## KurzweilAI Net

• warning: date(): It is not safe to rely on the system's timezone settings. You are *required* to use the date.timezone setting or the date_default_timezone_set() function. In case you used any of those methods and you are still getting this warning, you most likely misspelled the timezone identifier. We selected the timezone 'UTC' for now, but please set date.timezone to select your timezone. in /home3/kuehlebo/public_html/transcedo/modules/aggregator/aggregator.pages.inc on line 259.
• warning: date(): It is not safe to rely on the system's timezone settings. You are *required* to use the date.timezone setting or the date_default_timezone_set() function. In case you used any of those methods and you are still getting this warning, you most likely misspelled the timezone identifier. We selected the timezone 'UTC' for now, but please set date.timezone to select your timezone. in /home3/kuehlebo/public_html/transcedo/modules/aggregator/aggregator.pages.inc on line 259.
• warning: date(): It is not safe to rely on the system's timezone settings. You are *required* to use the date.timezone setting or the date_default_timezone_set() function. In case you used any of those methods and you are still getting this warning, you most likely misspelled the timezone identifier. We selected the timezone 'UTC' for now, but please set date.timezone to select your timezone. in /home3/kuehlebo/public_html/transcedo/modules/aggregator/aggregator.pages.inc on line 259.
• warning: date(): It is not safe to rely on the system's timezone settings. You are *required* to use the date.timezone setting or the date_default_timezone_set() function. In case you used any of those methods and you are still getting this warning, you most likely misspelled the timezone identifier. We selected the timezone 'UTC' for now, but please set date.timezone to select your timezone. in /home3/kuehlebo/public_html/transcedo/modules/aggregator/aggregator.pages.inc on line 259.
• warning: date(): It is not safe to rely on the system's timezone settings. You are *required* to use the date.timezone setting or the date_default_timezone_set() function. In case you used any of those methods and you are still getting this warning, you most likely misspelled the timezone identifier. We selected the timezone 'UTC' for now, but please set date.timezone to select your timezone. in /home3/kuehlebo/public_html/transcedo/modules/aggregator/aggregator.pages.inc on line 259.
• warning: date(): It is not safe to rely on the system's timezone settings. You are *required* to use the date.timezone setting or the date_default_timezone_set() function. In case you used any of those methods and you are still getting this warning, you most likely misspelled the timezone identifier. We selected the timezone 'UTC' for now, but please set date.timezone to select your timezone. in /home3/kuehlebo/public_html/transcedo/modules/aggregator/aggregator.pages.inc on line 259.
• warning: date(): It is not safe to rely on the system's timezone settings. You are *required* to use the date.timezone setting or the date_default_timezone_set() function. In case you used any of those methods and you are still getting this warning, you most likely misspelled the timezone identifier. We selected the timezone 'UTC' for now, but please set date.timezone to select your timezone. in /home3/kuehlebo/public_html/transcedo/modules/aggregator/aggregator.pages.inc on line 259.
• warning: date(): It is not safe to rely on the system's timezone settings. You are *required* to use the date.timezone setting or the date_default_timezone_set() function. In case you used any of those methods and you are still getting this warning, you most likely misspelled the timezone identifier. We selected the timezone 'UTC' for now, but please set date.timezone to select your timezone. in /home3/kuehlebo/public_html/transcedo/modules/aggregator/aggregator.pages.inc on line 259.
• warning: date(): It is not safe to rely on the system's timezone settings. You are *required* to use the date.timezone setting or the date_default_timezone_set() function. In case you used any of those methods and you are still getting this warning, you most likely misspelled the timezone identifier. We selected the timezone 'UTC' for now, but please set date.timezone to select your timezone. in /home3/kuehlebo/public_html/transcedo/modules/aggregator/aggregator.pages.inc on line 259.
• warning: date(): It is not safe to rely on the system's timezone settings. You are *required* to use the date.timezone setting or the date_default_timezone_set() function. In case you used any of those methods and you are still getting this warning, you most likely misspelled the timezone identifier. We selected the timezone 'UTC' for now, but please set date.timezone to select your timezone. in /home3/kuehlebo/public_html/transcedo/modules/aggregator/aggregator.pages.inc on line 259.
• warning: date(): It is not safe to rely on the system's timezone settings. You are *required* to use the date.timezone setting or the date_default_timezone_set() function. In case you used any of those methods and you are still getting this warning, you most likely misspelled the timezone identifier. We selected the timezone 'UTC' for now, but please set date.timezone to select your timezone. in /home3/kuehlebo/public_html/transcedo/modules/aggregator/aggregator.pages.inc on line 259.
• warning: date(): It is not safe to rely on the system's timezone settings. You are *required* to use the date.timezone setting or the date_default_timezone_set() function. In case you used any of those methods and you are still getting this warning, you most likely misspelled the timezone identifier. We selected the timezone 'UTC' for now, but please set date.timezone to select your timezone. in /home3/kuehlebo/public_html/transcedo/modules/aggregator/aggregator.pages.inc on line 259.
• warning: date(): It is not safe to rely on the system's timezone settings. You are *required* to use the date.timezone setting or the date_default_timezone_set() function. In case you used any of those methods and you are still getting this warning, you most likely misspelled the timezone identifier. We selected the timezone 'UTC' for now, but please set date.timezone to select your timezone. in /home3/kuehlebo/public_html/transcedo/modules/aggregator/aggregator.pages.inc on line 259.
• warning: date(): It is not safe to rely on the system's timezone settings. You are *required* to use the date.timezone setting or the date_default_timezone_set() function. In case you used any of those methods and you are still getting this warning, you most likely misspelled the timezone identifier. We selected the timezone 'UTC' for now, but please set date.timezone to select your timezone. in /home3/kuehlebo/public_html/transcedo/modules/aggregator/aggregator.pages.inc on line 259.
• warning: date(): It is not safe to rely on the system's timezone settings. You are *required* to use the date.timezone setting or the date_default_timezone_set() function. In case you used any of those methods and you are still getting this warning, you most likely misspelled the timezone identifier. We selected the timezone 'UTC' for now, but please set date.timezone to select your timezone. in /home3/kuehlebo/public_html/transcedo/modules/aggregator/aggregator.pages.inc on line 259.
• warning: date(): It is not safe to rely on the system's timezone settings. You are *required* to use the date.timezone setting or the date_default_timezone_set() function. In case you used any of those methods and you are still getting this warning, you most likely misspelled the timezone identifier. We selected the timezone 'UTC' for now, but please set date.timezone to select your timezone. in /home3/kuehlebo/public_html/transcedo/modules/aggregator/aggregator.pages.inc on line 259.
• warning: date(): It is not safe to rely on the system's timezone settings. You are *required* to use the date.timezone setting or the date_default_timezone_set() function. In case you used any of those methods and you are still getting this warning, you most likely misspelled the timezone identifier. We selected the timezone 'UTC' for now, but please set date.timezone to select your timezone. in /home3/kuehlebo/public_html/transcedo/modules/aggregator/aggregator.pages.inc on line 259.
• warning: date(): It is not safe to rely on the system's timezone settings. You are *required* to use the date.timezone setting or the date_default_timezone_set() function. In case you used any of those methods and you are still getting this warning, you most likely misspelled the timezone identifier. We selected the timezone 'UTC' for now, but please set date.timezone to select your timezone. in /home3/kuehlebo/public_html/transcedo/modules/aggregator/aggregator.pages.inc on line 259.
• warning: date(): It is not safe to rely on the system's timezone settings. You are *required* to use the date.timezone setting or the date_default_timezone_set() function. In case you used any of those methods and you are still getting this warning, you most likely misspelled the timezone identifier. We selected the timezone 'UTC' for now, but please set date.timezone to select your timezone. in /home3/kuehlebo/public_html/transcedo/modules/aggregator/aggregator.pages.inc on line 259.
• warning: date(): It is not safe to rely on the system's timezone settings. You are *required* to use the date.timezone setting or the date_default_timezone_set() function. In case you used any of those methods and you are still getting this warning, you most likely misspelled the timezone identifier. We selected the timezone 'UTC' for now, but please set date.timezone to select your timezone. in /home3/kuehlebo/public_html/transcedo/modules/aggregator/aggregator.pages.inc on line 259.
• warning: date(): It is not safe to rely on the system's timezone settings. You are *required* to use the date.timezone setting or the date_default_timezone_set() function. In case you used any of those methods and you are still getting this warning, you most likely misspelled the timezone identifier. We selected the timezone 'UTC' for now, but please set date.timezone to select your timezone. in /home3/kuehlebo/public_html/transcedo/modules/aggregator/aggregator.pages.inc on line 259.
• warning: date(): It is not safe to rely on the system's timezone settings. You are *required* to use the date.timezone setting or the date_default_timezone_set() function. In case you used any of those methods and you are still getting this warning, you most likely misspelled the timezone identifier. We selected the timezone 'UTC' for now, but please set date.timezone to select your timezone. in /home3/kuehlebo/public_html/transcedo/modules/aggregator/aggregator.pages.inc on line 259.
• warning: date(): It is not safe to rely on the system's timezone settings. You are *required* to use the date.timezone setting or the date_default_timezone_set() function. In case you used any of those methods and you are still getting this warning, you most likely misspelled the timezone identifier. We selected the timezone 'UTC' for now, but please set date.timezone to select your timezone. in /home3/kuehlebo/public_html/transcedo/modules/aggregator/aggregator.pages.inc on line 259.
• warning: date(): It is not safe to rely on the system's timezone settings. You are *required* to use the date.timezone setting or the date_default_timezone_set() function. In case you used any of those methods and you are still getting this warning, you most likely misspelled the timezone identifier. We selected the timezone 'UTC' for now, but please set date.timezone to select your timezone. in /home3/kuehlebo/public_html/transcedo/modules/aggregator/aggregator.pages.inc on line 259.
• warning: date(): It is not safe to rely on the system's timezone settings. You are *required* to use the date.timezone setting or the date_default_timezone_set() function. In case you used any of those methods and you are still getting this warning, you most likely misspelled the timezone identifier. We selected the timezone 'UTC' for now, but please set date.timezone to select your timezone. in /home3/kuehlebo/public_html/transcedo/modules/aggregator/aggregator.pages.inc on line 259.
• warning: date(): It is not safe to rely on the system's timezone settings. You are *required* to use the date.timezone setting or the date_default_timezone_set() function. In case you used any of those methods and you are still getting this warning, you most likely misspelled the timezone identifier. We selected the timezone 'UTC' for now, but please set date.timezone to select your timezone. in /home3/kuehlebo/public_html/transcedo/modules/aggregator/aggregator.pages.inc on line 259.
• warning: date(): It is not safe to rely on the system's timezone settings. You are *required* to use the date.timezone setting or the date_default_timezone_set() function. In case you used any of those methods and you are still getting this warning, you most likely misspelled the timezone identifier. We selected the timezone 'UTC' for now, but please set date.timezone to select your timezone. in /home3/kuehlebo/public_html/transcedo/modules/aggregator/aggregator.pages.inc on line 259.
• warning: date(): It is not safe to rely on the system's timezone settings. You are *required* to use the date.timezone setting or the date_default_timezone_set() function. In case you used any of those methods and you are still getting this warning, you most likely misspelled the timezone identifier. We selected the timezone 'UTC' for now, but please set date.timezone to select your timezone. in /home3/kuehlebo/public_html/transcedo/modules/aggregator/aggregator.pages.inc on line 259.
• warning: date(): It is not safe to rely on the system's timezone settings. You are *required* to use the date.timezone setting or the date_default_timezone_set() function. In case you used any of those methods and you are still getting this warning, you most likely misspelled the timezone identifier. We selected the timezone 'UTC' for now, but please set date.timezone to select your timezone. in /home3/kuehlebo/public_html/transcedo/modules/aggregator/aggregator.pages.inc on line 259.
• warning: date(): It is not safe to rely on the system's timezone settings. You are *required* to use the date.timezone setting or the date_default_timezone_set() function. In case you used any of those methods and you are still getting this warning, you most likely misspelled the timezone identifier. We selected the timezone 'UTC' for now, but please set date.timezone to select your timezone. in /home3/kuehlebo/public_html/transcedo/modules/aggregator/aggregator.pages.inc on line 259.
• warning: date(): It is not safe to rely on the system's timezone settings. You are *required* to use the date.timezone setting or the date_default_timezone_set() function. In case you used any of those methods and you are still getting this warning, you most likely misspelled the timezone identifier. We selected the timezone 'UTC' for now, but please set date.timezone to select your timezone. in /home3/kuehlebo/public_html/transcedo/modules/aggregator/aggregator.pages.inc on line 259.
• warning: date(): It is not safe to rely on the system's timezone settings. You are *required* to use the date.timezone setting or the date_default_timezone_set() function. In case you used any of those methods and you are still getting this warning, you most likely misspelled the timezone identifier. We selected the timezone 'UTC' for now, but please set date.timezone to select your timezone. in /home3/kuehlebo/public_html/transcedo/modules/aggregator/aggregator.pages.inc on line 259.
• warning: date(): It is not safe to rely on the system's timezone settings. You are *required* to use the date.timezone setting or the date_default_timezone_set() function. In case you used any of those methods and you are still getting this warning, you most likely misspelled the timezone identifier. We selected the timezone 'UTC' for now, but please set date.timezone to select your timezone. in /home3/kuehlebo/public_html/transcedo/modules/aggregator/aggregator.pages.inc on line 259.
• warning: date(): It is not safe to rely on the system's timezone settings. You are *required* to use the date.timezone setting or the date_default_timezone_set() function. In case you used any of those methods and you are still getting this warning, you most likely misspelled the timezone identifier. We selected the timezone 'UTC' for now, but please set date.timezone to select your timezone. in /home3/kuehlebo/public_html/transcedo/modules/aggregator/aggregator.pages.inc on line 259.
• warning: date(): It is not safe to rely on the system's timezone settings. You are *required* to use the date.timezone setting or the date_default_timezone_set() function. In case you used any of those methods and you are still getting this warning, you most likely misspelled the timezone identifier. We selected the timezone 'UTC' for now, but please set date.timezone to select your timezone. in /home3/kuehlebo/public_html/transcedo/modules/aggregator/aggregator.pages.inc on line 259.
• warning: date(): It is not safe to rely on the system's timezone settings. You are *required* to use the date.timezone setting or the date_default_timezone_set() function. In case you used any of those methods and you are still getting this warning, you most likely misspelled the timezone identifier. We selected the timezone 'UTC' for now, but please set date.timezone to select your timezone. in /home3/kuehlebo/public_html/transcedo/modules/aggregator/aggregator.pages.inc on line 259.
• warning: date(): It is not safe to rely on the system's timezone settings. You are *required* to use the date.timezone setting or the date_default_timezone_set() function. In case you used any of those methods and you are still getting this warning, you most likely misspelled the timezone identifier. We selected the timezone 'UTC' for now, but please set date.timezone to select your timezone. in /home3/kuehlebo/public_html/transcedo/modules/aggregator/aggregator.pages.inc on line 259.
• warning: date(): It is not safe to rely on the system's timezone settings. You are *required* to use the date.timezone setting or the date_default_timezone_set() function. In case you used any of those methods and you are still getting this warning, you most likely misspelled the timezone identifier. We selected the timezone 'UTC' for now, but please set date.timezone to select your timezone. in /home3/kuehlebo/public_html/transcedo/modules/aggregator/aggregator.pages.inc on line 259.
• warning: date(): It is not safe to rely on the system's timezone settings. You are *required* to use the date.timezone setting or the date_default_timezone_set() function. In case you used any of those methods and you are still getting this warning, you most likely misspelled the timezone identifier. We selected the timezone 'UTC' for now, but please set date.timezone to select your timezone. in /home3/kuehlebo/public_html/transcedo/modules/aggregator/aggregator.pages.inc on line 259.
• warning: date(): It is not safe to rely on the system's timezone settings. You are *required* to use the date.timezone setting or the date_default_timezone_set() function. In case you used any of those methods and you are still getting this warning, you most likely misspelled the timezone identifier. We selected the timezone 'UTC' for now, but please set date.timezone to select your timezone. in /home3/kuehlebo/public_html/transcedo/modules/aggregator/aggregator.pages.inc on line 259.
Accelerating Intelligence
Updated: 1 week 3 days ago

### US has potential to produce more than a billion tons of biomass annually by 2040

Tue, 07/19/2016 - 02:08

Oak Ridge National Laboratory | 2016 Billion-Ton Report

The U.S. has the potential to sustainably produce at least 1 billion dry tons of nonfood biomass resources annually by 2040, according to the 2016 Billion-Ton Report, jointly released by the U.S. Department of Energy and Oak Ridge National Laboratory. That amount would substantially decrease greenhouse gas emissions in the utility and transportation sectors and (as the domestic bioeconomy grows) reduce U.S. dependence on imported oil, the scientists project.

These renewable resources include agricultural, forestry and algal biomass, as well as waste. They encompass the current and future potential of biomass, from currently available logging and crop residues to future available algae and dedicated energy crops — all useable for the production of biofuel, biopower and bioproducts.

Current feedstock, sector consumption, and final product distribution, in million dry tons per year. Biomass resources are shown on the left and their allocations are shown on the right. The size of the flow is representative of the amount of biomass allocated to that end use. For this figure, contributions from landfill gas are represented as tons of biomass equivalent by applying a conversion factor of 0.2665 lb/scf (credit: U.S. DOE)

The report findings show that under a base-case scenario, the United States could increase its use of dry biomass resources from a current 400 million tons to 1.57 billion tons under a high-yield scenario.

The analysis was led by ORNL with contributions from 65 experts from federal agencies, national laboratories, universities (the University of Tennessee, North Carolina State University, South Dakota State University and Oregon State University), and private companies (Energetics, Inc. and Allegheny Science and Technology).

Proposed future feedstock supply system for transforming raw biomass into stable, tradeable
commodities suitable for long-distance transport and handling in existing infrastructure (credit: Idaho National Laboratory)

New to the 2016 report are assessments of potential biomass supplies from algae, from new energy crops (miscanthus, energy cane, eucalyptus), and from municipal solid waste. For the first time, the report also considers how the cost of pre-processing and transporting biomass to the biorefinery may impact feedstock availability.

Interactive tools available through the Bioenergy Knowledge Discovery Framework allow users to visualize biomass availability scenarios and  tailor the data by factors such as geographic area, biomass source and price. Researchers and decision makers can use these features to better inform national bioenergy policies and research, development and deployment strategies. Each diagram and map in the report is available in an interactive interface on the Bioenergy Knowledge Discovery Framework.

Volume 2 of the report, set for release later this year, will consist of a collection of analyses on the potential environmental sustainability effects of a subset of agricultural and forestry biomass production scenarios presented in volume 1. Volume 2 will also discuss algae sustainability, land use, and land management changes, and strategies to enhance environmental sustainability.

### Middle-age-plus memory decline may just be a matter of changing focus

Sat, 07/16/2016 - 02:35

When middle-aged and older adults were shown a series of faces, red regions of the brain were more active; these include an area in the medial prefrontal cortex that is associated with self-referential thinking. In young adults, by contrast, blue regions — which include areas important for memory and attention –+ were more active during this task. (credit: N. Rajah, McGill University)

Are you middle-aged or older and having problems remembering details, like where you left the keys or parked your car?

Cheer up, it may simply be the result of a change in what information your brain focuses on during memory formation and retrieval, rather than a decline in brain function, according to a study by McGill University researchers.

In the study, published in the journal, NeuroImage, 112 healthy adults ranging in age from 19 to 76 years were shown a series of faces. Participants were then asked to recall where a particular face appeared on the screen (left or right) and when it appeared (least or most recently). The researchers used functional MRI to analyze which parts of brain were activated during recall of these details.

Different parts of the brain involved

Senior author Natasha Rajah, Director of the Brain Imaging Centre, and colleagues found that young adults activated their visual cortex while successfully performing this task.

But for middle-aged and older adults, their medial prefrontal cortex was activated instead. That’s a part of the brain known to be involved with information having to do with one’s own life and introspection. This may reflect changes in what adults deem “important information” as they age, she said.

Rajah says middle-aged and older adults can improve their recall abilities by learning to focus on external rather than internal information, using mindfulness meditation, for example.*

Rajah is currently analyzing data from a similar study to discern if there are any gender differences in middle-aged brain function as it relates to memory. “At mid-life women are going through a lot of hormonal change. So we’re wondering how much of these results is driven by post-menopausal women.”

The research was supported by the Canadian Institutes of Health Research and by a grant from the Alzheimer’s Society of Canada.

* Other options to improve memory include:

• Peppermint tea or rosemary essential oil, scientists at Northumbria University found in studies with subjects over age 65, presented at the British Psychological Society’s Annual Conference in Nottingham in April. Rosemary aroma significantly enhanced prospective memory (for things you plan to do).
• Eight nutrients to protect the aging brain: cocoa flavanols, omega-3 fatty acids, phosphatidylserine and phosphatidic Acid, walnuts, citicoline, choline (found especially in eggs) and magnesium (avocado, soy beans, bananas and dark chocolate), and blueberries, according to a study published in the journal Food Technology. Details here.
Abstract of Changes in the modulation of brain activity during context encoding vs. context retrieval across the adult lifespan

Age-related deficits in context memory may arise from neural changes underlying both encoding and retrieval of context information. Although age-related functional changes in the brain regions supporting context memory begin at midlife, little is known about the functional changes with age that support context memory encoding and retrieval across the adult lifespan. We investigated how age-related functional changes support context memory across the adult lifespan by assessing linear changes with age during successful context encoding and retrieval. Using functional magnetic resonance imaging (fMRI), we compared young, middle-aged and older adults during both encoding and retrieval of spatial and temporal details of faces. Multivariate behavioral partial least squares (B-PLS) analysis of fMRI data identified a pattern of whole brain activity that correlated with a linear age term, and a pattern of whole brain activity that was associated with an age-by-memory phase (encoding vs. retrieval) interaction. Further investigation of this latter effect identified three main findings: 1) reduced phase-related modulation in bilateral fusiform gyrus, left superior/anterior frontal gyrus and right inferior frontal gyrus that started at midlife and continued to older age, 2) reduced phase-related modulation in bilateral inferior parietal lobule that occurred only in older age, and 3) changes in phase-related modulation in older but not younger adults in left middle frontal gyrus and bilateral parahippocampal gyrus that was indicative of age-related over-recruitment. We conclude that age-related reductions in context memory arise in midlife and are related to changes in perceptual recollection and changes in fronto-parietal retrieval monitoring.

### Mayo Clinic researchers discover drug combination that helps immune system attack cancer cells

Fri, 07/15/2016 - 09:13

Effects of combination drug treatment on tumor size in square millimeters over 67 days for multiple mice (credit: Soraya Zorro Manrique et al./Oncotarget)

Mayo Clinic researchers have developed a drug combination that could enhance the immune system’s ability to attack cancer cells. The drugs have shown a pronounced therapeutic effect against advanced and metastatic cancers in mice, according to a  study published in the July 12 edition of the online journal Oncotarget.

“Cancers can remain inconspicuous in the body for months to years before causing major problems, leading the immune system to coexist rather than to attack cancers,” explains Mayo Clinic cancer immunotherapist Peter Cohen, M.D.

The solution was to combine two drugs: toll-like receptor (TLR) agonists that can mimic invading bacteria (tricking the immune system into attacking cancer as if it were a life-threatening infection) and the chemotherapy agent cyclophosphamide. The combination resulted in permanent eradication of breast and pancreatic cancers, as well as widespread metastases.

The combined weekly treatment was very well tolerated and actually less toxic than either TLR agonists or cyclophosphamide given individually, they also found.

The drug combination also revealed an additional benefit: it activated monocytes (a type of white blood cell) to participate in the killing of cancer cells.

Mayo Clinic is continuing its research in an FDA-approved clinical trial. They are studying whether patients with advanced cancers, including pancreas, breast, colorectal, melanoma and others, respond similarly to mice when cyclophosphamide treatment is paired with the TLR agonist motolimod.

Mayo Clinic | Potential Immunotherapy Drug Combination for Targeting Advanced and Metastatic Cancers

Abstract of Definitive activation of endogenous antitumor immunity by repetitive cycles of cyclophosphamide with interspersed Toll-like receptor agonists

Many cancers both evoke and subvert endogenous anti-tumor immunity. However, immunosuppression can be therapeutically reversed in subsets of cancer patients by treatments such as checkpoint inhibitors or Toll-like receptor agonists (TLRa). Moreover, chemotherapy can leukodeplete immunosuppressive host elements, including myeloid-derived suppressor cells (MDSCs) and regulatory T-cells (Tregs). We hypothesized that chemotherapy-induced leukodepletion could be immunopotentiated by co-administering TLRa to emulate a life-threatening infection. Combining CpG (ODN 1826) or CpG+poly(I:C) with cyclophosphamide (CY) resulted in uniquely well-tolerated therapeutic synergy, permanently eradicating advanced mouse tumors including 4T1 (breast), Panc02 (pancreas) and CT26 (colorectal). Definitive treatment required endogenous CD8+ and CD4+ IFNγ-producing T-cells. Tumor-specific IFNγ-producing T-cells persisted during CY-induced leukopenia, whereas Tregs were progressively eliminated, especially intratumorally. Spleen-associated MDSCs were cyclically depleted by CY+TLRa treatment, with residual monocytic MDSCs requiring only continued exposure to CpG or CpG+IFNγ to effectively attack malignant cells while sparing non-transformed cells. Such tumor destruction occurred despite upregulated tumor expression of Programmed Death Ligand-1, but could be blocked by clodronate-loaded liposomes to deplete phagocytic cells or by nitric oxide synthase inhibitors. CY+TLRa also induced tumoricidal myeloid cells in naive mice, indicating that CY+TLRa’s immunomodulatory impacts occurred in the complete absence of tumor-bearing, and that tumor-induced MDSCs were not an essential source of tumoricidal myeloid precursors. Repetitive CY+TLRa can therefore modulate endogenous immunity to eradicate advanced tumors without vaccinations or adoptive T-cell therapy. Human blood monocytes could be rendered similarly tumoricidal during in vitro activation with TLRa+IFNγ, underscoring the potential therapeutic relevance of these mouse tumor studies to cancer patients.

Fri, 07/15/2016 - 07:43

Normal brain activity (credit: University of Virginia Health System)

In a discovery that raises fundamental questions about human behavior, researchers at the University of Virginia School of Medicine have found that the immune system directly affects — and even controls — our social behavior, such as our desire to interact with others. That finding could have significant implications for neurological diseases such as autism-spectrum disorders and schizophrenia, the researchers suggest.

“The brain and the adaptive immune system were thought to be isolated from each other, and any immune activity in the brain was perceived as sign of a pathology. And now, not only are we showing that they are closely interacting, but some of our behavior traits might have evolved because of our immune response to pathogens,” explained Jonathan Kipnis, chair of UVA’s Department of Neuroscience.

“It’s crazy, but maybe we are just multicellular battlefields for two ancient forces: pathogens and the immune system. Part of our personality may actually be dictated by the immune system.”

Evolutionary forces linking brains and pathogens

KurzweilAI has cited supporting evidence for that idea. For example, permanent stress may affect immune cells in the brain, leading to mental disorders and protective immune microglia cells also have direct involvement in creating the cellular networks at the core of brain behavior.

Last year, Kipnis, the director of UVA’s Center for Brain Immunology and Glia, and his team discovered that meningeal membranes (covering the brain and spinal cord) in the brain directly link the brain with the lymphatic system. That overturned decades of textbook teaching that the brain lacks a direct connection to the immune system.

Now, the researchers suggest, the relationship between people and pathogens could have directly affected the development of our social behavior. Social behavior (which is necessary for the survival of the species) allows pathogens to spread, so our immune systems may have developed to protect us from the diseases that accompany those interactions.

Specifically, the UVA researchers have now shown that a specific immune molecule, interferon gamma, seems to be critical for social behavior, and that a variety of creatures, such as flies, zebrafish, mice and rats, activate interferon gamma responses (as protection) when they are social.

Normally, this molecule is produced by the immune system in response to bacteria, viruses or parasites. But blocking the molecule in mice using genetic modification also made regions of the brain hyperactive, causing the mice to become less social. Restoring the molecule restored the brain connectivity and behavior to normal.

A hyperactive brain, triggered by a blocked immune system, may lead to less-social behavior (credit: University of Virginia Health System)

In a Nature paper outlining their findings, the researchers note the immune molecule plays a “profound role in maintaining proper social function.”

“It’s extremely critical for an organism to be social for the survival of the species. It’s important for foraging, sexual reproduction, gathering, hunting,” said Anthony J. Filiano, Hartwell postdoctoral fellow in the Kipnis lab and lead author of the study. “The hypothesis is that when organisms come together, you have a higher propensity to spread infection — you need to be social, but [in doing so] you have a higher chance of spreading pathogens.” Which explains why “interferon gamma, in evolution, has been used as a more efficient way to both boost social behavior while boosting an anti-pathogen response.”

Immune-system failure leads to social deficits

The researchers explain that a malfunctioning immune system may be responsible for “social deficits in numerous neurological and psychiatric disorders.” But exactly what this might mean for autism and other specific conditions requires further investigation.

It is unlikely that any one molecule will be responsible for disease or the key to a cure. The researchers believe that the causes are likely to be much more complex. But the discovery that the immune system — and possibly pathogens, by extension — can control our interactions raises many exciting avenues for scientists to explore, both in terms of battling neurological disorders and understanding human behavior.

Kipnis and his team worked closely with UVA’s Department of Pharmacology and with Vladimir Litvak’s research group at the University of Massachusetts Medical School. Litvak’s team developed a computational approach to investigate the complex dialogue between immune signaling and brain function in health and disease.

“Using this approach we predicted a role for interferon gamma, an important cytokine secreted by T lymphocytes, in promoting social brain functions,” Litvak said. “Our findings contribute to a deeper understanding of social dysfunction in neurological disorders, such as autism and schizophrenia, and may open new avenues for therapeutic approaches.”

The work was supported by NIH grants and the Hartwell Foundation.

Medicine Virginia | Shocking New Role Found for the Immune System: Controlling Social Interactions

Abstract of Unexpected role of interferon-γ in regulating neuronal connectivity and social behaviour

Immune dysfunction is commonly associated with several neurological and mental disorders. Although the mechanisms by which peripheral immunity may influence neuronal function are largely unknown, recent findings implicate meningeal immunity influencing behaviour, such as spatial learning and memory1. Here we show that meningeal immunity is also critical for social behaviour; mice deficient in adaptive immunity exhibit social deficits and hyper-connectivity of fronto-cortical brain regions. Associations between rodent transcriptomes from brain and cellular transcriptomes in response to T-cell-derived cytokines suggest a strong interaction between social behaviour and interferon-γ (IFN-γ)-driven responses. Concordantly, we demonstrate that inhibitory neurons respond to IFN-γ and increase GABAergic (γ-aminobutyric-acid) currents in projection neurons, suggesting that IFN-γ is a molecular link between meningeal immunity and neural circuits recruited for social behaviour. Meta-analysis of the transcriptomes of a range of organisms reveals that rodents, fish, and flies elevate IFN-γ/JAK-STAT-dependent gene signatures in a social context, suggesting that the IFN-γ signalling pathway could mediate a co-evolutionary link between social/aggregation behaviour and an efficient anti-pathogen response. This study implicates adaptive immune dysfunction, in particular IFN-γ, in disorders characterized by social dysfunction and suggests a co-evolutionary link between social behaviour and an anti-pathogen immune response driven by IFN-γ signalling.

### DNA origami creates a microscopic glowing Van Gogh

Fri, 07/15/2016 - 06:52

This reproduction of van Gogh’s The Starry Night contains 65,536 glowing pixels but is just the width of a dime across, as a proof-of-concept of precision placement of DNA origami (credit: Paul Rothemund and Ashwin Gopinath/Caltech)

Using folded DNA to precisely place glowing molecules within microscopic light resonators, researchers at Caltech have created one of the world’s smallest reproductions of Vincent van Gogh’s The Starry Night. The feat is a proof-of-concept of how precision placement of DNA origami can be used to build hybrid nanophotonic devices at smaller scales than ever before.

DNA origami, developed 10 years ago by Caltech’s research professor Paul Rothemund, is a technique that allows researchers to fold (in a test tube) a long strand of self-assembling DNA into any desired shape. The folded DNA then acts as a scaffold (support) onto which researchers can attach nanometer-scale components. KurzweilAI has reported extensively on DNA origami — most recently, an automated design method for creating nanoparticles for drug delivery and cell targeting, nanoscale robots, custom-tailored optical devices, and DNA as a data storage medium, for example.

Meanwhile, over the last seven years, Rothemund and associates have refined and extended DNA orgami so that DNA shapes can be precisely positioned on almost any surface used in the manufacture of computer chips. Now, in a Nature paper on July 11, they report the first application of the technique — using DNA origami to install fluorescent molecules into microscopic light sources for use in single-molecule detection, quantum computers, and other applications.

The work was supported by the Army Research Office, the Office of Naval Research, the Air Force Office of Scientific Research, and the National Science Foundation.

Abstract of Engineering and mapping nanocavity emission via precision placement of DNA origami

Many hybrid devices integrate functional molecular or nanoparticle components with microstructures, as exemplified by the nanophotonic devices that couple emitters to optical resonators for potential use in single-molecule detection, precision magnetometry, low threshold lasing and quantum information processing. These systems also illustrate a common difficulty for hybrid devices: although many proof-of-principle devices exist, practical applications face the challenge of how to incorporate large numbers of chemically diverse functional components into microfabricated resonators at precise locations. Here we show that the directed self-assembly of DNA origami onto lithographically patterned binding sites allows reliable and controllable coupling of molecular emitters to photonic crystal cavities (PCCs). The precision of this method is sufficient to enable us to visualize the local density of states within PCCs by simple wide-field microscopy and to resolve the antinodes of the cavity mode at a resolution of about one-tenth of a wavelength. By simply changing the number of binding sites, we program the delivery of up to seven DNA origami onto distinct antinodes within a single cavity and thereby digitally vary the intensity of the cavity emission. To demonstrate the scalability of our technique, we fabricate 65,536 independently programmed PCCs on a single chip. These features, in combination with the widely used modularity of DNA origami, suggest that our method is well suited for the rapid prototyping of a broad array of hybrid nanophotonic devices.

### Dark energy measured with record-breaking map of 1.2 million galaxies

Thu, 07/14/2016 - 10:20

One slice through the map of the large-scale structure of the Universe from the Sloan Digital Sky Survey and its Baryon Oscillation Spectroscopic Survey. Each dot in this picture indicates the position of a galaxy 6 billion years into the past. The image covers about 1/20th of the sky, a slice of the Universe 6 billion light-years wide, 4.5 billion light-years high, and 500 million light-years thick. Color indicates distance from Earth, ranging from yellow on the near side of the slice to purple on the far side. Galaxies are highly clustered, revealing superclusters and voids whose presence is seeded in the first fraction of a second after the Big Bang. This image contains 48,741 galaxies, about 3% of the full survey dataset. Gray patches are small regions without survey data. (credit: Daniel Eisenstein and SDSS-III)

A team of hundreds of physicists and astronomers have announced results from the largest-ever, three-dimensional map of distant galaxies, created to make one of the most precise measurements yet of the dark energy currently driving the accelerated expansion of the Universe.

“We have spent five years collecting measurements of 1.2 million galaxies over one quarter of the sky to map out the structure of the Universe over a volume of 650 cubic billion light years,” says Jeremy Tinker of New York University, a co-leader of the scientific team carrying out this effort. “This map has allowed us to make the best measurements yet of the effects of dark energy in the expansion of the Universe.”

These new measurements were carried out by the Baryon Oscillation Spectroscopic Survey (BOSS) program of the Sloan Digital Sky Survey-III. Shaped by a continuous tug-of-war between dark matter and dark energy, the map revealed by BOSS allows scientists to measure the expansion rate of the Universe and thus determine the amount of matter and dark energy that make up the present-day Universe. A collection of papers describing these results was submitted this week to the Monthly Notices of the Royal Astronomical Society.

Measuring the expansion rate of the Universe

BOSS measures the expansion rate of the Universe by determining the size of the baryonic acoustic oscillations (BAO) in the three-dimensional distribution of galaxies. The original BAO size is determined by pressure waves that traveled through the young Universe up to when it was only 400,000 years old (the Universe is presently 13.8 billion years old), at which point they became frozen in the matter distribution of the Universe.

The end result is that galaxies have a slight preference to be separated by a characteristic distance that astronomers call the acoustic scale. The size of the acoustic scale at 13.7996 billion years ago has been exquisitely determined from observations of the cosmic microwave background from the light emitted when the pressure waves became frozen. Measuring the distribution of galaxies since that time allows astronomers to measure how dark matter and dark energy have competed to govern the rate of expansion of the Universe.

“We’ve made the largest map for studying the 95% of the universe that is dark,” noted David Schlegel, an astrophysicist at Lawrence Berkeley National Laboratory (Berkeley Lab) and principal investigator for BOSS. “In this map, we can see galaxies being gravitationally pulled towards other galaxies by dark matter. And on much larger scales, we see the effect of dark energy ripping the universe apart.”

The Sloan Digital Sky Survey and its Baryon Oscillation Spectroscopic Survey has transformed a two-dimensional image of the sky (left panel) into a three-dimensional map spanning distances of billions of light years, shown here from two perspectives (middle and right panels). This map includes 120,000 galaxies over 10% of the survey area. The brighter regions correspond to the regions of the Universe with more galaxies and therefore more dark matter. (credit: Jeremy Tinker and SDSS-III)

Ariel Sanchez of the Max-Planck Institute of Extraterrestrial Physics led the effort to estimate the exact amount of dark matter and dark energy based on the BOSS data and explains: “Measuring the acoustic scale across cosmic history gives a direct ruler with which to measure the Universe’s expansion rate. With BOSS, we have traced the BAO’s subtle imprint on the distribution of galaxies spanning a range of time from 2 to 7 billion years ago.”

To measure the size of these ancient giant waves to such sharp precision, BOSS had to make an unprecedented and ambitious galaxy map, many times larger than previous surveys. At the time the BOSS program was planned, dark energy had been previously determined to significantly influence the expansion of the Universe starting about 5 billion years ago. BOSS was thus designed to measure the BAO feature from before this point (7 billion years ago) out to near the present day (2 billion years ago).

Jose Vazquez of Brookhaven National Laboratory combined the BOSS results with other surveys and searched for any evidence of unexplained physical phenomena in the results. “Our latest results tie into a clean cosmological picture, giving strength to the standard cosmological model that has emerged over the last eighteen years.”

Rita Tojeiro of the University of St. Andrews is the other co-leader of the BOSS galaxy clustering working group along with Tinker. “We see a dramatic connection between the sound wave imprints seen in the cosmic microwave background 400,000 years after the Big Bang to the clustering of galaxies 7-12 billion years later. The ability to observe a single well-modeled physical effect from recombination until today is a great boon for cosmology.”

The map also reveals the distinctive signature of the coherent movement of galaxies toward regions of the Universe with more matter, due to the attractive force of gravity. Crucially, the observed amount of infall is explained well by the predictions of general relativity.

“The results from BOSS provide a solid foundation for even more precise future BAO measurements, such as those we expect from the Dark Energy Spectroscopic Instrument (DESI),” says Natalie Roe, Physics Division director at Berkeley Lab. “DESI will construct a more detailed 3-dimensional map in a volume of space ten times larger to precisely characterize dark energy — and ultimately the future of our universe.”

Funding for SDSS-III has been provided by the Alfred P. Sloan Foundation, the Participating Institutions, the National Science Foundation, and the U.S. Department of Energy Office of Science.

Abstract of The clustering of galaxies in the completed SDSS-III Baryon Oscillation Spectroscopic Survey: cosmological analysis of the DR12 galaxy sample

We present cosmological results from the final galaxy clustering data set of the Baryon Oscillation Spectroscopic Survey, part of the Sloan Digital Sky Survey III. Our combined galaxy sample comprises 1.2 million massive galaxies over an effective area of 9329 deg^2 and volume of 18.7 Gpc^3, divided into three partially overlapping redshift slices centred at effective redshifts 0.38, 0.51, and 0.61. We measure the angular diameter distance DM and Hubble parameter H from the baryon acoustic oscillation (BAO) method after applying reconstruction to reduce non-linear effects on the BAO feature. Using the anisotropic clustering of the pre-reconstruction density field, we measure the product DM*H from the Alcock-Paczynski (AP) effect and the growth of structure, quantified by f{\sigma}8(z), from redshift-space distortions (RSD). We combine measurements presented in seven companion papers into a set of consensus values and likelihoods, obtaining constraints that are tighter and more robust than those from any one method. Combined with Planck 2015 cosmic microwave background measurements, our distance scale measurements simultaneously imply curvature {\Omega}_K =0.0003+/-0.0026 and a dark energy equation of state parameter w = -1.01+/-0.06, in strong affirmation of the spatially flat cold dark matter model with a cosmological constant ({\Lambda}CDM). Our RSD measurements of f{\sigma}_8, at 6 per cent precision, are similarly consistent with this model. When combined with supernova Ia data, we find H0 = 67.3+/-1.0 km/s/Mpc even for our most general dark energy model, in tension with some direct measurements. Adding extra relativistic species as a degree of freedom loosens the constraint only slightly, to H0 = 67.8+/-1.2 km/s/Mpc. Assuming flat {\Lambda}CDM we find {\Omega}_m = 0.310+/-0.005 and H0 = 67.6+/-0.5 km/s/Mpc, and we find a 95% upper limit of 0.16 eV/c^2 on the neutrino mass sum.

### A biocompatible, transparent therapeutic window to the brain

Thu, 07/14/2016 - 08:58

An illustration showing how the “window to the brain” transparent skull implant created by UC Riverside researchers would work (credit: UC Riverside)

Researchers at the University of California, Riverside have developed a transparent “window to the brain” — a skull implant that is biocompatible, infection-resistant, and does not need to be repetitively replaced.

Part of the ongoing “Window to the Brain” project, a multi-institution, cross-disciplinary effort, the idea is to use transparent skull implants to provide laser diagnosis and treatment of a wide variety of brain pathologies, including brain cancers, traumatic brain injury, stroke, and neurodegenerative diseases, without requiring repeated craniotomies (a surgical operation in which a bone flap is temporarily removed from the skull to access the brain). Such operations are vulnerable to bacterial infections.

A biocompatible transparent material

The researchers have developed a transparent version of the material yttria-stabilized zirconia (YSZ), a ceramic material used in hip implants and dental crowns.

The researchers implanted the material in a hamster, where it integrated into the host tissue without causing an immune response or other adverse effects, as they describe in a paper in the journal Nanomedicine: Nanotechnology, Biology and Medicine. The internal toughness of YSZ, which is more impact-resistant and biocompatible than the titanium, thermoplastic polymers, and glass-based materials developed by other researchers, makes it “the only transparent skull implant that could conceivably be used in humans,” according to the researchers.

Treating bacterial infections

Schematic diagram showing treatment of biofilm formation with near-infrared laser light via a transparent YSZ material, monitored by a thermal IR camera (credit: Yasaman Damestani et al./Lasers in Surgery and Medicine)

The scientists also developed a way to use the same laser light used in brain treatments to treat incidental bacterial infections. In a lab study, described in a paper in the journal Lasers in Surgery and Medicine, the researchers treated E. Coli infections by aiming laser light through the transparent implant, without having to remove the implant and without causing an immune response or other adverse effects to surrounding tissue.

“This was an important finding because it showed that the combination of our transparent implant and laser-based therapies enables us to treat not only brain disorders, but also to tackle bacterial infections that are common after cranial implants. These infections are especially challenging to treat because many antibiotics do not penetrate the blood brain barrier,” said Devin Binder, M.D., a neurosurgeon and neuroscientist in UCR’s School of Medicine and a collaborator on the project.

The Window to the Brain project is a multi-institution, interdisciplinary partnership led by Guillermo Aguilar, professor of mechanical engineering in UCR’s Bourns College of Engineering, and Santiago Camacho-López, from the Centro de Investigación Científica y de Educación Superior de Ensenada (CICESE) in Mexico.

Last October, the team received $3.6 million from the National Science Foundation’s Partnerships in International Research and Education (PIRE) program, which pairs U.S. universities with others around the world. An additional$1 million was from Consejo Nacional de Ciencia y Tecnología (CONACYT), Mexico’s entity in charge of promoting scientific and technological activities. The remainder of the money came from in-kind contributions from the Mexican universities.

The team’s long-term goal is to see the technology become the standard of care for patients with brain disorders.

Abstract of Inflammatory response to implantation of transparent nanocrystalline yttria-stabilized zirconia using a dorsal window chamber model

The long-range goal of the windows to the brain (WttB) is to improve patient care by providing a technique for delivery and/or collection of light into/from the brain, on demand, over large areas, and on a chronically-recurring basis without the need for repeated craniotomies. To evaluate the potential of nanocrystalline yttria-stabilized-zirconia (nc-YSZ) cranial implant for optical therapy and imaging, in vivo biocompatibility was studied using the dorsal window chamber model in comparison with control (no implant) and commercially available cranial implant materials (PEEK and PEKK). The host tissue response to implant was characterized by using transillumination and fluorescent microscopy to measure leukocyte adhesion, blood vessel diameter, blood flow rate, and vascular permeability over two weeks. The results indicated the lack of inflammatory reaction of the host tissue to nc-YSZ at the microscopic level, suggesting that nc-YSZ is a good alternative material for cranial implants.

Abstract of Evaluation of laser bacterial anti-fouling of transparent nanocrystalline yttria-stabilized-zirconia cranial implant

Background and Objective: The development and feasibility of a novel nanocrystalline yttria-stabilized-zirconia (nc-YSZ) cranial implant has been recently established. The purpose of what we now call “window to the brain (WttB)” implant (or platform), is to improve patient care by providing a technique for delivery and/or collection of light into/from the brain, on demand, over large areas, and on a chronically recurring basis without the need for repeated craniotomies. WttB holds the transformative potential for enhancing light-based diagnosis and treatment of a wide variety of brain pathologies including cerebral edema, traumatic brain injury, stroke, glioma, and neurodegenerative diseases. However, bacterial adhesion to the cranial implant is the leading factor for biofilm formation (fouling), infection, and treatment failure. Escherichia coli (E. coli), in particular, is the most common isolate in gram-negative bacillary meningitis after cranial surgery or trauma. The transparency of our WttB implant may provide a unique opportunity for non-invasive treatment of bacterial infection under the implant using medical lasers.

Study Design/Materials and Methods: A drop of a diluted overnight culture of BL21-293 E. coli expressing luciferase was seeded between the nc-YSZ implant and the agar plate. This was followed by immediate irradiation with selected laser. After each laser treatment the nc-YSZ was removed, and cultures were incubated for 24 hours at 37 °C. The study examined continuous wave (CW) and pulsed wave (PW) modes of near-infrared (NIR) 810 nm laser wavelength with a power output ranging from 1 to 3 W. During irradiation, the temperature distribution of nc-YSZ surface was monitored using an infrared thermal camera. Relative luminescence unit (RLU) was used to evaluate the viability of bacteria after the NIR laser treatment.

Results: Analysis of RLU suggests that the viability of E. coli biofilm formation was reduced with NIR laser treatment when compared to the control group (P < 0.01) and loss of viability depends on both laser fluence and operation mode (CW or PW). The results demonstrate that while CW laser reduces the biofilm formation more than PW laser with the same power, the higher surface temperature of the implant generated by CW laser limits its medical efficacy. In contrast, with the right parameters, PW laser produces a more moderate photothermal effect which can be equally effective at controlling bacterial growth.

Conclusions: Our results show that E. coli biofilm formation across the thickness of the nc-YSZ implant can be disrupted using NIR laser treatment. The results of this in vitro study suggest that using nc-YSZ as a cranial implant in vivo may also allow for locally selective, non-invasive, chronic treatment of bacterial layers (fouling) that might form under cranial implants, without causing adverse thermal damage to the underlying host tissue when appropriate laser parameters are used. Lasers Surg. Med. © 2016 Wiley Periodicals, Inc.

### Berkeley Lab scientists grow atomically thin transistors and circuits

Thu, 07/14/2016 - 05:39

This schematic shows the chemical assembly of two-dimensional crystals. Graphene is first etched into channels and the TMDC molybdenum disulfide (MoS2) begins to nucleate around the edges and within the channel. On the edges, MoS2 slightly overlaps on top of the graphene. Finally, further growth results in MoS2 completely filling the channels. (credit: Berkeley Lab)

In an advance that helps pave the way for next-generation electronics and computing technologies — and possibly paper-thin devices — scientists with the U.S. Department of Energy’s Lawrence Berkeley National Laboratory (Berkeley Lab) have developed a way to chemically assemble transistors and circuits that are only a few atoms thick.

In addition, their method yields functional structures at a scale large enough to begin thinking about real-world applications and commercial scalability.

They reported their research online July 11 in the journal Nature Nanotechnology.

The scientists controlled the synthesis of a transistor in which narrow channels were etched onto conducting graphene, and a semiconducting material called a transition-metal dichalcogenide (TMDC) was seeded in the blank channels.

Both of these materials are single-layered crystals and atomically thin, so the two-part assembly yielded electronic structures that are essentially two-dimensional, and cover an area a few centimeters long and a few millimeters wide.

“This is a big step toward a scalable and repeatable way to build atomically thin electronics or pack more computing power in a smaller area,” says Xiang Zhang, a senior scientist in Berkeley Lab’s Materials Sciences Division who led the study.

Their work is part of a new wave of research aimed at keeping pace with Moore’s Law, which holds that the number of transistors in an integrated circuit doubles approximately every two years. To keep this pace, scientists predict that integrated electronics will soon require transistors that measure less than ten nanometers in length.

“With silicon, this will be extremely challenging, because the thickness of the transistor’s channel will become greater than the channel length, ultimately leading to difficult electrostatic control via the transistor gate,” the authors note. Nanomaterials such as inorganic nanowires and Stanford/IBM’s carbon nanotubes have been proposed, but require impractical “precise placement and orientation using complex fabrication techniques,” the authors point out.

The two-dimensional solution for keeping up with Moore’s law

Optical image of the atomically thin graphene–MoS heterostructure. Arrows indicate nucleation (junctions) with graphene of the MoS2 areas, forming transistors. (credit: Mervin Zhao et al./Nature Nanotechnology)

So researchers have now looked to two-dimensional crystals that are only one molecule thick as alternative materials to keep up with Moore’s Law. Using that approach, the Berkeley Lab scientists developed a way to seed a single-layered semiconductor — in this case, the TMDC molybdenum disulfide (MoS2) — into channels lithographically etched within a sheet of conducting graphene. The two atomic sheets meet to form nanometer-scale junctions that make atomically thin transistors in which the graphene conductor efficiently injects current into the MoS2.

“This approach allows for the chemical assembly of electronic circuits, using two-dimensional materials, which show improved performance compared to using traditional metals to inject current into TMDCs,” says Mervin Zhao, a lead author and Ph.D. student in Zhang’s group at Berkeley Lab and UC Berkeley.

The scientists demonstrated the usefulness of the structure by assembling it into the logic circuitry of an inverter (NOT gate). This further underscores the technology’s ability to lay the foundation for a chemically assembled atomic computer, the scientists say. They also note that the two-dimensional crystals were synthesized at a wafer scale, so the scalable design is compatible with current semiconductor manufacturing.

The research was supported by the Office of Naval Research and the National Science Foundation. Scientists from Cornell University were also involved in the research.

Abstract of Large-scale chemical assembly of atomically thin transistors and circuits

Next-generation electronics calls for new materials beyond silicon, aiming at increased functionality, performance and scaling in integrated circuits. In this respect, two-dimensional gapless graphene and semiconducting transition-metal dichalcogenides have emerged as promising candidates due to their atomic thickness and chemical stability. However, difficulties with precise spatial control during their assembly currently impede actual integration into devices. Here, we report on the large-scale, spatially controlled synthesis of heterostructures made of single-layer semiconducting molybdenum disulfide contacting conductive graphene. Transmission electron microscopy studies reveal that the single-layer molybdenum disulfide nucleates at the graphene edges. We demonstrate that such chemically assembled atomic transistors exhibit high transconductance (10 µS), on–off ratio (∼106) and mobility (∼17 cm2 V−1 s−1). The precise site selectivity from atomically thin conducting and semiconducting crystals enables us to exploit these heterostructures to assemble two-dimensional logic circuits, such as an NMOS inverter with high voltage gain (up to 70).

### Allen Brain Observatory launched

Thu, 07/14/2016 - 05:17

The Allen Institute for Brain Science today announced the release of the Allen Brain Observatory.

This is standardized survey of cellular-level activity in the mouse visual system. The goal is to empower scientists to “investigate how circuits in the behaving mouse brain coordinate to drive activity and perception, and lays a crucial foundation for understanding perception, cognition and ultimately consciousness.”

The Allen Institute is known for its comprehensive brain atlases, with deep, high-quality data sets revealing where genes are expressed and how cells and connections are arranged in the mouse and human brain, according to Allan Jones, Ph.D., CEO of the Allen Institute.

With this new project, the researchers took a clever approach, combining a large variety of visual stimuli, including film clips and moving images, with the associated responses of neurons in four areas of the mouse visual cortex at multiple depths, sampling more than 18,000 neurons in total. The goal is to determine the “tuning,” or preference, of each individual neuron to visual features like motion and shape orientation, as well as complex images like natural scenes and movies that reveal integrative dynamics of visual processing.

Allen Institute | Allen Brain Observatory: Visualizing the brain in action

The data are presented as part of the suite of Allen Brain Atlas tools in the uniform and shareable Neurodata Without Borders file format, which allows scientists anywhere to easily mine and model the data. (The mouse is an important model system often used to understand the far less accessible and far larger human brain.) The data are presented in a novel visualization format through the Allen Brain Atlas data portal, and are accompanied by analysis tools and access to all raw data, which allows scientists to deeply explore the rules that govern how networks of cells in the visual cortex communicate.

“The Allen Brain Observatory is a stunning window into the visual brain of the mouse,” says Christof Koch, Ph.D., President and Chief Scientific Officer of the Allen Institute for Brain Science. “No one has ever taken this kind of standardized approach to surveying the active brain at cellular resolution in order to measure how the brain processes information in real time. This is a milestone in our quest to decode how the brain’s computations give rise to perception, behavior, and consciousness.

“Just like in astronomy, modelers and theoreticians worldwide can now study this wealth of data using their own analysis tools. If we want to understand higher-order brain functions, we need to understand not just the individual components of the brain but how they all work together.”

Understanding visual processing is a key gateway to understanding how other parts of the brain process information, and future releases of the Allen Brain Observatory will also explore the neural circuits that underlie more complex behaviors like decision-making, according to the researchers.

Allen Institute | Inside the Allen Brain Observatory

### FDA places hold on clinical trial of cancer treatment previously reported on KurzweilAI — UPDATE: FDA releases hold

Wed, 07/13/2016 - 19:33

Juno Therapeutics, Inc. announced July 7 that it has received notice from the FDA that it has placed a clinical hold on an immune-cell cancer treatment known as the “ROCKET” trial, which was reported on KurzweilAI on Mar. 10, 2016.

The clinical hold was initiated after two patient deaths, which followed the recent addition of fludarabine to the pre-conditioning regimen. Juno has proposed to the FDA to continue the ROCKET trial using JCAR015 with cyclophosphamide pre-conditioning alone.

Further information on Forbes.

UPDATE JULY 13, 2016: Juno Therapeutics announced Tuesday July 12 that the FDA has removed the hold and “the ROCKET trial will continue enrollment using JCAR015 with cyclophosphamide pre-conditioning only.” In related news, the Law Offices of Howard G. Smith announced an investigation on behalf of investors of Juno Therapeutics, Inc. (NASDAQ: JUNO) concerning the Company and its officers’ possible violations of federal securities laws and noted that “Juno’s share price fell significantly in value, dropping almost 32%.”

### How birds unlock their ultraviolet vision super-sense

Tue, 07/12/2016 - 11:39

Some birds have been found to be as intelligent as mammals. And some that can see ultraviolet (UV) light live in a super-sensory world apart, able to transmit and receive signals between each other in a way that is invisible to many other species.

Now the ability of finches, sparrows, and many other birds to see ultraviolet (UV) light is explained in a study published in the journal eLife by scientists at the Washington University School of Medicine in St. Louis.

Carotenoid pigments determine bird’s UV perception or not

The study reveals two essential adaptions that enable birds to expand their vision into the UV range: chemical changes in light-filtering pigments called carotenoids (such as carotene, found in carrots, associated with vitamin A) and the tuning of light-sensitive proteins called opsins (light-sensitive proteins), some of which are also used in optogenetics research.

Birds acquire carotenoids through their diets and process them in a variety of ways to shift their light absorption toward longer (visible light) or shorter (UV) wavelengths.

“There are two types of light-sensitive cells, called photoreceptors, in the eye: rods and cones. Cone photoreceptors are responsible for color vision. While humans have blue, green, and red-sensitive cones only, birds have a fourth cone type which is either violet or UV-sensitive, depending on the species,” says senior author Joseph Corbo, MD, PhD, Associate Professor of Pathology and Immunology.

UV vs visual perception by cones in the eye is fine-tuned by evolution

“Our approach showed that blue-cone sensitivity is fine-tuned through a change in the chemical structure of carotenoid pigments within the photoreceptor, allowing both violet and UV-sighted birds to maximize how many colors they can see.”

The study also revealed that sensitivity of the violet/UV cone and the blue cone in birds must move in sync to allow for optimum vision. Among bird species, there is a strong relationship between the light sensitivity of opsins within the violet/UV cone and mechanisms within the blue cone, which coordinate to ensure even UV vision.

Taken together, these results suggest that both blue and violet cone cells have adapted during evolution to enhance color vision in birds.

Birds have achieved UV vision by use of a specialized optical organelle, the pigmented cone oil droplet. These oil droplets are located in the path of light through the receptor and act as cutoff filters matched to the visual pigment sensitivity of each cone subtype.

Spectral filtering in bird cones. a) A flat-mounted chicken retina under brightfield illumination that shows the distinctive pigmentation of the cone oil droplets. (b) A diagram of the avian single cone photoreceptors showing the relative position of the oil droplet within the cells (top) and a representation of the spectral filtering cutoff effects of the droplet (bottom). (credit: Matthew B Toomey et al./eLife)

“The majority of bird species rely on vision as their primary sense, and color discrimination plays a crucial role in their essential behaviors, such as choosing mates and foraging for food. This explains why birds have evolved one of the most richly endowed color vision systems among vertebrates,” says first author Matthew Toomey, a postdoctoral fellow at the Washington University School of Medicine.

“The precise coordination of sensitivity and filtering in the visual system may, for example, help female birds discriminate very fine differences in the elaborate coloration of their suitors and choose the fittest mates. This refinement of visual sensitivity could also facilitate the search for hidden seeds, fruits, and other food items in the environment.”

The team now plans to investigate the underlying molecular mechanisms that help modify the carotenoid pigments and light-sensitive protein tuning in a wide range of bird species, to gather further insights into the evolution of UV vision.

Abstract of Complementary shifts in photoreceptor spectral tuning unlock the full adaptive potential of ultraviolet vision in birds

Color vision in birds is mediated by four types of cone photoreceptors whose maximal sensitivities (λmax) are evenly spaced across the light spectrum. In the course of avian evolution, the λmax of the most shortwave-sensitive cone, SWS1, has switched between violet (λmax > 400 nm) and ultraviolet (λmax < 380 nm) multiple times. This shift of the SWS1 opsin is accompanied by a corresponding short-wavelength shift in the spectrally adjacent SWS2 cone. Here, we show that SWS2 cone spectral tuning is mediated by modulating the ratio of two apocarotenoids, galloxanthin and 11’,12’-dihydrogalloxanthin, which act as intracellular spectral filters in this cell type. We propose an enzymatic pathway that mediates the differential production of these apocarotenoids in the avian retina, and we use color vision modeling to demonstrate how correlated evolution of spectral tuning is necessary to achieve even sampling of the light spectrum and thereby maintain near-optimal color discrimination.

### How to detect early signs of Alzheimer’s with a simple eye exam before symptoms appear

Tue, 07/12/2016 - 10:53

Monochromatic images of normal mouse retina at four wavelengths from blue (upper left) to red (lower right). Boxes in lower right show locations typical of amyloid (a substance found in the brain associated with Alzheimer’s). (credit: Swati S. More et al./IOVS)

University of Minnesota (UMN) scientists and associates have developed new technology that can detect signs of Alzheimer’s before the onset of symptoms — early enough to give drugs a chance to work — in mice and humans by simply examining the back of their eyes.

Looking at Alzheimer’s effects through the eye is a key advantage of the new technology. “The retina of the eye is not just ‘connected’ to the brain — it is part of the central nervous system,” said Swati More, PhD, of the Center for Drug Design at UMN, co-author of a paper recently published in Investigative Ophthalmology & Visual Science (IOVS).

The brain and retina undergo similar changes due to Alzheimer’s disease, he said, but “unlike the brain, the retina is easily accessible to us. We saw changes in the retinas of Alzheimer’s mice before the typical age at which neurological signs are observed.”

Human clinical trials are set to start in July to test the technology in humans who are 40–75 years old (for more information on participating in the clinical trial, you can visit the trial website).

Optical spectra recorded from human and mouse retina samples. Upper two lines show the intensity of light for different wavelengths of light from red (right side) to blue (left side) for a normal human retina (heavy line) and for an Alzheimer’s (AD) patients retina. Comparable mouse plots, shown below (WT = normal mouse; APP1/PS1 = Alzheimer’s model mouse), show a similar pattern. (credit: Swati S. More et al./IOVS)

Early detection of Alzheimer’s is critical for two reasons. “First, effective treatments need to be administered well before patients show actual neurological signs,” said co-author Robert Vince, PhD, of the Center for Drug Design at the University of Minnesota (UMN). “Second, since there are no available early detection techniques, drugs currently cannot be tested to determine if they are effective against early Alzheimer’s disease. An early diagnostic tool like ours could help the development of drugs as well.”

Abstract of Early Detection of Amyloidopathy in Alzheimer’s Mice by Hyperspectral Endoscopy

Purpose: To describe a spectral imaging system for small animal studies based on noninvasive endoscopy of the retina, and to present time-resolved spectral changes from live Alzheimer’s mice prior to cognitive decline, corroborating our previous in vitro findings.

Methods: Topical endoscope fundus imaging was modified to use a machine vision camera and tunable wavelength system for acquiring monochromatic images across the visible to near-infrared spectral range. Alzheimer’s APP/PS1 mice and age-matched, wild-type mice were imaged monthly from months 3 through 8 to assess changes in the fundus reflection spectrum. Optical changes were fit to Rayleigh light scatter models as measures of amyloid aggregation.

Results: Good quality spectral images of the central retina were obtained. Short-wavelength reflectance from Alzheimer’s mice retinae showed significant reduction over time compared to wild-type mice. Optical changes were consistent with an increase in Rayleigh light scattering in neural retina due to soluble Aβ1–42aggregates. The changes in light scatter showed a monotonic increase in soluble amyloid aggregates over a 6-month period, with significant build up occurring at 7 months.

Conclusions: Hyperspectral imaging technique can be brought inexpensively to the study of retinal changes caused by Alzheimer’s disease progression in live small animals. A similar previous finding of reduction in the light reflection over a range of wavelengths in isolated Alzheimer’s mice retinae, was reproducible in the living Alzheimer’s mice. The technique presented here has a potential for development as an early Alzheimer’s retinal diagnostic test in humans, which will support the treatment outcome.

### Locusts engineered as biorobotic sensing machines

Mon, 07/11/2016 - 09:26

Sensors placed on the insect monitor neural activity while they are freely moving, decoding the odorants present in their environment. (credit: Baranidharan Raman)

Washington University in St. Louis engineers have developed an innovatiave “bio-hybrid nose” that could be used in homeland security applications, such as detecting explosives, replacing state-of-the-art miniaturized chemical sensing devices limited to a handful of sensors.

Compare that to the locust antenna (where their chemical sensors are located): “it has several hundreds of thousands of sensors and of a variety of types,” says Baranidharan Raman, associate professor of biomedical engineering, who has received a three-year, \$750,000 grant from the Office of Naval Research (ONR).

The team previously found that locusts can correctly identify a particular odor, even with other odors present — and even in complex situations, such as overlapping with other scents or in different background conditions.

Replacing canines

In previous research, the opening of the locust maxillary palps to the trained odorant was used as an indicator of acquired memory. The palps were painted with non-odorous organic-chemical green paint to facilitate tracking. (credit: Debajit Saha et al./Nature Communications)

The ingenious idea in the new study by the Raman Lab is to remotely monitor neural activity from the insect brain while they are freely moving, exploring, and decoding the odorants present in their environment, which will require innovative low-power electronic components to collect, log, and transmit data.

The locusts could also collect samples using remote control. To do that, the engineers are developing a plasmonic “tattoo” made of a biocompatible silk to apply to the locusts’ wings. It will generate mild heat to help steer locusts to move toward particular locations by remote control. The tattoos, studded with plasmonic nanostructures, also can collect samples of volatile organic compounds in their proximity, which would allow the researchers to conduct secondary analysis of the chemical makeup of the compounds using more conventional methods.

“The canine olfactory system still remains the state-of-the-art sensing system for many engineering applications, including homeland security and medical diagnosis,” Raman said. “However, the difficulty and the time necessary to train and condition these animals, combined with lack of robust decoding procedures to extract the relevant chemical sending information from the biological systems, pose a significant challenge for wider application.

### This deadly soil bug can reach your brain in a day, end up in spinal cord

Mon, 07/11/2016 - 08:32

B. pseudomallei soil-dwelling bacterium endemic in tropical and subtropical regions worldwide, particularly in Thailand and northern Australia (credit: Wikipedia CC)

Imagine a  deadly bacteria that can be picked up by a simple sniff and can travel to your brain and spinal cord in just 24 hours. Or one that could just be quietly sitting there, waiting for an opportune moment. Or maybe just doing small incremental damage ever day over a lifetime … as you lose the function in your brain incrementally.

That’s the grisly finding (in mice), published in Immunity and Infection this week, of a new study by Australian Griffith University and Bond University scientists.

The pathogenic bacteria Burkholderia pseudomallei, which causes the potentially fatal disease melioidosis, kills 89,000 people around the world each year and is prevalent in northern Australia, where a person with melioidosis has a 20–50 per cent chance of dying once it infects the brain. The bacterium is found in the northern parts of the Northern Territory, including Darwin.

In Southeast Asia 50 per cent of the population may be positive for melioidosis, and in places like Cambodia the mortality rate is as high as 50 per cent.

But for the rest of us, the findings could also lead to discoveries of how the common staphylococcus and acne bacterium also end up in the spinal cord, as well as how chlamydia travels to the brain in Alzheimer’s patients. Or even explain common back problems, which could be where bacteria have infected your bone, causing pain that could be simply treated with antibiotics, according to the researchers.

Tracing the bacteria in mice brains and spinal cords

(Top) A schematic drawing of a mouse brain showing the location of various images. (Bottom) D: A B. pseudomallei rod (arrow) present in trigeminal nerve near the connection between the trigeminal nerve in the brain and the brainstem. (E) B. pseudomallei rod (arrow) with a fluorescent particle (arrow with tail) after the merge between the trigeminal nerve and brainstem. Scale bars in μm. (credit: James A. St John et al./Infection and Immunity)

The olfactory mucosa, located in the nose, is very close to the brain and it has long been known that viruses could reach the brain from the olfactory mucosa. But researchers have not understand exactly how the bacteria traveled to the brain and spinal cord, or just how quickly.

To find out, James St. John, PhD., Head of Griffith’s Clem Jones Centre for Neurobiology and Stem Cell Research, and associates infected mice with B. pseudomallei. They were able to trace the bacteria travels from the nerves in the nasal cavity before moving to the brain stem and then into the spinal cord. (He noted that this could also be a pathway for many other common bacteria.)

“Our latest results represent the first direct demonstration of transit of a bacterium from the olfactory mucosa to the central nervous system (CNS) via the trigeminal nerve; bacteria were found a considerable distance from the olfactory mucosa, in the brain stem, and even more remarkably in the spinal cord,” said professor Ifor Beacham from the Griffith Institute for Glycomics.

Researchers will now work on ways to stimulate supporting cells that could remove the bacteria. St. John said the work was important because the bacteria had the potential to be used as a bioweapon and knowing how to combat it was extremely important.

“Bacteria have been implicated as a major causative agent of some types of back pain. We now need to work out whether the bacteria that cause back pain also can enter the brainstem and spinal cord via the trigeminal nerve,” he added.

Abstract of Burkholderia pseudomallei rapidly infects the brainstem and spinal cord via the trigeminal nerve after intranasal inoculation

Infection with Burkholderia pseudomallei causes melioidosis, a disease with a high mortality rate (20% in Australia and 40% in south-east Asia). Neurological melioidosis is particularly prevalent in northern Australian patients and involves brainstem infection, which can progress to the spinal cord; however, the route by which the bacteria invade the central nervous system (CNS) is unknown. We have previously demonstrated that B. pseudomallei can infect the olfactory and trigeminal nerves within the nasal cavity following intranasal inoculation. As the trigeminal nerve projects into the brainstem, we investigated whether the bacteria could continue along this nerve to penetrate the CNS. After intranasal inoculation of mice, B. pseudomallei caused low-level localised infection within the nasal cavity epithelium, prior to invasion of the trigeminal nerve in small numbers. B. pseudomallei rapidly invaded the trigeminal nerve and crossed the astrocytic barrier to enter the brainstem within 24 hours and then rapidly progressed over 2000 μm into the spinal cord. To rule out that the bacteria used a haematogenous route, we used a capsule-deficient mutant of B. pseudomallei, which does not survive in the blood, and found that it also entered the CNS via the trigeminal nerve. This suggests that the primary route of entry is via the nerves that innervate the nasal cavity. We found that actin-mediated motility could facilitate initial infection of the olfactory epithelium. Thus, we have demonstrated that B. pseudomallei can rapidly infect the brain and spinal cord via the trigeminal nerve branches that innervate the nasal cavity.

### Neurons grown from stem cells in a dish reveal clues about autism

Sat, 07/09/2016 - 03:46

Salk researchers have turned the skin cells of people with autism spectrum disorder into neurons. These cells show specific defects (indicated by red and green dots in the neuron) compared with neurons derived from healthy people, including diminished ability to form excitatory connections with other neurons  (credit: Salk Institute)

Why do the brains of up to 30 percent of people with autism spectrum disorder grow faster than usual, early in life? A new study co-led by Salk Institute scientists has used a new stem cell reprogramming technique to find out.

Published July 6, 2016 in the journal Molecular Psychiatry, the Salk team found that stem cell-derived neurons made fewer connections in a dish compared to cells from healthy individuals. The scientists were also able to restore communication between the cells by adding IGF-1, a drug currently being evaluated in clinical trials of autism.*

Neurons derived from people with autism spectrum disorder, shown in the bottom panel, form fewer inhibitory connections, shown in the red stain, compared to those derived from healthy individuals (top panel). The total number of neurons that researchers were able to generate was about the same between the two groups. (credit: Salk Institute)

Autism affects approximately 1 out of every 68 children in the United States. It is characterized by problems communicating, difficulties interacting with others, and in repetitive behaviors, although the symptoms range dramatically in type and severity. There is no known cause of autism, according to the scientists.

Led by senior investigator Rusty Gage, a professor in Salk’s Laboratory of Genetics and holder of the Vi and John Adler Chair for Research on Age-Related Neurodegenerative Diseases, the researchers created stem cells from a subset of people with autism whose brains had grown as much as 23 percent faster than usual, but had subsequently normalized.

The neuron precursor cells derived from the patients multiplied faster than those of typically developing individuals. The finding supports a theory some experts have put forth that brain enlargement is caused by disruptions to the cell’s normal cycle of division, the researchers say. In addition, the stem cell-derived neurons of individuals with autism behaved abnormally, bursting with activity less often compared with those cells of healthy people.

Those neurons’ activity seemed to improve by adding IGF-1, which is known to enhance the connections between neurons. The group plans to use the patient cells to investigate the molecular mechanisms behind IGF-1’s effects, in particular probing for changes in gene expression with treatment.

Other authors on the study include researchers from the University of California, San Francisco; the University of California, Los Angeles; the University of California San Diego; Case Western Reserve University, University of Rochester School of Medicine and Dentistry, and Icahn School of Medicine at Mount Sinai.

The research was supported by the California Institute for Regenerative Medicine, the National Institutes of Health, The International Rett Syndrome Foundation, a NARSAD Independent Investigator Award, a NIMH Autism Center of Excellence Program Project grant, The Leona M. and Harry B. Helmsley Charitable Trust, The JPB Foundation, the Robert and Mary Jane Engman Foundation, the CDMRP Autism Research Program, the University of California, San Diego Clinical and Translational Research Institute, and Autism Speaks.

* In 2010, Gage, Carol Marchetto of Salk’s Laboratory of Genetics, Alysson Muotri of the University of California, San Diego, and their collaborators showed they could recreate features of Rett syndrome—a rare disorder that shares features of autism but is caused by mutations in a single gene—in a petri dish.

They did so by taking skin cells from patients, adding a mix of chemicals that instructed those cells to form stem cells, and in turn, coaxing their new stem cells into neurons. The ability to form what’s called induced pluripotent stem cells (iPSCs) from human cells was pioneered by researchers in 2007, but some scientists were initially skeptical that the new technology could lend insight into complex heritable disorders such as autism.

“In that study, induced pluripotent stem cells gave us a window into the birth of a neuron that we would not otherwise have,” says Marchetto, a senior staff scientist and the study’s first author. “Seeing features of Rett syndrome in a dish gave us the confidence to next study classical autism.”

Abstract of Altered proliferation and networks in neural cells derived from idiopathic autistic individuals

Autism spectrum disorders (ASD) are common, complex and heterogeneous neurodevelopmental disorders. Cellular and molecular mechanisms responsible for ASD pathogenesis have been proposed based on genetic studies, brain pathology and imaging, but a major impediment to testing ASD hypotheses is the lack of human cell models. Here, we reprogrammed fibroblasts to generate induced pluripotent stem cells, neural progenitor cells (NPCs) and neurons from ASD individuals with early brain overgrowth and non-ASD controls with normal brain size. ASD-derived NPCs display increased cell proliferation because of dysregulation of a β-catenin/BRN2 transcriptional cascade. ASD-derived neurons display abnormal neurogenesis and reduced synaptogenesis leading to functional defects in neuronal networks. Interestingly, defects in neuronal networks could be rescued by insulin growth factor 1 (IGF-1), a drug that is currently in clinical trials for ASD. This work demonstrates that selection of ASD subjects based on endophenotypes unraveled biologically relevant pathway disruption and revealed a potential cellular mechanism for the therapeutic effect of IGF-1.

### Molecular flip in crystals driven by light creates microrobotic propulsion

Sat, 07/09/2016 - 01:36

(a) Sequential micrographs of one cycle of self-oscillation observed under 435-nm light and schematic illustrations. (b) Schematic illustration showing setup. (credit: Tomonori Ikegami et al./Angewandte Chemie)

Hokkaido University researchers have designed a crystal material that continually flips between two positions like a paddle, propelling an attached structure, when stimulated by blue light. It could lead to bio-inspired microrobots that deliver drugs to target tissues, for example.

The team made azobenzene-oleic acid crystals, composed of an organic compound called azobenzene, commonly used in dye manufacturing, and oleic acid, commonly found in cooking oil. Azobenzene molecules take two structurally different forms: cis and trans, and they were found to switch back and forth when stimulated by the light.

The frequency of the motion also increased with increased light intensity. Some crystal complexes they created even exhibited swimming-like motions in the water, the researchers report. Previously reported light-responsive materials have been limited in their ability to deform, the researchers noted.

“The importance of this study lies in the realization of macroscopic self-oscillation by the repeated reversible reaction of a molecular machine with the cooperative transformation of a molecular assembly,” the researchers note in a paper published in the journal Angewandte Chemie. “These results provide a fundamental strategy for constructing dynamic self-organizations in supramolecular systems to achieve bioinspired molecular systems.”

Ikegami T. et. al. | A crystalline assembly of azobenzene derivative and oleate showed oscillatory bending-unbending motion under continuous 435-nm light irradiation.

Abstract of Dissipative and Autonomous Square-Wave Self-Oscillation of a Macroscopic Hybrid Self-Assembly under Continuous Light Irradiation

Building a bottom-up supramolecular system to perform continuously autonomous motions will pave the way for the next generation of biomimetic mechanical systems. In biological systems, hierarchical molecular synchronization underlies the generation of spatio-temporal patterns with dissipative structures. However, it remains difficult to build such self-organized working objects via artificial techniques. Herein, we show the first example of a square-wave limit-cycle self-oscillatory motion of a noncovalent assembly of oleic acid and an azobenzene derivative. The assembly steadily flips under continuous blue-light irradiation. Mechanical self-oscillation is established by successively alternating photoisomerization processes and multi-stable phase transitions. These results offer a fundamental strategy for creating a supramolecular motor that works progressively under the operation of molecule-based machines.

Fri, 07/08/2016 - 08:39

Facebook began today (Friday, July 8) rolling out a new beta-version feature for Messenger called “Secret Conversations,” allowing for “one-to-one secret conversations … that will be end-to-end encrypted and which can only be read on one device of the person you’re communicating with.”

Facebook suggests the feature will be useful for discussing an illness or sending financial information (as in the pictures above).  You can choose to set a timer to control the length of time each message you send remains visible within the conversation. (Rich content like GIFs, videos, and making payments are not supported.)

The technology, described in a technical whitepaper (open access), is based on the Signal Protocol developed by Open Whisper Systems, which is also used in Open Whisper Systems’ own Signal messaging app (Chrome, iOS, Android),  WhatsApp, and Google’s Allo (not yet launched).

Unlike WhatsApp and iMessage, which automatically encrypt every message, Secret Conversations only works from a single device and is opt-in, which “will likely rankle many privacy advocates,” says Wired .

But not as much as all of these encrypted services rankle law enforcement agencies, since the feature hampers surveillance capabilities, it adds.

### Robot mimics vertebrate motion

Fri, 07/08/2016 - 05:14

Pleurobot (credit: EPFL)

École polytechnique fédérale de Lausanne (EPFL) scientists have invented a new robot called “Pleurobot” that mimics the way salamanders walk and swim with unprecedented detail.

Aside from being cool (and a likely future Disney attraction), the researchers believe designing the robot will provide a new tool for understanding the evolution of vertebrate locomotion. That could lead to better understanding of how the spinal cord controls the body’s locomotion, which may help develop future therapies and neuroprosthetic devices for paraplegic patients and amputees.

Pleurobot mimics Salamander. Neurobiologists say electrical stimulation of the spinal cord is what determines whether the salamander walks, crawls or swims: At lowest level of stimulation, the salamander walks; with higher stimulation, its pace increases, and beyond some threshold the salamander begins to swim. (credit: EPFL)

Simulating the 3D motion of the salamander’s locomotion requires exceptional precision. The Biorobotics Laboratory scientists started by shooting detailed x-ray videos of the salamander species Pleurodeles waltl from the top and the side, tracking up to 64 points along its skeleton while it performed different types of motion in water and on the ground.

Auke Ijspeert and his team at EPFL then 3D-printed bones and motorized joints, and even created a “nervous system” using electronic circuitry, allowing the Pleurobot to walk, crawl, and even swim underwater.*

Ijspeert thinks that the design methodology used for the Pleurobot can help develop other types of “biorobots,” which could become important tools in neuroscience and biomechanics.

The research, described in the Royal Society journal Interface, received funding from the Swiss National Center of Competence in Research (NCCR) in Robotics and from the Swiss National Science Foundation.

École polytechnique fédérale de Lausanne | A new robot mimics vertebrate motion

* In the design process, the researchers identified the minimum number of motorized segments required, as well as the optimal placement along the robot’s body, to replicate many of the salamander’s types of movement. That made it possible to construct Pleurobot with fewer bones and joints than the real-life creature — only 27 motors and 11 segments along its spine (the real animal has 40 vertebrae and multiple joints, some of which can even rotate freely and move side-to-side or up and down).

Abstract of From cineradiography to biorobots: an approach for designing robots to emulate and study animal locomotion

Robots are increasingly used as scientific tools to investigate animal locomotion. However, designing a robot that properly emulates the kinematic and dynamic properties of an animal is difficult because of the complexity of musculoskeletal systems and the limitations of current robotics technology. Here, we propose a design process that combines high-speed cineradiography, optimization, dynamic scaling, three-dimensional printing, high-end servomotors and a tailored dry-suit to construct Pleurobot: a salamander-like robot that closely mimics its biological counterpart, Pleurodeles waltl. Our previous robots helped us test and confirm hypotheses on the interaction between the locomotor neuronal networks of the limbs and the spine to generate basic swimming and walking gaits. With Pleurobot, we demonstrate a design process that will enable studies of richer motor skills in salamanders. In particular, we are interested in how these richer motor skills can be obtained by extending our spinal cord models with the addition of more descending pathways and more detailed limb central pattern generator networks. Pleurobot is a dynamically scaled amphibious salamander robot with a large number of actuated degrees of freedom (DOFs: 27 in total). Because of our design process, the robot can capture most of the animal’s DOFs and range of motion, especially at the limbs. We demonstrate the robot’s abilities by imposing raw kinematic data, extracted from X-ray videos, to the robot’s joints for basic locomotor behaviours in water and on land. The robot closely matches the behaviour of the animal in terms of relative forward speeds and lateral displacements. Ground reaction forces during walking also resemble those of the animal. Based on our results, we anticipate that future studies on richer motor skills in salamanders will highly benefit from Pleurobot’s design.

### New tech could have helped police locate shooters in Dallas

Thu, 07/07/2016 - 10:07

Potential shooter location in Dallas (credit: Fox News)

JULY 8, 3:56 AM EDT — Livestreamed data from multiple users with cell phones and other devices could be used to help police locate shooters in a situation like the one going on right now in Dallas, says Jon Fisher, CEO of San Francisco-based CrowdOptic.

Here’s how it would work: You view (or record a video of) a shooter with your phone. Your location and the direction you are facing is now immediately available on your device and could be coordinated with data from other persons at the scene to triangulate the position of the shooter.

A CrowdOptic “cluster” with multiple people focused on the same object (credit: CrowdOptic)

This technology, called the “CrowdOptic Interactive Streaming platform,” is already in place, using Google Glass livestreaming, in several organizations, including UCSF Medical Center, Denver Broncos, and Futton, Inc. (working with Chinese traffic police).

Fisher told KurzweilAI his company’s software is also integrated with Cisco Jabber livestreaming video and conferencing products (and soon Spark), and with Sony SmartEyeglass, and that iOS and Android apps are planned.

CrowdOptic also has a product called CrowdOptic Eye, a “powerful, low-bandwidth live streaming device designed to … broadcast live video and two-way audio from virtually anywhere.”

“We’re talking about phones now, but think about all other devices, such as drones, that will be delivering these feeds to CNN and possibly local police,” he said.

“When all attempts to negotiate with the suspect, Micah Johnson, failed under the exchange of gunfire, the Department utilized the mechanical tactical robot, as a last resort, to deliver an explosion device to save the lives of officers and citizens. The robot used was the Remotec, Model  F-5, claw and arm extension with an explosive device of C4 plus ‘Det’ cord.  Approximate weight of total charge was one pound.” — Statement July 9, 2016 by Dallas police chief David O. Brown

The Dallas police department’s decision to use a robot to kill the shooter Thursday July 7, raises questions. For example: Why wasn’t a non-lethal method used with the robot, such as a tranquilizer dart, which also might have given police an opportunity to acquire more information, including the location of claimed bombs and cohorts possibly associated with the crime?

### Surprising discovery of highly dynamic changes in olfactory region of the adult mouse brain

Tue, 07/05/2016 - 07:52

In light brown, in the center of the image, a new adult-born neuron. The neurons in blue are synaptic partner neurons, which connect to the new neurons. The neurons in dark brown are pre-existing neurons. (credit: Institut Pasteur/PM Lledo)

Scientists from the Institut Pasteur and the CNRS have made the surprising discovery that new neurons formed in the olfactory bulb of adult mice are constantly reorganizing the billions of synaptic contacts they establish among themselves (also described as constant structural plasticity).

The researchers found this puzzling because constant structural plasticity is normally confined to specific critical periods after birth, and “plasticity in neural circuits must strike a balance between flexibility and stability so new information can be acquired while previously learned information can be retained,” they note in a paper published in the journal Neuron.

The olfactory bulb in rodents and the hippocampus in humans are two of the areas of the brain capable of constantly regenerating their neurons in adulthood, but it had not been known that olfactory neurons were able to reorganize synaptic contacts.

Watching the brain change through a porthole

To observe the ongoing formation of neuronal circuits, the scientists marked the new granule cell (GC) inter-neurons with a green fluorescent protein (GFP), to view the dynamic changes, using two-photon microscopy imaging via a cranial window.

These experiments were carried out over a period of several months, following the entire life cycle of the new neurons. In the first three weeks of their life, these new neurons extended their cellular projections, known as dendrites, to form several ramifications, which subsequently became very stable.

Sample images of the same adult-born granule cell (GC) inter-neuron dendritic segment at a 2-day interval for 20–22, 40–42, and 60–62 days after virus injection (for monitoring) showing stable (closed arrowheads with numbers indexing stable spines), new (open arrowheads), and lost (asterisks) spines (credit: Kurt A. Sailor et al./Neuron)

They next observed neuronal spines — the structure where synapses form — and demonstrated that 20% of the synapses between new and pre-existing neurons were changed on a daily basis — a phenomenon that was also observed in their synaptic partners, the principal olfactory bulb neurons.

Adjusting efficiently and reliably to ongoing sensory changes

Using computer-based models, the authors showed that these dynamics enabled the synaptic network to adjust efficiently and reliably to ongoing sensory changes in the environment, enabling optimal processing of sensory information by the olfactory bulb.

“Our findings suggest that the plasticity of this constantly regenerating region of the brain occurs with continuous physical formation and elimination of synaptic connections. This structural plasticity reveals a unique dynamic mechanism that is vital for the regeneration and integration of new neurons within the adult brain circuit,” concluded the scientists.

More generally, they said, this study suggests a universal plasticity mechanism in brain regions that is closely associated with memory and learning.

This research was supported by the Institut Pasteur and the CNRS and was funded by AG2R-La Mondiale, the French National Research Agency, the “Revive” LabEx, and the “Biopsy” LabEx.

Abstract of Persistent Structural Plasticity Optimizes Sensory Information Processing in the Olfactory Bulb

In the mammalian brain, the anatomical structure of neural circuits changes little during adulthood. As a result, adult learning and memory are thought to result from specific changes in synaptic strength. A possible exception is the olfactory bulb (OB), where activity guides interneuron turnover throughout adulthood. These adult-born granule cell (GC) interneurons form new GABAergic synapses that have little synaptic strength plasticity. In the face of persistent neuronal and synaptic turnover, how does the OB balance flexibility, as is required for adapting to changing sensory environments, with perceptual stability? Here we show that high dendritic spine turnover is a universal feature of GCs, regardless of their developmental origin and age. We find matching dynamics among postsynaptic sites on the principal neurons receiving the new synaptic inputs. We further demonstrate in silico that this coordinated structural plasticity is consistent with stable, yet flexible, decorrelated sensory representations. Together, our study reveals that persistent, coordinated synaptic structural plasticity between interneurons and principal neurons is a major mode of functional plasticity in the OB.