Integrated Calendar

The pre-industrial Holocene is unique among pastinterglacials due to a modest, but notable increase inatmospheric CO2 and methane (CH4) during the latter halfof the period despite an expected decrease given orbitalparameters. Although the causes for this increase,anthropogenic or natural are debated, all climate modelssimulate an increase in global mean temperature inresponse to the increase in the greenhouse gases. Yet,many proxy reconstructions, interpreted to reflect themean annual temperatures, indicate peak temperatures inthe first half of the Holocene, arguably exceeding modernmean annual temperatures followed by cooling through thepreindustrial period. This significant model-datadiscrepancy, known as the Holocene temperatureconundrum, and the debate on the cause of the CO2increase has undermined confidence in future climatemodel predications. In this talk I’ll offer new perspectiveson both issues.

As life expectancy increases, age-related diseases are becoming more prevalent. While these conditions are traditionally studied in isolation, mounting evidence points to shared, systemic mechanisms underlying these conditions. Our research highlights the vasculature as  a key player in organ homeostasis and repair, and a system shared across all organs—making its dysfunction potential driver of age-related pathologies.We demonstrate that manipulating VEGF signaling to counteract age-related microvascular rarefaction promotes comprehensive geroprotection, preserving organ function and delaying disease onset. Our findings also reveal a link between vascular rarefaction and altered RNA splicing. While hypoxia-driven and age-related changes in alternative RNA splicing have been studied independently, we propose a unifying mechanism that links the two. To explore this further, we also employ patient-derived organoids, which retain their biological age in culture, providing a robust in vitro platform to test anti-aging interventions.Our findings support a vascular theory of aging, identifying vascular health as a promising target to mitigate age-related diseases and promote healthier aging.

While sexual dimorphisms in brain structure and function are well-documented across species, the specific features and mechanisms underlying sex differences in individual neurons and how these differences drive behavior remain largely unknown. Most research has focused on sex-specific neurons, limiting insight into how shared neural circuits diverge between sexes. Using C. elegans, we investigated sex differences in shared neuronal modules through two approaches: 1. To explore circuit-level sex differences we dissected the neuronal properties of a sexually dimorphic circuit shared by both sexes, focusing on the circuit responsible for mechanosensation (the detection of mechanical stimulation), specifically touch sensation, in both sexes of C. elegans. We discovered that touch is detected through a distinctly different set of neurons in each sex, and this process involves unique molecules and receptors that operate in a sex-specific manner. One of these key molecules is the ion channel TMC-1, critical for hearing in humans. This study identified for the first time that touch can be sensed differently by the two sexes of an organism. 2. To investigate genetic sex differences at the level of individual sex-shared neurons, we mapped the nervous system of C. elegans in both sexes using single-cell RNA sequencing. By analyzing gene expression patterns in the nervous system of both sexes derived from the transcriptomic profiles, we discovered novel sexually dimorphic neurons and their relevance to behavior and neuronal function. We further conducted computational analysis on our single-cell data set to predict synaptic connectivity regulators based on gene expression, leading to the identification of several candidate genes now under investigation. Taken together, our work revealed multiple cellular and molecular pathways that operate differently between the sexes, shedding light on how an organism's sexual identity shapes the organization of its nervous system.

N2 fixation is the primary pathway by which bioavailable nitrogen is added to theoceans. However, the drivers of N2 fixation on orbital timescales are uncertain. Wepresent high-resolution foraminifera-bound (FB) δ15N records from the Westernand Eastern tropical Atlantic Ocean (WTA and ETA respectively) throughout thelate Pliocene (~3.60 to ~1.97 Ma), where WTA ODP Site 999 represents N2fixation changes and EEA ODP Site 662 represents changes in pycnocline δ15N.Our results show that, compared to the past 160 ka, N2 fixation in the WTA wassignificantly lower throughout the late Pliocene as reflected by an average of ~2 ‰higher FB-δ15N values. A possible explanation to the higher Pliocene FB-δ15N inthe WTA could be lower rates of global denitrification that were balanced by lowerglobal N2 fixation levels. We suggest that this reduced N2 fixation was due todecreased excess P in the pycnocline/subsurface ocean, driven by lower globalwater column denitrification. This finding implies a coupling between decreasedwater column denitrification and reduced level N2 fixation rates under warmerclimates.On orbital timescales, our N2 fixation record display obliquity-paced cycles thatprogressively intensified after the Northern Hemisphere glaciation intensification ~2.8 Ma, and the onset of equatorial upwelling pulses documented during glacialperiods in the EEA (ODP Site 662; [1]). The observed changes in N2 fixation of thelast 160 ka were previously explained by precession-paced upwelling in the EEAthat imported excess P into the oligotrophic WTA [2]. However, precessionalcyclicity is not dominant in the Pliocene FB- δ15N, which calls for other candidatesto explain the variations after 2.8 Ma. The best explanation is a response to sealevelpaced sedimentary denitrification. Glacial lower sea levels exposedcontinental shelves, reducing regional benthic denitrification and inhibiting thesupply of excess P, thereby limiting N2 fixation in the WTA, whereas interglacialsubmerged shelves increased excess P availability.

Given two distributions P, Q and an integer t, we analyze two sampling processes. In "random allocation," we first sample an index i uniformly from [t], then draw r_{i} ~ P and r_{j} ~ Q for all other j in [t]. In "Poisson sampling," we independently draw r_{i} ~ 1/t*P + (1-1/t)*Q for each i in [t]. We bound the difference between these processes' output distributions and the baseline of sampling r_{i} ~ Q for all i.

This theoretical result provides key insights for analyzing DP-SGD, a privacy-preserving variant of stochastic gradient descent. While Poisson subsampling has well-understood privacy guarantees, common implementations use element shuffling, which was recently shown to have larger privacy losses in certain regimes. Random allocation offers a middle ground, and we prove its privacy analysis reduces to comparing the distributions described above.

We show that these variants' privacy guarantees are within a constant factor of each other across all parameter regimes and converge asymptotically in t. Our proof has two key components: decomposing Poisson sampling into a mixture of random allocation processes, and showing that random allocation can be viewed as a modified Poisson process where sampling probabilities depend on previous outputs.

Joint work with Vitaly Feldman

Moiré materials built on transition metal dichalcogenide semiconductors have emerged as a tunable platform for simulating the Hubbard model on a triangular lattice. A natural question arises: Can the platform be tuned to yield a phase diagram similar to that in high-temperature cuprate superconductors? In this talk, I will discuss the emergence of “high-temperature” superconductivity near the Mott transition in a triangular moiré lattice with intermediate coupling strength. The emergent doping-temperature phase diagram looks remarkably similar to that in cuprate superconductors. I will also discuss the evolution of the phase diagram by tuning the band structure of the material by gating. The results could provide a new angle for understanding the phenomenon of high-temperature superconductivity in strongly correlated materials.