bluuebunny/crossref_metadata_2025 huggingface dataset:
Dual Band Second‐Order Topological Corner States in 2D Valley‐Hall Hexagonal Photonic Crystals
Authors: O Kang-Hyok , Kim Kwang-Hyon
Published: December 2021

Second‐order topological corner states are of great importance in the field of topological photonics. In particular, for realizing disorder‐immune coherent nanosources based on nonlinear processes one needs multiband topological corner states. This work reports dual band second‐order topological corner states in the structure of valley‐Hall hexagonal photonic crystals. When the ratio between the radii of dielectric cylinders in the unit cells continuously increases, bulk gap opening, appearance of edge states, edge gap opening, and generation of second‐order corner states successively occur in the first and third bandgaps. By changing the structural parameters, the eigenfrequencies of the corner states in both edge gaps can be flexibly adjusted. Compared with square‐lattice valley‐Hall systems, large difference of eigenfrequencies of corner states in dual bandgaps can be obtained with hexagonal photonic crystals, which is the key advantage of the proposed systems for applications in nonlinear coherent generations such as second‐harmonic generation. The numerical results show that the dual band second‐order corner states clearly exhibit robustness against structural defects, significantly distinguished from the defect states. The results presented in this work pave the way toward topologically protected coherent nanosources by nonlinear frequency conversion which are robust against structural disorder or defects.
Differences in health policies for drug availability in pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension across Latin America
Authors: Orozco‐Levi Mauricio , Cáneva Jorge , Fernandes Caio , Restrepo‐Jaramillo Ricardo , Zayas Nayeli , Conde Rafael , Diez Mirta , Jardim Carlos , Pacheco Gallego Manuel C. , Melatini Luciano , Valdéz Héctor , Pulido Tomás
Published: December 2021

Treatment for pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension in Latin America differs between countries, with regard to disease etiology, health insurance coverage, and drug availability. A group of experts from Latin America, met to share regional experiences and propose possible lines of collaboration. The available evidence, regional clinical practice data, and the global context of the proceedings of the 6th World Symposium on Pulmonary Hypertension, held in Nice, France, in February 2018, were analyzed. Here, we discuss some priority concepts identified that could guide transnational interaction and research strategies in Latin America: (1) despite being evidence‐based, the 6th World Symposium on Pulmonary Hypertension proceedings may not be applicable in Latin American countries; (2) proactive identification and diagnosis of patients in Latin America is needed; (3) education of physicians and standardization of appropriate treatment for pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension is vital; (4) our clinical experience for the treatment strategy for pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension is based on drug availability in Argentina, Brazil, Colombia and México; (5) there are difficulties inherent to the consultation of patients with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension, and access to treatment; (6) the importance of data generation and research of Latin American‐specific issues related to pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension is highlighted.
Pulsatile pulmonary artery pressure in a large animal model of chronic thromboembolic pulmonary hypertension: Similarities and differences with human data
Authors: Boulate David , Loisel Fanny , Coblence Mathieu , Provost Bastien , Todesco Alban , Decante Benoit , Beurnier Antoine , Herve Philippe , Perros Frédéric , Humbert Marc , Fadel Elie , Mercier Olaf , Chemla Denis
Published: December 2021

A striking feature of the human pulmonary circulation is that mean (mPAP) and systolic (sPAP) pulmonary artery pressures (PAPs) are strongly related and, thus, are essentially redundant. According to the empirical formula documented under normotensive and hypertensive conditions (mPAP = 0.61 sPAP + 2 mmHg), sPAP matches ~160%mPAP on average. This attests to the high pulsatility of PAP, as also witnessed by the near equality of PA pulse pressure and mPAP. Our prospective study tested if pressure redundancy and high pulsatility also apply in a piglet model of chronic thromboembolic pulmonary hypertension (CTEPH). At baseline (Week‐0, W0), Sham (n = 8) and CTEPH (n = 27) had similar mPAP and stroke volume. At W6, mPAP increased in CTEPH only, with a two‐ to three‐fold increase in PA stiffness and total pulmonary resistance. Seven CTEPH piglets were also studied at W16 at baseline, after volume loading, and after acute pulmonary embolism associated with dobutamine infusion. There was a strong linear relationship between sPAP and mPAP (1) at W0 and W6 (n = 70 data points,r² = 0.95); (2) in the subgroup studied at W16 (n = 21,r² = 0.97); and (3) when all data were pooled (n = 91,r² = 0.97, sPAP range 9–112 mmHg). The PA pulsatility was lower than that expected based on observations in humans: sPAP matched ~120%mPAP only and PA pulse pressure was markedly lower than mPAP. In conclusion, the redundancy between mPAP and sPAP seems a characteristic of the pulmonary circulation independent of the species. However, it is suggested that the sPAP thresholds used to define PH in animals are species‐ and/or model‐dependent and thus must be validated.
Remaining useful life prediction for bivariate deteriorating systems under dynamic operational conditions
Authors: Sun Fuqiang , Guo Hongxuan , Wang Ning , Zhang Wei
Published: December 2021

The existing studies on degradation modeling and remaining useful life (RUL) prediction have typically been conducted on the basis of the following two assumptions: one is the single degradation indicator, and the other is the neglect of the influence of dynamic operating conditions. However, they are oversimplified for the real‐world situations. In this paper, a bivariate degradation modeling method based on the Bayesian dynamic model (BDM) and a joint RUL distribution prediction method is proposed. The covariate model is adopted to illustrate the influence of the dynamic operating conditions on the degradation process. A time‐varying copula method is used to describe the joint RUL distributions of the bivariate system. A real case study on the microwave device is conducted to demonstrate the effectiveness and validity of the proposed method.
Development of a peak extraction method using the high‐resolution matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry and machine learning techniques: Analysis of peak shapes
Authors: Satoh Takaya , Takei Masahiko , Uematsu Fuminori
Published: December 2021

Rationale

Combining matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry (MALDI‐TOFMS) and Kendrick mass defect (KMD) analysis is a powerful tool for visualizing polymers in complex mass spectra. The identification of minor polymers by KMD analysis requires reduction of the broad noise peaks often observed in the low‐mass region.

Methods

A machine‐learning model was created using pix2pixHD. It converts an original mass spectrum into a pseudo‐mass spectrum that contains only the original peaks at m/z positions that the model judges as sharp single‐component peaks. It reduces noise by selecting only the m/z and intensity values from the original spectrum's peak list that correspond to peaks in the pseudo‐mass spectrum.

Results

A machine‐learning model was applied to a low‐concentration polymer mass spectrum observed at m/z <2000. Extracting single‐component peaks from the mass spectrum made the minor polymer series appear clearly in the KMD plot. The technique facilitated mass spectrometric imaging of the ultraviolet degradation of polyethylene terephthalate by plotting the polymers' spatial distributions. It could also distinguish between polymer series (before and after degradation) to identify their separate spatial distributions.

Conclusions

A machine‐learning method for peak extraction from high‐resolution MALDI‐TOFMS was developed. Single‐component peaks of the mass spectrum were distinguished from noise peaks by their peak shapes. Combining with KMD analysis facilitated the identification of minor polymer series in complex mass spectra.
Complex survival trial design by the product integration method
Authors: Tang Yongqiang
Published: December 2021

Nonproportional hazards (NPHs) are often observed in survival trials such as the immunotherapy cancer trials. Under NPH, the classical log‐rank test can be inefficient, and the estimated hazards ratio from the Cox model is difficult to interpret. The weighted log‐rank test, and the tests for comparing the restricted mean survival time or the milestone survival become increasingly popular in handling NPH. The sample size calculation for these tests may require high‐dimensional numerical integration. We present a sample size determination method for survival trials via product integration on the basis of a continuous‐time multistate Markov model. The main challenge of the method lies in the design of the multistate model under a complex NPH pattern, and this is illustrated for NPH induced by delayed effect with individual heterogeneity in the lag duration, cure fractions, and treatment switching due to disease progression or noncompliance. Numerical examples are presented to demonstrate the accuracy of the proposed method. We obtain the following findings. The powers of the tests for milestone survival and RMST depend on both the trial duration and milestone timepoint, and may not increase as the milestone timepoint increases. If the milestone timepoint is appropriately chosen, the RMST test can be more powerful than the conventional log‐rank test in the presence of diminishing treatment effect or in the proportional hazards cure model. In general, the RMST test yields lower power than a proper Fleming‐Harrington weighted log‐rank test.
Talent management in the “new normal”—Case study of Indian IT services multinationals in China
Authors: Thite Mohan , Rammal Hussain Gulzar , Ferreira João J. M.
Published: December 2021

Emerging market multinational corporations (MNCs) are coming under increasing scrutiny for their international performance. While the success of Indian IT multinationals in the West has been extensively researched and reported, there is a lack of research on their relative failure in China. The rise of economic nationalism and the COVID‐19 pandemic pose challenges for the mobility of professionals and the global talent management (GTM) strategy of MNCs. Through in‐depth interviews with senior managers from four well‐known Indian IT services multinationals, this article presents an evidence‐based critique of the design and implementation of their GTM strategy both inside and outside China. It focuses specifically on the quality of the IT talent pool in China, control and coordination issues, and the challenges of workforce localization.
Artificial virtuous agents: from theory to machine implementation
Authors: Stenseke Jakob
Published: December 2021

Virtue ethics has many times been suggested as a promising recipe for the construction of artificial moral agents due to its emphasis on moral character and learning. However, given the complex nature of the theory, hardly any work has de facto attempted to implement the core tenets of virtue ethics in moral machines. The main goal of this paper is to demonstrate how virtue ethics can be taken all the way from theory to machine implementation. To achieve this goal, we critically explore the possibilities and challenges for virtue ethics from a computational perspective. Drawing on previous conceptual and technical work, we outline a version of artificial virtue based on moral functionalism, connectionist bottom–up learning, and eudaimonic reward. We then describe how core features of the outlined theory can be interpreted in terms of functionality, which in turn informs the design of components necessary for virtuous cognition. Finally, we present a comprehensive framework for the technical development of artificial virtuous agents and discuss how they can be implemented in moral environments.
Production of galactosylated complex-type N-glycans in glycoengineered Saccharomyces cerevisiae
Authors: Piirainen Mari A. , Salminen Heidi , Frey Alexander D.
Published: December 2021

N-glycosylation is an important posttranslational modification affecting the properties and quality of therapeutic proteins. Glycoengineering in yeast aims to produce proteins carrying human-compatible glycosylation, enabling the production of therapeutic proteins in yeasts. In this work, we demonstrate further development and characterization of a glycoengineering strategy in a Saccharomyces cerevisiae Δalg3 Δalg11 strain where a truncated Man3GlcNAc2 glycan precursor is formed due to a disrupted lipid-linked oligosaccharide synthesis pathway. We produced galactosylated complex-type and hybrid-like N-glycans by expressing a human galactosyltransferase fusion protein both with and without a UDP-glucose 4-epimerase domain from Schizosaccharomyces pombe. Our results showed that the presence of the UDP-glucose 4-epimerase domain was beneficial for the production of digalactosylated complex-type glycans also when extracellular galactose was supplied, suggesting that the positive impact of the UDP-glucose 4-epimerase domain on the galactosylation process can be linked to other processes than its catalytic activity. Moreover, optimization of the expression of human GlcNAc transferases I and II and supplementation of glucosamine in the growth medium increased the formation of galactosylated complex-type glycans. Additionally, we provide further characterization of the interfering mannosylation taking place in the glycoengineered yeast strain.

Key points

• Glycoengineered Saccharomyces cerevisiae can form galactosylated N-glycans.

• Genetic constructs impact the activities of the expressed glycosyltransferases.

• Growth medium supplementation increases formation of target N-glycan structure.
A deletion containing a CTCF-element in intron 8 of the Bbs7 gene is partially responsible for juvenile obesity in the Berlin Fat Mouse
Authors: Krause Florian , Mohebian Kourosh , Delpero Manuel , Hesse Deike , Kühn Ralf , Arends Danny , Brockmann Gudrun A.
Published: December 2021

The Berlin Fat Mouse Inbred (BFMI) line is a model for juvenile obesity. Previous studies on crosses between BFMI and C57Bl/6N (B6N) have identified a recessive defect causing juvenile obesity on chromosome 3 (jObes1). Bbs7 was identified as the most likely candidate gene for the observed effect. Comparative sequence analysis showed a 1578 bp deletion in intron 8 of Bbs7 in BFMI mice. A CTCF-element is located inside this deletion. To investigate the functional effect of this deletion, it was introduced into B6N mice using CRISPR/Cas9. Two mice containing the target deletion were obtained (B6N Bbs7emI8∆1 and Bbs7emI8∆2) and were subsequently mated to BFMI and B6N to generate two families suitable for complementation. Inherited alleles were determined and body composition was measured by quantitative magnetic resonance. Evidence for a partial complementation (13.1–15.1%) of the jObes1 allele by the CRISPR/Cas9 modified B6N Bbs7emI8∆1 and Bbs7emI8∆2 alleles was found. Mice carrying the complementation alleles had a 23–27% higher fat-to-lean ratio compared to animals which have a B6N allele (P(Bbs7emI8∆1) = 4.25 × 10–7; P(Bbs7emI8∆2) = 3.17 × 10–5). Consistent with previous findings, the recessive effect of the BFMI allele was also seen for the B6N Bbs7emI8∆1 and Bbs7emI8∆2 alleles. However, the effect size of the B6N Bbs7emI8∆1 and Bbs7emI8∆2 alleles was smaller than the BFMI allele, and thus showed only a partial complementation. Findings suggest additional variants near Bbs7 in addition to or interacting with the deletion in intron 8.
On regular and random two-dimensional packing of crosses
Authors: Stannarius Ralf , Schulze Jonas
Published: December 2021

Packing problems, even of objects with regular geometries, are in general non-trivial. For few special shapes, the features of crystalline as well as random, irregular two-dimensional (2D) packing structures are known. The packing of 2D crosses does not yet belong to the category of solved problems. We demonstrate in experiments with crosses of different aspect ratios (arm width to length) which packing fractions are actually achieved by random packing, and we compare them to densest regular packing structures. We determine local correlations of the orientations and positions after ensembles of randomly placed crosses were compacted in the plane until they jam. Short-range orientational order is found over 2 to 3 cross lengths. Similarly, correlations in the spatial distributions of neighbors extend over 2 to 3 crosses. There is no simple relation between the geometries of the crosses and the peaks in the spatial correlation functions, but some features of the orientational correlations can be traced to typical local configurations.
Characteristics of healthy German children and adolescents across tertiles of calcaneal stiffness index
Authors: Heydenreich Juliane , Schweter Antje , Lührmann Petra
Published: December 2021

Aim

Identifying risk factors for low bone stiffness index (SI) might be one crucial strategy for osteoporosis prevention. Purpose was to characterize healthy schoolchildren across tertiles of SI.

Subject and methods

In 248 girls (13.4 ± 1.9 years, BMI: 20.2 ± 4.8 kg/m2) and 231 boys (13.6 ± 1.7 years, BMI: 19.3 ± 3.3 kg/m2), the following parameters were assessed: calcaneal SI (quantitative ultrasound), body composition (bioelectrical impedance analysis), Bone Healthy Eating Index (BoneHEI; food frequency questionnaire), and physical activity level (PAL; activity questionnaire). Participants were classified according to age- and sex-specific SI tertiles (low, medium, and high). Between-group comparisons were achieved by Kruskal–Wallis-H-tests (α = 0.05).

Results

Girls with low SI had significantly lower body mass (49.2 ± 16.7 vs 54.8 ± 12.2 kg; p < 0.01), BMI (19.6 ± 5.4 vs 21.3 ± 3.9 kg/m2; p < 0.0001), fat-free mass (36.3 ± 8.3 vs 39.5 ± 6.0 kg; p < 0.01), and fat mass (23.7 ± 9.1 vs 26.8 ± 7.2%; p < 0.05) compared to those with high SI. In boys, significant differences between low and high SI were obtained for PAL (1.49 ± 0.12 vs 1.56 ± 0.14; p < 0.01). BoneHEI was not significantly different between tertiles in both sexes.

Conclusion

Girls with low body mass and boys with low PAL have a higher risk for low SI. Schoolchildren should strive for normal body mass and perform regular physical activity.
Anterior Cingulate Cortex Mediates Hyperalgesia and Anxiety Induced by Chronic Pancreatitis in Rats
Authors: Ren Dan , Li Jia-Ni , Qiu Xin-Tong , Wan Fa-Ping , Wu Zhen-Yu , Fan Bo-Yuan , Zhang Ming-Ming , Chen Tao , Li Hui , Bai Yang , Li Yun-Qing
Published: December 2021

Central sensitization is essential in maintaining chronic pain induced by chronic pancreatitis (CP), but cortical modulation of painful CP remains elusive. Here, we examined the role of the anterior cingulate cortex (ACC) in the pathogenesis of abdominal hyperalgesia in a rat model of CP induced by intraductal administration of trinitrobenzene sulfonic acid (TNBS). TNBS treatment resulted in long-term abdominal hyperalgesia and anxiety in rats. Morphological data indicated that painful CP induced a significant increase in FOS-expressing neurons in the nucleus tractus solitarii (NTS) and ACC, and some FOS-expressing neurons in the NTS projected to the ACC. In addition, a larger portion of ascending fibers from the NTS innervated pyramidal neurons, the neural subpopulation primarily expressing FOS under the condition of painful CP, rather than GABAergic neurons within the ACC. CP rats showed increased expression of vesicular glutamate transporter 1, and increased membrane trafficking and phosphorylation of the N-methyl-D-aspartate receptor (NMDAR) subunit NR2B and the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) subunit GluR1 within the ACC. Microinjection of NMDAR and AMPAR antagonists into the ACC to block excitatory synaptic transmission significantly attenuated abdominal hyperalgesia in CP rats, which was similar to the analgesic effect of endomorphins injected into the ACC. Specifically inhibiting the excitability of ACC pyramidal cells via chemogenetics reduced both hyperalgesia and comorbid anxiety, whereas activating these neurons via optogenetics failed to aggravate hyperalgesia and anxiety in CP rats. Taken together, these findings provide neurocircuit, biochemical, and behavioral evidence for involvement of the ACC in hyperalgesia and anxiety in CP rats, as well as novel insights into the cortical modulation of painful CP, and highlights the ACC as a potential target for neuromodulatory interventions in the treatment of painful CP.
AI Startup Business Models
Authors: Weber Michael , Beutter Moritz , Weking Jörg , Böhm Markus , Krcmar Helmut
Published: December 2021

We currently observe the rapid emergence of startups that use Artificial Intelligence (AI) as part of their business model. While recent research suggests that AI startups employ novel or different business models, one could argue that AI technology has been used in business models for a long time already—questioning the novelty of those business models. Therefore, this study investigates how AI startup business models potentially differ from common IT-related business models. First, a business model taxonomy of AI startups is developed from a sample of 100 AI startups and four archetypal business model patterns are derived: AI-charged Product/Service Provider, AI Development Facilitator, Data Analytics Provider, and Deep Tech Researcher. Second, drawing on this descriptive analysis, three distinctive aspects of AI startup business models are discussed: (1) new value propositions through AI capabilities, (2) different roles of data for value creation, and (3) the impact of AI technology on the overall business logic. This study contributes to our fundamental understanding of AI startup business models by identifying their key characteristics, common instantiations, and distinctive aspects. Furthermore, this study proposes promising directions for future entrepreneurship research. For practice, the taxonomy and patterns serve as structured tools to support entrepreneurial action.
Agronomic performance of ten perennial ryegrass varieties on commercial grassland farms
Authors: Hearn C. , Egan M. , Berry D.P. , Geoghegan A. , O'Leary M. , Lynch M.B. , O'Donovan M.
Published: December 2021

Little information is available on the phenotypic performance of perennial ryegrass varieties when exposed to grazing conditions on commercial grassland farms. Grass varieties are classically evaluated in mechanically defoliated plot systems which, although designed to mimic grazing conditions, do not fully capture the range of stresses or interactions that a sward is subjected to under commercial settings or over any period longer than 4 years. The evolution of technology in the form of PastureBase Ireland has led to agronomic data of individual paddocks being made available for analysis over multiple years. Data used in the current study consisted of dry matter (DM) production and ground score data across a 7-year period from ten perennial ryegrass varieties grown as monocultures in 559 paddocks on 98 commercial farms. The results demonstrated how perennial ryegrass variety is associated with a range of agronomic performance traits on commercial farms; including total and seasonal DM production, grazing DM production and number of grazing events. Varieties with the highest total DM production also had the highest spring and mid-season DM production; autumn DM production was associated with the interaction between variety and year. The highest producing variety in the study, AberGain, produced 1342 kg DM/ha/year more than the mean of all other varieties. Variety differences manifested themselves as swards aged, with some varieties increasing in total DM production while others reduced in total DM production. The current work provides a basis for the consideration of on-farm variety assessment in the composition of future variety evaluation protocols.
HEADLESS MUSICAL SEEDS AND GESTURES WITH ADJECTIVES: AN INTERVIEW WITH KEIKO DEVAUX
Authors: Höstman Anna
Published: December 2021

Keiko Devaux (b. 1982) is a Canadian composer, originally from British Columbia, who now lives in Montréal. She began her musical career in piano-performance studies as well as composing, touring and recording several albums in independent rock bands. Her concert music is widely performed throughout Canada and Europe. From 2016–18, Keiko was the composer in residence of Le Nouvel Ensemble Moderne. She joined Salvatore Sciarrino's masterclasses at L'Accademia Musicale Chigiana in Siena, Italy, between the years 2017 and 2019. Keiko was commissioned by music@villaromana festival, Florence, to create Echoic Memories. She is the inaugural winner of the Azrieli Commission for Canadian Music (2020) and is also engaged in a two-year residency as a Carrefour composer with the National Arts Centre Orchestra (2020–22). This interview was conducted over Zoom in late spring 2020, in the midst of the Covid-19 pandemic.
Alastair White, RUNE, Tête à Tête Festival, Round Chapel, Hackney, London, 17 August 2021.
Authors: Haggett George K.
Published: December 2021

The setting is Khye-Rell, part of a web of worlds in our universe's distant future. In this society, history is forbidden. A young girl, Kes'Cha'Au’, crosses a series of ‘transdimensional canals’, journeying back through our own time and our looming ecological collapse. She reveals, at the heart of everything, the universe creating itself out of nothing: it inscribes itself like a rune.
Numbers in action
Authors: Burr David C. , Anobile Giovanni , Castaldi Elisa , Arrighi Roberto
Published: December 2021

To understand the number sense, we need to understand its function. We argue that numerosity estimation is fundamental not only for perception, but also preparation and control of action. We outline experiments that link numerosity estimation with action, pointing to a generalized numerosity system that serves both perception and action preparation.
Weighted numbers
Authors: Marinova Mila , Fedele Marta , Reynvoet Bert
Published: December 2021

Clarke and Beck (C&B) discuss in their sections on congruency and confounds (sects. 3 and 4) literature that has challenged the claim that the approximate number system (ANS) represents numerical content. We argue that the propositions put forward by these studies aren't that far from the indirect model of number perception suggested by C&B.
The number sense does not represent numbers, but cardinality comparisons
Authors: Bermúdez José Luis
Published: December 2021

Against Clarke and Beck's proposal that the approximate number system (ANS) represents natural and rational numbers, I suggest that the experimental evidence is better accommodated by the (much weaker) thesis that the ANS represents cardinality comparisons. Cardinality comparisons do not stand in arithmetical relations and being able to apply them does not involve basic arithmetical concepts and operations.
Ratio-based perceptual foundations for rational numbers, and perhaps whole numbers, too?
Authors: Hubbard Edward M. , Matthews Percival G.
Published: December 2021

Clarke and Beck suggest that the ratio processing system (RPS) may be a component of the approximate number system (ANS), which they suggest represents rational numbers. We argue that available evidence is inconsistent with their account and advocate for a two-systems view. This implies that there may be many access points for numerical cognition – and that privileging the ANS may be a mistake.
Not so rational: A more natural way to understand the ANS
Authors: Hecht Eli , Mills Tracey , Shin Steven , Phillips Jonathan
Published: December 2021

In contrast to Clarke and Beck's claim that that the approximate number system (ANS) represents rational numbers, we argue for a more modest alternative: The ANS represents natural numbers, and there are separate, non-numeric processes that can be used to represent ratios across a wide range of domains, including natural numbers.
Constructing rationals through conjoint measurement of numerator and denominator as approximate integer magnitudes in tradeoff relations
Authors: Zhang Jun
Published: December 2021

To investigate mechanisms of rational representation, I consider (1) construction of an ordered continuum of psychophysical scale of magnitude of sensation; (2) counting mechanism leading to an approximate numerosity scale for integers; and (3) conjoint measurement structure pitting the denominator against the numerator in tradeoff positions. Number sense of resulting rationals is neither intuitive nor expedient in their manipulation.
Helping Refugees Where They Are
Authors: Gerver Mollie
Published: December 2021

Some policies are not politically feasible. In the context of refugees, many claim it is not politically feasible to start admitting significantly more refugees into wealthy countries. In particular, it is not feasible for advocates of refugees to successfully persuade policymakers to adopt such a policy. A recent book by Alexander Betts argues that advocates should instead focus on developing the economies of lower-income countries where most refugees reside. This review essay argues that current data does not yet establish whether Betts's approach is more feasible than increasing refugee admissions to wealthy states. There are good reasons to suppose increasing refugees’ admissions to wealthy states is politically feasible, if we account for the ways citizens in wealthy states are harmed when refugees are not admitted, and for the ways citizens are harmed when immigration enforcement prevents refugees from arriving. Drawing on recent books on immigration, this essay demonstrates that enforcement against refugees constrains citizens’ freedom, well-being, and ability to hold their government to account. Further research can establish if citizens’ interest in reducing enforcement can be translated into policy changes that significantly increase the number of refugees admitted. Such research is necessary before concluding that only helping refugees in lower-income countries is feasible.
Treatment of chronic resistant paediatric idiopathic pericardial effusion with intrapericardial injection of corticosteroids 4-year-old girl with rapid full resolution after intrapericardial injection of corticosteroids
Authors: Othman Takhfif , Eldadah Osama
Published: December 2021

Non-steroidal anti-inflammatory drugs are the conventional treatment for pericarditis. However, some patients will still suffer from persistence pericardial effusion despite exhausting all conventional management options. A 4-year-old girl with idiopathic pericardial effusion who did not respond to 2 months of conventional therapy had complete resolution of effusion within 5 days, with no recurrence after administration of intrapericardial steroids. As far as we know, this is the first published paediatric case who has shown a similar outcome to that seen in adult studies.
Concept-less Schemata: The Reciprocity of Imagination and Understanding in Kant’s Aesthetics
Authors: Filieri Luigi
Published: December 2021

In this paper, I discuss Kant’s concept-less schematism (KU, 5: 287) in the thirdCritique1and make three claims: 1) concept-less schematism is entirely consistent with the schematism in the firstCritique; 2) concept-less schematism is schematism with noempiricalconcept as an outcome; and 3) in accordance with 1) and 2), the imagination is free to synthesize the given manifold and leads to judgements of taste without this meaning either that the categories play no role at all or that these judgements are full-fledged cognitive determining judgements. While most commentators read the freedom of the imagination as its independence from the understanding, I argue that the freedom of the imagination is based on a non-determining employment of the pure concepts of the understanding. The freedom of the aesthetic imagination consists in the temporal schematization of the categories without any complementary determination of the empirical concept.
Community Input Drives Superfund Research
Authors: Donovan Robin
Published: December 2021

Researchers identified geochemical tracers for lead and investigated Oklahomans’ concerns at the Tar Creek Superfund site.
Hundreds of Volcanic Explosions Detected Underwater at Kīlauea
Authors: Duncombe Jenessa
Published: December 2021

Hundreds of volcanic explosions detected underwater at KīlaueaThe explosions, identified during the 2018 eruption phase, offer a clear acoustic signal that researchers could use to measure ocean properties.
Spatiotemporal Characterization of Geophysical Signal Detection Capabilities of GRACE‐FO
Authors: Peidou Athina , Landerer Felix , Wiese David , Ellmer Matthias , Fahnestock Eugene , McCullough Christopher , Spero Robert , Yuan Dah‐Ning
Published: December 2021

The intersatellite range measurements between the Gravity Recovery and Climate Experiment Follow‐On (GRACE‐FO) satellite pair enable mapping time variations in Earth's gravity field. The Laser Ranging Interferometer (LRI) and Microwave Instrument (MWI) provide independent range measurements. We compare gravity fields derived from the two instruments. The LRI captures time‐variable gravity field signals up to 21 mHz (165 km half‐wavelength) globally, while MWI reaches frequencies up to 15 mHz (230 km). Time‐variable mass variations free from annual cycles and trends are sensed up to 15 mHz (LRI) and 11 mHz (320 km) (MWI). Both instruments are shown to be excellent tools for detection and monitoring of sub‐monthly geophysical signals. Along‐track global maps of sub‐monthly signals are expected to shed light on the high‐frequency behavior of a large number of geophysical processes.
A schizophrenia subgroup with elevated inflammation displays reduced microglia, increased peripheral immune cell and altered neurogenesis marker gene expression in the subependymal zone
Authors: North Hayley F. , Weissleder Christin , Fullerton Janice M. , Sager Rachel , Webster Maree J. , Weickert Cynthia Shannon
Published: December 2021

Inflammation regulates neurogenesis, and the brains of patients with schizophrenia and bipolar disorder have reduced expression of neurogenesis markers in the subependymal zone (SEZ), the birthplace of inhibitory interneurons. Inflammation is associated with cortical interneuron deficits, but the relationship between inflammation and reduced neurogenesis in schizophrenia and bipolar disorder remains unexplored. Therefore, we investigated inflammation in the SEZ by defining those with low and high levels of inflammation using cluster analysis of IL6, IL6R, IL1R1 and SERPINA3 gene expression in 32 controls, 32 schizophrenia and 29 bipolar disorder cases. We then determined whether mRNAs for markers of glia, immune cells and neurogenesis varied with inflammation. A significantly greater proportion of schizophrenia (37%) and bipolar disorder cases (32%) were in high inflammation subgroups compared to controls (10%, p < 0.05). Across the high inflammation subgroups of psychiatric disorders, mRNAs of markers for phagocytic microglia were reduced (P2RY12, P2RY13), while mRNAs of markers for perivascular macrophages (CD163), pro-inflammatory macrophages (CD64), monocytes (CD14), natural killer cells (FCGR3A) and adhesion molecules (ICAM1) were increased. Specific to high inflammation schizophrenia, quiescent stem cell marker mRNA (GFAPD) was reduced, whereas neuronal progenitor (ASCL1) and immature neuron marker mRNAs (DCX) were decreased compared to low inflammation control and schizophrenia subgroups. Thus, a heightened state of inflammation may dampen microglial response and recruit peripheral immune cells in psychiatric disorders. The findings elucidate differential neurogenic responses to inflammation within psychiatric disorders and highlight that inflammation may impair neuronal differentiation in the SEZ in schizophrenia.
Androgen receptor and MYC equilibration centralizes on developmental super-enhancer
Authors: Guo Haiyang , Wu Yiming , Nouri Mannan , Spisak Sandor , Russo Joshua W. , Sowalsky Adam G. , Pomerantz Mark M. , Wei Zhao , Korthauer Keegan , Seo Ji-Heui , Wang Liyang , Arai Seiji , Freedman Matthew L. , He Housheng Hansen , Chen Shaoyong , Balk Steven P.
Published: December 2021

Androgen receptor (AR) in prostate cancer (PCa) can drive transcriptional repression of multiple genes including MYC, and supraphysiological androgen is effective in some patients. Here, we show that this repression is independent of AR chromatin binding and driven by coactivator redistribution, and through chromatin conformation capture methods show disruption of the interaction between the MYC super-enhancer within the PCAT1 gene and the MYC promoter. Conversely, androgen deprivation in vitro and in vivo increases MYC expression. In parallel, global AR activity is suppressed by MYC overexpression, consistent with coactivator redistribution. These suppressive effects of AR and MYC are mitigated at shared AR/MYC binding sites, which also have markedly higher levels of H3K27 acetylation, indicating enrichment for functional enhancers. These findings demonstrate an intricate balance between AR and MYC, and indicate that increased MYC in response to androgen deprivation contributes to castration-resistant PCa, while decreased MYC may contribute to responses to supraphysiological androgen therapy.
Modular and stereoselective synthesis of tetrasubstituted vinyl sulfides leading to a library of AIEgens
Authors: Liu Xun-Shen , Tang Zhiqiong , Li Zhiming , Li Mingjia , Xu Lin , Liu Lu
Published: December 2021

Tetraarylethylenes exhibit intriguing photophysical properties and sulfur atom frequently play a vital role in organic photoelectric materials and biologically active compounds. Tetrasubstituted vinyl sulfides, which include both sulfur atom and tetrasubstituted alkenes motifs, might be a suitable skeleton for the discovery of the new material molecules and drug with unique functions and properties. However, how to modular synthesis these kinds of compounds is still challenging. Herein, a chemo- and stereo-selective Rh(II)-catalyzed [1,4]-acyl rearrangements of α-diazo carbonyl compounds and thioesters has been developed, providing a modular strategy to a library of 63 tetrasubstituted vinyl sulfides. In this transformation, the yield is up to 95% and the turnover number is up to 3650. The mechanism of this reaction is investigated by combining experiments and density functional theory calculation. Moreover, the “aggregation-induced emission” effect of tetrasubstituted vinyl sulfides were also investigated, which might useful in functional material, biological imaging and chemicalnsing via structural modification.
Live tumor imaging shows macrophage induction and TMEM-mediated enrichment of cancer stem cells during metastatic dissemination
Authors: Sharma Ved P. , Tang Binwu , Wang Yarong , Duran Camille L. , Karagiannis George S. , Xue Emily A. , Entenberg David , Borriello Lucia , Coste Anouchka , Eddy Robert J. , Kim Gina , Ye Xianjun , Jones Joan G. , Grunblatt Eli , Agi Nathan , Roy Sweta , Bandyopadhyaya Gargi , Adler Esther , Surve Chinmay R. , Esposito Dominic , Goswami Sumanta , Segall Jeffrey E. , Guo Wenjun , Condeelis John S. , Wakefield Lalage M. , Oktay Maja H.
Published: December 2021

Cancer stem cells (CSCs) play an important role during metastasis, but the dynamic behavior and induction mechanisms of CSCs are not well understood. Here, we employ high-resolution intravital microscopy using a CSC biosensor to directly observe CSCs in live mice with mammary tumors. CSCs display the slow-migratory, invadopod-rich phenotype that is the hallmark of disseminating tumor cells. CSCs are enriched near macrophages, particularly near macrophage-containing intravasation sites called Tumor Microenvironment of Metastasis (TMEM) doorways. Substantial enrichment of CSCs occurs on association with TMEM doorways, contributing to the finding that CSCs represent >60% of circulating tumor cells. Mechanistically, stemness is induced in non-stem cancer cells upon their direct contact with macrophages via Notch-Jagged signaling. In breast cancers from patients, the density of TMEM doorways correlates with the proportion of cancer cells expressing stem cell markers, indicating that in human breast cancer TMEM doorways are not only cancer cell intravasation portals but also CSC programming sites.
Copper depletion modulates mitochondrial oxidative phosphorylation to impair triple negative breast cancer metastasis
Authors: Ramchandani Divya , Berisa Mirela , Tavarez Diamile A. , Li Zhuoning , Miele Matthew , Bai Yang , Lee Sharrell B. , Ban Yi , Dephoure Noah , Hendrickson Ronald C. , Cloonan Suzanne M. , Gao Dingcheng , Cross Justin R. , Vahdat Linda T. , Mittal Vivek
Published: December 2021

Copper serves as a co-factor for a host of metalloenzymes that contribute to malignant progression. The orally bioavailable copper chelating agent tetrathiomolybdate (TM) has been associated with a significant survival benefit in high-risk triple negative breast cancer (TNBC) patients. Despite these promising data, the mechanisms by which copper depletion impacts metastasis are poorly understood and this remains a major barrier to advancing TM to a randomized phase II trial. Here, using two independent TNBC models, we report a discrete subpopulation of highly metastatic SOX2/OCT4+ cells within primary tumors that exhibit elevated intracellular copper levels and a marked sensitivity to TM. Global proteomic and metabolomic profiling identifies TM-mediated inactivation of Complex IV as the primary metabolic defect in the SOX2/OCT4+ cell population. We also identify AMPK/mTORC1 energy sensor as an important downstream pathway and show that AMPK inhibition rescues TM-mediated loss of invasion. Furthermore, loss of the mitochondria-specific copper chaperone, COX17, restricts copper deficiency to mitochondria and phenocopies TM-mediated alterations. These findings identify a copper-metabolism-metastasis axis with potential to enrich patient populations in next-generation therapeutic trials.
Spin-dependent vibronic response of a carbon radical ion in two-dimensional WS2
Authors: Cochrane Katherine A. , Lee Jun-Ho , Kastl Christoph , Haber Jonah B. , Zhang Tianyi , Kozhakhmetov Azimkhan , Robinson Joshua A. , Terrones Mauricio , Repp Jascha , Neaton Jeffrey B. , Weber-Bargioni Alexander , Schuler Bruno
Published: December 2021

Atomic spin centers in 2D materials are a highly anticipated building block for quantum technologies. Here, we demonstrate the creation of an effective spin-1/2 system via the atomically controlled generation of magnetic carbon radical ions (CRIs) in synthetic two-dimensional transition metal dichalcogenides. Hydrogenated carbon impurities located at chalcogen sites introduced by chemical doping are activated with atomic precision by hydrogen depassivation using a scanning probe tip. In its anionic state, the carbon impurity is computed to have a magnetic moment of 1 μB resulting from an unpaired electron populating a spin-polarized in-gap orbital. We show that the CRI defect states couple to a small number of local vibrational modes. The vibronic coupling strength critically depends on the spin state and differs for monolayer and bilayer WS2. The carbon radical ion is a surface-bound atomic defect that can be selectively introduced, features a well-understood vibronic spectrum, and is charge state controlled.
Liver MRI and clinical findings to predict response after drug eluting bead transarterial chemoembolization in hepatocellular carcinoma
Authors: Lee Jeong Yeop , Lee Byung Chan , Kim Hyoung Ook , Heo Suk Hee , Shin Sang Soo , Jeong Yong Yeon
Published: December 2021

To identify the gadoxetic acid (GA)-enhanced magnetic resonance imaging (MRI) and laboratory findings that enable prediction of treatment response and disease-free survival (DFS) after the first session of drug eluting bead transarterial chemoembolization (DEB-TACE) in patients with hepatocellular carcinoma (HCC). A total of 55 patients who underwent GA-enhanced MRI and DEB-TACE from January 2014 to December 2018 were included. All MRI features were reviewed by two radiologists. Treatment response was evaluated according to the modified Response Evaluation Criteria in Solid Tumors. Univariate and multivariate logistic regression analyses were used to determine predictive factors of treatment response and DFS, respectively. A total of 27 patients (49.1%) achieved complete response (CR) after one session of treatment. There were no significant differences between the two groups in terms of clinical and laboratory characteristics. Heterogeneous signal intensity in the hepatobiliary phase (HBP) was the only independent predictor of non-CR (odds ratio, 4.807; p = 0.048). Recurrent HCC was detected in 19 patients (70.4%) after CR. In the multivariate analysis, elevated serum alpha-fetoprotein (AFP) level (≥ 30 ng/mL) was the only significant parameter associated with DFS (hazard ratio, 2.916; p = 0.040). This preliminary study demonstrated that heterogeneous signal intensity in the HBP and high serum AFP were useful predictive factors for poor treatment response and short DFS after DEB-TACE, respectively.
Development and validation of a practical machine-learning triage algorithm for the detection of patients in need of critical care in the emergency department
Authors: Liu Yecheng , Gao Jiandong , Liu Jihai , Walline Joseph Harold , Liu Xiaoying , Zhang Ting , Wu Yunyang , Wu Ji , Zhu Huadong , Zhu Weiguo
Published: December 2021

Identifying critically ill patients is a key challenge in emergency department (ED) triage. Mis-triage errors are still widespread in triage systems around the world. Here, we present a machine learning system (MLS) to assist ED triage officers better recognize critically ill patients and provide a text-based explanation of the MLS recommendation. To derive the MLS, an existing dataset of 22,272 patient encounters from 2012 to 2019 from our institution’s electronic emergency triage system (EETS) was used for algorithm training and validation. The area under the receiver operating characteristic curve (AUC) was 0.875 ± 0.006 (CI:95%) in retrospective dataset using fivefold cross validation, higher than that of reference model (0.843 ± 0.005 (CI:95%)). In the prospective cohort study, compared to the traditional triage system’s 1.2% mis-triage rate, the mis-triage rate in the MLS-assisted group was 0.9%. This MLS method with a real-time explanation for triage officers was able to lower the mis-triage rate of critically ill ED patients.