巴黎五大学

While foundation models have revolutionized various domains, their application to time series classification remains rather under-explored, with existing literature predominantly focused on forecasting. To bridge this gap, we introduce \textbf{Mantis}, a transformer-based foundation model pre-trained exclusively on synthetic data via self-supervised contrastive learning. We demonstrate that effective tokenization is critical to unlocking the full potential of transformers, proposing a novel token generator unit. Furthermore, we introduce an enhanced test-time methodology that bridges the performance gap between Mantis and strong specialized approaches by leveraging intermediate-layer representations, self-ensembling, and cross-model embedding fusion. Extensive experiments demonstrate that Mantis establishes a new state-of-the-art, outperforming existing foundation models across four diverse dataset collections covering various application domains.

The zero-shot evaluation of time series foundation models (TSFMs) for classification typically uses a frozen encoder followed by a task-specific classifier. However, this practice violates the training-free premise of zero-shot deployment and introduces evaluation bias due to classifier-dependent training choices. To address this issue, we propose TIC-FM, an in-context learning framework that treats the labeled training set as context and predicts labels for all test instances in a single forward pass, without parameter updates. TIC-FM pairs a time series encoder and a lightweight projection adapter with a split-masked latent memory Transformer. We further provide theoretical justification that in-context inference can subsume trained classifiers and can emulate gradient-based classifier training within a single forward pass. Experiments on 128 UCR datasets show strong accuracy, with consistent gains in the extreme low-label situation, highlighting training-free transfer

Prostate cancer (PCa)-related deaths are mainly due to metastasis. The increase in de novo metastatic hormone-naive PCa (mHNPCs) highlights the urgent need for biomarkers and treatment strategies. We report in a cohort of French PCa patients that the levels of vitamin D and of prostate-specific antigen, the progression biomarker used clinically, are negatively associated. However, the impact of vitamin D receptor (VDR) signaling on prostate tumorigenesis remains unclear. Mice with PTEN inactivation in prostatic epithelial cells (PECs) at adulthood (Pten(i)pe-/- mice) faithfully recapitulate the human disease. We showed that inactivation of PTEN and VDR in PECs promotes tumor aggressiveness. We demonstrate that VDR loss induces oxidative stress, which in turn enhances PECs proliferation. Moreover, CXCL5 overexpression in PTEN- and VDR-deficient PECs promotes neutrophil infiltration. Importantly, our data highlight elevated circulating neutrophil levels as a biomarker of PCa dissemination and show the potency of targeting neutrophil chemotaxis to reduce liver micrometastases. Overall, this work provides major insights into how vitamin D signaling slows down tumorigenesis and opens new avenues for therapeutic and diagnostic strategies for mHNPC.

The coupled Arctic system is in rapid transition and is set to undergo further dramatic changes over the coming decades. These changes will lead most likely to an ice-free ocean in summer, expected before mid-century. The Arctic will become more strongly influenced by atmospheric and oceanographic processes characteristic of mid-latitudes, increasing the prevalence of contaminants and new biological species. This ongoing transition of the Arctic to a new state necessitates systematic monitoring of all sentinels (variables that make an essential contribution to characterizing the Earth's state) to improve our understanding of the system, enhance forecasting and support knowledge-based decisions. Here, we describe a sustained multi-decadal observation program to be implemented on the Tara Polar Station between 2026 and 2046. The monitoring program is designed as a series of year-long drift expeditions, called Tara Polaris, in the central Arctic Ocean, covering all seasons. The multidisciplinary data will bridge ecological, geochemical, biological, and physical parameters and processes in the atmosphere, sea ice and ocean. In addition, data collected with consistent methodologies over a 20-year period will make it possible to distinguish long-term trends from seasonal and interannual variability. In this paper, we discuss specific measurement challenges in each compartment (i.e., atmosphere, sea ice and ocean) along key sentinels and the most pressing scientific questions to be addressed. The expected outcomes of the Tara Polaris program will enable us to understand and quantify the main feedbacks of the coupled Arctic system, with their seasonal and interannual trends and spatial variability.

The worldwide incidence of type 1 diabetes continues to rise at an alarming rate. One hundred years after the introduction of insulin, the long-entertained hope of moving from symptomatic treatment to disease-modifying therapies is finally taking shape with regulatory approval of teplizumab to delay the onset of stage 3 disease. Here we review teplizumab’s mechanism of action, setting it against the background of emerging disease-modifying therapies for clinical practice, in language accessible to practicing clinicians. A clinical diagnosis of type 1 diabetes and insulin dependence results from progressive autoimmune destruction of pancreatic β-cells as part of a complicated dialogue between the immune system and the islet. Infusion with teplizumab, a humanized monoclonal antibody that binds the ε-chain of the T lymphocyte CD3 molecule, delays progression from stage 2 to clinical stage 3 type 1 diabetes by almost 3 years. The mechanism of action of teplizumab involves partial agonistic signaling via CD3/TCR and subsequent deactivation, promoting exhaustion of pancreatic β-cell-reactive CD8+ T lymphocytes and induction of regulatory T lymphocytes, thereby restoring self-tolerance. With regulatory approval of this agent, clinical practice has entered a new era for treating people with type 1 diabetes, in which disease modification can become the new standard of care. Implementation of global screening for autoantibodies and dysglycemia is underway, enabling efforts to intervene during asymptomatic stages of the disease before insulin treatment is required.