bluuebunny/crossref_metadata_2025 huggingface dataset:
Tropical cyclone-induced coastal sea level projection and the adaptation to a changing climate
Authors: Mori Nobuhito , Shimura Tomoya
Published: November 2022

Tropical cyclones (TCs) cause severe coastal flooding in the middle latitudes. While the IPCC Fifth Assessment Reports (AR5, 2013) have focused on mean sea-level rise, recent advances (e.g., IPCC Sixth Assessment Reports, AR6, 2021) have shown the importance of storm surges and wave changes in extreme water levels causing coastal flooding. Both TC intensity and track changes are linked to future changes in extreme storm surges and wave climates in middle latitudes. This brief review summarizes historical and future long-term changes in extreme water levels, the contribution of increased storm surges, and wave height by the monitoring data and climate projections. In addition, several examples of impact assessment of storm surges and extreme wave changes are presented.
Families of similar simplices inscribed in most smoothly embedded spheres
Authors: Cantarella Jason , Denne Elizabeth , McCleary John
Published: November 2022

Let

$\Delta $

denote a nondegenerate k-simplex in

$\mathbb {R}^k$

. The set

$\operatorname {\mathrm {Sim}}(\Delta )$

of simplices in

$\mathbb {R}^k$

similar to

$\Delta $

is diffeomorphic to

$\operatorname {O}(k)\times [0,\infty )\times \mathbb {R}^k$

, where the factor in

$\operatorname {O}(k)$

is a matrix called the pose. Among

$(k-1)$

-spheres smoothly embedded in

$\mathbb {R}^k$

and isotopic to the identity, there is a dense family of spheres, for which the subset of

$\operatorname {\mathrm {Sim}}(\Delta )$

of simplices inscribed in each embedded sphere contains a similar simplex of every pose

$U\in \operatorname {O}(k)$

. Further, the intersection of

$\operatorname {\mathrm {Sim}}(\Delta )$

with the configuration space of

$k+1$

distinct points on an embedded sphere is a manifold whose top homology class maps to the top class in

$\operatorname {O}(k)$

via the pose map. This gives a high-dimensional generalisation of classical results on inscribing families of triangles in plane curves. We use techniques established in our previous paper on the square-peg problem where we viewed inscribed simplices in spheres as transverse intersections of submanifolds of compactified configuration spaces.
Amefricanity: A Black Feminist Proposal for a Political Organization and Social Transformation
Authors: Pons Cardoso Cláudia , Castillo Espinosa Lia
Published: November 2022

This article analyzes the work and thought of Lélia Gonzalez on the experience of Black women in Brazil. It highlights her legacy within studies of Black Feminism in Latin America and the Caribbean, as well as the importance of her articulation between sex, class, and race with the intention of understanding the social inequality Indigenous and Black women suffer. Gonzalez's political-cultural category of Amefricanity is presented in this article as an instrument of analysis specific to the region, which promotes an epistemological shift within Black feminism. This category seeks to interpret the stories and survival strategies of previous generations of Black women on the continent, as well as to learn their methods and transgressive practices of asymmetrical power relations as pedagogical processes.
Prediction of spontaneous imbibition with gravity in porous media micromodels
Authors: Li Sheng , Liu Haihu , Wu Rui , Cai Jianchao , Xi Guang , Jiang Fei
Published: November 2022

In this work, theoretical modelling, quasi-three-dimensional (quasi-3D) simulations and micromodel experiments are conducted to study spontaneous imbibition with gravity in porous media micromodels. By establishing the force balance governing the spontaneous imbibition process, we develop a theoretical model for predicting the imbibition length against time in a rectangular capillary. The theoretical model is then extended to the prediction of a compact displacement process in a micromodel by using an equivalent width, which is derived by analogising the micromodel to a rectangular capillary. By simulating spontaneous imbibition in a rectangular capillary with various aspect ratios (

$\varepsilon$

), we show that the application condition of the quasi-3D method is

$\varepsilon \leqslant 1/3$

. Next, we simulate spontaneous imbibition in micromodels with various geometries and flow conditions. Fingering and compact displacement are identified for varying viscosity ratios and gravitational accelerations. At low (high) viscosity ratio of wetting to non-wetting fluids, an upward (downward) gravity can promote the stability of the wetting front, favouring the transition from fingering to compact displacement. In addition, we find that the depth-oriented interface curvature dominates the capillary effect during the imbibition, and such a mechanism is considered by introducing an equivalent contact angle into the theoretical model. With the help of equivalent width and contact angle, the theoretical model is shown to provide satisfactory prediction of the compact displacement process. Finally, a micromodel experiment is presented to further verify the developed theoretical model and the quasi-3D simulation.
Bakke Redux — Affirmative Action and Physician Diversity in Peril
Authors: Curfman Gregory
Published: November 2022

This article examines the legal arguments that may lead the Supreme Court to overrule precedent and strike down affirmative action in university admissions. Given the critical importance of a diverse physician workforce for our Nation’s health care system, the potential reversal of affirmative action admission programs in medical schools may have severe negative consequences. This article discusses the implications for health care should the Court issue an opinion restricting or eliminating affirmative action in higher education.
Mitochondrial Replacement Therapy: In Whose Interests?
Authors: Noohi Forough , Ravitsky Vardit , Knoppers Bartha Maria , Joly Yann
Published: November 2022

Mitochondrial replacement therapy (MRT), also called nuclear genome transfer and mitochondrial donation, is a new technique that can be used to prevent the transmission of mitochondrial DNA diseases. Apart from the United Kingdom, the first country to approve MRT in 2015, Australia became the second country with a clear regulatory path for the clinical applications of this technique in 2021. The rapidly evolving clinical landscape of MRT makes the elaboration and evaluation of the responsible use of this technology a pressing matter. As jurisdictions with less strict or non-existent reproductive laws are continuing to use MRT in the clinical context, the need to address the underlying ethical issues surrounding MRT’s clinical translation is fundamental.
A long-term mass-balance reconstruction (1974–2021) and a decadal in situ mass-balance record (2011–2021) of Rikha Samba Glacier, central Himalaya
Authors: Gurung Tika Ram , Kayastha Rijan Bhakta , Fujita Koji , Joshi Sharad Prasad , Sinisalo Anna , Kirkham James D.
Published: November 2022

Despite their importance for regional water resource planning and as indicators of climate change, records of in situ glacier mass balance remain short and spatially sparse in the Himalaya. Here, we present an updated series of in situ mass-balance measurements from Rikha Samba Glacier, Nepal, between 2011 and 2021. The updated in situ mass balance is −0.39 ± 0.32 m w.e. for this period. We use an energy-mass balance model to extend the annual mass-balance series back to 1974. The model is forced using daily meteorological variables from ERA5-Land reanalysis data that is linearly bias-corrected using observations from an automatic weather station situated near the glacier terminus. The modeled mass balance is consistent with the in situ mass-balance series measured 2011–2021 and with previous glaciological and geodetic estimates. The model results indicate a mass balance of −0.56 ± 0.27 m w.e. a−1over the reconstruction period of 1974–2021, which is comparable to the mass losses experienced by other Himalayan glaciers during this time. An assessment of the sensitivity of the glacier mass balance to meteorological forcing suggests that a change in temperature of ±1 K has a stronger effect on the calculated mass balance compared to a ±20% change in either precipitation, or relative humidity, or solar radiation.
Friedrichs extensions for Sturm–Liouville operators with complex coefficients and their spectra
Authors: Zheng Zhaowen , Qi Jiangang , Shao Jing
Published: November 2022

In this paper, we study the Friedrichs extensions of Sturm–Liouville operators with complex coefficients according to the classification of B. M. Brown et al. [3]. We characterize the Friedrichs extensions both by boundary conditions at regular endpoint and asymptotic behaviours of elements in the maximal operator domains at singular endpoint. Some of spectral properties are also involved.
Power-transfer and fixed-point analysis of sawtooth simulations of a current-carrying stellarator
Authors: López O.E. , Howell E.C. , Hanson J.D. , Maurer D.A.
Published: November 2022

Power-transfer and fixed-point analysis of previous NIMROD simulations (Roberds et al., Phys. Plasmas, vol. 23, issue 9, 2016, 092513) improved the understanding of the effect of 3D (non-axisymmetric equilibrium) magnetic fields on sawtooth oscillations in the Compact Toroidal Hybrid (CTH) experiment. Computing the locations of order-1 fixed points, their Greene's residues, and local values for the rotational transform results in a description of CTH sawteeth consistent with Kadomtsev's model. A power-transfer analysis quantifies the distribution of energy among toroidal Fourier modes and their nonlinear interactions. The Lorentz power transfer drives sawtooth growth, and it is unambiguously interpreted as the flow of energy from toroidal mode

$n'$

to mode

$n$

, catalysed by

$\boldsymbol {B}_{n-n'}$

. It has been reported previously that the CTH sawtooth frequency increases with the 3D field strength. This is attributed to an increased growth rate of the internal kink that drives sawtooth oscillations. Here, 3D fields remove energy from the kink, eliminating the possibility that these fields are an additional energy source that drives growth. Instead, 3D fields catalyse energy transfer from large-to-small scales, where magnetic reconnection is stronger. It is proposed that this energy transfer increases the reconnection rate at small scales, which is consistent with the increased growth rate observed at higher 3D field strengths.
On the control of electron heating for optimal laser radiation pressure ion acceleration
Authors: Chou H.-G. Jason , Grassi Anna , Glenzer Siegfried H. , Fiuza Frederico
Published: November 2022

We study the onset of electron heating in intense laser–solid interactions and its impact on the spectral quality of radiation pressure accelerated ions in both hole boring and light sail regimes. Two- and three-dimensional particle-in-cell (PIC) simulations are performed over a wide range of laser and target parameters and reveal how the pulse duration, profile, polarization and target surface stability control the electron heating, the dominant ion acceleration mechanisms and the ion spectra. We find that the onset of strong electron heating is associated with the growth of the Rayleigh–Taylor-like instability at the front surface and must be controlled to produce high-quality ion beams, even when circularly polarized lasers are employed. We define a threshold condition for the maximum duration of the laser pulse that allows mitigation of electron heating and radiation pressure acceleration of narrow energy spread ion beams. The model is validated by three-dimensional PIC simulations, and the few experimental studies that reported low energy spread radiation pressure accelerated ion beams appear to meet the derived criteria. The understanding provided by our work will be important in guiding future experimental developments, for example for the ultrashort laser pulses becoming available at state-of-the-art laser facilities, for which we predict that proton beams with

$\sim$

150–250 MeV,

$\sim$

30% energy spread, and a total laser-to-proton conversion efficiency of

$\sim$

20% can be produced.
Not just a hijack: Imaginary worlds can enhance individual and group-level fitness
Authors: Wilbanks Danica , Moon Jordan W. , Stewart Brent , Gray Kurt , Varnum Michael E. W.
Published: November 2022

Why has fiction been so successful over time? We make the case that fiction may have properties that enhance both individual and group-level fitness by (a) allowing risk-free simulation of important scenarios, (b) effectively transmitting solutions to common problems, and (c) enhancing group cohesion through shared consumption of fictive worlds.
Why do people create imaginary worlds? The case of Fanfiction
Authors: Rodríguez-Fuentes Bárbara , Ulloa José Luis
Published: November 2022

Dubourg and Baurmard ask why people consume fiction with imaginary worlds. We extend this inquiry to ask why people engage in creating imaginary worlds. In Fanfiction, the writing of fiction by fans involves both an immersive creative experience and a very interactive community that may explain the high (social) engagement of people with Fanfiction.
Imaginary worlds are awesome: Awe provides a key to understanding the individual and social functions of imaginary worlds
Authors: Goldy Sean P. , Piff Paul K.
Published: November 2022

Awe arises when one experiences something so extraordinary that it defies current understanding, prompting efforts to comprehend the initially incomprehensible. We situate awe within Dubourg and Baumard's framework for the prevalence and psychological underpinnings of imaginary worlds. We argue that imaginary worlds are powerful catalysts of awe, which, in turn, drive important individual and social outcomes.
Imaginary worlds through the evolutionary lens: Ultimate functions, proximate mechanisms, cultural distribution
Authors: Dubourg Edgar , Baumard Nicolas
Published: November 2022

We received several commentaries both challenging and supporting our hypothesis. We thank the commentators for their thoughtful contributions, bringing together alternative hypotheses, complementary explanations, and appropriate corrections to our model. Here, we explain further our hypothesis, using more explicitly the framework of evolutionary social sciences. We first explain what we believe is the ultimate function of fiction in general (i.e., entertainment) and how this hypothesis differs from other evolutionary hypotheses put forward by several commentators. We then turn to the proximate features that make imaginary worlds entertaining and, therefore, culturally successful. We finally explore how these insights may explain the distribution of imaginary worlds across time, space, age, and social classes.
The Making of Natural Infrastructure in China's Era of Ecological Civilization
Authors: Yeh Emily T.
Published: November 2022

Campaign-style environmental enforcement that involves the destruction of infrastructure has become increasingly common. Scholars have theorized such crackdowns as a form of bureaucratic control. These explanations are compelling, yet incomplete. This paper adopts an infrastructural lens to call attention to the fact of infrastructural demolition. I argue that the reduction of existing infrastructure to rubble is a way of clearing space for other kinds of infrastructure, specifically natural infrastructure, which has become central in the pursuit of ecological civilization. The creation of natural infrastructure requires calculative tools, which work to obscure the profoundly political nature of the natural infrastructure that they create through spatial zoning, ecological functional zoning and ecological conservation red lines (ECRLs). The article then scales down to two case studies of villages in post-earthquake Sichuan that are within ECRLs and designated for the function of providing ecosystem services. In both, infrastructure within scenic areas that was previously encouraged by the state and central to village livelihoods was suddenly destroyed following ecological civilization enforcement campaigns. The arrival of natural infrastructure marks a national-scale infrastructural time that promises a new future in which village-controlled scenic areas have no part, leading to a ruination of their imagined futures.
Temporal differences in snail diversity responses to wildfires and salvage logging
Authors: Puig-Gironès Roger , Santos Xavier , Bros Vicenç
Published: November 2022

Species tend to peak in abundance at different times after fires. Over time, species richness (α) and landscape heterogeneity are prone to increase and lead to greater between-site diversity (β). However, post-fire salvage logging can reduce β-diversity, both directly and through its influence on succession. The as-yet understudied response of land snails to long-term habitat modification after wildfires and forest management is important for decision-making in forest restoration and conservation. We expected to detect differences in land snails and diversity in both the short and long term and between treatments in a natural park in the Mediterranean Basin. However, our results showed that post-fire management was a non-significant variable for snail community diversity, the exception being open-habitat endemic species. Plant succession and leaf litter cover were the main variables that shaped snail diversity and abundance over time after fires. Eighteen years after a fire, the land snail diversity had improved and the community composition had diversified, irrespective of the post-fire treatment, but threatened species disappeared and the total snail numbers had notably declined. To preserve threatened open-habitat species, prescribed fires and livestock grazing are recommended in combination with mature areas that can act as shelters where forest snails can recover from future disturbances.
Mathematical model and stability analysis on the transmission dynamics of skin sores
Authors: Fantaye Abayneh Kebede , Goshu Masitawal Demsie , Zeleke Berhanu Belay , Gessesse Adane Abebaw , Endalew Mehari Fentahun , Birhanu Zerihun Kinfe
Published: November 2022

In this study, a non-linear deterministic model for the transmission dynamics of skin sores (impetigo) disease is developed and analysed by the help of stability of differential equations. Some basic properties of the model including existence and positivity as well as boundedness of the solutions of the model are investigated. The disease-free and endemic equilibrium were investigated, as well as the basic reproduction number, R0, also calculated using the next-generation matrix approach. When R0 < 1, the model's stability analysis reveals that the system is asymptotically stable at disease-free critical point globally as well as locally. If R0 > 1, the system is asymptotically stable at disease-endemic equilibrium both locally and globally. The long-term behaviour of the skin sores model's steady-state solution in a population is investigated using numerical simulations of the model.
Fear of Dementia and the Obligation to Provide Aggregate Research Results to Study Participants
Authors: Graham Mackenzie , Farina Francesca , Ritchie Craig W. , Lawlor Brian , Naci Lorina
Published: November 2022

A general obligation to make aggregate research results available to participants has been widely supported in the bioethics literature. However, dementia research presents several challenges to this perspective, particularly because of the fear associated with developing dementia. The authors argue that considerations of respect for persons, beneficence, and justice fail to justify an obligation to make aggregate research results available to participants in dementia research. Nevertheless, there are positive reasons in favor of making aggregate research results available; when the decision is made to do so, it is critical that a clear strategy for communicating results is developed, including what support will be provided to participants receiving aggregate research results.
‘Propitious contrast’: Romanian borrowing in a Balkan mirror, 1878–1913
Authors: Maerean Andreea-Alexandra , Pedersen Maja , Sharp Paul
Published: November 2022

How was Romania able to borrow cheaply on the international capital markets before World War I? We explore this within the context of its three southeast European neighbours, Bulgaria, Greece and Serbia, using a novel dataset of monthly bond prices from the Berlin and London stock exchanges. A comparison of country characteristics and panel data analysis suggests that Romania was able to borrow under more favourable conditions due to its abundant natural resources and desirable exports.
The most stable it'severbeen: the preterit/present perfect alternation in spoken Ontario English
Authors: FRANCO KARLIEN , TAGLIAMONTE SALI A.
Published: November 2022

English tense/aspect-marking is an area where variation abounds and where many theories have been formulated. Diachronic studies of the preterit/present perfect alternation indicate that the present perfect (e.g.I have eaten already) has been losing ground to the preterit (e.g.I ate already) (e.g. Elsness 1997, but see Hundt & Smith 2009, Werner 2014). However, few studies have examined this alternation in vernacular speech. This article fills this lacuna by analyzing spoken data from Ontario, Canada, from an apparent-time perspective. Using a large archive of multiple communities and people of different generations, we focus on linguistic contexts known to be variable, viz. with adverbs of indefinite time. Results indicate that, in contrast with previous studies, the alternation is mostly stable. We find evidence of change only with the adverbever. Where there is evidence of change, this change is different from the predictions in the literature, with the preterit increasing in frequency. We suggest that a minor constructionalization process operates in tandem with ongoing specialization of the preterit/present perfect contrast. Taken together, these results provide another example of the importance of including speech in research on language variation and change and of the unique contribution certain constructions make to more general systems of grammar.
Understanding the Drivers of Coastal Flood Exposure and Risk From 1860 to 2100
Authors: Lincke Daniel , Hinkel Jochen , Mengel Matthias , Nicholls Robert J.
Published: November 2022

Global coastal flood exposure (population and assets) has been growing since the beginning of the industrial age and is likely to continue to grow through 21st century. Three main drivers are responsible: (a) climate‐related mean sea‐level change, (b) vertical land movement contributing to relative sea‐level rise, and (c) socio‐economic development. This paper attributes growing coastal exposure and flood risk from 1860 to 2100 to these three drivers. For historic flood exposure (1860–2005) we find that the roughly six‐fold increase in population exposure and 53‐fold increase in asset exposure are almost completely explained by socio‐economic development (>97% for population and >99% for assets). For future exposure (2005–2100), assuming a middle‐of‐the‐road regionalized socio‐economic scenario (SSP2) without coastal migration and sea‐level rise according to RCP2.6 and RCP6.0, climate‐change induced sea‐level rise will become the most important driver for the growth in population exposure, while growth in asset exposure will still be mainly determined by socio‐economic development.
Multivariate Statistical Analysis of Hydrochemical and Microbiological Natural Tracers as a Tool for Understanding Karst Hydrodynamics (The Unica Springs, SW Slovenia)
Authors: Ćuk Đurović Marina , Petrič Metka , Jemcov Igor , Mulec Janez , Grudnik Zdenka Mazej , Mayaud Cyril , Blatnik Matej , Kogovšek Blaž , Ravbar Nataša
Published: November 2022

Various multivariate statistical techniques (MST) can provide valuable insights into water quality variability. Despite numerous studies in which these methods have been used, their potential has not been fully exploited. This paper presents an improved approach to better understand the hydrodynamics of karst systems. The integrated application of hierarchical cluster and principal component analysis in combination with factor analysis allowed the construction of an advanced multivariate chemograph. The analytical procedure was applied in a binary karst aquifer known for its complex hydrodynamics and mixing of water with similar hydrochemical composition. In addition, the study area provides access to an integral groundwater flow system (ponor‐cave‐spring) and offers extensive prior hydrogeological knowledge. The approach allowed reduction and discrimination of the main parameters affecting water quality characteristics. Their identification enabled recognition of three predominant recharge components: (a) stored water impact with Cl and electrical conductivity, (b) sinking stream impact with turbidity and bacteria composition and (c) karst aquifer impact with Ca/Mg ratio as principal parameters. The results supported innovative characterization of the dominant processes and isolation of temporal hydrodynamic phases of individual monitoring points within the aquifer system. On this basis, a spatio‐temporal conceptual model was developed and the hydrodynamic behavior of the main springs was revealed. The applied methodology demonstrated to be useful in ascertaining functioning of a complex karst system under flood event conditions.
Downward Trend in Methane Detected in a Northern Colorado Oil and Gas Production Region Using AIRS Satellite Data
Authors: Reddy P. J. , Taylor C.
Published: November 2022

The oil and gas (O&G) sector is estimated to be the largest contributor to anthropogenic methane (CH4) emissions in Colorado. Since 2004, the State of Colorado has implemented multiple regulations to significantly reduce emissions from the O&G sector. The Denver‐Julesburg Basin (DJ Basin) is a significant O&G producing region in northern Colorado, and O&G production here has steadily increased over the last decade. To assess CH4 trends in Northern Colorado, we selected CH4 retrievals from the NASA Atmospheric Infrared Sounder (AIRS) instrument for 2003–2020. The study grid cell includes Denver, Boulder, and much of the dense O&G production in the DJ Basin. We computed mean June‐August ascending node AIRS 700 hPa CH4 for each year and subtracted mean June–August CH4 sampled at NOAA's Niwot Ridge (NWR) station, a high‐altitude background site. Differences represent estimated enhancement over background. Linear regression shows an annual change of −2.84 ppb ± 0.8 ppb from 2012 to 2020 (R2 0.90) and an estimated reduction of 56% for 2012–2020, despite substantial increases in O&G production. Local CH4 enhancement is strongly correlated with surface measurements of ethane at Platteville which is in the center of the O&G fields (correlation coefficient 0.96), and this is evidence that reductions in O&G emissions are driving reductions in CH4. We conclude that AIRS CH4 can be used to measure the efficacy of emissions control programs in this region and that regulatory requirements are having an effect.
Future Changes in Tropical Cyclone Exposure and Impacts in Southeast Asia From CMIP6 Pseudo‐Global Warming Simulations
Authors: Tran Thao Linh , Ritchie Elizabeth A. , Perkins‐Kirkpatrick Sarah E. , Bui Hai , Luong Thang M.
Published: November 2022

In this Pseudo‐global Warming study, potential future changes in the Southeast Asia tropical cyclone (TC) exposure climatology are quantified. One hundred and seventeen landfalling TCs in the last 20 years are simulated with their current climate conditions and also with the Coupled Model Intercomparison Project Phase 6 (CMIP6) ensemble perturbed conditions under the SSP2‐4.5 and SSP3‐7.0 climate change scenarios. Our simulations suggest that landfalling TCs are projected to be 8% more intense at landfall, 2.8% faster and have smaller sizes by the end of the 21st century under the SSP3‐7.0 scenario. In addition, TC landfall locations shift northward with tracks extending further inland toward Laos and Thailand. In particular, TC exposures, wind and rainfall impacts significantly increase in the northern Philippines, Taiwan, southwestern coast of China, and northern Vietnam; and significantly decrease in the southern areas of Southeast Asia and the southeastern coast of China.
Improved Delineation of Urban Hydrological Processes in Coupled Regional Climate Models
Authors: Yu Miao , Wu Huan , Yin Jinfang , Liang Xudong , Miao Shiguang
Published: November 2022

As the resolution of global and regional numerical weather prediction (NWP) models increases, urban parameterizations are increasingly important because urbanization has significant impacts on the surface energy and water balance. However, NWP models tend to fail to accurately simulate the surface latent heat flux, with most urban canopy models lacking or oversimplifying urban hydrological and vegetation processes. In this study, we develop an urban hydrology scheme and couple it with WRF/BEP + BEM, which improves the regional model performance in urban areas at high resolution. The evaluation results show improved model accuracy not only for the surface latent heat flux but also for the air temperature and humidity. The vertical section analysis suggests that the urban hydrology scheme can have impacts on the boundary layer to a height of 1,000 m. Consequently, improved precipitation simulation causes reasonable prediction of urban surface water depth, which is valuable for early warning of waterlogging.
Observation of mechanical bound states in the continuum in an optomechanical microresonator
Authors: Yu Yue , Xi Xiang , Sun Xiankai
Published: November 2022

Bound states in the continuum (BICs) are a type of waves that are perfectly confined in the continuous spectrum of radiating waves without interaction with them. Here, we fabricated, with CMOS-compatible processes on a silicon chip, a wheel-shaped optomechanical microresonator, in which we experimentally observed the BIC in the micromechanical domain. The BIC results from destructive interference between two dissipative mechanical modes of the microresonator under broken azimuthal symmetry. Such BICs can be obtained from devices with large and robust supporting structures with variable sizes, which substantially reduces fabrication difficulty and allows for versatile application environments. Our results open a new way of phonon trapping in micromechanical structures with dissipation channels, and produce long phonon lifetimes that are desired in many mechanical applications such as mechanical oscillators, sensors, and quantum information processors.
Single-cell analyses reveal novel molecular signatures and pathogenesis in cutaneous T cell lymphoma
Authors: Xue Xiaotong , Wang Zhenzhen , Mi Zihao , Liu Tingting , Wang Chuan , Shi Peidian , Sun Lele , Yang Yongliang , Li Wenchao , Wang Zhe , Liu Hong , Zhang Furen
Published: November 2022

Sézary syndrome (SS) is a rare and aggressive type of cutaneous T cell lymphoma (CTCL) with a poor prognosis. Intra-tumoral heterogeneity caused by different disease compartments (e.g., skin, blood) and poor understanding of the pathogenesis has created obstacles to the precise diagnosis and targeted treatment of the disease. Here we performed a comprehensive analysis by integrating single-cell transcriptomic data of 40,333 peripheral blood mononuclear cells (PBMCs) and 41,580 skin cells, as well as single-cell chromatin accessibility data of 11,058 PBMCs from an SS patient and matched healthy controls (HCs). Validation and functional investigation were carried out in an independent cohort consisting of SS patients, mycosis fungoides (MF) patients, psoriatic erythroderma patients, and HCs, as well as multiple cell lines. The analysis revealed that skin-derived Sézary cells (SCs) had a shifting trend to more advanced mature phenotypes compared to blood-derived SCs. A series of specific marker genes (TOX, DNM3, KLHL42, PGM2L1, and SESN3) shared in blood- and skin-derived SCs were identified, facilitating the diagnosis and prognosis of MF/SS. Moreover, luciferase reporter assays and gene knockdown assays were used to verify that KLHL42 was transcriptionally activated by GATA3 in SS. Functional assays indicated that KLHL42 silencing significantly inhibited aggressive CTCL cell proliferation and promoted its apoptosis. Therefore, targeting inhibition KLHL42 might serve as a promising therapeutic approach in CTCL.
JUND/linc00976 promotes cholangiocarcinoma progression and metastasis, inhibits ferroptosis by regulating the miR-3202/GPX4 axis
Authors: Lei Shan , Cao Wenpeng , Zeng Zhirui , Zhang Zhixue , Jin Bangming , Tian Qianting , Wu Yingming , Zhang Tuo , Li Dahuan , Hu Chujiao , Lan Jinzhi , Zhang Jinjuan , Chen Tengxiang
Published: November 2022

Long noncoding RNAs (lncRNAs) are a novel class of noncoding RNAs that have emerged as critical regulators and biomarkers in various cancers. Nevertheless, the expression profile and mechanistic function of lncRNAs in cholangiocarcinoma (CCA) remain unclear. Herein, we examined the expression levels of linc00976 in clinical specimens and cell lines using reverse transcription-quantitative PCR. In total, 50 patients with CCA were enrolled to analyze the correlation between linc00976 expression and clinical characteristics of CCA. Loss- and gain-of-function experiments were performed to investigate the biological effects of linc00976 on proliferation, ferroptosis, migration, and invasion of CCA cells in vitro and in vivo. In situ hybridization, RNA immunoprecipitation, bioinformatic databases, RNA pull-down assay, a dual-luciferase reporter assay, mRNA sequencing, chromatin immunoprecipitation–PCR, and rescue experiments were performed to elucidate the underlying mechanisms of linc00976-induced competitive endogenous RNA regulatory networks. We characterized a novel and abundant lncRNA, linc00976, that functions as a pro-oncogenic regulator of CCA progression. Compared with normal controls, linc00976 was dramatically upregulated in CCA tissue samples and cell lines. Patients with CCA exhibiting high linc00976 expression had a highly advanced clinical stage, substantial lymph node metastasis, and poor overall survival. Knockdown of linc00976 significantly repressed proliferation and metastasis and promoted ferroptosis of CCA cells both in vitro and in vivo, whereas linc00976 overexpression exerted the opposite effect. Mechanistically, linc00976 competitively interacted with miR-3202 to upregulate GPX4 expression, thus contributing to the malignant biological behavior of CCA cells. Moreover, we demonstrated that JUND specifically interacts with the linc00976 promoter and activates linc00976 transcription. Accordingly, JUND promotes linc00976 transcription, and linc00976 plays a crucial role in accelerating CCA tumorigenesis and metastasis and inhibiting ferroptosis by modulating the miR-3202/GPX4 axis. These findings suggest that targeting linc00976 may afford a promising therapeutic strategy for patients with CCA.
An mTORC1 to HRI signaling axis promotes cytotoxicity of proteasome inhibitors in multiple myeloma
Authors: Darawshi Odai , Muz Barbara , Naamat Shiri Gershon , Praveen Bellam , Mahameed Mohamed , Goldberg Karin , Dipta Priya , Shmuel Miriam , Forno Francesca , Boukeileh Shatha , Pahima Hadas , Hermann Julia , Raab Marc S. , Poos Alexandra M. , Weinhold Niels , Rosenbluh Chaggai , Gatt Moshe E. , Palm Wilhelm , Azab Abdel Kareem , Tirosh Boaz
Published: November 2022

Multiple myeloma (MM) causes approximately 20% of deaths from blood cancers. Notwithstanding significant therapeutic progress, such as with proteasome inhibitors (PIs), MM remains incurable due to the development of resistance. mTORC1 is a key metabolic regulator, which frequently becomes dysregulated in cancer. While mTORC1 inhibitors reduce MM viability and synergize with other therapies in vitro, clinically, mTORC1 inhibitors are not effective for MM. Here we show that the inactivation of mTORC1 is an intrinsic response of MM to PI treatment. Genetically enforced hyperactivation of mTORC1 in MM was sufficient to compromise tumorigenicity in mice. In vitro, mTORC1-hyperactivated MM cells gained sensitivity to PIs and hypoxia. This was accompanied by increased mitochondrial stress and activation of the eIF2α kinase HRI, which initiates the integrated stress response. Deletion of HRI elevated the toxicity of PIs in wt and mTORC1-activated MM. Finally, we identified the drug PMA as a robust inducer of mTORC1 activity, which synergized with PIs in inducing MM cell death. These results help explain the clinical inefficacy of mTORC1 inhibitors in MM. Our data implicate mTORC1 induction and/or HRI inhibition as pharmacological strategies to enhance MM therapy by PIs.
Heme-deficient metabolism and impaired cellular differentiation as an evolutionary trade-off for human infectivity in Trypanosoma brucei gambiense
Authors: Horáková Eva , Lecordier Laurence , Cunha Paula , Sobotka Roman , Changmai Piya , Langedijk Catharina J. M. , Abbeele Jan Van Den , Vanhollebeke Benoit , Lukeš Julius
Published: November 2022

Resistance to African trypanosomes in humans relies in part on the high affinity targeting of a trypanosome lytic factor 1 (TLF1) to a trypanosome haptoglobin-hemoglobin receptor (HpHbR). While TLF1 avoidance by the inactivation of HpHbR contributes to Trypanosoma brucei gambiense human infectivity, the evolutionary trade-off of this adaptation is unknown, as the physiological function of the receptor remains to be elucidated. Here we show that uptake of hemoglobin via HpHbR constitutes the sole heme import pathway in the trypanosome bloodstream stage. T. b. gambiense strains carrying the inactivating mutation in HpHbR, as well as genetically engineered T. b. brucei HpHbR knock-out lines show only trace levels of intracellular heme and lack hemoprotein-based enzymatic activities, thereby providing an uncommon example of aerobic parasitic proliferation in the absence of heme. We further show that HpHbR facilitates the developmental progression from proliferating long slender forms to cell cycle-arrested stumpy forms in T. b. brucei. Accordingly, T. b. gambiense was found to be poorly competent for slender-to-stumpy differentiation unless a functional HpHbR receptor derived from T. b. brucei was genetically restored. Altogether, we identify heme-deficient metabolism and disrupted cellular differentiation as two distinct HpHbR-dependent evolutionary trade-offs for T. b. gambiense human infectivity.
Donor-strand exchange drives assembly of the TasA scaffold in Bacillus subtilis biofilms
Authors: Böhning Jan , Ghrayeb Mnar , Pedebos Conrado , Abbas Daniel K. , Khalid Syma , Chai Liraz , Bharat Tanmay A. M.
Published: November 2022

Many bacteria in nature exist in multicellular communities termed biofilms, where cells are embedded in an extracellular matrix that provides rigidity to the biofilm and protects cells from chemical and mechanical stresses. In the Gram-positive model bacteriumBacillus subtilis, TasA is the major protein component of the biofilm matrix, where it has been reported to form functional amyloid fibres contributing to biofilm structure and stability. Here, we present electron cryomicroscopy structures of TasA fibres, which show that, rather than forming amyloid fibrils, TasA monomers assemble into fibres through donor-strand exchange, with each subunit donating a β-strand to complete the fold of the next subunit along the fibre. Combining electron cryotomography, atomic force microscopy, and mutational studies, we show how TasA fibres congregate in three dimensions to form abundant fibre bundles that are essential forB. subtilisbiofilm formation. Our study explains the previously observed biochemical properties of TasA and shows how a bacterial extracellular globular protein can assemble from monomers into β-sheet-rich fibres, and how such fibres assemble into bundles in biofilms.
Centromere defects, chromosome instability, and cGAS-STING activation in systemic sclerosis
Authors: Paul Souren , Kaplan Mark H. , Khanna Dinesh , McCourt Preston M. , Saha Anjan K. , Tsou Pei-Suen , Anand Mahek , Radecki Alexander , Mourad Mohamad , Sawalha Amr H. , Markovitz David M. , Contreras-Galindo Rafael
Published: November 2022

Centromere defects in Systemic Sclerosis (SSc) have remained unexplored despite the fact that many centromere proteins were discovered in patients with SSc. Here we report that lesion skin fibroblasts from SSc patients show marked alterations in centromeric DNA. SSc fibroblasts also show DNA damage, abnormal chromosome segregation, aneuploidy (only in diffuse cutaneous (dcSSc)) and micronuclei (in all types of SSc), some of which lose centromere identity while retaining centromere DNA sequences. Strikingly, we find cytoplasmic “leaking” of centromere proteins in limited cutaneous SSc (lcSSc) fibroblasts. Cytoplasmic centromere proteins co-localize with antigen presenting MHC Class II molecules, which correlate precisely with the presence of anti-centromere antibodies. CENPA expression and micronuclei formation correlate highly with activation of the cGAS-STING/IFN-β pathway as well as markers of reactive oxygen species (ROS) and fibrosis, ultimately suggesting a link between centromere alterations, chromosome instability, SSc autoimmunity, and fibrosis.
Pre-equilibrium biosensors as an approach towards rapid and continuous molecular measurements
Authors: Maganzini Nicolò , Thompson Ian , Wilson Brandon , Soh Hyongsok Tom
Published: November 2022

Almost all biosensors that use ligand-receptor binding operate under equilibrium conditions. However, at low ligand concentrations, the equilibration with the receptor (e.g., antibodies and aptamers) becomes slow and thus equilibrium-based biosensors are inherently limited in making measurements that are both rapid and sensitive. In this work, we provide a theoretical foundation for a method through which biosensors can quantitatively measure ligand concentration before reaching equilibrium. Rather than only measuring receptor binding at a single time-point, the pre-equilibrium approach leverages the receptor’s kinetic response to instantaneously quantify the changing ligand concentration. Importantly, by analyzing the biosensor output in frequency domain, rather than in the time domain, we show the degree to which noise in the biosensor affects the accuracy of the pre-equilibrium approach. Through this analysis, we provide the conditions under which the signal-to-noise ratio of the biosensor can be maximized for a given target concentration range and rate of change. As a model, we apply our theoretical analysis to continuous insulin measurement and show that with a properly selected antibody, the pre-equilibrium approach could make the continuous tracking of physiological insulin fluctuations possible.
Biasing the conformation of ELMO2 reveals that myoblast fusion can be exploited to improve muscle regeneration
Authors: Tran Viviane , Nahlé Sarah , Robert Amélie , Desanlis Inès , Killoran Ryan , Ehresmann Sophie , Thibault Marie-Pier , Barford David , Ravichandran Kodi S. , Sauvageau Martin , Smith Matthew J. , Kmita Marie , Côté Jean-François
Published: November 2022

Myoblast fusion is fundamental for the development of multinucleated myofibers. Evolutionarily conserved proteins required for myoblast fusion include RAC1 and its activator DOCK1. In the current study we analyzed the contribution of the DOCK1-interacting ELMO scaffold proteins to myoblast fusion. When Elmo1−/− mice underwent muscle-specific Elmo2 genetic ablation, they exhibited severe myoblast fusion defects. A mutation in the Elmo2 gene that reduced signaling resulted in a decrease in myoblast fusion. Conversely, a mutation in Elmo2 coding for a protein with an open conformation increased myoblast fusion during development and in muscle regeneration. Finally, we showed that the dystrophic features of the Dysferlin-null mice, a model of limb-girdle muscular dystrophy type 2B, were reversed when expressing ELMO2 in an open conformation. These data provide direct evidence that the myoblast fusion process could be exploited for regenerative purposes and improve the outcome of muscle diseases.
Structural basis for the inactivation of cytosolic DNA sensing by the vaccinia virus
Authors: Rivera-Calzada Angel , Arribas-Bosacoma Raquel , Ruiz-Ramos Alba , Escudero-Bravo Paloma , Boskovic Jasminka , Fernandez-Leiro Rafael , Oliver Antony W. , Pearl Laurence H. , Llorca Oscar
Published: November 2022

Detection of cytosolic DNA is a central element of the innate immunity system against viral infection. The Ku heterodimer, a component of the NHEJ pathway of DNA repair in the nucleus, functions as DNA sensor that detects dsDNA of viruses that replicate in the cytoplasm. Vaccinia virus expresses two proteins, C4 and C16, that inactivate DNA sensing and enhance virulence. The structural basis for this is unknown. Here we determine the structure of the C16 – Ku complex using cryoEM. Ku binds dsDNA by a preformed ring but C16 sterically blocks this access route, abrogating binding to a dsDNA end and its insertion into DNA-PK, thereby averting signalling into the downstream innate immunity system. C4 replicates these activities using a domain with 54% identity to C16. Our results reveal how vaccinia virus subverts the capacity of Ku to recognize viral DNA.
Enantioselective Ugi and Ugi-azide reactions catalyzed by anionic stereogenic-at-cobalt(III) complexes
Authors: Sun Bing-Bing , Liu Kun , Gao Quan , Fang Wei , Lu Shuang , Wang Chun-Ru , Yao Chuan-Zhi , Cao Hai-Qun , Yu Jie
Published: November 2022

Ugi reactions and related variations are proven to be atom and step-economic strategies for construction of highly valuable peptide-like skeletons and nitrogenous heterocycles. The development of structurally diverse range of novel catalytic systems and the discovery of new approaches to accommodate a broader scope of terminating reagents for asymmetric Ugi four-component reaction is still in high demand. Here, we report a strategy that enables enantioselective Ugi four-component and Ugi-azide reactions employing anionic stereogenic-at-cobalt(III) complexes as catalysts. The key nitrilium intermediates, generated through the nucleophilic addition of isocyanides to the chiral ion-pair which consists of stereogenic-at-cobalt(III) complexes counteranion and a protonated iminium, are trapped by either carboxylic acids or in situ-generated hydrazoic acid, delivering α-acylamino amides and α-aminotetrazoles in good to excellent enantioselectivities (up to 99:1 e.r.).
Implications of oral streptococcal bacteriophages in autism spectrum disorder
Authors: Tong Zhan , Zhou Xin , Chu Yanan , Zhang Tianxu , Zhang Jie , Zhao Xiaoyan , Wang Zuqun , Ding Rui , Meng Qingren , Yu Jun , Wang Juan , Kang Yu
Published: November 2022

Growing evidence suggests altered oral and gut microbiota in autism spectrum disorder (ASD), but little is known about the alterations and roles of phages, especially within the oral microbiota in ASD subjects. We enrolled ASD (n = 26) and neurotypical subjects (n = 26) with their oral hygiene controlled, and the metagenomes of both oral and fecal samples (n = 104) are shotgun-sequenced and compared. We observe extensive and diverse oral phageome comparable to that of the gut, and clear signals of mouth-to-gut phage strain transfer within individuals. However, the overall phageomes of the two sites are widely different and show even less similarity in the oral communities between ASD and control subjects. The ASD oral phageome exhibits significantly reduced abundance and alpha diversity, but the Streptococcal phages there are atypically enriched, often dominating the community. The over-representation of Streptococcal phages is accompanied by enriched oral Streptococcal virulence factors and Streptococcus bacteria, all exhibiting a positive correlation with the severity of ASD clinical manifestations. These changes are not observed in the parallel sampling of the gut flora, suggesting a previously unknown oral-specific association between the excessive Streptococcal phage enrichment and ASD pathogenesis. The findings provide new evidence for the independent microbiome-mouth-brain connection, deepen our understanding of how the growth dynamics of bacteriophages and oral microbiota contribute to ASD, and point to novel effective therapeutics.