bluuebunny/crossref_metadata_2025 huggingface dataset:
Embracing Data Incompleteness for Better Earthquake Forecasting
Authors: Mizrahi Leila , Nandan Shyam , Wiemer Stefan
Published: December 2021

We propose two methods to calibrate the parameters of the epidemic‐type aftershock sequence (ETAS) model based on expectation maximization (EM) while accounting for temporal variation of catalog completeness. The first method allows for model calibration on long‐term earthquake catalogs with temporal variation of the completeness magnitude,mc. This calibration technique is beneficial for long‐term probabilistic seismic hazard assessment (PSHA), which is often based on a mixture of instrumental and historical catalogs. The second method generalizes the concept ofmc, considering rate‐ and magnitude‐dependent detection probability, and allows for self‐consistent estimation of ETAS parameters and high‐frequency detection incompleteness. With this approach, we aim to address the potential biases in parameter calibration due to short‐term aftershock incompleteness, embracing incompleteness instead of avoiding it. Using synthetic tests, we show that both methods can accurately invert the parameters of simulated catalogs. We then use them to estimate ETAS parameters for California using the earthquake catalog since 1932. To explore how model calibration, inclusion of small events, and accounting for short‐term incompleteness affect earthquakes' predictability, we systematically compare variants of ETAS models based on the second approach in pseudo‐prospective forecasting experiments for California. Our proposed model significantly outperforms the ETAS null model, with decreasing information gain for increasing target magnitude threshold. We find that the ability to include small earthquakes for simulation of future scenarios is the primary driver of the improvement and that accounting for incompleteness is necessary. Our results have significant implications for our understanding of earthquake interaction mechanisms and the future of seismicity forecasting.
Impact of COVID-19 in patients with multiple myeloma based on a global data network
Authors: Martinez-Lopez J. , Hernandez-Ibarburu G. , Alonso R. , Sanchez-Pina J. M. , Zamanillo I. , Lopez-Muñoz N. , Iñiguez Rodrigo , Cuellar C. , Calbacho M. , Paciello M. L. , Ayala R. , García-Barrio N. , Perez-Rey D. , Meloni L. , Cruz J. , Pedrera-Jiménez M. , Serrano-Balazote P. , de la Cruz J.
Published: December 2021

The COVID-19 pandemic has represented a major cause of morbidity/mortality worldwide, overstressing health systems. Multiple myeloma (MM) patients show an increased risk for infections and they are expected to be particularly vulnerable to SARS-CoV-2 infection. Here we have obtained a comprehensive picture of the impact of COVID-19 in MM patients on a local and a global scale using a federated data research network (TriNetX) that provided access to Electronic Medical Records (EMR) from Health Care Organizations (HCO) all over the world. Through propensity score matched analyses we found that the number of new diagnoses of MM was reduced in 2020 compared to 2019 (RR 0.86, 95%CI 0.76–0.96) and the survival of newly diagnosed MM cases decreased similarly (HR 0.61, 0.38–0.81). MM patients showed higher risk of SARS-CoV-2 infection (RR 2.09, 1.58–2.76) and a higher excess mortality in 2020 (difference in excess mortality 9%, 4.4–13.2) than non-MM patients. By interrogating large EMR datasets from HCO in Europe and globally, we confirmed that MM patients have been more severely impacted by COVID-19 pandemic than non-MM patients. This study highlights the necessity of extending preventive measures worlwide to protect vulnerable patients from SARS-CoV-2 infection by promoting social distancing and an intensive vaccination strategies.
Regeneration of immunocompetent B lymphopoiesis from pluripotent stem cells guided by transcription factors
Authors: Zhang Qi , Wu Bingyan , Weng Qitong , Hu Fangxiao , Lin Yunqing , Xia Chengxiang , Peng Huan , Wang Yao , Liu Xiaofei , Liu Lijuan , Xiong Jiapin , Geng Yang , Zhao Yalan , Zhang Mengyun , Du Juan , Wang Jinyong
Published: December 2021

Regeneration of functional B lymphopoiesis from pluripotent stem cells (PSCs) is challenging, and reliable methods have not been developed. Here, we unveiled the guiding role of three essential factors, Lhx2, Hoxa9, and Runx1, the simultaneous expression of which preferentially drives B lineage fate commitment and in vivo B lymphopoiesis using PSCs as a cell source. In the presence of Lhx2, Hoxa9, and Runx1 expression, PSC-derived induced hematopoietic progenitors (iHPCs) immediately gave rise to pro/pre-B cells in recipient bone marrow, which were able to further differentiate into entire B cell lineages, including innate B-1a, B-1b, and marginal zone B cells, as well as adaptive follicular B cells. In particular, the regenerative B cells produced adaptive humoral immune responses, sustained antigen-specific antibody production, and formed immune memory in response to antigen challenges. The regenerative B cells showed natural B cell development patterns of immunoglobulin chain switching and hypermutation via cross-talk with host T follicular helper cells, which eventually formed T cell-dependent humoral responses. This study exhibits de novo evidence that B lymphopoiesis can be regenerated from PSCs via an HSC-independent approach, which provides insights into treating B cell-related deficiencies using PSCs as an unlimited cell resource.
Observation of hybrid higher-order skin-topological effect in non-Hermitian topolectrical circuits
Authors: Zou Deyuan , Chen Tian , He Wenjing , Bao Jiacheng , Lee Ching Hua , Sun Houjun , Zhang Xiangdong
Published: December 2021

Robust boundary states epitomize how deep physics can give rise to concrete experimental signatures with technological promise. Of late, much attention has focused on two distinct mechanisms for boundary robustness—topological protection, as well as the non-Hermitian skin effect. In this work, we report the experimental realizations of hybrid higher-order skin-topological effect, in which the skin effect selectively acts only on the topological boundary modes, not the bulk modes. Our experiments, which are performed on specially designed non-reciprocal 2D and 3D topolectrical circuit lattices, showcases how non-reciprocal pumping and topological localization dynamically interplays to form various states like 2D skin-topological, 3D skin-topological-topological hybrid states, as well as 2D and 3D higher-order non-Hermitian skin states. Realized through our highly versatile and scalable circuit platform, theses states have no Hermitian nor lower-dimensional analog, and pave the way for applications in topological switching and sensing through the simultaneous non-trivial interplay of skin and topological boundary localizations.
Multiple site place-of-care manufactured anti-CD19 CAR-T cells induce high remission rates in B-cell malignancy patients
Authors: Maschan Michael , Caimi Paolo F. , Reese-Koc Jane , Sanchez Gabriela Pacheco , Sharma Ashish A. , Molostova Olga , Shelikhova Larisa , Pershin Dmitriy , Stepanov Alexey , Muzalevskii Yakov , Suzart Vinicius G. , Otegbeye Folashade , Wald David , Xiong Ying , Wu Darong , Knight Adam , Oparaocha Ibe , Ferencz Beatrix , Roy Andre , Worden Andrew , Kruger Winfried , Kadan Michael , Schneider Dina , Orentas Rimas , Sekaly Rafick-Pierre , de Lima Marcos , Dropulić Boro
Published: December 2021

Chimeric antigen receptor (CAR) T cells targeting the CD19 antigen are effective in treating adults and children with B-cell malignancies. Place-of-care manufacturing may improve performance and accessibility by obviating the need to cryopreserve and transport cells to centralized facilities. Here we develop an anti-CD19 CAR (CAR19) comprised of the 4-1BB co-stimulatory and TNFRSF19 transmembrane domains, showing anti-tumor efficacy in an in vivo xenograft lymphoma model. CAR19 T cells are manufactured under current good manufacturing practices (cGMP) at two disparate clinical sites, Moscow (Russia) and Cleveland (USA). The CAR19 T-cells is used to treat patients with relapsed/refractory pediatric B-cell Acute Lymphocytic Leukemia (ALL; n = 31) or adult B-cell Lymphoma (NHL; n = 23) in two independently conducted phase I clinical trials with safety as the primary outcome (NCT03467256 and NCT03434769, respectively). Probability of measurable residual disease-negative remission was also a primary outcome in the ALL study. Secondary outcomes include complete remission (CR) rates, overall survival and median duration of response. CR rates are 89% (ALL) and 73% (NHL). After a median follow-up of 17 months, one-year survival rate of ALL complete responders is 79.2% (95%CI 64.5‒97.2%) and median duration of response is 10.2 months. For NHL complete responders one-year survival is 92.9%, and median duration of response has not been reached. Place-of-care manufacturing produces consistent CAR-T cell products at multiple sites that are effective for the treatment of patients with B-cell malignancies.
Parallel-stacked aromatic molecules in hydrogen-bonded inorganic frameworks
Authors: Igarashi Masayasu , Nozawa Takeshi , Matsumoto Tomohiro , Yagihashi Fujio , Kikuchi Takashi , Sato Kazuhiko
Published: December 2021

By precisely constructing molecules and assembling these into well-defined supramolecular structures, novel physical properties and functionalities can be realized, and new areas of the chemical space can be accessed. In both materials science and biology, a deeper understanding of the properties and exploitation of the reversible character of weak bonds and interactions, such as hydrogen bonds and π–π interactions, is anticipated to lead to the development of materials with novel properties and functionalities. We apply the hydrogen-bonded organic frameworks (HOFs) strategy to inorganic materials science using the cubic octamer of orthosilicic acid, [Si8O12][OH]8, as a building block, and find that various types of hydrogen-bonded inorganic frameworks (HIFs). We succeed in parallel π-stacking pure benzene, thiophene, selenophene, p-benzoquinone, thiophene·p-benzoquinone, and benzene·p-benzoquinone polymers infinitely. These polymers interact via their π-systems by taking advantage of the flexible pores of the three-dimensional nano-honeycomb HIFs, which consist of periodic wide and narrow segments.
Breast tissue regeneration is driven by cell-matrix interactions coordinating multi-lineage stem cell differentiation through DDR1
Authors: Rauner Gat , Jin Dexter X. , Miller Daniel H. , Gierahn Todd M. , Li Carman M. , Sokol Ethan S. , Feng Yu-Xiong , Mathis Robert A. , Love J. Christopher , Gupta Piyush B. , Kuperwasser Charlotte
Published: December 2021

Mammary morphogenesis is an orchestrated process involving differentiation, proliferation and organization of cells to form a bi-layered epithelial network of ducts and lobules embedded in stromal tissue. We have engineered a 3D biomimetic human breast that makes it possible to study how stem cell fate decisions translate to tissue-level structure and function. Using this advancement, we describe the mechanism by which breast epithelial cells build a complex three-dimensional, multi-lineage tissue by signaling through a collagen receptor. Discoidin domain receptor tyrosine kinase 1 induces stem cells to differentiate into basal cells, which in turn stimulate luminal progenitor cells via Notch signaling to differentiate and form lobules. These findings demonstrate how human breast tissue regeneration is triggered by transmission of signals from the extracellular matrix through an epithelial bilayer to coordinate structural changes that lead to formation of a complex ductal-lobular network.
Distinct roles of KLF4 in mesenchymal cell subtypes during lung fibrogenesis
Authors: Chandran Rachana R. , Xie Yi , Gallardo-Vara Eunate , Adams Taylor , Garcia-Milian Rolando , Kabir Inamul , Sheikh Abdul Q. , Kaminski Naftali , Martin Kathleen A. , Herzog Erica L. , Greif Daniel M.
Published: December 2021

During lung fibrosis, the epithelium induces signaling to underlying mesenchyme to generate excess myofibroblasts and extracellular matrix; herein, we focus on signaling in the mesenchyme. Our studies indicate that platelet-derived growth factor receptor (PDGFR)-β+ cells are the predominant source of myofibroblasts and Kruppel-like factor (KLF) 4 is upregulated in PDGFR-β+ cells, inducing TGFβ pathway signaling and fibrosis. In fibrotic lung patches, KLF4 is down-regulated, suggesting KLF4 levels decrease as PDGFR-β+ cells transition into myofibroblasts. In contrast to PDGFR-β+ cells, KLF4 reduction in α-smooth muscle actin (SMA)+ cells non-cell autonomously exacerbates lung fibrosis by inducing macrophage accumulation and pro-fibrotic effects of PDGFR-β+ cells via a Forkhead box M1 to C-C chemokine ligand 2—receptor 2 pathway. Taken together, in the context of lung fibrosis, our results indicate that KLF4 plays opposing roles in PDGFR-β+ cells and SMA+ cells and highlight the importance of further studies of interactions between distinct mesenchymal cell types.
Large-scale genome-wide study reveals climate adaptive variability in a cosmopolitan pest
Authors: Chen Yanting , Liu Zhaoxia , Régnière Jacques , Vasseur Liette , Lin Jian , Huang Shiguo , Ke Fushi , Chen Shaoping , Li Jianyu , Huang Jieling , Gurr Geoff M. , You Minsheng , You Shijun
Published: December 2021

Understanding the genetic basis of climatic adaptation is essential for predicting species’ responses to climate change. However, intraspecific variation of these responses arising from local adaptation remains ambiguous for most species. Here, we analyze genomic data from diamondback moth (Plutella xylostella) collected from 75 sites spanning six continents to reveal that climate-associated adaptive variation exhibits a roughly latitudinal pattern. By developing an eco-genetic index that combines genetic variation and physiological responses, we predict that mostP. xylostellapopulations have high tolerance to projected future climates. Using genome editing, a key gene,PxCad, emerged from our analysis as functionally temperature responsive. Our results demonstrate thatP. xylostellais largely capable of tolerating future climates in most of the world and will remain a global pest beyond 2050. This work improves our understanding of adaptive variation along environmental gradients, and advances pest forecasting by highlighting the genetic basis for local climate adaptation.
Enantioselective access to tricyclic tetrahydropyran derivatives by a remote hydrogen bonding mediated intramolecular IEDHDA reaction
Authors: Jin Min , Tang Congyun , Li Yingying , Yang Shuai , Yang Ying-Tao , Peng Lin , Li Xiao-Nian , Zhang Wenjing , Zuo Zhili , Gagosz Fabien , Wang Liang-Liang
Published: December 2021

Inverse-electron-demand-hetero-Diels-Alder reactions of alkenes with α,β-unsaturated keto compounds allow rapid access to the tetrahydropyran ring found in numerous natural products and bioactive molecules. Despite its synthetic interest, catalytic asymmetric versions of this process remain underdeveloped, especially regarding the use of non-activated alkenes reacting with α,β-unsaturated ketone or aldehyde, for which no report can be found in the literature. Herein, we describe the catalytic inverse-electron-demand-hetero-Diels-Alder reactions between neutral alkenes and an α,β-unsaturated ketones or aldehydes to produce a variety of trans-fused [5,6,8] tricyclic structures containing a central, chiral tetrahydropyran ring. This complex transformation, which is achieved using a chiral phosphoric acid, allows for the formation of four stereogenic centers in a single step with high regio-, diastereo- and enantioselectivity (up to 99% ee). Such level of stereocontrol could be achieved by a key remote double hydrogen atom bonding interaction between the linear substrate and the catalyst.
Emergence of the London Millennium Bridge instability without synchronisation
Authors: Belykh Igor , Bocian Mateusz , Champneys Alan R. , Daley Kevin , Jeter Russell , Macdonald John H. G. , McRobie Allan
Published: December 2021

The pedestrian-induced instability of the London Millennium Bridge is a widely used example of Kuramoto synchronisation. Yet, reviewing observational, experimental, and modelling evidence, we argue that increased coherence of pedestrians’ foot placement is a consequence of, not a cause of the instability. Instead, uncorrelated pedestrians produce positive feedback, through negative damping on average, that can initiate significant lateral bridge vibration over a wide range of natural frequencies. We present a simple general formula that quantifies this effect, and illustrate it through simulation of three mathematical models, including one with strong propensity for synchronisation. Despite subtle effects of gait strategies in determining precise instability thresholds, our results show that average negative damping is always the trigger. More broadly, we describe an alternative to Kuramoto theory for emergence of coherent oscillations in nature; collective contributions from incoherent agents need not cancel, but can provide positive feedback on average, leading to global limit-cycle motion.
Creation of an unexpected plane of enhanced covalency in cerium(III) and berkelium(III) terpyridyl complexes
Authors: Gaiser Alyssa N. , Celis-Barros Cristian , White Frankie D. , Beltran-Leiva Maria J. , Sperling Joseph M. , Salpage Sahan R. , Poe Todd N. , Gomez Martinez Daniela , Jian Tian , Wolford Nikki J. , Jones Nathaniel J. , Ritz Amanda J. , Lazenby Robert A. , Gibson John K. , Baumbach Ryan E. , Páez-Hernández Dayán , Neidig Michael L. , Albrecht-Schönzart Thomas E.
Published: December 2021

Controlling the properties of heavy element complexes, such as those containing berkelium, is challenging because relativistic effects, spin-orbit and ligand-field splitting, and complex metal-ligand bonding, all dictate the final electronic states of the molecules. While the first two of these are currently beyond experimental control, covalent M‒L interactions could theoretically be boosted through the employment of chelators with large polarizabilities that substantially shift the electron density in the molecules. This theory is tested by ligating BkIIIwith 4’-(4-nitrophenyl)-2,2’:6’,2”-terpyridine (terpy*), a ligand with a large dipole. The resultant complex, Bk(terpy*)(NO3)3(H2O)·THF, is benchmarked with its closest electrochemical analog, Ce(terpy*)(NO3)3(H2O)·THF. Here, we show that enhanced Bk‒N interactions with terpy* are observed as predicted. Unexpectedly, induced polarization by terpy* also creates a plane in the molecules wherein the M‒L bonds trans to terpy* are shorter than anticipated. Moreover, these molecules are highly anisotropic and rhombic EPR spectra for the CeIIIcomplex are reported.
Underdiagnosis bias of artificial intelligence algorithms applied to chest radiographs in under-served patient populations
Authors: Seyyed-Kalantari Laleh , Zhang Haoran , McDermott Matthew B. A. , Chen Irene Y. , Ghassemi Marzyeh
Published: December 2021

Artificial intelligence (AI) systems have increasingly achieved expert-level performance in medical imaging applications. However, there is growing concern that such AI systems may reflect and amplify human bias, and reduce the quality of their performance in historically under-served populations such as female patients, Black patients, or patients of low socioeconomic status. Such biases are especially troubling in the context of underdiagnosis, whereby the AI algorithm would inaccurately label an individual with a disease as healthy, potentially delaying access to care. Here, we examine algorithmic underdiagnosis in chest X-ray pathology classification across three large chest X-ray datasets, as well as one multi-source dataset. We find that classifiers produced using state-of-the-art computer vision techniques consistently and selectively underdiagnosed under-served patient populations and that the underdiagnosis rate was higher for intersectional under-served subpopulations, for example, Hispanic female patients. Deployment of AI systems using medical imaging for disease diagnosis with such biases risks exacerbation of existing care biases and can potentially lead to unequal access to medical treatment, thereby raising ethical concerns for the use of these models in the clinic.
Regulation-based probabilistic substance quality index and automated geo-spatial modeling for water quality assessment
Authors: Nikitin Artyom , Tregubova Polina , Shadrin Dmitrii , Matveev Sergey , Oseledets Ivan , Pukalchik Maria
Published: December 2021

Natural environments are recognized as complex heterogeneous structures thus requiring numerous multi-scale observations to yield a comprehensive description. To monitor the current state and identify negative impacts of human activity, fast and precise instruments are in urgent need. This work provides an automated approach to the assessment of spatial variability of water quality using guideline values on the example of 1526 water samples comprising 21 parameters at 448 unique locations across the New Moscow region (Russia). We apply multi-task Gaussian process regression (GPR) to model the measured water properties across the territory, considering not only the spatial but inter-parameter correlations. GPR is enhanced with a Spectral Mixture Kernel to facilitate a hyper-parameter selection and optimization. We use a 5-fold cross-validation scheme along with$$R^2$$R2-score to validate the results and select the best model for simultaneous prediction of water properties across the area. Finally, we develop a novel Probabilistic Substance Quality Index (PSQI) that combines probabilistic model predictions with the regulatory standards on the example of the epidemiological rules and hygienic regulations established in Russia. Moreover, we provide an interactive map of experimental results at 100 m2resolution. The proposed approach contributes significantly to the development of flexible tools in environment quality monitoring, being scalable to different standard systems, number of observation points, and region of interest. It has a strong potential for adaption to environmental and policy changes and non-unified assessment conditions, and may be integrated into support-decision systems for the rapid estimation of water quality spatial distribution.
Bayesian analyses question the role of climate in Chulmun demography
Authors: Kim Habeom , Lee Gyoung-Ah , Crema Enrico R.
Published: December 2021

We investigate the relationship between climatic and demographic events in Korea during the Chulmun period (10,000–3,500 cal. BP) by analyzing paleoenvironmental proxies and14C dates. We focus on testing whether a cooling climate, and its potential negative impact on millet productivity around the mid 5th-millennium cal. BP, triggered the population decline suggested by the archaeological record. We employ a Bayesian approach that estimates the temporal relationship between climatic events and change-points in the rate of growth in human population as inferred from radiocarbon time frequency data. Our results do not support the climate-induced population decline hypothesis for three reasons. First, our Bayesian analyses suggest that the cooling event occurred after the start of the population decline inferred from the radiocarbon time–frequency record. Second, we did not find evidence showing a significant reduction of millet-associated dates occurring during the cooling climate. Third, we detected different magnitudes of decline in the radiocarbon time–frequency data in the inland and coastal regions, indicating that the even if cooling episodes were ultimately responsible of these population ‘busts’, their impact was most likely distinct between these regions. We discuss our results highlighting the long tradition of mobility-based subsistence strategy in coastal regions as a potential factor contributing to the regional differences we were able to detect.
Design, synthesis, and biological evaluation of novel urolithins derivatives as potential phosphodiesterase II inhibitors
Authors: Tang Long , Jiang Jianchun , Song Guoqiang , Wang Yajing , Zhuang Ziheng , Tan Ying , Xia Yan , Huang Xianfeng , Feng Xiaoqing
Published: December 2021

A series of urolithins derivatives were designed and synthesized, and their structures have been confirmed by 1H NMR, 13C NMR, and HR-MS. The inhibitory activity of these derivatives on phosphodiesterase II (PDE2) was thoroughly studied with 3-hydroxy-8-methyl-6H-benzo[C]chromen-6-one and 3-hydroxy-7,8,9,10-tetrahydro-6H-benzo[C] chromen-6-one as the lead compounds. The biological activity test showed that compound 2e had the best inhibitory activity on PDE2 with an IC50 of 33.95 μM. This study provides a foundation for further structural modification and transformation of urolithins to obtain PDE2 inhibitor small molecules with better inhibitory activity.
C-type lectin receptor DCIR contributes to hippocampal injury in acute neurotropic virus infection
Authors: Stoff Melanie , Ebbecke Tim , Ciurkiewicz Malgorzata , Pavasutthipaisit Suvarin , Mayer-Lambertz Sabine , Störk Theresa , Pavelko Kevin D. , Baumgärtner Wolfgang , Jung Klaus , Lepenies Bernd , Beineke Andreas
Published: December 2021

Neurotropic viruses target the brain and contribute to neurologic diseases. C-type lectin receptors (CLRs) are pattern recognition receptors that recognize carbohydrate structures on endogenous molecules and pathogens. The myeloid CLR dendritic cell immunoreceptor (DCIR) is expressed by antigen presenting cells and mediates inhibitory intracellular signalling. To investigate the effect of DCIR on neurotropic virus infection, mice were infected experimentally with Theiler’s murine encephalomyelitis virus (TMEV). Brain tissue of TMEV-infected C57BL/6 mice and DCIR−/−mice were analysed by histology, immunohistochemistry and RT-qPCR, and spleen tissue by flow cytometry. To determine the impact of DCIR deficiency on T cell responses upon TMEV infection in vitro,antigen presentation assays were utilised. Genetic DCIR ablation in C57BL/6 mice was associated with an ameliorated hippocampal integrity together with reduced cerebral cytokine responses and reduced TMEV loads in the brain. Additionally, absence of DCIR favoured increased peripheral cytotoxic CD8+T cell responses following TMEV infection. Co-culture experiments revealed that DCIR deficiency enhances the activation of antigen-specific CD8+T cells by virus-exposed dendritic cells (DCs), indicated by increased release of interleukin-2 and interferon-γ. Results suggest that DCIR deficiency has a supportive influence on antiviral immune mechanisms, facilitating virus control in the brain and ameliorates neuropathology during acute neurotropic virus infection.
Assessment of leaf morphological, physiological, chemical and stoichiometry functional traits for understanding the functioning of Himalayan temperate forest ecosystem
Authors: Rawat Monika , Arunachalam Kusum , Arunachalam Ayyandar , Alatalo Juha M. , Pandey Rajiv
Published: December 2021

Leaf functional traits support plant survival and growth in different stress and disturbed conditions and respond according to leaf habit. The present study examined 13 leaf traits (3 morphological, 3 chemical, 5 physiological, and 2 stoichiometry) of nine dominant forest tree species (3 coniferous, 3 deciduous broad-leaved, 3 evergreen broad-leafed) to understand the varied response of leaf habits. The hypothesis was to test if functional traits of the conifers, deciduous and evergreen differ significantly in the temperate forest and to determine the applicability of leaf economic theoryi.e., conservative vs. acquisitive resource investment, in the temperate Himalayan region. The attributes of the functional traitsi.e.,leaf area (LA), specific leaf area (SLA), leaf dry matter content (LDMC), leaf water content (LWC), stomatal conductance (Gs), and transpiration (E) followed the order deciduous > evergreen > coniferous. Leaf carbon and leaf C/N ratio showed the opposite pattern, coniferous > evergreen > deciduous. Chlorophyll (Chl) and photosynthetic rate (A) were highest for evergreen species, followed by deciduous and coniferous species. Also, structural equation modelling determined that morphological factors were negatively related to physiological and positively with chemical factors. Nevertheless, physiological and chemical factors were positively related to each other. The physiological traits were mainly regulated by stomatal conductance (Gs) however the morphological traits were determined by LDMC. Stoichiometry traits, such as leaf C/N, were found to be positively related to leaf carbon, and leaf N/P was found to be positively related to leaf nitrogen. The result of the leaf functional traits relationship would lead to precise prediction for the functionality of the temperate forest ecosystem at the regional scale.
Molecular insights into the electrowetting behavior of aqueous ionic liquids
Authors: Bhattacharjee Sanchari , Khan Sandip
Published: December 2021

olecular dynamics (MD) simulations were applied to investigate the wettability of aqueous hydrophilic and hydrophobic imidazolium-based ionic liquid (IL) nano-droplets on a graphite surface under a perpendicular electric field.
Gas phase protonated nicotine is a mixture of pyridine- and pyrrolidine-protonated conformers: implications for its native structure in the nicotinic acetylcholine receptor
Authors: Takeda Naoya , Hirata Keisuke , Tsuruta Kazuya , Santis Garrett D. , Xantheas Sotiris S. , Ishiuchi Shun-ichi , Fujii Masaaki
Published: December 2021

The infrared (IR) spectra of gas phase protonated nicotine has been measured in the never-before probed N–H “fingerprint region” (3200–3500 cm−1).
Revisiting the grammar of Tau aggregation and pathology formation: how new insights from brain pathology are shaping how we study and target Tauopathies
Authors: Limorenko Galina , Lashuel Hilal A.
Published: December 2021

We discuss novel approaches for embracing and reproducing complexity of Tau pathology required for developing disease-relevant diagnostics and effective therapies.
Boosting electrochemical nitrogen reduction to ammonia with high efficiency using a LiNb3O8 electrocatalyst in neutral media
Authors: Wang Qi , Fan Shuhui , Liu Leran , Wen Xiaojiang , Wu Yun , Yao Rui , Zhao Qiang , Li Jinping , Liu Guang
Published: December 2021

A LiNb3O8 electrocatalyst with Li+ incorporation and a hydrophobic surface presents an ammonia yield rate of 7.85 μg h−1 mgcat.−1 with a faradaic efficiency of 82.83% at −0.4 V vs. RHE under ambient conditions.
Dinitrogen-derived (diarylboryl)diazenido complexes with differing coordination to the thallium cation
Authors: Bouammali Amal , Coffinet Anaïs , Vendier Laure , Simonneau Antoine
Published: December 2021

N2-Derived boryldiazenido complexes are shown to offer differing coordination sites to the soft thallium cation depending on the boron's and phosphine ligand's substituents.
Metal-free, one-pot synthesis of 2-styrylquinolines via Friedländer annulation and sp3 C–H activation using 1,3-dimethylurea and l-tartaric acid (3 : 1) as a deep eutectic solvent
Authors: Satyanarayana Neeli , Sathish Kota , Nagaraju Sakkani , Pawar Ravinder , Faizan Mohmmad , Arumugavel Murgan , Shirisha Thangellapally , Kashinath Dhurke
Published: December 2021

Functionalized 2-styrylquinolines are prepared using DMU + l-(+)-tartaric acid as deep eutectic solvent. DFT calculations supported the experimental results on role of DES as catalyst. The absorption-emission spectra indicating that these compounds can be useful as fluorescent probes.
Reactivity switch-over of 4-hydroxydithiocoumarins under various conditions and their application in organic synthesis
Authors: Belal Md. , Mondal Santa , Yashmin Sabina , Khan Abu Taleb
Published: December 2021

Synthetic utilities of 4-hydroxydithiocoumarin were explored for the construction of numerous new heterocycles involving its three different reactive sites.
Synthesis of oxindoles bearing a stereogenic 3-fluorinated carbon center from 3-fluorooxindoles
Authors: Liu Yong-Liang , Wang Xiao-Ping , Wei Jie , Li Ya
Published: December 2021

The present review summarizes the advances in the synthesis of 3,3-disubstituted 3-fluorooxindole derivatives through the straightforward functionalization of 3-fluorooxindoles.
Hierarchical self-assembly of aromatic peptide conjugates into supramolecular polymers: it takes two to tango
Authors: Coste Maëva , Suárez-Picado Esteban , Ulrich Sébastien
Published: December 2021

The dynamic combination of aromatics and peptides yields functional supramolecular biopolymers which self-assemble hierarchically and adapt through non-covalent interactions and/or reversible covalent reactions.
Serine acetyltransferase from Neisseria gonorrhoeae; structural and biochemical basis of inhibition
Authors: Oldham Keely E. A. , Prentice Erica J. , Summers Emma L. , Hicks Joanna L.
Published: December 2021

Serine acetyltransferase (SAT) catalyzes the first step in the two-step pathway to synthesize l-cysteine in bacteria and plants. SAT synthesizes O-acetylserine from substrates l-serine and acetyl coenzyme A and is a key enzyme for regulating cellular cysteine levels by feedback inhibition of l-cysteine, and its involvement in the cysteine synthase complex. We have performed extensive structural and kinetic characterization of the SAT enzyme from the antibiotic-resistant pathogen Neisseria gonorrhoeae. Using X-ray crystallography, we have solved the structures of NgSAT with the non-natural ligand, l-malate (present in the crystallization screen) to 2.01 Å and with the natural substrate l-serine (2.80 Å) bound. Both structures are hexamers, with each monomer displaying the characteristic left-handed parallel β-helix domain of the acyltransferase superfamily of enzymes. Each structure displays both extended and closed conformations of the C-terminal tail. l-malate bound in the active site results in an interesting mix of open and closed active site conformations, exhibiting a structural change mimicking the conformation of cysteine (inhibitor) bound structures from other organisms. Kinetic characterization shows competitive inhibition of l-cysteine with substrates l-serine and acetyl coenzyme A. The SAT reaction represents a key point for the regulation of cysteine biosynthesis and controlling cellular sulfur due to feedback inhibition by l-cysteine and formation of the cysteine synthase complex. Data presented here provide the structural and mechanistic basis for inhibitor design and given this enzyme is not present in humans could be explored to combat the rise of extensively antimicrobial resistant N. gonorrhoeae.
Indicators of Communication Limitation in Dysarthria and Their Relation to Auditory-Perceptual Speech Symptoms: Construct Validity of the KommPaS Web App
Authors: Lehner Katharina , Ziegler Wolfram ,   KommPaS Study Group
Published: December 2021

Purpose:

Despite extensive research into communication-related parameters in dysarthria, such as intelligibility, naturalness, and perceived listener effort, the existing evidence has not been translated into a clinically applicable, comprehensive, and valid diagnostic tool so far. This study addresses Communication-Related Parameters in Speech Disorders (KommPaS), a new web-based diagnostic instrument for measuring indices of communication limitation in individuals with dysarthria through online crowdsourcing. More specifically, it answers questions about the construct validity of KommPaS.

In the first part, the interrelationship of the KommPaS variables
intelligibility, naturalness, perceived listener effort, and speech rate
were explored in order to draw a comprehensive picture of a patient's limitations and avoid the collection of redundant information. Second, the influences of motor speech symptoms on the KommPaS variables were studied in order to delineate the structural relationships between two complementary diagnostic perspectives.

Method:

One hundred persons with dysarthria of different etiologies and varying degrees of severity were examined with KommPaS to obtain layperson-based data on communication-level parameters, and with the Bogenhausen Dysarthria Scale (BoDyS) to obtain expert-based, function-level data on dysarthria symptoms. The internal structure of the KommPaS variables and their dependence on the BoDyS variables were analyzed using structural equation modeling.

Results:

Despite a high multicollinearity, all KommPaS variables were shown to provide complementary diagnostic information and their mutual interconnections were delineated in a path graph model. Regarding the influence of the BoDyS scales on the KommPaS variables, separate linear regression models revealed plausible predictor sets. A complete path model of KommPaS and BoDyS variables was developed to map the complex interplay between variables at the functional and the communication levels of dysarthria assessment.

Conclusion:

In validating a new clinical tool for the diagnostics of communication limitations in dysarthria, this study is the first to draw a comprehensive picture of how auditory-perceptual characteristics of dysarthria interact at the levels of expert-based functional and layperson-based communicative assessments.
Dynamic Norming for Systematic Analysis of Language Transcripts
Authors: Tucci Alexander , Plante Elena , Heilmann John J. , Miller Jon F.
Published: December 2021

Purpose:

This exploratory study sought to establish the psychometric stability of a dynamic norming system using the Systematic Analysis of Language Transcripts (SALT) databases. Dynamic norming is the process by which clinicians select a subset of the normative database sample matched to their individual client's demographic characteristics.

Method:

The English Conversation and Student-Selected Story (SSS) Narrative databases from SALT were used to conduct the analyses in two phases. Phase 1 was an exploratory examination of the standard error of measure (SEM) of six clinically relevant transcript metrics at predetermined sampling intervals to determine (a) whether the dynamic norming process resulted in samples with adequate stability and (b) the minimum sample size required for stable results. Phase 2 was confirmatory, as random samples were taken from the SALT databases to simulate clinical comparison samples. These samples were examined (a) for stability of SEM estimations and (b) to confirm the sample size findings from Phase 1.

Results:

Results of Phase 1 indicated that the SEMs for the six transcript metrics across both databases were low relative to each metric's scale. Samples as small as 40–50 children in the Conversation database and 20–30 children in the SSS Narrative database resulted in stable SEM estimations. Phase 2 confirmed these findings, indicating that age bands as small as ±4 months from a given center-point resulted in stable estimations provided there were approximately 35 children or more in the comparison sample.

Conclusion:

Psychometrically stable comparison samples can be achieved using SALT's dynamic norming system that are much smaller than the standard sample size recommended in most tests of children's language.
Providing Telepractice in Schools During a Pandemic: The Experiences and Perspectives of Speech-Language Pathologists
Authors: Hall-Mills Shannon , Johnson Lakeisha , Gross Melissa , Latham Don , Everhart Nancy
Published: December 2021

Purpose:

The main objective of this study was to gain insight into school-based speech-language pathologists' (SLPs') perspectives on and experiences with telepractice as a service delivery model at the onset of the COVID-19 global pandemic. A better understanding of the facilitating and challenging factors that belie telepractice-based services will guide the creation of training and resource development to further support remote speech-language services in schools.

Method:

Four focus group sessions using a semistructured format were conducted with 22 school-based SLPs from 14 states in the United States. The focus groups provided an opportunity for SLPs to reflect on their telepractice experiences, including pros and cons, necessary knowledge and skills, factors impacting telepractice service delivery, and student and family participation. Inductive thematic analysis was used to describe the collective experiences and perspectives of the participants.

Results:

Three themes regarding telepractice emerged: technology use, locus of control for decision making, and student and family engagement. Participants reported experiencing a range of successes and challenges when attempting to meet students' needs and identified gaps in resources and school capacity for telepractice.

Conclusions:

The findings revealed how school SLPs experienced telepractice service delivery during the remote learning portion of the 2019–2020 school year due to the onset of the COVID-19 pandemic. The study increases our understanding of factors that facilitated and challenged the effective delivery of speech-language services via telepractice. To assist SLPs in future telepractice efforts, implications for professional development and further research are provided.
Modelling an oscillator phase noise whose spectral density contains both 1/f2 and 1/f3 regions
Authors: Aqamolaei Masoumeh , Ahmadi Mohammad Mahdi
Published: December 2021

This paper introduces a new equation for modelling the phase noise spectrum of an oscillator. The new equation can model both of 1/f2 and 1/f3 regions in a phase noise spectrum. To verify the model and show its effectiveness, a mathematical analysis is performed on the effect of the oscillator phase noise on the performance of a continuous‐time delta‐sigma modulator. By comparing the results from the mathematical analysis with those from the Simulink simulation results, it is shown that using the proposed equation can properly predict the effect of oscillator phase noise on the modulator performance.
Non‐existence of (pm,k,1)$(p^m, k, 1)$ difference sets
Authors: Daza David , Martos C. , Trujillo C.
Published: December 2021

Let be an additive abelian group of size . A ‐subset of is called a ‐difference set if every non‐identity element in can be written in ways as the difference of two elements in . This letter proves the non‐existence of ‐difference sets, for all prime and .
A 50nV/√Hz 2‐channel time multiplexed bio‐chopper amplifier with current‐attenuated feedback resistor
Authors: Yuk Beomjin , Kim Byeongseol , Bae Joonsung
Published: December 2021

This paper presents 2‐channel time‐multiplexed chopper instrument amplifier for better gain accuracy and mismatch. Mostly, the current‐attenuated feedback resistor with a duty‐cycled resistor is adopted for boosting the RC time constant. It can achieve the high pass corner frequencies between 10 Hz and 320 Hz by a 3‐bit digitally controlled resistor bank of the attenuator. As a result, the instrument amplifier achieves 0.6% gain accuracy between two time‐multiplexed channels, 100 dB CMRR, ‐40 dB crosstalk, and noise densities of 50nV/√Hz. It is implemented in a 180‐nm CMOS technology. It occupies a 0.6 mm*0.6 mm chip area and consumes 1.5μA current consumption from a 1.8 V supply for each channel.
Hybrid clustering‐based bad data detection of PMU measurements
Authors: Zhu Yanming , Xu Xiaoyuan , Yan Zheng
Published: December 2021

Phasor measurement units (PMUs) have been widely deployed in power grids, while the bad PMU data problem threatens power system monitoring and control. This paper first gives the objective of the bad PMU data detection and gives an illustrative bad data instance. Then, the time‐series PMU data of neighbouring buses are cast as a two‐dimensional diagram, of which the spatio‐temporal correlation analysis is performed to design the normal and outlier data detection problem. Three clustering methods, including linear regression, density‐based spatial clustering of applications with noise (DBSCAN), and Gaussian mixture models (GMM) are ensembled for bad PMU data detection. Moreover, the statistical analysis and bound modification of data clustering are developed to further improve the detection accuracy. Finally, the procedure of the two‐stage bad PMU data detection is given, which consists of ensemble learning and modification. The proposed hybrid clustering‐based bad data detection is unsupervised and is applied to online bad PMU data detection with a short computation time. Visible and numerical case study results validate the outperformance of the proposed method.
Integrated control and monitoring of a smart charging station with a proposed data exchange protocol
Authors: Monadi Mehdi , Farzin Hossein , Salehizadeh Mohammad Reza , Rouzbehi Kumars
Published: December 2021

Expansion of electric vehicles’ (EVs’) charging stations is an unavoidable requirement in sustainable cities. Provision of safe protection and control infrastructure is one of the most important requirements for a reliable charging station. In this direction, a centralized protection, control and monitoring unit (PCMU) for smart charging stations is proposed here. PCMU communicates with chargers of the station, protective devices (e.g. relays and circuit breakers), local generating units and all other devices installed at the charging station to determine the station status and to detect/locate faults that may occur in the supply grid of the station. The PCMU includes a self‐healing technique which is one of the specialties of smart systems that assists network reliability to increase. One of the major contributions of this research is to propose a protocol for data exchange between the PCMU and the other components similar to the logic used in standard of IEC 61850. Also, potential impacts of implementation of the proposed unit on the most‐widely used reliability indices are discussed. The proposed protection strategy is examined via two case studies.
Resilient control of hybrid microgrid with harmonic‐unbalanced loads under outages and faults
Authors: Hemmati Reza , Faraji Hossien
Published: December 2021

A resilient control system in the island microgrid including AC and DC buses is designed here. The DC bus is supported by fuel cell, solar cell and battery and the AC bus is equipped with diesel generator and wind turbine. The AC bus is sectionalized into three sub‐buses that enables to continue operation when one section is not functioning. The connection between DC and AC buses is made by two parallel three‐phase lines each line made by three single‐phase inverters. The objectives are to eliminate the harmonics, the unbalanced load management, dealing with outage of resources and short circuits, providing backup strategies and supplying critical loads under all events. The simulations are performed by MATLAB/Simulink. It is demonstrated that the resilient control technique can achieve all the defined purposes at the same time. The harmonics are eliminated, the unbalanced load issues are dealt with and the microgrid has sufficient resilience against outages and faults.
An asymptotic preserving scheme for a tumor growth model of porous medium type
Authors: David Noemi , Ruan Xinran
Published: December 2021

Mechanical models of tumor growth based on a porous medium approach have been attracting a lot of interest both analytically and numerically. In this paper, we study the stability properties of a finite difference scheme for a model where the density evolves down pressure gradients and the growth rate depends on the pressure and possibly nutrients. Based on the stability results, we prove the scheme to be asymptotic preserving (AP) in the incompressible limit. Numerical simulations are performed in order to investigate the regularity of the pressure. We study the sharpness of theL4-uniform bound of the gradient, the limiting case being a solution whose support contains a bubble which closes-up in finite time generating a singularity, the so-called focusing solution.