bluuebunny/crossref_metadata_2025 huggingface dataset:
Two-stage complex action recognition framework for real-time surveillance automatic violence detection
Authors: Lopez Dylan Josh Domingo , Lien Cheng-Chang
Published: September 2023

Violent action classification in community-based surveillance is a particularly challenging concept in itself. The ambiguity of violence as a complex action can lead to the misclassification of violence-related crimes in detection models and the increased complexity of intelligent surveillance systems leading to greater costs in operations or cost of lives. This paper demonstrates a novel approach to performing automatic violence detection by considering violence as complex actions mitigating oversimplification or overgeneralization of detection models. The proposed work supports the notion that violence is a complex action and is classifiable through decomposition into more identifiable actions that could be easily recognized by human action recognition algorithms. A two-stage framework was designed to detect simple actions which are sub-concepts of violence in a two-stream action recognition architecture. Using a basic logistic regression layer, simple actions were further classified as complex actions for violence detection. Varying configurations of the work were tested, such as applying action silhouettes, varying activation caching sizes, and different pooling methods for post-classification smoothing. The framework was evaluated considering accuracy, recall, and operational speed considering its implications in community deployment. The experimental results show that the developed framework reaches 21 FPS operation speeds for real-time operations and 11 FPS for non-real-time operations. Using the proposed variable caching algorithm, median pooling results in accuracy reaching 83.08% and 80.50% for non-real-time and real-time operations. In comparison, applying max pooling results to recalls reached 89.55% and 84.93% for non-real-time and real-time operations, respectively. This paper shows that complex action decomposition is deemed to be an appropriate method through the comparable performance with existing efforts that have not considered violence as complex actions implying a new perspective for automatic violence detection in intelligent surveillance systems.
Analysis of the impact of demand response on the Norwegian energy system
Authors: Ahang Mohammadreza , Seljom Pernille Merethe Sire , Tomasgard Asgeir
Published: September 2023

European CO2 reduction goals have led to an increase in variable energy sources such as wind and solar, and consequently to an energy system that will need more flexibility in the future. In Norway, the hydropower reservoirs will enable the country to play a crucial role in European electrification by delivering flexibility to countries in Northern Europe. A further source of flexibility is demand response (DR) accumulated in residential, commercial, and industrial sectors. The paper discusses DR, load shifting, and load shedding based on the application of a stochastic TIMES model and it evaluates the role of DR in the Norwegian energy system towards 2050. The analysis shows that cost-efficient DR operation primarily comes from space heating in residential buildings. The use of DR, which is season-dependent, increases the volume of electricity trade, including electricity export and import to neighboring countries, and it smooths electricity prices. The implementation of DR in Norway leads to decreases in expected electricity price and total system cost by exporting flexible electricity and importing low price electricity. Additionally, it affects hydropower and reservoir management.
Factors associated with adherence to BRCA1/2 mutation testing after oncogenetic counseling in long-surviving patients with a previous diagnosis of breast or ovarian cancer
Authors: Actis Silvia , D’Alonzo Marta , Pace Luca , Mucciacito Serena , Bounous Valentina Elisabetta , Sgrò Luca Giuseppe , Mancarella Matteo , Ferrero Annamaria , Biglia Nicoletta
Published: September 2023

BRCA1/2 mutations account for 5 to 10% of breast and 15% of ovarian cancers. Various guidelines on BRCA1/2 genetic counseling and testing have been issued, and the criteria have evolved over the years. Oncogenetic counseling aims to inform patients about the possibility and implications of undergoing predictive testing and risk management programs. We analyzed a cohort of 50 subjects with a previous personal history of breast or ovarian cancer who had not been tested for BRCA1/2 mutations at the time of diagnosis but were found eligible according to the most recent guidelines. All patients were offered pre-test oncogenetic counseling and BRCA1/2 genetic testing. The mean time from cancer diagnosis to genetic counseling was over 10 years. We analyzed socio-demographic and psychological parameters associated with the decision to undergo BRCA1/2 genetic testing or the reasons behind the withdrawal. Thirty-nine patients underwent BRCA1/2 genetic testing. Patients who accept the genetic test communicate more easily with family members than those who refuse. Factors associated with test refusal are having a long-term partner and having a negative perception of life. There is a trend, although not statistically significant, toward younger age at cancer diagnosis, more likely to participate in cancer screening programs (71.8% vs. 45.5%), and more likely to have daughters (63.3% vs. 37.5%) in the group that accepted the test. The offer of BRCA testing was well accepted by our study population, despite the many years since the cancer diagnosis. With the perspective of further broadening the access criteria to genetic testing, it is important to understand how to best approach pre-test counseling in long-surviving patients with a previous diagnosis of cancer.
LED light can falsify pulse oximetry readings via the stroboscopic effect
Authors: Wald Martin , Erwin Peter , Annon-Eberharter Natalee , Werther Tobias
Published: September 2023

Because of its simplicity, pulse oximetry plays a ubiquitous role in neonatology. Its measurements are based on the absorption of light by hemoglobin. Ambient light can affect these values, therefore algorithms are designed to compensate for constant ambient light. Modern light-emitting diodes often flicker at a very high frequency. Such flickering ambient light can lead to significant measurement errors in saturation. To present a novel way in which light-emitting diodes influence the function of pulse oximeters and to demonstrate mathematically that a stroboscopic effect may well be responsible for this disturbance. Using publicly available data, a mathematical model of a pulse oximeter with a calibration curve and a proprietary measurement algorithm was created. This was used to simulate saturation measurements in flickering ambient light. To do this, photopletysmograms for red and infrared light at 98% oxygen saturation were mathematically superimposed on the light emission from an examination lamp used in the intensive care unit. From these results, presumable saturation measurements from a pulse oximeter were extrapolated. The light-emitting diodes in the examination lamp flicker at 207 Hz. The pulsating light from the light-emitting diodes causes superimposition of the photoplethysmogram due to the stroboscopic effect. With increasing brightness, the saturation dropped to 85% and the pulse rate to 108 bpm. The pulsed light of light-emitting diodes can distort pulse oximetry measurements. The stroboscopic effect leads to low saturation values, which can lead to the risk of blindness in premature infants due to excessive oxygenation.
Experimental investigation of UAV rotor aeroacoustics and aerodynamics with computational cross-validation
Authors: Kostek Anna A. , Lößle Felix , Wickersheim Robin , Keßler Manuel , Boisard Ronan , Reboul Gabriel , Visingardi Antonio , Barbarino Mattia , Gardner Anthony D.
Published: September 2023

The study provided a base of comparison of known computational techniques with different fidelity levels for performance and noise prediction of a single, fixed-pitch UAV rotor operating with varying flight parameters. The range of aerodynamic tools included blade element theory, potential flow methods (UPM, RAMSYS), lifting-line method (PUMA) and Navier–Stokes solver (FLOWer). Obtained loading distributions served as input for aeroacoustic codes delivering noise estimation for the blade passing frequency on a plane below the rotor. The resulting forces and noise levels showed satisfactory agreement with experimental data; however, differences in accuracy could be noticed depending on the computational method applied. The wake influence on the results was estimated based on vortex trajectories from simulations and those visible in background-oriented schlieren (BOS) pictures. The analysis of scattering effects showed that influence of ground and rotor platform on aeroacoustic results was observable even for low frequencies.
Leveraging research infrastructure co-location to evaluate constraints on terrestrial carbon cycling in northern European forests
Authors: Futter Martyn N. , Dirnböck Thomas , Forsius Martin , Bäck Jaana K. , Cools Nathalie , Diaz-Pines Eugenio , Dick Jan , Gaube Veronika , Gillespie Lauren M. , Högbom Lars , Laudon Hjalmar , Mirtl Michael , Nikolaidis Nikolaos , Poppe Terán Christian , Skiba Ute , Vereecken Harry , Villwock Holger , Weldon James , Wohner Christoph , Alam Syed Ashraful
Published: September 2023

Integrated long-term, in-situ observations are needed to document ongoing environmental change, to “ground-truth” remote sensing and model outputs and to predict future Earth system behaviour. The scientific and societal value of in-situ observations increases with site representativeness, temporal duration, number of parameters measured and comparability within and across sites. Research Infrastructures (RIs) can support harmonised, cross-site data collection, curation and publication. Integrating RI networks through site co-location and standardised observation methods can help answers three questions about the terrestrial carbon sink: (i) What are present and future carbon sequestration rates in northern European forests? (ii) How are these rates controlled? (iii) Why do the observed patterns exist? Here, we present a conceptual model for RI co-location and highlight potential insights into the terrestrial carbon sink achievable when long-term in-situ Earth observation sites participate in multiple RI networks (e.g., ICOS and eLTER). Finally, we offer recommendations to promote RI co-location.
Morelli-Włodarczyk cobordism and examples of rooftop flips
Authors: Barban Lorenzo , Franceschini Alberto
Published: September 2023

We introduce the notion of rooftop flip, namely a small modification among normal projective varieties which is modeled by a smooth projective variety of Picard number 2 admitting two projective bundle structures. Examples include the Atiyah flop and the Mukai flop, modeled respectively by $$\mathbb {P}^1\times \mathbb {P}^1$$

P

1

×

P

1

and by $$\mathbb {P}\left( T_{\mathbb {P}^2}\right) $$

P

T

P

2

. Using the Morelli-Włodarczyk cobordism, we prove that any smooth projective variety of Picard number 1, endowed with a $${\mathbb C}^*$$

C

∗

-action with only two fixed point components, induces a rooftop flip.
Exploring the Role of Sprint Biomechanics in Hamstring Strain Injuries: A Current Opinion on Existing Concepts and Evidence
Authors: Bramah Christopher , Mendiguchia Jurdan , Dos’Santos Thomas , Morin Jean-Benoȋt
Published: September 2023

Hamstring strain injuries are one of the most common injuries in sprint-based sports with the mechanism of injury considered the result of an interaction between applied mechanical strain and the capacity of the muscle to tolerate strain. To date, injury prevention and rehabilitation strategies have frequently focused on enhancing the capacity of the hamstrings to tolerate strain, with little consideration of factors directly influencing mechanical strain. Sprint running biomechanics are one factor proposed to influence the mechanical strain applied to the hamstrings that may be modified (towards reduced strain) within rehabilitation and injury prevention programs. This article aims to explore the theoretical mechanistic link between sprint running mechanics and hamstring strain injury, along with the available supporting evidence. In doing so, it hopes to provide practitioners with an understanding of mechanical parameters that may influence hamstring strain injury whilst also identifying areas for further research exploration.
Aussagekraft von Prokollagen Typ I aminoterminales Propeptid (P1NP) als Knochenaufbaumarker
Authors: Oremek G. M. , Holzgreve F. , Maurer-Grubinger C. , Diaremes P. , Erbe C. , Ohlendorf D.
Published: September 2023

Die vorliegende informative Zusammenfassung über den Knochenaufbaumarker Prokollagen Typ I aminoterminales Propeptid (P1NP) wird im Rahmen der Serie „Biomarker“ des Zentralblatts für Arbeitsmedizin, Arbeitsschutz und Ergonomie publiziert und dient als Fortbildung für Arbeitsmediziner*innen. Sie beschäftigt sich mit dem immer häufigeren Gebrauch der Bestimmung von spezifischen Markern bei sog. Manager-Vorsorgen und Check-up-Untersuchungen. P1NP zeigt eine hohe Sensitivität und Spezifität aber eignet sich grundsätzlich nicht als Screening-Parameter zur Frühdiagnostik oder für Vorsorgen, da es ein Marker zur Therapie‑, Verlaufs- und Rezidivkontrolle von Knochenmetastasen ist.
Zusammenhang zwischen Overcommitment und Burnout-Risiko bei ukrainischen und deutschen Kindergartenerzieherinnen
Authors: Kuhrmeier Marian , Darius Sabine , Lysak Maryna , Zavgorodnij Igor , Böckelmann Irina
Published: September 2023

Psychische Belastungen im Erzieherberuf können Beeinträchtigungen der Gesundheit bei den Erzieherinnen hervorrufen. Ziel der Querschnittsstudie war es, Zusammenhänge einer übersteigerten beruflichen Verausgabungsneigung (Overcommitment, OC) mit dem Burnout-Risiko länderübergreifend bei deutschen (D) und ukrainischen (U) Erzieherinnen zu analysieren. Die Stichprobe von 292 Befragten bestand aus 185 deutschen und 107 ukrainischen Kindergartenerzieherinnen. Das OC und das Burnout-Risiko wurden mittels standardisierter Fragebögen in deutscher bzw. russischer Sprache erhoben. Bei über 70 % der Studienteilnehmerinnen lag ein normales OC vor. 25,4 % der deutschen und 22,4 % der ukrainischen Erzieherinnen zeigten ein kritisches OC (> 18 Punkte) und teilweise bereits einige Burnout-Symptome. Ein Burnout-Risiko war insgesamt bei 4,9 % (D) bzw. 2,8 % (U) der Erzieherinnen vorhanden. In beiden Teilstichproben korrelierte das OC positiv mit den Dimensionen emotionale Erschöpfung (r = 0,410 (D); bzw. = 0,496 [U]) und Zynismus (r = 0,225 [D]; bzw. = 0,444 [U]) sowie dem Burnout-Risiko (r = 0,336 [D] bzw. = 0,495 [U]). Ein kritisches OC hat möglicherweise einen negativen Einfluss auf die psychische Gesundheit und kann das Burnout-Risiko erhöhen. Präventive Maßnahmen sollten, insbesondere bei Erzieherinnen mit einem kritischen OC, ergriffen werden, um den psychischen Beeinträchtigungen entgegenwirken zu können. Ressourcenorientierte Ansätze könnten das Angebot ergänzen.
Prospects of BRICS currency dominance in international trade
Authors: Coquidé Célestin , Lages José , Shepelyansky Dima L.
Published: September 2023

During the April 2023 Brazil–China summit, the creation of a trade currency supported by the BRICS countries was proposed. Using the United Nations Comtrade database, providing the frame of the world trade network associated to 194 UN countries during the decade 2010–2020, we study a mathematical model of influence battle of three currencies, namely, the US dollar, the euro, and such a hypothetical BRICS currency. In this model, a country trade preference for one of the three currencies is determined by a multiplicative factor based on trade flows between countries and their relative weights in the global international trade. The three currency seed groups are formed by 9 eurozone countries for the euro, 5 Anglo-Saxon countries for the US dollar and the 5 BRICS countries for the new proposed currency. The countries belonging to these 3 currency seed groups trade only with their own associated currency whereas the other countries choose their preferred trade currency as a function of the trade relations with their commercial partners. The trade currency preferences of countries are determined on the basis of a Monte Carlo modeling of Ising type interactions in magnetic spin systems commonly used to model opinion formation in social networks. We adapt here these models to the world trade network analysis. The results obtained from our mathematical modeling of the structure of the global trade network show that as early as 2012 about 58% of countries would have preferred to trade with the BRICS currency, 23% with the euro and 19% with the US dollar. Our results announce favorable prospects for a dominance of the BRICS currency in international trade, if only trade relations are taken into account, whereas political and other aspects are neglected.
From antimicrobial to anticancer: the pioneering works of Prof. Luiz Rodolpho Travassos on bioactive peptides
Authors: Koskela Saara A. , Figueiredo Carlos R.
Published: September 2023

Prof. Luiz Rodolpho Travassos, a distinguished Brazilian scientist, was instrumental in fostering an interdisciplinary research approach that seamlessly combined microbiology and oncology. This work has opened new pathways into the understanding of tumorigenesis and aided in the development of innovative therapeutic tools. One significant area of his work has been the exploration of bioactive peptides, many of which were first identified for their antimicrobial properties. These peptides demonstrate promise as potential cancer therapeutics due to their selectivity, cost-effectiveness, ease of synthesis, low antigenicity, and excellent tissue penetration. Prof. Travassos’ pioneering work uncovered on the potential of peptides derived from microbiological sources, such as those obtained using phage display techniques. More importantly, in international cooperation, peptides derived from complementarity-determining regions (CDRs) that showed antimicrobial activity against Candida albicans further showed to be promising tools with cytotoxic properties against cancer cells. Similarly, peptides derived from natural sources, such as the gomesin peptide, not only had shown antimicrobial properties but could treat cutaneous melanoma in experimental models. These therapeutic tools allowed Prof. Travassos and his group to navigate the intricate landscape of factors and pathways that drive cancer development, including persistent proliferative signaling, evasion of tumor suppressor genes, inhibition of programmed cell death, and cellular immortality. This review examines the mechanisms of action of these peptides, aligning them with the universally recognized hallmarks of cancer, and evaluates their potential as drug candidates. It highlights the crucial need for more selective, microbiology-inspired anti-cancer strategies that spare healthy cells, a challenge that current therapies often struggle to address. By offering a comprehensive assessment of Prof. Travassos’ innovative contributions and a detailed discussion on the increasing importance of microbiology-derived peptides, this review presents an informed and robust perspective on the possible future direction of cancer therapy.
Placental Pathology Findings in Unexplained Pregnancy Losses
Authors: Thompson Beatrix B. , Holzer Parker H. , Kliman Harvey J.
Published: September 2023

There are approximately 5 million pregnancies per year in the USA, with 1 million ending in miscarriage (a loss occurring prior to 20 weeks of gestation) and over 20,000 ending in stillbirth at or beyond 20 weeks of gestation. As many as 50% of these losses are unexplained. Our objective was to evaluate the effect of expanding the placental pathology diagnostic categories to include the explicit categories of (1) dysmorphic chorionic villi and (2) small placenta in examining previously unexplained losses. Using a clinical database of 1256 previously unexplained losses at 6–43 weeks of gestation, the most prevalent abnormality associated with each loss was determined through examination of its placental pathology slides. Of 1256 cases analyzed from 922 patients, there were 878 (69.9%) miscarriages and 378 (30.1%) antepartum stillbirths. We determined the pathologic diagnoses for 1150/1256 (91.6%) of the entire series, 777/878 (88.5%) of the miscarriages (< 20 weeks’ gestation), and 373/378 (98.7%) of the stillbirths (≥ 20 weeks’ gestation). The most common pathologic feature observed in unexplained miscarriages was dysmorphic chorionic villi (757 cases; 86.2%), a marker associated with genetic abnormalities. The most common pathologic feature observed in unexplained stillbirths was a small placenta (128 cases; 33.9%). Our classification system reinforced the utility of placental examination for elucidating potential mechanisms behind pregnancy loss. The improved rate of diagnosis appeared to be the result of filling a gap in previous pregnancy loss classification systems via inclusion of the categories of dysmorphic chorionic villi and small placenta.

Graphical Abstract
Mobile application development for estimation of permissible load on shallow and deep foundation using SPT data
Authors: Khatri Vishwas Nandkishor , Yadav Jitendra Singh , Sundriyal Shuvam
Published: September 2023

The present study demonstrates the development of an Android Application that aims to calculate the allowable bearing pressure for shallow foundations and safe load on pile foundations using the SPT data. The application was built using Android Studio 2020, utilizing XML for the User Interface and Java for the coding. The application offers support for various foundation types, including strip, square, rectangle, and circular shapes for shallow foundations and circular shape for pile foundations. The in-situ SPT data entered by the user was corrected and then processed to calculate soil properties. Subsequently, the bearing pressure for shallow foundation and safe load on the pile was computed adhering to relevant codes. The developed application was verified by comparing the results with already solved examples in the literature. The developed application may be considered under Intelligence in Geotechnics. The created application will be helpful for field engineers to estimate soil parameters and allowable bearing pressure on-site quickly. As a result, it decreases the amount of time and effort necessary for design and thus eliminates the need to refer to tables, codes, and consultants.
Citizens Under Compulsory Voting: A Three-Country Study
Authors: Dassonneville Ruth , Barbosa Thiago , Blais André , McAllister Ian , Turgeon Mathieu
Published: September 2023

A burgeoning literature studies compulsory voting and its effects on turnout, but we know very little about how compulsory voting works in practice. In this Element, the authors fill this gap by providing an in-depth discussion of compulsory voting rules and their enforcement in Australia, Belgium, and Brazil. By analysing comparable public opinion data from these three countries, they shed light on citizens' attitudes toward compulsory voting. The Element examines citizens' perceptions, their knowledge of the system, and whether they support it. The authors connect this with information on citizens' reported turnout and vote choice to assess who is affected by mandatory voting and why. The work clarifies that there is no single system of compulsory voting. Each country has its own set of rules, and most voters are unaware of how they are enforced.
Knowledge dimensions in prototyping: investigating the what, when and how of knowledge generation during product development
Authors: Goudswaard Mark , Real Ric , Snider Chris , Muñoz Camargo Luis Ernesto , Salgado Zamora Nicolas , Hicks Ben
Published: September 2023

Prototyping is a knowledge generation activity facilitating improved understanding of problem and solution spaces. This knowledge can be generated across a range of dimensions, termedknowledge dimensions (KDs), via a range of methods and media, each with their own inherent properties. This article investigates and characterises the relationships between prototypes and knowledge generated from prototyping activities during the design process, by establishing how different methods and media contribute across KDs. In so doing, it provides insights into prototyping activity, as well as affording a means by which prototyping knowledge generation may be studied in detail. The investigation considers sets of prototypes from eight parallel 16-week design projects, with subsequent investigation of the knowledge contributions that each prototype provides and at what stage of the design process. Results showed statistical significance supporting three inferences: i) teams undertaking the same design brief create similar knowledge profiles; ii) prototyping fidelity impacts KD contribution and iii) KDs align with the different phases of the project. This article demonstrates a means to describe and potentially prescribe knowledge generation activities through prototyping. Correspondingly, the article contends that consideration of KDs offers potential to improve aspects of the design process through better prototyping method selection and sequencing.
Measure-theoretic sequence entropy pairs and mean sensitivity
Authors: GARCÍA-RAMOS FELIPE , MUÑOZ-LÓPEZ VÍCTOR
Published: September 2023

We characterize measure-theoretic sequence entropy pairs of continuous actions of abelian groups using mean sensitivity. This addresses an open question of Li and Yu [On mean sensitive tuples. J. Differential Equations297 (2021), 175–200]. As a consequence of our results, we provide a simpler characterization of Kerr and Li’s independence sequence entropy pairs (
$\mu $
-IN-pairs) when the measure is ergodic and the group is abelian.
Statistical characterization of a shock interacting with an inclined gas column
Authors: Romero Brian E. , Reisner Jon M. , Vorobieff Peter , Poroseva Svetlana V.
Published: September 2023

We present a statistical characterization of the interaction between a planar shock and a finite-diameter, cylindrical column of dense gas based on three-dimensional, large-eddy simulation results. In the simulation, the column of gas is initially inclined at an angle

$\alpha _0$

with respect to the shock plane. Effects of the initial column angle on the mixing characteristics are examined at Mach number 2.0 for column incline angles

$1^\circ$

,

$5^\circ$

,

$10^\circ$

and

$30^\circ$

. Mean velocity profiles show that the column angle affects the gas velocity components in the vertical plane, but not in the spanwise direction. The gas undergoes higher initial upward acceleration at larger initial column incline angles. With time, the gas motion tends to become one-dimensional in the streamwise direction. Initially, velocity fluctuations are most intense within the interior of the column, but concentrate near the column leading edge over time. At high wavenumbers

$\kappa$

, the turbulent kinetic energy spectra follow a power-law scaling of

$\kappa ^{-1}$

. The structure functions of the mass fraction do not clearly demonstrate power-law scaling except at early times for

$\alpha _0=30^\circ$

, manifesting overall trends very similar to those observed in earlier experiments. Probability distributions of the mass fraction show independence of the mean and the standard deviation of the mixed gas on

$\alpha _0$

. The column angle was also found to have little effect on the mixing efficiency characterized by the molecular mixedness. Velocity components in the streamwise and transverse directions tend towards a bimodal distribution for larger

$\alpha _{0}$

.
On the low-frequency unsteadiness in shock wave–turbulent boundary layer interactions
Authors: Hao Jiaao
Published: September 2023

The shock wave–turbulent boundary layer interaction over a compression corner is studied using global stability analysis (GSA) and resolvent analysis based on a separation of scales between the low-frequency, large-scale motions and the turbulent fluctuations. The GSA identifies a leading stationary mode, which becomes globally unstable as the ramp angle is beyond a critical value. For globally stable flows, the resolvent analysis captures two-dimensional and three-dimensional local maxima in optimal gain, both of which are due to modal resonance between the forcing and the leading global mode. Notably, the frequency-premultiplied optimal gain associated with two-dimensional disturbances peaks at a low frequency. For different interaction strengths, the peak frequencies collapse onto a universal value of 0.015 when non-dimensionalized using the length of the separation region and the free-stream velocity. A numerical simulation perturbed with the corresponding optimal forcing reveals that the response is in the form of a back-and-forth shock motion.
A novel laser melting sampler for discrete, sub-centimeter depth-resolved analyses of stable water isotopes in ice cores
Authors: Motizuki Yuko , Nakai Yoichi , Takahashi Kazuya , Hirose Junya , Sahoo Yu Vin , Yumoto Masaki , Maruyama Masayuki , Sakashita Michio , Kase Kiwamu , Wada Satoshi , Motoyama Hideaki , Yano Yasushige
Published: September 2023

We developed a novel laser melting sampler (LMS) for ice cores to measure the stable water isotope ratios (δ18O and δD) as temperature proxies at sub-centimeter depth resolutions. In this LMS system, a 2 mm diameter movable evacuation nozzle holds an optical fiber through which a laser beam irradiates the ice core. The movable nozzle intrudes into the ice core, the laser radiation meanwhile melts the ice cylindrically, and the meltwater is pumped away simultaneously through the same nozzle and transferred to a vial for analysis. To avoid isotopic fractionation of the ice through vaporization, the laser power is adjusted to ensure that the temperature of the meltwater is always kept well below its boiling point. A segment of a Dome Fuji shallow ice core (Antarctica), using the LMS, was then demonstrated to have been discretely sampled with a depth resolution as small as 3 mm: subsequent analysis of δ18O, δD, and deuterium excess (d) was consistent with results obtained by hand segmentation within measurement uncertainties. With system software to control sampling resolution, the LMS will enable us to identify temperature variations that may be detectable only at sub-centimeter resolutions in ice cores.
A PROOF COMPLEXITY CONJECTURE AND THE INCOMPLETENESS THEOREM
Authors: KRAJÍČEK JAN
Published: September 2023

Given a sound first-order p-time theory T capable of formalizing syntax of first-order logic we define a p-time function

$g_T$

that stretches all inputs by one bit and we use its properties to show that T must be incomplete. We leave it as an open problem whether for some T the range of

$g_T$

intersects all infinite

${\mbox {NP}}$

sets (i.e., whether it is a proof complexity generator hard for all proof systems).

A propositional version of the construction shows that at least one of the following three statements is true:

1.

There is no p-optimal propositional proof system (this is equivalent to the non-existence of a time-optimal propositional proof search algorithm).

2.

$E \not \subseteq P/poly$

.

3.

There exists function h that stretches all inputs by one bit, is computable in sub-exponential time, and its range

$Rng(h)$

intersects all infinite

${\text {NP}}$

sets.
Reflections on Constitutional Adjudication in a Democracy
Authors: Paulus Andreas
Published: September 2023

This article examines the necessity for constitutional adjudication in a democracy. Democracy is not the government of the minority by the majority, but self-government of the people in a pluralist society. The article regards constitutional adjudication as a necessary component of a constitutional democracy to preserve self-government and individual rights as a pre-condition for the acceptance of majority decisions by the minority. Thus, constitutional adjudication is needed to uphold the possibility of democratic change and to protect individual rights also against the majority. Recent critique of individual decisions does not change this basic insight and practice of constitutional democracies.
Urban internationalism: Coventry, Kiel, reconstruction and the role of cities in British–German reconciliation, 1945–1949
Authors: Laucht Christoph , Allbeson Tom
Published: September 2023

This article addresses the beginnings of the twinning relationship between Coventry and Kiel to introduce and exemplify the idea of ‘urban internationalism’ as a new lens onto urban histories of town twinning initiatives and a contribution to the historiography of British town twinning. Focusing on paradiplomatic initiatives by municipal officials, religious dignitaries and other citizens in Coventry and Kiel, the article examines the role that cities played in British–German reconstruction and reconciliation in the period from the end of World War II until the formation of the Federal Republic of Germany in 1949.
Numerical Modeling of Earthquake Cycles Based On Navier‐Stokes Equations With Viscoelastic‐Plasticity Rheology
Authors: Yang Haibin , Moresi Louis , Weng Huihui , Giordani Julian
Published: September 2023

Visco‐elastic‐plastic modeling approaches for long‐term tectonic deformation assume that co‐seismic fault displacement can be integrated over 1000s–10,000s years (tens of earthquake cycles) with the appropriate failure law, and that short‐timescale fluctuations in the stress field due to individual earthquakes have no effect on long‐term behavior. Models of the earthquake rupture process generally assume that the tectonic (long‐range) stress field or kinematic boundary conditions are steady over the course of multiple earthquake cycles. This study is aimed to fill the gap between long‐term and short‐term deformations by modeling earthquake cycles with the rate‐and‐state frictional (RSF) relationship in Navier‐Stokes equations. We reproduce benchmarks at the earthquake timescale to demonstrate the effectiveness of our approach. We then discuss how these high‐resolution models degrade if the time‐step cannot capture the rupture process accurately and, from this, infer when it is important to consider coupling of the two timescales and the level of accuracy required. To build upon these benchmarks, we undertake a generic study of a thrust fault in the crust with a prescribed geometry. It is found that lower crustal rheology affects the periodic time of characteristic earthquake cycles and the inter‐seismic, free‐surface deformation rate. In particular, the relaxation of the surface of a cratonic region (with a relatively strong lower crust) has a characteristic double‐peaked uplift profile that persists for thousands of years after a major slip event. This pattern might be diagnostic of active faults in cratonic regions.
Copper Isotope Fractionation in Archean Hydrothermal Systems: Evidence From the Mesoarchean Carlow Castle Cu‐Co‐Au Deposit
Authors: Fox David C. M. , McGee Lucy E. , Farkaš Juraj , Payne Justin L. , Spinks Samuel C. , Barham Milo , Aspandiar Mehrooz
Published: September 2023

Copper isotope analysis has emerged as a promising tool for understanding genetic processes in Cu ore deposits. However, applications of this analytical technique to Archean Cu deposits have been extremely limited, even though Archean terranes are among the most economically endowed on Earth. As such, this study presents the first Cu isotope analysis of an Archean Cu deposit, the Mesoarchean Carlow Castle hydrothermal Cu‐Co‐Au deposit. Archean primary Cu sulfide ore samples and Cenozoic supergene Cu ore samples were analyzed. Primary ore samples are isotopically light, with δ65Cu values ranging between −0.80 ± 0.02‰ and 0.00 ± 0.007‰, whilst supergene samples are isotopically heavier and range between −0.50 ± 0.01‰ and 0.62 ± 0.005‰. In primary ore samples, a relationship is observed between the Cu isotope signature, ore grade, and alteration assemblage that records the isotopic and physicochemical evolution of the Carlow Castle deposit's hydrothermal ore‐forming system. A mafic igneous source is suggested as a metal source in the Carlow Castle Cu‐Co‐Au deposit. The limited heavy isotopic fractionation of supergene Cu ore samples in this study is interpreted to reflect limited redox cycling of Cu due to in situ oxidative weathering of vein‐hosted Cu sulfides in the overlying Cenozoic supergene system. This differs from previously studied deposits where significant Cu transport and multiple stages of isotopic enrichment are often evident in supergene Cu enrichment layers. The results of this study suggest that Cu isotope analysis could be valuable in understanding genetic processes in hydrothermal Cu deposits, including Archean ore deposits and terranes.
Magnetic Reconnection in the Martian Magnetotail: Occurrence Rate and Impact on Ion Loss
Authors: Wang Lei , Huang Can , Du Aimin , Ge Yasong , Chen Guo , Fan Jinqiao , Qin Jipeng
Published: September 2023

The current sheet is crucial in releasing magnetic free energy in cosmic plasmas via fast magnetic reconnection or wave excitation. This research investigates the characteristics of the Martian tail current sheet by analyzing data acquired from the Mars Atmosphere and Volatile EvolutioN spacecraft over 7 years. For the first time, we find that approximately 15% of the current sheet events display reconnection signatures, including Hall magnetic fields and fast proton flows. These reconnecting current sheets are detected more frequently on Mars than on Earth. The Martian tail current sheet is first demonstrated to be on the proton scale, which can explain the high reconnection occurrence rate. The research also reveals that the current sheets are thinner in regions closer to Mars and in the –E hemisphere. On average, reconnecting current sheets carry high fluxes of protons rather than oxygen ions.
Understanding the Sensitivity of the North Atlantic Subpolar Overturning in Different Resolution Versions of HadGEM3‐GC3.1
Authors: Petit T. , Robson J. , Ferreira D. , Jackson L. C.
Published: September 2023

The Atlantic Meridional Overturning Circulation (AMOC) is a key component of the global climate but is not simulated consistently across models or model resolutions. Here, we use a hierarchy of the global coupled model HadGEM3‐GC3.1, with ocean resolutions of 1°, ¼°, and 1/12°, to evaluate the subpolar AMOC and its sensitivity to horizontal resolution. In line with observations, the models show that the mean overturning and surface forced water mass transformation (SFWMT) are concentrated in the eastern subpolar gyre rather than in the Labrador Sea. However, the magnitude of the overturning along the OSNAP line at medium and high resolutions is 25% and 40% larger than in the observations, respectively. This disagreement in overturning strength is noted for both OSNAP East and OSNAP West, and is mainly due to anomalously large SFWMT rather than anomalously large interior mixing or overflow transport from the Nordic Seas. Over the Labrador Sea, the intensification of SFWMT with resolution is explained by a combination of two main biases. Anomalously warm surface water enhances heat loss and reduces the extension of marginal sea ice, which increases the surface density flux over the boundary of the basin. A bias in salinity leads to anomalously dense surface water that shifts the outcropping area of the AMOC isopycnal and results in intense dense water formation along the boundary of the basin at medium and high resolutions. Thus, our analysis sheds light on a range of model biases responsible for large overturning over the Labrador Sea in climate models.
Characterizing the mutational burden, DNA methylation landscape, and proteome of germ cell tumor-related somatic-type malignancies to identify the tissue-of-origin, mechanisms of therapy resistance, and druggable targets
Authors: Bremmer Felix , Pongratanakul Pailin , Skowron Margaretha , Che Yue , Richter Annika , Küffer Stefan , Reuter-Jessen Kirsten , Bohnenberger Hanibal , Pauls Stella , Kresbach Catena , Schüller Ulrich , Stühler Kai , Ströbel Philipp , Albers Peter , Nettersheim Daniel
Published: September 2023

Background

Germ cell tumors (GCT) might undergo transformation into a somatic-type malignancy (STM), resulting in a cell fate switch to tumors usually found in somatic tissues, such as rhabdomyosarcomas or adenocarcinomas. STM is associated with a poor prognosis, but the molecular and epigenetic mechanisms triggering STM are still enigmatic, the tissue-of-origin is under debate and biomarkers are lacking.

Methods

To address these questions, we characterized a unique cohort of STM tissues on mutational, epigenetic and protein level using modern and high-throughput methods like TSO assays, 850k DNA methylation arrays and mass spectrometry.

Results and conclusions

For the first time, we show that based on DNA methylation and proteome data carcinoma-related STM more closely resemble yolk-sac tumors, while sarcoma-related STM resemble teratoma. STM harbor mutations in FGF signaling factors (FGF6/23, FGFR1/4) highlighting the corresponding pathway as a therapeutic target. Furthermore, STM utilize signaling pathways, like AKT, FGF, MAPK, and WNT to mediate molecular functions coping with oxidative stress, toxin transport, DNA helicase activity, apoptosis and the cell cycle. Collectively, these data might explain the high therapy resistance of STM. Finally, we identified putative novel biomarkers secreted by STM, like EFEMP1, MIF, and DNA methylation at specific CpG dinucleotides.
Increased MCL1 dependency leads to new applications of BH3-mimetics in drug-resistant neuroblastoma
Authors: Jacob Maureen , Wiedemann Sara , Brücher Daniela , Pieper Nadja M. , Birkhold Moni , Särchen Vinzenz , Jeroch Jan , Demes Melanie C. , Gretser Steffen , Braun Yannick , Gradhand Elise , Rothweiler Florian , Michaelis Martin , Cinatl Jindrich , Vogler Meike
Published: September 2023

Background

Neuroblastoma is a paediatric cancer that is characterised by poor prognosis for chemoresistant disease, highlighting the need for better treatment options. Here, we asked whether BH3-mimetics inhibiting BCL2 proteins may eliminate chemoresistant neuroblastoma cells.

Methods

We utilised cisplatin-adapted neuroblastoma cell lines as well as patient tissues before and after relapse to study alterations of BCL2 proteins upon chemoresistance.

Results

In a direct comparison of cisplatin-resistant cells we identified a prominent loss of sensitivity to BCL2/BCL-XL inhibitors that is associated with an increase in MCL1 dependency and high expression of MCL1 in patient tumour tissues. Screening of FDA-approved anti-cancer drugs in chemoresistant cells identified therapeutics that may be beneficial in combination with the clinically tested BH3-mimetic ABT263, but no synergistic drug interactions with the selective MCL1 inhibitor S63845. Further exploration of potential treatment options for chemoresistant neuroblastoma identified immunotherapy based on NK cells as highly promising, since NK cells are able to efficiently kill both parental and chemoresistant cells.

Conclusions

These data highlight that the application of BH3-mimetics may differ between first line treatment and relapsed disease. Combination of NK cell-based immunotherapy with BH3-mimetics may further increase killing of chemoresistant neuroblastoma, outlining a new treatment strategy for relapsed neuroblastoma.
β2-AR inhibition enhances EGFR antibody efficacy hampering the oxidative stress response machinery
Authors: Del Vecchio Vitale , Mele Luigi , Panda Sameer Kumar , Sanchez-Pajares Ibone Rubio , Mosca Laura , Tirino Virginia , Barbieri Massimiliano , Bruzzese Francesca , Luciano Antonio , Marino Federica Zito , Accardo Marina , Nicoletti Giovanni Francesco , Papaccio Gianpaolo , Barbieri Antonio , Desiderio Vincenzo
Published: September 2023

The β2-Adrenergic receptor (β2-ARs) is a cell membrane-spanning G protein-coupled receptors (GPCRs) physiologically involved in stress-related response. In many cancers, the β2-ARs signaling drives the tumor development and transformation, also promoting the resistance to the treatments. In HNSCC cell lines, the β2-AR selective inhibition synergistically amplifies the cytotoxic effect of the MEK 1/2 by affecting the p38/NF-kB oncogenic pathway and contemporary reducing the NRF-2 mediated antioxidant cell response. In this study, we aimed to validate the anti-tumor effect of β2-AR blockade and the synergism with MEK/ERK and EGFR pathway inhibition in a pre-clinical orthotopic mouse model of HNSCC. Interestingly, we found a strong β2-ARs expression in the tumors that were significantly reduced after prolonged treatment with β2-Ars inhibitor (ICI) and EGFR mAb Cetuximab (CTX) in combination. The β2-ARs down-regulation correlated in mice with a significant tumor growth delay, together with the MAPK signaling switch-off caused by the blockade of the MEK/ERK phosphorylation. We also demonstrated that the administration of ICI and CTX in combination unbalanced the cell ROS homeostasis by blocking the NRF-2 nuclear translocation with the relative down-regulation of the antioxidant enzyme expression. Our findings highlighted for the first time, in a pre-clinical in vivo model, the efficacy of the β2-ARs inhibition in the treatment of the HNSCC, remarkably in combination with CTX, which is the standard of care for unresectable HNSCC.
Correlative CD4 and CD8 T-cell immunodominance in humans and mice: Implications for preclinical testing
Authors: Neto Tertuliano Alves Pereira , Sidney John , Grifoni Alba , Sette Alessandro
Published: September 2023

Antigen-specific T-cell recognition is restricted by Major Histocompatibility Complex (MHC) molecules, and differences between CD4 and CD8 immunogenicity in humans and animal species used in preclinical vaccine testing are yet to be fully understood. In this study, we addressed this matter by analyzing experimentally identified epitopes based on published data curated in the Immune Epitopes DataBase (IEDB) database. We first analyzed SARS-CoV-2 spike (S) and nucleoprotein (N), which are two common targets of the immune response and well studied in both human and mouse systems. We observed a weak but statistically significant correlation between human and H-2bmouse T-cell responses (CD8 S specific (r = 0.206,p = 1.37 × 10−13); CD4 S specific (r = 0.118,p = 2.63 × 10−5) and N specific (r = 0.179,p = 2.55 × 10−4)). Due to intrinsic differences in MHC molecules across species, we also investigated the association between the immunodominance of common Human Leukocyte Antigen (HLA) alleles for which HLA transgenic mice are available, namely, A*02:01, B*07:02, DRB1*01:01, and DRB1*04:01, and found higher significant correlations for both CD8 and CD4 (maximumr = 0.702,p = 1.36 × 10−31andr = 0.594,p = 3.04−122, respectively). Our results further indicated that some regions are commonly immunogenic between humans and mice (either H-2bor HLA transgenic) but that others are human specific. Finally, we noted a significant correlation between CD8 and CD4 S- (r = 0.258,p = 7.33 × 1021) and N-specific (r = 0.369,p = 2.43 × 1014) responses, suggesting that discrete protein subregions can be simultaneously recognized by T cells. These findings were confirmed in other viral systems, providing general guidance for the use of murine models to test T-cell immunogenicity of viral antigens destined for human use.