Unveiling the double-well energy landscape in a ferroelectric layer

The properties of ferroelectric materials, which were discovered almost a century ago¹ , have led to a huge range of applications, such as digital information storage² , pyroelectric energy conversion³ and neuromorphic computing⁴⁻⁵ . Recently, it was shown that ferroelectrics can have negative capacitance⁶⁻¹¹, which could improve the energy efficiency of conventional electronics beyond fundamental limits¹²⁻¹⁴. In Landau–Ginzburg–Devonshire theory¹⁵⁻¹⁷, this negative capacitance is directly related to the doublewell shape of the ferroelectric polarization–energy landscape, which was thought for more than 70 years to be inaccessible to experiments¹⁸. Here we report electrical measurements of the intrinsic double-well energy landscape in a thin layer of ferroelectric Hf₀.₅Zr₀.₅O₂. To achieve this, we integrated the ferroelectric into a heterostructure capacitor with a second dielectric layer to prevent immediate screening of polarization charges during switching. These results show that negative capacitance has its origin in the energy barrier in a double-well landscape. Furthermore, we demonstrate that ferroelectric negative capacitance can be fast and hysteresis-free, which is important for prospective applications¹⁹. In addition, the Hf₀.₅Zr₀.₅O₂ used in this work is currently the most industry-relevant ferroelectric material, because both HfO₂ and ZrO₂ thin films are already used in everyday electronics²⁰. This could lead to fast adoption of negative capacitance effects in future products with markedly improved energy efficiency

A 2500-yr late holocenemulti-proxy record of vegetation and hydrologic changes from a cave guano-clay sequence in SW Romania

We provide sedimentological, geochemical, mineral magnetic, stable carbon isotope, charcoal, and pollen-based evidence froma guano/clay sequence in Gaura cuMuscă Cave (SWRomania), fromwhichwe deduced that from ~1230 BC to ~AD 1240 climate oscillated betweenwet and dry. From ~1230 BC to AD 1000 the climate was wetter than the present, prompting flooding of the cave, preventing bats fromroosting, and resulting in a slowrate of clay accumulation. The second half of the MedievalWarm Period (MWP) was generally drier; the cave experienced occasional flash flooding in between which maternity bat roosts established in the cave. One extremely wet event occurred around AD 1170, when Fe/Mn and Ti/Zr ratios show the highest values coincident with a substantial increase of sediment load in the underground stream. The mineral magnetic characteristics for the second part of the MWP indicate the partial input of surface-sourced sediments reflecting agricultural development and forest clearance in the area. Pollen and microcharcoal studies confirm that the overall vegetation cover and human land use have not changed much in this region since the medieval times

Accurate Prediction of Secreted Substrates and Identification of a Conserved Putative Secretion Signal for Type III Secretion Systems

The type III secretion system is an essential component for virulence in many Gram-negative bacteria. Though components of the secretion system apparatus are conserved, its substrates—effector proteins—are not. We have used a novel computational approach to confidently identify new secreted effectors by integrating protein sequence-based features, including evolutionary measures such as the pattern of homologs in a range of other organisms, G+C content, amino acid composition, and the N-terminal 30 residues of the protein sequence. The method was trained on known effectors from the plant pathogen Pseudomonas syringae and validated on a set of effectors from the animal pathogen Salmonella enterica serovar Typhimurium (S. Typhimurium) after eliminating effectors with detectable sequence similarity. We show that this approach can predict known secreted effectors with high specificity and sensitivity. Furthermore, by considering a large set of effectors from multiple organisms, we computationally identify a common putative secretion signal in the N-terminal 20 residues of secreted effectors. This signal can be used to discriminate 46 out of 68 total known effectors from both organisms, suggesting that it is a real, shared signal applicable to many type III secreted effectors. We use the method to make novel predictions of secreted effectors in S. Typhimurium, some of which have been experimentally validated. We also apply the method to predict secreted effectors in the genetically intractable human pathogen Chlamydia trachomatis, identifying the majority of known secreted proteins in addition to providing a number of novel predictions. This approach provides a new way to identify secreted effectors in a broad range of pathogenic bacteria for further experimental characterization and provides insight into the nature of the type III secretion signal

Impact of primary kidney disease on the effects of empagliflozin in patients with chronic kidney disease: secondary analyses of the EMPA-KIDNEY trial

Background: The EMPA KIDNEY trial showed that empagliflozin reduced the risk of the primary composite outcome of kidney disease progression or cardiovascular death in patients with chronic kidney disease mainly through slowing progression. We aimed to assess how effects of empagliflozin might differ by primary kidney disease across its broad population. Methods: EMPA-KIDNEY, a randomised, controlled, phase 3 trial, was conducted at 241 centres in eight countries (Canada, China, Germany, Italy, Japan, Malaysia, the UK, and the USA). Patients were eligible if their estimated glomerular filtration rate (eGFR) was 20 to less than 45 mL/min per 1·73 m2, or 45 to less than 90 mL/min per 1·73 m2 with a urinary albumin-to-creatinine ratio (uACR) of 200 mg/g or higher at screening. They were randomly assigned (1:1) to 10 mg oral empagliflozin once daily or matching placebo. Effects on kidney disease progression (defined as a sustained ≥40% eGFR decline from randomisation, end-stage kidney disease, a sustained eGFR below 10 mL/min per 1·73 m2, or death from kidney failure) were assessed using prespecified Cox models, and eGFR slope analyses used shared parameter models. Subgroup comparisons were performed by including relevant interaction terms in models. EMPA-KIDNEY is registered with ClinicalTrials.gov, NCT03594110. Findings: Between May 15, 2019, and April 16, 2021, 6609 participants were randomly assigned and followed up for a median of 2·0 years (IQR 1·5–2·4). Prespecified subgroupings by primary kidney disease included 2057 (31·1%) participants with diabetic kidney disease, 1669 (25·3%) with glomerular disease, 1445 (21·9%) with hypertensive or renovascular disease, and 1438 (21·8%) with other or unknown causes. Kidney disease progression occurred in 384 (11·6%) of 3304 patients in the empagliflozin group and 504 (15·2%) of 3305 patients in the placebo group (hazard ratio 0·71 [95% CI 0·62–0·81]), with no evidence that the relative effect size varied significantly by primary kidney disease (pheterogeneity=0·62). The between-group difference in chronic eGFR slopes (ie, from 2 months to final follow-up) was 1·37 mL/min per 1·73 m2 per year (95% CI 1·16–1·59), representing a 50% (42–58) reduction in the rate of chronic eGFR decline. This relative effect of empagliflozin on chronic eGFR slope was similar in analyses by different primary kidney diseases, including in explorations by type of glomerular disease and diabetes (p values for heterogeneity all >0·1). Interpretation: In a broad range of patients with chronic kidney disease at risk of progression, including a wide range of non-diabetic causes of chronic kidney disease, empagliflozin reduced risk of kidney disease progression. Relative effect sizes were broadly similar irrespective of the cause of primary kidney disease, suggesting that SGLT2 inhibitors should be part of a standard of care to minimise risk of kidney failure in chronic kidney disease. Funding: Boehringer Ingelheim, Eli Lilly, and UK Medical Research Council

A Novel Factor Xa-Inhibiting Peptide from Centipedes Venom

Centipedes have been used as traditional medicine for thousands of years in China. Centipede venoms consist of many biochemical peptides and proteins. Factor Xa (FXa) is a serine endopeptidase that plays the key role in blood coagulation, and has been used as a new target for anti-thrombotic drug development. A novel FXa inhibitor, a natural peptide with the sequence of Thr-Asn-Gly-Tyr-Thr (TNGYT), was isolated from the venom of Scolopendra subspinipesmutilans using a combination of size-exclusion and reverse-phase chromatography. The molecular weight of the TNGYT peptide was 554.3 Da measured by electrospray ionization mass spectrometry. The amino acid sequence of TNGYT was determined by Edman degradation. TNGYT inhibited the activity of FXa in a dose-dependent manner with an IC(50) value of 41.14 mg/ml. It prolonged the partial thromboplastin time and prothrombin time in both in vitro and ex vivo assays. It also significantly prolonged whole blood clotting time and bleeding time in mice. This is the first report that an FXa inhibiting peptide was isolated from centipedes venom

Contribution à la connaissance des eaux souterraines du Danube à Vienne

Fondés sur le matériel recueilli pendant deux campagnes de recherches (1971-1980 et 1991-1993) dans les eaux souterraines du Danube à Vienne (zone Lobau), les auteurs font un bilan des Cladocères récoltés dans ce milieu. Parmi les 16 espèces inventoriées, 5 sont stygophiles : Alonella nana, Chydorus sphaericus, Alona guttata, Acroperus harpae et Biapertura affinis. Toutes les données montrent que les espèces benthiques des eaux souterraines du Lobau sont en liaison étroite avec celles de la surface (bras mort Eberschüttwasser), formant des populations communes «nappe alluviale-benthos» dont la dynamique est fortement influencée par le régime hydrologique

Bridging the quartet and pair pictures of isovector proton-neutron pairing

International audienceThe formal implications of a quartet coherent-state ansatz for proton-neutron pairing are analyzed. Its nonlinear annihilation operators, which generalize the BCS linear quasiparticle operators, are computed in the quartetting case. Their structure is found to generate nontrivial relationships between the many-body correlation functions. The intrinsic structure of the quartet coherent state is detailed as it hints to the precise correspondence between the quartetting picture and the symmetry restored pair condensate picture for the proton-neutron pairing correlations