December 24, 2015

Ann Makosinski, an 18-year old UBC student, won a $50,000 grant for her new invention, reports the Vancouver Sun. She won Shell Canada’s 2015 Quest Climate Grant for a coffee mug that charges a smartphone using the heat from the beverage.

“I now have a real opportunity to seek out partners to further the development of my product design and bring my technology to market,” she said.

Similar stories also appeared on Global, CTV, Vancity Buzz and others.

http://news.ubc.ca/2015/12/24/ubc-student-wins-50000-grant-for-edrink-invention/

December 24, 2015

Elizabeth W. Dunn and Ashley Whillans report on a study that shows that generosity can provide physical health benefits in the New York Times.

“We discovered that the more money people had reported spending on others, the lower their blood pressure was two years later,” they write. “Our research points to the conclusion that embracing the spirit of generosity may not only be heartwarming; it may also be good for the heart.”

http://news.ubc.ca/2015/12/24/give-if-you-know-whats-good-for-you/

December 23, 2015

Disease GWAS show substantial genetic overlap with longevity. Shown are results for coronary artery disease and Alzheimer’s disease. The y axis is the observed P values for longevity, and the x axis is the expected P values under the null hypothesis that the disease is independent of longevity. The cyan, blue and purple lines show the P values for longevity of the top 100, 250, and 500 disease SNPs from independent genetic loci, respectively. Red lines show the background distribution of longevity P values for all independent genetic loci tested in both the longevity and disease GWAS. The grey horizontal line corresponds to the threshold for nominal significance (P< = 0.05) for longevity. Significance of enrichment was determined with the hypergeometric test. (credit: Kristen Fortney et al./PLOS Genetics)

What’s the secret of centenarians who have health and diet habits similar to the average person but have remained active and alert at very old ages?

Genes. That’s according to scientists at Stanford University and the University of Bologna, who have written a new report published in PLOS Genetics, based on their finding of several disease variants that may be absent in centenarians compared to the general population.

Genetic studies so far have only identified a single gene (APOE, known to be involved in Alzheimer’s disease) that is different in centenarians versus normal agers.

Finding additional longevity genes

To find the additional longevity genes, the authors first developed a new statistical method called informed GWAS (genome-wide association studies), which uses knowledge from 14 diseases to narrow down the search genes associated with longevity.

Using iGWAS, the scientists found eight SNPs (single nucleotide polymorphisms — molecular variations at different locations on the gene) that are significant for the centenarians they studied, and they were able to validate four of these in replication studies of long-lived subjects.

The four “longevity loci” (gene locations) along with the APOE gene may provide clues about physiological mechanisms for successful aging. These loci are known to be involved in various processes including cell senescence, autoimmunity, and cell signaling, and also with Alzheimer’s disease.

The incidence of nearly all diseases increases with age, so understanding genetic factors for successful aging could have a large impact on health. Future work may lead to a better understanding of how these genes promote successful aging and could identify additional longevity genes by recruiting more centenarians for analysis.

Abstract of Genome-Wide Scan Informed by Age-Related Disease Identifies Loci for Exceptional Human Longevity

We developed a new statistical framework to find genetic variants associated with extreme longevity. The method, informed GWAS (iGWAS), takes advantage of knowledge from large studies of age-related disease in order to narrow the search for SNPs associated with longevity. To gain support for our approach, we first show there is an overlap between loci involved in disease and loci associated with extreme longevity. These results indicate that several disease variants may be depleted in centenarians versus the general population. Next, we used iGWAS to harness information from 14 meta-analyses of disease and trait GWAS to identify longevity loci in two studies of long-lived humans. In a standard GWAS analysis, only one locus in these studies is significant (APOE/TOMM40) when controlling the false discovery rate (FDR) at 10%. With iGWAS, we identify eight genetic loci to associate significantly with exceptional human longevity at FDR < 10%. We followed up the eight lead SNPs in independent cohorts, and found replication evidence of four loci and suggestive evidence for one more with exceptional longevity. The loci that replicated (FDR < 5%) includedAPOE/TOMM40 (associated with Alzheimer’s disease), CDKN2B/ANRIL (implicated in the regulation of cellular senescence), ABO (tags the O blood group), and SH2B3/ATXN2 (a signaling gene that extends lifespan in Drosophila and a gene involved in neurological disease). Our results implicate new loci in longevity and reveal a genetic overlap between longevity and age-related diseases and traits, including coronary artery disease and Alzheimer’s disease. iGWAS provides a new analytical strategy for uncovering SNPs that influence extreme longevity, and can be applied more broadly to boost power in other studies of complex phenotypes.

references:
Kristen Fortney, Edgar Dobriban, Paolo Garagnani, Chiara Pirazzini, Daniela Monti, Daniela Mari, Gil Atzmon, Nir Barzilai, Claudio Franceschi, Art B. Owen, Stuart K. Kim. Genome-Wide Scan Informed by Age-Related Disease Identifies Loci for Exceptional Human Longevity. PLOS Genetics, 2015; 11 (12): e1005728 DOI: 10.1371/journal.pgen.1005728 (open access)

http://www.kurzweilai.net/new-genes-associated-with-extreme-longevity-identified

December 23, 2015

Schematic of the leukocyte counting chip with lysing, quenching, and counter modules shown in different colors. The insert (upper left) is an enlarged view of the platinum microfabricated electrodes (yellow). (credit: U. Hassan et al./TECHNOLOGY)

A microfluidic biosensor that can count red blood cells, platelets, and white blood cells electrically using just one drop of blood (11 microL) has been developed by University of Illinois at Urbana-Champaign (UIUC) researchers, replacing the standard hematology analyzer, a large, expensive lab device that requires trained technicians and physical sample transportation.

The new biosensor can electrically count the different types of blood cells based on their size and membrane properties. To count leukocyte and its differentials, red blood cells are selectively lysed and the remaining white blood cells were individually counted. Specific cells like neutrophils are counted using multi-frequency analysis, which probe the membrane properties of the cells.

The device, which will use credit-card-size disposable cartridges, requires minimal or no experience. It is expected to find uses in hospitals at the bedside, private clinics, retail clinics, and the developing world.

Patients can perform the test at home in under 20 minutes and share the results with their primary care physicians electronically, reducing the cost of the test to less than $10, compared to $100 or more currently, says UIUc Professor Rashid Bashir, principal investigator.

The research appears in the December 2015 issue of the journal TECHNOLOGY

Abstract of A microfluidic biochip for complete blood cell counts at the point-of-care

Complete blood cell counts (CBCs) are one of the most commonly ordered and informative blood tests in hospitals. The results from a CBC, which typically include white blood cell (WBC) counts with differentials, red blood cell (RBC) counts, platelet counts and hemoglobin measurements, can have implications for the diagnosis and screening of hundreds of diseases and treatments. Bulky and expensive hematology analyzers are currently used as a gold standard for acquiring CBCs. For nearly all CBCs performed today, the patient must travel to either a hospital with a large laboratory or to a centralized lab testing facility. There is a tremendous need for an automated, portable point-of-care blood cell counter that could yield results in a matter of minutes from a drop of blood without any trained professionals to operate the instrument. We have developed microfluidic biochips capable of a partial CBC using only a drop of whole blood. Total leukocyte and their 3-part differential count are obtained from 10 μL of blood after on-chip lysing of the RBCs and counting of the leukocytes electrically using microfabricated platinum electrodes. For RBCs and platelets, 1 μL of whole blood is diluted with PBS on-chip and the cells are counted electrically. The total time for measurement is under 20 minutes. We demonstrate a high correlation of blood cell counts compared to results acquired with a commercial hematology analyzer. This technology could potentially have tremendous applications in hospitals at the bedside, private clinics, retail clinics and the developing world.

references:
U. Hassan, B. Reddy, G. Damhorst, O. Sonoiki, T. Ghonge, C. Yang, R. Bashir. A microfluidic biochip for complete blood cell counts at the point-of-care. TECHNOLOGY, 2015; 03 (04): 201 DOI: 10.1142/S2339547815500090

http://www.kurzweilai.net/microfluidic-biochip-for-simple-fast-low-cost-blood-cell-counts

Published on Dec 23, 2015

https://www.youtube.com/watch?v=xY_AOA-F0Jw

Published on Dec 23, 2015

https://www.youtube.com/watch?v=XIn2o53wbrQ

http://www.researchandmarkets.com/research/563j6r/iphone_6s_plus) has announced the addition of the “iPhone 6s Plus Rear Camera Module – Reverse Costing Analysis” report to their offering.
With the iPhone 6s Plus, Apple introduces a new rear camera module. The new device has similar structure and technology than the previous one, but it has higher resolution and smaller pixel size.

The iPhone 6s Plus camera module integrates the 12Mpixel resolution CMOS Image Sensor, with aperture of f/2.2 and a pixel size of 1.22µm. The decreasing of the pixel size implies the introduction of Deep Trench Isolation structure.

Respect to the iPhone 6 Plus, the logic ISP circuit with 45nm technology node process, the assembling structure and the 5-elements lens module are the same; otherwise technical ameliorations of the VCM brings to a better quality of the autofocus and the OIS.

The CIS is assembled in flip-chip on a ceramic substrate with a gold stud bumping process and uses the technology from Sony (Exmor-RS). The technology consists in a stacking of two separate chips using optimized processes: a pixel array circuit which uses a Back-Side Illuminated (BSI) technology, and a logic ISP circuit.

Key Topics Covered:

1. Introduction

2. Company Profile & Supply Chain

3. Physical Analysis

Camera Module View & Dimensions
Camera Module X-Ray
Camera Module Disassembly
CMOS Image Sensor
View & Dimensions
Pads, Tungsten Grid
TSV Connections
CIS Pixels
Logic Circuit (Transistors, SRAM)
Cross-Section: Camera Module Overview
Driver (Assembly & Process) & MLCC
Ceramic Substrate, IR Filter & FPC
Lenses, Housing, VCM, IOS
Cross-Section: CMOS Image Sensor Overview
Pad Trenches
Pixel Array Circuit
Logic Circuit
TSVs
4. Technology and Cost comparison with iPhone 5s and 6 Plus camera module

5. Manufacturing Process Flow

Global Overview
Logic Circuit Front-End Process
Pixel Array Circuit Front-End Process
BSI + TSV + Microlenses Process
CIS Wafer Fabrication Unit
6. Cost Analysis

Synthesis of the cost analysis
Main steps of economic analysis
Yields Hypotheses
CMOS Image Sensor Cost
Logic Circuit Front-End Cost
Pixel Array Front-end Cost
BSI , IOS & TSV Front-End Cost
Color Filters & Microlenses Front-End Cost
Total Front-End Cost
Back-End: Tests & Dicing
CIS Wafer and Die Cost
Camera Module Assembly Cost
Lens Module Cost
VCM Actuator Cost
Final Cost
Camera Module Cost
For more information visit http://www.researchandmarkets.com/research/563j6r/iphone_6s_plus

Read more: http://www.digitaljournal.com/pr/2785494#ixzz3vCKOJHrM

Should “clear out everything at once” — including Alzheimer’s, frontotemporal degeneration, Huntington’s, and Parkinson’s
December 23, 2015
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Rolipram drug activates the brain’s garbage disposal system, eliminating excess tau proteins (glowing red dots) associated with neurodegenerative diseases such as Alzheimer’s. (credit: Laboratory of Karen Duff/Columbia University Medical Center)

Rolipram, a drug that boosts activity in the brain’s “garbage disposal” system, can decrease levels of toxic proteins associated with Alzheimer’s disease and other neurodegenerative disorders and improve cognition in mice, a new study by neuroscientists has found.

Rolipram causes nausea, but similar drugs do not, and could be tested in clinical trials quickly, the researchers say.

“This has the potential to open up new avenues of treatment for Alzheimer’s and many other neurodegenerative diseases,” said study leader Karen E. Duff, PhD, professor of pathology and cell biology at Columbia University Medical Center (CUMC) and New York State Psychiatric Institute (NYSPI).

A “garbage-disposal” switch

To remain healthy, brain cells must continually clear out old, worn, or damaged proteins. This task is performed by a small molecular called the proteasome, which works like a kitchen garbage-disposal system, grinding up the old proteins so they can be recycled into new ones. However, in neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and Huntington’s, proteins tagged for destruction accumulate in the brain’s neurons. This suggests that the cell’s proteasomes are impaired.

The cause for this: tau — a protein that accumulates in Alzheimer’s and other brain diseases — sticks to the proteasome and jams up the protein garbage-disposal process, the researchers first discovered (using a genetically engineered mouse).

In the new research, administering rolipram activated the proteasome and restored protein disposal. The drug also improved memory in diseased mice to levels seen in healthy mice.

Rolipram has been tested before in mice, and was shown to improve memory. But the new research shows a previously unknown function of the drug: it produces a physical change in the proteasome and increases its activity.

Should ‘clear out everything at once’

Duff says we still don’t know exactly which form of a particular protein is toxic to the brain, which has made it difficult to develop drugs to treat neurodegenerative diseases. “In Alzheimer’s disease, the problem is compounded because several types of abnormal protein can accumulate in a person’s brain, including amyloid, tau, alpha-synuclein, and TDP43.

However, the researchers think that “a well-functioning proteasome will be able to clear out everything at once,” she says — including Alzheimer’s, frontotemporal degeneration, Huntington’s, and Parkinson’s.

The study was published Tuesday (Dec. 22) in the online edition of Nature Medicine. The National Institute of Health’s National Institute of Neurological Disorders and Stroke provided funding for the study.

Abstract of Tau-driven 26S proteasome impairment and cognitive dysfunction can be prevented early in disease by activating cAMP-PKA signaling

The ubiquitin proteasome system (UPS) degrades misfolded proteins including those implicated in neurodegenerative diseases. We investigated the effects of tau accumulation on proteasome function in a mouse model of tauopathy and in a cross to a UPS reporter mouse (line Ub-G76V-GFP). Accumulation of insoluble tau was associated with a decrease in the peptidase activity of brain 26S proteasomes, higher levels of ubiquitinated proteins and undegraded Ub-G76V-GFP. 26S proteasomes from mice with tauopathy were physically associated with tau and were less active in hydrolyzing ubiquitinated proteins, small peptides and ATP. 26S proteasomes from normal mice incubated with recombinant oligomers or fibrils also showed lower hydrolyzing capacity in the same assays, implicating tau as a proteotoxin. Administration of an agent that activates cAMP–protein kinase A (PKA) signaling led to attenuation of proteasome dysfunction, probably through proteasome subunit phosphorylation. In vivo, this led to lower levels of aggregated tau and improvements in cognitive performance.

references:
Natura Myeku, Catherine L Clelland, Sheina Emrani, Nikolay V Kukushkin, Wai Haung Yu, Alfred L Goldberg & Karen E Duff. Tau-driven 26S proteasome impairment and cognitive dysfunction can be prevented early in disease by activating cAMP-PKA signaling. Nature Medicine (2015) doi:10.1038/nm.4011

http://www.kurzweilai.net/a-garbage-disposal-drug-may-slow-alzheimers-and-other-neurodegenerative-diseases

https://www.youtube.com/watch?v=ZTfAYVeBU7c

December 22, 2015

Scanning electron microscope image of carbon nanotubes showing textured porosity (credit: Allison L. Yost et al./Microsystems & Nanoengineering)

Engineers at MIT have devised a new technique for trapping hard-to-detect molecules, using forests of coated carbon nanotubes.

The team modified a simple microfluidic channel with an array of vertically aligned carbon nanotubes — rolled lattices of carbon atoms that resemble tiny tubes of chicken wire.

Carbon-nanotube posts can trap cancer and other cells as they flow through a microfluidic device (credit: Brian Wardle)

The researchers had previously devised a method for standing carbon nanotubes on their ends, like trees in a forest (see “Trapping cancer cells with carbon nanotubes“). This 3-D array of permeable carbon nanotubes allows fluid to flow through a microfluidic device.

Now, in a study published this week in the Journal of Microengineering and Nanotechnology, the researchers have given the nanotube array the additional ability to trap specific particles. To do this, the team coated the array, layer by layer, with polymers of alternating electric charge.

Depending on the number of layers deposited, the researchers can create thicker or thinner nanotubes and thereby tailor the porosity of the forest to capture larger or smaller particles of interest. The nanotubes’ polymer coating can also be chemically manipulated to bind specific bioparticles flowing through the forest.

The combination of carbon nanotubes and multilayer coatings may help finely tune microfluidic devices to capture extremely small and rare particles, such as certain viruses and proteins, says Brian Wardle, professor of aeronautics and astronautics at MIT.

“There are smaller bioparticles that contain very rich amounts of information that we don’t currently have the ability to access in point-of-care [medical testing] devices like microfluidic chips,” says Wardle, who is a co-author on the paper. “Carbon nanotube arrays could actually be a platform that could target that size of bioparticle.”

What’s more, Wardle says, a three-dimensional forest of carbon nanotubes would provide much more surface area on which target molecules may interact, compared with the two-dimensional surfaces in conventional microfluidics.

Capturing specific particles of interest

To test this idea, the researchers used an established technique to treat the surface of the nanotubes with antibodies that bind to prostate specific antigen (PSA), a common experimental target.

A 3-D array of carbon nanotubes on a microfluidic device coated with successive layers of alternately charged polymer solutions (credit: Allison L. Yost et al./Microsystems & Nanoengineering)

The team integrated a 3-D array of carbon nanotubes into a microfluidic device by using chemical vapor deposition and photolithography to grow and pattern carbon nanotubes onto silicon wafers. They then grouped the nanotubes into a cylinder-shaped forest, measuring about 50 micrometers tall and 1 millimeter wide, and centered the array within a 3 millimeter-wide, 7-millimeter long microfluidic channel.

Polyelectrolyte multilayer (PEM) film deposition on carbon-nanotube surface (credit: Allison L. Yost et al./Microsystems & Nanoengineering)

The researchers coated the nanotubes in successive layers of alternately charged polymer solutions to create distinct, binding layers around each nanotube. To do so, they flowed each solution through the channel and found they were able to create a more uniform coating with a gap between the top of the nanotube forest and the roof of the channel. Such a gap allowed solutions to flow over, then down into the forest, coating each individual nanotube.

Carbon nanotube treated with antibodies for PSA capture (credit: Allison L. Yost et al./Microsystems & Nanoengineering)

After coating the nanotube array in layers of polymer solution, the researchers demonstrated that the array could be primed to detect a given molecule by treating it with antibodies that typically bind to prostate specific antigen (PSA). They pumped in a solution containing small amounts of PSA and found that the array captured the antigen effectively, throughout the forest, rather than just on the outer surface of a typical microfluidic element.

The polymer-coated arrays captured 40 percent more antigens, compared with arrays lacking the polymer coating.

Wardle says that the nanotube array is extremely versatile. The carbon nanotubes can be manipulated mechanically, electrically, and optically and the polymer coatings can be chemically altered to capture a wide range of particles. He says an immediate target may be biomarkers called exosomes, which are less than 100 nanometers wide and can be important signals of a disease’s progression.

“This type of device actually has all the characteristics and functionality that would allow you to go after bioparticles like exosomes and things that really truly are nanometer scale,” he noted.

This research was funded in part by the National Science Foundation.

Abstract of Layer-by-layer functionalized nanotube arrays: A versatile microfluidic platform for biodetection

We demonstrate the layer-by-layer (LbL) assembly of polyelectrolyte multilayers (PEM) on three-dimensional nanofiber scaffolds. High porosity (99%) aligned carbon nanotube (CNT) arrays are photolithographically patterned into elements that act as textured scaffolds for the creation of functionally coated (nano)porous materials. Nanometer-scale bilayers of poly(allylamine hydrochloride)/poly(styrene sulfonate) (PAH/SPS) are formed conformally on the individual nanotubes by repeated deposition from aqueous solution in microfluidic channels. Computational and experimental results show that the LbL deposition is dominated by the diffusive transport of the polymeric constituents, and we use this understanding to demonstrate spatial tailoring on the patterned nanoporous elements. A proof-of-principle application, microfluidic bioparticle capture using N-hydroxysuccinimide-biotin binding for the isolation of prostate-specific antigen (PSA), is demonstrated.

references:
Allison L. Yost, Setareh Shahsavari, Grinia M. Bradwell, Roberta Polak, Fabio Fachin, Robert E. Cohen, Gareth H. McKinley, Mehmet Toner, Michael F. Rubner & Brian L. Wardle. Layer-by-layer functionalized nanotube arrays: A versatile microfluidic platform for biodetection. Microsystems & Nanoengineering 1, Article number: 15037 (2015) ​doi:10.1038/micronano.2015.37 (open access)

http://www.kurzweilai.net/mit-uses-forests-of-carbon-nanotubes-with-antibodies-to-capture-hard-to-detect-molecules