bluuebunny/crossref_metadata_2025 huggingface dataset:
A variationally consistent hyperstatic reaction method for tunnel lining design
Authors: Bui Hoang‐Giang , Ninić Jelena , Do Ngoc‐Anh , Dias Daniel , Meschke Günther
Published: October 2021

In this technical note, a consistent finite element formulation of the Hyperstatic Reaction Method (HRM) for tunnel linings design is proposed by introducing a variational consistently linearized formulation. It permits to consider a nonlinear interaction between a lining structure and the surrounding ground. Recent advances of the HRM in regard to the consideration of the nonlinear response of the segmented tunnel lining exposed to design loads use an iterative algorithm for solving the nonlinear system of equations. In the proposed Variationally consistent Hyperstatic Reaction Method (VHRM), a distributed nonlinear spring model representing the interaction between the lining and the ground soils is considered in a variationally consistent format. Computing the tangential spring stiffness via consistent linearization, and using Newton‐Raphson iteration, requires significantly smaller number of iterations as compared to the original HRM model based on nodal springs. Furthermore, the method is applicable for simulations using solid finite elements (2D and 3D), as well as beam or finite shell elements, respectively.
A digital score of tumour‐associated stroma infiltrating lymphocytes predicts survival in head and neck squamous cell carcinoma
Authors: Shaban Muhammad , Raza Shan E Ahmed , Hassan Mariam , Jamshed Arif , Mushtaq Sajid , Loya Asif , Batis Nikolaos , Brooks Jill , Nankivell Paul , Sharma Neil , Robinson Max , Mehanna Hisham , Khurram Syed Ali , Rajpoot Nasir
Published: October 2021

The infiltration of T‐lymphocytes in the stroma and tumour is an indication of an effective immune response against the tumour, resulting in better survival. In this study, our aim was to explore the prognostic significance of tumour‐associated stroma infiltrating lymphocytes (TASILs) in head and neck squamous cell carcinoma (HNSCC) through an AI‐based automated method. A deep learning‐based automated method was employed to segment tumour, tumour‐associated stroma, and lymphocytes in digitally scanned whole slide images of HNSCC tissue slides. The spatial patterns of lymphocytes and tumour‐associated stroma were digitally quantified to compute the tumour‐associated stroma infiltrating lymphocytes score (TASIL‐score). Finally, the prognostic significance of the TASIL‐score for disease‐specific and disease‐free survival was investigated using the Cox proportional hazard analysis. Three different cohorts of haematoxylin and eosin (H&E)‐stained tissue slides of HNSCC cases (n = 537 in total) were studied, including publicly available TCGA head and neck cancer cases. The TASIL‐score carries prognostic significance (p = 0.002) for disease‐specific survival of HNSCC patients. The TASIL‐score also shows a better separation between low‐ and high‐risk patients compared with the manual tumour‐infiltrating lymphocytes (TILs) scoring by pathologists for both disease‐specific and disease‐free survival. A positive correlation of TASIL‐score with molecular estimates of CD8+ T cells was also found, which is in line with existing findings. To the best of our knowledge, this is the first study to automate the quantification of TASILs from routine H&E slides of head and neck cancer. Our TASIL‐score‐based findings are aligned with the clinical knowledge, with the added advantages of objectivity, reproducibility, and strong prognostic value. Although we validated our method on three different cohorts (n = 537 cases in total), a comprehensive evaluation on large multicentric cohorts is required before the proposed digital score can be adopted in clinical practice. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
Population pharmacokinetics and standard uptake value ratio of aducanumab, an amyloid plaque–removing agent, in patients with Alzheimer’s disease
Authors: Kandadi Muralidharan Kumar , Tong Xiao , Kowalski Kenneth G. , Rajagovindan Raj , Lin Lin , Budd Haberlain Samantha , Nestorov Ivan
Published: October 2021

Aducanumab is a human immunoglobulin G1 anti‐amyloid beta (Aβ) antibody currently being evaluated for potential treatment of patients with early Alzheimer’s disease. This paper describes the relationship between the population pharmacokinetics (PopPKs) and pharmacokinetics‐pharmacodynamics (PKs‐PDs) of aducanumab using data from phase I to III clinical studies, with standard uptake value ratio (SUVR) used as a PD marker. Across clinical studies, aducanumab was administered intravenously either as a single dose ranging from 0.3 to 60 mg/kg or as multiple doses of 1, 3, 6, or 10 mg/kg every 4 weeks. A titration regimen with maintenance doses of 3, 6, or 10 mg/kg was also evaluated. Aducanumab PK was characterized with a two‐compartment model with first‐order elimination. No nonlinearities in PKs were observed. The PopPK‐PD model was developed using a sequential estimation approach. The time course of amyloid plaques, as expressed by composite SUVR measured using positron emission tomography, was described using an indirect response model with drug effect stimulating the elimination of SUVR. None of the identified covariates on PK and the PopPK‐PD model were clinically relevant. The PopPK‐PD model showed that magnitude, duration, and consistency of dosing are important factors determining the degree of Aβ removal. The intrinsic pharmacology of aducanumab remained consistent across studies.
1550 nm‐Band InAs/InGaAlAs Quantum Dot Distributed Feedback Lasers Grown on InP(311)B Substrate with Side‐Wall Gratings Simultaneously Fabricated with a Ridge Waveguide
Authors: Kaneko Runa , Morita Ryosuke , Katsuhara Ryumi , Yabuki Ryota , Matsumoto Atsushi , Akahane Koichi , Matsushima Yuichi , Ishikawa Hiroshi , Utaka Katsuyuki
Published: October 2021

A 1550 nm‐band InAs/InGaAlAs quantum dot (QD) distributed feedback (DFB) laser is fabricated, in which the side‐wall grating is formed in a simultaneous process with the ridge waveguide, and room‐temperature continuous‐wave single‐mode oscillation is achieved. A rather low‐threshold current density of about 2.2 kA cm−2 is obtained. Side‐mode suppression ratios (SMSRs) are 28 dB just above the threshold current Ith and 44 dB at I/Ith = 2.0. Antireflection (AR) coating suppresses the amplified spontaneous emission (ASE) and increases the slope efficiency by a factor of 1.3.
Analysis of Light‐Emission Polarization Ratio in Deep‐Ultraviolet Light‐Emitting Diodes by Considering Random Alloy Fluctuations with the 3D k·p Method
Authors: Shen Huan-Ting , Chang Yu-Chieh , Wu Yuh-Renn
Published: October 2021

For nitride‐based AlGaN light‐emitting diodes, the fluctuations in the potential caused by alloy disorder can relax the compressive strain in the lower Al (higher Ga) composition sites. However, strain in the quantum wells impacts the bandgap and the transverse magnetic/transverse electric (TE) polarization ratio. Herein, the 6 × 6 k·p method combined with a 3D Poisson, drift diffusion, and localization landscape solver is used to study the changes in the polarization ratio due to random alloy fluctuations. The influence of different Al compositions in the buffer layer is studied. The results show that the TM polarization ratio with alloy fluctuations is higher than that without fluctuations. On increasing the Al composition in the buffer layer, the polarization ratio changes from 0.93 to −0.67 when the Al composition changes from 60% to 100%.
Optimizing the Oxygen Vacancies Concentration of Thin NiO Nanosheets for Efficient Selective CO2 Photoreduction
Authors: Xiang Junxiang , Zhang Tingshi , Cao Ruodan , Lin Mingxiong , Yang Bixia , Wen Yonglin , Zhuang Zanyong , Yu Yan
Published: October 2021

In designing highly efficient CO2 reduction reaction (CRR) photocatalysts with excellent selectivity and efficiency, a key limitation is the poor understanding on the mechanism response of the active sites of catalysts to CRR selectivity and activity. Herein, it is revealed how the concentration of point defect affects the CRR selectivity and activity of catalysts. Quasi‐2D NiO nanosheets (NSs) that are composed of NiO nanoparticles (NPs), and finely tuned the oxygen vacancies (OVs) concentration of the NSs by regulating the grain size (≈5–25 nm) of NPs are created. The NiO with moderate OVs concentration has the highest photocatalytic CRR efficiency and selectivity (V
CO = 17.2 μmol h−1, 98.3%), outperforming other prepared NiO catalysts and reported Ni‐based photocatalysts. Density functional theory calculation associated with the CO2 temperature‐programmed desorption confirms that the moderate OVs concentration enables strong CO2 binding to promote CO2 adsorption and activation and allows efficient charge transfer. In contrast, excessive OVs reduce the CO2 binding affinity and restrain charge mobility, both detrimental to the CRR performance.
Four-point correlation modular bootstrap for OPE densities
Authors: Cardona Carlos , Keeler Cynthia , Munizzi William
Published: October 2021

Abstract

In this work we apply the lightcone bootstrap to a four-point function of scalars in two-dimensional conformal field theory. We include the entire Virasoro symmetry and consider non-rational theories with a gap in the spectrum from the vacuum and no conserved currents. For those theories, we compute the large dimension limit (h/c ≫ 1) of the OPE spectral decomposition of the Virasoro vacuum. We then propose a kernel ansatz that generalizes the spectral decomposition beyond h/c ≫ 1. Finally, we estimate the corrections to the OPE spectral densities from the inclusion of the lightest operator in the spectrum.
Insulinautoimmunsyndrom
Authors: de Castro Tiago , Beier Christoph , Terkamp Christoph , Oehler Lucia , Schmidt Bernhard M. W. , Heck Johannes , Stichtenoth Dirk , Wedemeyer Heiner , Leitolf Holger
Published: October 2021

Eine 69-jährige Patientin mit rezidivierenden schweren Hypoglykämien wurde zur weiteren Diagnostik der Medizinischen Hochschule Hannover zugewiesen. Zuvor hatte die Patientin nach einem Stenting, das aufgrund einer peripheren arteriellen Verschlusskrankheit (pAVK) erforderlich war, mit einer Clopidogreleinnahme begonnen. Das Vorliegen eines Insulinoms und eines paraneoplastischen Syndroms wurde ausgeschlossen. Trotz niedrig normaler Blutzuckerkonzentrationen fanden sich erhöhte Insulin- und Insulinautoantikörperkonzentrationen. Diagnostiziert wurde ein Insulinautoimmunsyndrom, a.e. (am ehesten) ausgelöst durch vorausgegangene Clopidogreleinnahme. Eine Behandlung mithilfe der Immunadsorption wurde initiiert; diese erzielte eine signifikante Reduktion der hypoglykämischen Ereignisse und ein anhaltendes Therapieansprechen über 3 Monate.
Multimodal Assessments of Altered Sensation after Transoral Endoscopic Thyroidectomy
Authors: Liang Tsung‐Jung , Wang Kuo‐Chiang , Liu Shiuh‐Inn , Chen I.‐Shu , Wang Nai‐Yu
Published: October 2021

Background

Transoral endoscopic thyroidectomy, a novel technique, uses oral vestibule as the entry point and leaves no scar on the body surface. However, because the incisions are close to the mental nerve, nerve damage and the associated sensory impairment are concerning. Herein, we evaluated sensory alteration after transoral endoscopic thyroidectomy and determined factors associated with the prolonged sensory alteration.

Methods

Patients who underwent transoral endoscopic thyroidectomy were enrolled. Sensation over the lower lip, chin, and neck was evaluated before and after the surgery. A self‐assessment questionnaire, Semmes–Weinstein monofilament test, and two‐point discrimination test were used to subjectively and objectively evaluate sensory changes.

Results

Fifty‐one patients were enrolled; most of them reported altered sensation, with chin (72.5%) being the most common site, followed by lower lip (52.9%), upper neck (33.3%), and lower neck (5.9%) on postoperative day 2. The sensory disturbance resolved within 3 months. Factors associated with prolonged sensory alteration are male sex and old age. Fourteen patients (27.5%) experienced mild drooling from the mouth, which was usually self‐limiting in 1 month. Sensory impairments in light touch pressure threshold and two‐point discrimination were significant in the chin and neck on postoperative day 2 and at 1 week. The ability to discern two‐point was also compromised in the lower lip on postoperative day 2. All these significant changes normalized to preoperative baseline at 1 month.

Conclusions

There was an altered sensation after transoral endoscopic thyroidectomy with the most common and disturbed in the chin. Sensory impairment was usually transient and recovered in 3 months.
Fairness in ambulance routing for post disaster management
Authors: Aringhieri Roberto , Bigharaz Sara , Duma Davide , Guastalla Alberto
Published: October 2021

Disaster management generally includes the post-disaster stage, which consists of the actions taken in response to the disaster damages. These actions include the employment of emergency plans and assigned resources to (i) rescue affected people immediately, (ii) deliver personnel, medical care and equipment to the disaster area, and (iii) aid to prevent the infrastructural and environmental losses. In the response phase, humanitarian logistics directly influence the efficiency of the relief operation. Ambulances routing problem is defined as employing the optimisation tools to manage the flow of ambulances for finding the best ambulance tours to transport the injured to hospitals. Researchers pointed out the importance of equity and fairness in humanitarian relief services: managing the operations of ambulances in the immediate aftermath of a disaster must be done impartially and efficiently to rescue affected people with different priority in accordance with the restrictions. Our research aim is to find the best ambulance tours to transport the patients during a disaster in relief operations while considering fairness and equity to deliver services to patients in balance. The problem is formulated as a new variant of the team orienteering problem with hierarchical objectives to address also the efficiency issue. Due to the limitation of solving the proposed model using a general-purpose solver, we propose a new hybrid algorithm based on a machine learning and neighbourhood search. Based on a new set of realistic benchmark instances, our quantitative analysis proves that our algorithm is capable to largely reduce the solution running time especially when the complexity of the problem increases. Further, a comparison between the fair solution and the system optimum solution is also provided.
3D Knitted Preforms Using Large Circular Weft Knitting Machines
Authors: Peiner Christoph , Löcken Henning , Reinsch Leon , Gries Thomas
Published: October 2021

3D-knits are typically produced on flat knitting or special circular knitting machines in a time-consuming process. The utilisation of a sewing-like pattern opens up the potential of a 10–50 times faster production on common large circular knitting machines as compared to conventional flat knitting machines. Since common large circular knitting machines are not designed for this technology, the limitations and the stability of process conditions have been rarely studied. To further proof the feasibility and increase technological maturity, agile product development is conducted. As a concept product, a sports bra with customised cups is developed and demonstrated, which is knitted in a single step in approx. 5 min using the sewing-like pattern on a large circular knitting machine. The agile process is utilised to build process knowledge, develop a methodology for product design and to defined a descriptive process terminology. In order to further accelerate and digitize the production process, an algorithm is developed and implemented to convert CAD-data into machine readable knitting structures. The paper presents the basics of the 3D-Knit one large circular knitting machines and a defined terminology. Furthermore, process knowledge is built up and from this a sequence of development steps is derived. The development of a 3D-knitted sports bra is presented as a proof of concept of the technology. Further, the first steps for digitalising the product development process are given. The results open up application possibilities in sportswear, upholstery and aerospace with increased productivity and hence cost reduction.
NoBLE for Lattice Trees and Lattice Animals
Authors: Fitzner Robert , van der Hofstad Remco
Published: October 2021

We study lattice trees (LTs) and animals (LAs) on the nearest-neighbor lattice $${\mathbb {Z}}^d$$

Z

d

in high dimensions. We prove that LTs and LAs display mean-field behavior above dimension $$16$$

16

and $$17$$

17

, respectively. Such results have previously been obtained by Hara and Slade in sufficiently high dimensions. The dimension above which their results apply was not yet specified. We rely on the non-backtracking lace expansion (NoBLE) method that we have recently developed. The NoBLE makes use of an alternative lace expansion for LAs and LTs that perturbs around non-backtracking random walk rather than around simple random walk, leading to smaller corrections. The NoBLE method then provides a careful computational analysis that improves the dimension above which the result applies. Universality arguments predict that the upper critical dimension, above which our results apply, is equal to $$d_c=8$$

d
c

=
8

for both models, as is known for sufficiently spread-out models by the results of Hara and Slade mentioned earlier. The main ingredients in this paper are (a) a derivation of a non-backtracking lace expansion for the LT and LA two-point functions; (b) bounds on the non-backtracking lace-expansion coefficients, thus showing that our general NoBLE methodology can be applied; and (c) sharp numerical bounds on the coefficients. Our proof is complemented by a computer-assisted numerical analysis that verifies that the necessary bounds used in the NoBLE are satisfied.
The Role of Nonprofit–Private Collaboration for Nonprofits’ Organizational Resilience
Authors: Waerder Rebecca , Thimmel Simon , Englert Benedikt , Helmig Bernd
Published: October 2021

Growing social, political, and economic uncertainties have shown that organizational resilience is becoming increasingly important for nonprofit organizations (NPOs). To ensure their long-term survival, NPOs need to respond to extreme events and adapt their services and processes. The theoretical premise of resource dependence theory assumes that interactions between an organization and its environment are crucial for the long-term adaptation to adversities. The present study investigates the contributions of nonprofit–private collaborations to organizational resilience of NPOs in light of the refugee crisis in Germany in 2015. Findings from a multiple holistic case study design indicate that collaborations of nonprofits with for-profit organizations support NPOs with stability, resources, expertise, and compassion to overcome resource-based, conceptual, and emotional challenges.
Monoclonal Antibodies in the Management of Familial Hypercholesterolemia: Focus on PCSK9 and ANGPTL3 Inhibitors
Authors: Pirillo Angela , Catapano Alberico L. , Norata Giuseppe D.
Published: October 2021

Purpose of Review

Familial hypercholesterolemia (FH) is a monogenic disorder characterized by high plasma levels of low-density lipoprotein cholesterol (LDL-C) since birth and a high risk of premature cardiovascular disease. The genetic defect is carried in only one allele in heterozygous FH (HeFH) or in both in the most severe homozygous FH (HoFH). Current guidelines recommend to reduce substantially LDL-C levels in these high-risk patients, with the need to use association therapy combining agents with different mechanisms of action. As most cases of FH are attributable to mutations in the gene encoding the low-density lipoprotein receptor (LDLR), statins, even in combination with ezetimibe, are less effective in reducing LDL-C plasma levels in FH patients, who require a more intensive approach with additional lipid-lowering agents. Additional targets playing key roles in regulating LDL-C levels are represented by PCSK9 and ANGPTL3.

Recent Findings

Two monoclonal antibodies (mAbs) targeting PCSK9, evolocumab and alirocumab, significantly reduce LDL-C levels in HeFH patients. In patients with HoFH, the efficacy of mAbs to PCSK9 is strictly related to the presence of a residual LDLR activity; thus, patients carrying null mutations do not respond to the therapy with these mAbs, whereas some effects can be appreciated in HoFH bearing defective mutations. Conversely, evinacumab, the mAb targeting ANGPTL3, is highly effective in reducing LDL-C levels even in HoFH patients carrying nullLDLRmutations, thanks to its LDLR-independent mechanism of action.

Monoclonal antibodies inhibiting PCSK9 have shown a robust effect in FH patients presenting a residual LDLR activity, while ANGPTL3 inhibitors appear to be promising even in patients carrying nullLDLRmutations.
The Practice and Politics of Urban Climate Change Mitigation and Adaptation Efforts: The Case of Cairo
Authors: Dabaieh Marwa , Maguid Dalya , Abodeeb Rasha , Mahdy Deena El
Published: October 2021

Research on climate change mitigation and adaptation is pressing in order to understand its implications and risks in different urban areas. It is especially critical for those who face high degrees of urban inequality in the context of an uneven state presence. This paper is an explorative and investigative study which uses Cairo as a case. The focus of the study is on mapping state and private sector efforts in mitigating climate change issues, specifically for vulnerable groups who have limited access to public services. The study adopted an investigative approach where a literature search and bibliometric mapping were used to identify the gap in knowledge in the field of architecture and urban climate change mitigation and adaptation, followed by a field survey which included conducting interviews and questionnaires with different stakeholders from the public and private sector to investigate the link between the efforts for climate change mitigation. The explorative part of the study concluded that there is a huge knowledge gap in the Middle East and in Egypt when it comes to research efforts related to climate change with a focus on the built environment. The results of the investigative part of this study revealed that—apart from already limited efforts on ground—there is no synchronization in efforts between the public and private sector. Climate change issues are still not a priority when poverty, economy, and health are still a prime concern and take precedence over climate change. There is uneven presence of public efforts for climate change adaptation and mitigation. The efforts that do exist in the public sphere are self-help unorganized work (efforts) conducted by the civil society.
Computer Age Statistical Inference, Student Edition
Authors: Efron Bradley , Hastie Trevor
Published: October 2021

The twenty-first century has seen a breathtaking expansion of statistical methodology, both in scope and influence. 'Data science' and 'machine learning' have become familiar terms in the news, as statistical methods are brought to bear upon the enormous data sets of modern science and commerce. How did we get here? And where are we going? How does it all fit together? Now in paperback and fortified with exercises, this book delivers a concentrated course in modern statistical thinking. Beginning with classical inferential theories - Bayesian, frequentist, Fisherian - individual chapters take up a series of influential topics: survival analysis, logistic regression, empirical Bayes, the jackknife and bootstrap, random forests, neural networks, Markov Chain Monte Carlo, inference after model selection, and dozens more. The distinctly modern approach integrates methodology and algorithms with statistical inference. Each chapter ends with class-tested exercises, and the book concludes with speculation on the future direction of statistics and data science.
Eukarya biodiversity in the Thala Hills, East Antarctica
Authors: Lukashanets Dzmitry A. , Convey Peter , Borodin Oleg I. , Miamin Vladislav Ye. , Hihiniak Yury H. , Gaydashov Alexey A. , Yatsyna Aleksander P. , Vezhnavets Vasil V. , Maysak Natallia N. , Shendrik Tatyana V.
Published: October 2021

Knowledge of the biodiversity of the Thala Hills oasis (Enderby Land, East Antarctica) is very limited. Here, we integrate all information available since 1962, when the Russian ‘Molodyozhnaya’ station was established in the western part of the oasis. The published data on local eukaryote diversity (lichens, embryophytes, metazoans) include records of 90 species. Since 2008, Belarusian Antarctic Expedition researchers have worked in the eastern part of the oasis, accessible from the Belarusian station ‘Vechernyaya Mount'. This research revealed 95 species, including 44 species not recorded in the earlier published literature. The level of available information is uneven across major taxa. Lichens are the better-known group, with 51 species recorded in total, including 13 species recently recorded for the first time in the oasis. New records were also obtained for rotifers. Thala Hills biodiversity is consistent with wider patterns of Antarctic biogeography, with a high proportion of regionally endemic species (especially metazoans), the occurrence of both endemic and bipolar species of lichens and generally low numbers of cosmopolitan species (largely limited to aquatic rotifers, with the caveat that up-to-date taxonomic studies are required). The lack of data on marine macrobenthos, soil nematodes and terrestrial rotifers emphasizes the need for studies focusing on these groups.
Air Pollution Killed a Million People in Africa in 2019
Authors: Mambondiyani Andrew
Published: October 2021

Experts say nature-based mitigation strategies and investment in renewables could reduce both indoor and outdoor air pollution and stimulate sustainable and safe growth.
Quantifying Non‐Thermal Silicate Weathering Using Ge/Si and Si Isotopes in Rivers Draining the Yellowstone Plateau Volcanic Field, USA
Authors: Gaspard François , Opfergelt Sophie , Hirst Catherine , Hurwitz Shaul , McCleskey R. Blaine , Zahajská Petra , Conley Daniel J. , Delmelle Pierre
Published: October 2021

In active volcanic regions, high‐temperature chemical reactions in the hydrothermal system consume CO2 sourced from magma or from the deep crust, whereas reactions with silicates at shallow depths mainly consume atmospheric CO2. Numerous studies have quantified the load of dissolved solids in rivers that drain volcanic regions to determine chemical weathering rates and atmospheric CO2 consumption rates. However, the balance between thermal and non‐thermal components to riverine fluxes in these areas remains poorly constrained, hindering accurate estimates of atmospheric CO2 consumption rates. Here we use the Ge/Si ratio and the stable silicon isotopes (δ30Si) as tracers for quantifying non‐thermal silicon contributions in rivers draining the Yellowstone Plateau Volcanic Field, USA. The Ge/Si ratio (µmol.mol−1) was determined for seven thermal water samples (183 ± 22), eight rivers (35 ± 23) and six creeks flowing into Yellowstone Lake (5 ± 3) during base flow and during peak water discharge following snowmelt. The δ30Si value (‰) was determined for thermal waters (−0.09 ± 0.04), Yellowstone River at Yellowstone Lake outlet (1.91 ± 0.23) and creek samples (0.82 ± 0.29). The calculated atmospheric CO2 consumption associated with non‐thermal waters flowing through Yellowstone's rivers during peak discharge is ∼3.03 ton.km−2.yr−1, which is ∼2% of the annual mean atmospheric CO2 consumption in other volcanic regions. This study highlights the significance of quantifying seasonal variations in chemical weathering rates for improving estimates of atmospheric CO2 consumption rates in active volcanic regions.
Evaluation of Radiocarbon 14C Yield Under Conditions of Thunderstorms
Authors: Lyashuk V. I.
Published: October 2021

The knowledge of radioactive 14C yield under atmospheric thunderstorm flash conditions (the additional channel of 14C production relative to the main cosmogenic one) is important for radiocarbon analysis. A gross model for evaluation of the thunderstorm 14C yield simulated for the altitudes up to 15 km is proposed. It was observed that yield from the thunderstorm mechanisms of 14C creation cannot compete with cosmogenic production which is six orders of value larger. The obtained result allows us to eliminate the problematic issue on thunderstorm radiocarbon generation in the atmosphere as the additional significant source.
Spatiotemporal Patterns of Fractional Suspended Sediment Dynamics in Small Watersheds
Authors: Al‐Ghorani Nisreen G. , Hassan Marwan A. , Langendoen Eddy J.
Published: October 2021

Understanding suspended sediment dynamics and their driving factors is essential for effective watershed management. In this study, the spatiotemporal patterns of suspended sediment were identified for 11 sub‐watersheds of the Goodwin Creek, Mississippi, USA, for the period 1982–2002 using wavelet transforms. The continuous wavelet transform (CWT) results of streamflow time series showed that a near‐continuous annual periodicity influenced all stations over the study period, yet an overall decline occurred in wavelet spectral power of sediment load during the 1990s. This decline in sediment load is a result of the indirect effect of decreased cultivation on reducing the rate of peak flow and thus fluvial erosion processes. The CWTs of fine sediment (clays and silts) concentration (FSC) time series showed that factors other than land‐use (e.g., ponds, ephemeral gullies, and bed composition) better explain the variations in FSC. A comparison of CWTs of FSC at two stations with different bed composition in their channels showed that sandy channels are less responsive to erosion control measures compared to gravely channels indicating that they are major sources of sediment. A change in phase relationship between flow and FSC for the gravel‐dominated channel was associated with the transition in upland land‐use indicating a change in sediment supply mechanisms. The CWTs of sand concentrations reflected the spatiotemporal impact of bank materials, the growth cycle of riparian vegetation, and in‐channel sand availability on sand dynamics. While CWT‐based analysis is sensitive to input conditions, the method is able to provide valuable outcomes for distinguishing patterns in complex temporal datasets.
Exploiting rotational asymmetry for sub-50 nm mechanical nanocalligraphy
Authors: Farmakidis Nikolaos , Swett Jacob L. , Youngblood Nathan , Li Xuan , Evangeli Charalambos , Aggarwal Samarth , Mol Jan A. , Bhaskaran Harish
Published: October 2021

Nanofabrication has experienced extraordinary progress in the area of lithography-led processes over the last decades, although versatile and adaptable techniques addressing a wide spectrum of materials are still nascent. Scanning probe lithography (SPL) offers the capability to readily pattern sub-100 nm structures on many surfaces; however, the technique does not scale to dense and multi-lengthscale structures. Here, we demonstrate a technique, which we term nanocalligraphy scanning probe lithography (nc-SPL), that overcomes these limitations. Nc-SPL employs an asymmetric tip and exploits its rotational asymmetry to generate structures spanning the micron to nanometer lengthscales through real-time linewidth tuning. Using specialized tip geometries and by precisely controlling the patterning direction, we demonstrate sub-50 nm patterns while simultaneously improving on throughput, tip longevity, and reliability compared to conventional SPL. We further show that nc-SPL can be employed in both positive and negative tone patterning modes, in contrast to conventional SPL. This underlines the potential of this technique for processing sensitive surfaces such as 2D materials, which are prone to tip-induced shear or beam-induced damage.
Emerging roles of the Hedgehog signalling pathway in inflammatory bowel disease
Authors: Xie Zhuo , Zhang Mudan , Zhou Gaoshi , Lin Lihui , Han Jing , Wang Ying , Li Li , He Yao , Zeng Zhirong , Chen Minhu , Zhang Shenghong
Published: October 2021

The Hedgehog (Hh) signalling pathway plays a critical role in the growth and patterning during embryonic development and maintenance of adult tissue homeostasis. Emerging data indicate that Hh signalling is implicated in the pathogenesis of inflammatory bowel disease (IBD). Current therapeutic treatments for IBD require optimisation, and novel effective drugs are warranted. Targeting the Hh signalling pathway may pave the way for successful IBD treatment. In this review, we introduce the molecular mechanisms underlying the Hh signalling pathway and its role in maintaining intestinal homeostasis. Then, we present interactions between the Hh signalling and other pathways involved in IBD and colitis-associated colorectal cancer (CAC), such as the Wnt and nuclear factor-kappa B (NF-κB) pathways. Furthermore, we summarise the latest research on Hh signalling associated with the occurrence and progression of IBD and CAC. Finally, we discuss the future directions for research on the role of Hh signalling in IBD pathogenesis and provide viewpoints on novel treatment options for IBD by targeting Hh signalling. An in-depth understanding of the complex role of Hh signalling in IBD pathogenesis will contribute to the development of new effective therapies for IBD patients.
SARS-CoV-2 exploits host DGAT and ADRP for efficient replication
Authors: Yuan Shuofeng , Yan Bingpeng , Cao Jianli , Ye Zi-Wei , Liang Ronghui , Tang Kaiming , Luo Cuiting , Cai Jianpiao , Chu Hin , Chung Tom Wai-Hing , To Kelvin Kai-Wang , Hung Ivan Fan-Ngai , Jin Dong-Yan , Chan Jasper Fuk-Woo , Yuen Kwok-Yung
Published: October 2021

Coronavirus Disease 2019 (COVID-19) is predominantly a respiratory tract infection that significantly rewires the host metabolism. Here, we monitored a cohort of COVID-19 patients’ plasma lipidome over the disease course and identified triacylglycerol (TG) as the dominant lipid class present in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced metabolic dysregulation. In particular, we pinpointed the lipid droplet (LD)-formation enzyme diacylglycerol acyltransferase (DGAT) and the LD stabilizer adipocyte differentiation-related protein (ADRP) to be essential host factors for SARS-CoV-2 replication. Mechanistically, viral nucleo capsid protein drives DGAT1/2 gene expression to facilitate LD formation and associates with ADRP on the LD surface to complete the viral replication cycle. DGAT gene depletion reduces SARS-CoV-2 protein synthesis without compromising viral genome replication/transcription. Importantly, a cheap and orally available DGAT inhibitor, xanthohumol, was found to suppress SARS-CoV-2 replication and the associated pulmonary inflammation in a hamster model. Our findings not only uncovered the mechanistic role of SARS-CoV-2 nucleocapsid protein to exploit LDs-oriented network for heightened metabolic demand, but also the potential to target the LDs-synthetase DGAT and LDs-stabilizer ADRP for COVID-19 treatment.
K2P18.1 translates T cell receptor signals into thymic regulatory T cell development
Authors: Ruck Tobias , Bock Stefanie , Pfeuffer Steffen , Schroeter Christina B. , Cengiz Derya , Marciniak Paul , Lindner Maren , Herrmann Alexander , Liebmann Marie , Kovac Stjepana , Gola Lukas , Rolfes Leoni , Pawlitzki Marc , Opel Nils , Hahn Tim , Dannlowski Udo , Pap Thomas , Luessi Felix , Schreiber Julian A. , Wünsch Bernhard , Kuhlmann Tanja , Seebohm Guiscard , Tackenberg Björn , Seja Patricia , Döring Frank , Wischmeyer Erhard , Chasan Achmet Imam , Roth Johannes , Klotz Luisa , Meyer zu Hörste Gerd , Wiendl Heinz , Marschall Tobias , Floess Stefan , Huehn Jochen , Budde Thomas , Bopp Tobias , Bittner Stefan , Meuth Sven G.
Published: October 2021

It remains largely unclear how thymocytes translate relative differences in T cell receptor (TCR) signal strength into distinct developmental programs that drive the cell fate decisions towards conventional (Tconv) or regulatory T cells (Treg). Following TCR activation, intracellular calcium (Ca2+) is the most important second messenger, for which the potassium channel K2P18.1 is a relevant regulator. Here, we identify K2P18.1 as a central translator of the TCR signal into the thymus-derived Treg (tTreg) selection process. TCR signal was coupled to NF-κB-mediated K2P18.1 upregulation in tTreg progenitors. K2P18.1 provided the driving force for sustained Ca2+ influx that facilitated NF-κB- and NFAT-dependent expression of FoxP3, the master transcription factor for Treg development and function. Loss of K2P18.1 ion-current function induced a mild lymphoproliferative phenotype in mice, with reduced Treg numbers that led to aggravated experimental autoimmune encephalomyelitis, while a gain-of-function mutation in K2P18.1 resulted in increased Treg numbers in mice. Our findings in human thymus, recent thymic emigrants and multiple sclerosis patients with a dominant-negative missense K2P18.1 variant that is associated with poor clinical outcomes indicate that K2P18.1 also plays a role in human Treg development. Pharmacological modulation of K2P18.1 specifically modulated Treg numbers in vitro and in vivo. Finally, we identified nitroxoline as a K2P18.1 activator that led to rapid and reversible Treg increase in patients with urinary tract infections. Conclusively, our findings reveal how K2P18.1 translates TCR signals into thymic T cell fate decisions and Treg development, and provide a basis for the therapeutic utilization of Treg in several human disorders.
Juvenile hormone analog enhances Zika virus infection in Aedes aegypti
Authors: Alomar Abdullah A. , Eastmond Bradley H. , Alto Barry W.
Published: October 2021

In recent years, there has been a rise in the emergence of arboviruses of public health importance, including Zika, chikungunya, dengue, and yellow fever viruses. Insecticide-based mosquito control has been the primary method for mitigating transmission of arboviruses. The consequences for the application of insecticides include both lethal and sublethal effects, and associated development of insecticide resistance. However, little is known about the influence on arboviral transmission. Mosquitoes with phenotypes that exhibit insecticide resistance or experience sublethal effects may be associated with altered susceptibility to arbovirus infection and transmission. Juvenile hormone analogs (JHAs) are insecticides that prevent pupa to adult molting of mosquitoes by mimicking the action of their natural juvenile hormone. Here, we examined whether the JHA pyriproxyfen interacts with ambient temperature (20 °C and 30 °C) during juvenile stages to influence life-history traits, population growth (λ'), and Zika virus (ZIKV) infection in Aedes aegypti. Development time of females was lengthened at 20 °C and in the presence of JHA. Prevention of pupa to adult molting by JHA was differentially higher at elevated temperature than low temperature. Size of females was larger at 20 °C and smaller at 30 °C. Infection, disseminated infection, and transmission of ZIKV in females were enhanced by JHA at both 20 °C and 30 °C relative to the controls. These results demonstrate that mosquito life-history and vector competence parameters are strongly influenced by interactive effects of JHA and temperature. The JHA-induced enhancement of ZIKV infection in females should be a consideration when implementing JHA in vector control strategies.
Influence of climate factors on pediatric alopecia areata flares in Philadelphia, Pennsylvania
Authors: George Elisabeth A. , Castelo-Soccio Leslie , Putterman Elana , Kuhn Helena , Wambier Carlos , Qureshi Abrar , Cho Eunyoung
Published: October 2021

Patients with alopecia areata (AA) may experience episodic disease flares characterized by increasing hair loss that follow a seasonal pattern. However, no studies have examined whether specific climate factors contribute to the seasonal pattern of AA flares. Using Spearman rank correlation analyses, we assessed the association between climate variables and AA flare frequency per month in 336 children with AA in Philadelphia, Pennsylvania. Region-specific monthly values for average ambient temperature, air pressure, cloudiness, hours of sunlight, relative humidity, number of days with sun, number of days with rain, volume of precipitation, wind gust, wind speed, and UV index from January 2015 to December 2017 were obtained from World Weather Online. We found significant (P < 0.05) correlations between AA flare frequency and UV index (R = − 0.66), precipitation (R = − 0.66), number of days with rain (R = − 0.70), number of days with sun (R = 0.62), and air pressure (R = 0.80). Stratified analyses showed even stronger associations with UV index and precipitation in patients with an atopic comorbidity. New significant correlations appeared with temperature, wind speed, and UV index of the prior month. However, in patients who did not have atopic comorbidities, we generally observed weaker and non-significant correlations between climate and AA flare frequency. This study suggests that certain climate factors may mediate the seasonal pattern of AA flares and may contribute to AA pathogenesis. Atopic AA patients may be more susceptible to the influence of climate compared to those with no history of atopy.
Intubated COVID-19 predictive (ICOP) score for early mortality after intubation in patients with COVID-19
Authors: Nishikimi Mitsuaki , Rasul Rehana , Sison Cristina P. , Jafari Daniel , Shoaib Muhammad , Shinozaki Koichiro , Li Timmy , Hayashida Kei , Rolston Daniel M. , Hirsch Jamie S. , Becker Lance B. ,   The Northwell Health COVID-19 Research Consortium, Barish Matthew A. , Barnaby Douglas P. , Miyara Santiago J. , Burns Edith , Cohen Stuart L. , Cookingham Jennifer , Dominello Andrew J. , Johnson Jennifer C. , Kozel Zachary M. , Lima Brian , McGinn Ariana K. , Molmenti Ernesto P. , Monane Rachel , d. Paradis Marc
Published: October 2021

Patients with coronavirus disease 2019 (COVID-19) can have increased risk of mortality shortly after intubation. The aim of this study is to develop a model using predictors of early mortality after intubation from COVID-19. A retrospective study of 1945 intubated patients with COVID-19 admitted to 12 Northwell hospitals in the greater New York City area was performed. Logistic regression model using backward selection was applied. This study evaluated predictors of 14-day mortality after intubation for COVID-19 patients. The predictors of mortality within 14 days after intubation included older age, history of chronic kidney disease, lower mean arterial pressure or increased dose of required vasopressors, higher urea nitrogen level, higher ferritin, higher oxygen index, and abnormal pH levels. We developed and externally validated an intubated COVID-19 predictive score (ICOP). The area under the receiver operating characteristic curve was 0.75 (95% CI 0.73–0.78) in the derivation cohort and 0.71 (95% CI 0.67–0.75) in the validation cohort; both were significantly greater than corresponding values for sequential organ failure assessment (SOFA) or CURB-65 scores. The externally validated predictive score may help clinicians estimate early mortality risk after intubation and provide guidance for deciding the most effective patient therapies.
Spectroscopic evidence of mixed angular momentum symmetry in non-centrosymmetric Ru$$_7$$B$$_3$$
Authors: Datta Soumya , Vasdev Aastha , Ramachandran Ranjani , Halder Soumyadip , Motla Kapil , Kataria Anshu , Arushi  , Roy Chowdhury Rajeswari , Singh Ravi Prakash , Sheet Goutam
Published: October 2021

Superconducting crystals with a lack of inversion symmetry can potentially host unconventional pairing. However, till today, no direct conclusive experimental evidence of such unconventional order parameters in non-centrosymmetric superconductors has been reported. In this paper, through direct measurement of the superconducting energy gap by scanning tunnelling spectroscopy, we report the existence of both s-wave (singlet) and p-wave (triplet) pairing symmetries in non-centrosymmetric Ru$$_7$$

7

B$$_3$$

3

. Our temperature and magnetic field-dependent studies also indicate that the relative amplitudes of the singlet and triplet components change differently with temperature.
A primer on harnessing non-enzymatic post-translational modifications for drug design
Authors: Long Marcus J. C. , Ly Phillippe , Aye Yimon
Published: October 2021

Our primer discusses the current issues faced when medicinal chemists try to leverage highly reactive electrophiles for drug development.
Acoustically propelled nano- and microcones: fast forward and backward motion
Authors: Voß Johannes , Wittkowski Raphael
Published: October 2021

We focus on cone-shaped nano- and microparticles, which have recently been found to show strong propulsion when exposed to a traveling ultrasound wave, and study by computer simulations how their propulsion depends on the cones' aspect ratio.
Metal-free electrochemical synthesis of α-ketoamides via decarboxylative coupling of α-keto acids with isocyanides and water
Authors: Zhao Feng , Meng Na , Sun Ting , Wen Jiangwei , Zhao Xiaohui , Wei Wei
Published: October 2021

A mild and convenient electrochemical protocol has been developed for the preparation of α-ketoamides via a decarboxylative coupling reaction of α-keto acids with isocyanides and water.
Nickel-catalyzed direct cross-coupling of heterocyclic phosphonium salts with aryl bromides
Authors: Cui Yan-Ying , Li Wen-Xin , Ma Na-Na , Shen Chuanji , Zhou Xiaocong , Chu Xue-Qiang , Rao Weidong , Shen Zhi-Liang
Published: October 2021

The cross-couplings of heterocyclic phosphonium salts with aryl bromides proceeded effectively in the presence of nickel(ii) catalyst, bipyridine ligand, magnesium, and LiCl, providing an easy entry to 4-arylated pyridines, quinolines, and pyrazines.
Hierarchical three-dimensional copper selenide nanocube microelectrodes for improved carbon dioxide reduction reactions
Authors: Elakkiya Rajasekaran , Maduraiveeran Govindhan
Published: October 2021

One-step electrochemical fabrication of a series of hierarchical 3-D CuSe nanocubes assembled as domain nanocube-, branched nanocube-, and dendrite nanocube-like surface morphologies on Cu microelectrodes for improved CO2RR is reported.
Production of doxorubicin-loaded PCL nanoparticles through a flow-focusing microfluidic device: encapsulation efficacy and drug release
Authors: Heshmatnezhad Fazlollah , Solaimany Nazar Ali Reza , Aghaei Halimeh , Varshosaz Jaleh
Published: October 2021

The present study shows a facile route for producing doxorubicin (DOX)-loaded polycaprolactone (PCL) nanoparticles using a microfluidic device with a flow-focusing platform in a single step.
A cooperative afterglow enhancement in the second biological window of Na2CaSn2Ge3O12with co-doping of Pr3+–Yb3+
Authors: Gao Xiuping , Liu Tao , Jiang Xiaohui , Huang Kai , Liu Runlin , Zhou Jinyuan , Xie Erqing , Li Yang , Liu Weisheng , Wang Min , Han Gang
Published: October 2021

A novel near-infrared persistent luminescent phosphor Na2CaSn2Ge3O12(NCSGO) doped with Ho3+, Er3+, Tm3+and Yb3+was synthesized by a high-temperature solid-state reaction.
Dual self-trapped exciton emission of (TBA)2Cu2I4: optical properties and high anti-water stability
Authors: Peng Hui , Xiao Yonghao , Tian Ye , Wang Xinxin , Huang Tao , Dong Tiantian , Zhao Yueting , Wang Jianping , Zou Bingsuo
Published: October 2021

We report zero-dimensional organic copper iodide single crystals of (TBA)2Cu2I4 with high anti-water stability, which can be stable in water for 24 hours. Upon photoexcitation, this compound exhibits a cool-white emission.