bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of the clinical cardiac safety of pemigatinib, a fibroblast growth factor receptor inhibitor, in participants with advanced malignancies
Authors: Gong Xiaohua , Ji Tao , Liu Xiang , Chen Xuejun , Yeleswaram Swamy
Published: December 2021

Pemigatinib is a potent inhibitor of the fibroblast growth factor receptor (FGFR) family of receptors that is approved for the treatment of cholangiocarcinoma with FGFR2 fusion or other rearrangements. Data from a first‐in‐human clinical study were used to assess the potential for pemigatinib to produce clinically significant effects on heart rate (HR) and cardiac repolarization (QTc). A central tendency analysis for electrocardiogram (ECG) outliers and a plasma concentration‐QTc analysis were conducted to assess cardiac safety in the first‐in‐human pemigatinib study (FIGHT‐101; NCT02393248). The study included 113 participants who received at least one dose of pemigatinib as monotherapy and had at least one pair of plasma pharmacokinetic (PK) and ECG data points collected. Timed 12‐lead ECGs were performed within 15 min of PK blood draws. The ECG parameters for each dose group in the study varied within expectations for patients with advanced malignancies. Categorical analysis of QT interval corrected for HR by Fridericia's method did not reveal dose dependence in the incidence of outliers, and the results of the central tendency and concentration‐QTc analyses did not suggest a dose‐ or concentration‐dependent drug effect. Least squares mean change from baseline in HR was small and did not indicate a clinically relevant effect on HR, and no effect was observed on cardiac conduction as assessed by PR and QRS intervals. In conclusion, pemigatinib does not exhibit any clinically significant prolongation of QTc or dose‐dependent changes in HR.

Clinical trial registration: ClinicalTrials.gov NCT02393248.
A new management tactic for Eucryptorrhynchus scrobiculatus (Coleoptera: Curculionidae) based on factors influencing the weevil population density
Authors: Yang Kailang , Wen Junbao
Published: December 2021

BACKGROUND

The tree of heaven root weevil, Eucryptorrhynchus scrobiculatus (TRW), is one of the most damaging pests of Ailanthus altissima in China. A limited number of studies have examined the effects of different variables on the population density of TRW adults. We investigated the relative impacts of the diameter at breast height of host trees (DBH), number of tree species in plots (NTS), weed coverage rate of the host tree base (WCR), plot area (PA), distance from plots to the nearest farmland (DNF), nearest human community (DNHC), nearest irrigation canal (DNIC), and nearest road (DNR) on TRW population density. We then evaluated the effect of removing weeds at the base of the tree trunk (RW) on TRW population density.

RESULTS

We found that DBH, WCR, PA, and DNHC significantly affected the population density of TRW adults, whereas NTS, DNF, DNIC, and DNR did not. Adult TRW density was positively correlated with DBH, WCR, and PA but was negatively correlated with DNHC. Further field trials showed that RW treatments significantly reduced the density of adult TRW (an average annual reduction of 51.7% compared to untreated trees).

CONCLUSION

This information on the factors affecting the population density of TRW promoted the development of new TRW management strategies. Our results demonstrate that RW is an effective method for reducing the population density of TRW adults. Therefore, this new physical method using RW could be recommended as an alternative for TRW management in the framework of integrated pest management. © 2021 Society of Chemical Industry.
Estimation of multivariate treatment effects in contaminated clinical trials
Authors: Ye Zi , Harrar Solomon W.
Published: December 2021

The paper addresses estimating and testing treatment effects with multivariate outcomes in clinical trials where imperfect diagnostic devices are used to assign subjects to treatment groups. The paper focuses on the pre‐post design and proposes two novel methods for estimating and testing treatment effects. In addition, methods for sample size and power calculations are developed. The methods are compared with each other and with a traditional method in a simulation study. The new methods show significant advantages in terms of power, coverage probability, and required sample size. The application of the methods is illustrated with data from electroencephalogram (EEG) recordings of alcoholic and control subjects.
Energy efficient management for distributed state estimation under DoS attacks
Authors: Lei Hongyi , Yang Wen , Yu Yan
Published: December 2021

In this article, we consider the issue of energy efficient management for distributed state estimation over unknown packet‐dropping communication channels which are exposed to Denial‐of‐Service (DoS) attacks. After a packet is transmitted, the sensor determines whether to retransmit and the retransmission power levels based on the feedback information from the receiving sensor. We formulate the energy efficient management problem as a modified Markov decision problem (MMDP), and proposed an algorithm to seek a retransmission power schedule that achieves optimal tradeoff between energy consumption and communication rate for given channel noise power. In the case of unknown channel state, we design a statistical learning method to estimate channel noise power. Besides, inspired by the hypothesis testing, we design an anomaly detector to guarantee the instantaneity of channel noise power estimation and efficiency of energy management. Furthermore, we derive the optimal gain for each estimator, and provide a sufficient condition for the stability of estimator under the energy management. Finally, we verify the main results by numerical examples.
Adaptive fault‐tolerant optimized formation control for perturbed nonlinear multiagent systems
Authors: Ji Weiyu , Pan Yingnan , Zhao Meng
Published: December 2021

This article proposes an adaptive fault‐tolerant formation control strategy for strict‐feedback nonlinear multiagent systems with nonlinear faults and external disturbances. A simplified reinforcement learning algorithm is developed for approximating the optimized controller. Different from the existing optimized control results, the system dynamics is totally unknown in this article. In order to surmount “explosion of complexity”, the dynamic surface control technique is employed. A disturbance‐fault observer is employed to alleviate the influence caused by the external disturbances and the impact coming from the nonlinear faults. Based on the Lyapunov stability theorem, it can be demonstrated that all signals within the closed‐loop systems are semiglobal uniformly ultimately bounded and the optimized formation control performance can be guaranteed. Finally, some simulation results are exhibited the validity of the developed control method.
Coping strategies moderate the effect of perceived stress on sleep and health in older adults during the COVID‐19 pandemic
Authors: Tracy Eunjin L. , Chin Brian , Lehrer H. Matthew , Carroll Lucas W. , Buysse Daniel J. , Hall Martica H.
Published: December 2021

Stress in the context of the COVID‐19 pandemic may have a significant impact on health, including sleep health. Older adults may be particularly vulnerable. This study examined associations between perceived stress and sleep health, mental health, physical health, and overall perceived health outcomes among older adults. We also examined whether specific coping strategies moderate these associations. Older adults (n = 115; Mage = 68.62) reported perceived stress, coping strategies, global sleep quality, depressive symptoms, and perceived mental, physical, and overall health before and during the COVID‐19 pandemic. Stress‐health relationships were modelled with hierarchical linear regression. Higher perceived stress was associated with greater depressive symptoms and poorer mental health concurrently and longitudinally. Coping strategies moderated the association of perceived stress with physical health and overall perceived health. For example, higher perceived stress was associated with poorer overall perceived health among those with lower problem‐focussed coping, but not among those with higher problem‐focussed coping. Older adults may benefit from prevention and intervention strategies targeting stress management. Furthermore, identifying people with low problem‐focussed coping might be a useful strategy to prevent worsening health in future public health crises.
Degree assortativity in collaboration networks and invention performance
Authors: Khanna Rajat , Guler Isin
Published: December 2021

Research Summary

We investigate the implications of the degree assortativity of intra‐firm networks for firms' innovation performance. We argue that prevalent patterns of collaborative relationships between organizational members can lead to variations in the levels of degree assortativity in intra‐firm networks, ranging from disassortative structures (highly central members connect with peripheral members) to assortative ones (highly central members connect with other highly central members and vice versa). These patterns influence knowledge access and resource mobilization pathways and are thus associated with various firm‐level invention outcomes. Using coarsened exact matching methodology and controlling for other characteristics of the intra‐firm network structures, we find that assortative structures in the pharmaceutical industry are associated with larger invention output, but inventions originating from assortative structures have lower average novelty and impact.

Managerial Summary

A central challenge in knowledge‐based industries is the design of collaborative teams to increase innovative output. In this article, we show that firms in the pharmaceutical industry vary in the extent to which central inventors within a firm collaborate with peripheral inventors. Further, the ideal composition varies based on the desired innovative output: Firms with frequent collaborations between central inventors have higher inventive productivity, while firms with higher mixing between central and peripheral inventors generate inventions that are on average more novel and have higher impact. Results have implications for organizational design toward desired innovative outcomes, as well as management of strategic human capital.
Lattice Strain and Defects Analysis in Nanostructured Semiconductor Materials and Devices by High‐Resolution X‐Ray Diffraction: Theoretical and Practical Aspects
Authors: Dolabella Simone , Borzì Aurelio , Dommann Alex , Neels Antonia
Published: December 2021

The reliability of semiconductor materials with electrical and optical properties are connected to their structures. The elastic strain field and tilt analysis of the crystal lattice, detectable by the variation in position and shape of the diffraction peaks, is used to quantify defects and investigate their mobility. The exploitation of high‐resolution X‐ray diffraction‐based methods for the evaluation of structural defects in semiconductor materials and devices is reviewed. An efficient and non‐destructive characterization is possible for structural parameters such as, lattice strain and tilt, layer composition and thickness, lattice mismatch, and dislocation density. The description of specific experimental diffraction geometries and scanning methods is provided. Today's X‐ray diffraction based methods are evaluated and compared, also with respect to their applicability limits. The goal is to understand the close relationship between lattice strain and structural defects. For different material systems, the appropriate analytical methods are highlighted.
A student affairs imperative: Articulating and mitigating supervisory tensions
Authors: Green Melissa V. , Davis Tiffany J.
Published: December 2021

This article articulates tensions, or strains, that occur within the context of the supervisory relationship, how they arise, and explores some of their interpersonal and organizational impacts. The authors conclude the article with offering strategies supervisors can use to mitigate these tensions.
Strategies for supervising student and staff activists on college campuses
Authors: Evans Meg E. , Stewart Terah J.
Published: December 2021

In this article, authors explore and synthesize principles of the Identity‐Conscious Supervision model and the power‐conscious framework to guide supervisors in their approach to supporting both staff activists and student activists on their campus.
Generational perspective and influence within student affairs workplaces
Authors: Perkins Kelli A. , Herring Glenn
Published: December 2021

This article explores how changing generational demographics of student affairs professionals influence varied perspectives on workplaces in the field. Accordingly, this article grapples with how generational perspectives show up in supervision and influence the student affairs professional pipeline.
Quantification of faecal glucocorticoid metabolites as a measure of stress in the rock hyrax Procavia capensis living in an urban green space
Authors: Carlin E. , J. Somers M. , Scheun J. , Campbell R. , Ganswindt A.
Published: December 2021

Despite the abundance of rock hyrax Procavia capensis within South Africa's urban areas, there is not much information available about the effect of anthropogenic activities on rock hyrax wellbeing. To determine the potential impact of anthropogenic disturbance on adrenocortical activity, we conducted an ACTH challenge to identify a suitable enzyme‐immunoassay (EIA) for measuring faecal glucocorticoid metabolite (fGCM) concentrations in the rock hyrax. This study identified an 11β‐hydroxyaetiocholanolone EIA as the most suitable assay in this regard. The fGCM levels measured, indicate the physiological stress response in different rock hyrax populations, living in an area with varying degrees of anthropogenic activity (low, medium, high) within the National Botanical Garden of Pretoria, South Africa. The species' habituation to human numbers (weekly mean number of people) was examined by determining individual flight initiation distance (FID). Seasonally, there were overall higher fGCM concentrations in late spring compared to winter. The fGCM concentrations, although not significantly different but possibly biologically relevant, in the section with the lowest anthropogenic disturbance were ~10% higher compared to those in the section with medium disturbance, and ~20% higher compared to those in the section with the highest disturbance. Animal FID did not differ significantly between seasons but they did differ significantly between sections, and decreased in accordance with fGCM concentrations. The non‐invasive approach established in this study provides a foundation for assessing rock hyrax wellbeing, and can help better understand how anthropogenic presence is perceived as a stressor in this species.
Spatial machine learning: new opportunities for regional science
Authors: Kopczewska Katarzyna
Published: December 2021

This paper is a methodological guide to using machine learning in the spatial context. It provides an overview of the existing spatial toolbox proposed in the literature: unsupervised learning, which deals with clustering of spatial data, and supervised learning, which displaces classical spatial econometrics. It shows the potential of using this developing methodology, as well as its pitfalls. It catalogues and comments on the usage of spatial clustering methods (for locations and values, both separately and jointly) for mapping, bootstrapping, cross-validation, GWR modelling and density indicators. It provides details of spatial machine learning models, which are combined with spatial data integration, modelling, model fine-tuning and predictions to deal with spatial autocorrelation and big data. The paper delineates “already available” and “forthcoming” methods and gives inspiration for transplanting modern quantitative methods from other thematic areas to research in regional science.
The interplay between unexpected events and behavior in the development of explicit knowledge in implicit sequence learning
Authors: Lustig Clarissa , Esser Sarah , Haider Hilde
Published: December 2021

Some studies in implicit learning investigate the mechanisms by which implicitly acquired knowledge (e.g., learning a sequence of responses) becomes consciously aware. It has been suggested that unexpected changes in the own behavior can trigger search processes, of which the outcome then becomes aware. A consistent empirical finding is that participants who develop explicit knowledge show a sudden decrease in reaction times, when responding to sequential events. This so called RT-drop might indicate the point of time when explicit knowledge occurs. We investigated whether an RT-drop is a precursor for the development of explicit knowledge or the consequence of explicit knowledge. To answer this question, we manipulated in a serial reaction time task the timing of long and short stimulus-onset asynchronies (SOA). For some participants, the different SOAs were presented in blocks of either long or short SOAs, while for others, the SOAs changed randomly. We expected the participants who were given a blocked presentation to express an RT-drop because of the predictable timing. In contrast, randomly changing SOAs should hamper the expression of an RT-drop. We found that more participants in the blocked-SOA condition than in the random-SOA condition showed an RT-drop. Furthermore, the amount of explicit knowledge did not differ between the two conditions. The findings suggest that the RT-drop does not seem to be a presupposition to develop explicit knowledge. Rather, it seems that the RT-drop indicates a behavioral strategy shift as a consequence of explicit knowledge.
Adipocytokines and disease progression in endometrial cancer: a systematic review
Authors: Ray Irene , Meira Lisiane B. , Michael Agnieszka , Ellis Patricia E.
Published: December 2021

The objective of the study was to document the effect of adipocytokines on endometrial cancer progression. A search of the databases CINAHL, Medline, PubMed, Cochrane, Web of Science, Embase and Google Scholar was performed for English language articles from January 2000 to December 2020 using the keywords: (Endometrial cancer) AND (progression OR metastasis) AND (adipocytokine OR adiponectin OR leptin OR visfatin OR IL-6 OR TNF-α OR adipokine OR cytokine). Forty-nine studies on adipocytokines have been included in this review. Adiponectin has been linked with anti-proliferative and anti-metastatic effects on endometrial cancer cells and is associated with a better prognosis. Leptin, visfatin and resistin are linked to the stimulation of endometrial cancer growth, proliferation, invasion and metastasis and are associated with worse prognosis or with a higher grade/stage of endometrial cancer. IL-6, Il-11, IL-31, IL-33, TNF-α, TGF-β1, SDF-1 and CXCR are involved in endometrial cancer cell growth and metastasis or involved in epithelial mesenchymal transformation (EMT) or associated with advanced disease. Adipocytokines have been found to directly impact endometrial cancer cell proliferation, invasion and migration. These molecules and their signalling pathways may be used to determine prognosis and course of the disease and may also be exploited as potential targets for cancer treatment and prevention of progression.
Tax collection in the Roman Empire: a new institutional economics approach
Authors: Gutiérrez Óscar , Martínez-Esteller Marco
Published: December 2021

This paper reviews the Roman tax collection system since the Late Republic to the Principality, focusing on the transition from the tax-farming system to a more centralized, census-based administration. We attempt to justify this transition according to New Institutional Economic theories (Transaction Cost Economics and Property Rights Theory). The paper argues that, during the Republic, the auction-based system of tax farming ended up giving place to opportunistic behaviors and abusing practices due to information asymmetries and contract incompleteness, enhanced by the collusion of tax farmers and governors. The Principality improved the efficiency of the tax collection system through the introduction of a bureaucratic and census-based administration, which allowed imperial employees to monitor the tax-farming activities.
Research and Education Needs for Complex Generics
Authors: Stern Sydney , Coghlan Jill , Krishnan Vishalakshi , Raney Sam G. , Babiskin Andrew , Jiang Wenlei , Lionberger Robert , Xu Xiaoming , Schwendeman Anna , Polli James E.
Published: December 2021

Complex generics are generic versions of drug products that generally have complex active ingredients, complex formulations, complex routes of delivery, complex dosage forms, are complex drug-device combination products, or have other characteristics that can make it complex to demonstrate bioequivalence or to develop as generics. These complex products (i.e. complex generics) are an important element of the United States (U.S.) Food and Drug Administration’s (FDA’s) Generic Drug User Fee Amendments (GDUFA) II Commitment Letter. The Center for Research on Complex Generics (CRCG) was formed by a grant from the FDA to address challenges associated with the development of complex generics. To understand these challenges, the CRCG conducted a “Survey of Scientific Challenges in the Development of Complex Generics”. The three main areas of questioning were directed toward which (types of) complex products, which methods of analysis to support a demonstration of bioequivalence, and which educational topics the CRCG should prioritize. The survey was open to the public on a website maintained by the CRCG. Regarding complex products, the top three selections were complex injectables, formulations, and nanomaterials; drug-device combination products; and inhalation and nasal products. Regarding methods of analysis, the top three selections were locally-acting physiologically-based pharmacokinetic modeling; oral absorption models and bioequivalence; and data analytics and machine learning. Regarding educational topics, the top three selections were complex injectables, formulations, and nanomaterials; drug-device combination products; and data analytics, including quantitative methods and modeling & simulation. These survey results will help prioritize the CRCG’s initial research and educational initiatives.
Oddlab: fault-tolerant aware load-balancing framework for data center networks
Authors: Alawadi Aymen Hasan , Molnár Sándor
Published: December 2021

Data center networks (DCNs) act as critical infrastructures for emerging technologies. In general, a DCN involves a multi-rooted tree with various shortest paths of equal length from end to end. The DCN fabric must be maintained and monitored to guarantee high availability and better QoS. Traditional traffic engineering (TE) methods frequently reroute large flows based on the shortest and least-congested paths to maintain high service availability. This procedure results in a weak link utilization with frequent packet reordering. Moreover, DCN link failures are typical problems. State-of-the-art approaches address such challenges by modifying the network components (switches or hosts) to discover and avoid broken connections. This study proposes Oddlab (Odds labels), a novel deployable TE method to guarantee the QoS of multi-rooted data center (DC) traffic in symmetric and asymmetric modes. Oddlab creatively builds a heuristic model for efficient flow scheduling and faulty link detection by exclusively using the gathered statistics from the DCN data plane, such as residual bandwidth and the number of installed elephant flows. Besides, the proposed method is implemented in an SDN-based DCN without altering the network components. Our findings indicate that Oddlab can minimize the flow completion time, maximize bisection bandwidth, improve network utilization, and recognize faulty links with sufficient accuracy to improve DC productivity.
FertilityOnline: A Straightforward Pipeline for Functional Gene Annotation and Disease Mutation Discovery
Authors: Gao Jianing , Zhang Huan , Jiang Xiaohua , Ali Asim , Zhao Daren , Bao Jianqiang , Jiang Long , Iqbal Furhan , Shi Qinghua , Zhang Yuanwei
Published: December 2021

Exploring the genetic basis of human infertility is currently under intensive investigation. However, only a handful of genes have been validated in animal models as disease-causing genes in infertile men. Thus, to better understand the genetic basis of human spermatogenesis and bridge the knowledge gap between humans and other animal species, we construct the FertilityOnline, a database integrating the literature-curated functional genes during spermatogenesis into an existing spermatogenic database, SpermatogenesisOnline 1.0. Additional features, including the functional annotation and genetic variants of human genes, are also incorporated into FertilityOnline. By searching this database, users can browse the functional genes involved in spermatogenesis and instantly narrow down the number of candidates of genetic mutations underlying male infertility in a user-friendly web interface. Clinical application of this database was exampled by the identification of novel causative mutations in synaptonemal complex central element protein 1 (SYCE1) and stromal antigen 3 (STAG3) in azoospermic men. In conclusion, FertilityOnline is not only an integrated resource for spermatogenic genes but also a useful tool facilitating the exploration of the genetic basis of male infertility. FertilityOnline can be freely accessed at http://mcg.ustc.edu.cn/bsc/spermgenes2.0/index.html.
Search and Rescue in the Pacific West States
Authors: Ettinger Stephen , Long Andrea , Ganti Arun , Mortimer Roger B. , Chiang William , Spano Susanne
Published: December 2021

Introduction

The training practices and the level of medical oversight of search and rescue (SAR) organizations in the US National Park Service (NPS) Pacific west region is not known.

Methods

A database of SAR teams in the NPS Pacific west region was assembled using public sources. SAR team leaders received an electronic survey between May and December 2019. A descriptive analysis characterizing team size, technical and medical training protocols, and medical oversight was completed. Results are reported as median (interquartile range, range).

Results

Of the 250 SAR teams contacted, 39% (n=97) completed our survey. Annual mission volume was 25 (10–50, 1–200). Team size was 30 members (22–58, 1–405). SAR teams most frequently trained in helicopter operations (77%), low-angle rope rescue (75%), and avalanche rescue (43%). Nearly all teams (99%) had members with some medical training: first aid or cardiopulmonary resuscitation (89%), emergency medical technicians (75%), registered nurses or midlevel providers (52%), and physicians (40%). SAR members administered field medical care (84%), often in coordination with EMS (77%). Medical direction was present on a minority of teams (45%), most frequently by a provider specialized in emergency medicine (68%). Expanded medical procedures were permitted on 21% of SAR teams.

Conclusions

SAR teams across the NPS Pacific west region had composition and training standards similar to those surveyed previously in the US intermountain states. Healthcare professionals were present on most teams, typically as team members, not as medical directors. Few SAR teams use medical protocols in remote care environments.
Rationalizing (Vernünfteln)
Authors: Sticker Martin
Published: December 2021

Kant was a keen psychological observer and theorist of the forms, mechanisms and sources of self-deception. In this Element, the author discusses the role of rationalizing/Vernünfteln for Kant's moral psychology, normative ethics and philosophical methodology. By drawing on the full breadth of examples of rationalizing Kant discusses, the author shows how rationalizing can extend to general features of morality and corrupt rational agents thoroughly (albeit not completely and not irreversibly). Furthermore, the author explains the often-overlooked roles common human reason, empirical practical reason and even pure practical reason play for rationalizing. Kant is aware that rationality is a double-edged sword; reason is the source of morality and of our dignity, but it also enables us to seemingly justify moral transgressions to ourselves, and it creates an interest in this justification in the first place. Finally, this Element discusses whether Kant's ethical theory itself can be criticised as a product of rationalizing.
Stratification effects on shoaling internal solitary waves
Authors: Hartharn-Evans Samuel G. , Carr Magda , Stastna Marek , Davies Peter A.
Published: December 2021

This combined numerical/laboratory study investigates the effect of stratification form on the shoaling characteristics of internal solitary waves propagating over a smooth, linear topographic slope. Three stratification types are investigated, namely (i) thin tanh (homogeneous upper and lower layers separated by a thin pycnocline), (ii) surface stratification (linearly stratified layer overlaying a homogeneous lower layer) and (iii) broad tanh (continuous density gradient throughout the water column). It is found that the form of stratification affects the breaking type associated with the shoaling wave. In the thin tanh stratification, good agreement is seen with past studies. Waves over the shallowest slopes undergo fission. Over steeper slopes, the breaking type changes from surging, through collapsing to plunging with increasing wave steepness

$A_w/L_w$

for a given topographic slope, where

$A_w$

and

$L_w$

are incident wave amplitude and wavelength, respectively. In the surface stratification regime, the breaking classification differs from the thin tanh stratification. Plunging dynamics is inhibited by the density gradient throughout the upper layer, instead collapsing-type breakers form for the equivalent location in parameter space in the thin tanh stratification. In the broad tanh profile regime, plunging dynamics is likewise inhibited and the near-bottom density gradient prevents the collapsing dynamics. Instead, all waves either fission or form surging breakers. As wave steepness in the broad tanh stratification increases, the bolus formed by surging exhibits evidence of Kelvin–Helmholtz instabilities on its upper boundary. In both two- and three-dimensional simulations, billow size grows with increasing wave steepness, dynamics not previously observed in the literature.
Effects of an along-shelf current on the generation of internal tides near the critical latitude
Authors: He Yangxin , Lamb Kevin G.
Published: December 2021

The effects of along-shelf barotropic geostrophic currents on internal wave generation by the

$K_1$

tide interacting with a shelf at near-critical latitudes are investigated. The horizontal shear of the background current results in a spatially varying effective Coriolis frequency which modifies the slope criticality and potentially creates blocking regions where freely propagating internal tides cannot exist. This paper is focused on the barotropic to baroclinic energy conversion rate, which is affected by a combination of three factors: slope criticality, size and location of the blocking region where the conversion rate is extremely small and the internal tide (IT) beam patterns. All of these are sensitive to the current parameters. In our parameter space, the current can increase the conversion rate up to 10 times.
Geodetic Monitoring at Axial Seamount Since Its 2015 Eruption Reveals a Waning Magma Supply and Tightly Linked Rates of Deformation and Seismicity
Authors: Chadwick William W. , Wilcock William S. D. , Nooner Scott L. , Beeson Jeffrey W. , Sawyer Audra M. , Lau T.‐K.
Published: December 2021

Axial Seamount is a basaltic hot spot volcano with a summit caldera at a depth of ∼1,500 m below sea level, superimposed on the Juan de Fuca spreading ridge, giving it a robust and continuous magma supply. Axial erupted in 1998, 2011, and 2015, and is monitored by a cabled network of instruments including bottom pressure recorders and seismometers. Since its last eruption, Axial has re‐inflated to 85%–90% of its pre‐eruption level. During that time, we have identified eight discrete, short‐term deflation events of 1–4 cm over 1–3 weeks that occurred quasi‐periodically, about every 4–6 months between August 2016 and May 2019. During each short‐term deflation event, the rate of earthquakes dropped abruptly to low levels, and then did not return to higher levels until reinflation had resumed and returned near its previous high. The long‐term geodetic monitoring record suggests that the rate of magma supply has varied by an order of magnitude over decadal time scales. There was a surge in magma supply between 2011 and 2015, causing those two eruptions to be closely spaced in time and the supply rate has been waning since then. This waning supply has implications for eruption forecasting and the next eruption at Axial still appears to be 4–9 years away. We also show that the number of earthquakes per unit of uplift has increased exponentially with total uplift since the 2015 eruption, a pattern consistent with a mechanical model of cumulative rock damage leading to bulk failure during magma accumulation between eruptions.
3‐D Crustal Azimuthal Anisotropy Reveals Multi‐Stage Deformation Processes of the Sichuan Basin and Its Adjacent Area, SW China
Authors: Zhang Zhiqi , Yao Huajian , Wang Weitao , Liu Chuangming
Published: December 2021

The collision of the South China Block and the North China Block and the eastward extrusion of the Tibetan Plateau materials have caused complicated tectonic deformation and strong seismicity around the Sichuan Basin (SCB). In order to reveal regional stress distribution and deformation mechanisms, we invert for a 3‐D high‐resolution shear wave velocity and azimuthal anisotropy model from ambient noise tomography with data from 483 broadband seismographs deployed around the SCB. Our results reveal strong lateral contrasts of azimuthal anisotropy in the crust. The western Sichuan depression shows weak deformation. The central Sichuan uplift, used to be a stable microcontinent, shows relatively strong and coherent fossil anisotropy. In contrast, the eastern Sichuan folds shows strong anisotropy, indicating intense regional deformation. The fast axis direction is bifurcated when reaching the Longmenshan fault, which indicates the obstruction of the SCB to the crustal low velocity materials beneath the Songpan‐Ganzi Block. In the east, the rigid SCB and strike‐slip faults may transform the compressive stress to shear deformation in adjacent areas and cause a ring‐shaped anisotropy pattern below 15 km depth. Furthermore, anisotropy patterns display strong contrast at shallow depths in the Weiyuan and Changning regions, which may facilitate the accumulation of strain and more likely induce earthquakes during the shale gas exploration stage. Our new model provides important constraints for understanding the multi‐stage deformation processes in and around the SCB.
Characterizing the Roles of Biogeochemical Cycling and Ocean Circulation in Regulating Marine Copper Distributions
Authors: Cui Minming , Gnanadesikan Anand
Published: December 2021

Copper (Cu) is a key micronutrient for marine phytoplankton. Its oceanic biogeochemical cycle has elicited considerable attention due to dissolved Cu exhibiting a unique linear profile with depth. Several processes have been proposed for explaining this behavior. In this study, we characterize the relationships between the observed Cu, PO43−, and Si on a global scale. We find that the depth profiles of Cu resemble those of Si more than of PO43− in the global ocean. To understand their relationships, we couple the biogeochemical and internal circulation processes in a model, fitting optimal Cu:PO43− uptake ratios and remineralization length‐scales to replicate the marine Cu distributions. The modeling results suggest that Cu uptake needs in the Southern Ocean are substantially higher than those in other oceanic regions. In addition, our modeling results indicate a deep Cu remineralization in the global ocean. We offer an alternative mechanism that relies on biogeochemical cycling and internal circulation to produce the linear depth profiles of dissolved Cu. Our results suggest that diatoms are likely the major phytoplankton dominating oceanic Cu cycling.
Central Continental Boreal Summer “Warming Holes” Modulated by Atlantic Multidecadal Oscillation Via Low‐Level Jets
Authors: Pan Zaitao , Kumar Sanjiv , Zhang Yuanjie , Shi Chunhua
Published: December 2021

Despite the accelerated global warming, the central‐eastern U.S. experienced summer daytime cooling during the 20th century. A number of studies have attributed various factors responsible for this abnormal regional cooling, termed the “warming hole (WH)”. This study demonstrates that another WH also existed in the south‐central China that shares similar temporal trend and geographical location to the U.S. WH, including the cooling reversal around 1995. Generalizing the two WHs unravels that they both occurred (a) to the east of major mountain ranges, (b) in heavily cultivated agricultural regions, and (c) near the terminus of the low‐level jets. This study further finds that the WH patterns are the leading mode of surface maximum temperature variability in summer of their respective regions. The WH cooling was consistent with reduction in cloud‐forced solar radiation supported by moisture convergence through weakening of low‐level southerly flow downstream of China WH and strengthening of the southerly flow upstream of U.S. WH. The long‐term trends of WH temperature are highly correlated to the Atlantic Multidecadal Oscillation (AMO) and WH cooling turned into warming around 1995 when the AMO shifted to the positive phase, which combined with overall regional warming, may explain why the summer WH phenomenon has been in diminution for past two decades or so. Given the AMO's association with global climate trend, the WH phenomenon could also be viewed as a local thermal response to the global warming via AMO modulation of regional dynamic and moisture circulation.
Determining Spatial Scales of Soil Moisture—Cloud Coupling Pathways Using Semi‐Idealized Simulations
Authors: Sakaguchi K. , Berg L. K. , Chen J. , Fast J. , Newsom R. , Tai S.‐L. , Yang Z. , Gustafson W. I. , Gaudet B. J. , Huang M. , Pekour M. , Pressel K. , Xiao H.
Published: December 2021

The spatial scales of land‐atmosphere interactions over heterogeneous, realistic soil moisture patterns are critical to improve our understanding of land‐atmosphere interactions. However, these scales are poorly quantified. We use high‐resolution numerical experiments to quantify the spatial scales for a selected day during the Holistic Interactions of Shallow Clouds, Aerosols, and Land‐Ecosystems (HI‐SCALE) campaign in Oklahoma. A semi‐idealized approach (removing background winds and surface topography while retaining the real‐world data for other boundary conditions) enables examination of the local influence from the surface. Simulations that apply uniform surface, variable land cover with uniform soil moisture, and variable land cover with variable soil moisture are then compared. Land cover variations, especially water and urban surfaces, create two variance peaks in the surface sensible heat flux in the scales >10 km (meso‐β) and <6 km (meso‐γ). Both peaks are enhanced by the observation‐based soil moisture distribution that has most of its variance in the meso‐β scale. Atmospheric response in the meso‐β scale is hydrostatic with weak vertical motion. The land cover variations induce secondary circulations in the scales of 2.5–6 km. The additional soil moisture variability intensifies extreme circulations over dry soil patches and sharp sensible heat flux gradients, slightly extending the characteristic scales to 2.5–9 km. While their areal coverage is small, soil moisture variations on such “hotspots” lead to substantially larger convective cloud structure and domain‐mean rainfall, calling for a consideration of their non‐linear effect in large‐scale models.
Airborne Measurements of Surface Albedo and Leaf Area Index of Snow‐Covered Boreal Forest
Authors: Manninen Terhikki , Roujean Jean‐Louis , Hautecoeur Olivier , Riihelä Aku , Lahtinen Panu , Jääskeläinen Emmihenna , Siljamo Niilo , Anttila Kati , Sukuvaara Timo , Korhonen Lauri
Published: December 2021

Helicopter based simultaneous measurements of broadband surface albedo and the effective leaf area index (LAIeff) were carried out in subarctic area of Finnish Lapland in spring 2008, 2009, and 2010 under varying illumination and snow cover conditions. Vertical profile measurements show that the found relationship between albedo and LAIeff seems to be rather independent of the flight altitude and therefore the footprint scale. Actually, flights above 500 m in altitude revealed low variations of the surface albedo approaching an aerial average at 1 km, meaning that a footprint of 20 km is representative of the landscape. The albedo of the area was beta distributed, and without LAIeff values below 0.25, the average albedo value of the area would decrease from 0.49 to 0.44 showing the albedo sensitivity to sparse vegetation. The results agreed with the photon recollision probability based model PARAS and the MODIS satellite albedo product MCD43A3. However, differences between satellite based and airborne albedo values were noticed, which could be explained by a difference in footprint size and/or the strong local heterogeneity as certain flights were operated on specific targets.
Influence of stress induced by the first announced state of emergency due to coronavirus disease 2019 on outpatient blood pressure management in Japan
Authors: Kobayashi Kazuo , Chin Keiichi , Umezawa Shinichi , Ito Shun , Yamamoto Hareaki , Nakano Shiro , Takada Nobukazu , Hatori Nobuo , Tamura Kouichi
Published: December 2021

To prevent further spread of coronavirus disease 2019 (COVID-19), the Japanese government announced a state of emergency, resulting in major stress for the population. The aim of this study was to investigate a possible association between changes in daily stress and blood pressure (BP) in Japanese patients. We retrospectively investigated 748 patients with chronic disease who were treated by the Sagamihara Physicians Association to determine changes in stress during the COVID-19 state of emergency from 7 April to 31 May 2020. During the state of emergency, office BP significantly increased from 136.5 ± 17.5/78.2 ± 12.0 to 138.6 ± 18.6/79.0 ± 12.2 (p < 0.001 and p = 0.03, respectively). In contrast, home BP significantly decreased from 128.2 ± 10.3/75.8 ± 8.8 to 126.9 ± 10.2/75.2 ± 9.0 (p < 0.001 and p = 0.01, respectively), and the ratio of white coat hypertension was significantly increased (p < 0.001). Fifty-eight percent of patients worried about adverse effects of hypertension as a condition contributing to the severity and poor prognosis of COVID-19; decreased amounts of exercise and worsened diet compositions were observed in 39% and 17% of patients, respectively. In conclusion, a significant increase in office BP with the white coat phenomenon was observed during the state of emergency, as well as an increase in related stress. To prevent cardiovascular events, general practitioners should pay more attention to BP management during stressful global events, including the COVID-19 pandemic.
mTOR kinase is a therapeutic target for respiratory syncytial virus and coronaviruses
Authors: Huynh HoangDinh , Levitz Ruth , Huang Rong , Kahn Jeffrey S.
Published: December 2021

Therapeutic interventions targeting viral infections remain a significant challenge for both the medical and scientific communities. While specific antiviral agents have shown success as therapeutics, viral resistance inevitably develops, making many of these approaches ineffective. This inescapable obstacle warrants alternative approaches, such as the targeting of host cellular factors. Respiratory syncytial virus (RSV), the major respiratory pathogen of infants and children worldwide, causes respiratory tract infection ranging from mild upper respiratory tract symptoms to severe life-threatening lower respiratory tract disease. Despite the fact that the molecular biology of the virus, which was originally discovered in 1956, is well described, there is no vaccine or effective antiviral treatment against RSV infection. Here, we demonstrate that targeting host factors, specifically, mTOR signaling, reduces RSV protein production and generation of infectious progeny virus. Further, we show that this approach can be generalizable as inhibition of mTOR kinases reduces coronavirus gene expression, mRNA transcription and protein production. Overall, defining virus replication-dependent host functions may be an effective means to combat viral infections, particularly in the absence of antiviral drugs.
Bioinformatics analysis of long non-coding RNA-associated competing endogenous RNA network in schizophrenia
Authors: Sabaie Hani , Moghaddam Madiheh Mazaheri , Moghaddam Marziyeh Mazaheri , Ahangar Noora Karim , Asadi Mohammad Reza , Hussen Bashdar Mahmud , Taheri Mohammad , Rezazadeh Maryam
Published: December 2021

Schizophrenia (SCZ) is a serious psychiatric condition with a 1% lifetime risk. SCZ is one of the top ten global causes of disabilities. Despite numerous attempts to understand the function of genetic factors in SCZ development, genetic components in SCZ pathophysiology remain unknown. The competing endogenous RNA (ceRNA) network has been demonstrated to be involved in the development of many kinds of diseases. The ceRNA hypothesis states that cross-talks between coding and non-coding RNAs, including long non-coding RNAs (lncRNAs), via miRNA complementary sequences known as miRNA response elements, creates a large regulatory network across the transcriptome. In the present study, we developed a lncRNA-related ceRNA network to elucidate molecular regulatory mechanisms involved in SCZ. Microarray datasets associated with brain regions (GSE53987) and lymphoblasts (LBs) derived from peripheral blood (sample set B from GSE73129) of SCZ patients and control subjects containing information about both mRNAs and lncRNAs were downloaded from the Gene Expression Omnibus database. The GSE53987 comprised 48 brain samples taken from SCZ patients (15 HPC: hippocampus, 15 BA46: Brodmann area 46, 18 STR: striatum) and 55 brain samples taken from control subjects (18 HPC, 19 BA46, 18 STR). The sample set B of GSE73129 comprised 30 LB samples (15 patients with SCZ and 15 controls). Differentially expressed mRNAs (DEmRNAs) and lncRNAs (DElncRNAs) were identified using the limma package of the R software. Using DIANA-LncBase, Human MicroRNA Disease Database (HMDD), and miRTarBase, the lncRNA- associated ceRNA network was generated. Pathway enrichment of DEmRNAs was performed using the Enrichr tool. We developed a protein–protein interaction network of DEmRNAs and identified the top five hub genes by the use of STRING and Cytoscape, respectively. Eventually, the hub genes, DElncRNAs, and predictive miRNAs were chosen to reconstruct the subceRNA networks. Our bioinformatics analysis showed that twelve key DEmRNAs, including BDNF, VEGFA, FGF2, FOS, CD44, SOX2, NRAS, SPARC, ZFP36, FGG, ELAVL1, and STARD13, participate in the ceRNA network in SCZ. We also identified DLX6-AS1, NEAT1, MINCR, LINC01094, DLGAP1-AS1, BABAM2-AS1, PAX8-AS1, ZFHX4-AS1, XIST, and MALAT1 as key DElncRNAs regulating the genes mentioned above. Furthermore, expression of 15 DEmRNAs (e.g., ADM and HLA-DRB1) and one DElncRNA (XIST) were changed in both the brain and LB, suggesting that they could be regarded as candidates for future biomarker studies. The study indicated that ceRNAs could be research candidates for investigating SCZ molecular pathways.