bluuebunny/crossref_metadata_2025 huggingface dataset:
Understanding conformational diversity of heat shock protein 90 (HSP90) and binding features of inhibitors to HSP90 via molecular dynamics simulations
Authors: Yan Fangfang , Liu Xinguo , Zhang Shaolong , Zhang Qinggang , Chen Jianzhong
Published: September 2019

Heat shock protein 90 (HSP90) is a promising target for treatment of cancer, and inhibitor bindings can generate efficient suppression on tumor in multiple ways. In this work, 140‐ns molecular dynamics simulations were performed on six systems. Principal component analysis was subsequently carried out to explore the conformational diversity of HSP90. The results suggest that inhibitor bindings induce large conformational changes of HSP90, which tends to enlarge the volume of the binding pocket to facilitate the entrance of inhibitors. Hierarchical clustering analyses, the calculation of the energy contribution of each atom, and the analyses of hydrogen‐bonding interactions were performed. The results indicate that 20 residues in group A of the hierarchical tree are responsible for major contributions, and van der Waals interactions as well as hydrogen‐bonding interactions between important residues in HSP90 and key regions of inhibitors are the main force for promoting inhibitor bindings. We expect that this work can provide useful theoretical information for development of efficient inhibitors targeting HSP90.
IL‐37b alleviates inflammation in the temporomandibular joint cartilage via IL‐1R8 pathway
Authors: Luo Ping , Feng Chi , Jiang Chao , Ren Xiaochun , Gou Liming , Ji Ping , Xu Jie
Published: September 2019

Objectives

Interleukin (IL)‐37 is a natural suppressor of innate inflammation. This study was conducted to explore the anti‐inflammatory effects of IL‐37 in temporomandibular joint (TMJ) inflammation.

Materials and Methods

The expression of IL‐37 in the TMJ was measured using ELISA and IHC. Human TMJ chondrocytes were treated with IL‐37b and IL‐1β, and inflammation‐related factors were detected. siRNA‐IL‐1R8 was transfected into chondrocytes, and the affected pathways were detected. IL‐37b was used in disc‐perforation‐induced TMJ inflammation in SD rats. Micro‐CT, IHC, real‐time PCR and histological staining were used to quantify the therapeutic effect of IL‐37b.

Results

IL‐37 was expressed in the synovium and the disc of patients with osteoarthritis (OA) and in the articular cartilage of condylar fracture patients. IL‐37 was highly expressed in synovial fluid of patients with synovitis than in those with OA and disc displacement and was closely related to visual analogue scale (VAS) score. In vitro, IL‐37b suppressed the expression of pro‐inflammatory factors. In addition, IL‐37b exerted anti‐inflammatory effects via IL‐1R8 by inhibiting the p38, ERK, JNK and NF‐κB activation, while silencing IL‐1R8 led to inflammation and upregulation of these signals. In disc‐perforation‐induced TMJ inflammation in SD rats, IL‐37b suppressed inflammation and inhibited osteoclast formation to protect against TMJ.

Conclusions

IL‐37b may be a novel therapeutic agent for TMJ inflammation.
Intoxicants and the invention of ‘consumption’
Authors: Withington Phil
Published: September 2019

In 1600 the word ‘consumption’ was a term of medical pathology describing the ‘wasting, petrification of things’. By 1700 it was also a term of economic discourse: ‘In commodities, the value rises as its quantity is less and vent greater, which depends upon it being preferred in its consumption’. The article traces the emergence of this key category of economic analysis to debates over the economy in the 1620s and subsequent disputes over the excise tax, showing how ‘consumption’ was an early term in the developing lexicon of political economy. In so doing the article demonstrates the important role of ‘intoxicants’—that is, addictive and intoxicating commodities like alcohols and tobaccos—in shaping these early meanings and uses of ‘consumption’. It outlines the discursive importance of intoxicants, both as the foci for discussions of ‘superfluous’ and ‘necessary’ consumption and the target of legislation on consumption. It argues that while these discussions had an ideological dimension, or dimensions, they were also responses to material increases in the volume and diversity of intoxicants in early seventeenth‐century England. By way of conclusion the article suggests the significance of the Low Countries as a point of reference for English writers, as well as a more capacious and semantically sensitive approach to changes in early modern consumption practices.
Global vegetation biomass production efficiency constrained by models and observations
Authors: He Yue , Peng Shushi , Liu Yongwen , Li Xiangyi , Wang Kai , Ciais Philippe , Arain M. Altaf , Fang Yuanyuan , Fisher Joshua B. , Goll Daniel , Hayes Daniel , Huntzinger Deborah N. , Ito Akihiko , Jain Atul K. , Janssens Ivan A. , Mao Jiafu , Matteo Campioli , Michalak Anna M. , Peng Changhui , Peñuelas Josep , Poulter Benjamin , Qin Dahe , Ricciuto Daniel M. , Schaefer Kevin , Schwalm Christopher R. , Shi Xiaoying , Tian Hanqin , Vicca Sara , Wei Yaxing , Zeng Ning , Zhu Qiuan
Published: September 2019

Plants use only a fraction of their photosynthetically derived carbon for biomass production (BP). The biomass production efficiency (BPE), defined as the ratio of BP to photosynthesis, and its variation across and within vegetation types is poorly understood, which hinders our capacity to accurately estimate carbon turnover times and carbon sinks. Here, we present a new global estimation of BPE obtained by combining field measurements from 113 sites with 14 carbon cycle models. Our best estimate of global BPE is 0.41 ± 0.05, excluding cropland. The largest BPE is found in boreal forests (0.48 ± 0.06) and the lowest in tropical forests (0.40 ± 0.04). Carbon cycle models overestimate BPE, although models with carbon–nitrogen interactions tend to be more realistic. Using observation‐based estimates of global photosynthesis, we quantify the global BP of non‐cropland ecosystems of 41 ± 6 Pg C/year. This flux is less than net primary production as it does not contain carbon allocated to symbionts, used for exudates or volatile carbon compound emissions to the atmosphere. Our study reveals a positive bias of 24 ± 11% in the model‐estimated BP (10 of 14 models). When correcting models for this bias while leaving modeled carbon turnover times unchanged, we found that the global ecosystem carbon storage change during the last century is decreased by 67% (or 58 Pg C).
Migraine Awareness in Italy and the Myth of “Cervical Arthrosis”
Authors: Rota Eugenia , Zucco Riccardo , Guerzoni Simona , Cainazzo Maria M. , Pini Luigi A. , Catarci Teresa , Granella Franco
Published: September 2019

Objective

The primary aim of this study was to assess the degree of awareness migraine patients had of their condition. The secondary aims were to evaluate the frequency of an incorrect diagnosis of “cervical arthrosis” in patients unaware of having migraine and to compare the clinical features, diagnostic investigation, and treatment strategies between the 2 subgroups of migraineurs, that is, those with and without the incorrect diagnosis of “cervical arthrosis.”

Methods

Patients, between 18 and 65 years, were consecutively referred to 5 Headache Centers in 2 Italian regions for a first visit. They fulfilled the diagnostic criteria for migraine (with/without aura, episodic/chronic) and were enrolled in this cross‐sectional study. Each patient underwent a specific cranial/cervical musculoskeletal clinical examination.

Results

A total of 117/250 subjects (46.8%) were unaware that they suffered from migraine. In these unaware subjects, the most frequently reported diagnosis was “cervical arthrosis” in 34/117 (29.1%), followed by tension‐type headache in 23/117 (19%). The cervical region was the most common site of pain onset in the so‐called “cervical arthrosis” group (52.9%, P < .0001), where also more pericranial (58.8%; P = .041) and neck (70.6%; P = .009) muscle tenderness, restricted range of cervical vertical (47.1%; P < .001), and lateral (29.4%; P = .040) movements were reported. More “cervical arthrosis patients” had been referred to an Emergency Department (88.2%; P = .011) and had undergone more cervical spine radiography (23.5%; P = .003) and magnetic resonance imaging (20.6%; P = .044). While they had used fewer triptans (11.8%; P = .007) and received less pharmacological prophylaxis (2.9%; P = .004).

Conclusions

In our sample, there were high misdiagnosis rates for migraine sufferers in Italy. The most common misdiagnosis, that is, “cervical arthrosis,” led to misuse of healthcare facilities and had a negative impact on the migraine treatment.
Implementation of the three good questions—A feasibility study in Dutch hospital departments
Authors: Garvelink Mirjam M. , Jillissen Marja , Knops Anouk , Kremer Jan A. M. , Hermens Rosella P.M.G. , Meinders Marjan J.
Published: September 2019

Objectives

To determine the feasibility of pragmatic implementation strategies for three good questions (in Dutch: Drie Goede Vragen; 3GV. What are my options; what are the risks and benefits related to these options; and what does this mean for my situation?) to increase shared decision‐making (SDM) efforts in Dutch secondary care, and identify barriers and facilitators of implementation.

Methods

Convergent mixed‐method design: pre‐post surveys with patients attending one of six clinical departments in a Dutch Hospital, post‐intervention interviews with patients and health‐care professionals. Primary outcomes: feasibility (reach, use of 3GV). Secondary outcomes: SDM, experiences with 3GV and decision making. Interviews focused on barriers and facilitators of 3GV use. Interviews were content coded and categorized into determinants of behaviour change.

Results

35% of the respondents who had heard of 3GV (52%) used all three questions. 3GV use did not lead to more SDM (SDMQ9 M = Δ0.3;SE = 2.2) but patients felt empowered to decide (88%) and to SDM (86%). Barriers were as follows: time investment, other SDM projects and perception that the need to use 3GV differs per patient/consultation. Respondents preferred to use 3GV as they saw fit for the consultation, instead of literally asking them. Facilitators: easy, accessible information materials that can be flexibly used.

Conclusion

Implementation of 3GV seemed feasible, although influenced by contextual characteristics (eg type of decisions, patients, on‐going interventions). 3GV contributed to important elements of SDM, and respondents were willing to apply them in a way that suited their situation.

Practice implications

We recommend continuation of current and new implementation strategies to enable 3GV implementation in secondary care.
Tumour budding/T cell infiltrates in colorectal cancer: proposal of a novel combined score
Authors: Dawson Heather , Christe Lucine , Eichmann Micha , Reinhard Stefan , Zlobec Inti , Blank Annika , Lugli Alessandro
Published: September 2019

Aims

The tumour–node–metastasis classification system is used for prognostication purposes and to guide patient management. However, in colorectal cancer (CRC), additional markers are needed to stratify prognostic subgroups. Two promising markers have emerged from large bodies of research: tumour budding and T cell host response (CD3, CD8 and CD45RO infiltrates). However, attempts to combine these two parameters have been sparse. The aim of this study was to perform an assessment of potential protagonists that could be used in a combined score (budding/T cell score, BTS).

Methods and results

This descriptive, retrospective study was performed on a multipunch tissue microarray containing material from 345 patients with stages I–IV CRC. Areas from tumour centre, front and microenvironment were stained for pancytokeratin/CD3, pancytokeratin/CD8 and pancytokeratin/CD45RO. Tumour buds were scored manually and T cell infiltrates digitally using open‐source software. Tumour buds, T cell counts and combined BTS were associated with clinicopathological features and overall survival (OS). A higher combined BTS score (buds/CD8, tumour centre) performed better than budding or CD8/CD3 alone in predicting nodal metastases (P < 0.0001, OR = 1.466, 95% CI = 1.115–1.928). Only higher BTS (buds/CD3) were significantly associated with poorer OS on multivariate analysis (P = 0.012, hazard ratio = 1.218, 95% confidence interval = 1.044–1.419).

Conclusions

Although CD8+/CD3+ T cells are predictive of tumour biology in CRC, we found a combined BTS to be stronger in predicting survival and certain features with high clinical relevance, such as nodal metastases, in comparison to budding or T cells alone. Further studies combining T cell infiltrates and tumour budding are necessary to optimise risk assessment of CRC.
Safehavenness of the Chinese renminbi
Authors: Fong Tom Pak Wing , Wong Alfred Yun Tong
Published: September 2019

This paper investigates how safe (or risky) the Chinese renminbi is as an international currency from the perspectives of dollar‐ and euro‐based investors. It estimates the “safehavenness” of the currency, defined as the extent to which the currency plays the role of a safe haven, in both its onshore and offshore markets alongside 20 most‐traded currencies in the world, including those in the special drawings rights (SDR) basket. We find that the Chinese renminbi has generally registered a high level of safehavenness among the most‐traded currencies since it became actively traded in the offshore market. Compared with the other SDR currencies, it consistently ranks below the Japanese yen and U.S. dollar but above the British pound and euro on the scale of safehavenness. Despite market fragmentation, the safehavenness of the Chinese renminbi onshore (CNY) is very similar to, albeit marginally lower, that of the Chinese renminbi offshore (CNH), attributable possibly to a stronger price discovery process in the latter market. These estimation results show striking consistency between dollar‐ and euro‐based investors in their assessment across various time periods characterized by major structural differences.
A Look Back at the Beginnings of EVA and Value‐Based Management
Authors: Stern Joel M. , Willett Joseph T.
Published: September 2019

In this interview conducted five years ago, one of the pioneers of value‐based management discusses his life's work in converting principles of modern finance theory into performance evaluation and incentive compensation plans that have been adopted by many of the world's largest and most successful companies, including Coca‐Cola, SABMiller in London, Siemens in Germany, and the Godrej Group in India. The issues covered include the significance of dividend payouts (are dividends really necessary to support a company's stock price and, if so, why?) as well as the question of optimal capital structure (whether and why debt might be cheaper than equity).

But the most important focus of the interview is corporate performance measurement and the use of executive pay to strengthen management incentives to increase efficiency and value.

As Stern never tired of arguing, the widespread tendency of public companies to manage “for earnings”—or in accordance with what he refers to as “the accounting model of the firm”—often leads to value‐destroying decisions. As one example, the GAAP accounting principle that requires intangible investments like R&D and training to be written off in the year the money is spent is likely to cause significant underinvestment in such intangibles. At the same time, the failure of conventional income statements to reflect the cost of equity almost certainly encourages corporate overinvestment.

Stern's solution to this problem was an executive incentive compensation plan whose rewards were tied to increases in a measure of economic profit called economic value added, or EVA, which research has shown to have a significance relation to changes both in share value and the premium of market value over book value. Moreover, by combining such a plan with a “bonus bank” that pays out annual awards over a multiyear period, boards could ensure that management will be rewarded not for good luck but for sustainable improvements in performance.
Why EVA Bonus Plans Failed—and How to Revive Them
Authors: O'Byrne Stephen
Published: September 2019

Most companies rely heavily on earnings to measure their financial performance, but earnings growth has at least two important weaknesses as a proxy for investor wealth. Current earnings growth may come at the expense of future earnings through, say, shortsighted cutbacks in corporate investment, including R&D or advertising. But growth in earnings per share can also be achieved by “overinvesting”—that is, committing ever more capital to projects with expected rates of return that, although well below the cost of capital, exceed the after‐tax cost of debt. Stock compensation has been the conventional solution to the first problem because it's a discounted cash flow value that is assumed to discourage actions that sacrifice future earnings. Economic profit—in its most popular manifestation, EVA—has been the conventional solution to the second problem because it includes a capital charge that penalizes low‐return investment.

But neither of these conventional solutions appears to work very well in practice. Stock compensation isn't tied to business unit performance, and often fails to motivate corporate managers who believe that meeting consensus earnings is more important than investing to maintain future earnings. EVA often doesn't work well because increases in current EVA often come with reduced expectations of future EVA improvement—and reductions in current EVA are often accompanied by increases in future growth values. Since EVA bonus plans reward current EVA increases without taking account of changes in expected future growth values, they have the potential to encourage margin improvement that comes at the expense of business growth and discourage positive‐NPV investments that, because of longer‐run payoffs, reduce current EVA.

In this article, the author demonstrates the possibility of overcoming such short‐termism by developing an operating model of changes in future growth value that can be used to calibrate “dynamic” EVA improvement targets that more closely align EVA bonus plan payouts with investors’ excess returns. With the use of “dynamic” targets, margin improvements that come at the expense of business growth can be discouraged by raising EVA performance targets, while growth investments can be encouraged by the use of lower EVA targets.
Incidence of acute thermal esophageal injury after atrial fibrillation ablation guided by prespecified ablation index
Authors: Halbfass Philipp , Berkovitz Artur , Pavlov Borche , Sonne Kai , Nentwich Karin , Ene Elena , Hoerning Frank , Barth Sebastian , Zacher Michael , Deneke Thomas
Published: September 2019

Introduction

Ablation index (AI), a novel parameter defining energy application at single ablation lesions, calculated by integration of ablation time, energy, catheter stability, and contact force, has been documented to be associated with effective lesions and higher ablation efficacy. Using a prespecified target AI in addition to acute lesion efficacy may affect local collateral damage like esophageal thermal injury when used for guiding radiofrequency (RF) ablation at the posterior left atrial (LA) wall.

Methods and Results

Consecutive patients undergoing first AF ablations using AI were included. Ablation energy was reduced to 25 W when ablating at posterior LA wall. Two different individually defined AI target values were used (300 and 350 for posterior wall ablation). Esophageal endoscopy (EE) was performed 1 to 3 days after ablation procedure to document and categorize endoscopically detected esophageal thermal lesion (EDEL).

Two‐hundred and eleven consecutive patients with postprocedural EE were included. Incidence of EDEL was 14% (29 of 211 patients; mild category 1 lesions in 22 of 29 patients (76%) and severe category 2 lesions (ulcers > 5 mm) in 7 of 29 patients (24% of EDEL group, 3% of total group). Ablation time at posterior LA wall (9.5 vs 9.0 minutes [P = .67]) was comparable in patients with and without EDEL.

Conclusion

LA posterior wall RF ablation adopting AI ≤350 was associated with 14% esophageal thermal injury including 3% of severe esophageal thermal ulcers. This incidence is comparable to historic control groups with non AI–guided AF ablation.
Long non‐coding RNA TUG1 promotes airway remodelling by suppressing the miR‐145‐5p/DUSP6 axis in cigarette smoke‐induced COPD
Authors: Gu Wenchao , Yuan Yaping , Wang Linxuan , Yang Hua , Li Shanshan , Tang Zhijun , Li Qiang
Published: September 2019

Chronic obstructive pulmonary disease (COPD) is a progressive lung disease that is primarily caused by cigarette smoke (CS)‐induced chronic inflammation. In this study, we investigated the function and mechanism of action of the long non‐coding RNA (lncRNA) taurine‐up‐regulated gene 1 (TUG1) in CS‐induced COPD. We found that the expression of TUG1 was significantly higher in the sputum cells and lung tissues of patients with COPD as compared to that in non‐smokers, and negatively correlated with the percentage of predicted forced expiratory volume in 1 second. In addition, up‐regulation of TUG1 was observed in CS‐exposed mice, and knockdown of TUG1 attenuated inflammation and airway remodelling in a mouse model. Moreover, TUG1 expression was higher in CS extract (CSE)‐treated human bronchial epithelial cells and lung fibroblasts, whereas inhibition of TUG1 reversed CSE‐induced inflammation and collagen deposition in vitro. Mechanistically, TUG1 promoted the expression of dual‐specificity phosphatase 6 (DUSP6) by sponging miR‐145‐5p. DUSP6 overexpression reversed TUG1 knockdown‐mediated inhibition of inflammation and airway remodelling. These findings suggested an important role of TUG1 in the pathological alterations associated with CS‐mediated airway remodelling in COPD. Thus, TUG1 may be a promising therapeutic target in CS‐induced airway inflammation and fibroblast activation.
Aberrantly expressed long non‐coding RNAs in air pollution‐induced congenital defects
Authors: Li Zheng , Ma Jianqing , Li Xingye , Chan Matthew T. V. , Wu William K. K. , Wu Zhanyong , Shen Jianxiong
Published: September 2019

Air pollution has been a serious public health issue over the past few decades particularly in developing countries. Air pollution exposure during pregnancy poses potential threat to offspring as the deleterious substances might pass through placenta to alter foetal development. A growing number of studies have demonstrated that long non‐coding RNAs (lncRNAs) participate in the development of many diseases, including congenital defects. Here, we used RNA sequencing to identify differentially expressed lncRNAs in air pollution‐exposed rat embryos compared with control group. Our data suggested that 554 lncRNAs (216 up‐regulated and 338 down‐regulated) were significantly differentially expressed in the air pollution‐exposed embryos. Moreover, potential cellular functions of these deregulated lncRNAs were predicted via KEGG signal pathway/GO enrichment analyses, which suggested the possible involvements of neurological process, sensory perception of smell and the G‐protein signalling pathway. Furthermore, potential functional network of deregulated lncRNAs and their correlated mRNAs in the development of congenital spinal abnormality was established. Our data suggested that lncRNAs may play a vital role in the pathophysiology of air pollution‐exposed congenital spinal malformation.
Coordinate regulation of ELF5 and EHF at the chr11p13 CF modifier region
Authors: Swahn Hannah , Sabith Ebron Jey , Lamar Kay‐Marie , Yin Shiyi , Kerschner Jenny L. , NandyMazumdar Monali , Coppola Candice , Mendenhall Eric M. , Leir Shih‐Hsing , Harris Ann
Published: September 2019

E74‐like factor 5 (ELF5) and ETS‐homologous factor (EHF) are epithelial selective ETS family transcription factors (TFs) encoded by genes at chr11p13, a region associated with cystic fibrosis (CF) lung disease severity. EHF controls many key processes in lung epithelial function so its regulatory mechanisms are important. Using CRISPR/Cas9 technology, we removed three key cis‐regulatory elements (CREs) from the chr11p13 region and also activated multiple open chromatin sites with CRISPRa in airway epithelial cells. Deletion of the CREs caused subtle changes in chromatin architecture and site‐specific increases in EHF and ELF5. CRISPRa had most effect on ELF5 transcription. ELF5 levels are low in airway cells but higher in LNCaP (prostate) and T47D (breast) cancer cells. ATAC‐seq in these lines revealed novel peaks of open chromatin at the 5’ end of chr11p13 associated with an expressed ELF5 gene. Furthermore, 4C‐seq assays identified direct interactions between the active ELF5 promoter and sites within the EHF locus, suggesting coordinate regulation between these TFs. ChIP‐seq for ELF5 in T47D cells revealed ELF5 occupancy within EHF introns 1 and 6, and siRNA‐mediated depletion of ELF5 enhanced EHF expression. These results define a new role for ELF5 in lung epithelial biology.
Levetiracetam treatment ameliorates LRRK2 pathological mutant phenotype
Authors: Rassu Mauro , Biosa Alice , Galioto Manuela , Fais Milena , Sini Paola , Greggio Elisa , Piccoli Giovanni , Crosio Claudia , Iaccarino Ciro
Published: September 2019

Mutations in leucine‐rich repeat kinase 2 (LRRK2) are the most common genetic cause of Parkinson's disease (PD). The LRRK2 physiological and pathological function is still debated. However, different experimental evidence based on LRRK2 cellular localization and LRRK2 protein interactors suggests that LRRK2 may be part and regulate a protein network modulating vesicle dynamics/trafficking. Interestingly, the synaptic vesicle protein SV2A is part of this protein complex. Importantly, SV2A is the binding site of the levetiracetam (LEV), a compound largely used in human therapy for epilepsy treatment. The binding of LEV to SV2A reduces the neuronal firing by the modulation of vesicle trafficking although by an unclear molecular mechanism. In this short communication, we have analysed the interaction between the LRRK2 and SV2A pathways by LEV treatment. Interestingly, LEV significantly counteracts the effect of LRRK2 G2019S pathological mutant expression in three different cellular experimental models. Our data strongly suggest that LEV treatment may have a neuroprotective effect on LRRK2 pathological mutant toxicity and that LEV repositioning could be a viable compound for PD treatment.
Resveratrol decreases CD45+CD206− subtype macrophages in LPS‐induced murine acute lung injury by SOCS3 signalling pathway
Authors: Hu Lu , Chen Zhihong , Li Liyang , Jiang Zhilong , Zhu Lei
Published: September 2019

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) are life‐threatening condition in critically ill patients. Resveratrol (Res), a natural polyphenol, has therapeutic effect in animal model with ALI; however, whether Res attenuates ALI through modulation of macrophage phenotypes in the animal model remains unknown. We in this study treated LPS‐induced murine ALI with 30 mg/kg Res and observed significantly reduced severity of ALI in the Res‐treated mice 48 hours after Res treatment. Neutrophil infiltrates were significantly reduced, accompanied with lower infiltration of CD45+Siglec F− phenotype macrophages, but higher population of CD45+Siglec F+ and CD45+CD206+ alternatively activated macrophages (M2 cells) in the Res‐treated mice with ALI. In addition, the expression of IL‐1beta and CXCL15 cytokines was suppressed in the treated mice. However, Res treatment in mice with myeloid cell‐restricted SOCS3 deficiency did not significantly attenuate ALI severity and failed to increase population of both CD45+Siglec F+ and CD45+CD206+ M2 subtype macrophages in the murine ALI. Further studies in wild‐type macrophages revealed that Res treatment effectively reduced the expression of IL‐6 and CXCL15, and increased the expression of arginase‐1, SIRT1 and SOCS3. However, macrophages’ lack of SOCS3 expression were resistant to the Res‐induced suppression of IL‐6 and CXCL15 in vitro. Thus, we conclude that Res suppressed CD45+Siglec F− and CD45+CD206− M1 subtype macrophages through SOCS3 signalling in the LPS‐induced murine ALI.
Accuracy of single molecular biomarkers in saliva for the diagnosis of periodontitis: A systematic review and meta‐analysis
Authors: Arias‐Bujanda Nora , Regueira‐Iglesias Alba , Balsa‐Castro Carlos , Nibali Luigi , Donos Nikos , Tomás Inmaculada
Published: September 2019

Aim

To analyse, using a meta‐analytical approach, the diagnostic accuracy of single molecular biomarkers in saliva for the detection of periodontitis in systemically healthy subjects.

Materials and Methods

Articles on molecular biomarkers in saliva providing a binary contingency table (or sensitivity and specificity values and group sample sizes) in individuals with clinically diagnosed periodontitis were considered eligible. Searches for candidate articles were conducted in six electronic databases. The methodological quality was assessed through the tool Quality Assessment of Diagnostic Studies. Meta‐analyses were performed using the Hierarchical Summary Receiver Operating Characteristic model.

Results

Meta‐analysis was possible for 5 of the 32 biomarkers studied. The highest values of sensitivity for the diagnosis of periodontitis were obtained for IL1beta (78.7%), followed by MMP8 (72.5%), IL6 and haemoglobin (72.0% for both molecules); the lowest sensitivity value was for MMP9 (70.3%). In terms of specificity estimates, MMP9 had the best result (81.5%), followed by IL1beta (78.0%) and haemoglobin (75.2%); MMP8 had the lowest specificity (70.5%).

Conclusions

MMP8, MMP9, IL1beta, IL6 and Hb were salivary biomarkers with good capability to detect periodontitis in systemically healthy subjects. MMP8 and IL1beta are the most researched biomarkers in the field, both showing clinically fair effectiveness for the diagnosis of periodontitis.
Evidence for Production of Sexual Resting Cysts by the Toxic Dinoflagellate Karenia mikimotoi in Clonal Cultures and Marine Sediments
Authors: Liu Yuyang , Hu Zhangxi , Deng Yunyan , Tang Ying Zhong
Published: September 2019

The toxic dinoflagellate Karenia mikimotoi has been well‐known for causing large‐scale and dense harmful algal blooms (HABs) in coastal waters worldwide and serious economic loss in aquaculture and fisheries and other adverse effects on marine ecosystems. Whether K. mikimotoi forms resting cysts has been a puzzling issue regarding to the mechanisms of bloom initiation and geographic expansion of this species. We provide morphological and molecular confirmation of sexually produced thin‐walled resting cysts by K. mikimotoi based on observations of laboratory cultures and their direct detection in marine sediments. Light and scanning electron microscopy evidences for sexual reproduction include attraction and pairing of gametes, gamete fusion, formation of planozygote and thin‐walled cyst, and the documentation of the thin‐walled cyst germination processes. Evidence for cysts in marine sediments was in three aspects: positive PCR detection of cysts using species‐specific primers in the DNA extracted from whole sediments; fluorescence in situ hybridization detection of cysts using FISH probes; and single‐cell PCR sequencing for cysts positively labeled with FISH probes. The existence of sexually produced, thin‐walled resting cysts by K. mikimotoi provides a possible mechanism accounting for the initiation of annually recurring blooms at certain regions and global expansion of the species during the past decades.
RNA‐Seq of in planta‐expressed Magnaporthe oryzae genes identifies MoSVP as a highly expressed gene required for pathogenicity at the initial stage of infection
Authors: Shimizu Motoki , Nakano Yuki , Hirabuchi Akiko , Yoshino Kae , Kobayashi Michie , Yamamoto Kosuke , Terauchi Ryohei , Saitoh Hiromasa
Published: September 2019

The ascomycete fungus Magnaporthe oryzae is a hemibiotrophic pathogen that causes rice blast disease. Magnaporthe oryzae infects rice leaves, stems and panicles, and induces severe reductions in yield. Effector proteins secreted by M. oryzae in planta are thought to be involved its virulence activity. Here, using RNA‐sequencing (RNA‐Seq), we generated transcriptome data for M. oryzae isolate Ina168 during the initial stages of infection. We prepared samples from conidia (the inoculum) and from peeled epidermal cotyledon tissue of susceptible barley Hordeum vulgare ‘Nigrate’ at 12, 24, 36 and 48 hours post‐inoculation (hpi). We also generated a draft genome sequence of M. oryzae isolate Ina168 and used it as a reference for mapping the RNA‐Seq reads. Gene expression profiling across all stages of M. oryzae infection revealed 1728 putative secreted effector protein genes. We selected seven such genes that were strongly up‐regulated at 12 hpi and down‐regulated at 24 or 36 hpi and performed gene knockout analysis to determine their roles in pathogenicity. Knockout of MoSVP, encoding a small putative secreted protein with a hydrophobic surface binding protein A domain, resulted in a reduction in pathogenicity, suggesting that MoSVP is a novel virulence effector of M. oryzae.
Rediscovery of the lost endemic Micromeria cymuligera (Lamiaceae) in eastern Anatolia‐Turkey
Authors: Behçet Lütfi , Yapar Yakup
Published: September 2019

A rediscovery of the endemic Micromeria cymuligera is presented. This species is endemic to Turkey. While it was first collected by Haussknecht in 1865 from Kahramanmaraş and described by P. E. E. Boissier and C. Haussknecht in 1879, it was not recollected until 2011. We rediscovered two populations of this species in Bingöl (eastern Anatolia). The distribution range of the species, its ecology, and photos are presented. Additionally, we provide a revised description of this poorly known species and its morphological affinities are briefly discussed considering that it may possibly rather belong to the genus Mentha. Pollen characteristics and nutlet surface features were examined with light microscopy (LM) and scanning electron microscopy (SEM). Its current conservation status is re‐evaluated with respect to the most recent IUCN criteria.
Clinical features and outcomes of community‐acquired late‐onset sepsis: Focusing on group B Streptococcus and Escherichia coli
Authors: Yun Ki Wook , Park Sun Hyung , Cho Eun Young , Lee Hyunju
Published: September 2019

Background

Group B Streptococcus (GBS) and Escherichia coli are leading causes of late‐onset sepsis (LOS) and bacterial meningitis in neonates and infants. This study aimed to describe clinical characteristics and outcomes of community‐acquired (CA) LOS caused by GBS and E. coli.

Methods

A retrospective observational study was performed in three university hospitals in Korea. All infants aged <90 days who were diagnosed with GBS or E coli CA‐LOS from 2011 to 2017 were enrolled. Data on the clinical characteristics and outcomes of GBS and E. coli CA‐LOS were compared.

Results

Forty GBS and 43 E. coli CA‐LOS cases were identified, which mostly (82/83) included term or near‐term infants. Meningitis was identified in 54.1% of GBS CA‐LOS cases and in 30.3% of E. coli CA‐LOS cases, and 88.4% of E. coli CA‐LOS cases involved urosepsis. Ten percent each of GBS and non‐uropathogenic E. coli (non‐UPEC) meningitis cases and all uropathogenic E. coli (UPEC) meningitis cases were diagnosed by pleocytosis without bacterial growth in the cerebrospinal fluid (CSF). Patients with non‐culture‐proven meningitis had lower CSF pleocytosis and protein levels and higher CSF/serum glucose ratios than patients with culture‐proven meningitis (P < 0.05 for all). One patient died of CA‐LOS, which was accompanied by meningitis with extended‐spectrum β‐lactamase‐producing non‐UPEC. Neurological complications developed in 22.5% of GBS CA‐LOS cases and in 2.3% of E. coli CA‐LOS cases.

Conclusions

Neurological complications were frequently observed in GBS CA‐LOS cases, although no mortality was observed. Escherichia coli CA‐LOS generally developed as urosepsis, which caused non‐culture‐proven meningitis and had a favorable outcome.
A Dual Emissive Coumarin–urea Derivative with an Electron‐withdrawing Substituent in the Presence of Acetate Anion
Authors: Shinoda Tomoyuki , Nishimura Yoshinobu , Arai Tatsuo
Published: September 2019

We investigated the fluorescent properties, including the excited‐state intermolecular proton transfer, of urea derivatives comprising a coumarin ring, which is a widely used fluorophore. We prepared two different coumarin–urea derivatives, 6CU and 7CU, which bear a urea‐based substituent at the 6 and 7 positions of a coumarin ring, respectively. In the presence of the acetate ion, 7CU showed additional tautomer fluorescence emission with respect to 6CU, indicating that tautomer formation depends on the positions of the urea‐based substituent on the coumarin ring. Thus, the resonance structures of urea derivatives might play an important role in the behavior of dual fluorescence, which is an important phenomenon applicable to photochemical anion sensing. Moreover, in order to further improve the fluorescence properties of the mentioned derivatives, a CF3 group was introduced in a phenyl ring opposite to a coumarin ring. The fluorescence quantum yield of 7CUCF3 thus synthesized was 65 times as large as that of 7CU, an observation that renders 7CUCF3 a suitable anion sensor candidate. The results of this study will contribute to the development of new molecular designs for highly fluorescent sensing.
GmMAX2–D14 and –KAI interaction‐mediated SL and KAR signaling play essential roles in soybean root nodulation
Authors: Ahmad Muhammad Zulfiqar , Rehman Naveed ur , Yu Shuwei , Zhou Yuanze , Haq Basir ul , Wang Junjie , Li Penghui , Zeng Zhixiong , Zhao Jian
Published: September 2019

Despite of important functions of strigolactones (SLs) and karrikins (KARs) in plant development, plant–parasite and plant–fungi interactions, their roles in soybean–rhizobia interaction remain elusive. SL/KAR signaling genes GmMAX2a, GmD14s, and GmKAIs are activated by rhizobia infection. GmMAX2a restored atmax2 root hair defects and soybean root hairs were changed in GmMAX2a overexpression (GmMAX2a‐OE) or knockdown (GmMAX2a‐KD) mutants. GmMAX2a‐KD gave fewer, whereas GmMAX2a‐OE produced more nodules than GUS hairy roots. Mutation of GmMAX2a in its KD or OE transgenic hairy roots affected the rhizobia infection‐induced increases in early nodulation gene expression. Both mutant hairy roots also displayed the altered auxin, jasmonate and abscisic acid levels, as further verified by transcriptomic analyses of their synthetic genes. Overexpression of an auxin synthetic gene GmYUC2a also affected SL and KAR signaling genes. GmMAX2a physically interacted with SL/KAR receptors GmD14s, GmKAIs, and GmD14Ls with different binding affinities, depending on variations in the critical amino acids, forming active D14/KAI‐SCFMAX2 complexes. The knockdown mutant roots of the nodule‐specifically expressing GmKAIs and GmD14Ls gave fewer nodules, with altered expression of several early nodulation genes. The expression levels of GmKAIs, and GmD14Ls were markedly changed in GmMAX2a mutant roots, so did their target repressor genes GmD53s and GmSMAX1s. Thus, SL and KAR signaling were involved in soybean–rhizobia interaction and nodulation partly through interactions with hormones, and this may explain the different effects of MXA2 orthologs on legume determinate and indeterminate nodulation. The study provides fresh insights into the roles of GmMAX2‐mediated SL/KAR signaling in soybean root hair and nodule formation.
A New Class of Uniform Continuous Higher-Order Sliding Mode Controllers
Authors: Kamal Shyam , Ramesh Kumar P. , Chalanga Asif , Goyal Jitendra Kumar , Bandyopadhyay Bijnan , Fridman L.
Published: September 2019

This paper proposes a new class of uniform continuous higher-order sliding mode algorithm (UCHOSMA) for the arbitrary relative degree systems. The proposed methodology is a combination of two controllers where one of the components is a uniform super-twisting control which acts as the disturbance compensator and the second part gives the uniform finite time convergence for the disturbance free system. This algorithm provides uniform finite time convergence of the output and its higher derivatives using an absolutely continuous control signal and thus alleviating the chattering phenomenon. The attractive feature of the proposed controller is that irrespective of the different initial conditions, the control is able to bring the states of the system to the equilibrium point uniformly in finite time. The effectiveness of the proposed controller has been demonstrated with both simulation and experimental results.
Design, Optimization, and Analysis of Supersonic Radial Turbines
Authors: Inhestern Lukas Benjamin , Braun James , Paniagua Guillermo , Serrano Cruz José Ramón
Published: September 2019

New compact engine architectures such as pressure gain combustion require ad hoc turbomachinery to ensure an adequate range of operation with high performance. A critical factor for supersonic turbines is to ensure the starting of the flow passages, which limits the flow turning and airfoil thickness. Radial outflow turbines inherently increase the cross section along the flow path, which holds great potential for high turning of supersonic flow with a low stage number and guarantees a compact design. First, the preliminary design space is described. Afterward a differential evolution multi-objective optimization with 12 geometrical design parameters is deducted. With the design tool autoblade 10.1, 768 geometries were generated and hub, shroud, and blade camber line were designed by means of Bezier curves. Outlet radius, passage height, and axial location of the outlet were design variables as well. Structured meshes with around 3.7 × 106 cells per passage were generated. Steady three-dimensional (3D) Reynolds-averaged Navier–Stokes (RANS) simulations, enclosed by the k-omega shear stress transport turbulence model were solved by the commercial solver CFD++. The geometry was optimized toward low entropy and high-power output. To prove the functionality of the new turbine concept and optimization, a full wheel unsteady RANS simulation of the optimized geometry exposed to a nozzled rotating detonation combustor (RDC) has been performed and the advantageous flow patterns of the optimization were also observed during transient operation.
Mechanistic Study of Fines Migration in Porous Media Using Lattice Boltzmann Method Coupled With Rigid Body Physics Engine
Authors: Vasheghani Farahani Mehrdad , Foroughi Sajjad , Norouzi Sevda , Jamshidi Saeid
Published: September 2019

This paper presents a pore-scale model proposed for numerical simulation of fines migration in porous media. The model simulates the behavior of spherical particles with different radii in flow by coupling lattice Boltzmann method (LBM) as a computational fluid dynamics (CFD) solver for the simulation of the fluid flow with a rigid body physics engine responsible for the simulation of the particulate transports. To achieve this, the basic LBM algorithm was extended to treat the curved particle boundaries, and a fluid-particle force interaction was implemented in order to account for the exerted force acting on the particles by the fluid and subsequent particulate movements. The accuracy and reliability of the proposed numerical model were successfully validated by simulating Poiseuille flow and Stokes flow and comparing the simulation results with those of the analytical solution. Thereafter, it was employed to simulate the migration of fine particles through synthetic 2D porous media. The simulation results were also presented to investigate the influence of fines migration on the porosity and permeability of the medium, and more interestingly on the hydraulic tortuosity as a criterion for changes in preferential flow path. As will be shown, the developed numerical method is able to successfully capture major retention mechanisms responsible for fines migration associated formation damage including external cake formation by the large particles, internal cake formation by the small particles, pore plugging, and surface deposition. This work provides a framework for further investigations regarding pore-scale phenomena associated with fines migration in the porous media.
Optimal Power Tracking of DFIG-Based Wind Turbine Using MOGWO-Based Fractional-Order Sliding Mode Controller
Authors: Darvish Falehi Ali
Published: September 2019

The doubly fed induction generator (DFIG)-based wind turbine as a nonlinear, compound, and multivariable time-varying system encompasses several uncertainties especially unfamiliar disturbances and unmodeled dynamics. The design of a high-performance and reliable controller for this system is regarded as a complex task. In this paper, an effective and roust fractional-order sliding mode controller (FOSMC) has been designed to accurately regulate the active and reactive power of DFIG. FOSMC has overcome the system uncertainties and abated the chattering amplitude. Since tuning the FOSMC is a challenging assignment, the application of a multi-objective optimization algorithm can efficiently and precisely solve the design problem. In this regard, non-dominated sorting multi-objective gray wolf optimizer (MOGWO) is taken into account to optimally adjust the FOSMC. In a word, the simulation results have definitively validated robustness of MOGWO-based FOSMC in order to accurately track DFIG's active and reactive power.
Coffee bean, by near-ambient pressure XPS
Authors: Shah Dhruv , Bahr Stephan , Dietrich Paul , Meyer Michael , Thißen Andreas , Linford Matthew R.
Published: September 2019

Near-ambient pressure x-ray photoelectron spectroscopy (NAP-XPS) is a less traditional form of XPS that allows samples to be analyzed at relatively high pressures, i.e., up to 2500 Pa, or higher in some cases. NAP-XPS can probe moderately volatile liquids, biological samples, porous materials, and/or polymeric materials that outgas significantly. In this submission, we present NAP-XPS C 1s and O 1s narrow scans and a survey spectrum of a coffee bean, a material that would be difficult or even impossible to analyze by conventional XPS. Coffee beans are ground to produce coffee powder, which is the source of one of the world’s most common beverages, coffee. The survey spectrum shows small amounts of sulfur and calcium.
Searching for a Signature Pedagogy in Novice Coach Education
Authors: Walsh Julia , Carson Fraser
Published: September 2019

Despite the increased research interest in coach education there has been little consensus on how novice sports coaches should best be educated. For the coach developer this becomes problematic when trying to design quality-learning activities for novice coaches that provide a foundation for current and future learning. While the research available has focused on specific areas of best practice curriculum for coaches (e.g., planning; communication; coach-athlete relationships; leadership), there has been less interest in pedagogical practice of novice coach education. Signature pedagogies have been recognised as characteristic methods of teaching used by disciplines to organize the learning process into common elements to prepare future practitioners for their professional roles. For Shulman signature pedagogies scaffold the discipline’s habits of ‘head’ (content); habits of the ‘hand’ (skills); and habits of ‘heart’ (values). This suggests that deep understanding of the disciplines’ habits is necessary for the development of appropriate signature pedagogies that support novice learning. The purpose of this Insight paper is to explore the current literature for potential signature pedagogies that support novice coach learning and the coach developer in teaching. A reflective conclusion summarises the main points and considers the direction for future research.