bluuebunny/crossref_metadata_2025 huggingface dataset:
In-situ characterization of tool temperatures using in-tool integrated thermoresistive thin-film sensors
Authors: González Germán , Plogmeyer Marcel , Schoop Julius , Bräuer Günter , Schulze Volker
Published: January 2023

Metal cutting is characterized by high temperatures at the tool-workpiece interface. Although valuable information could be provided by the temperature values, their direct measurement still presents a challenge due to the high contact pressure and the inaccessibility of the process kinematic. In this research work, the current state of thin-film sensors for measuring temperatures on the chip-tool interface has been analyzed with a focus on the measuring phenomena: thermoelectricity and thermoresistivity. Thin-film sensors placed on the cutting tools in or close to the tool-chip contact area are expected to obtain accurate temperature information at the expense of a short lifetime. New insights into thin-film sensors manufacturing, design and calibration are presented, and a new concept of a three-point thermoresistive thin-film sensor is proposed. During orthogonal cutting tests the workpiece deformations were measured through high-speed imaging and the process temperatures were measured with thin-film sensors. In order to validate the temperatures and to obtain the temperature distribution on the cutting edge, Finite Element simulations were carried out. Finally, the potential of using cutting tools with integrated thin-film sensors for in-situ characterization is investigated and a statement for its limitations and potential applications is given.
A Review of Circulating Tumor DNA as a Biomarker Guide for Total Neoadjuvant Therapy in Patients with Locally Advanced Rectal Cancer
Authors: Yahya Jehan , Baber Miriam , Nabavizadeh Nima , Goodyear Shaun M. , Kardosh Adel
Published: January 2023

Purpose

Non-operative management of patients with locally advanced rectal cancer (LARC) is emerging as a popular approach for patients that have no evidence of disease following neoadjuvant therapy. However, high rates of local recurrence or distant metastases have highlighted the urgent need for robust biomarker strategies to aid clinical management of these patients.

Methods

This review summarizes recent advances in the utility of cell-free (cf) and circulating tumor (ct) DNA as potential biomarkers to help guide individualized non-operative management strategies for LARC patients receiving neoadjuvant therapy.

Results

Liquid biopsies and the detection of cfDNA/ctDNA is an emerging technology with the potential to provide a non-invasive approach to monitor disease response and improve the identification of patients with LARC that would best benefit from non-operative management.

Conclusions

Substantial work is still needed before cfDNA/ctDNA monitoring can be widely adopted in the clinical setting. Studies reviewed herein highlight several areas of opportunity for improving the effectiveness and utility of cfDNA/ctDNA for managing patients with LARC.
Self-control and debt decisions relationship: evidence for different credit options
Authors: Fernández-López Sara , Castro-González Sandra , Rey-Ares Lucía , Rodeiro-Pazos David
Published: January 2023

In recent years, households have become increasingly indebted, which constitutes a matter of concern. Based on a sample from the Spanish Survey of Financial Competences, this paper examines the relationship between self-control and consumer borrowing behaviour and, in so doing, it proposes a new multi-item scale of individual’s self-control in financial matters and considers several types of consumer debt, thus overcoming the main gaps identified in previous research. Empirical evidence reveals that, overall, self-control problems lead to more indebtedness. However, comprehensive analyses have demonstrated that the influence of self-control differs across an exhaustive range of credit options. In this regard, the lack of self-control increases the probability of taking out unsecured personal loans, loans from family or friends, and credit card use. Evidence suggests that individuals’ first impulse leads them to ask their social circle for a loan. Overall, individuals might be tempted to get indebted when they cannot make ends meet. However, this first impulse usually faces barriers from the supply perspective, so the evidence suggests that the effect of self-control on borrowing decisions might be shaped not only by the demand side of credit but also by the supply one.
Platyhelminth fauna of the Island of Sylt: a meta-analysis of distributional patterns and description of 19 new species
Authors: Armonies Werner
Published: January 2023

Over the past 70 years, numerous authors studied the platyhelminth fauna near the island of Sylt in the eastern North Sea, each with a specific focus on varying aspects of ecology, morphology or systematics, and most of them dealing with a single habitat type. These data are combined with new data to get a comprehensive view of species richness, the distribution of individual species across tidal levels and sediment types and the resulting communities. So far, 398 platyhelminth species have been recorded around Sylt island, plus a still growing number of unidentified or undescribed species, in particular from subtidal waters. The distribution over habitat types (as defined by sediment types and tidal level) is described for the known species. Neighbouring habitat types overlap in species composition, and faunal composition changes continuously over environmental gradients. The number of species recorded per habitat type mirrors the sampling intensity and varied between some 20 species in poorly studied habitats and 150 in the well-studied intertidal sand flats. Corrected for variations in sampling intensity, platyhelminth species richness showed no significant differences between sediment types and only moderate variation over tidal levels. On a larger spatial scale, three faunal assemblages can be differentiated: the supratidal harbours brackish-water species (mesohaline in the upper and polyhaline in the lower supratidal), the intertidal polyhaline-marine species with a wide tolerance of variations in physical factors and the subtidal marine (± stenohaline) species. With respect to sediment type, mud and sand dwellers are well separated in the supra- and subtidal belt but less in the intertidal. Provided these rules are general, I conclude platyhelminth species richness in a given section of coastline mainly depends on the ranges of environmental factors covered. Nineteen new species encountered during this study are described.
Biogeographic patterns in sea pens (Octocorallia: Pennatulacea)
Authors: García-Cárdenas Francisco J. , López-González Pablo J.
Published: January 2023

Pennatulaceans (Octocorallia: Pennatulacea) are among the most dominant octocoral species living in soft bottom communities. Some of them are cosmopolitan and have been recorded in all seas and oceans of the world, from shallow waters up to about 6260 m deep. In the present study, we try to find answers to questions about the biogeographical distribution of sea pens including most recently described species. We also evaluate the diversity and faunistic affinities among pennatulaceans of the world’s oceans, and determine the degree of faunistic isolation of the Mediterranean Sea from the Atlantic. Finally, we return to the old debate about the hypothetical oldest diversification center of sea pen lineages.
Moderators of the Effectiveness of UPcomplish on Office Workers’ Sedentary Behaviour, Quality of Life, and Psychosocial Determinants: A Stepped Wedge Design
Authors: Berninger Nathalie M. , Crutzen Rik , Ruiter Robert A. C. , Kok Gerjo , Plasqui Guy , ten Hoor Gill A.
Published: January 2023

Background

In the earlier developed and evaluated 12-week UPcomplish intervention, the aim was to reduce sedentary behaviour (SB) among office workers and increase their quality of life (QoL). In the current study, we explored moderators of effectiveness.

Method

We applied a stepped wedge design with five intervention groups starting with time lags of seven weeks (n = 142, 96 females). Participants wore the VitaBit to continuously measure SB and received surveys about QoL and psychosocial determinants at the beginning, middle, and end of the intervention. We regressed baseline participant characteristics and behaviours onto intra-individual improvements (centred around calendar week means) in determinants, SB, performance objectives, and QoL.

Results

Those scoring high in baseline intention, task performance, stress, vitality, and emotional well-being improved less in these variables. Baseline stress (β =  − 0.05 [SE = 0.01; 95% CI =  − 0.08, − 0.02;pcorrected = .02]) and emotional well-being (β = 0.02 [SE = 0.01; 95% CI = 0.01, 0.03;pcorrected = .02]) were associated with improvement in contextual performance. Baseline attitude (β =  − 12.92 [SE = 3.93; 95% CI =  − 20.80, − 5.04;pcorrected = .02]) and perceived behavioural control (PBC;β =  − 9.27 [SE = 3.04; 95% CI =  − 15.37, − 3.16;pcorrected = .03]) were negatively associated with improvements in emotional well-being. Post hoc analyses with a sub-group scoring lower in determinants revealed that improvement in PBC was positively associated with SB registration.

Conclusion

Participants scoring low in baseline determinants might profit from UPcomplish via an increase in PBC. In combination with changes within organizations (e.g. the implementation of standing desks), UPcomplish might potentially reduce SB.

Trial Registration

NL7503 — registered 1 February 2019.
Inner Speech and ‘Pure’ Thought – Do we Think in Language?
Authors: Kompa Nikola A.
Published: January 2023

While the idea that thinking is a form of silent self-talk goes back at least to Plato, it is not immediately clear how to state this thesis precisely. The aim of the paper is to spell out the notion that we think in language by recourse to recent work on inner speech. To that end, inner speech and overt speech are briefly compared. I then propose that inner speaking be defined as a mental episode that substantially engages the speech production system; the underlying model of speech production is sketched. Next, the cognitive role of inner speaking is explored, especially its role in thinking and reasoning. The question of whether it is a way of making thoughts accessible (to whomever) or whether it is a means of thinking itself is raised. I argue that there are two reasons for assuming that, occasionally, we think in language. More specifically, I will claim that some instances of thinking are instances of inner speaking as they exploit certain properties of natural language, and that some instances of inner speaking are instances of thinking as they play a decisive role in paradigmatic cases of thinking that result from internalizing and re-using certain social-linguistic practices. Finally, the Language-of-Thought hypothesis as an alternative account is critically discussed.
Challenges of Documenting Historic Water Systems
Authors: Cohen Anna S. , Cannon Molly Boeka , Jimenez Kelly N.
Published: January 2023

Geospatial research in archaeology often relies on datasets previously collected by other archaeologists or third-party groups, such as state or federal government entities. This article discusses our work with geospatial datasets for identifying, documenting, and evaluating prehistoric and historic water features in the western United States. As part of a project on water heritage and long-term views on water management, our research has involved aggregating spatial data from an array of open access and semi-open access sources. Here, we consider the challenges of working with such datasets, including outdated or disorganized information, and fragmentary data. Based on our experiences, we recommend best practices: (1) locating relevant data and creating a data organization method for working with spatial data, (2) addressing data integrity, (3) integrating datasets in systematic ways across research cohorts, and (4) improving data accessibility.
Selective energy and enstrophy modification of two-dimensional decaying turbulence
Authors: Nair Aditya G. , Hanna James , Aureli Matteo
Published: January 2023

In two-dimensional decaying homogeneous isotropic turbulence, kinetic energy and enstrophy are respectively transferred to larger and smaller scales. In such spatiotemporally complex dynamics, it is challenging to identify the important flow structures that govern this behaviour. We propose and employ numerically two flow-modification strategies that leverage the inviscid global conservation of energy and enstrophy to design external forcing inputs that change these quantities selectively and simultaneously, and drive the system towards steady-state or other late-stage behaviour. One strategy employs only local flow field information, while the other is global. We observe various flow structures excited by these inputs and compare them with recent literature. Energy modification is characterized by the excitation of smaller wavenumber structures in the flow than enstrophy modification.
The laminar seabed thermal boundary layer forced by propagating and standing free-surface waves
Authors: Michele S. , Borthwick A.G.L. , van den Bremer T.S.
Published: January 2023

A mathematical model is developed to investigate seabed heat transfer processes under long-crested ocean waves. The unsteady convection–diffusion equation for water temperature includes terms depending on the velocity field in the laminar boundary layer, analogous to mass transfer near the seabed. Here we consider regular progressive waves and standing waves reflected from a vertical structure, which complicate the convective term in the governing equation. Rectangular and Gaussian distributions of seabed temperature and heat flux are considered. Approximate analytical solutions are derived for uniform and trapezoidal currents, and compared against predictions from a numerical solver of the full equations. The effects of heat source profile, location and strength on heat transfer dynamics in the thermal boundary layer are explained, providing insights into seabed temperature forced convection mechanisms enhanced by free-surface waves.
THE EARLY RECEPTION OF APULEIUS: AN ECHO IN TERTULLIAN
Authors: Grillo Luca
Published: January 2023

Apuleius tells us of his own popularity as a writer, and yet both the literary and the material records are silent about his works for almost one hundred and fifty years after his death. Various attempts to identify allusions to his works before Lactantius and other fourth-century authors have proven unconvincing. This article suggests that there is a clear allusion to theMetamorphosesin Tertullian's treatiseAduersus Valentinianos(beginning of the third century). Tertullian uses Apuleius to denigrate the Valentinians and to assimilate the name of one of their gods to the braying of an ass.
Terahertz radiation in the interaction of a focused laser pulse with plasma
Authors: Frolov A.A.
Published: January 2023

The theory of terahertz (THz) wave emission at the oblique incidence of a focused s-polarized laser pulse on the boundary of a rarefied plasma is developed. The angular, spectral and energy characteristics of the THz signal as a function of the focal spot size and the incidence angle of laser radiation, as well as the plasma density, are investigated. It is shown that the THz radiation energy increases with a decrease in the laser pulse focal spot and has the maximum value when the tightly focused laser pulse is incident at the angle of total reflection on the plasma boundary.
Navigating the pitfalls of language standardisation: The imperfect binary of authenticity and anonymity in Creole-speaking Martinique
Authors: Ardoino Chiara
Published: January 2023

Standardisation is often touted as the default means to improve attitudes towards minoritised languages and prevent/reverse their obsolescence. However, standardisation can ‘tamper’ with the indexicalities of minoritised languages, potentially alienating their speakers. Two aspects of standardisation stand out as particularly problematic: the shift from ‘ideologies of authenticity’ to ‘ideologies of anonymity’ (Woolard 2016), and the resulting introduction/intensification of prescriptivism (Eckert 1983). Although much literature focuses on the irreconcilable nature of these ideologies, I show that their discursive manifestations are neither clear-cut nor always incompatible. First, I analyse a TV debate on the standardisation of Martinican Creole (MC), in which the fault-line between authenticity and anonymity is blurred and partially overcome. Next, I draw on a Martinican activist's Instagram profile to show how various discursive strategies and a positive take on language variation can help promote MC as an ‘anonymous’ language without forgoing its ‘authenticity’ or openly stigmatising spontaneous practices. (Minoritised languages, Creoles, Martinique, maintenance, standardisation, ideologies of authenticity, anonymity, prescriptivism, purism, Abstand)*
NLP startup funding in 2022
Authors: Dale Robert
Published: January 2023

It’s no secret that the commercial application of NLP technologies has exploded in recent years. From chatbots and virtual assistants to machine translation and sentiment analysis, NLP technologies are now being used in a wide variety of applications across a range of industries. With the increasing demand for technologies that can process human language, investors have been eager to get a piece of the action. In this article, we look at NLP startup funding over the past year, identifying the applications and domains that have received investment.
Frontiers of astrobiology and the humanities
Authors: Chela-Flores Julian
Published: January 2023

One of the main objectives of astrobiology is to understand the distribution of life in the universe, for microbial life, as well as for the search of extra-terrestrial intelligence, both of which would force upon us new problems in philosophy, including ethics and theology. The question of astrobiology and the humanities being such a broad topic, in the present paper we have limited our discussion of the Frontiers of Astrobiology and the Humanities to the single topic: ‘Independence of science (astrobiology) from philosophy and theology’. We have argued along the lines of this narrower thesis, but restricting our theological discussion strictly to a Judeo-Christian perspective.
Patient and family members’ experiences with language and environment when receiving bad news: A qualitative exploratory study
Authors: Miller Elizabeth M. , Porter Joanne E. , Barbagallo Michael S.
Published: January 2023

Objectives

Receiving bad news about one’s health can be devastating, yet little is known about how the therapeutic nature of the environment where bad news is delivered affects the experience. The current study aimed to explore how patients and their families were affected by the language and the built, natural, social, and symbolic environments when receiving bad news, through the Therapeutic Landscapes theoretical framework.

Methods

Patients diagnosed with a life-limiting illness living in regional Victoria who had a hospital admission within 24 months and a diagnostic/prognostic conversation were invited to participate, as well as a family member who witnessed the conversation. Participants were recruited through social media and snowballing, resulting in 14 online semi-structured interviews being conducted between November 2021 and March 2022, audio-recorded, and transcribed verbatim. Reflexive thematic analysis was used to develop the themes.

Results

Fourteen semi-structured interviews were conducted with women aged between 30 and 77 years. Interviews lasted between 45 and 120 minutes, with an average of 69 minutes, and were conducted online or via mobile phone. Four central themes were developed: “Hearing bad news for the first time,” “Preferences for having hard conversations,” “Creating a sense of safety for ongoing care,” and “The therapeutic nature of the ward.”

Significance of results

This body of work will help inform practice and future policy regarding bad news delivery and the design and aesthetics of environments where bad news is delivered. It is essential that bad news is delivered within a quiet, calm, and emotionally safe environment within a supportive therapeutic relationship.
The Edizione critica delle opere di Gioachino Rossini and Self-Borrowing
Authors: Malnati Andrea
Published: January 2023

Self-borrowing and Rossini: music theatre scholars are well acquainted with this topic. Many publications have been dedicated to it, most of which concentrate on compositional-analytic aspects, the artistic and communicational nature of self-borrowing and its reception in nineteenth-century periodicals. At present, however, no study has attempted to question the relation between Rossini's self-borrowings and the critical edition of his works. This is the issue to which this contribution is dedicated.

Beginning with the operating indications summarized by the editorial criteria provided for the Edizione critica delle opere di Gioachino Rossini – first published in 1974, and revised and updated in 2015 – this study compares the various methodological approaches adopted while preparing critical editions and dealing with the specific features of each passage in which self-borrowing appears. This comparison furthermore allows us to formulate a general overview of the entire editorial undertaking. This in turn will give us a glimpse of how principles such as the autograph's centrality and concepts such as authenticity and originality have often become problematic and have been put into question. Knowing that Rossini often rewrote the pieces he self-borrowed is fundamental for philologists working on the critical edition of his works. Decoding the modus operandi Rossini adopted in each case of self-borrowing is therefore equally important, and can help choose the sources closest to Rossini's idea of the self-borrowed pieces at the time of their reuse.
A Probit Multistate IRT Model With Latent Item Effect Variables for Graded Responses
Authors: Classe Franz L. , Steyer Rolf
Published: January 2023

Abstract: A probit multistate Item Response Theory (IRT) model for ordinal response variables is introduced. It comprises a reference latent state variable for each occasion of measurement and a latent item effect variable for each item except for one reference item. The latent item effect variable is defined as the difference between the latent state variable pertaining to the non-reference item and the latent state variable pertaining to the reference item. They are assumed to be identical for all occasions of measurement. The new model is applied to a real data example. Including item effect variables improve model fit considerably. Hence, the items are not strictly unidimensional within each occasion of measurement.
Drift Corrected Seafloor Pressure Observations of Vertical Deformation at Axial Seamount 2018–2021
Authors: Sasagawa Glenn S. , Zumberge Mark A. , Cook Matthew J.
Published: January 2023

Axial Seamount is a seafloor volcano with frequent eruptions and periodic cycles of inflation and deflation. Seafloor pressure gauges monitor vertical deformation with time, but inherent instrumental drift complicates and biases geodetic interpretation. A drift corrected pressure recorder was deployed on Axial Seamount on 6 July 2018, at coordinates 45° 57.29′ North latitude, −130° 0.56′ East longitude, depth 1,535 m. This system includes two independent quartz‐resonant pressure gauges, which nearly continuously observe the seafloor pressure. At regular intervals, the gauges are calibrated in situ with a modified deadweight tester at a pressure within 98% of the nominal seafloor pressure. Using the calibration data, the drift of each gauge has been modeled as a simple linear plus decaying exponential function of time. The two estimated linear sensor drift rates are 0.45 ± 0.12 and 0.36 ± 0.08 kPa/year; the modeled sensor drift represents a significant error if uncorrected. The standard deviations of the drift model residuals are of order 0.06 kPa or 6 mm depth equivalent. Once calibrated, the difference between the two seafloor pressure timeseries exhibits a RMS deviation of ±6 mm at the 90% confidence limit and a linear trend less than 1 mm/year. A time series from July 2018 to December 2021 tracks the inflation of Axial Seamount with differing inflation rates over different time intervals.
A Novel Approach to Quantify Sediment Transfer and Storage in Rivers—Testing Feldspar Single‐Grain pIRIR Analysis and Numerical Simulations
Authors: Guyez Anne , Bonnet Stéphane , Reimann Tony , Carretier Sébastien , Wallinga Jakob
Published: January 2023

Quantifying sediment transport and storage in fluvial systems is fundamental for understanding the transfer of eroded materials from source to sink. Here, we investigated the potential of a combined approach using a luminescence measured in modern fluvial sediments and numerical simulations to quantify transport and storage in rivers. We acquired luminescence data at the single‐grain scale on feldspar sediments of Waimakariri and Rakaia braided rivers (New Zealand) using a post infra‐red infra‐red stimulated luminescence protocol. We considered three metrics from the analysis of luminescence equivalent dose (De) distribution: the percentage of bleached and the percentage of saturated grains, and the meanDe. All three metrics show similar longitudinal trends along both rivers. To derive quantitative information on sediment transfer from these data, we developed a numerical model that simulates the longitudinal evolution ofDedistribution of a population of grains during transport and storage in floodplains. The model considers four main parameters: the transport length of grains during floods, their resting time between successive transport events, the bleaching probability (probability of the luminescence signal to be reset due to sunlight exposure during transport or rest), and the likelihood of partial bleaching. Identification of model parameters that best reproduce natural observations allowed estimating transit time of sediments between 2.1 and 10.3 Kyr (mean of 6.9  2.9 Kyr), corresponding to mean virtual transit velocity of 20–95 m.yr−1(mean of 46  28 m.yr−1). Our study illustrates the potential of the combined single‐grain luminescence and modeling approach to quantify sediment transfer in fluvial systems.
Late Miocene to Present Paleoclimatic and Paleoenvironmental Evolution of the South China Sea Recorded in the Magneto‐Cyclostratigraphy of IODP Site U1505
Authors: Nie Yunfeng , Wu Huaichun , Satolli Sara , Ferré Eric C. , Shi Meinan , Fang Qiang , Xu Ye , Zhang Shihong , Li Haiyan , Yang Tianshui
Published: January 2023

The continuous sedimentary cores recovered at the International Ocean Discovery Program (IODP) Site U1505, Expedition 368, provide an opportunity for paleoceanography and paleoclimate reconstruction in the continental margin of the northern South China Sea (SCS). In this study, we conducted detailed rock‐ and paleomagnetic studies on 420 discrete samples from the top ∼200 m of the synthetic records of Holes U1505C and U1505D. Rock magnetic analyses indicate that low‐coercivity pseudosingle domain magnetite dominates as the primary ferromagnetic mineral of Site U1505. The magnetostratigraphic age model was constructed by correlating the interpreted polarity sequence with the Geomagnetic Polarity Time Scale 2020 with the constraints of the biostratigraphic data and the distribution probability of the age of each polarity zone provided by a Dynamic Time Warping algorithm. The Milankovitch cycles of the short eccentricity, obliquity, and precession cycles were identified in the magnetic susceptibility (MS) and natural gamma radiation (NGR) series based on paleomagnetic results. We established an ∼9 Myr high‐resolution astronomical time scale by tuning the MS and NGR records to the global oxygen isotope curves, the obliquity, and the eccentricity curves of the La2004 astronomical solution. Our new age model reveals detailed sedimentation rate variations and a ∼500 kyr hiatus across the Brunhes‐Matuyama boundary related to local tectonic activity. These results lay the foundation for understanding the paleoceanography and paleoclimate evolution of the SCS.
Origin of Late Triassic Granitoids of the Coastal Cordillera of Southern Central Chile (34°–37°S): Multi‐Isotopic Evidence of Slab Tearing Effects on Pre‐Andean Magmagenesis
Authors: Rossel Pablo , Gianni Guido M. , Reinoso Valeria , Fanning C. Mark , Ducea Mihai N. , Muñoz Tamara , Salvat Daniela
Published: January 2023

The Coastal Cordillera of Central Chile (34°–37°S) holds a series of Late Triassic granitoids classically interpreted as early Andean subduction‐related magmatism based on their arc‐like geochemical signature. Here, we present geochemical, isotopic, and geochronological data and a tomotectonic analysis that challenge this idea indicating a local interruption of the normal subduction process likely associated with a slab‐tearing event. Our results suggest that the source of the magmas is related to melting of asthenospheric mantle and crustal rocks of a metasedimentary Paleozoic complex. We suggest that partial melting of these sources was triggered by a slab tear‐related asthenosphere upwelling producing high‐silica S/I‐ and S‐Type granites of the Constitución and Hualpén areas, and anorogenic A‐Type granitoids in Cobquecura area. Also, partial melting of a metasomatized asthenospheric mantle plus continental crust that experienced previous high‐temperature hydrothermal alteration would have generated high‐silica magmas with low δ18O, high Pb, CHUR‐like 87Sr/86Sr, and 143Nd/144Nd ratios that originated La Estrella Granite. Our results offer an alternative explanation for the existence of subtle magmatic arc‐like geochemical signatures in the study area and support a segmentation of the active margin during the Late Triassic. The widespread upper‐plate magmatic record of slab‐tearing, spanning the Coastal Cordillera of Central Chile to the intraplate Neuquén basin in Argentina, and the lower mantle record of a slab gap, detected in ours and previous tomotectonic analyses, make the Late Triassic slab‐tearing event in southwestern Pangea the most robustly constrained pre‐Cenozoic slab tear process so far.
Scaling of Floods With Geomorphologic Characteristics and Precipitation Variability Across the Conterminous United States
Authors: Najibi Nasser , Devineni Naresh
Published: January 2023

Accurate flood risk assessment requires a comprehensive understanding of flood sensitivity to regional drivers and climate factors. This paper presents the scaling of floods (duration, peak, volume) with geomorphologic characteristics of the basin (i.e., drainage area, slope, elevation) and precipitation patterns (rainfall accumulation, variability). Long‐term daily streamflow observations over the 20th and early 21st centuries from Hydro‐Climatic Data Network streamgages across the conterminous United States are used to create a flood event database based on their flood stage information. Antecedent daily rainfall accumulation and variability corresponding to these floods are computed using Global Historical Climatology Network daily data set. Two Bayesian scaling models are developed, and the spatial organization of scaling exponents is investigated. The baseline model quantifies the scaling of floods to geomorphologic characteristics. The dynamic model quantifies the scaling of floods to antecedent precipitation distribution which is further conditioned on geomorphologic characteristics. Results show that small and low‐elevation basins have a stronger response to antecedent rainfall distribution in amplifying flood peaks, while high‐elevation steeper basins have a lower response for flood duration and volume. The dynamic models demonstrate that there are significant variations in the flood scaling rates, with the largest rates up to 40% and 4.5% for flood duration, 64% and 44% for peak, and 98% and 40% for volume found across the Northeast, Coastal Southeast, and Northwest with intensifying rainfall accumulation and variability, respectively. This study advances flood predictions by better informing the flood attributes in the context of dynamical land‐atmosphere perturbations.
Regorafenib induces Bim-mediated intrinsic apoptosis by blocking AKT-mediated FOXO3a nuclear export
Authors: Sun Beini , Chen Hongce , Wang Xiaoping , Chen Tongsheng
Published: January 2023

Regorafenib (REGO) is a synthetic oral multi-kinase inhibitor with potent antitumor activity. In this study, we investigate the molecular mechanisms by which REGO induces apoptosis. REGO induced cytotoxicity, inhibited the proliferation and migration ability of cells, and induced nuclear condensation, and reactive oxygen species (ROS)-dependent apoptosis in cancer cells. REGO downregulated PI3K and p-AKT level, and prevented FOXO3a nuclear export. Most importantly, AKT agonist (SC79) not only inhibited REGO-induced FOXO3a nuclear localization and apoptosis but also restored the proliferation and migration ability of cancer cells, further demonstrating that REGO prevented FOXO3a nuclear export by deactivating PI3K/AKT. REGO treatment promotes Bim expression via the FOXO3a nuclear localization pathway following PI3K/AKT inactivation. REGO induced Bim upregulation and translocation into mitochondria as well as Bim-mediated Bax translocation into mitochondria. Fluorescence resonance energy transfer (FRET) analysis showed that REGO enhanced the binding of Bim to Bak/Bax. Knockdown of Bim, Bak and Bax respectively almost completely inhibited REGO-induced apoptosis, demonstrating the key role of Bim by directly activating Bax/Bak. Knockdown of Bax but not Bak inhibited REGO-induced Drp1 oligomerization in mitochondria. In conclusion, our data demonstrate that REGO promotes apoptosis via the PI3K/AKT/FOXO3a/Bim-mediated intrinsic pathway.
Copper intrauterine device increases vaginal concentrations of inflammatory anaerobes and depletes lactobacilli compared to hormonal options in a randomized trial
Authors: Brown Bryan P. , Feng Colin , Tanko Ramla F. , Jaumdally Shameem Z. , Bunjun Rubina , Dabee Smritee , Happel Anna-Ursula , Gasper Melanie , Nyangahu Donald D. , Onono Maricianah , Nair Gonasagrie , Palanee-Phillips Thesla , Scoville Caitlin W. , Heller Kate , Baeten Jared M. , Bosinger Steven E. , Burgener Adam , Passmore Jo-Ann S. , Heffron Renee , Jaspan Heather B.
Published: January 2023

Effective contraceptives are a global health imperative for reproductive-aged women. However, there remains a lack of rigorous data regarding the effects of contraceptive options on vaginal bacteria and inflammation. Among 218 women enrolled into a substudy of the ECHO Trial (NCT02550067), we evaluate the effect of injectable intramuscular depot medroxyprogesterone acetate (DMPA-IM), levonorgestrel implant (LNG), and a copper intrauterine device (Cu-IUD) on the vaginal environment after one and six consecutive months of use, using 16S rRNA gene sequencing and multiplex cytokine assays. Primary endpoints include incident BV occurrence, bacterial diversity, and bacterial and cytokine concentrations. Secondary endpoints are bacterial and cytokine concentrations associated with later HIV seroconversion. Participants randomized to Cu-IUD exhibit elevated bacterial diversity, increased cytokine concentrations, and decreased relative abundance of lactobacilli after one and six months of use, relative to enrollment and other contraceptive options. Total bacterial loads of women using Cu-IUD increase 5.5 fold after six months, predominantly driven by increases in the concentrations of several inflammatory anaerobes. Furthermore, growth ofL. crispatus(MV-1A-US) is inhibited by Cu2+ions below biologically relevant concentrations, in vitro. Our work illustrates deleterious effects on the vaginal environment induced by Cu-IUD initiation, which may adversely impact sexual and reproductive health.
A supramolecular cucurbit[8]uril-based rotaxane chemosensor for the optical tryptophan detection in human serum and urine
Authors: Krämer Joana , Grimm Laura M. , Zhong Chunting , Hirtz Michael , Biedermann Frank
Published: January 2023

Sensing small biomolecules in biofluids remains challenging for many optical chemosensors based on supramolecular host-guest interactions due to adverse interplays with salts, proteins, and other biofluid components. Instead of following the established strategy of developing alternative synthetic binders with improved affinities and selectivity, we report a molecular engineering approach that addresses this biofluid challenge. Here we introduce a cucurbit[8]uril-based rotaxane chemosensor feasible for sensing the health-relevant biomarker tryptophan at physiologically relevant concentrations, even in protein- and lipid-containing human blood serum and urine. Moreover, this chemosensor enables emission-based high-throughput screening in a microwell plate format and can be used for label-free enzymatic reaction monitoring and chirality sensing. Printed sensor chips with surface-immobilized rotaxane-microarrays are used for fluorescence microscopy imaging of tryptophan. Our system overcomes the limitations of current supramolecular host-guest chemosensors and will foster future applications of supramolecular sensors for molecular diagnostics.
Enhancing CAR-T cell functionality in a patient-specific manner
Authors: Zhang David K. Y. , Adu-Berchie Kwasi , Iyer Siddharth , Liu Yutong , Cieri Nicoletta , Brockman Joshua M. , Neuberg Donna , Wu Catherine J. , Mooney David J.
Published: January 2023

Patient responses to autologous CD19 chimeric antigen receptor (CAR) T-cell therapies are limited by insufficient and inconsistent cellular functionality. Here, we show that controlling the precise level of stimulation during T-cell activation to accommodate individual differences in the donor cells will dictate the functional attributes of CAR-T cell products. The functionality of CAR-T cell products, consisting of a diverse set of blood samples derived from healthy donors, acute lymphoblastic leukemia (ALL), and chronic lymphocytic lymphoma (CLL) patient samples, representing a range of patient health status, is tested upon culturing on artificial antigen-presenting cell scaffolds to deliver T-cell stimulatory ligands (anti-CD3/anti-CD28) at highly defined densities. A clear relationship is observed between the dose of stimulation, the phenotype of the T-cell blood sample prior to T-cell activation, and the functionality of the resulting CAR-T cell products. We present a model, based on this dataset, that predicts the precise stimulation needed to manufacture a desired CAR-T cell product, given the input T-cell attributes in the initial blood sample. These findings demonstrate a simple approach to enhance CAR-T functionality by personalizing the level of stimulation during T-cell activation to enable flexible manufacturing of more consistent and potent CAR-T cells.
Design principles of improving the dose-response alignment in coupled GTPase switches
Authors: Qiao Lingxia , Ghosh Pradipta , Rangamani Padmini
Published: January 2023

“Dose-response alignment” (DoRA), where the downstream response of cellular signaling pathways closely matches the fraction of activated receptor, can improve the fidelity of dose information transmission. The negative feedback has been experimentally identified as a key component for DoRA, but numerical simulations indicate that negative feedback is not sufficient to achieve perfect DoRA, i.e., perfect match of downstream response and receptor activation level. Thus a natural question is whether there exist design principles for signaling motifs within only negative feedback loops to improve DoRA to near-perfect DoRA. Here, we investigated several model formulations of an experimentally validated circuit that couples two molecular switches—mGTPase (monomeric GTPase) and tGTPase (heterotrimeric GTPases) — with negative feedback loops. In the absence of feedback, the low and intermediate mGTPase activation levels benefit DoRA in mass action and Hill-function models, respectively. Adding negative feedback has versatile roles on DoRA: it may impair DoRA in the mass action model with low mGTPase activation level and Hill-function model with intermediate mGTPase activation level; in other cases, i.e., the mass action model with a high mGTPase activation level or the Hill-function model with a non-intermediate mGTPase activation level, it improves DoRA. Furthermore, we found that DoRA in a longer cascade (i.e., tGTPase) can be obtained using Hill-function kinetics under certain conditions. In summary, we show how ranges of activity of mGTPase, reaction kinetics, the negative feedback, and the cascade length affect DoRA. This work provides a framework for improving the DoRA performance in signaling motifs with negative feedback.
High-throughput phase elucidation of polycrystalline materials using serial rotation electron diffraction
Authors: Luo Yi , Wang Bin , Smeets Stef , Sun Junliang , Yang Weimin , Zou Xiaodong
Published: January 2023

Rapid phase elucidation of polycrystalline materials is essential for developing new materials of chemical, pharmaceutical and industrial interest. Yet, the size and quantity of many crystalline phases are too small for routine X-ray diffraction analysis. This has become a workflow bottleneck in materials development, especially in high-throughput synthesis screening. Here we demonstrate the application of serial rotation electron diffraction (SerialRED) for high-throughput phase identification of complex polycrystalline zeolite products. The products were prepared from a combination of multiple framework T atoms ([Si,Ge,Al] or [Si,Ge,B]) and a simple organic structure-directing agent. We show that using SerialRED, five zeolite phases can be identified from a highly complex mixture. This includes phases with ultra-low contents undetectable using X-ray diffraction and phases with identical crystal morphology and similar unit cell parameters. By automatically and rapidly examining hundreds of crystals, SerialRED enables high-throughput phase analysis and allows the exploration of complex synthesis systems. It provides new opportunities for rapid development of polycrystalline materials.
L-form conversion in Gram-positive bacteria enables escape from phage infection
Authors: Wohlfarth Jan C. , Feldmüller Miki , Schneller Alissa , Kilcher Samuel , Burkolter Marco , Meile Susanne , Pilhofer Martin , Schuppler Markus , Loessner Martin J.
Published: January 2023

At the end of a lytic bacteriophage replication cycle in Gram-positive bacteria, peptidoglycan-degrading endolysins that cause explosive cell lysis of the host can also attack non-infected bystander cells. Here we show that in osmotically stabilized environments, Listeria monocytogenes can evade phage predation by transient conversion to a cell wall-deficient L-form state. This L-form escape is triggered by endolysins disintegrating the cell wall from without, leading to turgor-driven extrusion of wall-deficient, yet viable L-form cells. Remarkably, in the absence of phage predation, we show that L-forms can quickly revert to the walled state. These findings suggest that L-form conversion represents a population-level persistence mechanism to evade complete eradication by phage attack. Importantly, we also demonstrate phage-mediated L-form switching of the urinary tract pathogen Enterococcus faecalis in human urine, which underscores that this escape route may be widespread and has important implications for phage- and endolysin-based therapeutic interventions.
Environmental ranking of European industrial facilities by toxicity and global warming potentials
Authors: Erhart Szilárd , Erhart Kornél
Published: January 2023

We present a methodology to develop the integrated toxicity and climate change risk assessment of Europe based facilities, industries and regions. There is an increasingly important need for large scale sustainability measurement solutions for company reporting with high granularity. In this paper we measure key aspects of Sustainable Development Goals in terms of human, cancer and non-cancer toxicity, ecotoxicity together with global warming impact potentials from point source pollutant releases of more than 10,000 companies and their 33,000 facilities in Europe from 2001 to 2017, by using the European Pollutant Release and Transfer Register. For our assessment, we deploy a scientific consensus model, USEtox for characterizing human and ecotoxicological impacts of chemicals and the global warming potential values from the Intergovernmental Panel on Climate Change. We discuss water and air emissions of dozens of pollutants in urban, rural, coastal and inland areas. Companies in the electricity production sector are estimated to have the largest human toxicity impact potential (46% of total) and the largest global warming impact potential (50%), while companies in the sewerage sector have the largest ecotoxicity impact potential (50%). In the overall economy, the correlation between facilities’ global warming and toxicity impact potentials is positive, however, not very strong. Therefore, we argue that carbon footprint of industrial organizations can be only used as a climate change risk indicator, but not as an overall environmental performance indicator. We confirm impact potentials of major pollutants in previous research papers (Hg accounting for 76% of the total human toxicity and Zn accounting for 68% of total ecotoxicity), although we draw the attention to the limitations of USEtox in case of metals. From 2001 to 2017 total human toxicity dropped by 28%, although the downward trend reversed in 2016. Ecotoxicity and global warming impact potentials remained unchanged in the same period. Finally, we show that the European pollutant release monitoring data quality could be further improved, as only three quarters of the toxic releases are measured in the Member States of the European Union, and a high share of toxic pollutant releases are only estimated in some countries. Of the measured or calculated toxic releases, only one third is reported according to the most robust CEN/ISO standards and about one fifth according to the least preferred other methods, like engineering judgements.
Machine-learning-based spectral methods for partial differential equations
Authors: Meuris Brek , Qadeer Saad , Stinis Panos
Published: January 2023

Spectral methods are an important part of scientific computing’s arsenal for solving partial differential equations (PDEs). However, their applicability and effectiveness depend crucially on the choice of basis functions used to expand the solution of a PDE. The last decade has seen the emergence of deep learning as a strong contender in providing efficient representations of complex functions. In the current work, we present an approach for combining deep neural networks with spectral methods to solve PDEs. In particular, we use a deep learning technique known as the Deep Operator Network (DeepONet) to identify candidate functions on which to expand the solution of PDEs. We have devised an approach that uses the candidate functions provided by the DeepONet as a starting point to construct a set of functions that have the following properties: (1) they constitute a basis, (2) they are orthonormal, and (3) they are hierarchical, i.e., akin to Fourier series or orthogonal polynomials. We have exploited the favorable properties of our custom-made basis functions to both study their approximation capability and use them to expand the solution of linear and nonlinear time-dependent PDEs. The proposed approach advances the state of the art and versatility of spectral methods and, more generally, promotes the synergy between traditional scientific computing and machine learning.