Deep Big Simple Neural Nets Excel on Handwritten Digit Recognition

Good old on-line back-propagation for plain multi-layer perceptrons yields a very low 0.35% error rate on the famous MNIST handwritten digits benchmark. All we need to achieve this best result so far are many hidden layers, many neurons per layer, numerous deformed training images, and graphics cards to greatly speed up learning.Comment: 14 pages, 2 figures, 4 listing

Growth and Geographic Variation in Hospitalizations with Resistant Infections, United States, 2000–2005

From 2000 through 2005, hospitalizations with resistant infections (methicillin-resistant Staphylococcus aureus, Clostridium difficile–associated disease, vancomycin-resistant enterococcus, Pseudomonas aeruginosa, and Candida infection) nearly doubled, from 499,702 to 947,393. Regional variations noted in the aggregate and by individual infection may help clarify modifiable risk factors driving these infections

Calorie restriction does not elicit a robust extension of replicative lifespan in Saccharomyces cerevisiae

Calorie restriction (CR) is often described as the most robust manner to extend lifespan in a large variety of organisms. Hence, considerable research effort is directed toward understanding the mechanisms underlying CR, especially in the yeast Saccharomyces cerevisiae. However, the effect of CR on lifespan has never been systematically reviewed in this organism. Here, we performed a meta-analysis of replicative lifespan (RLS) data published in more than 40 different papers. Our analysis revealed that there is significant variation in the reported RLS data, which appears to be mainly due to the low number of cells analyzed per experiment. Furthermore, we found that the RLS measured at 2% (wt/vol) glucose in CR experiments is partly biased toward shorter lifespans compared with identical lifespan measurements from other studies. Excluding the 2% (wt/vol) glucose experiments from CR experiments, we determined that the average RLS of the yeast strains BY4741 and BY4742 is 25.9 buds at 2% (wt/vol) glucose and 30.2 buds under CR conditions. RLS measurements with a microfluidic dissection platform produced identical RLS data at 2% (wt/vol) glucose. However, CR conditions did not induce lifespan extension. As we excluded obvious methodological differences, such as temperature and medium, as causes, we conclude that subtle method-specific factors are crucial to induce lifespan extension under CR conditions in S. cerevisiae

Shortest-Path Network Analysis Is a Useful Approach toward Identifying Genetic Determinants of Longevity

Background Identification of genes that modulate longevity is a major focus of aging-related research and an area of intense public interest. In addition to facilitating an improved understanding of the basic mechanisms of aging, such genes represent potential targets for therapeutic intervention in multiple age-associated diseases, including cancer, heart disease, diabetes, and neurodegenerative disorders. To date, however, targeted efforts at identifying longevity-associated genes have been limited by a lack of predictive power, and useful algorithms for candidate gene-identification have also been lacking. Methodology/Principal Findings We have utilized a shortest-path network analysis to identify novel genes that modulate longevity in Saccharomyces cerevisiae. Based on a set of previously reported genes associated with increased life span, we applied a shortest-path network algorithm to a pre-existing protein–protein interaction dataset in order to construct a shortest-path longevity network. To validate this network, the replicative aging potential of 88 single-gene deletion strains corresponding to predicted components of the shortest-path longevity network was determined. Here we report that the single-gene deletion strains identified by our shortest-path longevity analysis are significantly enriched for mutations conferring either increased or decreased replicative life span, relative to a randomly selected set of 564 single-gene deletion strains or to the current data set available for the entire haploid deletion collection. Further, we report the identification of previously unknown longevity genes, several of which function in a conserved longevity pathway believed to mediate life span extension in response to dietary restriction. Conclusions/Significance This work demonstrates that shortest-path network analysis is a useful approach toward identifying genetic determinants of longevity and represents the first application of network analysis of aging to be extensively validated in a biological system. The novel longevity genes identified in this study are likely to yield further insight into the molecular mechanisms of aging and age-associated disease

Prime Focus Spectrograph (PFS) for the Subaru Telescope: Overview, recent progress, and future perspectives

PFS (Prime Focus Spectrograph), a next generation facility instrument on the 8.2-meter Subaru Telescope, is a very wide-field, massively multiplexed, optical and near-infrared spectrograph. Exploiting the Subaru prime focus, 2394 reconfigurable fibers will be distributed over the 1.3 deg field of view. The spectrograph has been designed with 3 arms of blue, red, and near-infrared cameras to simultaneously observe spectra from 380nm to 1260nm in one exposure at a resolution of ~1.6-2.7A. An international collaboration is developing this instrument under the initiative of Kavli IPMU. The project is now going into the construction phase aiming at undertaking system integration in 2017-2018 and subsequently carrying out engineering operations in 2018-2019. This article gives an overview of the instrument, current project status and future paths forward.Comment: 17 pages, 10 figures. Proceeding of SPIE Astronomical Telescopes and Instrumentation 201

Treatment of gram-positive deep sternal wound infections in cardiac surgery -experiences with daptomycin-

The reported incidence of deep sternal wound infection (DSWI) after cardiac surgery is 0.4-5% with Staphylococcus aureus being the most common pathogen isolated from infected wound sternotomies and bacteraemic blood cultures. This infection is associated with a higher morbidity and mortality than other known aetiologies. Little is reported about the optimal antibiotic management. The aim of the study is to quantify the application of daptomycin treatment of DSWI due to gram-positive organisms post cardiac surgery

Role of CBP and SATB-1 in Aging, Dietary Restriction, and Insulin-Like Signaling

Increased transcriptional complex activity, or pharmacological mimics of increased complex activity, predict lifespan in mice and mediate the protective effects of dietary restriction during aging

Elevated Proteasome Capacity Extends Replicative Lifespan in Saccharomyces cerevisiae

Aging is characterized by the accumulation of damaged cellular macromolecules caused by declining repair and elimination pathways. An integral component employed by cells to counter toxic protein aggregates is the conserved ubiquitin/proteasome system (UPS). Previous studies have described an age-dependent decline of proteasomal function and increased longevity correlates with sustained proteasome capacity in centenarians and in naked mole rats, a long-lived rodent. Proof for a direct impact of enhanced proteasome function on longevity, however, is still lacking. To determine the importance of proteasome function in yeast aging, we established a method to modulate UPS capacity by manipulating levels of the UPS–related transcription factor Rpn4. While cells lacking RPN4 exhibit a decreased non-adaptable proteasome pool, loss of UBR2, an ubiquitin ligase that regulates Rpn4 turnover, results in elevated Rpn4 levels, which upregulates UPS components. Increased UPS capacity significantly enhances replicative lifespan (RLS) and resistance to proteotoxic stress, while reduced UPS capacity has opposing consequences. Despite tight transcriptional co-regulation of the UPS and oxidative detoxification systems, the impact of proteasome capacity on lifespan is independent of the latter, since elimination of Yap1, a key regulator of the oxidative stress response, does not affect lifespan extension of cells with higher proteasome capacity. Moreover, since elevated proteasome capacity results in improved clearance of toxic huntingtin fragments in a yeast model for neurodegenerative diseases, we speculate that the observed lifespan extension originates from prolonged elimination of damaged proteins in old mother cells. Epistasis analyses indicate that proteasome-mediated modulation of lifespan is at least partially distinct from dietary restriction, Tor1, and Sir2. These findings demonstrate that UPS capacity determines yeast RLS by a mechanism that is distinct from known longevity pathways and raise the possibility that interventions to promote enhanced proteasome function will have beneficial effects on longevity and age-related disease in humans

The MDT-15 Subunit of Mediator Interacts with Dietary Restriction to Modulate Longevity and Fluoranthene Toxicity in Caenorhabditis elegans

Dietary restriction (DR), the limitation of calorie intake while maintaining proper nutrition, has been found to extend life span and delay the onset of age-associated disease in a wide range of species. Previous studies have suggested that DR can reduce the lethality of environmental toxins. To further examine the role of DR in toxin response, we measured life spans of the nematode Caenorhabditis elegans treated with the mutagenic polyaromatic hydrocarbon, fluoranthene (FLA). FLA is a direct byproduct of combustion, and is one of U.S. Environmental Protection Agency's sixteen priority environmental toxins. Treatment with 5 µg/ml FLA shortened the life spans of ad libitum fed nematodes, and DR resulted in increased sensitivity to FLA. To determine the role of detoxifying enzymes in the toxicity of FLA, we tested nematodes with mutations in the gene encoding the MDT-15 subunit of mediator, a transcriptional coactivator that regulates genes involved in fatty acid metabolism and detoxification. Mutation of mdt-15 increased the life span of FLA treated animals compared to wild-type animals with no difference observed between DR and ad libitum fed mdt-15 animals. We also examined mutants with altered insulin-IGF-1-like signaling (IIS), which is known to modulate life span and stress resistance in C. elegans independently of DR. Mutation of the genes coding for the insulin-like receptor DAF-2 or the FOXO-family transcription factor DAF16 did not alter the animals' susceptibility to FLA compared to wild type. Taken together, our results suggest that certain compounds have increased toxicity when combined with a DR regimen through increased metabolic activation. This increased metabolic activation appears to be mediated through the MDT-15 transcription factor and is independent of the IIS pathway

Simple model systems: a challenge for Alzheimer's disease

The success of biomedical researches has led to improvement in human health and increased life expectancy. An unexpected consequence has been an increase of age-related diseases and, in particular, neurodegenerative diseases. These disorders are generally late onset and exhibit complex pathologies including memory loss, cognitive defects, movement disorders and death. Here, it is described as the use of simple animal models such as worms, fishes, flies, Ascidians and sea urchins, have facilitated the understanding of several biochemical mechanisms underlying Alzheimer's disease (AD), one of the most diffuse neurodegenerative pathologies. The discovery of specific genes and proteins associated with AD, and the development of new technologies for the production of transgenic animals, has helped researchers to overcome the lack of natural models. Moreover, simple model systems of AD have been utilized to obtain key information for evaluating potential therapeutic interventions and for testing efficacy of putative neuroprotective compounds