bluuebunny/crossref_metadata_2025 huggingface dataset:
Simultaneous Bayesian Estimation of Non‐Planar Fault Geometry and Spatially‐Variable Slip
Authors: Dutta Rishabh , Jónsson Sigurjón , Vasyura‐Bathke Hannes
Published: June 2021

Large earthquakes are usually modeled with simple planar fault surfaces or a combination of several planar fault segments. However, in general, earthquakes occur on faults that are non‐planar and exhibit significant geometrical variations in both the along‐strike and down‐dip directions at all spatial scales. Mapping of surface fault ruptures and high‐resolution geodetic observations are increasingly revealing complex fault geometries near the surface and accurate locations of aftershocks often indicate geometrical complexities at depth. With better geodetic data and observations of fault ruptures, more details of complex fault geometries can be estimated resulting in more realistic fault models of large earthquakes. To address this topic, we here parametrize non‐planar fault geometries with a set of polynomial parameters that allow for both along‐strike and down‐dip variations in the fault geometry. Our methodology uses Bayesian inference to estimate the non‐planar fault parameters from geodetic data, yielding an ensemble of plausible models that characterize the uncertainties of the non‐planar fault geometry and the fault slip. The method is demonstrated using synthetic tests considering slip spatially distributed on a single continuous finite non‐planar fault surface with varying dip and strike angles both in the down‐dip and along‐strike directions. The results show that fault‐slip estimations can be biased when a simple planar fault geometry is assumed in presence of significant non‐planar geometrical variations. Our method can help to model earthquake fault sources in a more realistic way and may be extended to include multiple non‐planar fault segments or other geometrical fault complexities.
Monsoon‐Facilitated Off‐Shelf Transport of Dissolved Aluminum Across the East China Sea During Summer
Authors: Wang Zhaowei , Xuan Jiliang , Li Faming , Ren Jingling , Huang Daji , Zhang Jing
Published: June 2021

The continental shelf pump is believed to be important in transporting terrestrial materials across the East China Sea (ECS). More than 300 water samples collected from the ECS and a numerical model were used to identify the cross‐shelf exchanges of dissolved aluminum (Al) in the ECS in summer. The results indicated that dissolved Al concentrations ranged from <1.0 to 242 nM, with the highest concentrations observed in the Zhe‐Min coastal waters, while the lowest concentrations were determined to be in Kuroshio deep waters. The Kuroshio surface waters receive additional dissolved Al from the ECS continental shelf through a cross‐shelf exchange process. By using dissolved Al as a tracer, evidence was found about the cross‐shelf transport of Al in the ECS. Cross‐shelf transport of dissolved Al was associated with fluctuations in the Taiwan Strait Warm Water, and the driving mechanisms were analyzed using a momentum equation. Ekman transport promoted by the summer monsoon was the key physical mechanism controlling the off‐shelf transport of dissolved Al. Quantitative calculations showed that the ECS was a net source of dissolved Al to adjacent waters, of which almost 65% of the output entered the East/Japan Sea, while the remaining 35% entered the Kuroshio currents. Our results highlight the importance of cross‐shelf transport processes to the distribution and cycling of biogenic elements within the marginal seas of China, and highlight the wider implications for biogeochemical cycles throughout the western Pacific Ocean.
Characterization of the Multicellular Membrane‐Bearing Algae From the Kuanchuanpu Biota (Cambrian: Terreneuvian)
Authors: Zheng Yajuan , Tang Qingqin , Liu Ping , Sun Jie , Yao Xiaoyong , Hao Wenjing , Yang Xiaoguang , Guo Junfeng , Uesugi Kentaro , Komiya Tsuyoshi , Han Jian
Published: June 2021

The diversity of small shelly fossils (SSFs) demonstrates that multicellular organisms underwent large‐scale radiation at the beginning of the Cambrian, which is highlighted by the coexistence of various metazoans and the occurrence of their embryo fossils. However, little is known about early Cambrian eukaryotic multicellular algae, the primary producers that replaced oxygenic cyanobacteria and played a crucial ecological role in matter cycling and energy dynamics in marine ecosystems. In this study, hundreds of microscopic three‐dimensionally preserved multicellular aggregate fossils were obtained from the Kuanchuanpu Formation (Cambrian: Terreneuvian, ca. 535 Ma) in southern Shaanxi, South China, which consisted of several tightly packed multicellular clumps encapsulated in a thin organic membrane. Synchrotron tomography analysis further revealed that the cells of the whole aggregate, although partitioned into different clumps by a gelatinous membrane, were distinctly differentiated into an outer conical cell layer and an inner spherical‐cell layer, thus suggesting of a cortex‐medulla‐like differentiation. These characteristics resemble those of multicellular algae (e.g.,Wengania,Gremiphyca, andThallophyca) from the Weng'an biota (Ediacaran, South China) in morphology, size, and internal cell structure. Furthermore, a potential asexual life cycle for these membranous algae was proposed based on their morphological and structural characteristics.
Investigating the Plate Kinematics of the Bay of Biscay Using Deformable Plate Tectonic Models
Authors: King Michael T. , Welford J. Kim , Cadenas Patricia , Tugend Julie
Published: June 2021

The plate kinematics of the Iberian plate and their implications on the plate tectonic evolution of the Bay of Biscay during rifting and subsequent opening of the southern North Atlantic continue to be topics of scientific discussion and debate. Constrained by previous plate reconstruction, geophysical, and geological studies, deformable plate tectonic reconstructions of the Bay of Biscay‐Parentis rift system are created in this study using the GPlates software. These deformable plate models are used to investigate the kinematics of the Landes High, Le Danois High, and Ebro Block previously recognized as independent continental blocks within deformable regions. A comparison between results calculated via deformable plate models with previously published and newly presented gravity inversion crustal thickness estimates provided a good metric for delineating the most probable plate kinematic scenario for the Bay of Biscay‐Parentis system and investigating the effect of the plate kinematic scenarios on the present‐day structure. The preferred plate kinematic model implies a transtensional Bay of Biscay‐Parentis rift system from the Jurassic to Early Cretaceous, with the onset of significant crustal thinning initiating during the Late Jurassic (∼150 Ma) induced by the motion of the Landes High and its interplay with the Ebro Block. Aside from demonstrating the role of the Landes High and its suggested interplay with structural inheritance on the deformation experienced within the Bay of Biscay, the timing and orientation of regional stress directions, and the velocities induced by the preferred deformable model provide good comparisons with previously calculated subsidence rates.
Regional Forecasting of Fine Particulate Matter Concentrations: A Novel Hybrid Model Based on Principal Component Regression and EOF
Authors: Wu Xianghua , Xie Kang , Liu Jane , Liu Duanyang , Zhou Jieqin , Tang Lili
Published: June 2021

When many cities need quantitative forecasts of air quality to adjust industrial production plans and urbanization development, how to build an efficient forecast model remain a challenge. Methodology for quantitative prediction of air quality can no longer rely on single‐site observations, and thus approaches that require fewer input data and are more efficient and more reliable need to be explored. This paper proposes the principles and steps of a new model using the empirical orthogonal function (EOF) and principal component regression (PCR), which is a hybrid EOF‐PCR approach that decomposes the panel data of PM2.5 and predictors into spatial structures (EOFs) and time expansion coefficients (ECs) by EOF analysis, establishes the PCR of the ECs of PM2.5, and simulates the PM2.5 concentrations in each city by projecting the fitted ECs through EOFs. The very heart of the new model is the PCR modeling and projection. The results are presented for PM2.5 concentrations over Jiangsu Province in eastern China. The results show that this EOF‐PCR model, which is based on EC1s with a cumulative variance contribution rate above 90%, has an average prediction accuracy of 65%. The model performs best in spring and autumn, better in summer and worst in winter. Most predictors have a maximum lag of a week, and they are quite different among seasons. Considering the influence of the spatial distributions of predictors, rather than covariates at a single site, this model can reflect regional influences and effectively improve the simulation effect.
Role of the Summer Monsoon Variability in the Collapse of the Ming Dynasty: Evidences From Speleothem Records
Authors: Zhao Jingyao , Cheng Hai , Yang Yan , Liu Wen , Zhang Haiwei , Li Xianglei , Li Hanying , Ait‐Brahim Yassine , Pérez‐Mejías Carlos , Qu Xiaoli
Published: June 2021

Climatic changes have played an important role in societal reorganizations. Particularly, the late 16th and early 17th century coincided with severely cold condition, extremely weak summer monsoon and widespread population decline in China. Here we present new speleothem oxygen isotope records across North and South China, which in concert with historical documents, allow us to characterize the “Late Ming Weak Monsoon Periods” (LMWMP) at an unprecedented annual temporal resolution. Our analysis suggests that as a weak summer monsoon event not seen for nearly 500 years in China, the LMWMP spatiotemporally coincided with the late Ming Dynasty peasant uprising (1627–1658 CE), and thus the transition from Ming to Qing Dynasty. This suggests a plausible role of climate change in shaping the important chapters of the Chinese history. In addition, both speleothem and historical documents reveal that the LMWMP appears to be a north to south time‐transgressive event on decadal‐timescale.
Electrostatic Solitary Waves in the Earth's Bow Shock: Nature, Properties, Lifetimes, and Origin
Authors: Wang R. , Vasko I. Y. , Mozer F. S. , Bale S. D. , Kuzichev I. V. , Artemyev A. V. , Steinvall K. , Ergun R. , Giles B. , Khotyaintsev Y. , Lindqvist P.‐A. , Russell C. T. , Strangeway R.
Published: June 2021

We present a statistical analysis of >2,100 bipolar electrostatic solitary waves (ESWs) collected from 10 quasi‐perpendicular Earth's bow shock crossings by Magnetospheric Multiscale spacecraft. We developed and implemented a correction procedure for reconstruction of actual electric fields, velocities, and other properties of ESW, whose spatial scales are typically comparable with or smaller than spatial distance between voltage‐sensitive probes. We found that more than 95% of the ESW are of negative polarity with amplitudes typically below a few Volts and 0.1Te (5–30 V or 0.1–0.3Te for a few percent of ESW), spatial scales of 10–100 m or λD–10λD, and velocities from a few tens to a few hundred km/s that is on the order of local ion‐acoustic speed. The spatial scales of ESW are correlated with local Debye length λD. The ESW have electric fields generally oblique to magnetic field and they propagate highly oblique to shock normal N; more than 80% of ESW propagate within 30° of the shock plane LM. In the shock plane, ESW typically propagates within a few tens of degrees of local magnetic field projection BLM and preferentially opposite to N × BLM. We argue that the ESW of negative polarity are ion holes produced by ion‐ion streaming instabilities. We estimate ion hole lifetimes to be 10–100 ms, or 1–10 km in terms of traveling distance. The revealed statistical properties will be useful for quantitative studies of electron thermalization in the Earth's bow shock.
Forward stimulated Brillouin scattering and opto-mechanical non-reciprocity in standard polarization maintaining fibres
Authors: Bashan Gil , Diamandi Hilel Hagai , London Yosef , Sharma Kavita , Shemer Keren , Zehavi Elad , Zadok Avi
Published: June 2021

Opto-mechanical interactions in guided wave media are drawing great interest in fundamental research and applications. Forward stimulated Brillouin scattering, in particular, is widely investigated in optical fibres and photonic integrated circuits. In this work, we report a comprehensive study of forward stimulated Brillouin scattering over standard, panda-type polarization maintaining fibres. We distinguish between intra-polarization scattering, in which two pump tones are co-polarized along one principal axis, and inter-polarization processes driven by orthogonally polarized pump waves. Both processes are quantified in analysis, calculations and experiment. Inter-modal scattering, in particular, introduces cross-polarization switching of probe waves that is non-reciprocal. Switching takes place in multiple wavelength windows. The results provide a first demonstration of opto-mechanical non-reciprocity of forward scatter in standard fibre. The inter-polarization process is applicable to distributed sensors of media outside the cladding and coating boundaries, where light cannot reach. The process may be scaled towards forward Brillouin lasers, optical isolators and circulators and narrowband microwave-photonic filters over longer sections of off-the-shelf polarization maintaining fibres.
Dynamics of amygdala connectivity in bipolar disorders: a longitudinal study across mood states
Authors: Rey Gwladys , Bolton Thomas A. W. , Gaviria Julian , Piguet Camille , Preti Maria Giulia , Favre Sophie , Aubry Jean-Michel , Van De Ville Dimitri , Vuilleumier Patrik
Published: June 2021

Alterations in activity and connectivity of brain circuits implicated in emotion processing and emotion regulation have been observed during resting-state for different clinical phases of bipolar disorders (BD), but longitudinal investigations across different mood states in the same patients are still rare. Furthermore, measuring dynamics of functional connectivity patterns offers a powerful method to explore changes in the brain’s intrinsic functional organization across mood states. We used a novel co-activation pattern (CAP) analysis to explore the dynamics of amygdala connectivity at rest in a cohort of 20 BD patients prospectively followed-up and scanned across distinct mood states: euthymia (20 patients; 39 sessions), depression (12 patients; 18 sessions), or mania/hypomania (14 patients; 18 sessions). We compared them to 41 healthy controls scanned once or twice (55 sessions). We characterized temporal aspects of dynamic fluctuations in amygdala connectivity over the whole brain as a function of current mood. We identified six distinct networks describing amygdala connectivity, among which an interoceptive-sensorimotor CAP exhibited more frequent occurrences during hypomania compared to other mood states, and predicted more severe symptoms of irritability and motor agitation. In contrast, a default-mode CAP exhibited more frequent occurrences during depression compared to other mood states and compared to controls, with a positive association with depression severity. Our results reveal distinctive interactions between amygdala and distributed brain networks in different mood states, and foster research on interoception and default-mode systems especially during the manic and depressive phase, respectively. Our study also demonstrates the benefits of assessing brain dynamics in BD.
Associations of body composition and physical fitness with gestational diabetes and cardiovascular health in pregnancy: Results from the HealthyMoms trial
Authors: Henriksson Pontus , Sandborg Johanna , Söderström Emmie , Leppänen Marja H. , Snekkenes Victoria , Blomberg Marie , Ortega Francisco B. , Löf Marie
Published: June 2021

The aim of this study was to examine associations of body composition (fat mass index, % fat mass, fat-free mass index, body mass index) and physical fitness (cardiorespiratory fitness and handgrip strength) with gestational diabetes and cardiovascular health in early pregnancy. This cross-sectional study utilized baseline data (n = 303) collected in early pregnancy from the HealthyMoms trial. Body composition was measured using air-displacement plethysmography, cardiorespiratory fitness was assessed by means of the 6-min walk test and handgrip strength using a dynamometer. Logistic regression was used to estimate odds ratios (ORs) for gestational diabetes as well as high (defined as 1 SD above the mean) blood pressure, homeostatic model assessment for insulin resistance (HOMA-IR), and metabolic syndrome score (MetS score) per 1 SD increase in body composition and fitness variables. Fat mass index, % fat mass and body mass index were all strongly associated with gestational diabetes (ORs: 1.72–2.14, P ≤ 0.003), HOMA-IR (ORs: 3.01–3.80, P < 0.001), blood pressure (ORs: 1.81–2.05, P < 0.001) and MetS score (ORs: 3.29–3.71, P < 0.001). Associations with fat-free mass index were considerably weaker (ORs: 1.26–1.82, P = 0.001–0.15) and were strongly attenuated after adjustments for fat mass index (ORs: 0.88–1.54, P = 0.039–0.68). Finally, greater cardiorespiratory fitness was associated with lower risk of high HOMA-IR and MetS score (ORs: 0.57–0.63, P  ≤ 0.004) although these associations were attenuated when accounting for fat mass index (ORs: 1.08-1.11, P ≥ 0.61). In conclusion, accurately measured fat mass index or % fat mass were strongly associated with gestational diabetes risk and markers of cardiovascular health although associations were not stronger than the corresponding ones for body mass index. Fat-free mass index had only weak associations with gestational diabetes and cardiovascular health which support that the focus during clinical care would be on excess fat mass and not fat-free mass.
The combination of CUDC-907 and gilteritinib shows promising in vitro and in vivo antileukemic activity against FLT3-ITD AML
Authors: Qiao Xinan , Ma Jun , Knight Tristan , Su Yongwei , Edwards Holly , Polin Lisa , Li Jing , Kushner Juiwanna , Dzinic Sijana H. , White Kathryn , Wang Jian , Lin Hai , Wang Yue , Wang Liping , Wang Guan , Taub Jeffrey W. , Ge Yubin
Published: June 2021

About 25% of patients with acute myeloid leukemia (AML) harbor FMS-like tyrosine kinase 3 (FLT3) internal tandem duplication (ITD) mutations and their prognosis remains poor. Gilteritinib is a FLT3 inhibitor approved by the US FDA for use in adult FLT3-mutated relapsed or refractory AML patients. Monotherapy, while efficacious, shows short-lived responses, highlighting the need for combination therapies. Here we show that gilteritinib and CUDC-907, a dual inhibitor of PI3K and histone deacetylases, synergistically induce apoptosis in FLT3-ITD AML cell lines and primary patient samples and have striking in vivo efficacy. Upregulation of FLT3 and activation of ERK are mechanisms of resistance to gilteritinib, while activation of JAK2/STAT5 is a mechanism of resistance to CUDC-907. Gilteritinib and CUDC-907 reciprocally overcome these mechanisms of resistance. In addition, the combined treatment results in cooperative downregulation of cellular metabolites and persisting antileukemic effects. CUDC-907 plus gilteritinib shows synergistic antileukemic activity against FLT3-ITD AML in vitro and in vivo, demonstrating strong translational therapeutic potential.
H3K36 methyltransferase NSD1 regulates chondrocyte differentiation for skeletal development and fracture repair
Authors: Shao Rui , Zhang Zhong , Xu Zhan , Ouyang Huiling , Wang Lijun , Ouyang Hongwei , Greenblatt Matthew , Chen Xi , Zou Weiguo
Published: June 2021

Chondrocyte differentiation is a critical process for endochondral ossification, which is responsible for long bone development and fracture repair. Considerable progress has been made in understanding the transcriptional control of chondrocyte differentiation; however, epigenetic regulation of chondrocyte differentiation remains to be further studied. NSD1 is a H3K36 (histone H3 at lysine 36) methyltransferase. Here, we showed that mice with Nsd1 deficiency in Prx1+ mesenchymal progenitors but not in Col2+ chondrocytes showed impaired skeletal growth and fracture healing accompanied by decreased chondrogenic differentiation. Via combined RNA sequencing (RNA-seq) and chromatin immunoprecipitation sequencing (ChIP-seq) analysis, we identified sex determining region Y box 9 (Sox9), the key transcription factor of chondrogenic differentiation, as a functional target gene of NSD1. Mechanistically, NSD1 regulates Sox9 expression by modulating H3K36me1 and H3K36me2 levels in the Sox9 promoter region, constituting a novel epigenetic regulatory mechanism of chondrogenesis. Moreover, we found that NSD1 can directly activate the expression of hypoxia-inducible factor 1α (HIF1α), which plays a vital role in chondrogenic differentiation through its regulation of Sox9 expression. Collectively, the results of our study reveal crucial roles of NSD1 in regulating chondrogenic differentiation, skeletal growth, and fracture repair and expand our understanding of the function of epigenetic regulation in chondrogenesis and skeletal biology.
Targeting angiogenesis for fracture nonunion treatment in inflammatory disease
Authors: Wang Cuicui , Ying Jun , Nie Xiaolei , Zhou Tianhong , Xiao Ding , Swarnkar Gaurav , Abu-Amer Yousef , Guan Jianjun , Shen Jie
Published: June 2021

Atrophic fracture nonunion poses a significant clinical problem with limited therapeutic interventions. In this study, we developed a unique nonunion model with high clinical relevance using serum transfer-induced rheumatoid arthritis (RA). Arthritic mice displayed fracture nonunion with the absence of fracture callus, diminished angiogenesis and fibrotic scar tissue formation leading to the failure of biomechanical properties, representing the major manifestations of atrophic nonunion in the clinic. Mechanistically, we demonstrated that the angiogenesis defect observed in RA mice was due to the downregulation of SPP1 and CXCL12 in chondrocytes, as evidenced by the restoration of angiogenesis upon SPP1 and CXCL12 treatment in vitro. In this regard, we developed a biodegradable scaffold loaded with SPP1 and CXCL12, which displayed a beneficial effect on angiogenesis and fracture repair in mice despite the presence of inflammation. Hence, these findings strongly suggest that the sustained release of SPP1 and CXCL12 represents an effective therapeutic approach to treat impaired angiogenesis and fracture nonunion under inflammatory conditions.
Solvent-induced electrochemistry at an electrically asymmetric carbon Janus particle
Authors: Liu Albert Tianxiang , Kunai Yuichiro , Cottrill Anton L. , Kaplan Amir , Zhang Ge , Kim Hyunah , Mollah Rafid S. , Eatmon Yannick L. , Strano Michael S.
Published: June 2021

Chemical doping through heteroatom substitution is often used to control the Fermi level of semiconductor materials. Doping also occurs when surface adsorbed molecules modify the Fermi level of low dimensional materials such as carbon nanotubes. A gradient in dopant concentration, and hence the chemical potential, across such a material generates usable electrical current. This opens up the possibility of creating asymmetric catalytic particles capable of generating voltage from a surrounding solvent that imposes such a gradient, enabling electrochemical transformations. In this work, we report that symmetry-broken carbon particles comprised of high surface area single-walled carbon nanotube networks can effectively convert exothermic solvent adsorption into usable electrical potential, turning over electrochemical redox processes in situ with no external power supply. The results from ferrocene oxidation and the selective electro-oxidation of alcohols underscore the potential of solvent powered electrocatalytic particles to extend electrochemical transformation to various environments.
The steroid-hormone ecdysone coordinates parallel pupariation neuromotor and morphogenetic subprograms via epidermis-to-neuron Dilp8-Lgr3 signal induction
Authors: Heredia Fabiana , Volonté Yanel , Pereirinha Joana , Fernandez-Acosta Magdalena , Casimiro Andreia P. , Belém Cláudia G. , Viegas Filipe , Tanaka Kohtaro , Menezes Juliane , Arana Maite , Cardoso Gisele A. , Macedo André , Kotowicz Malwina , Prado Spalm Facundo H. , Dibo Marcos J. , Monfardini Raquel D. , Torres Tatiana T. , Mendes César S. , Garelli Andres , Gontijo Alisson M.
Published: June 2021

Innate behaviors consist of a succession of genetically-hardwired motor and physiological subprograms that can be coupled to drastic morphogenetic changes. How these integrative responses are orchestrated is not completely understood. Here, we provide insight into these mechanisms by studying pupariation, a multi-step innate behavior of Drosophila larvae that is critical for survival during metamorphosis. We find that the steroid-hormone ecdysone triggers parallel pupariation neuromotor and morphogenetic subprograms, which include the induction of the relaxin-peptide hormone, Dilp8, in the epidermis. Dilp8 acts on six Lgr3-positive thoracic interneurons to couple both subprograms in time and to instruct neuromotor subprogram switching during behavior. Our work reveals that interorgan feedback gates progression between subunits of an innate behavior and points to an ancestral neuromodulatory function of relaxin signaling.
Overcoming the water oxidative limit for ultra-high-workfunction hole-doped polymers
Authors: Koh Qi-Mian , Tang Cindy Guanyu , Ang Mervin Chun-Yi , Choo Kim-Kian , Seah Qiu-Jing , Png Rui-Qi , Chua Lay-Lay , Ho Peter K. H.
Published: June 2021

It is widely thought that the water-oxidation reaction limits the maximum work function to about 5.25 eV for hole-doped semiconductors exposed to the ambient, constrained by the oxidation potential of air-saturated water. Here, we show that polymer organic semiconductors, when hole-doped, can show work functions up to 5.9 eV, and yet remain stable in the ambient. We further show that de-doping of the polymer is not determined by the oxidation of bulk water, as previously thought, due to its general absence, but by the counter-balancing anion and its ubiquitously hydrated complexes. The effective donor levels of these species, representing the edge of the ‘chemical’ density of states, can be depressed to about 6.0 eV below vacuum level. This can be achieved by raising the oxidation potential for hydronium generation, using large super-acid anions that are themselves also stable against oxidation. In this way, we demonstrate that poly(fluorene-alt-triarylamine) derivatives with tethered perfluoroalkyl-sulfonylimidosulfonyl anions can provide ambient solution-processability directly in the ultrahigh-workfunction hole-doped state to give films with good thermal stability. These results lay the path for design of soft materials for battery, bio-electronic and thermoelectric applications.
Private communication with quantum cascade laser photonic chaos
Authors: Spitz Olivier , Herdt Andreas , Wu Jiagui , Maisons Grégory , Carras Mathieu , Wong Chee-Wei , Elsäßer Wolfgang , Grillot Frédéric
Published: June 2021

Mid-infrared free-space optical communication has a large potential for high speed communication due to its immunity to electromagnetic interference. However, data security against eavesdroppers is among the obstacles for private free-space communication. Here, we show that two uni-directionally coupled quantum cascade lasers operating in the chaotic regime and the synchronization between them allow for the extraction of the information that has been camouflaged in the chaotic emission. This building block represents a key tool to implement a high degree of privacy directly on the physical layer. We realize a proof-of-concept communication at a wavelength of 5.7 μm with a message encryption at a bit rate of 0.5 Mbit/s. Our demonstration of private free-space communication between a transmitter and receiver opens strategies for physical encryption and decryption of a digital message.
Multimodal host–guest complexation for efficient and stable perovskite photovoltaics
Authors: Zhang Hong , Eickemeyer Felix Thomas , Zhou Zhiwen , Mladenović Marko , Jahanbakhshi Farzaneh , Merten Lena , Hinderhofer Alexander , Hope Michael A. , Ouellette Olivier , Mishra Aditya , Ahlawat Paramvir , Ren Dan , Su Tzu-Sen , Krishna Anurag , Wang Zaiwei , Dong Zhaowen , Guo Jinming , Zakeeruddin Shaik M. , Schreiber Frank , Hagfeldt Anders , Emsley Lyndon , Rothlisberger Ursula , Milić Jovana V. , Grätzel Michael
Published: June 2021

Formamidinium lead iodide perovskites are promising light-harvesting materials, yet stabilizing them under operating conditions without compromising optimal optoelectronic properties remains challenging. We report a multimodal host–guest complexation strategy to overcome this challenge using a crown ether, dibenzo-21-crown-7, which acts as a vehicle that assembles at the interface and delivers Cs+ ions into the interior while modulating the material. This provides a local gradient of doping at the nanoscale that assists in photoinduced charge separation while passivating surface and bulk defects, stabilizing the perovskite phase through a synergistic effect of the host, guest, and host–guest complex. The resulting solar cells show power conversion efficiencies exceeding 24% and enhanced operational stability, maintaining over 95% of their performance without encapsulation for 500 h under continuous operation. Moreover, the host contributes to binding lead ions, reducing their environmental impact. This supramolecular strategy illustrates the broad implications of host–guest chemistry in photovoltaics.
Endometrial receptivity and implantation require uterine BMP signaling through an ACVR2A-SMAD1/SMAD5 axis
Authors: Monsivais Diana , Nagashima Takashi , Prunskaite-Hyyryläinen Renata , Nozawa Kaori , Shimada Keisuke , Tang Suni , Hamor Clark , Agno Julio E. , Chen Fengju , Masand Ramya P. , Young Steven L. , Creighton Chad J. , DeMayo Francesco J. , Ikawa Masahito , Lee Se-Jin , Matzuk Martin M.
Published: June 2021

During early pregnancy in the mouse, nidatory estrogen (E2) stimulates endometrial receptivity by activating a network of signaling pathways that is not yet fully characterized. Here, we report that bone morphogenetic proteins (BMPs) control endometrial receptivity via a conserved activin receptor type 2 A (ACVR2A) and SMAD1/5 signaling pathway. Mice were generated to contain single or double conditional deletion of SMAD1/5 and ACVR2A/ACVR2B receptors using progesterone receptor (PR)-cre. Female mice with SMAD1/5 deletion display endometrial defects that result in the development of cystic endometrial glands, a hyperproliferative endometrial epithelium during the window of implantation, and impaired apicobasal transformation that prevents embryo implantation and leads to infertility. Analysis of Acvr2a-PRcre and Acvr2b-PRcre pregnant mice determined that BMP signaling occurs via ACVR2A and that ACVR2B is dispensable during embryo implantation. Therefore, BMPs signal through a conserved endometrial ACVR2A/SMAD1/5 pathway that promotes endometrial receptivity during embryo implantation.
Towards an engineering theory of evolution
Authors: Castle Simeon D. , Grierson Claire S. , Gorochowski Thomas E.
Published: June 2021

Biological technologies are fundamentally unlike any other because biology evolves. Bioengineering therefore requires novel design methodologies with evolution at their core. Knowledge about evolution is currently applied to the design of biosystems ad hoc. Unless we have an engineering theory of evolution, we will neither be able to meet evolution’s potential as an engineering tool, nor understand or limit its unintended consequences for our biological designs. Here, we propose the evotype as a helpful concept for engineering the evolutionary potential of biosystems, or other self-adaptive technologies, potentially beyond the realm of biology.
Anchor extension: a structure-guided approach to design cyclic peptides targeting enzyme active sites
Authors: Hosseinzadeh Parisa , Watson Paris R. , Craven Timothy W. , Li Xinting , Rettie Stephen , Pardo-Avila Fátima , Bera Asim K. , Mulligan Vikram Khipple , Lu Peilong , Ford Alexander S. , Weitzner Brian D. , Stewart Lance J. , Moyer Adam P. , Di Piazza Maddalena , Whalen Joshua G. , Greisen Per , Christianson David W. , Baker David
Published: June 2021

Despite recent success in computational design of structured cyclic peptides, de novo design of cyclic peptides that bind to any protein functional site remains difficult. To address this challenge, we develop a computational “anchor extension” methodology for targeting protein interfaces by extending a peptide chain around a non-canonical amino acid residue anchor. To test our approach using a well characterized model system, we design cyclic peptides that inhibit histone deacetylases 2 and 6 (HDAC2 and HDAC6) with enhanced potency compared to the original anchor (IC50 values of 9.1 and 4.4 nM for the best binders compared to 5.4 and 0.6 µM for the anchor, respectively). The HDAC6 inhibitor is among the most potent reported so far. These results highlight the potential for de novo design of high-affinity protein-peptide interfaces, as well as the challenges that remain.
Systems genetics in diversity outbred mice inform BMD GWAS and identify determinants of bone strength
Authors: Al-Barghouthi Basel M. , Mesner Larry D. , Calabrese Gina M. , Brooks Daniel , Tommasini Steven M. , Bouxsein Mary L. , Horowitz Mark C. , Rosen Clifford J. , Nguyen Kevin , Haddox Samuel , Farber Emily A. , Onengut-Gumuscu Suna , Pomp Daniel , Farber Charles R.
Published: June 2021

Genome-wide association studies (GWASs) for osteoporotic traits have identified over 1000 associations; however, their impact has been limited by the difficulties of causal gene identification and a strict focus on bone mineral density (BMD). Here, we use Diversity Outbred (DO) mice to directly address these limitations by performing a systems genetics analysis of 55 complex skeletal phenotypes. We apply a network approach to cortical bone RNA-seq data to discover 66 genes likely to be causal for human BMD GWAS associations, including the genesSERTAD4andGLT8D2. We also perform GWAS in the DO for a wide-range of bone traits and identifyQsox1as a gene influencing cortical bone accrual and bone strength. In this work, we advance our understanding of the genetics of osteoporosis and highlight the ability of the mouse to inform human genetics.
Attosecond intra-valence band dynamics and resonant-photoemission delays in W(110)
Authors: Heinrich S. , Saule T. , Högner M. , Cui Y. , Yakovlev V. S. , Pupeza I. , Kleineberg U.
Published: June 2021

Time-resolved photoelectron spectroscopy with attosecond precision provides new insights into the photoelectric effect and gives information about the timing of photoemission from different electronic states within the electronic band structure of solids. Electron transport, scattering phenomena and electron-electron correlation effects can be observed on attosecond time scales by timing photoemission from valence band states against that from core states. However, accessing intraband effects was so far particularly challenging due to the simultaneous requirements on energy, momentum and time resolution. Here we report on an experiment utilizing intracavity generated attosecond pulse trains to meet these demands at high flux and high photon energies to measure intraband delays between sp- and d-band states in the valence band photoemission from tungsten and investigate final-state effects in resonant photoemission.
Selection on heritable social network positions is context-dependent in Drosophila melanogaster
Authors: Wice Eric Wesley , Saltz Julia Barbara
Published: June 2021

Social group structure is highly variable and can be important for nearly every aspect of behavior and its fitness consequences. Group structure can be modeled using social network analysis, but we know little about the evolutionary factors shaping and maintaining variation in how individuals are embedded within their networks (i.e., network position). While network position is a pervasive target of selection, it remains unclear whether network position is heritable and can respond to selection. Furthermore, it is unclear how environmental factors interact with genotypic effects on network positions, or how environmental factors shape selection on heritable network structure. Here we show multiple measures of social network position are heritable, using replicate genotypes and replicate social groups of Drosophila melanogaster flies. Our results indicate genotypic differences in network position are largely robust to changes in the environment flies experience, though some measures of network position do vary across environments. We also show selection on multiple network position metrics depends on the environmental context they are expressed in, laying the groundwork for better understanding how spatio-temporal variation in selection contributes to the evolution of variable social group structure.
Unique structure of active platinum-bismuth site for oxidation of carbon monoxide
Authors: Nan Bing , Fu Qiang , Yu Jing , Shu Miao , Zhou Lu-Lu , Li Jinying , Wang Wei-Wei , Jia Chun-Jiang , Ma Chao , Chen Jun-Xiang , Li Lina , Si Rui
Published: June 2021

As the technology development, the future advanced combustion engines must be designed to perform at a low temperature. Thus, it is a great challenge to synthesize high active and stable catalysts to resolve exhaust below 100 °C. Here, we report that bismuth as a dopant is added to form platinum-bismuth cluster on silica for CO oxidation. The highly reducible oxygen species provided by surface metal-oxide (M-O) interface could be activated by CO at low temperature (~50 °C) with a high CO2 production rate of 487 μmolCO2·gPt−1·s−1 at 110 °C. Experiment data combined with density functional calculation (DFT) results demonstrate that Pt cluster with surface Pt−O−Bi structure is the active site for CO oxidation via providing moderate CO adsorption and activating CO molecules with electron transformation between platinum atom and carbon monoxide. These findings provide a unique and general approach towards design of potential excellent performance catalysts for redox reaction.
A new high-voltage calcium intercalation host for ultra-stable and high-power calcium rechargeable batteries
Authors: Xu Zheng-Long , Park Jooha , Wang Jian , Moon Hyunseok , Yoon Gabin , Lim Jongwoo , Ko Yoon-Joo , Cho Sung-Pyo , Lee Sang-Young , Kang Kisuk
Published: June 2021

Rechargeable calcium batteries have attracted increasing attention as promising multivalent ion battery systems due to the high abundance of calcium. However, the development has been hampered by the lack of suitable cathodes to accommodate the large and divalent Ca2+ ions at a high redox potential with sufficiently fast ionic conduction. Herein, we report a new intercalation host which presents 500 cycles with a capacity retention of 90% and a remarkable power capability at ~3.2 V (vs. Ca/Ca2+) in a calcium battery. The cathode material derived from Na0.5VPO4.8F0.7 is demonstrated to reversibly accommodate a large amount of Ca2+ ions, forming a series of CaxNa0.5VPO4.8F0.7 (0 < x < 0.5) phases without any noticeable structural degradation. The robust framework enables one of the smallest volume changes (1.4%) and the lowest diffusion barriers for Ca2+ among the cathodes reported to date, offering the basis for the outstanding cycle life and power capability.
GATA3 induces mitochondrial biogenesis in primary human CD4+ T cells during DNA damage
Authors: Callender Lauren A. , Schroth Johannes , Carroll Elizabeth C. , Garrod-Ketchley Conor , Romano Lisa E. L. , Hendy Eleanor , Kelly Audrey , Lavender Paul , Akbar Arne N. , Chapple J. Paul , Henson Sian M.
Published: June 2021

GATA3 is as a lineage-specific transcription factor that drives the differentiation of CD4+ T helper 2 (Th2) cells, but is also involved in a variety of processes such as immune regulation, proliferation and maintenance in other T cell and non-T cell lineages. Here we show a mechanism utilised by CD4+ T cells to increase mitochondrial mass in response to DNA damage through the actions of GATA3 and AMPK. Activated AMPK increases expression of PPARG coactivator 1 alpha (PPARGC1A or PGC1α protein) at the level of transcription and GATA3 at the level of translation, while DNA damage enhances expression of nuclear factor erythroid 2-related factor 2 (NFE2L2 or NRF2). PGC1α, GATA3 and NRF2 complex together with the ATR to promote mitochondrial biogenesis. These findings extend the pleotropic interactions of GATA3 and highlight the potential for GATA3-targeted cell manipulation for intervention in CD4+ T cell viability and function after DNA damage.
Layered double hydroxide membrane with high hydroxide conductivity and ion selectivity for energy storage device
Authors: Hu Jing , Tang Xiaomin , Dai Qing , Liu Zhiqiang , Zhang Huamin , Zheng Anmin , Yuan Zhizhang , Li Xianfeng
Published: June 2021

Membranes with fast and selective ions transport are highly demanded for energy storage devices. Layered double hydroxides (LDHs), bearing uniform interlayer galleries and abundant hydroxyl groups covalently bonded within two-dimensional (2D) host layers, make them superb candidates for high-performance membranes. However, related research on LDHs for ions separation is quite rare, especially the deep-going study on ions transport behavior in LDHs. Here, we report a LDHs-based composite membrane with fast and selective ions transport for flow battery application. The hydroxide ions transport through LDHs via vehicular (standard diffusion) & Grotthuss (proton hopping) mechanisms is uncovered. The LDHs-based membrane enables an alkaline zinc-based flow battery to operate at 200 mA cm−2, along with an energy efficiency of 82.36% for 400 cycles. This study offers an in-depth understanding of ions transport in LDHs and further inspires their applications in other energy-related devices.
TET1-mediated DNA hydroxymethylation regulates adult remyelination in mice
Authors: Moyon Sarah , Frawley Rebecca , Marechal Damien , Huang Dennis , Marshall-Phelps Katy L. H. , Kegel Linde , Bøstrand Sunniva M. K. , Sadowski Boguslawa , Jiang Yong-Hui , Lyons David A. , Möbius Wiebke , Casaccia Patrizia
Published: June 2021

The mechanisms regulating myelin repair in the adult central nervous system (CNS) are unclear. Here, we identify DNA hydroxymethylation, catalyzed by the Ten-Eleven-Translocation (TET) enzyme TET1, as necessary for myelin repair in young adults and defective in old mice. Constitutive and inducible oligodendrocyte lineage-specific ablation of Tet1 (but not of Tet2), recapitulate this age-related decline in repair of demyelinated lesions. DNA hydroxymethylation and transcriptomic analyses identify TET1-target in adult oligodendrocytes, as genes regulating neuro-glial communication, including the solute carrier (Slc) gene family. Among them, we show that the expression levels of the Na+/K+/Cl− transporter, SLC12A2, are higher in Tet1 overexpressing cells and lower in old or Tet1 knockout. Both aged mice and Tet1 mutants also present inefficient myelin repair and axo-myelinic swellings. Zebrafish mutants for slc12a2b also display swellings of CNS myelinated axons. Our findings suggest that TET1 is required for adult myelin repair and regulation of the axon-myelin interface.
Temporal evolution of cellular heterogeneity during the progression to advanced AR-negative prostate cancer
Authors: Brady Nicholas J. , Bagadion Alyssa M. , Singh Richa , Conteduca Vincenza , Van Emmenis Lucie , Arceci Elisa , Pakula Hubert , Carelli Ryan , Khani Francesca , Bakht Martin , Sigouros Michael , Bareja Rohan , Sboner Andrea , Elemento Olivier , Tagawa Scott , Nanus David M. , Loda Massimo , Beltran Himisha , Robinson Brian , Rickman David S.
Published: June 2021

Despite advances in the development of highly effective androgen receptor (AR)-directed therapies for the treatment of men with advanced prostate cancer, acquired resistance to such therapies frequently ensues. A significant subset of patients with resistant disease develop AR-negative tumors that lose their luminal identity and display neuroendocrine features (neuroendocrine prostate cancer (NEPC)). The cellular heterogeneity and the molecular evolution during the progression from AR-positive adenocarcinoma to AR-negative NEPC has yet to be characterized. Utilizing a new genetically engineered mouse model, we have characterized the synergy between Rb1 loss and MYCN (encodes N-Myc) overexpression which results in the formation of AR-negative, poorly differentiated tumors with high metastatic potential. Single-cell-based approaches revealed striking temporal changes to the transcriptome and chromatin accessibility which have identified the emergence of distinct cell populations, marked by differential expression of Ascl1 and Pou2f3, during the transition to NEPC. Moreover, global DNA methylation and the N-Myc cistrome are redirected following Rb1 loss. Altogether, our data provide insight into the progression of prostate adenocarcinoma to NEPC.
Feeding diversified protein sources exacerbates hepatic insulin resistance via increased gut microbial branched-chain fatty acids and mTORC1 signaling in obese mice
Authors: Choi Béatrice S.-Y. , Daniel Noëmie , Houde Vanessa P. , Ouellette Adia , Marcotte Bruno , Varin Thibault V. , Vors Cécile , Feutry Perrine , Ilkayeva Olga , Ståhlman Marcus , St-Pierre Philippe , Bäckhed Fredrik , Tremblay Angelo , White Phillip J. , Marette André
Published: June 2021

Animal models of human diseases are classically fed purified diets that contain casein as the unique protein source. We show that provision of a mixed protein source mirroring that found in the western diet exacerbates diet-induced obesity and insulin resistance by potentiating hepatic mTORC1/S6K1 signaling as compared to casein alone. These effects involve alterations in gut microbiota as shown by fecal microbiota transplantation studies. The detrimental impact of the mixed protein source is also linked with early changes in microbial production of branched-chain fatty acids (BCFA) and elevated plasma and hepatic acylcarnitines, indicative of aberrant mitochondrial fatty acid oxidation. We further show that the BCFA, isobutyric and isovaleric acid, increase glucose production and activate mTORC1/S6K1 in hepatocytes. Our findings demonstrate that alteration of dietary protein source exerts a rapid and robust impact on gut microbiota and BCFA with significant consequences for the development of obesity and insulin resistance.
Implications of incidental findings from lung screening for primary care: data from a UK pilot
Authors: Bartlett Emily C. , Belsey Jonathan , Derbyshire Jane , Morris Katie , Chen Michelle , Addis James , Martins Maria , Ridge Carole A. , Desai Sujal R. , Mirsadraee Saeed , Padley Simon , Whiteside Sarah , Vaghani Pritti , Morjaria Jaymin B. , Kemp Samuel V. , Devaraj Anand
Published: June 2021

Regional lung cancer screening (LCS) is underway in England, involving a “lung health check” (LHC) and low-dose CT scan for those at high risk of cancer. Incidental findings from LHCs or CTs are usually referred to primary care. We describe the proportion of participants referred from the West London LCS pilot to primary care, the indications for referral, the number of general practitioner (GP) attendances and consequent changes to patient management, and provide an estimated cost-burden analysis for primary care. A small proportion (163/1542, 10.6%) of LHC attendees were referred to primary care, primarily for suspected undiagnosed chronic obstructive pulmonary disease (55/163, 33.7%) or for QRISK® (63/163, 38.7%) assessment. Ninety one of 159 (57.2%) participants consenting to follow-up attended GP appointments; costs incurred by primary care were estimated at £5.69/LHC participant. Patient management changes occurred in only 36/159 (22.6%) referred participants. LHCs result in a small increase to primary care workload provided a strict referral protocol is adhered to. Changes to patient management arising from incidental findings referrals are infrequent.