And now, the next step in neuron building! You can see all the previous steps and shortcuts here. Step 4 is adding intrinsic channels to your neuron.Potassium Channel (source)Pretty much all neurons need sodium and potassium channels so they can fire action potentials, but other channels such as calcium channels are also commonly seen in computational models. To add these channels you have to extract the parameters from known data. This means extracting Boltzmann curves and time constant information so you can tell the channel which voltages activate it and inactivate it and how fast to open and close. Activation (Boltzmann) curve for fast sodium channelThis step is tricky and can take a long time, but there is some software that can help. The Enguage Digitizer is one tool I could not live without. Enguage is basically a tool that allows you to manually trace curves from published figures to get the curve data as an excel or .csv file. First you add axis points using the button at the top that has red plus signs on it. You tell the software what values each of the 3 corners of the graph are. Then you click the blue plus signs button and start to trace your graph, like so:using Enguage digitizer to extract channel dataThen you export the data as whichever type of file you want. Pretty nice!I like to have the data this way because then I can overlay this figure trace with any other trace I want and can manually fit an equation to it.Channels are a hugely important part of a computational model. A recent paper from Eve Marder's lab shows that even with a very simple morphological model (just a soma), interesting electrical characteristics can be seen simply by manipulating the channels. Kispersky et al., 2012 from Figure 1Kispersky et al., (2012) introduce an interesting paradox. They show that when you increase the sodium channel conductance you see more action potentials with low current injections (like 200pA). This is expected because the sodium channel is what causes the upswing of the action potential and more sodium is thought to mean more excitability. However, the authors find that when a high current injection is given (like 10nA), the increased sodium channel conductance actually decreases the firing rate. This is counter-intuitive because it goes against the more sodium=more excitability rule.This is a pretty cool finding published in the Journal of Neuroscience using only a simple one-compartment model. The finding is based entirely on channel manipulation, and demonstrates how important these intrinsic channels are to any computational model. © TheCellularScaleKispersky TJ, Caplan JS, & Marder E (2012). Increase in sodium conductance decreases firing rate and gain in model neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience, 32 (32), 10995-1004 PMID: 22875933... Read more »
Kispersky TJ, Caplan JS, & Marder E. (2012) Increase in sodium conductance decreases firing rate and gain in model neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience, 32(32), 10995-1004. PMID: 22875933
A neurobiology team at the University of Pittsburgh has given a Jan Scheuermann the power to do something that a degenerative disease had taken away. Thanks to a brain-computer interface and a robotic arm she affectionately calls “Hector,” Jan is now able to feed herself, despite her paralysis.... Read more »
Collinger, J., Wodlinger, B., Downey, J., Wang, W., Tyler-Kabara, E., Weber, D., McMorland, A., Velliste, M., Boninger, M., & Schwartz, A. (2012) High-performance neuroprosthetic control by an individual with tetraplegia. The Lancet. DOI: 10.1016/S0140-6736(12)61816-9
You can usually tell when a material is about to fail, you might see sagging, cracks, dents, holes, etc. But sometimes materials can fail suddenly—without warning— this known as catastrophic [...]... Read more »
Jin, X., Götz, M., Wille, S., Mishra, Y., Adelung, R., & Zollfrank, C. (2012) A Novel Concept for Self-Reporting Materials: Stress Sensitive Photoluminescence in ZnO Tetrapod Filled Elastomers. Advanced Materials. DOI: 10.1002/adma.201203849
The race is on to create a biofuel that sucks carbon out of the sky and locks it away where it can’t warm the planet
THE green sludge burbles away quietly in its tangle of tubes in the Spanish desert. Soaking up sunshine and carbon dioxide from a nearby factory, it grows quickly. Every day, workers skim off some sludge and take it away to be transformed into oil. People do in a single day what it took geology 400 million years to accomplish.
Indeed, this is no ordinary oil. It belongs to a magical class of “carbon negative” fuels, ones that take carbon out of the atmosphere and lock it away for good. The basic idea is fairly simple. You grow plants, in this case algae, which naturally draw CO2 from the atmosphere. After you extract the oil, you’re left with a residue that holds a substantial portion of the carbon. This residue is the key to carbon negativity. If you can store the carbon where it won’t decompose and return to the air, more CO2 is taken out of the atmosphere than the fuel emits.
Such carbon negative fuels are no accounting sleight of hand – they could be the most realistic short-term solution we have to curb climate change. And although it is still early days, companies like General Electric, BP and Google are putting their money behind the idea.... Read more »
Bob Holmes. (2012) Biofuel that's better than carbon neutral. New Scientist. info:/
The number and types of medical apps for physicians and other medical providers is rapidly increasing. Smart phone apps (i.e. iPhone and Android apps) have the potential to allow physicians real time access to medical records, treatment guidelines and medical reference information. As these apps increase in number and type, it will be important to understand the facilitators and barriers to implementation in the medical setting. Additionally, research will be needed to document whether physician apps actually improve the quality of care. What seems in theory to be important, may fall short in actual clinical practice settings.A recent survey of medical student and junior physician use of smartphone apps in the UK has recently been published in the journal BioMed Central. Karl Frederick Braekken Payne and colleagues surveyed 257 medical students and 131 junior physicians about their ownership and use of smartphones and smartphone apps.Seventy nine percent of the UK medical students surveyed owned a smartphone with the iPhone being the most common type (3:1 over the an Android smartphone). Among junior physicians surveyed, 75% owned a smart phone again with the iPhone owning a significant 4:1 advantage. The following key findings were documented in the study:Medical students used their smartphones for both medical school education and clinical rotation functionsThe majority of users had relatively few medical related apps (1-5 apps) on their smartphonesThe majority of junior resident physicians used their medical related smartphone apps 20 minutes per day or lessMedical students were more likely to use their smartphone apps more than 20 minutes per day in clinical rotationsThe attached chart shows they types of medical related smartphone apps that were used often, very often or constantly in the medical student and junior physician groups.The medical student group tended to more frequently use drug reference, disease management and procedure/case documentation apps compared to the junior physician group.The junior physician group tended to use medical calculator/clinical score apps more frequently. It is unclear whether these trends represent true cohort differences between medical students and junior physicians or a tendency with increased skill level to become less reliant on smartphone app use.One of the barriers to smartphone and smartphone app use in the study was cost. Medical students and junior physician noted device cost and app cost were barriers to medical related smartphone app implementation.The survey also showed that medical students and junior physicians at times did not use available apps in the presence of patients or medical supervisors. One concern was that smartphone app use could be misinterpreted as just checking personal email or web-surfing.There would seem to be an important opportunity to grow the use of smartphones for documentation of educational experiences. Medical students and junior physicians are increasingly required to document the number and type of procedure experiences during training. The smartphone (with central backup) would seem to be an important tool for this process.The research study authors conclude that their survey showed "junior doctors and medical students are overwhelmingly enthusiastic and endorse organisational associated apps that help their learning activities". Clearly there are also barriers that need to be overcome.It will be important that medical related app development be paired with research studies of their implementation and value of such devices in the medical care setting.Readers with more interest in the details of this survey can access the free article by clicking on the PMID link below.Top figure is an iPod screen shot of the medical related drug reference app Epocrates from the author's files.The figure is an original figure for this post produced from data provided in the manuscript.Payne KF, Wharrad H, & Watts K (2012). Smartphone and medical related App use among medical students and junior doctors in the United Kingdom (UK): a regional survey. BMC medical informatics and decision making, 12 PMID: 23110712... Read more »
Payne KF, Wharrad H, & Watts K. (2012) Smartphone and medical related App use among medical students and junior doctors in the United Kingdom (UK): a regional survey. BMC medical informatics and decision making, 121. PMID: 23110712
Recently, scientists from MIT published a research paper in the journal Nature in which they showed their work of “Extremely metal-poor gas at a redshift of 7”. They utilized infrared spectrometer, which they placed onto the Magellan Telescope, a massive ground-based telescope in Chile. They calculated the elements and based on the observations about the heavy elements they believe that the earliest stars might have been formed 750 million years after the formation of Universe.
“The first stars will form in different spots in the universe … it’s not like they flashed on at the same time,” Robert Simcoe, an associate professor of physics at MIT, said in a statement. “But this is the time that it starts getting interesting.”
In another study published recently in the journal Science, researchers were able to study the light from the stars that are just 0.6 billion years old.
Mark A. Holland, who is BS, Engineering Physics at Universitry of Maine, Orono, ME, and worked in BAE Systems, The MITRE Corporation and Operations Research, Inc., and one of the respected readers of SayPeople.com, has commented and pointed to another time of the earliest formation of stars that is very much less than the present finding. He said,
I thought the Hubble Space Telescope had detected a galaxy (UDFj-39546284) with a red-shift of about 10 back in 2009 or 2010. That would mean that not only had stars formed, but entire galaxies had organized by about 480 million years after the Big Bang. When the James Webb Space Telescope comes on-line, we will be able to look a lot further back in time, and I expect we will find that stars were shining even then. There is a good summary article on the discovery of UDFj-39546284 on the Space Telescope website (http://www.spacetelescope.org/news/heic1103/). Cornell University’s website also has the abstract of a paper by R. J. Bouwens (Leiden), P. A. Oesch (UCSC), et. al. on the work performed to confirm the Hubble Ultra Deep Field — Infrared (HUDF-IR) observations (see http://arxiv.org/abs/1211.3105).
Another interesting point is the most distant object recently found by NASA using Hubble and Spitzer space telescopes. That is the most distant galaxy ever found and it is named is MACS0647-JD. This galaxy is found to be the youngest object found in the universe i.e. it’s age is thought to be about 420 million years. This finding can show that the earliest stars were there after 420 million years of the formation of the universe.
In another interesting research, scientists have proposed a mechanism through which they simulated “the distribution of the first stars at redshift 20 (cosmic age of around 180 million years)”. They have based their research on the moving speed of the stars and the influence of the radiation from the earliest stars on the older stars.
Visbal, E., Barkana, R., Fialkov, A., Tseliakhovich, D., & Hirata, C. (2012). The signature of the first stars in atomic hydrogen at redshift 20 Nature DOI: 10.1038/nature11177
Pletsch, H., Guillemot, L., Fehrmann, H., Allen, B., Kramer, M., Aulbert, C., Ackermann, M., Ajello, M., de Angelis, A., Atwood, W., Baldini, L., Ballet, J., Barbiellini, G., Bastieri, D., Bechtol, K., Bellazzini, R., Borgland, A., Bottacini, E., Brandt, T., Bregeon, J., Brigida, M., Bruel, P., Buehler, R., Buson, S., Caliandro, G., Cameron, R., Caraveo, P., Casandjian, J., Cecchi, C., Celik, O., Charles, E., Chaves, R., Cheung, C., Chiang, J., Ciprini, S., Claus, R., Cohen-Tanugi, J., Conrad, J., Cutini, S., D'Ammando, F., Dermer, C., Digel, S., Drell, P., Drlica-Wagner, A., Dubois, R., Dumora, D., Favuzzi, C., Ferrara, E., Franckowiak, A., Fukazawa, Y., Fusco, P., Gargano, F., Gehrels, N., Germani, S., Giglietto, N., Giordano, F., Giroletti, M., Godfrey, G., Grenier, I., Grondin, M., Grove, J., Guiriec, S., Hadasch, D., Hanabata, Y., Harding, A., den Hartog, P., Hayashida, M., Hays, E., Hill, A., Hou, X., Hughes, R., Johannesson, G., Jackson, M., Jogler, T., Johnson, A., Johnson, W., Kataoka, J., Kerr, M., Knodlseder, J., Kuss, M., Lande, J., Larsson, S., Latronico, L., Lemoine-Goumard, M., Longo, F., Loparco, F., Lovellette, M., Lubrano, P., Massaro, F., Mayer, M., Mazziotta, M., McEnery, J., Mehault, J., Michelson, P., Mitthumsiri, W., Mizuno, T., Monzani, M., Morselli, A., Moskalenko, I., Murgia, S., Nakamori, T., Nemmen, R., Nuss, E., Ohno, M., Ohsugi, T., Omodei, N., Orienti, M., Orlando, E., de Palma, F., Paneque, D., Perkins, J., Piron, F., Pivato, G., Porter, T., Raino, S., Rando, R., Ray, P., Razzano, M., Reimer, A., Reimer, O., Reposeur, T., Ritz, S., Romani, R., Romoli, C., Sanchez, D., Parkinson, P., Schulz, A., Sgro, C., do Couto e Silva, E., Siskind, E., Smith, D., Spandre, G., Spinelli, P., Suson, D., Takahashi, H., Tanaka, T., Thayer, J., Thayer, J., Thompson, D., Tibaldo, L., Tinivella, M., Troja, E., Usher, T., Vandenbroucke, J., Vasileiou, V., Vianello, G., Vitale, V., Waite, A., Winer, B., Wood, K., Wood, M., Yang, Z., & Zimmer, S. (2012). Binary Millisecond Pulsar Discovery via Gamma-Ray Pulsations Science, 338 (6112), 1314-1317 DOI: 10.1126/science.1229054
Ackermann, M., Ajello, M., Allafort, A., Schady, P., Baldini, L., Ballet, J., Barbiellini, G., Bastieri, D., Bellazzini, R., Blandford, R., Bloom, E., Borgland, A., Bottacini, E., Bouvier, A., Bregeon, J., Brigida, M., Bruel, P., Buehler, R., Buson, S., Caliandro, G., Cameron, R., Caraveo, P., Cavazzuti, E., Cecchi, C., Charles, E., Chaves, R., Chekhtman, A., Cheung, C., Chiang, J., Chiaro, G., Ciprini, S., Claus, R., Cohen-Tanugi, J., Conrad, J., Cutini, S., D'Ammando, F., de Palma, F., Dermer, C., Digel, S., do Couto e Silva, E., Dominguez, A., Drell, P., Drlica-Wagner, A., Favuzzi, C., Fegan, S., Focke, W., Franckowiak, A., Fukazawa, Y., Funk, S., Fusco, P., Gargano, F., Gasparrini, D., Gehrels, N., Germani, S., Giglietto, N., Giordano, F., Giroletti, M., Glanzman, T., Godfrey, G., Grenier, I., Grove, J., Guiriec, S., Gustafsson, M., Hadasch, D., Hayashida, M., Hays, E., Jackson, M., Jogler, T., Kataoka, J., Knodlseder, J., Kuss, M., Lande, J., Larsson, S., Latronico, L., Longo, F., Loparco, F., Lovellette, M., Lubrano, P., Mazziotta, M., McEnery, J., Mehault, J., Michelson, P., Mizuno, T., Monte, C., Monzani, M., Morselli, A., Moskalenko, I., Murgia, S., Tramacere, A., Nuss, E., Greiner, J., Ohno, M., Ohsugi, T., Omodei, N., Orienti, M., Orlando, E., Ormes, J., Paneque, D., Perkins, J., Pesce-Rollins, M., Piron, F., Pivato, G., Porter, T., Raino, S., Rando, R., Razzano, M., Razzaque, S., Reimer, A., Reimer, O., Reyes, L., Ritz, S., Rau, A., Romoli, C., Roth, M., Sanchez-Conde, M., Sanchez, D., Scargle, J., Sgro, C., Siskind, E., Spandre, G., Spinelli, P., Stawarz, L., Suson, D., Takahashi, H., Tanaka, T., Thayer, J., Thompson, D., Tibaldo, L., Tinivella, M., Torres, D., Tosti, G., Troja, E., Usher, T., Vandenbroucke, J., Vasileiou, V., Vianello, G., Vitale, V., Waite, A., Winer, B., Wood, K., & Wood, M. (2012). The Imprint of the Extragalactic Background Light in the Gamma-Ray Spectra of Blazars Science, 338 (6111), 1190-1192 DOI: 10.1126/science.1227160
Simcoe, R., Sullivan, P., Cooksey, K., Kao, M., Matejek, M., & Burgasser, A. (2012). Extremely metal-poor gas at a redshift of 7 Nature, 492 (7427), 79-82 DOI: 10.1038/nature11612... Read more »
Visbal, E., Barkana, R., Fialkov, A., Tseliakhovich, D., & Hirata, C. (2012) The signature of the first stars in atomic hydrogen at redshift 20. Nature. DOI: 10.1038/nature11177
Pletsch, H., Guillemot, L., Fehrmann, H., Allen, B., Kramer, M., Aulbert, C., Ackermann, M., Ajello, M., de Angelis, A., Atwood, W.... (2012) Binary Millisecond Pulsar Discovery via Gamma-Ray Pulsations. Science, 338(6112), 1314-1317. DOI: 10.1126/science.1229054
Ackermann, M., Ajello, M., Allafort, A., Schady, P., Baldini, L., Ballet, J., Barbiellini, G., Bastieri, D., Bellazzini, R., Blandford, R.... (2012) The Imprint of the Extragalactic Background Light in the Gamma-Ray Spectra of Blazars. Science, 338(6111), 1190-1192. DOI: 10.1126/science.1227160
The United States could eliminate the need for crude oil by using a combination of coal, natural gas and non-food crops to make synthetic fuel, a team of Princeton researchers has found.
Besides economic and national security benefits, the plan has potential environmental advantages. Because plants absorb carbon dioxide to grow, the United States could cut vehicle greenhouse emissions by as much as 50 percent in the next several decades using non-food crops to create liquid fuels, the researchers said.
Synthetic fuels would be an easy fit for the transportation system because they could be used directly in automobile engines and are almost identical to fuels refined from crude oil. That sets them apart from currently available biofuels, such as ethanol, which have to be mixed with gas or require special engines.... Read more »
John Sullivan. (2012) Synthetic fuels could eliminate entire U.S. need for crude oil, create 'new economy'. Princeton University Office of Engineering Communications. info:/
If the idea that matter can be organized in a way that’s similar to binary code seems implausible, get ready for a shock: It can. An MIT team has created a milli-motein — a tiny device made of millimeter-sized components with a motorized design inspired by proteins. Milli-moteins can naturally fold themselves into almost any shape imaginable.... Read more »
Peter Suciu. (2012) MIT's Milli-Motein: Things Just Got a Lot More Interesting. TechNewsWorld. info:/
I’ve previously discussed how to sort CTCs, and the standards used to characterize device performance. Today, I’ll explain what some of the most common evaluation metrics are, and place them in context of eventual clinical/industrial application.... Read more »
Marrinucci Dena, Bethel Kelly, Lazar Daniel, Fisher Jennifer, Huynh Edward, Clark Peter, Bruce Richard, Nieva Jorge, & Kuhn Peter. (2010) Cytomorphology of circulating colorectal tumor cells:a small case series. Journal of oncology. PMID: 20111743
Kirby Brian J, Jodari Mona, Loftus Matthew S, Gakhar Gunjan, Pratt Erica D, Chanel-Vos Chantal, Gleghorn Jason P, Santana Steven M, Liu He, & Smith James P. (2012) Functional characterization of circulating tumor cells with a prostate-cancer-specific microfluidic device. PloS one. PMID: 22558290
In my “How to Sort CTCs” series, I covered a variety of sorting methodologies used for patient prognosis. However, before clinical implementation, it is important characterize device performance with a series of standards. This is impossible to do with a patient blood sample, because there is an unknown number of CTCs floating around with other blood cells, which can be effected by the cancer treatment process (e.g. radiation patients often have anemia)1. Furthermore, this is all changing dynamically as a function of both time and treatment.... Read more »
Kirby Brian J, Jodari Mona, Loftus Matthew S, Gakhar Gunjan, Pratt Erica D, Chanel-Vos Chantal, Gleghorn Jason P, Santana Steven M, Liu He, & Smith James P. (2012) Functional characterization of circulating tumor cells with a prostate-cancer-specific microfluidic device. PloS one. PMID: 22558290
Lazar Daniel C, Cho Edward H, Luttgen Madelyn S, Metzner Thomas J, Uson Maria Loressa, Torrey Melissa, Gross Mitchell E, & Kuhn Peter. (2012) Cytometric comparisons between circulating tumor cells from prostate cancer patients and the prostate-tumor-derived LNCaP cell line. Physical biology. PMID: 22306736
Powell Ashley A, Talasaz Amirali H, Zhang Haiyu, Coram Marc A, Reddy Anupama, Deng Glenn, Telli Melinda L, Advani Ranjana H, Carlson Robert W, & Mollick Joseph A. (2012) Single cell profiling of circulating tumor cells: transcriptional heterogeneity and diversity from breast cancer cell lines. PloS one. PMID: 22586443
Magbanua Mark Jesus M, Sosa Eduardo V, Roy Ritu, Eisenbud Lauren E, Scott Janet H, Olshen Adam, Pinkel Dan, Rugo Hope, & Park John W. (2012) Genomic profiling of isolated circulating tumor cells from metastatic breast cancer patients. Cancer research. PMID: 23135909
Hofman V. J., Ilie M. I., Bonnetaud C., Selva E., Long E., Molina T., Vignaud J. M., Flejou J. F., Lantuejoul S., & Piaton E. (2010) Cytopathologic Detection of Circulating Tumor Cells Using the Isolation by Size of Epithelial Tumor Cell Method: Promises and Pitfalls. American Journal of Clinical Pathology, 135(1), 146-156. DOI: 10.1309/AJCP9X8OZBEIQVVI
Stott Shannon L, Hsu Chia-Hsien, Tsukrov Dina I, Yu Min, Miyamoto David T, Waltman Belinda A, Rothenberg S Michael, Shah Ajay M, Smas Malgorzata E, & Korir George K. (2010) Isolation of circulating tumor cells using a microvortex-generating herringbone-chip. Proceedings of the National Academy of Sciences of the United States of America. PMID: 20930119
Cho Edward H, Wendel Marco, Luttgen Madelyn, Yoshioka Craig, Marrinucci Dena, Lazar Daniel, Schram Ethan, Nieva Jorge, Bazhenova Lyudmila, & Morgan Alison. (2012) Characterization of circulating tumor cell aggregates identified in patients with epithelial tumors. Physical biology. PMID: 22306705
Tormoen Garth W, Cianchetti Flor A, Bock Paul E, & McCarty Owen J T. (2012) Development of coagulation factor probes for the identification of procoagulant circulating tumor cells. Frontiers in oncology. PMID: 22973554
Neurons don't grow in a vacuum. They have white fibers, other neurons, blood vessels and all sorts of other obstacles to grow around.Some NeuroArt (source)A recent paper from France details the making of a 3D environment that can facilitate 'realistic' neural growth. Labour et al. (2012) created a collagen biomimetic matrix which contains neural growth factor (NGF). Labour et al., (2012) Figure 3These scanning electron microscope images show the porous fibril texture of the collagen matrix. Most of the paper is spent explaining the methods for making this biomimetic matrix, but they also actually grow some pseudo-neurons (PC-12 cells) on the matrix. They show that when cultured on top of this collagen surface, the cells extend neurons in three dimensions into the matrices and are affected by the NGF. (when there is no NGF, the neurites don't grow and the cells die.) This paper is mostly about the methods, but I like the new possibilities that growing 3D cells opens up. With these biomimetic collagen matrices, the factors that cause specific dendritic arborizations in three dimensions can be analyzed. The environment can be completely controlled and the neurons easily visualized during growth. The authors suggest using these matrices to study neurodegeneration as well.Another interesting thing this paper introduced me to is the 'graphical abstract.' I didn't know that that was a thing, but it seems like a good idea. However, trying to summarize an entire paper in one figure seems pretty difficult. Here is their attempt:Labour et al. (2012) graphical abstractI think it does actually get the feel of the paper across pretty well, though it's not really informative without the actual abstract next to it. © TheCellularScaleLabour MN, Banc A, Tourrette A, Cunin F, Verdier JM, Devoisselle JM, Marcilhac A, & Belamie E (2012). Thick collagen-based 3D matrices including growth factors to induce neurite outgrowth. Acta biomaterialia, 8 (9), 3302-12 PMID: 22617741... Read more »
Labour MN, Banc A, Tourrette A, Cunin F, Verdier JM, Devoisselle JM, Marcilhac A, & Belamie E. (2012) Thick collagen-based 3D matrices including growth factors to induce neurite outgrowth. Acta biomaterialia, 8(9), 3302-12. PMID: 22617741
GPS shoes can point to where you're going, but how will they know where to go? By consulting the map uploaded via USB and its own GPS receivers, wirelessly communicating with each other. For future models, you could probably set up WiFi to let your shoes download more information, talk with other people's shoes and modify your route on the go. So your footware might need its own network access, like agent Maxwell Smart's left shoe with a mobile subscription plan. The "No place like home" shoes are built around two microcontrollers called Arduinos: A magnet in the right shoe and sensor in the left shoe communicate with each other and with the GPS antenna in the red tag at the back. Clicking the heels starts the GPS. So all you need to do is to close your eyes and tap your heels together. And there will be no need to follow the yellow brick road or say the magic words.The smart shoes - designed by artist Dominic Wilcox and custom-made by Stamp Shoes might be a bit costly: £1,100 (about $1,750). A bit less sophisticated Aetrex Navistar GPS shoes developed for sufferers of Altzheimer's disease and dementia cost $299.99, and come with two monthly subscription plans - a basic 30 minute tracking plan, which reports every 30 minutes ($34.99) and for an additional $5 per month a premier 10 minute tracking plan. Nike was offering their own GPS footware too, for fitness enthusiasts, but decided that it's cheaper to use iPhone's location sensor to figure distance and serve as a pedometer.Yet, sensors in high-tech shoes could be helpful. For example, they could detect if their owner is tired or exhausted. Fatigue Monitoring System (FAMOS, recently developed and tested in patients with multiple sclerosis (MS) and healthy individuals) continuously measures motions of feet, in addition to electrocardiogram, body-skin temperature and electromyogram. And the system can reliably distinguish the symptoms of fatigue. The shoe sensors could provide a wealth of information about motion and assess such things as the risk of falling. And this information can be combined with data collected through other channels. Aurametrix, for example, can determine how food, air quality, the weather and various activities affect energy levels and generate suggestions on what to do - at the right time and right place. Systems like Aurametrix could eventually integrate our observations with data coming from smart objects such as shoes and heart monitors, to speed up not only walking but also the understanding of the human body, for a healthier world.PUBLICATIONS Yu F, Bilberg A, Stenager E, Rabotti C, Zhang B, & Mischi M (2012). A wireless body measurement system to study fatigue in multiple sclerosis. Physiological measurement, 33 (12), 2033-2048 PMID: 23151461Marschollek, M., Rehwald, A., Wolf, K., Gietzelt, M., Nemitz, G., zu Schwabedissen, H., & Schulze, M. (2011). Sensors vs. experts - A performance comparison of sensor-based fall risk assessment vs. conventional assessment in a sample of geriatric patients BMC Medical Informatics and Decision Making, 11 (1) DOI: 10.1186/1472-6947-11-48... Read more »
Yu F, Bilberg A, Stenager E, Rabotti C, Zhang B, & Mischi M. (2012) A wireless body measurement system to study fatigue in multiple sclerosis. Physiological measurement, 33(12), 2033-2048. PMID: 23151461
Marschollek, M., Rehwald, A., Wolf, K., Gietzelt, M., Nemitz, G., zu Schwabedissen, H., & Schulze, M. (2011) Sensors vs. experts - A performance comparison of sensor-based fall risk assessment vs. conventional assessment in a sample of geriatric patients. BMC Medical Informatics and Decision Making, 11(1), 48. DOI: 10.1186/1472-6947-11-48
Most CTC sorting devices target some observed cancer cell phenotype that was determined from studying tumor tissue directly, or from using immortalized cancer cell lines. This means that active sorting techniques, like size-based selection and immunocapture, require some level of a priori knowledge about CTCs before you can engineer a device to capture them. Microscopic characterization is one CTC identification method that circumvents this problem, fixing (killing) the cells, and then using imaging in combination with rapid scanning to look at almost everything present in the blood sample. Electrokinetic separation of cancer cells is another, but enables live cell isolation without knowing its physical or biochemical properties beforehand.... Read more »
A discussion of the recent advances in space exploration, looking specifically at the Mars Rover landing as well as other space phenomena during 2012. ... Read more »
E Markham. (2012) Curious Cosmos. Blogspot. info:/
Following my series of posts on the link between the square root of a stochastic process and quantum mechanics (see here, here, here, here, here), that I proved to exist both theoretically and experimentally, I am pleased to let you know that the first paper of my collaboration with Alfonso Farina and Matteo Sedehi was [...]... Read more »
Marco Frasca. (2012) Quantum mechanics is the square root of a stochastic process. arXiv. arXiv: 1201.5091v2
Farina, A., Giompapa, S., Graziano, A., Liburdi, A., Ravanelli, M., & Zirilli, F. (2011) Tartaglia-Pascal’s triangle: a historical perspective with applications. Signal, Image and Video Processing. DOI: 10.1007/s11760-011-0228-6
I had thought that once I graduated college, annoying student publications would quit being so… annoying. Alas, this isn’t the case. A previous article examined the quality of analysis at the Carolina Review, UNC’s ‘journal of conservative thought and opinion’; let’s see if things have approved any in the handful of years that I’ve been [...]... Read more »
One day on, and still struggling with the chemistry behind gene regulation. Let no biologist ever tell me again not to use acronyms (yes, I am looking at you!). But it is interesting. I learned a lot about ChIP, histone modifications, etc, etc. This is an amazing world, where specific histone complex protein residues get methylated, acetylated, citrullinated, and phosphorylated. Of course, all this is in the context of the ENCODE meeting we have tomorrow at BiGCaT, where I will try to cover a paper by Thurman et al.
In that paper, Thurman studies the links between DNase I hypersensitive sites (DHSs) and markers of regulation. These DHSs are areas between histones where the DNA is free of histone proteins. There are remarkable images around showing histones as beads on a string, and the distances in nucleotides between histones is in fact not that large. In fact, a histone, despite a large complex, sterically hindering 50% of the DNA access does not stop translation; the transcription complexes apparently have no trouble passing the histones, as described by Felsenfeld et al. Quite amazing!
Now, those histones are chemically modified with acetyl, methyl, phosphates, and other groups. At well-describes residues, and each easily regulates modification of other steps. And everything regulates gene expression. Oh, and as we say yesterday, all that is regulated by metabolites, which in turn... Lovely. Try modeling that mathematically :) Here's what Abcam has to say about it:
Acetylation is generally linked to gene activation. Acetylation on Lys-10 (H3K9ac) impairs methylation at Arg-9 (H3R8me2s). Acetylation on Lys-19 (H3K18ac) and Lys-24 (H3K24ac) favors methylation at Arg-18 (H3R17me). Citrullination at Arg-9 (H3R8ci) and/or Arg-18 (H3R17ci) by PADI4 impairs methylation and represses transcription. Asymmetric dimethylation at Arg-18 (H3R17me2a) by CARM1 is linked to gene activation. Symmetric dimethylation at Arg-9 (H3R8me2s) by PRMT5 is linked to gene repression. Asymmetric dimethylation at Arg-3 (H3R2me2a) by PRMT6 is linked to gene repression and is mutually exclusive with H3 Lys-5 methylation (H3K4me2 and H3K4me3). H3R2me2a is present at the 3' of genes regardless of their transcription state and is enriched on inactive promoters, while it is absent on active promoters. Methylation at Lys-5 (H3K4me), Lys-37 (H3K36me) and Lys-80 (H3K79me) are linked to gene activation. Methylation at Lys-5 (H3K4me) facilitates subsequent acetylation of H3 and H4. ... ...
And that goes on for a while. Ambitiously, I started converting things I read into a WikiPathways:
I think that will keep me busy for a while. I won't even attempt to complete it further tonight. I have given up on that about an hour ago. In fact, I returned to the paper by Thurman, as I still have to figure out how their experimental methods work. In fact, how does one even detect the chemical modification of a histone, and to which DNA sequence on any of the chromosomes it belongs?? I mean, that's not AFM or STM, I say...
No, it's ChiP. ChIP on a chip, in fact. They have antibodies are stick particularly to a histones with one particular modification. That is how I actually ended up on that Abcam web page in the first place. Check out this nice western blot. With a huge antibody detecting whether there is an acetyl modification. Wicked!
Well, earlier I learned that proteins detecting methylated CpG bases not because of the methyl group (which amazed me already), but by a distorted hydration in the major groove due to MeCP2 binding. Seriously! Eat that, organic chemist friends!
So, Thurman and friends find distal DHSs and relate these to cis-regulatory elements. To some extend, puzzling, because the above tells us that a lot of regulatory work is happening outside those DHSs. But then again, I did read today about DNA methylation triggering histone modifications. It seems there is so much interactions going on, that it resembles a melting pot. Oh wait, that makes sense; it's one big one pot synthesis anyway.
The paper discusses an enormous amount of experimental work, and I cannot seem to be able to make sense of it all. There are striking aspects to it, which I will touch upon momentarily. But I cannot help but mentioning that I am not sure they could either. Their Discussion section leaves something to be desired, like an actual discussion. Instead, they just summarize the paper.
They used ChIP with Cell Signaling's 9751 antibody recognizing H3K4me3, with formaldehyde-induced crosslinking. It actually turns out, that the peaks for this modification are right on top of the DNA part from which the transcript is made, in line with Felsenfeld's observation. Upstream of that, where the promotors are expected, that is where DNase I signals are found. That is, I think this means that the DHS upstream of the histone where transcription starts is where the promotor regulation happens. With transcription factors (TFs), of course. And in those DHS regions, that is where DNA methylation happens, and Thurman finds DNA methylation in those regions, inhibiting TFs binding, because the already mentioned MeCP2 already takes that place.
Now, then they make a jump from this low level chemistry, to a genome wide landscape. Well, they actually start with that, but as a chemist, I am more of a bottom-up guy (that is an IT method). They report that most DHSs are found in introns and at distal locations. The first is striking: the ratio between intron/exon is >99. Does that imply that exons basically are always DNA wrapped around histones?? Does that actually then tell me that transcription actually sort of requires steric hindrance of the histone?? Ha, those diagrams biologists would be even more misleading that they have been to me (don't ask me how long it took me to learn that there are some 10-40 mitochondria per cell! and I still do not know if all copies in the cell have the same DNA, or if they are more like a population like your microbiome).
Now, distal DHSs are the second largest group, and capture some 40-45% of all DHSs. Distal means typically more than 2.5 kb away from the TSS (transcriptional start sites). Most of them are somewhere between 10 and 50 kb away. Now, isn't that something? That is distant indeed!
What? Still with me? Let's do some math. It's hard, and I hope to get it right. A human has about 3 billion base pairs (I'll take the WikiPedia count). The paper finds almost 3 million DHSs. That means that the average distance between DHSs is about 1 kb. Compare that to their diagram 1b, outline in the previous paragraph. That means that the DHSs must be very densely placed around the transcribed genes. Indeed, they report ratios of up to and above a 100 fold increase. It must be like that, because otherwise, you cannot get those distances for distal DHSs.
Now, another interesting aspect of the paper, is that they find different DHSs for different cell types. That, in fact, increases the average distance between DHSs: those 3 million they find is for 125 cell lines, and more DHSs are found in less then 20 cell lines. Only promotor-related DHSs seem to be more persistent between cell lines. This implies that different cell lines, have different genes unfolded in nucleosome/DHS rich areas (defining the chromatin accessibility), triggering different gene expression. That all makes sense, and rather existing too. As such, it seems to me that this map effectively gives a predictive model, indicating which genes are expressed in which cell types.
A further question they ask is if DNA (not histone) methylation is the cause of the result of DHSs. The confirm earlier found correlation between DNA methylation and gene silencing. They basically question if the things like MeCP2 binding happen because no transcription factor is in the way, or that TF cannot bind because MeCP2 is there. Chemically, these are perhaps equivalent: they have competing binding affinities. Except that the methylation must happen at some point too. The suggest that that may be due DNA getting randomly methylated, perhaps not unlike passive demethylation. Chemically, that does not make sense to. I would guess there are many chemical species in the cell that would get more easily methylated... They believe to have found evidence for passive deposition, but also find positive correlation between methylation and gene expression. I would say, the answer is still out there.
OK, that's about how far I got now. The last two pages I have to read again, and see what papers I need to read to make sense of that. And I will try ... Read more »
Thurman, R., Rynes, E., Humbert, R., Vierstra, J., Maurano, M., Haugen, E., Sheffield, N., Stergachis, A., Wang, H., Vernot, B.... (2012) The accessible chromatin landscape of the human genome. Nature, 489(7414), 75-82. DOI: 10.1038/nature11232
Steps 1 and 2 of neuron-building, as well as an important set of shortcuts can be found in the How to Build a Neuron index. Step 3 is deciding which simulation software or programming language you want to use. Simulated Neuron in Genesis (source)The big two are Genesis and Neuron. They are pretty similar in a lot of ways, but Genesis runs in Linux and Neuron runs in windows. However, you can run Genesis in windows if you install the Linux environment Cygwin.Both programs can read in morphological data, but they use different syntax and coding procedures. There are other types of neural simulators as well, and an ongoing problem in the field of computational neuroscience is compatibility between programs. If someone has done the work to make a beautiful Purkinje cell in Genesis like the one above, it will take a lot of time and effort to translate that neuron into a different simulator such as Neuron. Gleeson et al., (2010) explains this problem and presents a possible solution in the form of the "Neuron Open Markup Language" or NeuroML. "Computer modeling is becoming an increasingly valuable tool in the study of the complex interactions underlying the behavior of the brain. Software applications have been developed which make it easier to create models of neural networks as well as detailed models which replicate the electrical activity of individual neurons. The code formats used by each of these applications are generally incompatible however, making it difficult to exchange models and ideas between researchers....Creating a common, accessible model description format will expose more of the model details to the wider neuroscience community, thus increasing their quality and reliability, as for other Open Source software. NeuroML will also allow a greater “ecosystem” of tools to be developed for building, simulating and analyzing these complex neuronal systems." -Gleeson et al (2010) Author SummaryNeuroML is basically a "simulator-independent" neuronal description language. A neuron built with or converted to NeuroML should be able to run on Neuron, Genesis, and plenty of other platforms. Gleeson et al. validated NeuroML by using a simulated pyramidal neuron converted to NeuroML format and run with several different simulators.Gleeson et al., (2010) Figure 7Zooming in:Neuron, Genesis, Moose, Psics comparisonAll the simulators overlay so tightly that you can barely tell that they are separate lines.So when building you neuron, take care to follow the NeuroML format and then you and others can use it with any simulator you want. © TheCellularScaleGleeson P, Crook S, Cannon RC, Hines ML, Billings GO, Farinella M, Morse TM, Davison AP, Ray S, Bhalla US, Barnes SR, Dimitrova YD, & Silver RA (2010). NeuroML: a language for describing data driven models of neurons and networks with a high degree of biological detail. PLoS computational biology, 6 (6) PMID: 20585541... Read more »
Gleeson P, Crook S, Cannon RC, Hines ML, Billings GO, Farinella M, Morse TM, Davison AP, Ray S, Bhalla US.... (2010) NeuroML: a language for describing data driven models of neurons and networks with a high degree of biological detail. PLoS computational biology, 6(6). PMID: 20585541
Expendable objects were not innovated recently. Although washi are now linked to origami, for instance, people have been using the small sheets as disposable facial tissues since at least the seventeenth century, when the litter of Hasekura Tsunenaga's retinue reportedly surprised French courtiers. Similarly, around 200,000 to 400,000 years earlier, hominins near present-day Tel Aviv temporarily used flint flakes to carve meat, later startling archeologists with the "short-lived usage" of their discarded "meat-cutting blades," perhaps "the world's oldest known disposable knives."... Read more »
Liu, Q., Shi, S., Du, L., Wang, Y., Cao, J., Xu, C., Fan, F., Giesy, J., . (2012) Environmental and health challenges of the global growth of electronic waste,. Environmental Science and Pollution Research, 2460-2462. DOI: 10.1007/s11356-012-0923-z
Wang, F., Huisman, J., Meskers, C., Schluep, M., Stevels, A., . (2012) The Best-of-2-Worlds philosophy: Developing local dismantling and global infrastructure network for sustainable e-waste treatment in emerging economies. Waste Management, 2134-2146. DOI: 10.1016/j.wasman.2012.03.029
It sounds like something dreamt up by a science fiction writer, but scientists have created a walking ‘bio-bot’ made from rat heart cells and hydrogels, using a 3-D printer. The biological machines are 7 millimetres long, and resemble a miniature springboard with one long, thin leg that is supported by a stouter supporting leg. The [...]... Read more »
Chan, V., Park, K., Collens, M., Kong, H., Saif, T., & Bashir, R. (2012) Development of Miniaturized Walking Biological Machines. Scientific Reports. DOI: 10.1038/srep00857
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