“Now everyone knows I’m a serial killer” Spontaneous Intentionality in Conversational Metaphor and Story-Telling

Drawing on data from a series of informal conversations about public safety and police-community relations, we distinguish between a speaker’s generalized communicative intentions with respect to metaphor use and story-telling, based on what Chafe (1994, p. 145) calls “unifying ideas that persist in semiactive consciousness” and the spontaneous intentions that arise within the short-term focus or spotlight of consciousness and guide the production of actual utterances. Although speakers occasionally enter a conversation with a fixed intention to express an idea with a particular metaphor, tell a particular story in a particular style, or accomplish some other speech act, such as persuading or informing, more commonly in ordinary conversations speakers begin with only a generalized intention to engage in the social interaction, sometimes but not always accompanied by generalized intentions regarding a particular topic or a particular form of expression. We argue that these “unifying ideas” interact with the contents of the short-term focus or spotlight of consciousness to generate spontaneous communicative intentions that in turn guide the production of metaphors, stories, and other language segments. Often these spontaneous communicative intentions arise interactively in response to other participants’ utterances; sometimes they arise in response to unforeseen opportunities in the speaker’s own utterances. Consequently, in ordinary casual conversations the spontaneous communicative intentions behind metaphor, story-telling and humor are often formed ‘on the fly,’ in response to the dynamic social interaction, and sometimes as a result of collaboration with other participants

Pairing and alpha-like quartet condensation in N=Z nuclei

We discuss the treatment of isovector pairing by an alpha-like quartet condensate which conserves exactly the particle number, the spin and the isospin. The results show that the quartet condensate describes accurately the isovector pairing correlations in the ground state of systems with an equal number of protons and neutronsComment: 4 pages, to appear in Journal of Physics: Conference Serie

Progress and perspective on different strategies to achieve wake-up-free ferroelectric hafnia and zirconia-based thin films

In the last decade orthorhombic hafnia and zirconia films have attracted tremendous attention arising from the discovery of ferroelectricity at the nanoscale. However, an initial wake-up pre-cycling is usually needed to achieve a ferroelectric behaviour in these films. Recently, different strategies, such as microstructure tailoring, defect, bulk and interface engineering, doping, NH3 plasma treatment and epitaxial growth, have been employed to obtain wake-up free orthorhombic ferroelectric hafnia and zirconia films. In this work we review recent developments in obtaining polar hafnia and zirconia-based thin films without the need of any wake-up cycling. In particular, we discuss the rhombohedral phase of hafnia/ zirconia, which under a constrained environment exhibits wake-up-free ferroelectric behaviour. This phase could have a strong impact on the current investigations of ferroelectric binary oxide materials and pave the way toward exploiting ferroelectric behaviour for next-generation memory and logic gate applications.This work was supported by the Portuguese Foundation for Science and Technology (FCT) in the framework of the Strategic Funding Contract UIDB/04650/2020 and by DST-SERB, Govt. of India through Grant Nr. ECR/2017/00006. R. F. Negrea and L. Pintilie acknowledge funding through project CEPROFER/ PN-III-P4-ID-PCCF-2016-0047 (contract 16/2018, funded by UEFISCDI). J.L.M-D. thanks the Royal Academy of Engineering Chair in Emerging Technologies Grant, CIET1819_24, the EPSRC grant EP/T012218/1- ECCS – EPSRC, and the grant EU-H2020-ERC-ADG # 882929, EROS

Progress and perspective on different strategies to achieve wake-up-free ferroelectric hafnia and zirconia-based thin films

In the last decade orthorhombic hafnia and zirconia films have attracted tremendous attention arising from the discovery of ferroelectricity at the nanoscale. However, an initial wake-up pre-cycling is usually needed to achieve a ferroelectric behaviour in these films. Recently, different strategies, such as microstructure tailoring, defect, bulk and interface engineering, doping, NH3 plasma treatment and epitaxial growth, have been employed to obtain wake-up free orthorhombic ferroelectric hafnia and zirconia films. In this work we review recent developments in obtaining polar hafnia and zirconia-based thin films without the need of any wake-up cycling. In particular, we discuss the rhombohedral phase of hafnia/ zirconia, which under a constrained environment exhibits wake-up-free ferroelectric behaviour. This phase could have a strong impact on the current investigations of ferroelectric binary oxide materials and pave the way toward exploiting ferroelectric behaviour for next-generation memory and logic gate applications.This work was supported by the Portuguese Foundation for Science and Technology (FCT) in the framework of the Strategic Funding Contract UIDB/04650/2020 and by DST-SERB, Govt. of India through Grant Nr. ECR/2017/00006. R. F. Negrea and L. Pintilie acknowledge funding through project CEPROFER/ PN-III-P4-ID-PCCF-2016-0047 (contract 16/2018, funded by UEFISCDI). J.L.M-D. thanks the Royal Academy of Engineering Chair in Emerging Technologies Grant, CIET1819_24, the EPSRC grant EP/T012218/1- ECCS – EPSRC, and the grant EU-H2020-ERC-ADG # 882929, EROS

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