bluuebunny/crossref_metadata_2025 huggingface dataset:
Thyrotropin receptor antibodies and Graves’ orbitopathy
Authors: Diana T. , Ponto K. A. , Kahaly G. J.
Published: August 2020

Context and purpose

The thyrotropin receptor (TSHR) is the key autoantigen in Graves’ disease (GD) and associated orbitopathy (GO). Antibodies targeting the TSHR (TSHR-Ab) impact the pathogenesis and the course of GO. This review discusses the role and clinical relevance of TSHR-Ab in GO.

Methods

Review of the current and pertinent literature.

Results

GO is the most common extrathyroidal manifestation of GD and is caused by persistent, unregulated stimulation of TSHR-expressing orbital target cells (e.g. fibroblasts and pre-adipocytes). Serum TSHR-Ab and more specifically, the stimulatory Ab (TSAb) are observed in the vast majority of patients with GD and GO. TSHR-Ab are a sensitive serological parameter for the differential diagnosis of GO. TSHR-Ab can be detected either with conventional binding immunoassays that measure binding of Ab to the TSHR or with cell-based bioassays that provide information on their functional activity and potency. Knowledge of the biological activity and not simply the presence or absence of TSHR-Ab has relevant clinical implications e.g. predicting de-novo development or exacerbation of pre-existing GO. TSAb are specific biomarkers of GD/GO and responsible for many of its clinical manifestations. TSAb strongly correlate with the clinical activity and clinical severity of GO. Further, the magnitude of TSAb indicates the onset and acuity of sight-threatening GO (optic neuropathy). Baseline serum values of TSAb and especially dilution analysis of TSAb significantly differentiate between thyroidal GD only versus GD + GO.

Conclusion

Measurement of functional TSHR-Ab, especially TSAb, is clinically relevant for the differential diagnosis and management of GO.
Axial Turbine Performance Estimation During Dynamic Operations
Authors: Nicoara Razvan , Vilag Valeriu , Vilag Jeni , Kolozvary Zoltan
Published: August 2020

During service, a turbine engine undergoes frequently dynamic operations. Because of the changes in mass flow, temperature, pressure, as well as the different reaction of the components of turbine to these changes, the turbine performances may vary significantly. It is critical to understand and quantify these variations to design and integrate the turbine to the engine. This paper presents a study of the performances and the variation of the performances for an axial gas turbine across its operating envelope. Numerical simulations are used to describe the flow across the turbine and to estimate the turbine maps. Using theoretical charts for typical turbine thermal expansion, the variation of tip clearance across the working line is approximated. Because of the changes of the tip clearance, using a single geometry may not supply relevant information during real dynamic operations. In order to eliminate these additional errors in the numerical study, a number of turbines maps are recalculated for different tip clearances, respectively to engine regimes. With the resulting data, the working line is recalculated across multiple maps. The comparison between the two working lines is presented as well as the study of performance variation of the turbine across the operation envelope and the influence of tip clearance at different regimes.
CASCO: a simulator of load paths in 2D frames during progressive collapse
Authors: Masoero Enrico
Published: August 2020

Modern structural design software can simulate complex collapse dynamics, but the main physical processes driving collapse propagation are often hidden among structure-specific details. As a result, it is still unclear which structural geometries and material properties should be preferred when approaching the design of a damage-tolerant structure. This manuscript presents a new approach to explore the relationships between structural geometry, local mechanical properties, and collapse propagation. The insight comes from a unique ability to trace the evolution of load paths during collapse, achieved by combining energy conservation with local mechanisms of plastic failure and a few simplifying assumptions. The method is implemented in a new simulator of collapse of 2D frames, called CASCO and programmed in MATLAB. Simulation results for reinforced concrete frames predict collapse loads and mechanisms in agreement with fully non-linear, dynamic simulations, while also providing a graphical description of the evolving structural topology during collapse. A first application of CASCO to mechanically homogeneous and heterogeneous frames, indicates certain evolutions in number and density of load paths during collapse that may be targetted to improve collapse resistance.
Methods for training collaborative biostatisticians
Authors: Pomann Gina-Maria , Boulware L. Ebony , Cayetano Shari Messinger , Desai Manisha , Enders Felicity T. , Gallis John A. , Gelfond Jonathan , Grambow Steven C. , Hanlon Alexandra L. , Hendrix Angelean , Kulkarni Pandurang , Lapidus Jodi , Lee Hui-Jie , Mahnken Jonathan D. , McKeel Julie P. , Moen Rebecca , Oster Robert A. , Peskoe Sarah , Samsa Greg , Stewart Thomas G. , Truong Tracy , Wruck Lisa , Thomas Samantha M.
Published: August 2020

The emphasis on team science in clinical and translational research increases the importance of collaborative biostatisticians (CBs) in healthcare. Adequate training and development of CBs ensure appropriate conduct of robust and meaningful research and, therefore, should be considered as a high-priority focus for biostatistics groups. Comprehensive training enhances clinical and translational research by facilitating more productive and efficient collaborations. While many graduate programs in Biostatistics and Epidemiology include training in research collaboration, it is often limited in scope and duration. Therefore, additional training is often required once a CB is hired into a full-time position. This article presents a comprehensive CB training strategy that can be adapted to any collaborative biostatistics group. This strategy follows a roadmap of the biostatistics collaboration process, which is also presented. A TIE approach (Teach the necessary skills, monitor the Implementation of these skills, and Evaluate the proficiency of these skills) was developed to support the adoption of key principles. The training strategy also incorporates a “train the trainer” approach to enable CBs who have successfully completed training to train new staff or faculty.
Television advertisements for high-sugar foods and beverages: effect on children’s snack food intake
Authors: Kearney Justin , Fitzgerald Rhian , Burnside Girvan , Higham Susan , Flannigan Norah , Halford Jason C.G. , Boyland Emma J.
Published: August 2020

Energy-dense food advertising affects children’s eating behaviour. However, the impact of high-sugar food advertising specifically on the intake of sweet foods is underexplored. This study sought to determine whether children would increase their intake of sugar and total energy following high-sugar food advertising (relative to toy advertising) and whether dental health, weight status and socio-economic status (SES) would moderate any effect. In a crossover, randomised controlled trial, 101 UK children (forty male) aged 8–10 years were exposed to high-sugar food/beverage and toy advertisements embedded within a cartoon. Their subsequent intake of snack foods and beverages varying in sugar content was measured. A dental examination was performed, and height and weight measurements were taken. Home postcode provided by parents was used to assign participants to SES quintiles. Children consumed a significantly greater amount of energy (203·3 (95 % CI 56·5, 350·2) kJ (48·6 (95 % CI 13·5, 83·7) kcal); P = 0·007) and sugar (6·0 (95 % CI 1·3, 10·7) g; P = 0·012) following food advertisements compared with after toy advertisements. This was driven by increased intake of the items with most sugar (chocolate and jelly sweets). Children of healthy weight and with dental caries had the greatest intake response to food advertising exposure, but there were no differences by SES. Acute experimental food advertising exposure increases food intake in children. Specifically, high-sugar food and beverage advertising promotes the consumption of high-sugar food items. The debate around the negative health effects of food advertising on children should be widened to include dental health as well as overall dietary health and obesity.
Informed Trading in the Stock Market and Option-Price Discovery
Authors: Collin-Dufresne Pierre , Fos Vyacheslav , Muravyev Dmitry
Published: August 2020

When activist shareholders file Schedule 13D filings, the average stock-price volatility drops by approximately 10%. Prior to filing days, volatility information is reflected in option prices. Using a comprehensive sample of trades by Schedule 13D filers that reveals on what days and in what markets they trade, we show that on days when activists accumulate shares, option-implied volatility decreases, implied volatility skew increases, and implied volatility time slope increases. The evidence is consistent with a theoretical model where it is common knowledge that informed trading occurs only in the stock market and market makers update option prices based on stock-price and order-flow dynamics.
Investigating cultural differences in the effects of expressive suppression when processing traumatic distressing material
Authors: Nagulendran Amanda , Norton Peter J. , Jobson Laura
Published: August 2020

Background:

While suppression is associated with detrimental post-traumatic psychological adjustment, research has not considered the effect of culture on this relationship.

Aims:

This study investigated cultural differences in the effects of expressive suppression, whilst watching a traumatic film, on subjective distress, psychophysiological responses and intrusive memory.

Method:

Australians of European heritage or East Asian Australian participants (n = 82) were randomly assigned to either a suppression group (instructed to suppress their emotions during the film) or a control group (no instructions regarding emotion management). Electrodermal activity, heart rate and heart rate variability (root mean square of the successive differences; RMSSD) were measured pre-, during and post-film. Participants reported the number of film-related intrusions in the 5 min and 7 days post-viewing.

Results:

While the European Australian group did not differ significantly on RMSSD, the East Asian suppression group scored significantly higher on RMSSD during the film than the East Asian control group. Second, those in the suppression groups, regardless of cultural background, reported significantly fewer intrusions immediately post-film than controls. Third, we found that for the European Australian group, change in heart rate interacted with group (control versus suppression) when predicting weekly intrusions. However, for the East Asian group change in heart rate did not interact with group when predicting weekly intrusions.

Conclusions:

The findings are discussed in the context of current research on culture and emotion regulation and implications for post-traumatic stress disorder.
Transmit Beamforming for Phased Array Based on Constrained Wind‐Driven Optimization Method
Authors: Xu L. , Zhang Z. K.
Published: August 2020

In this paper, we present a novel improved wind‐driven optimization (IWDO) for transmit beamforming of phased array radar, which is assumed as a multiple constraints optimization problem. First, the emitted signal model and objective functions of optimization with constraints are presented. Second, all air parcels are divided into feasible and infeasible parcels, and then the target function and constraint violation of air parcels are evaluated. Finally, the constrained optimization problem is converted into the nonconstraint problem, and the proposed modified wind‐driven optimization (WDO) has been applied for the optimal design of beamforming with null steering. The simulation results show that the proposed method outperforms conventional optimization methods in the optimal beamforming by achieving more reduction in the null steering and obtaining accurate peak power.
Iran's Agriculture in the Anthropocene
Authors: Maghrebi Mohsen , Noori Roohollah , Bhattarai Rabin , Mundher Yaseen Zaher , Tang Qiuhong , Al‐Ansari Nadhir , Danandeh Mehr Ali , Karbassi Abdolreza , Omidvar Javad , Farnoush Hossein , Torabi Haghighi Ali , Kløve Bjørn , Madani Kaveh
Published: August 2020

The anthropogenic impacts of development and frequent droughts have limited Iran's water availability. This has major implications for Iran's agricultural sector which is responsible for about 90% of water consumption at the national scale. This study investigates if declining water availability impacted agriculture in Iran. Using the Mann‐Kendall and Sen's slope estimator methods, we explored the changes in Iran's agricultural production and area during the 1981–2013 period. Despite decreasing water availability during this period, irrigated agricultural production and area continuously increased. This unsustainable agricultural development, which would have been impossible without the overabstraction of surface and ground water resources, has major long‐term water, food, environmental, and human security implications for Iran.
Grain‐Boundary Diffusion Creep of Olivine: 2. Solidus Effects and Consequences for the Viscosity of the Oceanic Upper Mantle
Authors: Yabe K. , Hiraga T.
Published: August 2020

In Part 1 of this study (Yabe et al., 2020, https://doi.org/10.1029/2020JB019415), we established an olivine grain‐boundary diffusion creep law that incorporates the chemically induced enhancement of creep rates, which becomes significant with increasing temperature. The effect was attributed to grain‐boundary disordering that starts at ~0.92 × solidus (bulk eutectic temperature). In this study, we estimated solidus temperatures of the samples used in the previous diffusion creep experiments. These temperatures were used to compare previously reported diffusion creep rates for olivine with our established diffusion creep law. We found that the law explains a difference of up to 2 orders of magnitude in olivine creep rates at the same temperatures, stresses, grain sizes, and water contents in the previous studies. The geotherm normalized by the mantle solidus was calculated for the upper mantle with water contents ranging from 0 to 300 μg/g, which predicts depths where grain‐boundary diffusion creep is enhanced due to grain‐boundary disordering. Constructed viscosity‐depth profiles reveal a very thin mantle lithosphere beneath mid‐ocean ridges, with development of the lithosphere away from the ridge, leaving a low‐viscosity region below. Given a grain size of 1 mm and depending on the water content, a viscosity of 2–5 × 1019 Pa·s is predicted for the low‐viscosity mantle beneath 50‐million‐year‐old seafloor.
Vortex and Biogeochemical Dynamics for the Hypoxia Formation Within the Coastal Transition Zone off the Pearl River Estuary
Authors: Li Dou , Gan Jianping , Hui Rex , Liu Zhiqiang , Yu Liuqian , Lu Zhongming , Dai Minhan
Published: August 2020

Satellite‐derived chlorophyll data, in situ measurements, and time series buoy monitoring revealed the persistent and deteriorating seasonal eutrophication and hypoxia with two distinct centers in the coastal transition zone (CTZ) between the Pearl River Estuary and the adjacent continental shelf off Hong Kong. We used a process‐oriented coupled physical‐biogeochemical numerical model to investigate the intrinsic physical and biogeochemical dynamics under the extrinsic forcing of wind, river discharge, and tides for the hypoxia formation in the CTZ. We found that the convergence induced by cyclonic vortices in the CTZ, which were formed by the buoyancy‐driven currents and wind‐driven shelf currents, created the stable water column with weak mixing and long residence time and accumulated nutrients and organic matter for the eutrophication and hypoxia development. The biophysical responses to spring‐neap cycle further demonstrated the coherent linkages of oceanic currents, vortex formation, and convergence of organic matter within the CTZ and indicated the critical role of mixing in the dissolved oxygen (DO) budgets during the spring‐neap tidal cycle. The study found that biogeochemical substances and processes are necessary conditions for eutrophication and hypoxia formation, and when these necessary conditions are combined with the favorable hydrodynamic conditions, they form a sufficient condition for eutrophication and hypoxia formation in the CTZ.
Interannual Variability of the Mid‐Atlantic Bight Cold Pool
Authors: Chen Zhuomin , Curchitser Enrique N.
Published: August 2020

The Mid‐Atlantic Bight (MAB) Cold Pool is a bottom‐trapped, cold (temperature below 10°C) and fresh (practical salinity below 34) water mass that is isolated from the surface by the seasonal thermocline and is located over the midshelf and outer shelf of the MAB. The interannual variability of the Cold Pool with regard to its persistence time, volume, temperature, and seasonal along‐shelf propagation is investigated based on a long‐term (1958–2007) high‐resolution regional model of the northwest Atlantic Ocean. A Cold Pool Index is defined and computed in order to quantify the strength of the Cold Pool on the interannual timescale. Anomalous strong, weak, and normal years are categorized and compared based on the Cold Pool Index. A detailed quantitative study of the volume‐averaged heat budget of the Cold Pool region (CPR) has been examined on the interannual timescale. Results suggest that the initial temperature and abnormal warming/cooling due to advection are the primary drivers in the interannual variability of the near‐bottom CPR temperature anomaly during stratified seasons. The long persistence of temperature anomalies from winter to summer in the CPR also suggests a potential for seasonal predictability.
Impacts of Protected Area Deforestation on Dry‐Season Regional Climate in the Brazilian Amazon
Authors: De Sales Fernando , Santiago Thais , Biggs Trent Wade , Mullan Katrina , Sills Erin O. , Monteverde Corrie
Published: August 2020

Rainforest in protected areas in the Brazilian Amazon is at risk due to increasing economic pressures and recent weakening of environmental agencies and legislation by the federal administration. This study examines the impacts of deforestation in protected areas on dry‐season precipitation in the Brazilian state of Rondônia located in the southwestern Brazilian Amazon. Regional‐climate model simulations indicate that clearing protected forests in Rondônia would result in substantial changes to the surface energy balance, including increased sensible and decreased latent heat flux. Consequent changes to low‐level wind circulation would enhance moisture flux convergence and convection over the newly deforested areas, leading to enhanced rainfall in those areas. However, deforestation of protected areas would decrease dry season rainfall up to 30% in the existing agricultural region, with potentially important negative impacts on agricultural production. Additionally, our results indicate that following deforestation, the newly degraded areas will experience warmer and drier afternoons that could place the remaining natural vegetation under vapor deficit stress.
Emergency response strategy for containing COVID-19 within a psychiatric specialty hospital in the epicenter of the COVID-19 epidemic in China
Authors: Ma Jun , Zhong Hao , Jiang Min , Zeng Kuan , Zhong Baoliang , Liu Lianzhong , Liu Xuebing
Published: August 2020

Coronavirus disease 2019 (COVID-19) has been recognized as a global pandemic, and psychiatric institutions located in the epicenter of the epidemic in China are facing severe challenges in fighting the epidemic. This article presents the accumulated experience of the authors during the process of combating COVID-19 in a psychiatric hospital. The aim of this article is to provide a reference for psychiatric specialty hospitals and institutions that treat large populations of chronically ill patients in other parts of the world.
Molecular design principles of Lysine-DOPA wet adhesion
Authors: Li Yiran , Cheng Jing , Delparastan Peyman , Wang Haoqi , Sigg Severin J. , DeFrates Kelsey G. , Cao Yi , Messersmith Phillip B.
Published: August 2020

The mussel byssus has long been a source of inspiration for the adhesion community. Recently, adhesive synergy between flanking lysine (Lys, K) and 3,4-Dihydroxyphenylalanine (DOPA, Y) residues in the mussel foot proteins (Mfps) has been highlighted. However, the complex topological relationship of DOPA and Lys as well as the interfacial adhesive roles of other amino acids have been understudied. Herein, we study adhesion of Lys and DOPA-containing peptides to organic and inorganic substrates using single-molecule force spectroscopy (SMFS). We show that a modest increase in peptide length, from KY to (KY)3, increases adhesion strength to TiO2. Surprisingly, further increase in peptide length offers no additional benefit. Additionally, comparison of adhesion of dipeptides containing Lys and either DOPA (KY) or phenylalanine (KF) shows that DOPA is stronger and more versatile. We furthermore demonstrate that incorporating a nonadhesive spacer between (KY) repeats can mimic the hidden length in the Mfp and act as an effective strategy to dissipate energy.
Multiplexed Optical Sensors in Arrayed Islands of Cells for multimodal recordings of cellular physiology
Authors: Werley Christopher A. , Boccardo Stefano , Rigamonti Alessandra , Hansson Emil M. , Cohen Adam E.
Published: August 2020

Cells typically respond to chemical or physical perturbations via complex signaling cascades which can simultaneously affect multiple physiological parameters, such as membrane voltage, calcium, pH, and redox potential. Protein-based fluorescent sensors can report many of these parameters, but spectral overlap prevents more than ~4 modalities from being recorded in parallel. Here we introduce the technique, MOSAIC, Multiplexed Optical Sensors in Arrayed Islands of Cells, where patterning of fluorescent sensor-encoding lentiviral vectors with a microarray printer enables parallel recording of multiple modalities. We demonstrate simultaneous recordings from 20 sensors in parallel in human embryonic kidney (HEK293) cells and in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), and we describe responses to metabolic and pharmacological perturbations. Together, these results show that MOSAIC can provide rich multi-modal data on complex physiological responses in multiple cell types.
Low temperature synthesis of plasmonic molybdenum nitride nanosheets for surface enhanced Raman scattering
Authors: Guan Haomin , Yi Wencai , Li Tao , Li Yahui , Li Junfang , Bai Hua , Xi Guangcheng
Published: August 2020

Molybdenum nitride (δ–MoN) is an important functional material due to its impressive catalytic, energy storage, and superconducting properties. However, the synthesis of δ–MoN usually requires extremely harsh conditions; thus, the insight into δ−MoN is far behind that of oxides and sulfides of molybdenum. Herein, we report that ultrathin δ−MoN nanosheets are prepared at 270 °C and 12 atm. WN, VN, and TiN nanosheets are also synthesized by this method. The δ−MoN nanosheets show strong surface plasmon resonance, high conductivity, excellent thermal and chemical stability as well as a high photothermal conversion efficiency of 61.1%. As a promising surface enhanced Raman scattering substrate, the δ−MoN nanosheets exhibit a 8.16 × 106 enhanced factor and a 10−10 level detection limit for polychlorophenol.
Mammalian histones facilitate antimicrobial synergy by disrupting the bacterial proton gradient and chromosome organization
Authors: Doolin Tory , Amir Henry M. , Duong Leora , Rosenzweig Rachel , Urban Lauren A. , Bosch Marta , Pol Albert , Gross Steven P. , Siryaporn Albert
Published: August 2020

First proposed as antimicrobial agents, histones were later recognized for their role in condensing chromosomes. Histone antimicrobial activity has been reported in innate immune responses. However, how histones kill bacteria has remained elusive. The co-localization of histones with antimicrobial peptides (AMPs) in immune cells suggests that histones may be part of a larger antimicrobial mechanism in vivo. Here we report that histone H2A enters E. coli and S. aureus through membrane pores formed by the AMPs LL-37 and magainin-2. H2A enhances AMP-induced pores, depolarizes the bacterial membrane potential, and impairs membrane recovery. Inside the cytoplasm, H2A reorganizes bacterial chromosomal DNA and inhibits global transcription. Whereas bacteria recover from the pore-forming effects of LL-37, the concomitant effects of H2A and LL-37 are irrecoverable. Their combination constitutes a positive feedback loop that exponentially amplifies their antimicrobial activities, causing antimicrobial synergy. More generally, treatment with H2A and the pore-forming antibiotic polymyxin B completely eradicates bacterial growth.
MGMT genomic rearrangements contribute to chemotherapy resistance in gliomas
Authors: Oldrini Barbara , Vaquero-Siguero Nuria , Mu Quanhua , Kroon Paula , Zhang Ying , Galán-Ganga Marcos , Bao Zhaoshi , Wang Zheng , Liu Hanjie , Sa Jason K. , Zhao Junfei , Kim Hoon , Rodriguez-Perales Sandra , Nam Do-Hyun , Verhaak Roel G. W. , Rabadan Raul , Jiang Tao , Wang Jiguang , Squatrito Massimo
Published: August 2020

Temozolomide (TMZ) is an oral alkylating agent used for the treatment of glioblastoma and is now becoming a chemotherapeutic option in patients diagnosed with high-risk low-grade gliomas. The O-6-methylguanine-DNA methyltransferase (MGMT) is responsible for the direct repair of the main TMZ-induced toxic DNA adduct, the O6-Methylguanine lesion. MGMT promoter hypermethylation is currently the only known biomarker for TMZ response in glioblastoma patients. Here we show that a subset of recurrent gliomas carries MGMT genomic rearrangements that lead to MGMT overexpression, independently from changes in its promoter methylation. By leveraging the CRISPR/Cas9 technology we generated some of these MGMT rearrangements in glioma cells and demonstrated that the MGMT genomic rearrangements contribute to TMZ resistance both in vitro and in vivo. Lastly, we showed that such fusions can be detected in tumor-derived exosomes and could potentially represent an early detection marker of tumor recurrence in a subset of patients treated with TMZ.
The Human LL-37(17-29) antimicrobial peptide reveals a functional supramolecular structure
Authors: Engelberg Yizhaq , Landau Meytal
Published: August 2020

Here, we demonstrate the self-assembly of the antimicrobial human LL-37 active core (residues 17–29) into a protein fibril of densely packed helices. The surface of the fibril encompasses alternating hydrophobic and positively charged zigzagged belts, which likely underlie interactions with and subsequent disruption of negatively charged lipid bilayers, such as bacterial membranes. LL-3717–29 correspondingly forms wide, ribbon-like, thermostable fibrils in solution, which co-localize with bacterial cells. Structure-guided mutagenesis analyses supports the role of self-assembly in antibacterial activity. LL-3717–29 resembles, in sequence and in the ability to form amphipathic helical fibrils, the bacterial cytotoxic PSMα3 peptide that assembles into cross-α amyloid fibrils. This argues helical, self-assembling, basic building blocks across kingdoms of life and points to potential structural mimicry mechanisms. The findings expose a protein fibril which performs a biological activity, and offer a scaffold for functional and durable biomaterials for a wide range of medical and technological applications.
Association of low-dosage systemic corticosteroid use with disease burden in asthma
Authors: Matsunaga Kazuto , Adachi Mitsuru , Nagase Hiroyuki , Okoba Tomoko , Hayashi Nobuya , Tohda Yuji
Published: August 2020

There is an ongoing debate about the benefit–risk balance of systemic corticosteroids (SCS) in asthma treatment. We investigated the associations between SCS use and disease burden in a database cohort of asthmatics, categorized into SCS and non-SCS prescription at baseline and quartiles (Q) by cumulative SCS dosage. Of the 10,579 patients, the SCS cohort comprised 3103 patients (29.3%). Mean SCS dosages at baseline were 0.08, 0.29, 0.79, and 4.58 mg/day in Q1, Q2, Q3, and Q4, respectively. Similar SCS dosages were used within each quartile throughout the study period. No remarkable changes in asthma severity or control status were observed. All SCS cohorts had a higher risk of intermittent SCS exposure during the observation period. SCS use was associated with osteoporosis, diabetes, anxiety/neurosis, and depression. SCS-dependent treatment does not necessarily lead to the future improvement of asthma control; rather, it may negatively impact systemic health, even at mean dosages <5 mg/day.
Transcriptome analysis of blood and spleen in virulent and avirulent mouse malaria infection
Authors: Zhao Yuancun , Hosking Caroline , Cunningham Deirdre , Langhorne Jean , Lin Jing-wen
Published: August 2020

Malaria is a devastating infectious disease and the immune response is complex and dynamic during a course of a malarial infection. Rodent malaria models allow detailed time-series studies of the host response in multiple organs. Here, we describe two comprehensive datasets containing host transcriptomic data from both the blood and spleen throughout an acute blood stage infection of virulent or avirulent Plasmodium chabaudi infection in C57BL/6 mice. The mRNA expression profiles were generated using Illumina BeadChip microarray. These datasets provide a groundwork for comprehensive and comparative studies on host gene expression in early, acute and recovering phases of a blood stage infection in both the blood and spleen, to explore the interaction between the two, and importantly to investigate whether these responses differ in virulent and avirulent infections.
Laser cavitation rheology for measurement of elastic moduli and failure strain within hydrogels
Authors: Luo Justin C. , Ching Herman , Wilson Bryce G. , Mohraz Ali , Botvinick Elliot L. , Venugopalan Vasan
Published: August 2020

We introduce laser cavitation rheology (LCR) as a minimally-invasive optical method to characterize mechanical properties within the interior of biological and synthetic aqueous soft materials at high strain-rates. We utilized time-resolved photography to measure cavitation bubble dynamics generated by the delivery of focused 500 ps duration laser radiation at λ = 532 nm within fibrin hydrogels at pulse energies ofEp = 12, 18 µJ and within polyethylene glycol (600) diacrylate (PEG (600) DA) hydrogels atEp = 2, 5, 12 µJ. Elastic moduli and failure strains of fibrin and PEG (600) DA hydrogels were calculated from these measurements by determining parameter values which provide the best fit of the measured data to a theoretical model of cavitation bubble dynamics in a Neo-Hookean viscoelastic medium subject to material failure. We demonstrate the use of this method to retrieve the local, interior elastic modulus of these hydrogels and both the radial and circumferential failure strains.
Mebendazole is unique among tubulin-active drugs in activating the MEK–ERK pathway
Authors: Andersson Claes R. , Selvin Tove , Blom Kristin , Rubin Jenny , Berglund Malin , Jarvius Malin , Lenhammar Lena , Parrow Vendela , Loskog Angelica , Fryknäs Mårten , Nygren Peter , Larsson Rolf
Published: August 2020

We recently showed that the anti-helminthic compound mebendazole (MBZ) has immunomodulating activity in monocyte/macrophage models and induces ERK signalling. In the present study we investigated whether MBZ induced ERK activation is shared by other tubulin binding agents (TBAs) and if it is observable also in other human cell types. Curated gene signatures for a panel of TBAs in the LINCS Connectivity Map (CMap) database showed a unique strong negative correlation of MBZ with MEK/ERK inhibitors indicating ERK activation also in non-haematological cell lines. L1000 gene expression signatures for MBZ treated THP-1 monocytes also connected negatively to MEK inhibitors. MEK/ERK phosphoprotein activity testing of a number of TBAs showed that only MBZ increased the activity in both THP-1 monocytes and PMA differentiated macrophages. Distal effects on ERK phosphorylation of the substrate P90RSK and release of IL1B followed the same pattern. The effect of MBZ on MEK/ERK phosphorylation was inhibited by RAF/MEK/ERK inhibitors in THP-1 models, CD3/IL2 stimulated PBMCs and a MAPK reporter HEK-293 cell line. MBZ was also shown to increase ERK activity in CD4+ T-cells from lupus patients with known defective ERK signalling. Given these mechanistic features MBZ is suggested suitable for treatment of diseases characterized by defective ERK signalling, notably difficult to treat autoimmune diseases.
Utility of modified vascular corrosion casting technique in the diagnosis of fetal ductus arteriosus abnormalities
Authors: Wang Yu , Zhang Jiaqi , Zeng He , Cao Haiyan , Si Ziyi , Feng Wei , Xie Mingxing
Published: August 2020

The anatomy of ductus arteriosus (DA) can be varied in different congenital heart defects (CHDs), and it is difficult to fully discover the DA and other associated cardiac anomalies by prenatal ultrasound. This study was aimed to use the modified vascular corrosion casting technique to prepare fetal cardiovascular casts with DA anomalies, assess the casting effectiveness in evaluating the great vessels of the fetal heart and investigate the utility of cardiovascular casting for the demonstration of fetal DA abnormalities. This retrospective study enrolled fourteen fetuses (23 to 28+2 gestational weeks) with severe CHDs diagnosed by prenatal echocardiography and casting technique from January 2013 to July 2019. The sonographic features of DAs were carefully observed and other associated cardiovascular anomalies were also evaluated during the screening. The architectures of DAs and the whole cardiovascular system were observed and analyzed, and then the cast findings were compared with prenatal ultrasonic results. In fourteen cases, 18 ductal abnormities were indicated by prenatal echocardiography in fourteen cases, while 25 were revealed by casting. Cast findings included 4 cases of ductal stenosis, 1 case of ductal dilation, 6 cases of ductal circuity, 3 cases of right-sided ductus, 5 cases of anomalous ductal connection, 1 case of bilateral ductus and 5 cases of absent ductus. Cast findings consisted with ultrasound in 10 ductal abnormalities, revealed additional 15 ductal abnormalities miss-diagnosed by sonography, and corrected 6 abnormalities misdiagnosed prenatally. Meanwhile, 3 ductal abnormalities (reversed flow) could not be demonstrated by casts but only by ultrasound. Cast models can visually display the anatomical characteristics of ductus arteriosus, and could be successfully used in the demonstration of ductus abnormalities in fetuses with severe CHDs. Comparing with ultrasound, casting technique has its own superiority in exhibiting ductus abnormalities, especially in certain types such as course, origin and absence abnormalities of ductus.
Experimental realisation of tunable ferroelectric/superconductor $$({\text {B}} {\text {T}} {\text {O}}/{\text {Y}} {\text {B}}{\text {C}} {\text {O}})_{{\text {N}}}/{\text {S}}{\text {T}}{\text {O}}$$ 1D photonic crystals in the whole visible spectrum
Authors: González Luz E. , Ordoñez John E. , Melo-Luna Carlos A. , Mendoza Evelyn , Reyes David , Zambrano Gustavo , Porras-Montenegro Nelson , Granada Juan C. , Gómez Maria E. , Reina John H.
Published: August 2020

Emergent technologies that make use of novel materials and quantum properties of light states are at the forefront in the race for the physical implementation, encoding and transmission of information. Photonic crystals (PCs) enter this paradigm with optical materials that allow the control of light propagation and can be used for optical communication, and photonics and electronics integration, making use of materials ranging from semiconductors, to metals, metamaterials, and topological insulators, to mention but a few. Here, we show how designer superconductor materials integrated into PCs fabrication allow for an extraordinary reduction of electromagnetic waves damping, making possible their optimal propagation and tuning through the structure, below critical superconductor temperature. We experimentally demonstrate, for the first time, a successful integration of ferroelectric and superconductor materials into a one-dimensional (1D) PC composed of $$({\text {B}}{\text {T}}{\text {O}}/{\text {Y}}{\text {B}}{\text {C}} {\text {O}})_{{\text {N}}}/{\text {S}}{\text {T}}{\text {O}}$$(BTO/YBCO)N/STO bilayers that work in the whole visible spectrum, and below (and above) critical superconductor temperature $$T_C=80\, {\hbox {K}}$$TC=80K. Theoretical calculations support, for different number of bilayers N, the effectiveness of the produced 1D PCs and may pave the way for novel optoelectronics integration and information processing in the visible spectrum, while preserving their electric and optical properties.
Monitoring soil radon during the 2016–2017 central Italy sequence in light of seismicity
Authors: Soldati Gaia , Cannelli Valentina , Piersanti Antonio
Published: August 2020

The radioactive nature of radon makes it a powerful tracer for fluid movements in the crust, and a potentially effective marker to study processes connected with earthquakes preparatory phase. To explore the feasibility of using soil radon variations as earthquakes precursor, we analyse the radon concentration data recorded by two stations located close to the epicentre of the strongest mainshock (Mw 6.5 on October 30, 2016) of the seismic sequence which affected central Italy from August 2016. The two stations CTTR and NRCA operate in the framework of the permanent Italian Radon monitoring Network and recorded almost continuously since 2012 and 2016, respectively, the latter being installed just after the first mainshock of the sequence (Mw 6.0 on August 24, 2016). An increase of radon emanation is clearly visible about 2 weeks before the Mw 6.5 event on both the time series, more pronounced on NRCA, nearer to the epicentre, suggesting the possibility of a direct association with the earthquake occurrence. An independently developed detection algorithm aimed at highlighting the connections between radon emission variations and major earthquakes occurrence succeeds in forecasting the Mw 6.5 mainshock on NRCA time series. The resulting time advance of the alarm is consistent with that obtained using a Bayesian approach to compute the a posteriori probability of multiple change points on the radon time series of NRCA. Moreover, it is in agreement with the delay time which maximizes the correlation between radon and seismic anomalies. Applying the detection algorithm to CTTR time series returns alarms for both the Mw 6.0 event, with epicentre closer to this station, and the stronger Mw 6.5 event, but with a higher number of false detections. Finally, we found that a preliminary correction of the bias introduced by variations of meteorological parameters does not affect our main finding of an increase in radon concentration before the major mainshocks. Our study confirms that, although much work is still needed, a monitoring approach based on a permanent dense network is crucial for making radon time series analysis an effective complement to traditional seismological tools.
A lncRNA landscape in breast cancer reveals a potential role for AC009283.1 in proliferation and apoptosis in HER2-enriched subtype
Authors: Cedro-Tanda Alberto , Ríos-Romero Magdalena , Romero-Córdoba Sandra , Cisneros-Villanueva Mireya , Rebollar-Vega Rosa Gloria , Alfaro-Ruiz Luis Alberto , Jiménez-Morales Silvia , Domínguez-Reyes Carlos , Villegas-Carlos Felipe , Tenorio-Torres Alberto , Bautista-Piña Veronica , Beltrán-Anaya Fredy Omar , Hidalgo-Miranda Alfredo
Published: August 2020

Breast cancer is the most commonly diagnosed neoplasm in women worldwide with a well-recognized heterogeneous pathology, classified into four molecular subtypes: Luminal A, Luminal B, HER2-enriched and Basal-like, each one with different biological and clinical characteristics. Long non-coding RNAs (lncRNAs) represent 33% of the human transcriptome and play critical roles in breast carcinogenesis, but most of their functions are still unknown. Therefore, cancer research could benefit from continued exploration into the biology of lncRNAs in this neoplasm. We characterized lncRNA expression portraits in 74 breast tumors belonging to the four molecular subtypes using transcriptome microarrays. To infer the biological role of the deregulated lncRNAs in the molecular subtypes, we performed co-expression analysis of lncRNA–mRNA and gene ontology analysis. We identified 307 deregulated lncRNAs in tumor compared to normal tissue and 354 deregulated lncRNAs among the different molecular subtypes. Through co-expression analysis between lncRNAs and protein-coding genes, along with gene enrichment analysis, we inferred the potential function of the most deregulated lncRNAs in each molecular subtype, and independently validated our results taking advantage of TCGA data. Overexpression of the AC009283.1 was observed in the HER2-enriched subtype and it is localized in an amplification zone at chromosome 17q12, suggesting it to be a potential tumorigenic lncRNA. The functional role of lncRNA AC009283.1 was examined through loss of function assays in vitro and determining its impact on global gene expression. These studies revealed that AC009283.1 regulates genes involved in proliferation, cell cycle and apoptosis in a HER2 cellular model. We further confirmed these findings through ssGSEA and CEMITool analysis in an independent HER2-amplified breast cancer cohort. Our findings suggest a wide range of biological functions for lncRNAs in each breast cancer molecular subtype and provide a basis for their biological and functional study, as was conducted for AC009283.1, showing it to be a potential regulator of proliferation and apoptosis in the HER2-enriched subtype.
Effects of maneuver of hair-washing motion and gender on oxygen uptake and ventilation in healthy people
Authors: Takahata Miki , Ishizawa Masao , Uchiumi Takuya , Yamaki Michiyasu , Sato Toshiaki
Published: August 2020

It is known that patients with chronic obstructive pulmonary disease experience dyspnea during unsupported arm exercise (UAE). We examined the respiratory variables in during a hair-washing motion for healthy young people requiring the UAE to find the effects across gender, motion, and speed. In this study, 33 healthy young people were enrolled. Participants performed the following four types of hair-washing motions: both hands with fast speed, both hands with slow speed, one hand with fast speed, and one hand with slow speed. The respiratory variables such as oxygen uptake ($${\dot{\text{V}}}$$V˙O2), carbon dioxide output ($${\dot{\text{V}}}$$V˙CO2), and respiratory rate (RR), or minute ventilation ($${\dot{\text{V}}}$$V˙E) were measured. Regarding $${\dot{\text{V}}}$$V˙O2, $${\dot{\text{V}}}$$V˙CO2, and RR during the rest period and in each motion, $${\dot{\text{V}}}$$V˙O2 and $${\dot{\text{V}}}$$V˙CO2 in males were significantly greater than those in females. RR in the female participants had greater value than that in males. Among the maneuvers, $${\dot{\text{V}}}$$V˙O2, $${\dot{\text{V}}}$$V˙CO2 or $${\dot{\text{V}}}$$V˙E during a hair-washing motion with both hands were greater than those during hair-washing motion with one hand. $${\dot{\text{V}}}$$V˙O2, $${\dot{\text{V}}}$$V˙CO2, RR, or $${\dot{\text{V}}}$$V˙E during a hair-washing motion with both hands fast speed was greater than those during a hair-washing motion with slow speed. In conclusion, this study showed the effects owing to the differences in motion maneuvers and gender during UAE in healthy young people. These suggest a need to consider motion maneuver or gender when teaching motion methods of activities of daily living on the patients.
TAO-DFT investigation of electronic properties of linear and cyclic carbon chains
Authors: Seenithurai Sonai , Chai Jeng-Da
Published: August 2020

It has been challenging to adequately investigate the properties of nanosystems with radical nature using conventional electronic structure methods. We address this challenge by calculating the electronic properties of linear carbon chains (l-CC[n]) and cyclic carbon chains (c-CC[n]) withn= 10–100 carbon atoms, using thermally-assisted-occupation density functional theory (TAO-DFT). For all the cases investigated,l-CC[n]/c-CC[n] are ground-state singlets, andc-CC[n] are energetically more stable thanl-CC[n]. The electronic properties ofl-CC[n]/c-CC[n] reveal certain oscillation patterns for smallern, followed by monotonic changes for largern. For the smaller carbon chains, odd-numberedl-CC[n] are more stable than the adjacent even-numbered ones;c-CC[$$4m+2$$4m+2]/c-CC[4m] are more/less stable than the adjacent odd-numbered ones, wheremare positive integers. Asnincreases,l-CC[n]/c-CC[n] possess increasing polyradical nature in their ground states, where the active orbitals are delocalized over the entire length ofl-CC[n] or the whole circumference ofc-CC[n].
Optical detection of electron spin dynamics driven by fast variations of a magnetic field: a simple method to measure $$T_1$$, $$T_2$$, and $$T_2^*$$ in semiconductors
Authors: Belykh V. V. , Yakovlev D. R. , Bayer M.
Published: August 2020

We develop a simple method for measuring the electron spin relaxation times$$T_1$$T1,$$T_2$$T2and$$T_2^*$$T2∗in semiconductors and demonstrate its exemplary application ton-type GaAs. Using an abrupt variation of the magnetic field acting on electron spins, we detect the spin evolution by measuring the Faraday rotation of a short laser pulse. Depending on the magnetic field orientation, this allows us to measure either the longitudinal spin relaxation time$$T_1$$T1or the inhomogeneous transverse spin dephasing time$$T_2^*$$T2∗. In order to determine the homogeneous spin coherence time$$T_2$$T2, we apply a pulse of an oscillating radiofrequency (rf) field resonant with the Larmor frequency and detect the subsequent decay of the spin precession. The amplitude of the rf-driven spin precession is significantly enhanced upon additional optical pumping along the magnetic field.
miR-4634 augments the anti-tumor effects of RAD001 and associates well with clinical prognosis of non-small cell lung cancer
Authors: Liu Sile , Zang Hongjing , Zheng Hongmei , Wang Weiyuan , Wen Qiuyuan , Zhan Yuting , Yang Yang , Ning Yue , Wang Haihua , Fan Songqing
Published: August 2020

MicroRNA (miRNA) is involved in the physiological and pathological processes of various malignancies. In this study, miRNA microarray analysis showed that miR-4634 levels in A549 cells increased significantly after everolimus (RAD001) treatment. Decreased expression of miR-4634 was also found in non-small-cell lung carcinoma (NSCLC) cell lines and patients’ tumors by qPCR. Additionally, a combination of miR-4634 and RAD001 exerted synergistic antitumor efficacy by inhibiting cell proliferation, migration, and colony formation. High expression of miR-4634 was significantly more common in non-cancerous lung tissue than adenocarcinoma or squamous cell carcinoma tissue (72.8%, 45.7%, and 50.9%, respectively; P < 0.001). Furthermore, high expression of miR-4634 was found to be more frequent in patients without lymph node metastasis (P = 0.037) by in-situ hybridization. Importantly, through univariate and multivariate analysis, high miR-4634 expression was associated with better prognosis of NSCLC patients. In conclusion, miR-4634 may act as a tumor suppressor in NSCLC, and to augment the efficacy of RAD001, co-treatment of miR-4634 and RAD001 might be a potential mTOR-targeted cancer therapy strategy for NSCLC patients. High expression of miR-4634 could be an independent good prognostic biomarker for NSCLC.