bluuebunny/crossref_metadata_2025 huggingface dataset:
Generative adversarial networks for construction of virtual populations of mechanistic models: simulations to study Omecamtiv Mecarbil action
Authors: Parikh Jaimit , Rumbell Timothy , Butova Xenia , Myachina Tatiana , Acero Jorge Corral , Khamzin Svyatoslav , Solovyova Olga , Kozloski James , Khokhlova Anastasia , Gurev Viatcheslav
Published: October 2021

Biophysical models are increasingly used to gain mechanistic insights by fitting and reproducing experimental and clinical data. The inherent variability in the recorded datasets, however, presents a key challenge. In this study, we present a novel approach, which integrates mechanistic modeling and machine learning to analyze in vitro cardiac mechanics data and solve the inverse problem of model parameter inference. We designed a novel generative adversarial network (GAN) and employed it to construct virtual populations of cardiac ventricular myocyte models in order to study the action of Omecamtiv Mecarbil (OM), a positive cardiac inotrope. Populations of models were calibrated from mechanically unloaded myocyte shortening recordings obtained in experiments on rat myocytes in the presence and absence of OM. The GAN was able to infer model parameters while incorporating prior information about which model parameters OM targets. The generated populations of models reproduced variations in myocyte contraction recorded during in vitro experiments and provided improved understanding of OM’s mechanism of action. Inverse mapping of the experimental data using our approach suggests a novel action of OM, whereby it modifies interactions between myosin and tropomyosin proteins. To validate our approach, the inferred model parameters were used to replicate other in vitro experimental protocols, such as skinned preparations demonstrating an increase in calcium sensitivity and a decrease in the Hill coefficient of the force–calcium (F–Ca) curve under OM action. Our approach thereby facilitated the identification of the mechanistic underpinnings of experimental observations and the exploration of different hypotheses regarding variability in this complex biological system.
The Emirates Exploration Imager (EXI) Instrument on the Emirates Mars Mission (EMM) Hope Mission
Authors: Jones A. R. , Wolff M. , Alshamsi M. , Osterloo M. , Bay P. , Brennan N. , Bryant K. , Castleman Z. , Curtin A. , DeVito E. , Drake V. A. , Ebuen D. , Espejo J. , Farren J. , Fenton B. , Fisher C. , Fisher M. , Fortier K. , Gerwig S. , Heberlein B. , Jeppesen C. , Khoory M. A. , Knappmiller S. , Knavel J. , Koski K. , Looney K. , Lujan P. , Miller M. , Newcomb G. , Otzinger G. , Passe H. , Pilinski E. , Reed H. , Shuping R. , Sicken P. , Summers D. , Wade S. , Walton L. , Yaptengco J. L.
Published: October 2021

The Emirates Exploration Imager (EXI) on-board the Emirates Mars Mission (EMM) offers both regional and global imaging capabilities for studies of the Martian atmosphere. EXI is a framing camera with a field-of-view (FOV) that will easily capture the martian disk at the EMM science orbit periapsis. EXI provides 6 bandpasses nominally centered on 220, 260, 320, 437, 546, 635 nm using two telescopes (ultraviolet (UV) and visible(VIS)) with separate optics and detectors. Images of the full-disk are acquired with a resolution of 2–4 km per pixel, where the variation is driven by periapsis and apoapsis points of the orbit, respectively. By combining multiple observations within an orbit with planetary rotation, EXI is able to provide diurnal sampling over most of the planet on the scale of 10 days. As a result, the EXI dataset allows for the delineation of diurnal and seasonal timescales in the behavior of atmospheric constituents such as water ice clouds and ozone.

This combination of temporal and spatial distinguishes EXI from somewhat similar imaging systems, including the Mars Color Imager (MARCI) onboard the Mars Reconnaissance Orbiter (MRO) (Malin et al. in Icarus 194(2):501–512, 2008) and the various cameras on-board the Hubble Space Telescope (HST; e.g., James et al. in J. Geophys. Res. 101(E8):18,883–18,890, 1996; Wolff et al. in J. Geophys. Res. 104(E4):9027–9042, 1999). The former, which has comparable spatial and spectral coverage, possesses a limited local time view (e.g., mid-afternoon). The latter, which provides full-disk imaging, has limited spatial resolution through most of the Martian year and is only able to provide (at most) a few observations per year given its role as a dedicated, queue-based astrophysical observatory. In addition to these unique attributes of the EXI observations, the similarities with other missions allows for the leveraging of both past and concurrent observations. For example, with MARCI, one can build on the ∼6 Mars years of daily global UV images as well as those taken concurrently with EXI.
QRev: migrating quantum code towards hybrid information systems
Authors: Pérez-Castillo Ricardo , Jiménez-Navajas Luis , Piattini Mario
Published: October 2021

Quantum computing is now a reality, and its incomparable computational power has led companies to show a great interest in being able to work with quantum software in order to support part of their current and future business operations. However, the quantum computing paradigm differs significantly from its classical counterparts, which has brought about the need to revolutionise how the future software is designed, built, and operated in order to work with quantum computers. Since companies cannot discard all their current (and probably mission-critical) information systems, they must adapt their classical information systems to new specific quantum applications, thus evolving towards hybrid information systems. Unfortunately, there are no specific methods with which to deal with this challenge. We believe that reengineering, and more specifically, software modernisation using model-driven engineering principles, could be useful as regard migrating classical systems and existing quantum programs towards hybrid information systems. This paper, therefore, presents QRev, a reverse engineering tool that analyses quantum programs developed in Q# in order to identify its components and interrelationships, and then generates abstract models that can be used in software modernisation processes. The platform-independent models are generated according to the Knowledge Discovery Metamodel (KDM) standard. QRev is validated in a case study involving five quantum programs in order to demonstrate its effectiveness and scalability. The main implication of the study is that QRev can be used in order to attain KDM models, which can subsequently be employed to restructure or add new quantum functionality at a higher abstraction level, i.e. independently of the specific quantum technology.
Veränderungsmessung und Rückfälligkeit im Risikoorientierten Sanktionenvollzug
Authors: Treuthardt Daniel , Kröger Melanie
Published: October 2021

Mit der Einführung des Risikoorientierten Sanktionenvollzugs (ROS) in der Schweiz sollen Rückfälle größtmöglich reduziert und die Ressourcen der Straftäter*innen gestärkt werden. Um diesem Anspruch gerecht zu werden, wird ROS fortlaufend evaluiert und weiterentwickelt. Nun soll eine konzipierte Veränderungsmessung überprüft werden, die ROS erweitern und die Abbildung von Veränderungen transparenter und nachvollziehbarer machen könnte. Neben den demografischen und Rückfalldaten werden diverse personen- und umweltbezogene Aspekte herangezogen. Konkret wird anhand von 302 Fällen betrachtet, ob im Verlauf der Sanktion eine Verbesserung der personen- und umweltbezogenen Aspekte stattgefunden hat. Anschließend wird analysiert, ob Verbesserungen der personen- und umweltbezogenen Variablen Zusammenhänge zur Rückfälligkeit aufweisen. Ebenso wird betrachtet, ob eine gute Passung von forensischem Bedarf und juristischen Rahmenbedingungen mit den Variablen sowie der Rückfälligkeit zusammenhängt. Des Weiteren wird anhand von Vergleichsdaten aus einer Stichprobe vor der Einführung von ROS die Wirksamkeit von ROS in Bezug auf Rückfälligkeit untersucht. Die untersuchten Bereiche weisen teilweise signifikante Ergebnisse auf. So deuten die Befunde darauf hin, dass die Veränderungsmessung grundsätzlich eine sinnvolle Ergänzung im ROS-Prozess darstellt. Außerdem kann die Wirksamkeit von ROS bestätigt werden. Abschließend werden Limitationen diskutiert und ein Ausblick gegeben.
Future care for long-term cancer survivors: towards a new model
Authors: Provencio M. , Romero N. , Tabernero J. , Vera R. , Baz D. V. , Arraiza A. , Camps C. , Felip E. , Garrido P. , Gaspar B. , Llombart M. , López A. , Magallón I. , Ibáñez V. M. , Olmos J. M. , Mur C. , Navarro-Ruiz A. , Pastor A. , Peiró M. , Polo J. , Rodríguez-Lescure Á.
Published: October 2021

Purpose

The increase in the prevalence "long-term cancer survivor” (LCS) patients is expected to increase the cost of LCS care. The aim of this study was to obtain information that would allow to optimise the current model of health management in Spain to adapt it to one of efficient LCS patient care.

Methods

This qualitative study was carried out using Delphi methodology. An advisory committee defined the criteria for participation, select the panel of experts, prepare the questionnaire, interpret the results and draft the final report.

Results

232 people took part in the study (48 oncologists). Absolute consensus was reached in three of the proposed sections: oncological epidemiology, training of health professionals and ICT functions.

Conclusion

The role of primary care in the clinical management of LCS patients needs to be upgraded, coordination with the oncologist and hospital care is essential. The funding model needs to be adapted to determine the funding conditions for new drugs and technologies.
Finanzielle Kompetenzen und Defizite in Deutschland – eine aktuelle Bestandsaufnahme
Authors: Bachmann Ronald , Rulff Christian , Schmidt Christoph M.
Published: October 2021

Die Anforderungen an die Finanzkompetenzen der Bevölkerung steigen aus einer Reihe von Gründen weiter an. Anhand des Datensatzes „Private Haushalte und ihre Finanzen“ zeigt diese Studie, dass in Deutschland generell ein relativ hohes Niveau an Finanzkompetenz vorliegt; dennoch besteht hier Verbesserungspotenzial. Dies gilt insbesondere für bestimmte sozio-demographische Gruppen wie Frauen, Personen mit Migrationshintergrund sowie finanzschwache Haushalte. Hieraus ergibt sich Handlungsbedarf, der für verschiedene Felder diskutiert wird. Es wird insbesondere empfohlen, Finanzbildung stärker in die Lehrpläne von Schulen zu integrieren, die Ausbildung von Lehrern in diesem Bereich zu verbessern, Bildungs- und Informationsangebote für Erwachsene zu stärken und die Transparenz von Finanz- und Versicherungsprodukten zu erhöhen.
Freedom of Expression
Authors: Tourkochoriti Ioanna
Published: October 2021

Two legal systems founded from similar Enlightenment philosophical and political values use state coercion differently to regulate a core liberty: the freedom of expression. This comparative study of France and the United States proposes a novel theory of how the limits of freedom of expression are informed by different revolutionary experiences and constitutional and political arrangements. Ioanna Tourkochoriti argues that the different ways freedom of expression is balanced against other values in France and the United States can be understood in reference to the role of the government and the understanding of republicanism and liberty. This understanding affects how jurists define the content and the limits of a liberty and strike a balance between liberties in conflict. Exploring both the legal traditions of the two countries, this study sheds new light on the broader historical, social and philosophical contexts in which jurists operate.
How We Resist Metaphors
Authors: GIBBS RAYMOND W. , SIMAN JOSIE
Published: October 2021

abstract

Most people love metaphor, but we still sometimes find ourselves resisting their presence or meanings for various reasons. We resist metaphors both as a general strategy (e.g., “Metaphors are meaningless” or “Mixed metaphor are incoherent”), and as a response to some metaphors in very specific situational and discourse contexts (e.g., “I do not like the idea that my cancer treatment is seen as a war against my body”). People resist metaphors they have produced, metaphors imposed on them by others, and metaphors that they find to be offensive or that negatively stigmatize other individuals, or groups of people. But metaphors are also resisted for their lack of explanatory power in, for instance, scientific communities. There are also many ironies associated with metaphor resistance, such as consciously resisting some metaphor while still being governed by that same metaphor in our unconscious thinking and actions. Most generally, though, metaphor resistance is its own kind of metaphorical action. Taking a dynamic systems approach to resistance to metaphors, we discuss several implications of these observations for theories of metaphorical thought and language.
Comparison of aerobic rice cultivation using drip systems with conventional flooding
Authors: Bozkurt Çolak Y.
Published: October 2021

In this study, yield and water productivity response of rice to various irrigation levels applied with subsurface and surface drip systems in 2019 and 2020 in the Mediterranean Region of Turkey was evaluated in comparison with conventional flooding (CF). The treatments consisted of two irrigation methods namely surface drip (DI) and subsurface drip systems (SDI), three irrigation levels designated as plant pan coefficients (I1.00: Evaporation from Class A pan (Ep) × 1.00; I1.25: Ep × 1.25 and I1.50: Ep × 1.50) and CF as control. The effects of drip systems and coefficients on yield and yield components were statistically significant (P < 0.01). DI produced higher yield than SDI. CF produced significantly greater yield than both DI and SDI systems. With two drip systems, average water savings of 60.5% in I1.00, 54.5% in I1.25 and 49% in I1.50 were achieved as compared to CF. However, yield reductions of 15% in I1.50, 20% in I1.25, 29% in I1.00 were observed for DI; corresponding values for SDI were 20, 28 and 44%, respectively. Drip irrigation in aerobic rice production system had almost twice the water productivity based on total irrigation water applied (WPI) or total water input (irrigation + rainfall) (WPI+P) compared with CF. During the study years, the highest WPI and WPI+P values were found in DI-I1.00 (0.81–0.73 kg/m3) and (0.85 and 0.74 kg/m3), respectively. In conclusion, DI-I1.50 treatment is recommended for sustainable aerobic rice production since DI-I1.50 resulted in water saving of 49% but yield decrease of 15% as compared to CF.
Real-time single-frequency precise positioning with Galileo satellites
Authors: Bahadur Berkay
Published: October 2021

Following substantial progress achieved recently, the Galileo constellation provides a considerable satellite resource for the GNSS applications. In this regard, the performance assessment of real-time single-frequency precise positioning with Galileo satellites is the main objective of this research. For this purpose, several experimental tests were conducted in this study with two single-frequency positioning models, namely single-frequency code-based positioning and code-phase combination. The results show that Galileo presents an adequate number of visible satellites sufficient for single-frequency positioning. Also, the study demonstrates that, in comparison to GPS observations, Galileo observations have a significantly lower noise level. For the single-frequency code-based positioning, Galileo presents a better positioning accuracy than GPS by 25⋅8% on average. When compared with GPS, a 9⋅4% better positioning accuracy is acquired from Galileo for the single-frequency code-phase combination, with its average convergence time shorter than GPS by a ratio of 24⋅4%.
The Nicaraguan Revolution's Challenge to the Monroe Doctrine: Sandinistas and Western Europe, 1979–1990
Authors: van Ommen Eline
Published: October 2021

This article analyzes the revolutionary diplomacy of the Sandinista National Liberation Front (FSLN) through the prism of Nicaraguan and Western European relations during the final decade of the Cold War. It contends that —despite the FSLN's ideological affiliation with Third World national liberation movements, Cuba, and the socialist bloc—the campaign to influence Western European foreign policies was central to the Sandinista government's international strategy. By pushing Western European governments to play a prominent role in Central America's violent Cold War conflicts, the Sandinistas sought to undermine US power in the isthmus and alter the inter-American dynamics that shaped their region's history up to the late 1970s. Furthermore, by building financial ties with Western European countries, the FSLN could avoid complete financial dependency on the Soviet bloc and strengthen Nicaragua's image as a nonaligned state. The Sandinistas’ campaign to challenge US hegemony in Central America through a pragmatic outreach to Western Europe was largely successful, but it came at the cost of implementing domestic reforms that ran counter to their own ambitions. Ultimately, this prompted the FSLN to hold elections in 1990, which resulted in their removal from power.
Analogic Perspective-Taking and Attitudes Toward Political Organizations: An Experiment with a Teachers’ Union
Authors: Hertel-Fernandez Alexander , Porter Ethan
Published: October 2021

Attitudes toward social out-groups can be improved through “analogic perspective-taking,” whereby respondents are encouraged to use an analogy to take the perspective of the group. It is unclear, however, whether analogic perspective-taking can improve attitudes toward political organizations; how perspective-taking fares compared to the provision of narrative alone; and the limits of the attitude changes it creates. We report results from an experiment that tested analogic perspective-taking exercises about members of teachers’ unions. While perspective-taking improves attitudes toward unions, union members, and willingness to pay more in education taxes, it also increases support for some antiunion policies. A second study suggests that the bidirectional policy effects are attributable to subjects’ difficulty distinguishing pro- from antiunion policies. Analogic perspective-taking can improve attitudes toward social and political groups. But narrative exchange is not always superior to narrative provision, and both approaches may yield mixed effects on policy attitudes.
How Does Threat Modulate the Motivational Effects of Reward on Attention?
Authors: Kim Andy J. , Anderson Brian A.
Published: October 2021

Abstract. Studies on attentional bias have overwhelmingly focused on the priority of different stimuli and have rarely manipulated the state of the observer. Recently, the threat of unpredictable shock has been utilized to experimentally induce anxiety and investigate how negative arousal modulates attentional control. Experimentally induced anxiety has been shown to reduce the attentional priority afforded to reward-related stimuli while enhancing the efficiency of goal-directed attentional control. It is unclear which of these two influences might dominate when attending to reward-related stimuli is consistent with task goals and by extension what the scope of the modulatory influence of threat on attention is. In contrast to paradigms in the visual domain, a novel auditory identification task has demonstrated a robust influence of target-value associations on selective attention. In the present study, we examined how the threat of shock modulates the influence of learned value on voluntary attention. In both threat and no-threat conditions, we replicate prior findings of voluntary prioritization of reward-associated sounds. However, unlike in studies measuring involuntary attentional capture, threat did not modulate the influence of reward on attention. Our findings highlight important limitations to when and how threat modulates the control of attention, contextualizing prior findings.
Multi‐Objective Adaptive Surrogate Modeling‐Based Optimization for Distributed Environmental Models Based on Grid Sampling
Authors: Sun Ruochen , Duan Qingyun , Huo Xueli
Published: October 2021

Parameter optimization is needed for reliable simulations and predictions of natural processes by environmental models. The surrogate modeling‐based approach is an efficient way to reduce the number of model evaluations needed for optimization. However, building a surrogate of a distributed environmental model with many output variables over a large spatial domain is computationally intensive as it involves a large number of expensive model simulations on many spatial grid cells. In this study, a novel calibration method called the multi‐objective adaptive surrogate modeling‐based optimization using grid sampling (MO‐ASMOGS) is introduced. This method constructs the response surface surrogate of the original model more efficiently by using both parameter and spatial grid sampling. The spatial grid sampling strategy utilizes the evolutionary elitism and adaptive sampling concepts, thus allowing the surrogate model to be built using a fraction of the total grid cells over a large region. We apply MO‐ASMOGS to calibrating the Noah‐MP model against two surface fluxes: the gross primary production (GPP) and the latent heat flux (LH), over two plant function types (PFTs) across the continental United States. The results demonstrate that the MO‐ASMOGS method can significantly improve the GPP and LH simulations. The new method needs only a small portion of the total grid cells sampled for a given PFT to achieve comparable optimization results obtained by MO‐ASMO using all grid cells. This method can be very valuable in improving model calibration of computationally intensive distributed environmental models.
Supercell Thunderstorms Shake Up the Stratosphere
Authors: Wilkerson Jordan
Published: October 2021

Supercell storm tops may act like mountains that obstruct winds, transforming their flow into violent turbulence that mixes near-surface air with the stratosphere above.
Could AI Be Useful for Arctic Communities Facing Sea Ice Loss?
Authors: Basilio Humberto
Published: October 2021

The forecasting tool IceNet promises to be a useful tool for evaluating sea ice loss in the Arctic. But ethical and logistic considerations have to be taken before scientific and Indigenous communities start working together.
Bifurcated Current Sheets in Mercury's Magnetotail: Observations and Implications
Authors: Al Asad Manar M. , Johnson Catherine L. , Philpott Lydia C.
Published: October 2021

Cross‐tail current sheets play an important role in magnetospheric dynamics and plasma transport. We present a comprehensive study of the structure and behavior of Mercury's cross‐tail current sheet, as well as constraints on the plasma environment imposed by this structure, using magnetic field measurements from the MESSENGER spacecraft. We find that the current sheet dominantly exhibits a bifurcated, or double‐peaked, current density structure throughout the tail region, but that a single‐peaked sheet is sometimes observed. The time‐averaged current distribution in the nightside magnetosphere is as follows: close to the planet on the midnight plane at an altitude of 0.15 RM (where RM is Mercury radius = 2,440 km), current density peaks are 0.2 RM north and south of the magnetic equator. The peak‐to‐peak separation decreases with down‐tail distance, until the current density profile resembles that of a single‐peaked sheet. We find no correlation between the sheet geometry and long‐period variations in solar wind and magnetospheric conditions. We attribute the observed bifurcated structure in the current sheet to non‐adiabatic behavior (Speiser orbits) of the major plasma constituents in Mercury's magnetosphere (H+, Na+ and, to a lesser extent e−). Finally, we infer the spatial distribution of the current carriers by comparing a simple model of their resultant current sheets to observations. We find that, close to the planet, a combination of planetary sodium ions and solar wind protons with energies of a few keV are the main current carriers, but in the far‐tail region, the current is dominantly carried by solar wind protons.
Formation Mechanism of Warm SST Anomalies in 2010s Around Hawaii
Authors: Takahashi Naoya , Richards Kelvin J. , Schneider Niklas , Annamalai H. , Hsu Wei‐Ching , Nonaka Masami
Published: October 2021

Warm sea surface temperature (SST) anomalies have been observed in the subtropical North Pacific around Hawaii in the recent decade, appearing from 2013. We examined the formation mechanisms of the warm SST anomalies in terms of relative contribution of atmospheric surface forcing and oceanic dynamics, using the latest reanalysis products from ECMWF (ERA5 for atmosphere and ORAS5 for ocean). Results of the mixed layer temperature budget diagnosis in the target area (10–20°N and 180°–160°W) indicates that contributions from anomalous latent heat fluxes to the subtropical SST anomalies are dominant. Oceanic advective contributions play a secondary role, dampen the SST anomalies, and are negatively correlated (r = −0.38) with the latent heat fluxes. For example, the +1.0 K SST increased from 2011 to 2015 results from +1.5 K contributions from sum of surface heat flux and −0.5 K from meridional oceanic advection. The anti‐correlation between atmospheric forcing and oceanic meridional advection reflects co‐variations of wind‐driven latent heat flux and meridional Ekman advection due to the weakening of the zonal component of the surface winds.
Rheological and Mechanical Layering of the Crust Underneath Thumbprint Terrains in Arcadia Planitia, Mars
Authors: De Toffoli B. , Massironi M. , Mazzarini F. , Bistacchi A.
Published: October 2021

In the area of Arcadia Planitia in the Northern hemisphere of Mars, mounds indicating fluid and sediment emissions have been already recognized. Here, we show that through fractal and fracture‐spacing analyses of a large vent population it is possible to infer the mechanical layering of the underlying subsurface. Our work includes the mapping of an entire population of 9,028 vents over an area of 122,000 km2. The analysis of mound distribution at the surface led to the formulation of inferences about the subsurface feeding conduits, and to the identification of three mechanical discontinuities at c. 4–5, c. 14–23, and c. 50–55 km. This evidence matches the mechanical stratigraphy recorded by the InSight NASA mission, and is in agreement with independent previous subsurface global modeling, supporting our conclusions.
Pancreatic cancer cells render tumor-associated macrophages metabolically reprogrammed by a GARP and DNA methylation-mediated mechanism
Authors: Zhang Mengwen , Pan Xingyi , Fujiwara Kenji , Jurcak Noelle , Muth Stephen , Zhou Jiaojiao , Xiao Qian , Li Anqi , Che Xu , Li Zihai , Zheng Lei
Published: October 2021

How tumor-associated macrophages transit from a predominant antitumor M1-like phenotype to a protumoral M2-like phenotype during the development of pancreatic ductal adenocarcinoma (PDA) remains to be elucidated. We thus conducted a study by employing a PDA-macrophage co-culture system, an “orthotopic” PDA syngeneic mouse model, and human PDA specimens, together with macrophages derived from GARP knockout mice and multiple analytic tools including whole-genome RNA sequencing, DNA methylation arrays, multiplex immunohistochemistry, metabolism measurement, and invasion/metastasis assessment. Our study showed that PDA tumor cells, through direct cell–cell contact, induce DNA methylation and downregulation of a panel of glucose metabolism and OXPHOS genes selectively in M1-like macrophages, leading to a suppressed glucose metabolic status in M1-like but not in M2-like macrophages. Following the interaction with PDA tumor cells, M1-like macrophages are reprogrammed phenotypically to M2-like macrophages. The interaction between M1-like macrophages and PDA cells is mediated by GARP and integrin αV/β8, respectively. Blocking either GARP or integrin would suppress tumor-induced DNA methylation in Nqo-1 gene and the reprogramming of M1-like macrophages. Glucose-response genes such as Il-10 are subsequently activated in tumor-educated M1-like macrophages. Partly through Il-10 and its receptor Il-10R on tumor cells, M1-like macrophages functionally acquire a pro-cancerous capability. Both exogenous M1-like and M2-like macrophages promote metastasis in a mouse model of PDA while such a role of M1-like macrophages is dependent on DNA methylation. Our results suggest that PDA cells are able to reprogram M1-like macrophages metabolically and functionally through a GARP-dependent and DNA methylation-mediated mechanism to adopt a pro-cancerous fate.
Autophagy is induced and modulated by cholesterol depletion through transcription of autophagy-related genes and attenuation of flux
Authors: Shapira Keren E. , Shapira Guy , Schmukler Eran , Pasmanik-Chor Metsada , Shomron Noam , Pinkas-Kramarski Ronit , Henis Yoav I. , Ehrlich Marcelo
Published: October 2021

Perturbations to cellular homeostasis, including reduction of the cholesterol level, induce autophagy, a self-digestion process of cellular constituents through an autophagosomal–lysosomal pathway. In accord with its function as a membrane organizer and metabolic sentinel, the cellular response to cholesterol depletion comprises multiple phenomena, including the activation of transcriptional responses, accumulation of reactive oxygen species (ROS), and activation of stress-related signaling pathways. However, the molecular mechanisms by which cholesterol depletion regulates autophagy and the putative involvement of transcriptional responses, ROS and/or stress-related signaling in autophagy regulation in this biological context are not fully understood. Here, we find that cholesterol depletion regulates autophagy at three different levels. First, employing RNA-seq, we show that cholesterol depletion increases the expression of autophagy-related genes independent of ROS or JNK activity. Second, analysis of LC3 lipidation and intracellular localization, and of p62 levels and degradation kinetics, reveals that cholesterol depletion mediates autophagy induction while interfering with autophagic flux. Of note, only the latter depends on ROS accumulation and JNK activity. In view of the common use of cholesterol-reducing drugs as therapeutic agents, our findings have important implications for multiple cellular settings in which autophagy plays a prominent role.
Pupil responses associated with the perception of gravitational vertical under directional optic flows
Authors: Park Joo Hyun , Cho Sung Ik , Choi June , Han JungHyun , Rah Yoon Chan
Published: October 2021

This study assessed the pupil responses in the sensory integration of various directional optic flows during the perception of gravitational vertical. A total of 30 healthy participants were enrolled with normal responses to conventional subjective visual vertical (SVV) which was determined by measuring the difference (error angles) between the luminous line adjusted by the participants and the true vertical. SVV was performed under various types of rotational (5°/s, 10°/s, and 50°/s) and straight (5°/s and 10°/s) optic flows presented via a head-mounted display. Error angles (°) of the SVV and changes in pupil diameters (mm) were measured to evaluate the changes in the visually assessed subjective verticality and related cognitive demands. Significantly larger error angles were measured under rotational optic flows than under straight flows (p < 0.001). The error angles also significantly increased as the velocity of the rotational optic flow increased. The pupil diameter increased after starting the test, demonstrating the largest diameter during the final fine-tuning around the vertical. Significantly larger pupil changes were identified under rotational flows than in straight flows. Pupil changes were significantly correlated with error angles and the visual analog scale representing subjective difficulties during each test. These results suggest increased pupil changes for integrating more challenging visual sensory inputs in the process of gravity perception.
Transcriptomic analysis of Rhodococcus opacus R7 grown on polyethylene by RNA-seq
Authors: Zampolli Jessica , Orro Alessandro , Manconi Andrea , Ami Diletta , Natalello Antonino , Di Gennaro Patrizia
Published: October 2021

Plastic waste management has become a global issue. Polyethylene (PE) is the most abundant synthetic plastic worldwide, and one of the most resistant to biodegradation. Indeed, few bacteria can degrade polyethylene. In this paper, the transcriptomic analysis unveiled for the first time Rhodococcus opacus R7 complex genetic system based on diverse oxidoreductases for polyethylene biodegradation. The RNA-seq allowed uncovering genes putatively involved in the first step of oxidation. In-depth investigations through preliminary bioinformatic analyses and enzymatic assays on the supernatant of R7 grown in the presence of PE confirmed the activation of genes encoding laccase-like enzymes. Moreover, the transcriptomic data allowed identifying candidate genes for the further steps of short aliphatic chain oxidation including alkB gene encoding an alkane monooxygenase, cyp450 gene encoding cytochrome P450 hydroxylase, and genes encoding membrane transporters. The PE biodegradative system was also validated by FTIR analysis on R7 cells grown on polyethylene.
Chronic kidney disease and pregnancy outcomes
Authors: Dvořák Jan , Koucký Michal , Jančová Eva , Mysliveček Marek , Tesař Vladimír , Pařízek Antonín
Published: October 2021

Pregnancy complicated by CKD is currently not fully understood topic. Outcome of pregnancy in patients with CKD is related to impaired glomerular filtration rate and the degree of proteinuria. In our study we evaluated the association of serum creatinine level and proteinuria with both maternal and fetal outcomes in the cohort of 84 pregnant patients with CKD. In CKD group we confirmed negative correlation of highest serum creatinine level in pregnancy to fetal weight (p value < 0.001) and gestation period (p value < 0.001). Likewise, negative correlation of preconception serum creatinine to fetal weight (p value < 0.001) and gestation period (p value 0.002). Negative correlation of proteinuria to gestation period (p value < 0.001) and fetal weight (p value < 0.001) was also demonstrated. CKD is serious risk factor for pregnancy outcome. Proteinuria and serum creatinine level should be examined before pregnancy and regularly monitored during pregnancy. Higher serum creatinine levels and higher proteinuria predispose to shorter gestation period and lower birth weight of the neonate.
A visualized ratiometric fluorescence sensing system for copper ions based on gold nanoclusters/perovskite quantum dot@SiO2 nanocomposites
Authors: Xue Wanying , Zhong Jiangyan , Wu Haishan , Zhang Jianhua , Chi Yuwu
Published: October 2021

Green light-emitting SiO2-encapsulated single perovskite quantum dot (PQD@SiO2) core-shell nanostructures are composited with red light-emitting gold nanoclusters (AuNCs) to obtain a visualized ratiometric fluorescence sensor for the detection of Cu2+.
Steric control of sorting regimes in self-assembled cages
Authors: Walker Samuel E. , Boer Stephanie A. , Malcomson Thomas , Paterson Martin J. , Tuck Kellie L. , Turner David R.
Published: October 2021

Self-sorting regimes are controlled by adjusting steric interactions in self-assembled coordination cages and equilibration followed by HPLC. Statistical or biased distributions can be obtained, including isolation of a single heteroleptic species.
Simple and effective purification of a SGLT-2 inhibitor cocrystal Rongliflozin l-pyroglutamic acid: coformer-induced purification
Authors: Chen Dao-Qian , Gu Zheng , Wu Yu-Sheng , Yuan Wei-Hui , Li Zheng
Published: October 2021

We report and design a simple and robust process to obtain a single and pure crystalline form I (1) of the cocrystal, containing Rongliflozin (2) with l-pyroglutamic acid (l-PA), based on coformer-induced purification (CoIP).
A study on the multiferroic properties of semi-hydrogenated X2H (X = C, Si, and Ge) monolayer films
Authors: Zhang Shijun , Geng Chenduo , Wu Chunxiang , Zhou Pengxia , Dong Zhengchao , Zhong Chonggui
Published: October 2021

The 19% strained Si2H and Ge2H monolayers are predicted to be multiferroics with FM and large FE polarization and a low reversal barrier.
The porphyrin center as a regulator for metal–ligand covalency and π hybridization in the entire molecule
Authors: Büchner Robby , Fondell Mattis , Haverkamp Robert , Pietzsch Annette , Vaz da Cruz Vinícius , Föhlisch Alexander
Published: October 2021

The porphyrin center is shown to control both the covalency of the central complex and π hybridization with peripheral substituents.
Reaction of potassium phosphide KP(iPr)Ter with chalcogens, heteroallenes and an acyl chloride
Authors: Szych Lilian Sophie , Lüdtke Karsten Paul , Pilopp Yannic , Bresien Jonas , Villinger Alexander , Schulz Axel
Published: October 2021

Investigations on the reactivity of phosphide KP(iPr)R1 toward chalcogens, heteroallenes and an acyl chloride are reported, revealing the distinct nucleophilicity of the potassium phosphide.
Active role of lignin in anchoring wood-based stabilizers to the emulsion interface
Authors: Carvalho Danila M. de , Lahtinen Maarit H. , Bhattarai Mamata , Lawoko Martin , Mikkonen Kirsi S.
Published: October 2021

Lignin moieties anchoring and delivering wood-based stabilizers to the interface improve the physical stabilization of emulsions.
Field supported slow magnetic relaxation in a quasi-one-dimensional copper(ii) complex with a pentaheterocyclic triphenodioxazine
Authors: Korchagin D. V. , Ivakhnenko E. P. , Demidov O. P. , Akimov A. V. , Morgunov R. B. , Starikov A. G. , Palii A. V. , Minkin V. I. , Aldoshin S. M.
Published: October 2021

A new copper(ii) complex (I) was obtained by the reaction of a sterically crowded 2,4-di-(tert-butyl)-9-chloro-benzo[5,6][1,4]oxazine[2,3-b]phenoxazine bridging ligand with Cu(ii) hexafluoroacetylacetonate.
Simple-structure small molecular acceptors based on a benzodithiophenedione core: synthesis, optoelectronic and photovoltaic properties
Authors: Zhu Mengbing , Yu Xiankang , Huang Jingwei , Xia Hao , Zhu Jianing , Peng Wenhong , Tan Hua , Zhu Weiguo
Published: October 2021

The fluorine-free simple-structure acceptor presents matched energy levels and higher charge mobilities, thus enhanced photovoltaic properties.
Total syntheses of (+)-adunctins C and D: assignment of their absolute configurations
Authors: Xiao Jian , Zhao Jun , Wang Ya-Wen , Luo Gan , Peng Yu
Published: October 2021

The first asymmetric synthesis of adunctins C and D was achieved, thus enabling the assignment of the absolute configurations of these two natural products.
Preliminary Evaluation of Applicants to Master's Programs in Speech-Language Pathology Using Vignettes and Criteria From a Holistic Review Process
Authors: Girolamo Teresa M. , Politzer-Ahles Stephen , Ghali Samantha , Williams Brittany Theresa
Published: October 2021

Purpose:

Little is known about how others evaluate applicants to master's programs in speech-language pathology along criteria used during holistic review despite more programs adopting holistic review. This knowledge gap limits our understanding of whether holistic admissions may offer a more equitable pathway to entering speech-language pathology. This study investigated how faculty and PhD students evaluated applicants to master's speech-language pathology programs along criteria used during holistic review.

Method:

We administered a survey online through a Qualtrics platform. Respondents (
N
= 66) were faculty and PhD candidates in U.S. speech-language-hearing departments. Survey blocks included demographics, professional background, and vignettes. Vignettes featured profiles of applicants to master's programs in speech-language pathology. Vignettes systematically varied in the indicators of applicant criteria, which were specified at low, moderate, or high levels or not specified. After reading each vignette, respondents rated the applicant and indicated their admissions decision. Analysis included descriptives.

Results:

Relative to an applicant who was at a high level for all indicators except cultural and linguistic diversity, respondents ranked applicants who varied in their indicators of criteria levels lower. Respondents were also less likely to make an explicit “accept” decision (vs. “waitlist” or “reject”) for this latter group of applicants.

Conclusions:

Even when implementing criteria used during holistic review, applicants who vary from a “high-achieving” stereotype may still face barriers to entry. Future work is needed to understand the precise nature of how holistic admissions review may play out in actual practice and help increase diversity in the profession.
Amount of Frequency Compression in Bimodal Cochlear Implant Users Is a Poor Predictor for Audibility and Spatial Hearing
Authors: Sharma Snandan , Nogueira Waldo , van Opstal A. John , Chalupper Josef , Mens Lucas H. M. , van Wanrooij Marc M.
Published: October 2021

Purpose:

Speech understanding in noise and horizontal sound localization is poor in most cochlear implant (CI) users with a hearing aid (bimodal stimulation). This study investigated the effect of static and less-extreme adaptive frequency compression in hearing aids on spatial hearing. By means of frequency compression, we aimed to restore high-frequency audibility, and thus improve sound localization and spatial speech recognition.

Method:

Sound-detection thresholds, sound localization, and spatial speech recognition were measured in eight bimodal CI users, with and without frequency compression. We tested two compression algorithms: a static algorithm, which compressed frequencies beyond the compression knee point (160 or 480 Hz), and an adaptive algorithm, which aimed to compress only consonants leaving vowels unaffected (adaptive knee-point frequencies from 736 to 2946 Hz).

Results:

Compression yielded a strong audibility benefit (high-frequency thresholds improved by 40 and 24 dB for static and adaptive compression, respectively), no meaningful improvement in localization performance (errors remained > 30 deg), and spatial speech recognition across all participants. Localization biases without compression (toward the hearing-aid and implant side for low- and high-frequency sounds, respectively) disappeared or reversed with compression. The audibility benefits provided to each bimodal user partially explained any individual improvements in localization performance; shifts in bias; and, for six out of eight participants, benefits in spatial speech recognition.

Conclusions:

We speculate that limiting factors such as a persistent hearing asymmetry and mismatch in spectral overlap prevent compression in bimodal users from improving sound localization. Therefore, the benefit in spatial release from masking by compression is likely due to a shift of attention to the ear with the better signal-to-noise ratio facilitated by compression, rather than an improved spatial selectivity.

Supplemental Material

https://doi.org/10.23641/asha.16869485
Chemical Analysis by LC-MS of Cannabis sativa Root Samples from Northeast Brazil and Evaluation of Antitussive and Expectorant Activities
Authors: Menezes Pedro Modesto Nascimento , Pereira Emanuella Chiara Valença , Lima Kátia Simoni Bezerra , Silva Bismarques Augusto Oliveira da , Brito Mariana Coelho , Araújo Tarcísio Cícero de Lima , Neto Janaine Almeida , Ribeiro Luciano Augusto de Araujo , Silva Fabrício Souza , Rolim Larissa Araújo
Published: October 2021

Cannabis sativa is a millenary medicinal plant. However, contrary to worldwide paradigm-shifting, countries like Brazil still prohibit C. sativa cultivation and its medicinal use, even though many populations use aerial parts and roots of this plant for healthcare. As such, the objective of this work was to identify substances in the samples of the C. sativa roots, tracing a correlation with antitussive and expectorant effects. Therefore, samples of C. sativa roots were donated by the Polícia Federal Brasileira, and its aqueous extract (AECsR) was prepared with subsequent lyophilization, to maintain the material stability. After that, the material was analyzed by LC-MS to observe its chemical profile. Four samples (AECsR-A, B, C, and D) were tested in animal models of citric acid-induced cough (0.4 M) and phenol red expectoration (500 mg/kg). Using LC-MS it was possible to identify 5 molecules in C. sativa roots:
p-coumaroyltyramine, tetrahydrocannabinol-C4, feruoiltyramine, anhydrocanabisativine, and cannabisativine. In experimental protocols, male mice (Mus musculus) were treated with samples of AECsR at doses of 12.5, 25, or 50 mg/kg regardless of the pharmacological test. In these tests, all samples showed the potential to treat cough and promote fluid expectoration, differing only in the dose at which these effects were observed. Therefore, the data showed that the C. sativa roots of the Brazilian Northeast showed antitussive and expectorant effects, even with intense secondary metabolitesʼ variation, which alters its potency, but not its effect. This highlights the importance of this medicinal plant for future therapy and corroborates to traditional use.
New Perspectives for the Use of Potentilla alba Rhizomes to Treat Thyroid Gland Impairments
Authors: Augustynowicz Daniel , Podolak Magdalena , Latté Klaus Peter , Tomczyk Michał
Published: October 2021

Potentilla alba is a valuable medicinal plant that has been highly praised even before its first appearance in herbal books; however, it has now been forgotten in Western Europe. Currently, this species is used in Eastern Europe as a remedy to treat dysentery and various thyroid gland dysfunctions. The present review summarizes the advances in the phytochemical, pharmacological, and toxicological research related to this plant species. Clinical trials that have been conducted to date support its traditional use for treating thyroid disorders, although its exact mechanism of action, bioavailability, and pharmacokinetics data are missing.
Chemistry of the Heterotriquinanes and Heterotriquinacenes
Authors: Mascal Mark , Hafezi Nema
Published: October 2021

Triquinanes are tricyclic hydrocarbons that have fused cyclopentane rings. Although there are linear and angular triquinanes that are doubly fused, this Account focuses exclusively on the ‘triquinacane’, or triply fused structure with a heteroatom (nitrogen or oxygen) on the C
3v symmetry axis. Azatriquinane- and oxatriquinane-based species tend to show remarkable and often unexpected chemistry, and have variously comprised the most basic trialkyl amine, a superbasic proton chelate, trigonal pyramidal ligand platforms, novel calixiform hosts, aromatic hemispheres of hetero-C20 fullerenes, cocrystallizing agents for eliminating rotational disorder in fullerene crystals, the first water-stable, chromatographable trialkyloxonium species, the first isolable allylic oxonium species, world-record C–O bond lengths, rapid SN2 reaction at a tertiary center, and R4O2+ (oxadionium) species.

1 Introduction

2 Azatriquinane

3 Azatriquinacene

4 Aromatic Azatriquinacene-Based Systems

5 Oxatriquinane

6 Tetravalent Oxygen

7 Oxatriquinacene

8 The Future
Black Aorta from Alkaptonuria
Authors: Laurent James P. , Galvin Sean D.
Published: October 2021

A-76-year old male with a past history of alkaptonuria with ochronosis (homogentisic acid deposition in tissues) had symptomatic aortic stenosis. Surgical replacement of the valve was undertaken, and he was noted to have a severely pigmented and porcelain aorta.