Mismatch and synchronization:Influence of asymmetries in systems of two delay-coupled lasers

We study the synchronization properties of the delay dynamics of two identical semiconductor lasers coupled through a semitransparent mirror. Via an analytical and numerical approach, we investigate the influence of asymmetries, in particular mismatches of self- and cross-coupling strength and differences in self- and cross-coupling delay. We show that the former mismatch affects the stability of the zero-lag state but not the dynamics within the synchronization manifold, while the latter mismatch does not affect the quality of synchronization but alters the dynamics significantly. Our results are extended to different unidirectional coupling schemes. This is highly relevant for communication schemes utilizing chaotic dynamics. Finally, the influence of nonlinear gain saturation on the dynamics and stability of synchronization is discussed

Solution Structure of a CUE-Ubiquitin Complex Reveals a Conserved Mode of Ubiquitin Binding

AbstractMonoubiquitination serves as a regulatory signal in a variety of cellular processes. Monoubiquitin signals are transmitted by binding to a small but rapidly expanding class of ubiquitin binding motifs. Several of these motifs, including the CUE domain, also promote intramolecular monoubiquitination. The solution structure of a CUE domain of the yeast Cue2 protein in complex with ubiquitin reveals intermolecular interactions involving conserved hydrophobic surfaces, including the Leu8-Ile44-Val70 patch on ubiquitin. The contact surface extends beyond this patch and encompasses Lys48, a site of polyubiquitin chain formation. This suggests an occlusion mechanism for inhibiting polyubiquitin chain formation during monoubiquitin signaling. The CUE domain shares a similar overall architecture with the UBA domain, which also contains a conserved hydrophobic patch. Comparative modeling suggests that the UBA domain interacts analogously with ubiquitin. The structure of the CUE-ubiquitin complex may thus serve as a paradigm for ubiquitin recognition and signaling by ubiquitin binding proteins

The impact of bark beetle infestations on monoterpene emissions and secondary organic aerosol formation in western North America

Over the last decade, extensive beetle outbreaks in western North America have destroyed over 100 000 km2 of forest throughout British Columbia and the western United States. Beetle infestations impact monoterpene emissions through both decreased emissions as trees are killed (mortality effect) and increased emissions in trees under attack (attack effect). We use 14 yr of beetle-induced tree mortality data together with beetle-induced monoterpene emission data in the National Center for Atmospheric Research (NCAR) Community Earth System Model (CESM) to investigate the impact of beetle-induced tree mortality and attack on monoterpene emissions and secondary organic aerosol (SOA) formation in western North America. Regionally, beetle infestations may have a significant impact on monoterpene emissions and SOA concentrations, with up to a 4-fold increase in monoterpene emissions and up to a 40% increase in SOA concentrations in some years (in a scenario where the attack effect is based on observed lodgepole pine response). Responses to beetle attack depend on the extent of previous mortality and the number of trees under attack in a given year, which can vary greatly over space and time. Simulated enhancements peak in 2004 (British Columbia) and 2008 (US). Responses to beetle attack are shown to be substantially larger (up to a 3-fold localized increase in summertime SOA concentrations) in a scenario based on bark-beetle attack in spruce trees. Placed in the context of observations from the IMPROVE network, the changes in SOA concentrations due to beetle attack are in most cases small compared to the large annual and interannual variability in total organic aerosol which is driven by wildfire activity in western North America. This indicates that most beetle-induced SOA changes are not likely detectable in current observation networks; however, these changes may impede efforts to achieve natural visibility conditions in the national parks and wilderness areas of the western United States.National Science Foundation (U.S.) (ATM- 0929282)National Science Foundation (U.S.) (ATM-0939021)National Science Foundation (U.S.) (ATM-0938940)United States. Dept. of Energy. Office of Scienc

Observations and assessment of forest carbon dynamics following disturbance in North America

Disturbance processes of various types substantially modify ecosystem carbon dynamics both temporally and spatially, and constitute a fundamental part of larger landscape-level dynamics. Forests typically lose carbon for several years to several decades following severe disturbance, but our understanding of the duration and dynamics of post-disturbance forest carbon fluxes remains limited. Here we capitalize on a recent North American Carbon Program disturbance synthesis to discuss techniques and future work needed to better understand carbon dynamics after forest disturbance. Specifically, this paper addresses three topics: (1) the history, spatial distribution, and characteristics of different types of disturbance (in particular fire, insects, and harvest) in North America; (2) the integrated measurements and experimental designs required to quantify forest carbon dynamics in the years and decades after disturbance, as presented in a series of case studies; and (3) a synthesis of the greatest uncertainties spanning these studies, as well as the utility of multiple types of observations (independent but mutually constraining data) in understanding their dynamics. The case studies—in the southeast U.S., central boreal Canada, U.S. Rocky Mountains, and Pacific Northwest—explore how different measurements can be used to constrain and understand carbon dynamics in regrowing forests, with the most important measurements summarized for each disturbance type. We identify disturbance severity and history as key but highly uncertain factors driving post-disturbance carbon source-sink dynamics across all disturbance types. We suggest that imaginative, integrative analyses using multiple lines of evidence, increased measurement capabilities, shared models and online data sets, and innovative numerical algorithms hold promise for improved understanding and prediction of carbon dynamics in disturbance-prone forests

A Conditional Yeast E1 Mutant Blocks the Ubiquitin–Proteasome Pathway and Reveals a Role for Ubiquitin Conjugates in Targeting Rad23 to the Proteasome

E1 ubiquitin activating enzyme catalyzes the initial step in all ubiquitin-dependent processes. We report the isolation of uba1-204, a temperature-sensitive allele of the essential Saccharomyces cerevisiae E1 gene, UBA1. Uba1-204 cells exhibit dramatic inhibition of the ubiquitin–proteasome system, resulting in rapid depletion of cellular ubiquitin conjugates and stabilization of multiple substrates. We have employed the tight phenotype of this mutant to investigate the role ubiquitin conjugates play in the dynamic interaction of the UbL/UBA adaptor proteins Rad23 and Dsk2 with the proteasome. Although proteasomes purified from mutant cells are intact and proteolytically active, they are depleted of ubiquitin conjugates, Rad23, and Dsk2. Binding of Rad23 to these proteasomes in vitro is enhanced by addition of either free or substrate-linked ubiquitin chains. Moreover, association of Rad23 with proteasomes in mutant and wild-type cells is improved upon stabilizing ubiquitin conjugates with proteasome inhibitor. We propose that recognition of polyubiquitin chains by Rad23 promotes its shuttling to the proteasome in vivo

From Human Days to Machine Seconds: Automatically Answering and Generating Machine Learning Final Exams

A final exam in machine learning at a top institution such as MIT, Harvard, or Cornell typically takes faculty days to write, and students hours to solve. We demonstrate that large language models pass machine learning finals at a human level, on finals available online after the models were trained, and automatically generate new human-quality final exam questions in seconds. Previous work has developed program synthesis and few-shot learning methods to solve university-level problem set questions in mathematics and STEM courses. In this work, we develop and compare methods that solve final exams, which differ from problem sets in several ways: the questions are longer, have multiple parts, are more complicated, and span a broader set of topics. We curate a dataset and benchmark of questions from machine learning final exams available online and code for answering these questions and generating new questions. We show how to generate new questions from other questions and course notes. For reproducibility and future research on this final exam benchmark, we use automatic checkers for multiple-choice, numeric, and questions with expression answers. We perform ablation studies comparing zero-shot learning with few-shot learning and chain-of-thought prompting using GPT-3, OPT, Codex, and ChatGPT across machine learning topics and find that few-shot learning methods perform best. We highlight the transformative potential of language models to streamline the writing and solution of large-scale assessments, significantly reducing the workload from human days to mere machine seconds. Our results suggest that rather than banning large language models such as ChatGPT in class, instructors should teach students to harness them by asking students meta-questions about correctness, completeness, and originality of the responses generated, encouraging critical thinking in academic studies.Comment: 9 page

Inefficient Quality Control of Thermosensitive Proteins on the Plasma Membrane

BACKGROUND: Misfolded proteins are generally recognised by cellular quality control machinery, which typically results in their ubiquitination and degradation. For soluble cytoplasmic proteins, degradation is mediated by the proteasome. Membrane proteins that fail to fold correctly are subject to ER associated degradation (ERAD), which involves their extraction from the membrane and subsequent proteasome-dependent destruction. Proteins with abnormal transmembrane domains can also be recognised in the Golgi or endosomal system and targeted for destruction in the vacuole/lysosome. It is much less clear what happens to membrane proteins that reach their destination, such as the cell surface, and then suffer damage. METHODOLOGY/PRINCIPAL FINDINGS: We have tested the ability of yeast cells to degrade membrane proteins to which temperature-sensitive cytoplasmic alleles of the Ura3 protein or of phage lambda repressor have been fused. In soluble form, these proteins are rapidly degraded upon temperature shift, in part due to the action of the Doa10 and San1 ubiquitin ligases and the proteasome. When tethered to the ER protein Use1, they are also degraded. However, when tethered to a plasma membrane protein such as Sso1 they escape degradation, either in the vacuole or by the proteasome. CONCLUSIONS/SIGNIFICANCE: Membrane proteins with a misfolded cytoplasmic domain appear not to be efficiently recognised and degraded once they have escaped the ER, even though their defective domains are exposed to the cytoplasm and potentially to cytoplasmic quality controls. Membrane tethering may provide a way to reduce degradation of unstable proteins

Monoubiquitination of syntaxin 3 leads to retrieval from the basolateral plasma membrane and facilitates cargo recruitment to exosomes

Syntaxin 3 (Stx3), a SNARE protein located and functioning at the apical plasma membrane of epithelial cells, is required for epithelial polarity. A fraction of Stx3 is localized to late endosomes/lysosomes, although how it traffics there and its function in these organelles is unknown. Here we report that Stx3 undergoes monoubiquitination in a conserved polybasic domain. Stx3 present at the basolateral—but not the apical—plasma membrane is rapidly endocytosed, targeted to endosomes, internalized into intraluminal vesicles (ILVs), and excreted in exosomes. A nonubiquitinatable mutant of Stx3 (Stx3-5R) fails to enter this pathway and leads to the inability of the apical exosomal cargo protein GPRC5B to enter the ILV/exosomal pathway. This suggests that ubiquitination of Stx3 leads to removal from the basolateral membrane to achieve apical polarity, that Stx3 plays a role in the recruitment of cargo to exosomes, and that the Stx3-5R mutant acts as a dominant-negative inhibitor. Human cytomegalovirus (HCMV) acquires its membrane in an intracellular compartment and we show that Stx3-5R strongly reduces the number of excreted infectious viral particles. Altogether these results suggest that Stx3 functions in the transport of specific proteins to apical exosomes and that HCMV exploits this pathway for virion excretion