152 research outputs found

    Sost and its paralog Sostdc1 coordinate digit number in a Gli3-dependent manner.

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    WNT signaling is critical in most aspects of skeletal development and homeostasis, and antagonists of WNT signaling are emerging as key regulatory proteins with great promise as therapeutic agents for bone disorders. Here we show that Sost and its paralog Sostdc1 emerged through ancestral genome duplication and their expression patterns have diverged to delineate non-overlapping domains in most organ systems including musculoskeletal, cardiovascular, nervous, digestive, reproductive and respiratory. In the developing limb, Sost and Sostdc1 display dynamic expression patterns with Sost being restricted to the distal ectoderm and Sostdc1 to the proximal ectoderm and the mesenchyme. While Sostdc1(-/-) mice lack any obvious limb or skeletal defects, Sost(-/-) mice recapitulate the hand defects described for Sclerosteosis patients. However, elevated WNT signaling in Sost(-/-); Sostdc1(-/-) mice causes misregulation of SHH signaling, ectopic activation of Sox9 in the digit 1 field and preaxial polydactyly in a Gli1- and Gli3-dependent manner. In addition, we show that the syndactyly documented in Sclerosteosis is present in both Sost(-/-) and Sost(-/-); Sostdc1(-/-) mice, and is driven by misregulation of Fgf8 in the AER, a region lacking Sost and Sostdc1 expression. This study highlights the complexity of WNT signaling in skeletal biology and disease and emphasizes how redundant mechanism and non-cell autonomous effects can synergize to unveil new intricate phenotypes caused by elevated WNT signaling

    The AGE Presents Introduction to Geroscience video lecture series.

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    The AGE Presents Introduction to Geroscience video lecture series is a collection of high-quality didactic video lectures and associated teaching materials focused on foundational topics in aging biology. The videos are made freely available on YouTube and are targeted toward an audience familiar with concepts learned in the first year of a college undergraduate biology/biomedical major. Members of the American Aging Association also receive the original lecture slides and lecture notes, with additional course materials to be developed in the future. We expect that these lectures will enhance understanding of geroscience among the general public while also providing tools that educators can use in the classroom for high school, undergraduate, and graduate level curricula

    Toward a Core Design to Distribute an Execution on a Many-Core Processor

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    International audienceThis paper presents a parallel execution model and a many-core processor design to run C programs in parallel. The model automatically builds parallel sections of machine instructions from the run trace. It parallelizes instructions fetches, renamings, executions and retirements. Predictor based fetch is replaced by a fetch-decode-and-partly-execute stage able to compute in-order most of the control instructions. Tomasulo's register renaming is extended to memory with a technique to match consumer/producer pairs. The Reorder Buffer is adapted to allow parallel retirement. The model is presented on a sum reduction example which is also used to give a short analytical evaluation of the model performance potential

    ParaDIME: Parallel Distributed Infrastructure for Minimization of Energy for data centers

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    Dramatic environmental and economic impact of the ever increasing power and energy consumption of modern computing devices in data centers is now a critical challenge. On the one hand, designers use technology scaling as one of the methods to face the phenomenon called dark silicon (only segments of a chip function concurrently due to power restrictions). On the other hand, designers use extreme-scale systems such as teradevices to meet the performance needs of their applications which in turn increases the power consumption of the platform. In order to overcome these challenges, we need novel computing paradigms that address energy efficiency. One of the promising solutions is to incorporate parallel distributed methodologies at different abstraction levels. The FP7 project ParaDIME focuses on this objective to provide different distributed methodologies (software-hardware techniques) at different abstraction levels to attack the power-wall problem. In particular, the ParaDIME framework will utilize: circuit and architecture operation below safe voltage limits for drastic energy savings, specialized energy-aware computing accelerators, heterogeneous computing, energy-aware runtime, approximate computing and power-aware message passing. The major outcome of the project will be a noval processor architecture for a heterogeneous distributed system that utilizes future device characteristics, runtime and programming model for drastic energy savings of data centers. Wherever possible, ParaDIME will adopt multidisciplinary techniques, such as hardware support for message passing, runtime energy optimization utilizing new hardware energy performance counters, use of accelerators for error recovery from sub-safe voltage operation, and approximate computing through annotated code. Furthermore, we will establish and investigate the theoretical limits of energy savings at the device, circuit, architecture, runtime and programming model levels of the computing stack, as well as quantify the actual energy savings achieved by the ParaDIME approach for the complete computing stack with the real environment

    Using TMS to evaluate a causal role for right posterior temporal cortex in talker-specific phonetic processing

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    Available online 21 April 2023Theories suggest that speech perception is informed by listeners’ beliefs of what phonetic variation is typical of a talker. A previous fMRI study found right middle temporal gyrus (RMTG) sensitivity to whether a phonetic variant was typical of a talker, consistent with literature suggesting that the right hemisphere may play a key role in conditioning phonetic identity on talker information. The current work used transcranial magnetic stimulation (TMS) to test whether the RMTG plays a causal role in processing talker-specific phonetic variation. Listeners were exposed to talkers who differed in how they produced voiceless stop consonants while TMS was applied to RMTG, left MTG, or scalp vertex. Listeners subsequently showed near-ceiling performance in indicating which of two variants was typical of a trained talker, regardless of previous stimulation site. Thus, even though the RMTG is recruited for talker-specific phonetic processing, modulation of its function may have only modest consequences.This research was supported by NSF 1554810 (PI: EBM), NIH NIDCD 2R01 DC013064 (PI: EBM) and NSF NRT 1747486 (PI: JSM). This research was supported in part by the Basque Government through the BERC 2022–2025 program, by the Spanish State Research Agency through BCBL Severo Ochoa excellence accreditation CEX2020-001010- S and award PID2020-119131 GB-I000

    The Portrayal of Complementary and Alternative Medicine in Mass Print Magazines Since 1980

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    Objectives: The objectives of this study were to examine and describe the portrayal of complementary and alternative medicine (CAM) in mass print media magazines. Design: The sample included all 37 articles found in magazines with circulation rates of greater than 1 million published in the United States and Canada from 1980 to 2005. The analysis was quantitative and qualitative and included investigation of both manifest and latent magazine story messages. Results: Manifest analysis noted that CAM was largely represented as a treatment for a patient with a medically diagnosed illness or specific symptoms. Discussions used biomedical terms such as patient rather than consumer and disease rather than wellness. Latent analysis revealed three themes: (1) CAMs were described as good but not good enough; (2) individualism and consumerism were venerated; and (3) questions of costs were raised in the context of confusion and ambivalence
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