Moonshots for aging

As the global population ages, there is increased interest in living longer and improving one's quality of life in later years. However, studying aging - the decline in body function - is expensive and time-consuming. And despite research success to make model organisms live longer, there still aren't really any feasible solutions for delaying aging in humans. With space travel, scientists couldn't know what it would take to get to the moon. They had to extrapolate from theory and shorter-range tests. Perhaps with aging, we need a similar moonshot philosophy. And though "shot" might imply medicine, perhaps we need to think beyond biological interventions. Like the moon, we seem a long way away from provable therapies to increase human healthspan (the healthy period of one's life) or lifespan (how long one lives). This review therefore focuses on radical proposals. We hope it might stimulate discussion on what we might consider doing significantly differently than ongoing aging research

Initial Findings on Visual Acuity Thresholds in an African Elephant (\u3cem\u3eLoxodonta africana\u3c/em\u3e)

There are only a few published examinations of elephant visual acuity. All involved Asian elephants (Elephas maximus) and found visual acuity to be between 8′ and 11′ of arc for a stimulus near the tip of the trunk, equivalent to a 0.50 cm gap, at a distance of about 2 m from the eyes. We predicted that African elephants (Loxodonta africana) would have similarly high visual acuity, necessary to facilitate eye-trunk coordination for feeding, drinking and social interactions. When tested on a discrimination task using Landolt-C stimuli, one African elephant cow demonstrated a visual acuity of 48′ of arc. This represents the ability to discriminate a gap as small as 2.75 cm in a stimulus 196 cm from the eye. This single-subject study provides a preliminary estimate of the visual acuity of African elephants

The 2008 Super Tuesday Tornado Outbreak: Synthetic Dual Doppler Analysis of Contrasting Tornadic Storm Types

During the Super Tuesday Tornado Outbreak on 5-6 February, a significant number of storms passed within about 40 km of WSR-88D radars. This distance, combined with the significant motion vector (from the southwest at 20-25 m per second) of relatively steady storms, is amenable to a synthetic dual Doppler analysis during the times when the storms passed the WSR-88D locations. Nine storms will be analyzed using the SDD technique. The following table provides their general characteristics and nearest approach to the 88D radars. For this data set, storm structure ranges from isolated supercell to QLCS. Each storm will be analyzed for a 40-60 min period during passage by the WSR-88D radar to determine general storm properties. Analysis of high-resolution single Doppler data around the time of passage (plus or minus 30 min), combined with 1-2 SDD analyses, will be used to examine the kinematic structure of low-level circulations (e.g., mesocyclone, downdraft) and the relation to the parent storm. This analysis may provide insights on the fundamental differences between cyclonic circulations in supercell storms and those within QCLS's

Surface and Buried Landmine Scene Generation and Validation Using the Digital Imaging and Remote Sensing Image Generation Model

Detection and neutralization of surface-laid and buried landmines has been a slow and dangerous endeavor for military forces and humanitarian organizations throughout the world. In an effort to make the process faster and safer, scientists have begun to exploit the ever-evolving passive electro-optical realm, both from a broadband perspective and a multi or hyperspectral perspective. Carried with this exploitation is the development of mine detection algorithms that take advantage of spectral features exhibited by mine targets, only available in a multi or hyperspectral data set. Difficulty in algorithm development arises from a lack of robust data, which is needed to appropriately test the validity of an algorithm’s results. This paper discusses the development of synthetic data using the Digital Imaging and Remote Sensing Image Generation (DIRSIG) model. A synthetic landmine scene has been modeled after data collected at a US Army arid testing site by the University of Hawaii’s Airborne Hyperspectral Imager (AHI). The synthetic data has been created and validated to represent the surrogate minefield thermally, spatially, spectrally, and temporally over the 7.9 to 11.5 micron region using 70 bands of data. Validation of the scene has been accomplished by direct comparison to the AHI truth data using qualitative band to band visual analysis, Rank Order Correlation comparison, Principle Components dimensionality analysis, and an evaluation of the R(x) algorithm’s performance. This paper discusses landmine detection phenomenology, describes the steps taken to build the scene, modeling methods utilized to overcome input parameter limitations, and compares the synthetic scene to truth data

Identification of a transporter complex responsible for the cytosolic entry of nitrogen-containing bisphosphonates

Nitrogen-containing-bisphosphonates (N-BPs) are widely prescribed to treat osteoporosis and other bone-related diseases. Although previous studies established that N-BPs function by inhibiting the mevalonate pathway in osteoclasts, the mechanism by which N-BPs enter the cytosol from the extracellular space to reach their molecular target is not understood. Here we implemented a CRISPRi-mediated genome-wide screen and identified SLC37A3 (solute carrier family 37 member A3) as a gene required for the action of N-BPs in mammalian cells. We observed that SLC37A3 forms a complex with ATRAID (all-trans retinoic acid-induced differentiation factor), a previously identified genetic target of N-BPs. SLC37A3 and ATRAID localize to lysosomes and are required for releasing N-BP molecules that have trafficked to lysosomes through fluid-phase endocytosis into the cytosol. Our results elucidate the route by which N-BPs are delivered to their molecular target, addressing a key aspect of the mechanism of action of N-BPs that may have significant clinical relevance

Studying the interface between croconic acid thin films and substrates using a slow positron beam

Croconic acid (CA) is the first organic ferroelectric with a spontaneous polarity in bulk samples comparable to its inorganic counterparts. As a natural extension of study, ultrathin CA films (∼nm scale) were investigated to reveal ferroelectric effects in films on different substrates for their fundamental and industrial significance. However, the void defect at the interface between the film and substrate is presumed to interfere with surface effects. In this work, a non-invasive technique, a slow positron beam, coupled with Doppler broadening energy spectroscopy (DBES), is applied to study the void defects within the interfacial layer between CA films and Si and SiO2 substrates. The effect of external electric field on defect formation is also investigated and an underlying mechanism is proposed

Recombinant Incretin-Secreting Microbe Improves Metabolic Dysfunction in High-Fat Diet Fed Rodents

peer-reviewedThe gut hormone glucagon-like peptide (GLP)-1 and its analogues represent a new generation of anti-diabetic drugs, which have also demonstrated propensity to modulate host lipid metabolism. Despite this, drugs of this nature are currently limited to intramuscular administration routes due to intestinal degradation. The aim of this study was to design a recombinant microbial delivery vector for a GLP-1 analogue and assess the efficacy of the therapeutic in improving host glucose, lipid and cholesterol metabolism in diet induced obese rodents. Diet-induced obese animals received either Lactobacillus paracasei NFBC 338 transformed to express a long-acting analogue of GLP-1 or the isogenic control microbe which solely harbored the pNZ44 plasmid. Short-term GLP-1 microbe intervention in rats reduced serum low-density lipoprotein cholesterol, triglycerides and triglyceride-rich lipoprotein cholesterol substantially. Conversely, extended GLP-1 microbe intervention improved glucose-dependent insulin secretion, glucose metabolism and cholesterol metabolism, compared to the high-fat control group. Interestingly, the microbe significantly attenuated the adiposity associated with the model and altered the serum lipidome, independently of GLP-1 secretion. These data indicate that recombinant incretin-secreting microbes may offer a novel and safe means of managing cholesterol metabolism and diet induced dyslipidaemia, as well as insulin sensitivity in metabolic dysfunction