bluuebunny/crossref_metadata_2025 huggingface dataset:
Production and certification of BOTS-1: bovine muscle–certified reference material for incurred veterinary drug residues
Authors: McRae Garnet , Leek Donald M. , Meija Juris , Shurmer Bryn , Lehotay Steven J. , Polzer Joachim , Melanson Jeremy E. , Mester Zoltan
Published: June 2023

A freeze-dried bovine muscle–certified reference material (CRM), known as BOTS-1 (DOI: https://doi.org/10.4224/crm.2018.bots-1), containing incurred residues of commonly used veterinary drugs was produced and certified for the mass fraction of eight veterinary drug residues. Value assignment was carried out using liquid chromatography tandem mass spectrometry (LC–MS/MS) methods in conjunction with isotope dilution and standard addition approaches involving stable isotope internal standards. Data from the National Research Council of Canada (NRC), Canadian Food Inspection Agency (CFIA), United States Department of Agriculture (USDA), and the Federal Office of Consumer Protection and Food Safety in Germany (BVL) were used for value assignment. Results for two drug residues were also obtained through an international inter-laboratory comparison CCQM-K141/P178 organized under the auspices of the International Bureau of Weights and Measures (BIPM). Quantitative NMR (1H-qNMR) was used to characterize primary standards of all veterinary drugs certified. The certified mass fractions of the veterinary drug residues were 490 ± 100 µg/kg for chlorpromazine, 44 ± 4.4 µg/kg for ciprofloxacin, 3.3 ± 1.4 µg/kg for clenbuterol, 9.5 ± 0.8 µg/kg for dexamethasone, 57 ± 4.8 µg/kg for enrofloxacin, 3.0 ± 0.4 µg/kg for meloxicam, 12.4 ± 1.2 µg/kg for ractopamine, and 2290 ± 120 µg/kg for sulfadiazine with expanded uncertainties quoted (95% confidence) which include the effects due to between-bottle inhomogeneity, instability during long-term storage and transportation, and characterization.
Improving clinical diagnostic accuracy and management of False penile fractures characterizing typical clinical presentation: a systematic review and meta-analysis
Authors: Agostini Edoardo , Vinci Antonio , Bardhi Dorian , Ingravalle Fabio , Muselli Mario , Milanese Giulio
Published: June 2023

Purpose

False penile fractures (FPF) represent a rare sexual emergency characterized by blunt trauma of penis in the absence of albuginea’s injury, with or without lesion of dorsal penile vein. Their presentation is often indistinguishable from true penile fractures (TPF). This overlapping of clinical presentation, and lack of knowledge about FPF, can lead surgeons often to proceed directly to surgical exploration without further examinations. The aim of this study was to define a typical presentation of false penile fractures (FPF) emergency, identifying in absence of “snap” sound, slow detumescence, penile shaft ecchymosis, and penile deviation main clinical signs.

Methods

We performed a systematic review and meta-analysis based on Medline, Scopus and Cochrane following a protocol designed a priori, to define sensitivity of “snap” sound absence, slow detumescence and penile deviation.

Results

Based on the literature search of 93 articles, 15 were included (73 patients). All patients referred pain, most of them during coitus (n = 57; 78%). Detumescence occurred in 37/73 (51%), and all patients described detumescence occurrence as “slow”. The results show that single anamnestic item have a high-moderate sensibility in the diagnosis of FPF, and the highest sensitive item was penile deviation (sensibility = 0.86). However, when more than one item is present, overall sensitivity increases greatly, closing to 100% (95% Confidence Interval 92–100).

Conclusion

Surgeons can consciously decide between additional exams, a conservative approach, and rapid intervention using these indicators to detect FPF. Our findings identified symptoms with excellent specificity for FPF diagnosis, giving clinicians more useful tools for making decisions.
Rod-shaped microparticles — an overview of synthesis and properties
Authors: Wittmann Martin , Henze Kelly , Yan Kai , Sharma Vandana , Simmchen Juliane
Published: June 2023

Micro particles come in a wide variety of architectural designs and shapes. It is time to look beyond the conventional spherical morphology and focus on anisotropic systems. Rod-shaped micro particles in particular exhibit numerous unique behaviors based on their structural characteristics. Because of their various shapes, architectures, and material compositions, which are based on the wide range of synthesis possibilities, they possess an array of interesting characteristics and applications. This review summarizes and provides an overview of the substantial amount of work that has already been published in the field of rod-shaped micro particles. Nevertheless, it also reveals limitations and potential areas for development.
LncRNA KCNQ10T1 shuttled by bone marrow mesenchymal stem cell-derived exosome inhibits sepsis via regulation of miR-154-3p/RNF19A axis
Authors: Yuan Haojie , Yu Junbo , Liu Chun , Zhao Heyan , Xue Jianhua , Liu Jiajia , Yang Yang
Published: June 2023

This study aims to discuss the role of exosomes KCNQ10T1 derived from bone marrow mesenchymal stem cells (BMMSCs) in sepsis and to further investigate its potential molecular mechanisms. Exosomes extracted from BMMSCs are identified by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and western blot. Fluorescence labeling is applied to detect the internalization of exosomes in receptors. The proliferation ability, migration ability, and invasion ability of HUVECs are determined by CCK-8, EdU, wound healing, and Transwell. The levels of inflammatory cytokines in sepsis cells are quantitatively detected by ELISA. Kaplan–Meier survival curve is used to describe the overall survival. RT-qPCR is used to detect mRNA expression of related genes. Bioinformatics analysis is performed to search the downstream target of KCNQ1OT1 and miR-154-3p and the interaction is verified by luciferase reporter assay. Exosomes derived from BMMSCs alleviated the toxicity in sepsis cell models and animal models. In mice with septic cell models, exosomal KCNQ10T1 was down-regulated and associated with lower survival. Overexpression of KCNQ10T1 inhibited the proliferation and metastasis of LPS-induced HUVECs. Further research illustrated that miR-154-3p was the downstream target gene of KCNQ1OT1 and RNF19A was the downstream target gene of miR-154-3p. Importantly, functional research findings indicated that KCNQ1OT1 regulated sepsis progression by targeting miR-154-3p/RNF19A axis. Our study demonstrates that the exosomal KCNQ1OT1 suppresses sepsis via mediating miR-154-3p/RNF19A, which provides a latent target for sepsis treatment.
Convergent morphology and anatomy in the microphyllous leaves of selected heathland Myrtaceae and Asteraceae
Authors: Dörken Veit M. , Ladd Philip G. , Parsons Robert F.
Published: June 2023

Key message

We examined leaves of a suite of microphyllous woody plants and describe a little-known form of leaf peltation for the first time and also investigate strongly reflexed leaves in two distantly related lineages.

Plants cope with a range of environmental conditions, especially related to water relations, and have developed an array of physiological and structural solutions to maintain a functional water balance. There has been considerable recent work on physiological solutions to water deficit but little attention paid to leaf characteristics. In many species there is a change in leaf form from seedlings to adults. We examine such changes in several small-leaved species from the distantly related Asteraceae and Myrtaceae, some of which develop micropeltate or reflexed leaves as adults. All are native to dry or seasonally dry sites. Three major morphological groups were recognised as follows: (1) leaves erect, nonpeltate and scale-like (Ozothamnus hookeri), (2) leaves erect and peltate (Phaenocoma prolifera,Regelia inops), (3) Leaves reflexed (Olearia lepidophylla,Ozothamnus scutellifolius,Ozothamnus reflexifolius,Melaleuca diosmifolia). The microphyllous peltation inP. proliferaandR. inopsin the absence of a meristematic fusion/bridge differs from typically peltate leaves. These small-leaved taxa occur in open, high light environments which are very different from the mesic, shaded understorey habitats of typical peltate-leaved plants. Many small-leaved species have leaves closely appressed to the stem and often with recurved margins. The erect leaves are functionally similar to reflexed leaves. Environmental filtering leads to superficially similar plant forms that may have somewhat different ontological origins. Such morphological forms are examples of convergent evolution in distantly related species but within each family are likely phylogenetically related.
JAMsFace: joint adaptive margins loss for deep face recognition
Authors: Khalifa Aly , Al-Hamadi Ayoub
Published: June 2023

Deep feature learning has become crucial in large-scale face recognition, and margin-based loss functions have demonstrated impressive success in this field. These methods aim to enhance the discriminative power of the softmax loss by increasing the feature margin between different classes. These methods assume class balance, where a fixed margin is sufficient to squeeze intra-class variation equally. However, real-face datasets often exhibit imbalanced classes, where the fixed margin is suboptimal, limiting the discriminative power and generalizability of the face recognition model. Furthermore, margin-based approaches typically focus on enhancing discrimination either in the angle or cosine space, emphasizing one boundary while disregarding the other. To overcome these limitations, we propose a joint adaptive margins loss function (JAMsFace) that learns class-related margins for both angular and cosine spaces. This approach allows adaptive margin penalties to adjust adaptively for different classes. We explain and analyze the proposed JAMsFace geometrically and present comprehensive experiments on multiple face recognition benchmarks. The results show that JAMsFace outperforms existing face recognition losses in mainstream face recognition tasks. Specifically, JAMsFace advances the state-of-the-art face recognition performance on LFW, CPLFW, and CFP-FP and achieves comparable results on CALFW and AgeDB-30. Furthermore, for the challenging IJB-B and IJB-C benchmarks, JAMsFace achieves impressive true acceptance rates (TARs) of 89.09% and 91.81% at a false acceptance rate (FAR) of 1e-4, respectively.
Magnetoelectric ring sensor—modelling and experimentation
Authors: Kuczynski Karol , Lisicki Maciej , Bilski Piotr , Szymanski Jerzy , Bilski Adrian
Published: June 2023

The paper presents the theoretical model and implementation of the magnetoelectric ring sensor. The designed device is capable of measuring the constant magnetic field of low amplitudes (even several dozen nT). To determine its capabilities and resolution, the hysteresis characteristics were evaluated and measured. Besides the theoretical description of the sensor, two heuristic approaches were used to approximate the internal characteristics (including the hysteresis loop), solving the regression task: a multilayered perceptron and support vector machine. Experiments show that the former has minimally Mean Square Error, which suggests its better applicability for heuristic modeling of the real-world device.
Pain improvement and reoperation rate after full-endoscopic decompression for lateral recess stenosis: a 10-year follow-up
Authors: Kesornsak Withawin , Kuansongtham Verapan , Lwin Khin Myat Myat , Pongpirul Krit
Published: June 2023

Purpose

To share long-term clinical outcomes and our experience with full-endoscopic interlaminar decompression (FEI) for lateral recess stenosis (LRS).

Methods

We included all patients who underwent FEI for LRS from 2009 to 2013. VAS for leg pain, ODI, neurological findings, radiographic findings, and complications were analyzed at one week, one month, three months, and one year postoperation. The telephone interview for local patients with simple questions was done approximately ten years after the operation. International patients receive an email with the same questionnaire as local patients during the same follow-up period.

Results

One hundred and twenty-nine patients underwent FEI for LRS with complete data during 2009–2013. Most of the patients (70.54%) had LRS radiculopathy for less than one year, mainly L4-5 (89.92%), followed by L5-S1 (17.83%). Early outcomes three months after surgery showed that most patients (93.02%) reported significant pain relief, and 70.54% reported no pain at their ODI scores were significantly reduced from 34.35 to 20.32% (p = 0.0052). In contrast, the mean VAS for leg pain decreased substantially by 3.77 points (p < 0.0001). There were no severe complications. At ten years of follow-up, 62 patients responded to the phone call or email. 69.35% of the patients reported having little or no back or leg pain, did not receive any further lumbar surgery, and were still satisfied with the result of the surgery. There were six patients (8.06%) who underwent reoperation.

Conclusion

FEI for LRS was satisfactory at 93.02%, with a low complication rate during the early follow-up period. Its effect seems to decline slightly in the long term at a 10-year follow-up. 8.06% of the patients subsequently underwent reoperation.
$$\Delta $$ Baryon Spectroscopy in Lattice QCD
Authors: Hockley Liam , Kamleh Waseem , Leinweber Derek , Thomas Anthony
Published: June 2023

A variational analysis is performed within the framework of lattice QCD to extract the masses of the spin-3/2 positive parity $$ \Delta ^+ $$

Δ
+

baryons, including radial excitations. 2 + 1 flavour dynamical gauge-field configurations provided by the PACS-CS collaboration via the ILDG are considered. To improve our interpolator basis, we perform an iterative process of source and sink smearing and solve a generalised eigenvalue problem using the resulting fermion operators. We obtain a clear signal for the ground and first excited states at a light quark mass corresponding to $$ m_\pi = 413$$

m
π

=
413

 MeV. Furthermore, we show that one can use the eigenvectors obtained in this method to investigate the nature of these states, allowing us to classify our results as 1s and 2s states for the ground and first excited states respectively. Finally, we briefly highlight the method of Hamiltonian effective field theory which can be used to make comparison with quark model expectations.
Data-driven aggregate modeling of a semiconductor wafer fab to predict WIP levels and cycle time distributions
Authors: Deenen Patrick C. , Middelhuis Jeroen , Akcay Alp , Adan Ivo J. B. F.
Published: June 2023

In complex manufacturing systems, such as a semiconductor wafer fabrication facility (wafer fab), it is important to accurately predict cycle times and work-in-progress (WIP) levels. These key performance indicators are commonly predicted using detailed simulation models; however, the detailed simulation models are computationally expensive and have high development and maintenance costs. In this paper, we propose an aggregate modeling approach, where each work area, i.e., a group of functionally similar workstations, in the wafer fab is aggregated into a single-server queueing system. The parameters of the queueing system can be derived directly from arrival and departure data of that work area. To obtain fab-level predictions, our proposed methodology builds a network of aggregate models, where the network represents the entire fab consisting of different work areas. The viability of this method in practice is demonstrated by applying it to a real-world wafer fab. Experiments show that the proposed model can make accurate predictions, but also provide insights into the limitations of aggregate modeling.
Item-Specific Factors in IRTree Models: When They Matter and When They Don’t
Authors: Meiser Thorsten , Reiber Fabiola
Published: June 2023

Lyu et al. (Psychometrika, 2023) demonstrated that item-specific factors can cause spurious effects on the structural parameters of IRTree models for multiple nested response processes per item. Here, we discuss some boundary conditions and argue that person selection effects on item parameters are not unique to item-specific factors and that the effects presented by Lyu et al. (Psychometrika, 2023) may not generalize to the family of IRTree models as a whole. We conclude with the recommendation that IRTree model specification should be guided by theoretical considerations, rather than driven by data, in order to avoid misinterpretations of parameter differences.
On the Effect of Testing Frequency on High and Very High Cycle Fatigue Behavior of AA2024-T3, Ti-6Al-4V, and Inconel 718
Authors: Kuliiev Ruslan , Riekehr Stefan , Ventzke Volker , Keller Sören , Kashaev Nikolai
Published: June 2023

An increase of testing frequency to reduce the testing time could affect the fatigue behavior of metallic materials. The current paper investigates the effect of testing frequency on the high and very high cycle fatigue behavior of AA2024, Ti-6Al-4V, and Inconel 718 alloys tested at 20, 90, and 1000 Hz. To quantify the effect of testing frequency a two-parameter Weibull distribution and Basquin’s equation were utilized as well as the threshold stress intensity factor range was determined. Fatigue crack initiation sites were evaluated on the fracture surface with respect to different testing frequencies. The results showed that changes in the testing frequency significantly influence the mechanical response of the Ti-6Al-4V alloy, while no substantial impact on the fatigue properties of AA2024 and Inconel 718 alloys was identified. The findings of the study contribute to a more complete knowledge of the frequency sensitivity of the alloys and provide valuable insights for the design and evaluation of materials used in high-frequency applications.
Laser-based ultrasonic measurement of the influence of PBF-LB/M-typical thermal cycles on sheet metal components of hybrid parts
Authors: Hafenecker Jan , Rigas Nikolaos , Merklein Marion
Published: June 2023

In order to cope with the upcoming challenges from industrial trends, such as mass customization, hybrid parts made out of sheet metal and additively manufactured components offer a possible approach. Hybrid parts can be used for instance in the field of medical and aerospace industries. The combination of the two technologies forming and additive manufacturing allows to use the advantages of each while at the same time avoiding the disadvantages. During the additive manufacturing process, however, the sheet metal substrates, which are a component of the later part, are subjected to heat input such as substrate heating and laser radiation. Each heat input has a different temperature and duration, which are simulated to detect changes in the material properties. Experiments are performed for 316L and Ti-6Al-4 V, which are both commonly used in additive manufacturing. The investigations aim at proving that the substrate heating has no influence on either material. To investigate the influence of substrate heating during additive manufacturing, tensile tests in heat-treated state as well as laser-based ultrasonic measurements are used to detect changes in mechanical or microstructural properties. However, the heat input of the laser is expected to lead to a phase transformation for the titanium alloy due to the high cooling rate. Therefore, the feasibility of using a laser based ultrasonic measurement system to detect microstructural changes during heat input similar to the laser radiation during laser-based powder bed fusion processes is tested. Based on the results, the substrate heating does not influence the sheet material, despite long holding times. However, the short laser beam-like heat inputs lead to phase transformations for the titanium alloy, which can be detected temperature and time dependent via laser-based ultrasonic measurements.
Fluorescence Turn-On/Off Responses of In (III)-MOF to Short-Chain Perfluorocarboxylic Acids
Authors: Lv Jie , Xie Yabo , Xie Lin-Hua , Li Jian-Rong
Published: June 2023

Short-chain perfluorocarboxylic acids (PFCAs) are a class of persistent organic pollutants that are widely used as substitutes for long-chain PFCAs. However, they also pose a non-negligible risk to ecosystems. In this study, we demonstrated that a fluorescent metal–organic framework (MOF) (named V-101) constructed from In3+ and an aromatic-rich tetratopic carboxylate ligand 5-[2,6-bis (4-carboxyphenyl) pyridin-4-yl] isophthalic acid (H4BCPIA) exhibited highly efficient turn-off and turn-on fluorescence responses toward five short-chain PFCAs in water and methanol, respectively. The limits of detection of V-101 toward five short-chain PFCAs are down to μg/L level, and it showed good anti-interference abilities toward short-chain PFCAs in the presence of common metal ions. The major mechanisms associated with fluorescence responses were molecular collisions and interactions between V-101 and short-chain PFCAs. This work demonstrates that the structure variety of MOFs imparts them with the potential of MOFs in the detection of short-chain PFCAs for pollution control.
An archaeometallurgical investigation of iron smithing in Swahili contexts and its wider implications
Authors: Baužytė Ema , LaViolette Adria , Fleisher Jeffrey , Juma Abdurahman , Horton Mark , Mapunda Bertram , Wynne-Jones Stephanie
Published: June 2023

This paper presents the most extensive archaeometallurgical study of iron-smithing debris excavated in East Africa. It presents an integrated methodology, including morphological, chemical, petrographic, and contextual analysis of iron slag excavated from secondary ironworking contexts. Iron slag from three Swahili sites was analysed—Unguja Ukuu located on the southwestern coast of Zanzibar, and Tumbe and Chwaka situated in the north-east of Pemba Island. The results suggest that Unguja Ukuu smithing is associated with oxidising hearth atmospheres and high amounts of CaO, while slag from Tumbe and Chwaka indicates reducing hearth atmospheres and high silica:alumina ratios, potentially pointing to the use of a flux. Distinct technical traditions can be seen at Unguja Ukuu when compared to Tumbe and Chwaka, suggesting a regional rather than chronological pattern. Temporal continuity is evident throughout the occupation of Unguja Ukuu and between sites of different periods in north-western Pemba. The spatial distribution of iron slag at these sites suggests that smithing was taking place across the extent of Unguja Ukuu, while slag scatters were more localised and disassociated from domestic contexts at Tumbe and Chwaka. The wealth of information on technological and organisational aspects of smithing obtained during this study indicates that an integrated methodology can yield valuable data for a variety of smithing sites, irrespective of excavation strategies.
Choosing the site, getting the stones, building the dolmens: local sourcing of andesites at the El Pozuelo megalithic complex (Huelva, Spain)
Authors: Linares-Catela José Antonio , Donaire Romero Teodosio , Mora Molina Coronada , Cáceres Puro Luis Miguel
Published: June 2023

The geoarchaeological study focuses on the lithological characterization and provenance determination of the rocks of the El Pozuelo dolmens. The difficulty of identifying volcanic rocks in the intensely altered and deformed environment of the Iberian Pyrite Belt has required the implementation of a research methodology combining the archaeological and geological analysis of the megaliths and the area surrounding the Los Llanetes group. A total of 29 thin sections and 14 geochemical analyses (ICP-AES, ICP-MS and REE) have been carried out on samples from the dolmens and potential source areas, focusing on the chemical elements considered immobile during alteration processes. The petrological analyses confirm the identification of different andesite lithotypes and enable us to correlate the rocks used in the construction of the megaliths with source areas and quarries located within a 50–350 m radius. Several patterns are observed in the selection of the rocks, based on the material, visual and symbolic properties of the different lithologies. Foliated andesite is the most common stone used in the monuments, due to its excellent physical properties and technological suitability for extraction and transformation into megalithic supports. Other types of andesite (sheared, massive and amphibole-phyric), white quartz, ferruginous agglomerate and gabbro were also used for different architectural purposes. The results confirm the importance of locally available suitable rocks in determining site location, raw material procurement and monument construction during the Late Neolithic.
„Ich bretter durch die Stadt mit ’n Lambo Gallardo“
Authors: Bock Katharina , Dollinger Bernd , Rieger Julia
Published: June 2023

Während in Publikationen und Auseinandersetzungen mit Gangsta-Rap vor allem populäre Rapper*innen und deren Produktionen im Vordergrund stehen, befassen sich vergleichsweise wenige Arbeiten empirisch mit der Fan-Perspektive. In diesem Zusammenhang sind insbesondere Fragen nach der Aneignung von Gangsta-Rap weitgehend unbeantwortet. Vor diesem Hintergrund präsentiert der Beitrag das Fallbeispiel eines jugendlichen Gangsta-Rap-Fans, der die Musik nicht nur gerne hört, sondern diese auch selbst produziert. Im Rahmen einer Analyse narrativer Aneignung von Gangsta-Rap zeichnet der Beitrag nach, wie der 14-jährige Salim auf zentrale Figuren, Topoi und Techniken des Musikgenres in seinen Rap-Eigenproduktionen Bezug nimmt, mit verschiedenen Themen experimentiert, diese z. T. reproduziert, sie mit der eigenen (realen und erwünschten) Lebensrealität verknüpft und sich so Gangsta-Rap in unterschiedlichen Selbsterzählungen kreativ zu eigen macht.
Neutralizing RGMa with Elezanumab Promotes Cerebroprotection and Recovery in Rabbit Middle Cerebral Artery Occlusion
Authors: Jacobson Peer B. , Mothe Andrea , Levy Aharon , Krakovsky Michael , Hooker Bradley A. , Zhang Xiaomeng , Mollon Jennifer , Mordashova Yulia , Droescher Mathias , Weiss Sabine , Barghorn Stefan , Dreher Ingeborg , Awwad Khader , Nimmrich Volker , Huang Lili , Fung Emma , Buck Wayne R. , Pfleeger Kimberly , Ziemann Adam , Smith Elaine , Fox Gerard B. , Tator Charles H. , Gold Michael
Published: June 2023

Repulsive guidance molecule A (RGMa) is an inhibitor of neuronal growth and survival which is upregulated in the damaged central nervous system following acute spinal cord injury (SCI), traumatic brain injury, acute ischemic stroke (AIS), and other neuropathological conditions. Neutralization of RGMa is neuroprotective and promotes neuroplasticity in several preclinical models of neurodegeneration and injury including multiple sclerosis, AIS, and SCI. Given the limitations of current treatments for AIS due to narrow time windows to intervention (TTI), and restrictive patient selection criteria, there is significant unmet need for therapeutic agents that enable tissue survival and repair following acute ischemic damage for a broader population of stroke patients. In this preclinical study, we evaluated whether elezanumab, a human anti-RGMa monoclonal antibody, could improve neuromotor function and modulate neuroinflammatory cell activation following AIS with delayed intervention times up to 24 h using a rabbit embolic permanent middle cerebral artery occlusion model (pMCAO). In two replicate 28-day pMCAO studies, weekly intravenous infusions of elezanumab, over a range of doses and TTIs of 6 and 24 h after stroke, significantly improved neuromotor function in both pMCAO studies when first administered 6 h after stroke. All elezanumab treatment groups, including the 24 h TTI group, had significantly less neuroinflammation as assessed by microglial and astrocyte activation. The novel mechanism of action and potential for expanding TTI in human AIS make elezanumab distinct from current acute reperfusion therapies, and support evaluation in clinical trials of acute CNS damage to determine optimal dose and TTI in humans.

Graphical Abstract

A: Ramified/resting astrocytes and microglia in a normal, uninjured rabbit brain. B: Rabbit pMCAO brain illustrating lesion on right side of brain (red), surrounded by penumbra (pink) during acute phase post stroke, with minimal injury to left brain hemisphere. Penumbra characterized by activated astrocytes and microglia (region in crosshair within circle), with upregulation of free and bound RGMa. C: Elezanumab binds to both free and bound RGMa, preventing full activation of astrocytes and microglia. D: Elezanumab is efficacious in rabbit pMCAO with a 4 × larger TTI window vs. tPA (6 vs. 1.5 h, respectively). In human AIS, tPA is approved for a TTI of 3-4.5 h. Elezanumab is currently being evaluated in a clinical Ph2 study of AIS to determine the optimal dose and TTI (NCT04309474).
Modelling of aircraft trajectories for emergency landing using kinematoid chains
Authors: Flämig Steffen , Graefenhan Matthias , Schiffmann Wolfram
Published: June 2023

Most methods that compute trajectories for un- or low-powered flight operate under simplifying assumptions such as constant curve radii and wind conditions. Likewise, changes of air density with altitude that lead to significant differences between equivalent airspeed (EAS) und true airspeed (TAS) are often not considered. Some approaches are based on Dubins paths, which are introduced in Dubins LE (Am J Math 79: 497, 1957). They combine three sections to form a trajectory, which is the shortest from a given start to an end position (In the original work, the position extended by the heading, is referred to as configuration. Since configuration has a different connotation in our context, we use the term state, which can contain other parameters in addition to the position and the heading, e.g. orientation, configuration of landing flaps, landing gear, etc.). A maximum distant landing spot can be reached this way. Often, the targeted landing spot is closer to the aircraft. If it is approached using a Dubins Path, the excess height must be dealt with. Here, we present a method addressing the problem directly, namely finding a trajectory which reduces the excess height over its entire length. Furthermore, it takes spatial and temporal changes of wind and air density into account. Several conditions influence the final shape of the trajectory. For example, avoidance of obstacles and predefined areas is easily achieved. Our method is motivated by kinematic chains, which are used in robotics and computer animation. We extend and modify this principle by incrementally transferring start and end states of the trajectory, modelled as state vectors, into each other. The resulting intermediate states form ends of chain links. To connect initial and final states through the resulting chain, we solve the inverse kinematic problem known from robotics. We extend it by several conditions, which are derived from the flight mechanical characteristics of the modeled aircraft on the one hand and from the desired properties of the trajectory on the other. Using practical examples, we will show the performance of this method, which we have efficiently implemented on off-the-shelf hardware. The method is suitable for systems that assist in the event of engine failures as well as for modeling planned un- or low-powered flights like continuous descent approaches or return flights of space gliders.
Shakespeare without Print
Authors: Menzer Paul
Published: June 2023

Everything we know about Shakespeare – his world, his words, his work – is preconceived by print. This knowledge extends to cultural expressions that seek to evade ink, paper, and moveable type, such as performance, such as acting. Print privileges qualities quite alien to performance, however: standardization, reproducibility, and, above all, uniformity. Thus the master tropes of print occlude rather than clarify our thinking about acting. How might we think about Shakespeare and performance without print? Examining texts both early and modern, Shakespeare without Print contends that Shakespeare and performance has long been dominated by a medium alien to its expression, print, a foreign government that forecloses alternative conceptualizations and practices. Through a series of discrete but linked excursions into the relationship between Shakespearean print and Shakespearean performance, this Element auditions alternative prepositions to enfranchise scholars and practitioners from print, which currently binds and determines our various approaches to Shakespearean performance.
On sparsity, power-law, and clustering properties of graphex processes
Authors: Caron François , Panero Francesca , Rousseau Judith
Published: June 2023

This paper investigates properties of the class of graphs based on exchangeable point processes. We provide asymptotic expressions for the number of edges, number of nodes, and degree distributions, identifying four regimes: (i) a dense regime, (ii) a sparse, almost dense regime, (iii) a sparse regime with power-law behaviour, and (iv) an almost extremely sparse regime. We show that, under mild assumptions, both the global and local clustering coefficients converge to constants which may or may not be the same. We also derive a central limit theorem for subgraph counts and for the number of nodes. Finally, we propose a class of models within this framework where one can separately control the latent structure and the global sparsity/power-law properties of the graph.
From Iran to the Netherlands, and everywhere in between
Authors: Ballière Louise
Published: June 2023

A migrant's journey is no linear trajectory from A to B. It is a fragmented and complex move over different regions with alternating periods of mobility and immobility. This article researches the complex dynamics of irregular migration from Iran to the Netherlands, and everywhere in between. Through a historical comparison of the life stories of Iranian asylum seekers in the Netherlands in two time periods (1988–1989 and 2009–2010), it studies the routes they took, their relations with human smugglers, and their interactions with immigration policies and border managements along the way. It shows migrants' and smugglers’ flexibility and capacity to adapt to ever-changing circumstances. Migration politics and border controls, along with their increasing limitations on legal migration channels, are indeed crucial in the understanding of irregular migration practices and the ever-growing involvement of facilitating services. Through a combination of this migration policy research and the migration trajectory research, the paper explores these dynamics and the interactions between migrants, smugglers, and state policies in every phase of their journey from Iran to the Netherlands, and everywhere in between.
Identity Matters: Foetuses, Gametes, and Futures like Ours
Authors: Rimell Nicholas
Published: June 2023

Recently, a number of philosophers have argued that, despite appearances, the success of Don Marquis's well-known future-like-ours argument against abortion does not turn, in an important way, on the metaphysics of identity. I argue that this is false. The success of Marquis's argument turns on precisely two issues: first, whether it is prima facie seriously wrong to deprive something of a future like ours; second, whether, in a counterfactual circumstance in which an abortion does not occur, the foetus is numerically identical with something that, later on, experiences a life like ours. Since the former claim is plausible (albeit disputable), the success of Marquis's argument does turn on the metaphysics of identity in an important way. Before defending a positive argument for this position, I consider what I take to be the most promising way of challenging it. This involves a recent objection to Marquis by Tim Burkhardt (2021). Burkhardt claims that his objection floats free of the metaphysics of identity. I argue that it fails to do so, and that in fact it fails outright. I end by considering the relationship between my arguments and the question of what matters in survival.
Alternatives to antibiotics in veterinary medicine: considerations for the management of Johne's disease
Authors: O'Connell Laura M. , Coffey Aidan , O'Mahony Jim M.
Published: June 2023

Antibiotic resistance has become a major health concern globally, with current predictions expecting deaths related to resistant infections to surpass those of cancer by 2050. Major efforts are being undertaken to develop derivative and novel alternatives to current antibiotic therapies in human medicine. What appears to be lacking however, are similar efforts into researching the application of those alternatives, such as (bacterio)phage therapy, in veterinary contexts. Agriculture is still undoubtedly the most prominent consumer of antibiotics, with up to 70% of annual antibiotic usage attributed to this sector, despite policies to reduce their use in food animals. This not only increases the risk of resistant infections spreading from farm to community but also the risk that animals may acquire species-specific infections that subvert treatment. While these diseases may not directly affect human welfare, they greatly affect the profit margin of industries reliant on livestock due to the cost of treatments and (more frequently) the losses associated with animal death. This means actively combatting animal infection not only benefits animal welfare but also global economies. In particular, targeting recurring or chronic conditions associated with certain livestock has the potential to greatly reduce financial losses. This can be achieved by developing novel diagnostics to quickly identify ill animals alongside the design of novel therapies. To explore this concept further, this review employs Johne's disease, a chronic gastroenteritis condition that affects ruminants, as a case study to exemplify the benefits of rapid diagnostics and effective treatment of chronic disease, with particular regard to the diagnostic and therapeutic potential of phage.
Looking beyond the constituent power theory: The theory of equitable elite bargaining
Authors: Sethi Amal
Published: June 2023

The constituent power theory, which served critical functions for several years, has outlived its utility as the preeminent yardstick to measure the normative legitimacy of a constitution. As the theory stands, it cannot apply on its own terms to most instances of modern constitution-making. At the same time, it is highly susceptible to being used to legitimize authoritarian outcomes. The scholarly literature that attempts to reimagine or expand the theory is scant and unable to overcome its problems. In response, this article develops an alternative standard: the theory of equitable elite bargaining. This theory provides that a constitution is normatively legitimate if it is the product of an equitable bargain between elites from most major political groups in society at the moment of constitution-making. The theory of equitable elite bargaining is applicable to the realities of modern constitution-making and makes it more difficult to legitimize authoritarian constitutions. Further, both representation-based and consequentialist arguments can justify a constitution drafted in accordance with the theory as normatively legitimate. The theory imposes a standard that can result in arduous constitution-making processes and moderated constitutional content. Additionally, its focus on elites poses challenging questions. However, this article will argue that the net benefits of this theory warrant its consideration as a new standard to assess normative constitutional legitimacy.
Role of Mixed Layer Depth in Kuroshio Extension Decadal Variability
Authors: Tozuka Tomoki , Toyoda Takahiro , Cronin Meghan F.
Published: June 2023

Sea surface temperature (SST) anomalies in the Kuroshio Extension (KE) have been suggested to play a crucial role in decadal climate variability of the North Pacific affecting global climate and marine ecosystem variability. By analyzing the mixed layer heat budget, taking into account seasonality and mixed layer depth (MLD) variations, we here show for the first time that the KE SST front undergoes large decadal variations mainly owing to decadal modulations of the effective heat capacity affecting the SST sensitivity to surface heat fluxes during 1982–2015. More specifically, when the mixed layer becomes anomalously thick (shallow) to the south (north) of the front, it becomes less (more) sensitive to wintertime surface cooling. As a result, the SST front is strengthened, with positive (negative) SST anomalies to the south (north). A heat conservation model suggests that MLD anomalies are mainly due to thermocline depth anomalies.
Evaluation of the Stratospheric Contribution to the Inter‐Annual Variabilities of Tropospheric Methane Growth Rates
Authors: Zhang Peixuan , Zhang Yuzhong , Liang Ruosi , Chen Wei , Xie Xinchun
Published: June 2023

Tropospheric methane (CH4) shows large inter‐annual variability in its growth rates on top of decadal trends, which is usually interpreted as changes in sources or sinks. The contribution of the stratosphere‐troposphere exchange (STE) is often omitted in such analyses. Here, we quantify annual anomalies of stratosphere‐troposphere CH4 fluxes using varied model‐ or observation‐based methods. Globally, the inter‐annual variability (standard deviation) of this flux during 2000–2020 is 2.0 Tg a−1, producing a variability of ∼0.6 ppb a−1 at the surface, which is only ∼20% of observed surface CH4 growth rate variability. Compared to global averages, high latitudes experience a larger STE‐induced surface variability, which is 80% of the observed surface anomalies in the Antarctic and 44% in the Arctic. Our results suggest that although the STE process is a minor contributor globally, it has a considerable impact over polar regions on the inter‐annual variability of surface CH4 growth rates.
The Thermal Plumbing System of Stromboli Volcano, Aeolian Islands (Italy) Inferred From Electrical Conductivity and Induced Polarization Tomography
Authors: Revil A. , Finizola A. , Johnson T. , Ricci T. , Gresse M. , Delcher E. , Barde‐Cabusson S. , Duvillard P. A. , Ripepe M.
Published: June 2023

We performed the first 3D island‐scale tomography of the electrical conductivity of Stromboli volcano (Aeolian Islands, Italy) using 2D acquisition lines (37.2 km) and a total of 18,880 measurements and 2,402 unique electrode locations. This 3D data set was inverted using a Gauss‐Newton algorithm, parallel‐processing on an unstructured tetrahedral mesh containing 678,420 finite‐element nodes and 3,580,145 elements to account for the topography of the volcanic island. The tomogram exhibits a conductive body (10−2–1.0 S m−1) consistent with the location of CO2 and temperature anomalies observed at the ground surface. It corresponds to the hydrothermal system with high electrical conductivity associated with alteration. In order to confirm this interpretation, a 2.5D large‐scale induced polarization tomography was performed crossing the volcano. The joint interpretation of the conductivity and normalized chargeability is done with a petrophysical model previously tested and verified at both shield‐ and strato‐volcanoes. This model implies that alteration (through the effect of the cation exchange capacity associated with clay minerals and zeolites) plays a strong role in both controlling the electrical conductivity and normalized chargeability at Stromboli volcano. A temperature tomogram, derived from the geoelectrical measurements, is consistent with surface temperature anomalies and the Very Long Period (VLP) seismicity related to the mild‐explosive activity. This survey displays at 600 m a.s.l. a lateral shift in the highest temperature location, also corresponding to the source of VLP seismicity. Structural boundaries have a major role in the hottest hydrothermal fluids rising below the active crater terrace of Stromboli volcano.
Observation and Process Understanding of Typical Cloud Holes Above Lakes Over the Tibetan Plateau
Authors: Yao Xiangnan , Yang Kun , Letu Husi , Zhou Xu , Wang Yan , Ma Xiaogang , Lu Hui , La Zhu
Published: June 2023

Understanding cloud distribution over lakes is crucial to determine input radiation and precipitation for lake thermal and water balance processes. Based on Himawari‐8 satellite observation and Weather Research and Forecasting model results, this study examines the influences of lakes on daytime cloud cover during warm seasons over the Tibetan Plateau (TP), which is home to thousands of lakes. Observation shows the existence of cloud holes and narrow cloud rings around the lakes, that is, fewer clouds over the lakes and more clouds along the shoreline, which has rarely been reported and is considered typical to TP by comparison with lakes outside of TP. The threshold size of lakes that can produce the shoreline cloud ring is identified to be about 300 km2, as a conservative estimate. We further highlight the importance of atmosphere advection/background wind in the formation of lake‐associated clouds. Lake breeze forms under weak background winds and the downdraft branch inhibits cloud formation over the lakes; while the updraft branch causes convection to form clouds over lakeshores. However, strong background winds do not favor lake breeze formation, changing cloud distribution over the lakes. Fewer clouds are also found in the downwind regions, and this influence is at a distance comparable to the lake scale. Due to fewer clouds over lakes, shortwave radiation is significantly larger (∼100 W/m2) and longwave radiation is smaller (∼a few W/m2) than that of the further land region. Therefore, the above observational facts provide a new perspective to advance the understanding of lake‐air interactions.
Triple network model of brain connectivity changes related to adverse mood effects in an oral contraceptive placebo-controlled trial
Authors: Hidalgo-Lopez Esmeralda , Engman Jonas , Poromaa Inger Sundström , Gingnell Malin , Pletzer Belinda
Published: June 2023

Combined oral contraceptives (COC) are among the most commonly used contraceptive methods worldwide, and mood side effects are the major reason for discontinuation of treatment. We here investigate the directed connectivity patterns associated with the mood side effects of an androgenic COC in a double-blind randomized, placebo-controlled trial in women with a history of affective COC side effects (n = 34). We used spectral dynamic causal modeling on a triple network model consisting of the default mode network (DMN), salience network (SN) and executive control network (ECN). Within this framework, we assessed the treatment-related changes in directed connectivity associated with adverse mood side effects. Overall, during COC use, we found a pattern of enhanced connectivity within the DMN and decreased connectivity within the ECN. The dorsal anterior cingulate cortex (SN) mediates an increased recruitment of the DMN by the ECN during treatment. Mood lability was the most prominent COC-induced symptom and also arose as the side effect most consistently related to connectivity changes. Connections that were related to increased mood lability showed increased connectivity during COC treatment, while connections that were related to decreased mood lability showed decreased connectivity during COC treatment. Among these, the connections with the highest effect size could also predict the participants’ treatment group above chance.