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A concerted neuron–astrocyte program declines in ageing and schizophrenia
No full textHuman brains vary across people and over time; such variation is not yet understood in cellular terms. Here we describe a relationship between people’s cortical neurons and cortical astrocytes. We used single-nucleus RNA sequencing to analyse the prefrontal cortex of 191 human donors aged 22–97 years, including healthy individuals and people with schizophrenia. Latent-factor analysis of these data revealed that, in people whose cortical neurons more strongly expressed genes encoding synaptic components, cortical astrocytes more strongly expressed distinct genes with synaptic functions and genes for synthesizing cholesterol, an astrocyte-supplied component of synaptic membranes. We call this relationship the synaptic neuron and astrocyte program (SNAP). In schizophrenia and ageing—two conditions that involve declines in cognitive flexibility and plasticity —cells divested from SNAP: astrocytes, glutamatergic (excitatory) neurons and GABAergic (inhibitory) neurons all showed reduced SNAP expression to corresponding degrees. The distinct astrocytic and neuronal components of SNAP both involved genes in which genetic risk factors for schizophrenia were strongly concentrated. SNAP, which varies quantitatively even among healthy people of similar age, may underlie many aspects of normal human interindividual differences and may be an important point of convergence for multiple kinds of pathophysiology.Version of Recor
Advice for New York State and International Policymakers Regarding Sovereign Debt Reforms at the State Level
No full textThe possibility of sovereign debt legislation at the state level has been an underexplored area in sovereign debt policy—that is until the New York State Legislature became the center of serious contention over three proposed bills during the last two legislative sessions. The bills pitted social activists seeking to help relieve sovereign debts against bond-market organizations claiming that the bills would drive business out of New York State and raise the cost of financing for developing countries. Rhetoric flew and lobbying was intense. Yet a constructive outcome was achieved: two of the bills were dropped while the New York Senate passed the third bill after incorporating significant changes required by the market. The purpose of this working paper is to recount the legislative history of these three bills and to use their differing features—and outcomes—to draw policy rules regarding the appropriate scope of sovereign debt reforms carried out at the state level.Version of Recor
Top to Bottom: Best-case Standard Errors for Calibrated Model Parameters
No full textCalibration is a moment-matching procedure that selects the parameters of a structural model to match empirical moments drawn from potentially many different data sources. However, if the moments are diversely sourced, then their underlying correlation structure, which is necessary for the computation of standard errors of calibrated model parameters, is likely unknown. This paper derives a lower bound on the standard errors of calibrated model parameters which corresponds to the best-case standard errors using only the readily estimable point estimates and marginal variances of the empirical moments. We prove that the problem of finding the best-case standard errors is equivalent to solving a simple semidefinite program. We then compare this methodology to a procedure by Cocci and Plagborg-Møller (2023) that derives the worst-case standard errors. We apply both methodologies to two empirical applications: a model of multiproduct firms facing a price setting decision under a fixed menu cost and a heterogenous agent New Keynesian model
A New Spin on the Origin of Biological Homochirality
No full textEssential molecules of life—amino acids, nucleic acids, and sugars—are chiral; they exist in mirror-symmetrical pairs. However, biological systems exclusively use only one form of these pairs: right-handed sugars and nucleic acids, along with left-handed amino acids. This phenomenon characterizes life as homochiral. However, the origins of this asymmetry remain elusive, and it is this long-standing mystery that we address in this thesis.
The chiral-induced spin selectivity (CISS) effect has established a strong coupling between electron spin and molecular chirality and this coupling paves the way for breaking the chiral molecular symmetry by spin-selective processes. Achiral magnetic surfaces, when spin-polarized, can function as chiral agents due to the CISS effect, serving as templates for the asymmetric crystallization of chiral molecules.
In this thesis, we studied the spin-selective crystallization of racemic ribo-aminooxazoline (RAO), a central precursor of RNA, on magnetite surfaces—achieving homochirality in two crystallization steps. Moreover, we have shown the chirality-induced avalanche magnetization of magnetite by RAO molecules, which verifies the reciprocal nature of the effect and allows for a cooperative feedback between chiral molecules and magnetic surfaces. Finally, based on empirical evidence, we propose a pathway through which the achieved homochirality in a single chiral compound, RAO, can efficiently propagate throughout the entire prebiotic network, starting from D-nucleic acids, to L-peptides, and then to homochiral metabolites.
Our results demonstrate a prebiotically plausible way of achieving systems-level homochirality from completely racemic starting materials through a process initiated by the physical environment
Migrants can be a transformative force for sustainable development
No full textDrawing on findings from a PNAS Special Feature on Migration and Sustainability, organized by the authors and available (OA) here: https://www.pnas.org/topic/554Can the movement of people (including those displaced by climate change) aid sustainable solutions to environmental problems? Our research suggests that it can. Migration is good for society in circumstances when it reduces inequality, enhances overall wellbeing, and does not place greater environmental burdens on the regions where people move to or from
Exponentially Faster Submodular Maximization in Practice via Low Adaptivity Algorithms
No full textAcross machine learning, social network analysis, and algorithms, many fundamental objectives we care to optimize are submodular, such as influence, innovation diffusion, clustering, mutual information, feature selection, and data summarization. Whereas typical applications across these domains include problem instances defined on massive data sets, maximizing a submodular function subject to a cardinality constraint is NP-hard, and current state-of-the-art serial algorithms achieve an optimal approximation only after a number of queries that is linearly increasing in the size of the data.
Recently, there has been a great deal of research on parallel algorithms whose theoretical runtime on an idealized parallel machine is exponentially faster than algorithms used for submodular maximization over the past 40 years. However, it is computationally infeasible to use these algorithms in practice even on small data sets because the non-asymptotic number of iterations and queries they require depend on large constants and high-degree polynomials in terms of the precision and confidence of their approximations.
This dissertation describes a new parallel algorithm called Fast Adaptive Sequencing Technique (Fast) for maximizing a monotone submodular function under a cardinality constraint k. The design principles behind the Fast algorithm are a significant departure from those of recent theoretically fast algorithms. These design principles yield theoretic guarantees that are competitive with recent theoretically fast algorithms, but practical performance that is orders of magnitude faster than state-of-the-art algorithms used in practice. Specifically, Fast obtains an approximation that is arbitrarily close to the optimal 1 − 1/e guarantee in an asymptotic parallel runtime (adaptivity) that is O(log(n) log^2(log k)) using O(n log log(k)) total queries. In terms of practical parallel runtimes, we show that Fast is orders of magnitude faster than any known algorithm for submodular maximization, including hyper-optimized parallel versions of state-of-the-art serial algorithms, by running experiments on large data sets
Integrated Sources on Thin-Film Lithium Niobate
No full textPhotonic integrated circuits have played a crucial role in the miniaturization and efficiency improvement of many optical components. While many material platforms have played host to excellent photonic devices, in recent years, thin-film lithium niobate (TFLN) on insulator has emerged as a promising photonic platform, owing to its large electro-optic effect, low-loss waveguides, and wafer scalability. Devices on TFLN have witnessed remarkable developments over the past decade, most notably in the realization of high-bandwidth, high-efficiency, and low-loss electro-optic modulators. However, the excellent material properties of the TFLN platform extend beyond EO modulation, making it a candidate platform for many high performance chip-scale optical systems.
This dissertation presents work in bringing various functionalities of sources typically realized in bulk systems onto the TFLN platform. Among those included are on-chip pulse and frequency comb generation in lieu of bulk mode-locked lasers, high performance optical isolators using electro-optic modulation in lieu of bulk magneto-optic isolators, and an on-chip, narrow-linewidth extended cavity laser. Included is work involving an emerging technology known as photonic wire bonding, which shows promise as a future integration method to bridge platforms and functionalities.
The first half of the thesis concerns the manipulation of continuous-wave light for frequency comb sources. I start by presenting ultrashort pulse generation using cascaded electro-optic amplitude and phase modulators combined with off-chip dispersion, realized using two designs, the second of which is packaged using the novel photonic wire bonding scheme. I then show how, by interfacing the pulse generation chip with a high-Q resonator with matched free spectral range, broadband spectrum generation can occur with relatively low average on-chip power.
An outstanding challenge for future integrated photonic systems is in the implementation of on-chip gain, which usually involves integration of III-V semiconductor materials to realize integrated lasers and detectors. The second half of the thesis concerns the integration of high-performance lasers onto the TFLN platform. I show how an electro-optic TFLN phase modulator can be used to realize a high-performance, broadband, and low-loss optical isolator, which is a necessary component for any future work with on-chip lasers. Finally, I show the demonstration of a narrow-linewidth, high-power, tunable extended cavity diode laser using InP and TFLN and integrated using photonic wire bonding
Respect Your Elders? The Economic Origins and Political Consequences of Attitudes Toward the Aged
No full textRespect for elders (or lack thereof) is a central pillar of many social structures, where norms range from filial piety to geronticide. Despite their importance and substantial cultural variation, these beliefs are not well understood. What caused this variation, and what consequences do these beliefs have today? To answer this question, I create a measure of historical attitudes toward elders based on over 400 folklore motifs spanning 1,200 cultures. I first validate the persistence of this measure using data on modern beliefs, including on implicit bias and old-age mortality. Then, guided by models from evolutionary anthropology, I examine the hypothesis that the valuation of elders is related to the applicability of their experience within the next generation. Using environmental stability and the complexity of tradition as instruments, I provide estimates which suggest a causal interpretation of my results. Next, I examine contemporary consequences of these norms. First, I associate higher valuation of elders with older elected leaders at both the between- and within-country level. Motivated by the implication in my model that traditionalism and deference to elders makes gerontocracy more desirable, I show an association between positive norms toward elders and lower ancestral and contemporary democracy. I use this fact to motivate an instrumented mediation analysis model to further test my findings, and finally provide additional evidence by associating positive attitudes with a lower likelihood for the onset of democracy
Why Is Dollar Debt Cheaper? Evidence from Peru
No full textIn emerging markets, a significant share of corporate loans are denominated in dollars. Using novel data that enables us to see currency and the cost of credit, in addition to several other transaction-level characteristics, we re-examine the reasons behind dollar credit popularity. We find that a dollar-denominated loan has an interest rate that is 2% lower per year than a loan in Peruvian Soles. Expectations of exchange rate movements do not explain this difference. We show that this interest rate differential for lending rates is closely matched by the differential in the deposit market. Our results suggest that the preference for dollar loans is rooted on the local household preference for dollar savings and a banking sector that is closely matching its foreign assets and liabilities. We find that borrower competitive pressure increases the pass-through of this differential.Accepted Manuscrip
