Lifeboat Foundation

Chengyi wang*, sanyuan chen*, yu wu*, ziqiang zhang, long zhou, shujie liu, zhuo chen, yanqing liu, huaming wang, jinyu li, lei he, sheng zhao, furu wei.

Microsoft

Abstract. We introduce a language modeling approach for text to speech synthesis (TTS). Specifically, we train a neural codec language model (called VALL-E) using discrete codes derived from an off-the-shelf neural audio codec model, and regard TTS as a conditional language modeling task rather than continuous signal regression as in previous work. During the pre-training stage, we scale up the TTS training data to 60K hours of English speech which is hundreds of times larger than existing systems. VALL-E emerges in-context learning capabilities and can be used to synthesize high-quality personalized speech with only a 3-second enrolled recording of an unseen speaker as an acoustic prompt. Experiment results show that VALL-E significantly outperforms the state-of-the-art zero-shot TTS system in terms of speech naturalness and speaker similarity. In addition, we find VALL-E could preserve the speaker’s emotion and acoustic environment of the acoustic prompt in synthesis.

Patreon: https://www.patreon.com/seanmcarroll.
Blog post with audio player, show notes, and transcript: https://www.preposterousuniverse.com/podcast/2022/02/07/183-…e-physics/

Modern particle physics is a victim of its own success. We have extremely good theories — so good that it’s hard to know exactly how to move beyond them, since they agree with all the experiments. Yet, there are strong indications from theoretical considerations and cosmological data that we need to do better. But the leading contenders, especially supersymmetry, haven’t yet shown up in our experiments, leading some to wonder whether anthropic selection is a better answer. Michael Dine gives us an expert’s survey of the current situation, with pointers to what might come next.

Continue reading “Mindscape 183 | Michael Dine on Supersymmetry, Anthropics, and the Future of Particle Physics” »

Last week, Rice University in Houston announced that one of its assistant professors of bioengineering, Jerzy Szablowski, received a Young Faculty Award from DARPA to research non-genetic drugs that can “temporarily enhance the human body’s resilience to extreme cold exposure.”

Thermogenesis is the use of energy to create heat, and our bodies have two different ways of doing this. One is shivering, which we’re all familiar with. The other, which Szablowski simply calls non-shivering thermogenesis, involves burning off brown adipose tissue (BAT), or brow n fat.

This type of fat exists specifically to warm us up when we get cold; it stores energy and only activates in cold temperatures. Most of our body fat is white fat. It builds up when we ingest more calories than we burn and stores those calories for when we don’t get enough energy from food. An unfortunate majority of American adults have the opposite problem: too much white fat, which increases the risk of conditions like heart disease and Type 2 diabetes.

Molecular detective work is zeroing in on the origins of sexual reproduction. The protein tools for cell mergers seem to have long predated sex — so what were they doing?

Cellular reprogramming builds on the Nobel Prize-winning work of Shinya Yamanaka, who showed that adult cells could be transformed back into stem cells by exposing them to a specific set of genome-regulating proteins known as transcription factors. The Salk team’s innovation was to reduce the exposure times to the so-called Yamanaka factors, which they found could reverse epigenetic changes to the cells without reverting them to stem cells.

While the approach led to clear increases in lifespan in prematurely aging mice, the fact that no one had been able to replicate the result in healthy mice since then raised doubts about the approach. “Different groups have tried this experiment, and the data have not been positive so far,” Alejandro Ocampo, from the University of Lausanne in Switzerland, who carried out the original Salk experiments, told MIT Technology Review.

But now, Rejuvenate Bio claims that when they exposed healthy mice near the end of their lives to a subset of the Yamanaka factors, they lived for another 18 weeks on average, compared to just 9 weeks for those that didn’t undergo cellular reprogramming.

Using the James Webb Space Telescope, scientists say they’ve now observed galaxies from when the universe was just 330 million years old.

Aging is a complex process best characterized as the chronic dysregulation of cellular processes leading to deteriorated tissue and organ function. While aging cannot currently be prevented, its impact on lifespan and healthspan in the elderly can potentially be minimized by interventions that aim to return these cellular processes to optimal function. Recent studies have demonstrated that partial reprogramming using the Yamanaka factors (or a subset; OCT4, SOX2, and KLF4; OSK) can reverse age-related changes in vitro and in vivo. However, it is still unknown whether the Yamanaka factors (or a subset) are capable of extending the lifespan of aged wild type mice. Here, we show that systemically delivered AAVs, encoding an inducible OSK system, in 124-week-old mice extends the median remaining lifespan by 109% over wild-type controls and enhances several health parameters. Importantly, we observed a significant improvement in frailty scores indicating that we were able to improve the healthspan along with increasing the lifespan. Furthermore, in human keratinocytes expressing exogenous OSK, we observed significant epigenetic markers of age-reversal, suggesting a potential reregulation of genetic networks to a younger, potentially healthier state. Together, these results may have important implications for the development of partial reprogramming interventions to reverse age-associated diseases in the elderly.

All authors performed the work while employed at Rejuvenate Bio Inc. Rejuvenate Bio is a therapeutics company translating gene therapies to treat age-related diseases.

Year 2017 face_with_colon_three

Biological molecules, like organisms themselves, are subject to genetic drift and may even become “extinct”. Molecules that are no longer extant in living systems are of high interest for several reasons including insight into how existing life forms evolved and the possibility that they may have new and useful properties no longer available in currently functioning molecules. Predicting the sequence/structure of such molecules and synthesizing them so that their properties can be tested is the basis of “molecular resurrection” and may lead not only to a deeper understanding of evolution, but also to the production of artificial proteins with novel properties and even to insight into how life itself began.

Year 2013 face_with_colon_three

Francisco José Soler Gil, Manuel Alfonseca, Fine Tuning Explained? Multiverses and Cellular Automata, Journal for General Philosophy of Science / Zeitschrift für allgemeine Wissenschaftstheorie, Vol. 44, No. 1 (July 2013), pp. 153–172.