruise-only would cost the clients approximately $4,350 for just the 7-night cruise, and the commission (assuming 10%) is roughly $360. However, if you sell a cruise tour package including a 6-night pre-cruise land package, the client total is $7,900 and your commission nearly doubles, jumping to $716. The land portions of cruise tours are typically fully commissionable. There are no NCCFs (non-commission cruise fares) to complicate the math. Read the rest of this entry »
When my internet provider bought out a competitor the switch made my life miserable. I had all sorts of problems, and let's just say that I wasn't a happy surfer.
My local newspaper printed an article about the whole mess mentioning how clients were more than mildly upset. When I saw my cable company in the headline, my attention was drawn to the article. It said in effect, "Hey bub, if you are the recipient from this bogus treatment, I'm talking to you." Read the rest of this entry »
Before social media, the Internet, and cell phones, there was Sky Bird Travel & Tours. With over four decades at the front line of the travel industry, we've forged solid relationships with major airlines from all over the world. These airline partners trust us to pass along their best deals to our community of trusted travel agents. Competitive net fares from Sky Bird Travel & Tours provides financial advantages to our travel agents, so they can offer their clients incredible deals on vacations all over the world while securing higher commissions. Read the rest of this entry »
Back in 2010 my Mom was diagnosed with Stage 4 cancer and we made the decision, as a family, for hospice care. Between surgeries, hospital stays, and her passing, it was a grueling couple of weeks. While all this was going on, I attempted to take care of my current clients. I was in no shape to take on new ones at the time. Read the rest of this entry »
Relying on memory is a fatal practice. Here is the long and short of it: Write everything down. Take notes.
Memories can be short. Nights are for sleeping, not tossing and turning trying to remember if you have forgotten some important issue for tomorrow's sales presentation. Read the rest of this entry »
Peter Wen has worked at Chinatour.com for just over 3 years and is currently the Sales Director at the company. Born and raised in China, Peter came to the United States to pursue a graduate degree and eventually graduated from Georgia Institute of Technology with a Master's degree in Economics in 2012. Although working in the travel industry wasn't his first choice, he found himself highly passionate about helping travel agents know more about the ancient country of China. His ultimate goal is make China a more popular destination in the industry and help travel agents realize how easy and profitable it is to sell China packages. Read the rest of this entry »
Kelly Bergin served as vice president of business development for OASIS from 2009 through 2014 after spending over 25 years in the travel industry. She was recently promoted to President, responsible for helping new sellers of travel launch their careers and aiding established agents in growing their business as successful entrepreneurs.
The travel industry veteran owned her own leisure travel agency in Salt Lake City for seven years and previously worked as a business development manager for both Princess Cruises and Funjet Vacations prior to that. Read the rest of this entry »
It's that time of year again. While other people are decorating their homes with decorative gourds and trying to cram pumpkin spice into every conceivable foodstuff, I'm doing early brainstorming for Wave Season.
I mean, it's not that pumpkin spice is necessarily a bad thing, but I'd rather spend my time trying to hone my storytelling skills and my ability to paint vivid pictures with words. I know an awful lot of people in the Upper Midwest area of the country, and they're going to start seeing snow any day now. Read the rest of this entry »
A true gem in the crown of South Africa, Cape Town is one of the most progressive and contemporary cities in Africa. From delightful wines to thrilling wildlife encounters, everyone will find something to treasure in Cape Town.
Xiamen is known as one of China's "most livable" cities, and with its tree-lined beaches, countless attractions and lush surrounding countryside, it's little wonder visitors are drawn here. Even if it's for only a short stay, one should never miss the opportunity to visit the "gateway" to China. Located at the southeast coast of China, Xiamen is one of the major port cities in the Fujian Provence. Popular with both Chinese and international tourists, the city is famous for its island seascapes, subtropical climate, rich history and customs, and great regional cuisine.
Xiamen has been a major trading port for hundreds of years as it boasts a broad deep-water gulf, and thanks to its year-round temperate climate, isn't subject to freezing or silting. This makes it a perfect port-of-call for commercial vessels and cruise ships alike. Read the rest of this entry »
The original vacationer's dream, Havana charmed many a traveler in its heyday before the Communist revolution in the 1950's. With travel restrictions on US citizens easing and relations between the two countries warming, Cuba is poised to reclaim its title as one of the hottest Caribbean travel destinations. Havana, its capital city, is already getting out her best dress for new visitors, made of salsa dancing, vintage cars, and a survivalist spirit found nowhere else. Let Downtown Travel be your guide to this mesmerizing Caribbean paradise. Read the rest of this entry »
|Courtesy of Open Jaw and Sean Kapitain


text:
Page 1
An Integrative -omics Approach to Identify Functional
Sub-Networks in Human Colorectal Cancer
Rod K. Nibbe1,2*, Mehmet Koyutu ¨rk1,3, Mark R. Chance1,4
1Center for Proteomics & Bioinformatics, Case Western Reserve University, Cleveland, Ohio, United States of America, 2Department of Pharmacology, Case Western
Reserve University, Cleveland, Ohio, United States of America, 3Department of Electrical Engineering & Computer Science, Case Western Reserve University, Cleveland,
Ohio, United States of America, 4Department of Physiology & Biophysics, Case Western Reserve University, Cleveland, Ohio, United States of America
Emerging evidence indicates that gene products implicated in human cancers often cluster together in ''hot spots'' in
protein-protein interaction (PPI) networks. Additionally, small sub-networks within PPI networks that demonstrate
synergistic differential expression with respect to tumorigenic phenotypes were recently shown to be more accurate
classifiers of disease progression when compared to single targets identified by traditional approaches. However, many of
these studies rely exclusively on mRNA expression data, a useful but limited measure of cellular activity. Proteomic profiling
experiments provide information at the post-translational level, yet they generally screen only a limited fraction of the
proteome. Here, we demonstrate that integration of these complementary data sources with a ''proteomics-first'' approach
can enhance the discovery of candidate sub-networks in cancer that are well-suited for mechanistic validation in disease.
We propose that small changes in the mRNA expression of multiple genes in the neighborhood of a protein-hub can be
synergistically associated with significant changes in the activity of that protein and its network neighbors. Further, we
hypothesize that proteomic targets with significant fold change between phenotype and control may be used to ''seed'' a
search for small PPI sub-networks that are functionally associated with these targets. To test this hypothesis, we select
proteomic targets having significant expression changes in human colorectal cancer (CRC) from two independent 2-D gel-
based screens. Then, we use random walk based models of network crosstalk and develop novel reference models to
identify sub-networks that are statistically significant in terms of their functional association with these proteomic targets.
Subsequently, using an information-theoretic measure, we evaluate synergistic changes in the activity of identified sub-
networks based on genome-wide screens of mRNA expression in CRC. Cross-classification experiments to predict disease
class show excellent performance using only a few sub-networks, underwriting the strength of the proposed approach in
discovering relevant and reproducible sub-networks.
Citation: Nibbe RK, Koyutu ¨rk M, Chance MR (2010) An Integrative -omics Approach to Identify Functional Sub-Networks in Human Colorectal Cancer. PLoS
Comput Biol 6(1): e1000639. doi:10.1371/journal.pcbi.1000639
Editor: Nathan D. Price, University of Illinois at Urbana-Champaign, United States of America
Received May 19, 2009; Accepted December 11, 2009; Published January 15, 2010
Copyright: ? 2010 Nibbe et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This work was supported, in whole or in part, by National Institutes of Health Grants UL1-RR024989 from the National Center for Research Resources
(Clinical and Translational Science Awards), P30-CA043703 from the Case Western Reserve University Cancer Center Proteomics Core, and T32-GM008803 from the
NIGMS (Institutional National Research Service Award). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of
the manuscript.
Competing Interests: None
* E-mail: firstname.lastname@example.com
Colorectal cancer (CRC) is the second leading cause of cancer
death in adult Americans [1]. Interest in this complex disease is
represented by a very mature body of research, much of it at the
genomic level. Yet the identification and verification of proteins
that have a functional role in the patho-physiology of CRC
remains an important goal as proteins directly mediate the
functions dysregulated in the disease. Modern, high-throughput
proteomic methods provide one way of profiling the significant
changes in protein expression of tumor samples with respect to
control, using tissue biopsies obtained from patients diagnosed
with this disease [2–5].
Proteomic screening techniques are particularly useful for
furthering the understanding of the mechanisms that underlie
complex phenotypes like CRC, in that they provide information at
the post-translational level. However, due to various biological and
experimental constraints (e.g., ascertainment bias and physical
properties of proteins), proteomic methods may screen only a
limited fraction of proteins and protein isoforms present in cells
and tissues. We propose that this limitation may be mitigated
through the integration of proteomic data with genome scale data
sources, such as measurements of gene expression. In addition,
protein-protein interaction (PPI) databases, which are rapidly
growing in terms of both the quality and quantity of their
annotations, provide another source of genome scale data
integration [6]. Such integrative approaches can potentially lead
to functional inference at the systems level, through identification
of pathways and molecular sub-networks that are implicated in
In support of this approach, a recent review by Ideker and
Sharan [7] summarizes studies that indicate that genes with a role
in cancer tend to cluster together on well-connected sub-networks
of protein-protein interactions. This suggests a hypothesis that
the synergistic expression of multiple cancer-related genes at
the level of mRNA can co-regulate the expression of proteins in
their immediate ''network neighborhood''. These differentially
expressed proteins may be captured by expression proteomics
PLoS Computational Biology | www.ploscompbiol.org1 January 2010 | Volume 6 | Issue 1 | e1000639
Page 2
experiments, thus their network neighborhood should provide an
ideal starting place to search for sub-networks with a possible role
in the disease.
The effectiveness of network-based approaches to the identifi-
cation of multiple disease markers has been demonstrated in the
context of various diseases, including Huntington's disease [8], the
inflammatory response [9], and human breast cancer [10].
Furthermore, it was recently shown that ''differentially expressed
sub-network markers'' were more accurate predictors of metastasis
in breast cancer (compared to single gene markers) [11]. However,
existing approaches are generally limited to mRNA expression
data in terms of quantification of molecular expression, which
captures post-transcriptional activity only to a limited extent
[12,13]. Consequently, inclusion of protein expression data in the
search for sub-network markers has the potential to improve the
effectiveness of systems biology approaches [14]. However, it
remains largely unknown how a network-based approach may be
enhanced when starting with proteomic data.
In this paper, we propose a novel computational approach that
takes into account certain topological features of the interactome,
namely connectivity and proximity, for searching the neighbor-
hoods of proteomic targets to find significant sub-networks
implicated in CRC. In doing so, we partly overcome (i) the bias
inherent in proteomic profiling experiments, particularly those
that are gel-based, which are typically limited to capturing changes
only in relatively abundant proteins and (ii) the noise, missing data,
and ascertainment bias in PPI data. This is accomplished by
assessing the functional association between proteins based on the
quantification of the statistical significance of network crosstalk
through information-flow based modeling of the PPI network and
development of a reference model that takes into account the
network connectivity of proteomic targets. We hypothesize that
identification of candidate sub-networks with a significant
association to proteomic targets can reveal proteins that are not
detected to be differentially expressed at the level of the proteome,
but whose activity in the network may play a key role in
maintaining the phenotype. Consequently, the proposed frame-
work provides a means for expanding proteome expression data to
infer a role for proteins that exhibit significant crosstalk to the
proteomic targets. The flow of the proposed computational
framework is illustrated in Figure 1.
A key objective of this study is to systematically elaborate a
proteomics-driven approach as a sound method for inferring small
sub-networks implicated in complex phenotypes, and ultimately
make these methods practically available to a wider community of
researchers working in this area. For this purpose, we ground our
approach on the hypothesis that the observed fold change of
the proteomic targets may be associated with the synergistic
dysregulation of their interacting partners at the level of mRNA.
From a computational perspective, our hypothesis is based on the
premise that sub-networks which exhibit significant association
with the proteomic targets should also show a significant change in
activity between control and cancer. To test this hypothesis, we
first score each protein in the network based on their crosstalk with
the proteomic targets. In order to account for noise, incomplete-
ness of data, and ascertainment bias, we also develop novel
methods for assessing the significance of these ''crosstalk scores''.
Then, for each proteomic target, we identify a candidate sub-
network that is composed of its interacting partners with significant
crosstalk scores. Subsequently, using an information theoretic
measure, we evaluate the synergistic differential expression of these
candidate sub-networks between control and disease, based on
changes in mRNA expression obtained from microarray experi-
ments performed on tissue biopsies collected from a cohort of
patients with CRC. Finally, using the sub-networks that exhibit
significant synergistic dysregulation as features, we develop
classifiers to predict disease class across different data sets.
The proposed computational approach for assessing functional
association between proteomic targets and other proteins uses a
random-walk based algorithm. Recently, Kohler et al. [15] and
Chen et al. [16] used similar network algorithms to prioritize
candidate disease genes implicated by linkage analysis in a variety
of human diseases. Vanunu and Sharan [17] developed a global,
propagation-based method that exploits information on known
causal disease genes and PPI confidence scores. Their method
more accurately recovered known disease gene relationships
compared to several other extant methods. In contrast to these
applications and rather than using raw scores obtained by such
information flow based algorithms, we develop reference models to
assess the statistical significance of these scores, with a view to
identifying proteins that are significantly associated with proteomic
targets. Furthermore, our biological hypothesis, which drives our
approach, is that targets (proteomic or genomic) significant for the
CRC phenotype may reside in or near cancer hotspots in the
network, and thus present an ideal starting place to search for
high-value sub-networks associated with the disease. Therefore,
our computational approach does not rely on canonical disease-
related genes or proteins; rather, it is a global, unbiased search that
tries to identify network interactions statistically significant with
respect to all targets in an experimentally-derived set.
Our previous work in this area [5] was limited in scope due to
the lack of access to the topology of the commercial PPI we
employed. This prevented us from assessing the importance of
topology for sub-network generation, which is the primary focus of
our computational approach in this study. Likewise, our network
scoring and statistical hypothesis testing were all greatly limited in
the previous work due to incomplete access to an unpublished
microarray data. For the same reason we were practically
prevented from iteratively adjusting network search parameters
Author Summary
Intensive research on cancer has led to an understanding
of many individual genes that may be important for the
initiation and progression of tumors. However, since
cancer is a progressive disease that results from accumu-
lation of multiple mutations likely acting in concert,
individual markers can only provide limited insights into
cellular mechanisms that underlie tumorigenesis. For this
reason, recent studies focus on identification of ''sub-
network markers'', that is, functionally associated genes
that exhibit coordinate changes in molecular expression
during cancer progression. However, expression of genes
is most frequently interrogated at the mRNA level, which
captures functional activity of genes only to a limited
extent. Screening of protein expression, on the other hand,
provides information on the abundance of functional gene
products, but its scale is often limited compared to
screening of mRNA expression. In this article, we develop a
proteomics-driven computational method that searches
for sub-network markers in human colorectal cancer,
based on a seed of differentially expressed proteins
identified by proteomic screening. Our results show that
significant changes in the expression of these proteins is
likely to be associated with coordinate changes in the
expression of the genes whose products are functionally
associated with these proteins. This analysis leads to novel
insights in the synergistic processes that underlie tumor-
Functional Sub-Networks in Human Colorectal Cancer
PLoS Computational Biology | www.ploscompbiol.org2 January 2010 | Volume 6 | Issue 1 | e1000639
Page 3
in the commercial software that would have generated a large list
of candidate sub-networks for scoring.
Here we describe a new network search method for finding
high-value candidate sub-networks associated with CRC. To
overcome the limitations of the previous study and to permit
independent evaluation of our methods, we utilize a public PPI
(HPRD) and public microarrays (Gene Expression Omnibus) to
evaluate performance using two independent sets of proteomic
targets obtained by 2D-PAGE that are also publically available.
We compare this result to that obtained using a set of CRC driver
gene mutants as seeds for the network search. The basis for this
test is the hypothesis that if mutated gene products map to cancer
hotspots on the network, they would be similarly useful as seeds for
our network search algorithm. To reveal the practical utility of our
integrative approach, and to extend it beyond merely a theoretical
computational framework, we validate by western blot several
targets in a sub-network predicted by our method to be
dysregulated, using a cohort of tissue biopsies not used in the
original proteomic screen. Finally, we employ a cross-validation
approach to compare the disease classification performance of the
proteomic-versus genomic-derived sub-networks.
Our results show that the proposed proteomics-driven ap-
proach, as it integrates a variety of biologically relevant data, can
identify significant sub-networks implicated in a complex pheno-
type, i.e. CRC. The definition of terminology frequently used in
this paper is provided in Table 1.
We searched the PPI network obtained from the Human
Protein Reference Database (HPRD) for CRC-implicated sub-
networks using two distinct sets of proteomic targets from Nibbe et
al. [5] (n=67) and Friedman et al. [2] (n=55). Both sets contain
significant targets of CRC obtained by a proteomic screen using
tissue biopsies (tumor and matched controls) obtained from twelve
and six patients, respectively (see Proteomic Methods for details of
the screen performed in our lab). We call these targets proteomic
seeds. The HPRD PPI network was downloaded from the HPRD
website on September 2008 and contained 35023 binary inter-
actions between 9299 proteins, as well as 1060 protein complexes
consisting of 2146 proteins. We integrated the binary interactions
and protein complexes using a matrix model (e.g., each complex is
represented as a clique between the proteins in the complex), to
obtain a PPI network composed of 42781 binary interactions
among 9442 proteins. 60 of the proteomic seeds from the data of
Nibbe et al. had at least one interaction in HPRD, while 37 of the
Figure 1. Schematic of an integrated, proteomics-first approach for the discovery of functional, candidate sub-networks in a
disease phenotype. Disease targets significant for a phenotype (e.g. cancer) are used to seed an information-flow based search of the human
interactome for candidate sub-networks subsequently classified as crosstalkers or interactors. Candidate sub-networks are then scored between test
and control (e.g. normal vs. tumor) using the mutual information of aggregate mRNA expression data as a proxy for synergistic dysregulation. High-
scoring sub-networks may be experimentally validated for their role in disease.
Functional Sub-Networks in Human Colorectal Cancer
PLoS Computational Biology | www.ploscompbiol.org3 January 2010 | Volume 6 | Issue 1 | e1000639
Page 4
seeds from the data of Friedman et al. had at least one interaction
in HPRD. 14 of the proteins in the two seed sets were common.
For every protein in HPRD, our procedure assigns a score
based on the protein's proximity and connectivity to all the seeds
(see Materials and Methods). If the score is not significant
(p,0.001) but the protein directly interacts with one or more of
the seeds, we call it an interactor, whereas a crosstalker is any protein
whose score is significant. Note that a crosstalker is generally (but
not necessarily always) an interactor since a significant crosstalk
score for a protein indicates that it is in the network neighborhood
of one or more of the seeds, however, there are many interactors
that do not qualify as crosstalkers. Overall, this procedure revealed
233 crosstalkers for Nibbe seeds, and 210 crosstalkers for Fried-
man seeds.
Subsequently, for each proteomic seed in each set, a candidate
sub-network consisting of its interactors, termed the interactor
sub-network, was obtained, resulting in a total of 55 interactor sub-
networks (46 for Nibbe seeds exclusively, 23 for Friedman seeds
exclusively, and 14 additional sub-networks for both). Similarly,
for each seed in both sets, a crosstalker sub-network was obtained.
Thus, for every seed there are two corresponding sub-networks, an
interactor sub-network and a crosstalker sub-network. The
proteins in an interactor sub-network are merely characterized
by their direct interactions with the corresponding proteomic seed.
By contrast, proteins in a crosstalker sub-network are character-
ized by their degree of functional association with all proteomic
Relationship of Expression between Crosstalkers and
Individual Proteins in HPRD at the Level of mRNA
We evaluated the individual differential gene expression of each
crosstalker identified using the Nibbe and Friedman proteomic
seeds using two microarray datasets obtained from GEO
(GSE10950 & GSE8671). GSE8671 represents 64 experiments
using mRNA isolated from tissue biopsies obtained from 32
patients (matched tumor and adjacent normal mucosa) performed
on an Affymetrix GeneChip (Human U133 Plus 2.0). Similarly,
GSE10950 represents 48 experiments on matched tissue biopsies
(24 patients) performed on an Illumina array (Human ref-8, v2.0).
The cumulative distribution of individual differential expression
scores for proteomic seeds, (and a seed of CRC driver genes
discussed later), as well as all proteins in the network computed as
Table 1. Definition of terminology used frequently in this paper.
Term Definition
Proteomic seed A protein that is significantly differentially expressed between tumor and control, as identified by
proteomic screening.
Proteomic seed set A set of proteomic seeds that are identified together in one proteomic screening cohort.
Network crosstalk The degree of network proximity and connectivity between (groups) of proteins, modeled as the
amount of ''information flow'' between these proteins in a PPI network.
Crosstalker A protein that exhibits statistically significant network crosstalk with proteins in a particular
proteomic seed set.
Interactor sub-network A sub-network of the PPI network induced by the interacting partners of a particular proteomic seed.
Crosstalker sub-network A sub-network of the PPI network induced by the interacting partners of a particular proteomic seed,
which are also identified as crosstalkers with respect to the corresponding proteomic seed set.
Synergy or Synergistic dysregulationCoordinate mRNA-level differential expression of a group of genes in the phenotype.
Figure 2. Crosstalkers are not significant at level of individual
mRNA expression. Cumulative distribution of differential expression
for crosstalkers identified using two proteomic seeds (Nibbe et al.,
Friedman et al.), a seed of CRC driver genes (Sjo ¨blom et al.), and all
proteins in the HPRD PPI network, as quantified by mutual information
with phenotype, using GSE8671 and GSE10950.
Functional Sub-Networks in Human Colorectal Cancer
PLoS Computational Biology | www.ploscompbiol.org4 January 2010 | Volume 6 | Issue 1 | e1000639
Page 5
(please see the Materials and Methods section for details on how
differential expression is quantified). As seen in the figure, we found
no significant difference in the distribution of individual differential
expression of the crosstalkers, as compared to the distribution of
differential expression of all proteins in the HPRD network. This
observation indicates that at the level of individual genes, significant
network crosstalk with proteomic seeds in CRC is not associated
with transcriptomic dysregulation in CRC.
Synergistic Regulation of Sub-Networks Induced by
Proteomic Seeds
Forthepurposeofdiscussion wewillrefertoa sub-networkbythe
proteomic seed that induced the sub-network (e.g. TCP1). For each
version of each sub-network we computed the mutual information
(MI) of each sub-network between control and tumor using the
mRNA expression data from microarrays GSE10950 and
GSE8671 (see Computational Methods), and we used this score to
estimate the significance of the various networks in differentiating
the phenotype (Figure 1). The comparison of mutual information
for the two versions of each sub-network associated with the Nibbe
seed is shown in Figure 3. We plotted the results only for those
(crosstalker) sub-networks where the mutual information exceeded
0.35 (approximately 1s from random mean). The purpose of this
analysis is to understand how the synergy of each crosstalker sub-
network compares to that of its corresponding interactor sub-
network. The MI and significance scores for all sub-networks can be
found in Supplemental Table S1.
Of the 46 candidate sub-networks associated with Nibbe
proteomic seeds, 10 unique interactor sub-networks (green
squares) exhibited significant MI scores. For five of these sub-
networks (CCT2, TCP1, SYNCRIP, HNRPF and HNRPH1) the
crosstalker version of the sub-networks was found to have
enhanced MI on one or the other microarray datasets. Two
crosstalker sub-networks (red diamonds), CCT2 and TCP1, show
improvement over their corresponding interactor sub-network on
both arrays. Notably, on GSE10950, the mutual information score
of the TPI1 crosstalker sub-network is significant, while the
corresponding interactor sub-network failed to show significance.
Figure 4 shows the corresponding plots for the Friedman
proteomic seeds. Here, seven unique interactor sub-networks have
significant MI scores; two of them (ANXA3 and PSMA6) were
common to both sets of microarray data. For the Friedman seeds,
the crosstalkers for candidate sub-network TUBA1B showed
dramatically increased mutual information compared to its
interactor network. Furthermore, four other crosstalker sub-
networks (associated with MYL9, GARS, ANXA3 and GSTP1) all
revealed much higher synergy compared to their corresponding
interactor sub-networks, two of which (MYL9, GSTP1) failed to
show significance on either array. We discuss a possible
explanation for these findings in the Discussion section.
Figures 5a and 5b show unions of crosstalker sub-networks
associated with the Friedman and Nibbe seeds, respectively, for
which the synergy was higher than the corresponding interactor
sub-network. The graphs reveal that many proteomic seeds reside
within or near dense sub-networks of crosstalkers.
Post-Trancriptional Dysregulation of TCP1 Sub-Network
We observed that several of the sub-networks generated using
the two proteomic seed sets contained proteins in common. In
particular, certain sub-units of the TCP1 complex exhibited
marked crosstalk in the sub-network induced by CCT2 in the
Nibbe seed, and TUBA1B in the Friedman seed (Figure 4). In
addition, we had previously shown [5] that certain sub-units of this
complex (CCT3, CCT5, and CCT7) were also significant for the
late-stage CRC phenotype, as revealed by a similar network
scoring methodology but using a commercial PPI unrelated to
TCP1 (or TCPa) is a hetero-oligomeric complex comprised of
two stacked ring structures, each composed of eight known
subunits and plays a functional role in maintaining the CRC
phenotype. Specifically, it was shown [18] to be required for the
proper biogenesis of PLK1, a kinase that has a critical role in
cytokinesis. However, other than their role as sub-units in the
formation of the TCP complex little is known about the
independent role, if any, of these sub-units in CRC [19].
Consequently, these targets present an opportunity for follow-on
mechanistic studies. For this reason, we verified the protein
expression of TCP1, CCT3, CCT5, CCT7, and PLK1 by western
blot in a separate cohort of three patient sample pairs not used in
screening phase, and compared this to the average expression at
the level of mRNA (Figure 6). Consistent with our hypothesis, the
data indicate co-regulation at the level of mRNA and protein, but
also reveal the wide variability of expression of these targets among
individual patients. CCT3 and CCT7 were dramatically over-
expressed in two patients (507 and 534), but less so in patient 540,
which was similar to the pattern for PLK1.
Synergistic Dysregulation of Sub-Networks Induced by
CRC Driver-Gene Seeds
Although these data show that proteomic seeds are well-suited
for identifying synergistically dysregulated sub-networks, we
wished to investigate the power of genetically identified seed sets
in discovering significant sub-networks. As CRC is commonly
thought to be caused by the accumulation of somatic mutations, a
number of cancer research labs have collaborated to conduct
whole genome sequencing to identify the genes thought to be
''drivers'' in cancer, i.e. those represented by the set of genes that
appeared most frequently mutated in a robust cohort of clinical
biopsies. The results of one such study on human breast and colon
cancer were recently reported by Sjo ¨blom et al. [20]. We
hypothesized that the gene products of the CRC driver genes
reported in this study would be located at hotspots in the
interactome. Further, if the mutations lead to dysregulation of
neighboring genes at the level of mRNA, then the seed should
reveal significant sub-networks using our method. Additionally,
since there is less bias in PCR sequencing and high genome
coverage, at least as compared to proteomic profiling, we supposed
that driver gene seeds (n=42) might be superior both in terms of
the number and significance of the sub-networks identified.
As shown in Figure 7, when scored by GSE8671, only four
significant sub-networks were found. Strikingly, for every one of
them, only the crosstalker sub-networks were significant. Using
GSE10950, seven sub-networks of crosstalkers were significant,
including all four found on GSE8671. For all but two of the sub-
networks(P2RX7, OBSCN), the crosstalkers show substantially higher
synergistic differential expression as compared to their interactor
counterparts. Notably, APC, a tumor suppressor gene widely viewed
as the ''gate-keeper'' in CRC, was associated with a significantly
dysregulated sub-network with respect to both arrays, and of all the
genes in the driver seed it was found to be mutated in the highest
percentage (90%) of the clinical samples. This expected finding may
be viewed as a positive control for our analytical method.
In terms of the overall number of significant sub-networks
identified, however, there was no apparent improvement using the
driver gene seed set versus either proteomic seed set. Additionally,
a number of the significant crosstalk sub-networks identified by the
proteomic seeds show markedly higher synergy (MI.0.60) than all
but one (EVL) of the sub-networks found by the driver gene seed.
Functional Sub-Networks in Human Colorectal Cancer
PLoS Computational Biology | www.ploscompbiol.org5 January 2010 | Volume 6 | Issue 1 | e1000639


text:
In this review, we push the low-light limits of Sony's premium compact point and shoot. We love the idea of a truly pocketable camera that can also capture photos of the Milky Way, but how good is the Sony RX100 series really? Can it actually compete with a large sensor DSLR or interchangeable lens mirrorless camera?
How to Process Milky Way Astrophotography in Adobe Lightroom
In this tutorial, I step through the basic RAW Lightroom post processing method that I use on most of my astrophotography.
Sony FE 28mm f/2 Astrophotography Review
Sony just released their most affordable full frame prime lens for their E-mount cameras: the Sony FE 28mm f/2. In this short review, we test it out for use with astrophotography along with its accessory SEL075UWC Ultra Wide Angle and SEL075FEC Fisheye conversion lenses.
Canon EF 50mm f/1.8 STM Astrophotography Review
There's a new nifty 50 in town. In this short review we test out the Canon EF 50mm f/1.8 STM, Canon's latest iteration of their affordable 50mm lens. At about $125, it's the cheapest Canon prime lens available, making it an attractive addition to any Canon kit. Let's see how it does with astrophotography.
Star Trails and Moonlit Landscapes Tutorial
"The first time I made a photograph of a moonlit landscape, I literally said "wow" out loud. I couldn't believe how much detail the moonlight brought out of the photograph." In this tutorial, Tyler Sichelski walks through his process for shooting and processing surreal long exposure landscapes under the light of the Moon.
A Practical Guide to Lens Aberrations and the Lonely Speck Aberration Test
In this article I review one of the most common problems that affects the design of our camera lenses: aberrations.
I hope to give you practical knowledge about the common technical problems of lens design and how they actually affect your photos. Most of all, this article is here to help you understand one aspect of why one lens will produce a better, more accurate photo than another. It's an especially nice bit of knowledge to have when choosing equipment for use in even basic astrophotography.
This is sort of a pixel peepers' article: you could go through your entire photography career and never learn about lens aberrations and be just fine. But if you like the idea of understanding the fine details behind lens performance — and how it affects your photos — this article is for you.
Voigtländer 15mm f/4.5 Heliar III Astrophotography Review
I recently had the opportunity to shoot some astrophotography with an interesting lens: the Voigtlander 15mm f/4.5 Heliar III. With its rather modest/slow/dark f/4.5 aperture, the 15mm Heliar III isn't the most obvious choice for shooting the night sky, but in reality it actually performed well, especially when paired with the Sony a7II. This review is as much a test of the lens as it is an experiment shooting the Milky Way with a slow lens. Read on for more about my experience shooting the night sky with the Voigtländer 15mm f/4.5 Heliar III.


text:
Ever heard of or listened to the a capella group called 'The Filharmonic'? Well, chances are you have after seeing the movie' Pitch Perfect 2′ or watching Season 4 of 'The Sing-Off' on NBC.
Of late, I have been corresponding with one of its members (beat boxer Niko del Rey) who has shared with me some introductory facts that you might find interesting.
"I noticed your blog is very influential within the Filipino community and thought about reaching out to see if you would be interested in helping us promote our group." wrote Niko.
I readily said yes, of course. So for the uninitiated, here's the 411 on the talented group:
"…we are an L.A.-based Filipino-American Boy Band with the interest of promoting our culture and sound. We have only been together for 2 years (May 2013) and we have a lot of hopes and dreams of making our passion for performing into a reality. We are doing our best to make the Filipino culture known here in the states as well as around the world. We recently made an appearance on the new hit movie, Pitch Perfect 2, and have performed with groups like AJ Rafael, Linkin Park, The Black Eyed Peas, and Pentatonix, in addition to going on a nation-wide tour. Alongside with that, we have appeared on national television twice for NBC's The Sing-Off and the Late Late show with James Corden."
Check out the group's video featuring their cover of Jessie J's 'Spotlight'.
courtesy of The Filharmonic
Below is their TV guesting (with Anna Kendrick) on 'The Late Late Show with James Corden'.
courtesy of The Late Late Show with James CordenThe Filharmonic is made up of vocalists VJ Rosales, Trace Gaynor, Joe Caigoy and Barry Fortgang, plus vocal bass Jules Cruz and beatboxer Niko del Rey. To watch the group's other performances, visit their Youtube channel. You can also follow them on Twitter and Instagram @TheFilharmonic.
Credits for the last group photo go to Ben Miller.


text:
APP OF THE DAY: Vimeo review (Windows Phone 7)
While YouTube might boast the bigger audience, there is no denying that the videos on Vimeo are, how shall we put this, more crafted.
Vimeo has released its Windows Phone 7 app, something that Google's YouTube has still failed to do, offering a host of features and ways to catch up with the latest videos on the service on the go, but is it better than the website? We get downloading and uploading to find out.
- Platform
- Windows Phone 7
- Price
- Free
- Where
- Marketplace
Download the free app and you are instantly presented with a welcome page offering quick links to a host of goodies.
There is the facility to search the entire Vimeo catalogue, the ability to see "my videos", which videos you have ticked the "likes" button for, the ones you've opted to "watch later" and even "collections".
Swipe to the right and there's featured content, letting you instantly enjoy recommendations either from the Vimeo team, or by the most-viewed content on the video site.
Swipe again and you have the chance to explore via Vimeo's numerous categories. Whether your interests are in Art, Comedy, Experimental [oh errr] or Sports the Vimeo app has you covered.
Each video has all the details you would expect to see, the ability to set to watch later and like, as well as the chance to read and make comments. You can also share videos via email, social, and SMS.
Where the app gets a little more interesting than just another way to view the video site is that you are also able to upload video to Vimeo as well over 3G if you wish.
Opting to upload video fires up the camera's video functionality - although don't expect to get anything other than that. There are no focus controls, or effects, or the ability to upload videos you've previously captured - something of a missed opportunity.
If you're a fan of Vimeo then this app will serve you well, allowing you to quickly catch up on the wealth of videos on the site in a handy-to-eat app format. We would have liked more control over the upload feature and of the video functionality when you come to actually capture something, but at least Vimeo has included 3G support.
The Vimeo app for Windows Phone 7 is available now in the Marketplace.
Twitter Moments explained: The best of Twitter - all under one tab
This guy plays all the bad iOS GTA clones so you don't have to
What is Google's Now on Tap and how does it work?
YouTube Kids app adds new parental controls to combat safety complaints
- Twitter Moments explained: The best of Twitter - all under one tab
- This guy plays all the bad iOS GTA clones so you don't have to
- What is Google's Now on Tap and how does it work?
- YouTube Kids app adds new parental controls to combat safety complaints
- Starbucks Mobile Order and Pay service goes live in UK
- Apple OS X El Capitan review: Tweaks rather than overhaul for free OS update
- Chromecast 2 hands-on: All-new shape and a full-featured app to go with it
- Microsoft Office for iPad Pro needs a 365 subscription if you want to edit docs
- Full Twitch apps finally coming soon to PS4, PS3, PS Vita, and PS TV
- Best 3D Touch apps for iPhone 6S and 6S Plus
- Microsoft Surface Book vs Surface Pro 4: What's the difference?
- When is Android 6.0 Marshmallow coming to my phone?
- Microsoft Surface Book vs Apple MacBook Pro with Retina display: What's the difference?
- Which iPhone is best for you? iPhone 5S, iPhone 6, iPhone 6S, iPhone 6 Plus or iPhone 6S Plus?
- Chromecast Audio review: Simply connect your disconnected speakers
- Microsoft Lumia 950 vs Lumia 950 XL vs Lumia 930: What's the difference?
- Microsoft Surface Book: Everything you need to know about the world's fastest laptop
- Microsoft Lumia 950 and Lumia 950 XL confirmed: What's the story?
- Microsoft Surface Pro 4 vs Surface Pro 3: What's the difference?
- Spectre x2 is HP's thinnest 2-in-1 ever and it's powerful too


text:
Cells in the very early embryo are interchangeable and undergo rapid division. Soon, however, they begin differentiating into more specific types, finally becoming specialized cells like neurons, blood, or muscle. As they differentiate, they should stop dividing and usually become embedded in particular tissues. Some tumor cells are more like stem cells because they are identical, they divide quickly, and in the worst case ?metastasize ?they wander through the body and implant themselves in new tissues.
Specialized cells may die through age or injuries, so the body keeps stocks of stem cells on hand to generate replacements. Usually the stem cell divides into two types: one that is just like the parent, which is kept to maintain the stock, and another that differentiates. This is what happens with neuroblasts. Cell division creates one large neuroblast and a smaller cell that can become part of a nerve. This process is controlled by events that happen prior to division. The parent cell becomes asymmetrical: it collects a set of special molecules, including Prospero and other proteins, in the area that will bud off and become the specialized cell.
"This asymmetry provides the new cell with molecules it needs to launch new genetic programs that tell it what to become," says Cayetano Gonz�lez, whose group began the project at EMBL and has continued the work as they moved to the IRBB-PCB. "The current study investigates what happens when the process of localizi
Source:European Molecular Biology Laboratory


text:
Yes, what if you wanted to remove the album from the collection though? There doesn't appear to be an easy way
Type: Posts; User: stubby; Keyword(s):
Yes, what if you wanted to remove the album from the collection though? There doesn't appear to be an easy way
I had a problem with finding out how to delete tracks as well.
May I put in the suggestion of binding the delete key to the delete function? Also, right clicking on the album sidebar should allow...
That's bloody brilliant =)
Did you deselect the xvideo thing?
Thanks for the guide. Just to clarify,
sudo apt-get install realplayer
installs realplayer 8
sudo apt-get install realplay
installs realplayer 10 if you have the PLF repositories in your...
any chance to get drupal to work with php5?
funny, i just installed the game on windows.
it's ok, nothing revolutionary
Xubuntu, if there was adequate support.
Are there any guides to follow?
I was thinking of using my video card (Geforce 4 Ti 4200) as it has TV in and TV out to capture stuff from the video surveillance.
Although motion sounds cool,...
You need to select a theme that is based on clearlooks to be able to see the animation
Yes I'm very interested in this as well, although my source will be from a live security camera.
The tools should be the same though, hopefully
will the sources for breezy-extra be available as well ? ever?
i tried
deb-src http://ubuntu-backports.mirrormax.net/ breezy-extras main restricted universe multiverse
but didn't work
this should be plastered all over ubuntuforums so that people know which sources list to use.
Yeah I noticed that too.
Works great for me.
Good to know that something is being done about backports, and to know where backports stands in relation to everything.
It's been tragic seeing how everything went to the dog house these few weeks
I guess whenever whoever is in charge gets off their ****.
Doesn't look like anytime soon though
that's all i needed to hear =)
My notebook is a Pentium M, so is that the 686 kernel ?
to be honest i found it hard trying to use ubuntuforums (and vBulletin boards in general). I just don't like how everything's arranged.
The only forum that i truly find easy to use would be
how hard is it to remove this from being a sticky ?
if there was a wiki documentation team i'd be more then willing to help out
goto the directory where it is saved then type:
and it should run
Yup, everything seems to be doing well... Java seems to be working in firefox also
to compile c++ (.cpp) programs you use g++, instead of plain c (.c) program, which uses gcc
Seems you figured it out, Just posting in case anyone else comes searching.


text:
Joseph Reshard Crawford III ▪ Twitter: @JoeCrawford5
Position: Small Forward ▪ Shoots: Right
Height: 6-5 ▪ Weight: 210 lbs.
Born: June 17, 1986 in Detroit, Michigan
Relatives: Brother of Jordan Crawford
High School: Renaissance in Detroit, Michigan
Recruiting Rank: 2004 (14)
College: University of Kentucky
Draft: Los Angeles Lakers, 2nd round (28th pick, 58th overall), 2008 NBA Draft
NBA Debut: April 8, 2009
D-League: 93 G, 16.8 PPG, 3.5 RPG, 2.5 APG (Full Record)
Other Pages: College Basketball Stats
Sponsor this page for $10 and help Basketball-Reference.com provide this service. Your message will replace this ad.


text:
Council confronts panhandling, camping
Two behaviors attributed to homeless or transient people are now misdemeanor crimes in Tracy.
The City Council adds $500,000 to the sports complex construction. Comments (1)
The Banta Elementary School District raised almost $40,000 during the annual celebration on Saturday. Comments (0)
The heart of the 2015 football season begins tonight when teams from the Tri-City Athletic League begin their five-game league season. Comments (0)
Editor Michael Langley illuminate some topics that journalists rarely speak of.
Submit letters to the editor of up to 300 words to firstname.lastname@example.com or 95 W. 11th St., Ste 101 in Tracy.
Anne Marie Fuller shows us how many things we can do in Tracy this month.
Submit letters to the editor of up to 300 words to email@example.com or 95 W. 11th St., Ste 101.
Sam Matthews found out that Tracy airport may soon train airline pilots — again.
Sam Matthews has the crop report for Tracy's local fruit, nuts, legumes and vegetables.
Sam Matthews takes a swing at Yogi Berra's legacy and plans for an aquatic center.
If you know the answer or can't wait until next week to get it, email Sam Matthews at email@example.com or call 830-4234.
Last week's Remember When mystery photo showed nine of 10 Tracy Boy Scouts and Explorers and their leader leaving Tracy for the National Boy Scout Jamboree in Farragut, Idaho, in July 1973. The Scouts were members of Troop 505 and Explorer Post 505.
If you know the answer or can't wait to get it, email Sam Matthews at email@example.com or call 830-4234.
12:00 am | See more
News Updates Tracy Press
Would you like to receive our daily news? Sign up today!
© Copyright 2015, Golden State Newspapers, Tracy, CA. Powered by BLOX Content Management System from TownNews.com. Privacy Policy