bluuebunny/crossref_metadata_2025 huggingface dataset:
Immunogenic senescence sensitizes lung cancer to LUNX-targeting therapy
Authors: Jiao Defeng , Zheng Xiaohu , Du Xianghui , Wang Dong , Hu Ziming , Sun Rui , Tian Zhigang , Fu Binqing , Wei Haiming
Published: October 2021

The higher immunogenicity of tumors usually predicts favorable therapeutic responses. Tumor antigens dominate the immunogenic character within tumors. We investigated if there was a targetable tumor antigen during immunogenic chemotherapy within lung cancer. Chemotherapy-induced immunogenic senescence was demonstrated using a multi-marker, three-step workflow, and RNA-sequencing data. The ability of anti-lung-specific X protein (LUNX) antibody to suppress the survival of senescent lung cancer cells was evaluated in vitro and in vivo using real-time cytotoxicity analysis and xenograft mouse models, respectively. The induction of cellular senescence by immunogenic chemotherapy boosted cell-surface shuttling of LUNX and enhanced the immunogenic features of senescent tumor cells, which sensitized lung cancer cells to anti-LUNX antibody-mediated therapy and contributed to tumor suppression. The immunogenic senescence-mediated anti-tumor response was triggered by the direct action of antibody on tumor cells, strengthened by natural-killer cells through an antibody-dependent cell-mediated cytotoxicity response, and ultimately, led to tumor control. Our findings suggest that LUNX is a lung cancer targetable-immunogenic antigen. The proportion of lung cancers responding to LUNX-targeting therapy could be expanded substantially by immunogenic chemotherapy that induces senescence-associated translocation of LUNX to the plasma membrane.
Factors affecting adherence to disease-modifying therapies in multiple sclerosis: systematic review
Authors: Washington Francesca , Langdon Dawn
Published: October 2021

People with multiple sclerosis (MS) face challenges adhering to disease-modifying drug (DMD) treatment. Poor adherence to treatment reduces its clinical effectiveness which can adversely impact disease progression, MS-related hospitalisation, and mortality rates. Understanding the barriers to adherence is essential to addressing these issues in clinical practice and a consolidation of the literature had not yet been carried out. A systematic search was carried out using the electronic databases PsycINFO, and PubMed (Medline) using the search terms treatment compliance or treatment adherence and multiple sclerosis or MS. Studies included adults, with a diagnosis of relapsing–remitting MS (RRMS) (sample > 80% RRMS), taking a DMD. The studies used an adequate measurement of treatment adherence and analysed possible factors associated with adherence. A total of 349 studies were retrieved, of which 24 were considered eligible for inclusion. Overall adherence rates of the included studies ranged from 52 to 92.8%. Narrative synthesis revealed the most prevalent factors associated with adherence were age, gender, depression, cognition, treatment satisfaction, injection-site reactions, and injection anxiety. There was contradictory evidence for disability in association with treatment adherence. The findings should be used to inform the development of targeted patient support programs which improve treatment compliance. The review also highlights the opportunities for advancing research into treatment adherence in MS.
Involvement of cortico-efferent tracts in flail arm syndrome: a tract-of-interest-based DTI study
Authors: Rosenbohm Angela , Del Tredici Kelly , Braak Heiko , Huppertz Hans-Jürgen , Ludolph Albert C. , Müller Hans-Peter , Kassubek Jan
Published: October 2021

Background

Flail arm syndrome is a restricted phenotype of motor neuron disease that is characterized by progressive, predominantly proximal weakness and atrophy of the upper limbs.

Objective

The study was designed to investigate specific white matter alterations in diffusion tensor imaging (DTI) data from flail arm syndrome patients using a hypothesis-guided tract-of-interest-based approach to identify in vivo microstructural changes according to a neuropathologically defined amyotrophic lateral sclerosis (ALS)-related pathology of the cortico-efferent tracts.

Methods

DTI-based white matter mapping was performed both by an unbiased voxel-wise statistical comparison and by a hypothesis-guided tract-wise analysis of fractional anisotropy (FA) maps according to the neuropathological ALS-propagation pattern for 43 flail arm syndrome patients vs 43 ‘classical’ ALS patients vs 40 matched controls.

Results

The analysis of white matter integrity demonstrated regional FA reductions for the flail arm syndrome group predominantly along the CST. In the tract-specific analysis according to the proposed sequential cerebral pathology pattern of ALS, the flail arm syndrome patients showed significant alterations of the specific tract systems that were identical to ‘classical’ ALS if compared to controls.

Conclusions

The DTI study including the tract-of-interest-based analysis showed a microstructural involvement pattern in the brains of flail arm syndrome patients, supporting the hypothesis that flail arm syndrome is a phenotypical variant of ALS.
Correlation between the optic nerve pial diameter and radial peripapillary vascular changes in primary open-angle glaucoma
Authors: Montorio Daniela , Cennamo Gilda , Breve Maria Angelica , Menna Feliciana , Reibaldi Michele , Cennamo Giovanni , Morra Vincenzo Brescia
Published: October 2021

Purpose

To assess the optic nerve pial diameter (ONPD) in patients with primary open-angle glaucoma (POAG) using standardized A-scan ultrasound and to evaluate the correlation between the ONPD and structural, vascular optic nerve head features and visual field parameters in glaucomatous eyes.

Methods

In this prospective study, we enrolled 126 eyes of 63 POAG patients and 124 eyes of 62 healthy controls. In all subjects, the ONPD was evaluated by means of A-scan ultrasound. Spectral domain (SD)-OCT was used to assess ganglion cell complex (GCC), retinal nerve fiber layer (RNFL), thicknesses, and the optic nerve head (ONH) morphology. OCTA measured the vessel density (VD) of radial peripapillary capillary (RPC) plexus.

Results

The ONPD showed a statistically significant reduction in POAG group with respect to controls (p < 0.001). SD-OCT and OCTA parameters showed a significant impairment in patient group with respect to controls (p < 0.001). The ONH analysis revealed significantly lower values in rim area (p = 0.009) and an increased cup-to-disc area ratio (p = 0.013) and cup volume (p < 0.001) in patients with respect to controls. Significant correlations were shown in POAG group between ONPD and RPC plexus (p = 0.006). Moreover, significant correlation was also found between ONPD and structural SD-OCT parameters (p = 0.001) and between ONPD and visual field parameters (p = 0.001).

Conclusions

The standardized A-scan ultrasound measurements of the ONPD showed a significant correlation with structural and vascular glaucomatous changes measured by means of SD-OCT and OCTA. These results confirm the diagnostic reliability of the ultrasound evaluation in glaucoma optic neuropathy.
Combination of treosulfan, fludarabine and cytarabine as conditioning in patients with acute myeloid leukemia, myelodysplastic syndrome and myeloproliferative neoplasms
Authors: O‘Hagan Henderson Samantha , Frietsch Jochen J. , Hilgendorf Inken , Hochhaus Andreas , Köhne Claus-Henning , Casper Jochen
Published: October 2021

Purpose

Treosulfan and fludarabine (Treo/Flu) were successfully introduced into toxicity-reduced conditioning for SCT. However, the risk of post-SCT relapse remains a matter of concern. We report the results of a novel individual treatment approach with Treo/Flu and cytarabine (Treo/Flu/AraC) conditioning prior to allogeneic SCT in patients with acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), or myeloproliferative neoplasms (MPN).

Methods

Seventy-seven patients (median age 54 years) at high risk of disease relapse due to unfavorable cytogenetics or failure to achieve complete remission prior to SCT were included. Median follow-up was 3.2 years.

Results

The 1-, 2- and 3-year RFS rates were 49.4%, 41.7%, and 37.6% and OS rates were 59.3%, 49.3%, and 45.4%, respectively. Cumulative incidence of NRM was 10% at 100 days, 18.8% at 1 year and 20.1% at 2 years. The cumulative incidence of relapse increased from 31% at 1 year to 38.5% after 3 years. The cumulative incidences of engraftment, chimerism, graft-versus-host disease (GvHD) and toxicities were acceptable and comparable with similar patients conditioned with Treo/Flu or FLAMSA-RIC.

Conclusion

In conclusion, Treo/Flu/AraC provides tolerable, feasible, and effective conditioning for patients with AML, MDS or MPN, even in advanced disease states. The incidence of NRM and relapse is acceptable in this heavily pre-treated population with high-risk disease. Future research will aim to confirm these initial findings and include a larger number of participants in a prospective trial.
Representing Polar Questions
Authors: Tian Ye , van Tiel Bob , Clin Élise , Breheny Richard
Published: October 2021

Although the linguistic properties of polar questions have been extensively studied, comparatively little is known about how polar questions are processed in real time. In this paper, we report on three eye-tracking experiments on the processing of positive and negative polar questions in English and French. Our results show that in the early stages, participants pay attention to both positive and negative states of affairs for both positive and negative questions. In the late stages, positive and certain negative polar questions were associated with a bias for the positive state, and this bias appears to be pragmatic in nature. We suggest that different biases in mental representations reflect the hearer’s reasoning about the speaker’s purposes of enquiry.
Simultaneous monitoring of the values of CD, Crosstalk and OSNR phenomena in the physical layer of the optical network using CNN
Authors: Mrozek Tomasz , Perlicki Krzysztof
Published: October 2021

The aim of the research was to explore the possibilities of using the Asynchronous Delay Tap Sampling (ADTS) and Convolutional Neural Network (CNN) methods to monitor the simultaneously occurring phenomena in the physical layer of the optical network. The ADTS method was used to create a data sets showing the combination of Chromatic Dispersion (CD), Crosstalk and Optical to Signal Noise Ratio (OSNR) as optical disturbances in graphic form. Data were generated for 10 GB/s, Non-return-to-zero On–off keying (NRZ-OOK) and Differential Phase Shift Keying (DPSK) modulation and bit delays: 1 bit, 0.5 bit and 0.25 bit. A total of 6 data sets of 62,000 images each were obtained. The learning process was carried out for the number of epochs 50 and 1000. From the obtained learning results of the network, models with the best $$R^{2}$$

R
2

matching factor were selected. The learned models were further used to study the recognition of three phenomena simultaneously. The tests were carried out on sets of 2500 images in a combination of interference in the following ranges: 400–1600 ps/nm for CD and 10–30 dB for Crosstalk and OSNR. Very good results were obtained for recognizing simultaneously occurring phenomena using models learned up to 1000 epoch. Accuracy of over 99% was obtained for CD and Crosstalk for both modulations. In the case of the OSNR phenomenon, slightly weaker results were obtained above 96% in most cases. For models taught up to 50 epoch, very good results were obtained for the CD phenomenon (over 99%). For Crosstalk weaker results for OOK modulation were obtained. Poor results were obtained for the OSNR phenomenon, where recognition accuracy ranged from 50 to 80%, depending on the type of modulation and bit delay. Based on the conducted research, it was established that the use of ADTS and CNN methods enables monitoring of simultaneously occurring CD, Crosstalk and OSNR interference in the physical layer of the optical network, while maintaining the requirements for Optical Performance Monitoring systems. These requirements are met for network models learned up to 1000 epoch.
Competency of groundwater recharge of irrigated cotton field subjacent to sowing methods, plastic mulch, water productivity, and yield under climate change
Authors: Saeed Muhammad , Maqbool Ahsan , Ashraf Muhammad Adnan , Arshad Muhammad , Mehmood Kashif , Usman Muhammad , Farid Muhammad Arslan
Published: October 2021

Irrigated agriculture is a foremost consumer of water resources to fulfill the demand for food and fiber with an increasing population under climate changes; cotton is no exception. Depleting groundwater recharge and water productivity is critical for the sustainable cotton crop yield peculiarly in the semiarid region. This study investigated the water productivity and cotton yield under six different treatments: three sowing methods, i.e., flat, ridge, and bed planting with and without plastic mulch. Cotton bed planting without mulch showed maximum water productivity (0.24 kg.m−3) and the highest cotton yield (1946 kg.ha−1). Plastic mulching may reduce water productivity and cotton yield. HYDRUS-1D unsaturated flow model was used to access the groundwater recharge for 150 days under six treatments after model performance evaluation. Maximum cumulative recharge was observed 71 cm for the flat sowing method without plastic mulch. CanESM2 was used to predict climate scenarios for RCP 2.6, 4.5, and 8.5 for the 2050s and 2080s by statistical downscale modeling (SDSM) using historical data from 1975 to 2005 to access future groundwater recharge flux. Average cumulative recharge flux declined 36.53% in 2050 and 22.91% in 2080 compared to 2017 without plastic mulch. Multivariate regression analysis revealed that a maximum 23.78% reduction in groundwater recharge could influence future climate change. Further study may require to understand the remaining influencing factor of depleting groundwater recharge. Findings highlight the significance of climate change and the cotton sowing method while accessing future groundwater resources in irrigated agriculture.
The gold complex auranofin: new perspectives for cancer therapy
Authors: Abdalbari Farah H. , Telleria Carlos M.
Published: October 2021

Advanced stages of cancer are highly associated with short overall survival in patients due to the lack of long-term treatment options following the standard form of care. New options for cancer therapy are needed to improve the survival of cancer patients without disease recurrence. Auranofin is a clinically approved agent against rheumatoid arthritis that is currently enrolled in clinical trials for potential repurposing against cancer. Auranofin mainly targets the anti-oxidative system catalyzed by thioredoxin reductase (TrxR), which protects the cell from oxidative stress and death in the cytoplasm and the mitochondria. TrxR is over-expressed in many cancers as an adaptive mechanism for cancer cell proliferation, rendering it an attractive target for cancer therapy, and auranofin as a potential therapeutic agent for cancer. Inhibiting TrxR dysregulates the intracellular redox state causing increased intracellular reactive oxygen species levels, and stimulates cellular demise. An alternate mechanism of action of auranofin is to mimic proteasomal inhibition by blocking the ubiquitin–proteasome system (UPS), which is critically important in cancer cells to prevent cell death when compared to non-cancer cells, because of its role on cell cycle regulation, protein degradation, gene expression, and DNA repair. This article provides new perspectives on the potential mechanisms used by auranofin alone, in combination with diverse other compounds, or in combination with platinating agents and/or immune checkpoint inhibitors to combat cancer cells, while assessing the feasibility for its repurposing in the clinical setting.
Preliminary evaluation of a natural surfactant extracted from Myrtus communis plant for enhancing oil recovery from carbonate oil reservoirs
Authors: Nowrouzi Iman , Mohammadi Amir H. , Manshad Abbas Khaksar
Published: October 2021

Surfactants are among the materials used to improve water properties for injection into oil reservoirs, and reduce injection phase and crude oil interfacial tension (IFT). Recently, the interest in the use of natural surfactants has increased and is constantly on the rise to solve some challenges of using chemical surfactants such as incompatibility with the environment and the high cost. In this study, we have used aqueous extract ofpowdered leaf of Myrtus communisas an available source of natural surfactant. The extracted surfactant was characterized by TGA,1H NMR and FTIR techniques. The surfactant efficiency was demonstrated by performing some experiments including IFT and injection of chemical slug and surfactant into carbonate plugs. The surfactant adsorption on carbonate rock was also studied. It was observed that this natural surfactant can reduce IFT to 0.861 mN/m at surfactant critical micelle concentration (CMC) of 5000 ppm. This minimum IFT was further reduced at optimum salinity and alkali. Finally, an increase of 14.3% oil recovery by surfactant flooding and 16.4% oil recovery by ASP slug injection containing NaOH alkali and partially hydrolyzed polyacrylamide (PHPA) polymer with 0.5 PV volume from carbonate plugs was achieved.
Refining the in vitro release test method for a dapivirine-releasing vaginal ring to match in vivo performance
Authors: Murphy Diarmaid J. , Lim Deanna , Armstrong Ryan , McCoy Clare F. , Bashi Yahya H. Dallal , Boyd Peter , Derrick Tiffany , Spence Patrick , Devlin Bríd , Malcolm R. Karl
Published: October 2021

Previously reported in vitro release test methods for drug-releasing vaginal rings containing poorly water-soluble drugs have described use of water-alcohol systems or surfactant solutions in efforts to maintain sink conditions. Here, as part of efforts to more closely match in vitro and in vivo release for the 25 mg dapivirine matrix-type silicone elastomer vaginal ring for HIV prevention, we have investigated alternatives to the 1:1 v/v water/isopropanol medium described previously. Specifically, we evaluated dapivirine release from rings into (i) monophasic water/isopropanol mixtures of varying compositions and (ii) biphasic buffer/octanol systems using pH 4.2 and pH 7.0 buffers. The rate and mechanism of dapivirine release were dependent upon the isopropanol concentration in the release medium, in accordance with the observed trend in drug solubility. At 0 and 10% v/v isopropanol concentrations, dapivirine release followed a partition-controlled mechansim. For media containing ≥ 20% v/v isopropanol, in vitro release of dapivirine was significantly increased and obeyed permeation-controlled kinetics. Cumulative release of ~3.5 mg dapivirine over 28 days was obtained using a water isopropanol mixture containing 20% v/v isopropanol, similar to the ~4 mg dapivirine released in vivo. Dapivirine release into the biphasic buffer/octanol system (intended to mimic the fluid/tissue environment in vivo) was constrained by the limited solubility of dapivirine in the buffer component in which the ring resided, such that cumulative dapivirine release was consistently lower than that observed with the 20% v/v isopropanol in water medium. Release into the biphasic system was also pH dependent, in line with dapivirine’s pKaand with potential implications for in vivo release and absorption in women with elevated vaginal pH.

Graphical abstract
Light-off Investigation of Oxymethylene Ether (OME) Considering the Presence of the Exhaust Components Heptane, Carbon, and Nitrogen Monoxide
Authors: Rümmele Florian , Susdorf Alexander , Haider Syed Muhammad Salman , Szolak Robert
Published: October 2021

Synthetic fuels and fuel blends like OMEs can contribute to tank-to-wheel CO2 emission savings. At the same time, it is known that these fuels have a lower exhaust temperature compared to conventional diesel. This effect has major impact on the exhaust after-treatment system, particularly in cold start conditions. This paper investigates the light-off behavior of exhaust gases containing OMEs by temperature-programmed oxidation experiments using a state-of-the-art oxidation catalyst. The main side product of catalytic oxidation of OMEs between 100 °C and the oxidation temperature T50, which was around 160 °C, was shown to be formaldehyde. While alkane oxidation, in this case heptane, was little influenced by OME oxidation, the oxidation temperature T50 of CO increases by more than 10 °C by OME addition. Nitrogen monoxide impeded the oxidation of OME in a similar way to the other components investigated. Due to the amount of FA produced and its toxicity, it could be concluded that it is necessary to heat up exhaust after-treatment systems of OME diesel engines even faster than conventional diesel exhaust after-treatment systems. The relatively high reactivity of OME on oxidation catalyst can be used by active thermal management approaches.
Leaching of Cu, Zn, and Pb from Sulfidic Tailings Under the Use of Sulfuric Acid and Chloride Solutions
Authors: Schueler Tamara A. , de Aguiar Paula F. , Vera Ysrael M. , Goldmann Daniel
Published: October 2021

The imbalance between raw materials of high economic importance and their supply has increased the search for new approaches to obtain valuable elements from mining tailings. In this study, the extraction of copper, zinc, and lead from sulfidic tailing in sulfate–chloride media was investigated. A 33 Box–Behnken design was applied to evaluate three variables over a 4-h testing period: sulfuric acid concentration (0.01–1.0 mol/L H2SO4), sodium chloride (10–60 g/L NaCl), and temperature (20–70 °C). The design showed two optimum working regions: a combination of a high NaCl level, low H2SO4 level, and medium temperature level for lead leaching, while for copper and zinc, a combination of a medium–high H2SO4 level and a high temperature level. The concentration of NaCl had only a slight impact on their leaching. Based on these results, two-stage leaching was performed. The first stage was carried out under an experimental condition that favored the leaching of lead (60 g/L NaCl, 0.01 mol/L H2SO4, 45 °C, 1 h, 10:1 liquid-to-solid ratio), whereas the second stage maximized the leaching of copper and zinc (60 g/L NaCl, 0.5 mol/L H2SO4, 70 °C, 24 h, 10:1 liquid-to-solid ratio). The global leaching rate was 66.8 ± 3.0% copper, 84.1 ± 5.2% zinc, and 93.9 ± 3.2% lead. The iron and arsenic content were also leached by about 20 and 50% at the end of the second stage. The study demonstrated that the use of sulfate–chloride media in a two-stage leaching considerably improved the extraction of the desired metals and was, therefore, suitable for their recovery.

Graphical Abstract
Implementation and evaluation of the DAOM framework and support tool for designing blockchain decentralized applications
Authors: Udokwu Chibuzor , Brandtner Patrick , Norta Alex , Kormiltsyn Alexandr , Matulevičius Raimundas
Published: October 2021

Inter-organizational collaboration is an important aspect of organizational operations. Traditional systems that support organizations in executing these collaborations are inefficient, not inter-operable and insecure. Novel functions provided by blockchain technology yields the potential for addressing problems that affect organizational collaborations by enabling tamper-proof, transparent, and secure systems for the exchange of information between organizations. Still, a proper approach for building blockchain-decentralized applications (DApps) that support inter-organizational collaborations is missing. The DAOM framework addresses this gap by providing a model-driven design approach for building DApps. This paper shows the development of the semantics of the DAOM framework, implementation of the support tool, and the evaluation of the DAOM framework and support tool. We conducted an evaluation to understand the usefulness of the DAOM framework in developing blockchain DApps and the effectiveness of the support tool in producing DAOM diagram models. The evaluation result shows that the framework is useful and applicable for developing DApps for inter-organizational collaborations. Furthermore, evaluation of the tool support shows that DApps can be modelled efficiently and correctly with the implemented enterprise-modelling software.
COVID-19 and mental health in children and adolescents: a diagnostic panel to map psycho-social consequences in the pandemic context
Authors: Baumann Menno
Published: October 2021

Since the beginning of the COVID-19 pandemic, much research has been done on the psycho-social consequences, especially for children, adolescents and families. In the long run, there is a large set of quantitative data available. However, these still seem to be not well understood. Theoretical classifications of the evidence also diagnostic tools still seem to be open. This paper elaborates a possible systematisation based on theoretical models of systemic self-organisation theories. This leads to a model for a comprehensive psycho-social child-in-environment diagnostic to map potential problem areas. Such a theoretical framing should enable both: a deeper understanding of the impact of pandemics on young people and hypotheses for intervention strategies in the context of pandemic management as well as in the context of diagnostic-systemic interventions in psycho-social working settings. In the coming months and years, it will be essential to be able to understand and describe psychosocial disabilities that have developed in the context of the pandemic in a differentiated way in order to establish targeted interventions.
Do coherent structures organize scalar mixing in a turbulent boundary layer?
Authors: Eisma Jerke , Westerweel Jerry , van de Water Willem
Published: October 2021

A scalar emanating from a point source in a turbulent boundary layer does not mix homogeneously, but is organized in large regions with little variation of the concentration: uniform concentration zones. We measure scalar concentration using laser-induced fluorescence and, simultaneously, the three-dimensional velocity field using tomographic particle image velocimetry in a water tunnel boundary layer. We identify uniform concentration zones using both a simple histogram technique, and more advanced cluster analysis. From the complete information on the turbulent velocity field, we compute two candidate velocity structures that may form the boundaries between two uniform concentration zones. One of these structures is related to the rate of point separation along Lagrangian trajectories and the other one involves the magnitude of strong shear in snapshots of the velocity field. Therefore, the first method allows for the history of the flow field to be monitored, while the second method only looks at a snapshot. The separation of fluid parcels in time was measured in two ways: the exponential growth of the separation as time progresses (related to finite-time Lyapunov exponents and unstable manifolds in the theory of dynamical systems), and the exponential growth as time moves backward (stable manifolds). Of these two, a correlation with the edges of uniform concentration zones was found for the past Lyapunov field but not with the time-forward future field. The magnitude of the correlation is comparable to that of the regions of strong shear in the instantaneous velocity field.
Ontogeny in the steinmanellines (Bivalvia: Trigoniida): an intra- and interspecific appraisal using the Early Cretaceous faunas from the Neuquén Basin as a case study
Authors: Milla Carmona Pablo S. , Lazo Dario G. , Soto Ignacio M.
Published: October 2021

Despite the paleontological relevance and paleobiological interest of trigoniid bivalves, our knowledge of their ontogeny—an aspect of crucial evolutionary importance—remains limited. Here, we assess the intra- and interspecific ontogenetic variations exhibited by the genus Steinmanella Crickmay (Myophorellidae: Steinmanellinae) during the early Valanginian–late Hauterivian of Argentina and explore some of their implications. The (ontogenetic) allometric trajectories of seven species recognized for this interval were estimated from longitudinal data using 3D geometric morphometrics, segmented regressions, and model selection tools, and then compared using trajectory analysis and allometric spaces. Our results show that within-species shell shape variation describes biphasic ontogenetic trajectories, decoupled from ontogenetic changes shown by sculpture, with a gradual decay in magnitude as ontogeny progresses. The modes of change characterizing each phase (crescentic growth and anteroposterior elongation, respectively) are conserved across species, thus representing a feature of Steinmanella ontogeny; its evolutionary origin is inferred to be a consequence of the rate modification and allometric repatterning of the ancestral ontogeny. Among species, trajectories are more variable during early ontogenetic stages, becoming increasingly conservative at later stages. Trajectories’ general orientation allows recognition of two stratigraphically consecutive groups of species, hinting at a potentially higher genus-level diversity in the studied interval. In terms of functional morphology, juveniles had a morphology more suited for active burrowing than adults, whose features are associated with a sedentary lifestyle. The characteristic disparity of trigoniids could be related to the existence of an ontogenetic period of greater shell malleability betrayed by the presence of crescentic shape change.
Experiences of influencing one's own life when living with working-age dementia
Authors: Issakainen Mervi , Mäki-Petäjä-Leinonen Anna , Heimonen Sirkkaliisa , Nedlund Ann-Charlotte , Astell Arlene , Boger Jennifer , Rissanen Sari , Nygård Louise
Published: October 2021

Having opportunities to make decisions and choices regarding one's life is crucial when living with dementia. This inter-disciplinary study draws on the concept of relational autonomy to explore how working-age people living dementia seek to influence their lives, and what makes it easier or more difficult for them in their everyday life. The data consist of three focus group discussions conducted with 12 retired adults who developed dementia while still employed. The results illuminate various resources that enable a person to (a) handle their difficulties at work and related consequences with dignity, (b) manage everyday tasks and live a fulfilling life, and (c) fight the stigma associated with (working-age) dementia. Challenges related to these aspects reported by the participants reveal gaps and obstacles that impede the full realisation of the rights of people living with early onset dementia. This research highlights the need for workplace education for different stakeholders, equal and ongoing access to guidance and counselling for younger people who live with dementia, and an effort by society as a whole to eradicate stigma.
Amygdala responses to threat in violence-exposed children depend on trauma context and maternal caregiving
Authors: Stevens Jennifer S. , van Rooij Sanne J.H. , Stenson Anais F. , Ely Timothy D. , Powers Abigail , Clifford Aimee , Kim Ye Ji , Hinrichs Rebecca , Tottenham Nim , Jovanovic Tanja
Published: October 2021

Early life adversity (ELA) has been linked with increased arousal responses to threat, including increased amygdala reactivity. Effects of ELA on brain function are well recognized, and emerging evidence suggests that caregivers may influence how environmental stressors impact children’s brain function. We investigated the hypothesis that positive interaction between mother and child can buffer against ELA effects on children’s neural responses to threat, and related symptoms. N = 53 mother–child pairs (children ages 8–14 years) were recruited from an urban population at high risk for violence exposure. Maternal caregiving was measured using the Parenting Questionnaire and in a cooperation challenge task. Children viewed fearful and neutral face stimuli during functional magnetic resonance imaging. Children who experienced greater violence at home showed amygdala sensitization, whereas children experiencing more school and community violence showed amygdala habituation. Sensitization was in turn linked with externalizing symptoms. However, maternal warmth was associated with a normalization of amygdala sensitization in children, and fewer externalizing behaviors prospectively up to 1 year later. Findings suggested that the effects of violence exposure on threat-related neural circuitry depend on trauma context (inside or outside the home) and that primary caregivers can increase resilience.
Extensional equality preservation and verified generic programming
Authors: BOTTA NICOLA , BREDE NURIA , JANSSON PATRIK , RICHTER TIM
Published: October 2021

In verified generic programming, one cannot exploit the structure of concrete data types but has to rely onwell chosensets of specifications or abstract data types (ADTs). Functors and monads are at the core of many applications of functional programming. This raises the question of what useful ADTs for verified functors and monads could look like. The functorial map of many important monads preserves extensional equality. For instance, if$$f,g \, : \, A \, \to \, B$$are extensionally equal, that is,$$\forall x \in A$$,$$f \, x = g \, x$$, then$$map \, f \, : \, List \, A \to List \, B$$and$$map \, g$$are also extensionally equal. This suggests thatpreservation of extensional equalitycould be a useful principle in verified generic programming. We explore this possibility with a minimalist approach: we deal with (the lack of) extensional equality in Martin-Löf’s intensional type theories without extending the theories or using full-fledged setoids. Perhaps surprisingly, this minimal approach turns out to be extremely useful. It allows one to derive simple generic proofs of monadic laws but also verified, generic results in dynamical systems and control theory. In turn, these results avoid tedious code duplication and ad-hoc proofs. Thus, our work is a contribution toward pragmatic, verified generic programming.
The Micro‐Broadband Receiver (μBBR) on the Very‐Low‐Frequency Propagation Mapper CubeSat
Authors: Marshall Robert A. , Sousa Austin , Reid Riley , Wilson Gordon , Starks Michael , Ramos Daniel , Ballenthin John , Quigley Steven , Kay Ron , Patton James , Coombs Joseph , Fennelly Judy , Linscott Ivan , Inan Umran S.
Published: October 2021

The very low frequency (VLF) propagation mapper (VPM) is a 6U CubeSat designed to measure VLF radio waves in Low‐Earth Orbit. The science goals of the VPM mission are to measure VLF signals broadcast by the DSX mission, and to study natural and anthropogenic signals (from lightning and VLF transmitters) in the near‐Earth space environment. The primary payload consists of an electric field dipole antenna deployed to 2 meters in length, and a magnetic search coil deployed 50 cm from the spacecraft. Signals from these two sensors are conditioned by analog electronics, sampled, and then processed digitally into downloadable data products. The VPM mission was launched in January 2020; science operations began in March 2020 and continued through September, when contact with the spacecraft was lost. This paper describes the mission goals and instrument designs in detail, as well as some examples of the VPM data set.
Geochemical and Isotopic Evolution of Late Oligocene Magmatism in Quchan, NE Iran
Authors: Moghadam H. S. , Li Q. L. , Kirchenbaur M. , Garbe‐Schönberg D. , Lucci F. , Griffin W. L. , Ghorbani G.
Published: October 2021

Magmatic activity that accompanied the collision between Arabia and Eurasia at ∼27 Ma, provides unique opportunities for understanding the triggers and magma reservoirs for collisional magmatism and its different styles in magmatic fronts and back‐arcs. We present new ages and geochemical‐isotopic results for magmatic rocks that formed during the collision between Arabia and Eurasia in NE Iran, which was a back‐arc region to the main magmatic arcs of Iran. Our new zircon U‐Pb ages indicate that collisional magmatism began at ∼24 Ma in the NE Iran back‐arc, although magmatism in this area started in the Late Cretaceous time and continued until the Pleistocene. The collisional igneous rocks are characteristically bimodal, and basaltic‐andesitic and dacitic‐rhyolitic components show significant isotopic differences; εNd(t) = +4.4 to +7.4 and εHf(t) = +5.4 to +9.5 for mafic rocks and εNd(t) = +0.2 to +8.4 and εHf(t) = +3.4 to +12.3 for silicic rocks. The isotopic values and modeling suggest that fractional crystallization and assimilation‐fractional crystallization played important roles in the genesis of felsic rocks in the NE Iran collisional zone. Trace element and isotopic modeling further emphasize that the main triggers of the magmatism in NE Iran comprise a depleted to the enriched mantle and the Cadomian continental crust of Iran. Our results also emphasize the temporal magmatic variations in the NE Iran back‐arc from Late Cretaceous to Pleistocene.
Role of Ducting in Relativistic Electron Loss by Whistler‐Mode Wave Scattering
Authors: Artemyev A. V. , Demekhov A. G. , Zhang X.‐J. , Angelopoulos V. , Mourenas D. , Fedorenko Yu V. , Maninnen J. , Tsai E. , Wilkins C. , Kasahara S. , Miyoshi Y. , Matsuoka A. , Kasahara Y. , Mitani T. , Yokota S. , Keika K. , Hori T. , Matsuda S. , Nakamura S. , Kitahara M. , Takashima T. , Shinohara I.
Published: October 2021

Resonant interactions of energetic electrons with electromagnetic whistler‐mode waves (whistlers) contribute significantly to the dynamics of electron fluxes in Earth's outer radiation belt. At low geomagnetic latitudes, these waves are very effective in pitch angle scattering and precipitation into the ionosphere of low equatorial pitch angle, tens of keV electrons and acceleration of high equatorial pitch angle electrons to relativistic energies. Relativistic (hundreds of keV), electrons may also be precipitated by resonant interaction with whistlers, but this requires waves propagating quasi‐parallel without significant intensity decrease to high latitudes where they can resonate with higher energy low equatorial pitch angle electrons than at the equator. Wave propagation away from the equatorial source region in a non‐uniform magnetic field leads to ray divergence from the originally field‐aligned direction and efficient wave damping by Landau resonance with suprathermal electrons, reducing the wave ability to scatter electrons at high latitudes. However, wave propagation can become ducted along field‐aligned density peaks (ducts), preventing ray divergence and wave damping. Such ducting may therefore result in significant relativistic electron precipitation. We present evidence that ducted whistlers efficiently precipitate relativistic electrons. We employ simultaneous near‐equatorial and ground‐based measurements of whistlers and low‐altitude electron precipitation measurements by ELFIN CubeSat. We show that ducted waves (appearing on the ground) efficiently scatter relativistic electrons into the loss cone, contrary to non‐ducted waves (absent on the ground) precipitating only keV electrons. Our results indicate that ducted whistlers may be quite significant for relativistic electron losses; they should be further studied statistically and possibly incorporated in radiation belt models.
A Recirculating Eddy Promotes Subsurface Particle Retention in an Antarctic Biological Hotspot
Authors: Hudson K. , Oliver M. J. , Kohut J. , Dinniman M. S. , Klinck J. M. , Moffat C. , Statscewich H. , Bernard K. S. , Fraser W.
Published: October 2021

Palmer Deep Canyon is one of the biological hotspots associated with deep bathymetric features along the West Antarctic Peninsula. The upwelling of nutrient‐rich Upper Circumpolar Deep Water to the surface mixed layer in the submarine canyon has been hypothesized to drive increased phytoplankton biomass, attracting krill, penguins and other top predators to the area. However, observations in Palmer Deep Canyon lack a clear in‐situ upwelling signal, laboratory experiments do not illustrate a physiological response by phytoplankton to Upper Circumpolar Deep Water, and surface residence times are too short for phytoplankton populations to reasonably respond to any locally upwelled nutrients. This suggests that local upwelling may not be the mechanism that links Palmer Deep Canyon to increased biological activity. Previous observations of isopycnal doming within the canyon suggested that a subsurface recirculating feature may be present. Here, using in‐situ measurements and a circulation model, we demonstrate that the presence of a recirculating eddy may contribute to the maintenance of the biological hotspot by increasing residence times at depth and retaining a distinct layer of biological particles. Neutrally buoyant particle simulations showed that residence times increase to ∼175 days at 150 m within the canyon during the austral summer. In‐situ particle scattering, flow cytometry, and water samples from within the subsurface eddy suggest that retained particles are detrital in nature. Our results suggest that this seasonal, retentive feature in Palmer Deep Canyon is important to the retention of biological material and may contribute to the maintenance of this hotspot.
Reactivation of Non‐Optimally Orientated Faults Due to Glacially Induced Stresses
Authors: Steffen Rebekka , Steffen Holger
Published: October 2021

The deformation due to an ice load is accompanied by displacement and stress changes. These stress changes are known to have created large‐magnitude earthquakes along pre‐existing faults during and after deglaciation of the Late Quaternary ice sheets. However, these so‐called glacially induced faults have been found to be not optimally orientated in their respective regional stress regime. Here, we analyzed the potential of non‐optimally orientated fault reactivation within a glacially induced stress field as well as changes of the stress regimes due to these additional stresses. A finite element model is used to estimate glacially induced stresses, which are then combined with background stress magnitudes. Non‐optimally orientated faults can be reactivated by glacially induced stresses within thrust‐, strike‐slip‐, and normal‐faulting stress regimes, but depending on their location with respect to the ice sheet and their orientation within the regional stress field. While faults with large variations of dip and strike outside of the ice sheet are prone to reactivation when the background stress field is a normal‐ or strike‐slip‐faulting stress regime, faults within a thrust‐faulting stress regime can also be reactivated within the ice margin during and after the deglaciation. Outside the ice margin, instabilities in a thrust‐faulting stress regime develop along the intermediate principal stress axis. Stress regime changes can occur for all background stress states. Finally, we find that certain conditions in a strike‐slip‐faulting stress regime can also explain the observed glacially induced thrust faults in Northern Europe.
Everolimus and plicamycin specifically target chemoresistant colorectal cancer cells of the CMS4 subtype
Authors: Deng Jiayin , Tian Ai-Ling , Pan Hui , Sauvat Allan , Leduc Marion , Liu Peng , Zhao Liwei , Zhang Shuai , Chen Hui , Taly Valérie , Laurent-Puig Pierre , Senovilla Laura , Li Yingqiu , Kroemer Guido , Kepp Oliver
Published: October 2021

Colorectal cancers (CRC) can be classified into four consensus molecular subtypes (CMS), among which CMS1 has the best prognosis, contrasting with CMS4 that has the worst outcome. CMS4 CRC is notoriously resistant against therapeutic interventions, as demonstrated by preclinical studies and retrospective clinical observations. Here, we report the finding that two clinically employed agents, everolimus (EVE) and plicamycin (PLI), efficiently target the prototypic CMS4 cell line MDST8. As compared to the prototypic CMS1 cell line LoVo, MDST8 cells treated with EVE or PLI demonstrated stronger cytostatic and cytotoxic effects, increased signs of apoptosis and autophagy, as well as a more pronounced inhibition of DNA-to-RNA transcription and RNA-to-protein translation. Moreover, nontoxic doses of EVE and PLI induced the shrinkage of MDST8 tumors in mice, yet had only minor tumor growth-reducing effects on LoVo tumors. Altogether, these results suggest that EVE and PLI should be evaluated for their clinical activity against CMS4 CRC.
Mechanisms and regulation of organic acid accumulation in plant vacuoles
Authors: Huang Xiao-Yu , Wang Chu-Kun , Zhao Yu-Wen , Sun Cui-Hui , Hu Da-Gang
Published: October 2021

In fleshy fruits, organic acids are the main source of fruit acidity and play an important role in regulating osmotic pressure, pH homeostasis, stress resistance, and fruit quality. The transport of organic acids from the cytosol to the vacuole and their storage are complex processes. A large number of transporters carry organic acids from the cytosol to the vacuole with the assistance of various proton pumps and enzymes. However, much remains to be explored regarding the vacuolar transport mechanism of organic acids as well as the substances involved and their association. In this review, recent advances in the vacuolar transport mechanism of organic acids in plants are summarized from the perspectives of transporters, channels, proton pumps, and upstream regulators to better understand the complex regulatory networks involved in fruit acid formation.
Global greenhouse gas emissions from residential and commercial building materials and mitigation strategies to 2060
Authors: Zhong Xiaoyang , Hu Mingming , Deetman Sebastiaan , Steubing Bernhard , Lin Hai Xiang , Hernandez Glenn Aguilar , Harpprecht Carina , Zhang Chunbo , Tukker Arnold , Behrens Paul
Published: October 2021

Building stock growth around the world drives extensive material consumption and environmental impacts. Future impacts will be dependent on the level and rate of socioeconomic development, along with material use and supply strategies. Here we evaluate material-related greenhouse gas (GHG) emissions for residential and commercial buildings along with their reduction potentials in 26 global regions by 2060. For a middle-of-the-road baseline scenario, building material-related emissions see an increase of 3.5 to 4.6 Gt CO2eq yr-1 between 2020–2060. Low- and lower-middle-income regions see rapid emission increase from 750 Mt (22% globally) in 2020 and 2.4 Gt (51%) in 2060, while higher-income regions shrink in both absolute and relative terms. Implementing several material efficiency strategies together in a High Efficiency (HE) scenario could almost half the baseline emissions. Yet, even in this scenario, the building material sector would require double its current proportional share of emissions to meet a 1.5 °C-compatible target.
Changing the game of time resolved X-ray diffraction on the mechanochemistry playground by downsizing
Authors: Lampronti Giulio I. , Michalchuk Adam A. L. , Mazzeo Paolo P. , Belenguer Ana M. , Sanders Jeremy K. M. , Bacchi Alessia , Emmerling Franziska
Published: October 2021

Time resolved in situ (TRIS) monitoring has revolutionised the study of mechanochemical transformations but has been limited by available data quality. Here we report how a combination of miniaturised grinding jars together with innovations in X-ray powder diffraction data collection and state-of-the-art analysis strategies transform the power of TRIS synchrotron mechanochemical experiments. Accurate phase compositions, comparable to those obtained by ex situ measurements, can be obtained with small sample loadings. Moreover, microstructural parameters (crystal size and microstrain) can be also determined with high confidence. This strategy applies to all chemistries, is readily implemented, and yields high-quality diffraction data even using a low energy synchrotron source. This offers a direct avenue towards the mechanochemical investigation of reactions comprising scarce, expensive, or toxic compounds. Our strategy is applied to model systems, including inorganic, metal-organic, and organic mechanosyntheses, resolves previously misinterpreted mechanisms in mechanochemical syntheses, and promises broad, new directions for mechanochemical research.