Palaeoclimate modelling of monsoons during past warm periods

Three past warm periods were chosen to provide out-of-sample tests for those state-of-the-art climate models by phase 4 of the Palaeoclimate Model Intercomparison Project (PMIP4): the mid-Holocene (6,000 years ago), the Last Interglacial (more precisely 127,000 years ago) and the mid-Pliocene Warm Period (roughly 3.2 million years ago). Experiments were designed for each warm period with improved boundary conditions and protocols; called midHolocene, lig127k and midPliocene- eoi400 respectively. This work looks at the monsoon behaviour across the three PMIP4 experiments for the first time, to improve the understanding of palaeomonsoon and to evaluate the performance of current state-of-art models. Results of this work indicate that both the orbit-induced experiments (midHolocene and lig127k) show enhanced monsoons in the Northern Hemisphere and weakened monsoons in the Southern Hemisphere as expected. The lig127k simulations have stronger response than the midHolocene, because of their stronger orbital forcings. Simulated anomalies are generally in good agreement with climate proxy reconstructions, but both experiments underestimate the amplification of the northern African monsoon as well as Arctic warming. The midPliocene-eoi400 simulations indicate a global warming with a clear pattern of polar amplification, wetter tropics, and enhanced monsoons but with uncertainties. An idealised aerosol experiment highlights the potential importance of uncertainty in the aerosol specifications in the experiment protocol to simulating the mPWP climate. Analyses on the data-model mismatch highlight the source and importance of uncertainties during different time periods. Despite the existing uncertainties in the simulations, the results of the three experiments are useful for understanding climate response and quantitatively evaluating model performance. The findings from this thesis, combined with future work, improve our understanding of monsoon forced responses and could help to ensure that the next generation of climate models provides more confident projections of future climate change

All-optical switching of magnetic domains in Co/Gd heterostructures with Dzyaloshinskii-Moriya Interaction

Given the development of hybrid spintronic-photonic devices and chiral magnetic structures, a combined interest in all-optical switching (AOS) of magnetization and current-induced domain wall motion in synthetic ferrimagnetic structures with strong Dzyaloshinskii-Moriya Interaction (DMI) is emerging. In this study, we report a study on single-pulse all-optical toggle switching and asymmetric bubble expansion in specially engineered Co/Gd-based multilayer structures. In the absence of any external magnetic fields, we look into the AOS properties and the potential role of the DMI on the AOS process as well as the stability of optically written micro-magnetic domains. Particularly, interesting dynamics are observed in moon-shaped structures written by two successive laser pulses. The stability of domains resulting from an interplay of the dipolar interaction and domain-wall energy are compared to simple analytical models and micromagnetic simulations

Tuning the Dzyaloshinskii-Moriya Interaction in Pt/Co/MgO heterostructures through MgO thickness

The interfacial Dzyaloshinskii-Moriya interaction (DMI) in the ferromagnetic/heavy metal ultra-thin film structures , has attracted a lot of attention thanks to its capability to stabilize Neel-type domain walls (DWs) and magnetic skyrmions for the realization of non-volatile memory and logic devices. In this study, we demonstrate that magnetic properties in perpendicularly magnetized Ta/Pt/Co/MgO/Pt heterostructures, such as magnetization and DMI, can be significantly influenced through both the MgO and the Co ultrathin film thickness. By using a field-driven creep regime domain expansion technique, we find that non-monotonic tendencies of DMI field appear when changing the thickness of MgO and the MgO thickness corresponding to the largest DMI field varies as a function of the Co thicknesses. We interpret this efficient control of DMI as subtle changes of both Pt/Co and Co/MgO interfaces, which provide a method to investigate ultra-thin structures design to achieve skyrmion electronics.Comment: 18 pages, 11 figure

Analysing the PMIP4-CMIP6 collection: a workflow and tool (pmip_p2fvar_analyzer v1)

Experiment outputs are now available from the Coupled Model Intercomparison Project's sixth phase (CMIP6) and the past climate experiments defined in the Palaeoclimate Modelling Intercomparison Project's fourth phase (PMIP4). All of this output is freely available from the Earth System Grid Federation (ESGF). Yet there is overhead in analysing this resource that may prove complicated or prohibitive. Here we document the steps taken by ourselves to produce ensemble analyses covering past and future simulations. We outline the strategy used to curate, adjust the monthly calendar aggregation and process the information downloaded from the ESGF. The results of these steps were used to perform analysis for several of the initial publications arising from PMIP4. We provide post-processed fields for each simulation, such as climatologies and common measures of variability. Example scripts used to visualise and analyse these fields are provided for several important case studies

Memories are One-to-Many Mapping Alleviators in Talking Face Generation

Talking face generation aims at generating photo-realistic video portraits of a target person driven by input audio. Due to its nature of one-to-many mapping from the input audio to the output video (e.g., one speech content may have multiple feasible visual appearances), learning a deterministic mapping like previous works brings ambiguity during training, and thus causes inferior visual results. Although this one-to-many mapping could be alleviated in part by a two-stage framework (i.e., an audio-to-expression model followed by a neural-rendering model), it is still insufficient since the prediction is produced without enough information (e.g., emotions, wrinkles, etc.). In this paper, we propose MemFace to complement the missing information with an implicit memory and an explicit memory that follow the sense of the two stages respectively. More specifically, the implicit memory is employed in the audio-to-expression model to capture high-level semantics in the audio-expression shared space, while the explicit memory is employed in the neural-rendering model to help synthesize pixel-level details. Our experimental results show that our proposed MemFace surpasses all the state-of-the-art results across multiple scenarios consistently and significantly.Comment: Project page: see https://memoryface.github.i

Enhanced Interfacial Dzyaloshinskii-Moriya Interaction in annealed Pt/Co/MgO structures

The interfacial Dzyaloshinskii-Moriya interaction (iDMI) is attracting great interests for spintronics. An iDMI constant larger than 3 mJ/m^2 is expected to minimize the size of skyrmions and to optimize the DW dynamics. In this study, we experimentally demonstrate an enhanced iDMI in Pt/Co/X/MgO ultra-thin film structures with perpendicular magnetization. The iDMI constants were measured using a field-driven creep regime domain expansion method. The enhancement of iDMI with an atomically thin insertion of Ta and Mg is comprehensively understood with the help of ab-initio calculations. Thermal annealing has been used to crystallize the MgO thin layer for improving tunneling magneto-resistance (TMR), but interestingly it also provides a further increase of the iDMI constant. An increase of the iDMI constant up to 3.3 mJ/m^2 is shown, which could be promising for the scaling down of skyrmion electronics

Structure-Based Design of Non-Natural Amino Acid Inhibitors of Amyloid Fibrillation

Many globular and natively disordered proteins can convert into amyloid fibers. These fibers are associated with numerous pathologies1 as well as with normal cellular functions2,3, and frequently form during protein denaturation4,5. Inhibitors of pathological amyloid fibers could serve as leads for therapeutics, provided the inhibitors were specific enough to avoid interfering with normal processes. Here we show that computer-aided, structure-based design can yield highly specific peptide inhibitors of amyloid formation. Using known atomic structures of segments of amyloid fibers as templates, we have designed and characterized an all D-amino acid inhibitor of fibrillation of the tau protein found in Alzheimer’s disease, and a non-natural L-amino acid inhibitor of an amyloid fiber that enhances sexual transmission of HIV. Our results indicate that peptides from structure-based designs can disrupt the fibrillation of full-length proteins, including those like tau that lack fully ordered native structures

Neglected intrapulmonary arteriovenous anastomoses: A comparative study of pulmonary right-to-left shunts in patients with patent foramen ovale

ObjectivePulmonary right-to-left shunt (P-RLS) and patent foramen ovale right-to-left shunt (PFO-RLS) often appear in combination, and there are often differences and connections between them. Intrapulmonary arteriovenous anastomoses (IPAVAs), as part of P-RLS, are often overlooked because there are no technologies to detect and identify them. This study aimed to further clarify the incidence and characteristics of P-RLS with the help of contrast transesophageal echocardiography (c-TEE) and contrast transthoracic echocardiography (c-TTE), providing a reference for clinically relevant research and patent foramen ovale (PFO) management disposal decisions.MethodsWe retrospectively investigated 414 subjects who came to our hospital for c-TEE from October 2021 to July 2022, and all subjects completed c-TTE simultaneously. 7 Patients who were newly diagnosed with an atrial septal defect were excluded. Eventually, 407 patients were included in this study. Among them, 157 patients with PFO (58 patients were treated with PFO closure subsequently) and 250 patients without PFO confirmed by c-TEE were finally enrolled. In the process, we observed and analysed the presence of P-RLS.ResultsA total of 407 patients were included in the final analysis and divided into PFO group (N = 157) and non-PFO group (N = 250) according to the results of c-TEE. Whether at rest or after Valsalva maneuver, the incidence of P-RLS was significantly higher under c-TEE than under c-TTE in the two groups (P < 0.001). For both c-TTE and c-TEE, the incidence of P-RLS was slightly higher after Valsalva maneuver than at rest, but the difference was not significant (c-TTE: rest vs. Valsalva maneuver, P = 0.214; c-TEE: rest vs. Valsalva maneuver, P = 0.076). The Valsalva maneuver increased the incidence of P-RLS in the group without PFO, which was more significant in c-TEE (c-TTE: rest vs. Valsalva maneuver, P = 0.591; c-TEE: rest vs. Valsalva maneuver, P = 0.008). In both groups, the P-RLS semiquantitative grading was statistical significance under different states and examinations (P < 0.001).ConclusionThe vast majority of P-RLS are grade 1–2 and are derived from physiological IPAVAs. Even so, attention should be given to the differentiation between P-RLS and PFO-RLS. c-TEE is an effective method to detect P-RLS; however, the recruitments of c-TEE and Valsalva maneuver to P-RLS should be noted

A cyclic peptidic serine protease inhibitor:increasing affinity by increasing peptide flexibility

Peptides are attracting increasing interest as protease inhibitors. Here, we demonstrate a new inhibitory mechanism and a new type of exosite interactions for a phage-displayed peptide library-derived competitive inhibitor, mupain-1 (CPAYSRYLDC), of the serine protease murine urokinase-type plasminogen activator (uPA). We used X-ray crystal structure analysis, site-directed mutagenesis, liquid state NMR, surface plasmon resonance analysis, and isothermal titration calorimetry and wild type and engineered variants of murine and human uPA. We demonstrate that Arg6 inserts into the S1 specificity pocket, its carbonyl group aligning improperly relative to Ser195 and the oxyanion hole, explaining why the peptide is an inhibitor rather than a substrate. Substitution of the P1 Arg with novel unnatural Arg analogues with aliphatic or aromatic ring structures led to an increased affinity, depending on changes in both P1 - S1 and exosite interactions. Site-directed mutagenesis showed that exosite interactions, while still supporting high affinity binding, differed substantially between different uPA variants. Surprisingly, high affinity binding was facilitated by Ala-substitution of Asp9 of the peptide, in spite of a less favorable binding entropy and loss of a polar interaction. We conclude that increased flexibility of the peptide allows more favorable exosite interactions, which, in combination with the use of novel Arg analogues as P1 residues, can be used to manipulate the affinity and specificity of this peptidic inhibitor, a concept different from conventional attempts at improving inhibitor affinity by reducing the entropic burden

Structure-Based Design of Non-Natural Amino Acid Inhibitors of Amyloid Fibrillation

Many globular and natively disordered proteins can convert into amyloid fibers. These fibers are associated with numerous pathologies1 as well as with normal cellular functions2,3, and frequently form during protein denaturation4,5. Inhibitors of pathological amyloid fibers could serve as leads for therapeutics, provided the inhibitors were specific enough to avoid interfering with normal processes. Here we show that computer-aided, structure-based design can yield highly specific peptide inhibitors of amyloid formation. Using known atomic structures of segments of amyloid fibers as templates, we have designed and characterized an all D-amino acid inhibitor of fibrillation of the tau protein found in Alzheimer’s disease, and a non-natural L-amino acid inhibitor of an amyloid fiber that enhances sexual transmission of HIV. Our results indicate that peptides from structure-based designs can disrupt the fibrillation of full-length proteins, including those like tau that lack fully ordered native structures.We thank M.I. Ivanova, J. Corn, T. Kortemme, D. Anderson, M.R. Sawaya, M. Phillips, S. Sambashivan, J. Park, M. Landau, Q. Zhang, R. Clubb, F. Guo, T. Yeates, J. Nowick, J. Zheng, and M.J. Thompson for discussions, HHMI, NIH, NSF, the GATES foundation, and the Joint Center for Translational Medicine for support, R. Peterson for help with NMR experiments, E. Mandelkow for providing tau constructs, R. Riek for providing amyloid beta, J. Stroud for amyloid beta preparation. Support for JK was from the Damon Runyon Cancer Research Foundation, for HWC by the Ruth L. Kirschstein National Research Service Award, for JM from the programme for junior-professors by the ministry of science, Baden-Württemberg, and for SAS by a UCLA-IGERT bioinformatics traineeship