bluuebunny/crossref_metadata_2025 huggingface dataset:
The efficient in‐situ reduction and cyclization reaction of aromatic aldehyde, 1,3‐cyclopentanedione (tetronic acid), and nitro‐compound under SnCl2·2H2O‐THF medium
Authors: Xu Hui , Li Lei , Dai Lei , Mao Kaimin , Kou Wang , Lin Cong , Rong Liangce
Published: December 2017

An efficient in‐situ reduction and cyclization reaction for the synthesis of pyrazolo[4,3‐f]quinoline, pyrazolo[3,4‐f]quinoline, and pyrazolo[3,2‐f]quinoline derivatives directly form 5‐nitroindazole, 6‐nitroindazole and 5‐nitroindole in the presence of SnCl2·2H2O was reported. Compared to traditional synthetic methods, this approach has the advantages of stable reagents, easy obtaining raw material, and high yields. In this research, SnCl2·2H2O is the efficient reducing agent for the in‐situ reduction and cyclization reaction of nitro‐compound. In addition, this process provided an alternative approach for the synthesis of target compounds.
Copper nanoclusters conjugated silica nanoparticles modified on carbon paste as an electrochemical sensor for the determination of dopamine
Authors: Tashkhourian J. , Sheydaei O. , Nami‐Ana S.F.
Published: December 2017

An electrochemical sensor based on modification of carbon paste electrode by glutathione‐capped copper nanoclusters silica nanoparticles (CuNCs/SiO2NPs) composite for determination of dopamine in the presence of ascorbic acid was presented. Transmission electron microscopy, scanning electron microscopy, energy dispersive X‐Ray analysis, X‐ray photoelectron spectroscopy, Fourier‐transform infrared spectroscopy, X‐ray diffraction and electrochemical impedance spectroscopy were used for characterization of the developed electrode. The electrochemical behavior of dopamine on CuNCs/SiO2NPs/carbon paste electrode was investigated by cyclic voltammetry and differential pulse voltammetry. Dopamine was determined in the range of 10.0 – 900.0 μM, and the limit of detection was obtained as 0.43 μM. The electrochemical behaviors of the coexisting electroactive species, which often cause interference with the determination of dopamine, were investigated. The results show that the developed electrode does not show any interference with respect to coexisting species, even in the presence of ascorbic acid. The developed electrochemical sensor was further employed for the determination of dopamine in human blood plasma, with a good recovery.
Aliphatic SPI charge‐transfer complex hybrid films for high temperature polymer electrolyte membrane fuel cells
Authors: Christiani Liana , Sasaki Kazunari , Nishihara Masamichi
Published: December 2017

A new method to synthesize polymer electrolyte membranes based on charge‐transfer (CT) complexes for high temperature fuel cells is investigated. Aliphatic sulfonated polyimide (SPI) CT complex hybrid films are prepared. Aliphatic units are introduced into the SPI main chain to increase the elasticity compared with aromatic SPI films. Electron‐donating compounds are included to form a CT complex, resulting in improved control over mechanical strength, water uptake, and thermal stability. The resulting thermal properties of the SPI CT films are sufficient to operate at elevated temperature (up to 120 °C), and the proton conductivity is comparable to that of Nafion 115. These films are thus promising alternative membranes for high temperature polymer electrolyte fuel cell applications. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 46087.
Effect of titanium dioxide on the UV‐C ageing behavior of silicone rubber
Authors: Zhang Hui , Yang Hao , Shentu Baoqing , Chen Songjun , Chen Ming
Published: December 2017

The ultraviolet (UV)‐C ageing behavior of silicone rubber (SiR) incorporated with titanium dioxide nanoparticles (nano‐TiO2) was studied under UV‐C radiation. The SiR incorporated with nano‐TiO2 displayed excellent physical properties when exposed to UV‐C radiation. With the increase of the ageing time, the SiR with nano‐TiO2 showed no significant change in crosslinking density and Shore A hardness. Moreover, compared with the SiR without nano‐TiO2, the SiR incorporated with nano‐TiO2 also exhibited high retention ratio in tensile properties, especially elongation at break. It was found that nano‐TiO2 was a good ultraviolet light stabilizer during the UV ageing process of SiR and the optimum content of nano‐TiO2 was 2 phr. The results of Fourier transform infrared spectroscopy and X‐ray photoelectron spectroscopy showed the appearance of OH and CO and the decrease of the intensity of SiC2O2 in SiR samples during the process of UV‐C ageing. Based on these results, a possible UV ageing mechanism of SiR could be proposed. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 46099.
Synthesis of novel benzimidazole acrylonitriles for inhibition of Plasmodium falciparum growth by dual target inhibition
Authors: Sharma Kalicharan , Shrivastava Apeksha , Mehra Ram N. , Deora Girdhar S. , Alam Mohammad M. , Zaman Mohammad S. , Akhter Mymoona
Published: December 2017

Antimalarial drug resistance has emerged as a threat for treating malaria, generating a need to design and develop newer, more efficient antimalarial agents. This research aimed to identify novel leads as antimalarials. Dual receptor mechanism could be a good strategy to combat developing drug resistance. A series of benzimidazole acrylonitriles containing 18 compounds were designed, synthesized and evaluated for cytotoxicity, heme binding, ferriprotoporphyrin IX biomineralisation inhibition, and falcipain‐2 enzyme assay. Furthermore, in silico docking and MD simulation studies were also performed.The tests revealed quite encouraging results. Three compounds, viz. R‐01 (0.69 μM), R‐04 (1.60 μM), and R‐08 (1.61 μM), were found to have high antimalarial activity. These compounds were found to be in bearable cytotoxicity limits and their biological assay suggested that they had inhibitory activity against falcipain‐2 and hemozoin formation. The docking revealed the binding mode of benzimidazole acrylonitrile derivatives and MD simulation studies revealed that the protein‐ligand complex was stable. The agents exhibit good hemozoin formation inhibition activity and, hence, may be utilized as leads to design a newer drug class to overcome the drug resistance of hemozoin formation inhibitors such as chloroquine.
It Is Time to Re‐Evaluate the Peer Review Process for Preclinical Research
Authors: Bhattacharya Rajat , Ellis Lee M.
Published: December 2017

Problems in peer review, the backbone of maintaining high standards in scientific publishing, have led to wide spread discontent within the scientific community. Training in the peer review process and a simpler format to assist in decision making are possible courses to improve and expedite the process of peer review and scientific publishing.
Systematic review and network meta-analysis of methods of mesh fixation during laparoscopic ventral hernia repair
Authors: Baker J J , Öberg S , Andresen K , Klausen T W , Rosenberg J
Published: December 2017

Background

Ventral hernia repairs are common and have high recurrence rates. They are usually repaired laparoscopically with an intraperitoneal mesh, which can be fixed in various ways. The aim was to evaluate the recurrence rates for the different fixation techniques.

Methods

This systematic review included studies with human adults with a ventral hernia repaired with an intraperitoneal onlay mesh. The outcome was recurrence at least 6 months after operation. Cohort studies with 50 or more participants and all RCTs were included. PubMed, Embase and the Cochrane Library were searched on 22 September 2016. RCTs were assessed with the Cochrane risk-of-bias assessment tool and cohort studies with the Newcastle–Ottawa scale. Studies comparing fixation techniques were included in a network meta-analysis, which allowed comparison of more than two fixation techniques.

Results

Fifty-one studies with a total of 6553 participants were included. The overall crude recurrence rates with the various fixation techniques were: absorbable tacks, 17·5 per cent (2 treatment groups); absorbable tacks with sutures, 0·7 per cent (3); permanent tacks, 7·7 per cent (20); permanent tacks with sutures, 6·0 per cent (25); and sutures, 1·5 per cent (6). Six studies were included in a network meta-analysis, which favoured fixation with sutures. Although statistical significance was not achieved, there was a 93 per cent chance of sutures being better than one of the other methods.

Conclusion

Both crude recurrence rates and the network meta-analysis favoured fixation with sutures during laparoscopic ventral hernia repair.
Liquid chromatographic methods for the therapeutic drug monitoring of methotrexate as clinical decision support for personalized medicine: A brief review
Authors: Silva Mónica Francisco , Ribeiro Cláudia , Gonçalves Virgínia M. F. , Tiritan Maria Elizabeth , Lima Áurea
Published: December 2017

Methotrexate (MTX) is an antifolate drug used for several diseases. Depending on the disease, MTX can be administered at low dose (LDMTX) in some autoimmune diseases, like rheumatoid arthritis, or at high dose (HDMTX) in some cancers, such as acute lymphoblastic leukemia. After absorption, MTX is metabolized in the liver to 7‐hydroxymethotrexate and in the intestine to 2,4‐diamino‐N10‐methylpteroic acid (DAMPA). Moreover, inside red blood cells, MTX is converted to active metabolites, MTX polyglutamates (MTXPGs), contributing to its pharmacodynamics. Owing to its narrow therapeutic range, and inter‐ and intra‐patient variability, either noneffectiveness and/or toxicity may occur. Because of the existence of a relationship between drug therapeutic outcome and its systemic concentration, therapeutic drug monitoring (TDM) may ensure the effectiveness and safety of MTX use. In order to monitor the optimization of patient clinical response profile, several analytical methods have been described for TDM in biological samples. These include liquid chromatography (LC) coupled with ultraviolet detection, fluorescence detection or mass spectrometry, each one presenting advantages and drawbacks. This paper reviews the most commonly used techniques for sample preparation and critically discusses the current LC methods applied for the TDM of MTX in biological samples, at LDMTX and HDMTX.
Biotransformation and metabolic profile of Xian‐Ling‐Gu‐Bao capsule, a traditional Chinese medicine prescription, with rat intestinal microflora by ultra‐performance liquid chromatography coupled with quadrupole time‐of‐flight tandem mass spectrometry analysis
Authors: Gao Meng‐xue , Tang Xi‐yang , Zhang Feng‐xiang , Yao Zhi‐hong , Yao Xin‐sheng , Dai Yi
Published: December 2017

Xian‐Ling‐Gu‐Bao capsule (XLGB), a well‐known traditional Chinese medicine prescription, has been used for the prevention and treatment of osteoporosis. The safety and efficacy of XLGB have been confirmed based on the principle of evidence‐based medicine. XLGB is usually administered orally, after which its multiple components are brought into contact with intestinal microflora in the alimentary tract and biotransformed. However, investigations on the comprehensive metabolic profile of XLGB are absent. In this study, 12 representative compounds bearing different typical structures (including iridoid glycosides, prenylated flavonol glycosides, prenylated flavonoids, triterpenoid saponins, steroidal saponins, coumarins and monoterpene phenols) were selected and then investigated for their biotransformation in rat intestinal microflora. In addition, the metabolic profile of XLGB in rat intestinal microflora was investigated by ultra‐performance liquid chromatography coupled with quadrupole time‐of‐flight tandem mass spectrometry. As a result, a total of 87 biotransformation components were identified from incubated solutions of 12 representative compounds and XLGB, which underwent 16 metabolic reactions (including deglycosylation, glycosylation, dehydrogenation, hydrogenation, oxidation, epoxidation, hydroxylation, dehydration, hydration, hydrolysis, methylation, isomerization, cyclization, pyrolysis reaction, amino acid conjugation and nucleophilic addition reaction with NH3). This demonstrated that the deglycosylation reaction by cleavage of the sugar moieties is the main metabolic pathway of a variety of glycosides, including prenylated flavonol glycosides, coumarin glycosides, iridoid glycosides and saponins. In addition, compared with the biotransformation of 12 representative compounds, a different biotransformed fate was observed in the XLGB incubated samples of rat intestinal microflora. It is worth noting that the amino acid conjugation was first discovered in the metabolism of prenylated flavonol glycosides in rat intestinal microflora.
A fast and accurate isotope dilution GC‐IT‐MS/MS method for determination of eugenol in different tissues of fish: Application to a depletion study in mandarin fish
Authors: Liu Yongtao , Ai Xiaohui , Li Le , Li Jincheng , Yang Hong
Published: December 2017

An accurate, rapid and effective method was established for determination of eugenol in plasma, muscle, skin, liver, kidney and gill of fish using gas chromatography–ion trap tandem mass spectrometry. Samples of muscle, skin, liver, kidney and gill were prepared using the modified QuEChERS (quick, easy, cheap, effective, rugged and safe) procedure, and a plasma sample was prepared by a liquid–liquid extraction procedure. Eugenol was monitored in <7 min using an electron‐ionization source in MS/MS mode and quantified by an internal standard of eugenol‐d3. The limit of detection was 5.0 μg/kg, and the limit of quantification was 10.0 μg/kg. The calibration curve was linear in the range of 5–1000 μg/L (R2 = 0.9996). Intra‐ and inter‐day precisions of eugenol expressed as relative standard deviation were within 9.74%, and the accuracy exhibited a relative error ranging from −2.20 to 8.89%. The developed method was successfully used to study the elimination regularity of eugenol in mandarin fish.
Simultaneous determination of etonogestrel and ethinyl estradiol in human plasma by UPLC‐MS/MS and its pharmacokinetic study
Authors: Nair Sneha G. , Patel Daxesh P. , Gonzalez Frank J. , Patel Bhargav M. , Singhal Puran , Chaudhary Darshan V.
Published: December 2017

A selective, sensitive and rapid ultra‐performance liquid chromatography tandem mass spectrometry method was developed and validated for the simultaneous determination of etonogestrel (ENG) and ethinyl estradiol (EE) in human plasma. The analytes and their deuterated internal standards, ENG‐d7 and EE‐d4, were extracted from plasma samples by solid‐phase extraction on HyperSep™ Retain PEP cartridges. The chromatographic analysis was performed on an Acquity UPLC HSS Cyano column, 100 Å (50 × 2.1 mm, 1.8 μm), column using gradient mobile phase, acetonitrile and 2.0 mm ammonium trifluoroacetate at 0–1.7 min (65:35, v/v) and 1.8–2.7 min (95:5, v/v) with 0.250 mL/min flow rate. Analytes and IS protonated precursor → product ion transitions (ENG, m/z 325.2 → 257.2; EE, m/z 530.2 → 171.2; ENG‐d7, m/z 332.2 → 263.2; EE‐d4, m/z 534.2 → 171.2) were monitored on a Triple Quadrupole Mass spectrometer (TQMS), operating in multiple reaction monitoring and positive ionization mode. The calibration curves were established at 10.00–2500 pg/mL for ENG and 1.500–150.0 pg/mL for EE with a correlation coefficient (r2) ≥0.9996 for both. The validated method was successfully applied to support a bioequivalence study of 0.15 mg ENG and EE 0.03 mg tablet formulation, administered in 24 healthy Indian females. Method reliability was assessed by reanalysis of 94 incurred study samples.
Extracellular matrix remodeling and TGF‐β1/Smad signaling in diabetic colon mucosa
Authors: D'Arpino Maria Cecilia , Fuchs Alicia G. , Sánchez Sara S. , Honoré Stella M.
Published: December 2017

Diabetes is associated with metabolic and functional alterations in the gut. Using an experimental model of streptozotocin (STZ)‐induced diabetes in rodents, we analyzed the extracellular matrix (ECM) and TGF‐β/Smad signaling in the colon mucosa. Male rats were divided into normal control, diabetic and insulin treated diabetic groups during 4 and 9 weeks. Sirius red staining showed marked increase in the extracellular matrix deposition in diabetic mucosa. High levels of fibrillar collagen (I and III) and fibronectin mRNAs were also detected with an imbalance between MMPs/TIMPs activities. Moreover, an increased mesenchymal cell proliferation together with an enhanced expression of myofibroblasts markers vimentin and α‐SMA were observed. TGF‐β/Smad signaling‐related genes were determined using RT‐PCR, Western blotting, and immunohistochemistry. Diabetic rats showed a significant up‐regulation of TGF‐β1, TGF‐β receptors and the effectors p‐Smad2/3 in the mucosa compared with control rats. Insulin treatment attenuated the stimulating effect of diabetes on colon ECM deposition and TGF‐β/Smad signaling. In conclusion, the overall results showed a deregulation of the TGFβ1 pathway associated with the appearance of myofibroblasts and the accumulation of ECM in the mucosa of diabetic colon. These data provide the first in vivo evidence that TGF‐β1/Smad is a key component of intestinal tissue remodeling in diabetes.
Optimizing hemodynamics of transcatheter aortic valve‐in‐valve implantation in 19‐mm surgical aortic prostheses
Authors: Patel Jayendrakumar S. , Krishnaswamy Amar , White Jonathon , Mick Stephanie , Navia Jose , Mehta Anand , Bakaeen Faisal , Popovic Zoran , Svensson Lars , Kapadia Samir R.
Published: December 2017

Objective

To demonstrate the feasibility of achieving good hemodynamic results with valve‐in‐valve transcatheter aortic valve replacement (ViV TAVR) for degenerated 19 mm surgical bioprosthetic valves.

Background

Considerable controversy exists regarding ViV TAVR within 19mm surgical prostheses due to concerns of elevated valve gradients and mortality.

Methods

Among all patient undergoing ViV TAVR between 7/2016 and 4/2017 for symptomatic severe bioprosthetic aortic stenosis (AS), five had a 19 mm surgical valve in place and were included in this publication. None of the patients had patient‐prosthesis mismatch. Aggressive post‐dilation was performed in four out of five cases using a special technique we describe below.

Results

In all cases, mean aortic valve (AV) gradients significantly improved post‐ViV TAVR, particularly after post‐dilation. Interestingly, high pressure post‐dilation of the ViV resulted in an increase in the diameter of surgical valve stent frame dimensions in nearly all patients who underwent post‐dilation.

Conclusions

Good hemodynamic outcome is possible with aggressive post‐dilation in patients with 19 mm failed surgical bioprostheses. High‐risk patients with 19 mm failed surgical prostheses who do not otherwise have viable surgical options should be considered for ViV TAVR.
Deferred lesion failure in diabetes: A truly bad actor
Authors: Seto Arnold H. , Kern Morton J.
Published: December 2017

Key Points

DM patients with stenoses whose FFR > 0.80 have a relatively high 14% rate of deferred lesion failure (i.e., revascularization or MI).

IDDM and prior revascularization were independent predictors of deferred lesion failure

FFR predicts outcomes, but is a less effective predictor in diabetics due to diffuse atherosclerosis microvascular disease.
A cardiologist's nightmare: Coronary obstruction during transcatheter aortic valve implantation: How to identify patients at highest risk for this complication
Authors: Shatila Wassim , Krajcer Zvonimir
Published: December 2017

Key Points

Transcatheter aortic valve implantation (TAVI) is associated with several complications including coronary obstruction (CO)

CO occurs in ∼1% of patients and mostly in patients receiving the SAPIEN XT valve

Possible predictors of CO include coronary height <10 mm and aortic sinus diameter of <30 mm.
Vulnerable plaques, more than meets the i
Authors: Mehanna Emile , Abbott J. Dawn
Published: December 2017

Key Points

Intravascular imaging plays a key role in the identification of mechanisms of acute coronary syndromes

Post processing IVUS algorithms (IMAP‐IVUS and VH‐IVUS) for tissue characterization have not been widely adopted due to current limitations

Future development will allow easier, faster, and more accurate identification of vulnerable plaques, ultimately allowing prognostication of various interventions.
Suture‐induced arthritis as a clinical mimicker of septic arthritis
Authors: Mizuno Nazuna , Mizuno Akira
Published: December 2017

Key Clinical Message

Foreign body‐induced arthritis is a rare etiology of mono‐arthritis. It should be suspected in the case of postoperative arthritis, even if some decades have passed since surgery. Histopathology of the tissues is required for a definitive diagnosis, and debridement is essential for complete recovery.
A “tilt” toward cinefluoroscopy
Authors: Lampropoulos Konstantinos , Bakalakos Athanasios , Bazoukis George , Saplaouras Athanasios , Sakellaropoulou Antigoni , Anagnostou Aikaterini , Tse Gary , Tsamatsoulis Michalis , Charitos Christos
Published: December 2017

Key Clinical Message

Fluoroscopy permits rapid and straightforward assessment of mechanical valve function and allows a distinction between normal and malfunctional prostheses, acting as a complementary diagnostic step.
Multi‐Functional Peptide–MicroRNA Nanocomplex for Targeted MicroRNA Delivery and Function Imaging
Authors: Xiao Xiao , Wang Xingxing , Wang Yuqi , Yu Tianren , Huang Lei , Chen Lei , Li Jinbo , Zhang Chenyu , Zhang Yan
Published: December 2017

Targeted delivery of microRNA (miRNA) mimics into specific cells/tissues and real‐time monitoring on the biological function of delivered miRNA mimics at molecular level represent two major challenges in the development of miRNA‐based therapeutics. Here we report a highly efficient method to address these two challenges simultaneously by using the self‐assembled nanocomplex formed by miRNA mimics with a multi‐functional peptide conjugate. Using the nanocomplex formed by tumor‐suppressive miR‐34a and the multi‐functional peptide conjugate FA‐R9‐FPcas3, we demonstrated the highly efficient and target‐selective delivery of miR‐34a into HeLa cells and tumors. With the activatable fluorescence probe integrated in the peptide conjugate FA‐R9‐FPcas3, the intracellular function of miR‐34a delivered by the nanocomplex to upregulate active Caspase‐3 was imaged in real‐time. The nanocomplex also showed significant therapeutic effects to induce apoptosis in HeLa cells and to suppress tumor growth upon tail vein injection into living mice bearing subcutaneous HeLa tumors.
Stereoselective Transfer Semi‐Hydrogenation of Alkynes to E‐Olefins with N‐Heterocyclic Silylene–Manganese Catalysts
Authors: Zhou Yu‐Peng , Mo Zhenbo , Luecke Marcel‐Philip , Driess Matthias
Published: December 2017

The synthesis and structures of the first SiII‐donor supported manganese(II) complexes [L1]MnCl2, [L2]MnCl2, and [L3]2MnCl2 are reported, bearing a pincer‐type bis(NHSi)‐pyridine ligand L1, bidentate bis(NHSi)‐ferrocene ligand L2, and two monodentate NHSi ligands L3 (NHSi = N‐heterocyclic silylene), respectively. They act as unprecedented very active and stereoselective Mn‐based precatalysts (1 mol % loading) in transfer semi‐hydrogenations of alkynes to give the corresponding E‐olefins using ammonia–borane as a convenient hydrogen source under mild reaction conditions. Complex [L1]MnCl2 shows the best catalytic performance with quantitative conversion rates and excellent E‐stereoselectivities (up to 98 %) for different alkyne substrates. Different types of functional groups can be tolerated, except CN, NH2, NO2, and OH groups at the phenyl group of 1‐phenyl substituted alkynes.
Numerical simulation on movement behaviours of cylindrical particles in a circulating fluidized bed
Authors: Cai Jie , Wu Chuan‐yu , Zhao Xiaobao , Gu Zhongzhu , Wu Wei , Peng Zhengbiao
Published: December 2017

The movement behaviours of cylindrical particles in a circulating fluidized bed were studied with a three‐dimensional multi‐way coupled model of cylindrical particle flow. In this model, the translation and rotation of individual cylindrical particles were solved directly by Newton‐Euler dynamics. The interaction between cylindrical particles was handled in line with rigid impact dynamics and the modified Nanbu collision probability method. The coupling algorithm between the motion of cylindrical particles and turbulent flow was disposed using the correlation between Lagrangian time scales and the closure model. Numerical simulation indicates that cylindrical particles in the near‐wall region reach the exit of the riser faster than those in other regions. The majority of collisions between cylindrical particles occur in the annular region between the central and near‐wall regions. In the horizontal direction, the horizontal velocity components of cylindrical particles vary slightly and distribute randomly, whilst the vertical velocity component exhibits produced variation from the near‐wall region to the central region. Further, the rotation of a cylindrical particle around its axis is shown to be significantly weaker than those around the two other orthometric axes. The collisions of cylindrical particles affect the distribution of horizontal velocity components of cylindrical particles more evidently.
Dynamic mutual information similarity based transient process identification and fault detection
Authors: He Yuchen , Zhou Le , Ge Zhiqiang , Song Zhihuan
Published: December 2017

Industrial process status can be modified according to continuous operations, which are required by different production specifications. Commonly, in a multimode process, attention was always paid to stable modes, while transitions were neglected. In a transition process, the process may be externally time varying or nonstationary so that the identification and the modelling are intractable to implement using traditional statistical methods. In this article, a transition identification and process monitoring method is proposed to handle the above problems based on a novel dynamic mutual information similarity (DMIS) analysis. Firstly, a multimode process is represented by a series of overlapping moving windows to consider the local information. In order to extract the corresponding dynamic information, each of these windows is modelled using the dynamic partial least squares (DPLS) method. Then, the mutual information algorithm is introduced to calculate the similarity between different latent variables. The hierarchical clustering method is employed to transfer the similarity information into a visualized dendrogram where the whole process, including a transition, is divided into several segments. The statistical characteristics in each segment are relatively stable and can be characterized by conventional multivariate statistical process control methods. Online identification and fault detection are then carried out for the multimode process through a series of DPLS models, established in the offline steps. The feasibility and effectiveness of the proposed method are validated by the Tennessee Eastman (TE) benchmark and a real process. The results of the proposed methods have shown superior performance compared to previous works.
High Purity Isolation and Sensitive Quantification of Extracellular Vesicles Using Affinity to TIM4
Authors: Yoshida Takeshi , Ishidome Takamasa , Hanayama Rikinari
Published: December 2017

Almost all types of cells secrete extracellular vesicles (EVs), including exosomes and microvesicles. EVs carry various proteins, lipids, mRNAs, and microRNAs, and may participate in many aspects of physiological and pathophysiological processes. Various studies are currently being conducted to develop therapeutic and diagnostic methods targeting or utilizing EVs. Therefore, developing ideal methods for isolating and quantifying EVs is an active area of research. EVs express phosphatidylserine on their outer lipid bilayer. This unit describes an affinity‐based method for isolating EVs using TIM4, which binds phosphatidylserine in a specific and calcium‐dependent manner. EVs captured by TIM4 can be easily released by addition of a chelating agent, or can be retained for quantification by ELISA or flow cytometry. These methods enable the isolation of highly purified EVs and the sensitive quantification of EVs, which will accelerate EV research beyond what has been achievable with conventional methods. © 2017 by John Wiley & Sons, Inc.
In Vitro Dissection of Autophagy
Authors: Zhang Min , Liu Dawei , Ge Liang
Published: December 2017

Autophagy is an essential cellular process for bulk degradation of cytoplasmic components through the lysosome. Underlying this process is an intricate interaction between protein factors and the cell endomembrane system, leading to a gradual maturation of the autophagic membrane. This structure sequesters a portion of the cytoplasm by the formation of a double‐membrane compartment called the autophagosome. The autophagosome then delivers the cargo to the lysosome to complete degradation. The molecular mechanism accounting for the generation of the autophagic membrane is a longstanding question. Here, a cell‐free approach that has been established to understand the mechanism of early autophagic membrane generation is described. This system has provided insight into the membrane source of the autophagosome, the early protein‐membrane associations, and the membrane remodeling that generates the autophagosomal precursors. The cell‐free assay, in combination with other established approaches (e.g., cell imaging), will facilitate a deeper understanding of the mechanism of autophagy. © 2017 by John Wiley & Sons, Inc.
Emerging Innovative Therapeutic Approaches Leveraging Cyclin‐Dependent Kinase Inhibitors to Treat Advanced Breast Cancer
Authors: Cruz Marcelo , Reinert Tomás , Cristofanilli Massimo
Published: December 2017

Estrogen receptor‐positive (ER+) tumors represent the most common form of breast cancer. Although endocrine therapy (ET) results in benefit for the majority of these patients, disease progression invariably occurs. The discovery of the relation between cyclin‐dependent kinases (CDKs) and the ER pathways is one of the major advances in unveiling mechanisms of resistance to ET. In this article we review the role of CDK4/6 inhibitors in ER + breast cancer patients.
Towards Sustainable H2 Production: Rational Design of Hydrophobic Triphenylamine‐based Dyes for Sensitized Ethanol Photoreforming
Authors: Dessì Alessio , Monai Matteo , Bessi Matteo , Montini Tiziano , Calamante Massimo , Mordini Alessandro , Reginato Gianna , Trono Cosimo , Fornasiero Paolo , Zani Lorenzo
Published: December 2017

Donor–acceptor dyes are a well‐established class of photosensitizers, used to enhance visible‐light harvesting in solar cells and in direct photocatalytic reactions, such as H2 production by photoreforming of sacrificial electron donors (SEDs). Amines—typically triethanolamine (TEOA)—are commonly employed as SEDs in such reactions. Dye‐sensitized photoreforming of more sustainable, biomass‐derived alcohols, on the other hand, was only recently reported by using methanol as the electron donor. In this work, several rationally designed donor–acceptor dyes were used as sensitizers in H2 photocatalytic production, comparing the efficiency of TEOA and EtOH as SEDs. In particular, the effect of hydrophobic chains in the spacer and/or the donor unit of the dyes was systematically studied. The H2 production rates were higher when TEOA was used as SED, whereas the activity trends depended on the SED used. The best performance was obtained with TEOA by using a sensitizer with just one bulky hydrophobic moiety, propylenedioxythiophene, placed on the spacer unit. In the case of EtOH, the best‐performing sensitizers were the ones featuring a thiazolo[5,4‐d]thiazole internal unit, needed for enhancing light harvesting, and carrying alkyl chains on both the donor part and the spacer unit. The results are discussed in terms of reaction mechanism, interaction with the SED, and structural/electrochemical properties of the sensitizers.
Parasite spillover: indirect effects of invasive Burmese pythons
Authors: Miller Melissa A. , Kinsella John M. , Snow Ray W. , Hayes Malorie M. , Falk Bryan G. , Reed Robert N. , Mazzotti Frank J. , Guyer Craig , Romagosa Christina M.
Published: December 2017

Identification of the origin of parasites of nonindigenous species (NIS) can be complex. NIS may introduce parasites from their native range and acquire parasites from within their invaded range. Determination of whether parasites are non‐native or native can be complicated when parasite genera occur within both the NIS’ native range and its introduced range. We explored potential for spillover and spillback of lung parasites infecting Burmese pythons (Python bivittatus) in their invasive range (Florida). We collected 498 indigenous snakes of 26 species and 805 Burmese pythons during 2004–2016 and examined them for lung parasites. We used morphology to identify three genera of pentastome parasites, Raillietiella, a cosmopolitan form, and Porocephalus and Kiricephalus, both New World forms. We sequenced these parasites at one mitochondrial and one nuclear locus and showed that each genus is represented by a single species, R. orientalis, P. crotali, and K. coarctatus. Pythons are host to R. orientalis and P. crotali, but not K. coarctatus; native snakes are host to all three species. Sequence data show that pythons introduced R. orientalis to North America, where this parasite now infects native snakes. Additionally, our data suggest that pythons are competent hosts to P. crotali, a widespread parasite native to North and South America that was previously hypothesized to infect only viperid snakes. Our results indicate invasive Burmese pythons have affected parasite‐host dynamics of native snakes in ways that are consistent with parasite spillover and demonstrate the potential for indirect effects during invasions. Additionally, we show that pythons have acquired a parasite native to their introduced range, which is the initial condition necessary for parasite spillback.
How to deal with ground truthing affected by human‐induced habitat change?: Identifying high‐quality habitats for the Critically Endangered Red Siskin
Authors: Sánchez‐Mercado Ada , Rodríguez‐Clark Kathryn M. , Miranda Jhonathan , Ferrer‐Paris José Rafael , Coyle Brian , Toro Samuel , Cardozo‐Urdaneta Arlene , Braun Michael J.
Published: December 2017

Species distribution models (SDM) can be valuable for identifying key habitats for conservation management of threatened taxa, but anthropogenic habitat change can undermine SDM accuracy. We used data for the Red Siskin (Spinus cucullatus), a critically endangered bird and ground truthing to examine anthropogenic habitat change as a source of SDM inaccuracy. We aimed to estimate: (1) the Red Siskin's historic distribution in Venezuela; (2) the portion of this historic distribution lost to vegetation degradation; and (3) the location of key habitats or areas with both, a high probability of historic occurrence and a low probability of vegetation degradation. We ground‐truthed 191 locations and used expert opinion as well as landscape characteristics to classify species' habitat suitability as excellent, good, acceptable, or poor. We fit a Random Forest model (RF) and Enhanced Vegetation Index (EVI) time series to evaluate the accuracy and precision of the expert categorization of habitat suitability. We estimated the probability of historic occurrence by fitting a MaxLike model using 88 presence records (1960–2013) and data on forest cover and aridity index. Of the entire study area, 23% (20,696 km2) had a historic probability of Red Siskin occurrence over 0.743. Furthermore, 85% of ground‐truthed locations had substantial reductions in mean EVI, resulting in key habitats totaling just 976 km2, in small blocks in the western and central regions. Decline in Area of Occupancy over 15 years was between 40% and 95%, corresponding to an extinction risk category between Vulnerable and Critically Endangered. Relating key habitats with other landscape features revealed significant risks and opportunities for proposed conservation interventions, including the fact that ongoing vegetation degradation could limit the establishment of reintroduced populations in eastern areas, while the conservation of remaining key habitats on private lands could be improved with biodiversity‐friendly agri‐ and silviculture programs.
A spatiotemporal analysis of acoustic interactions between great reed warblers (Acrocephalus arundinaceus) using microphone arrays and robot audition software HARK
Authors: Suzuki Reiji , Matsubayashi Shiho , Saito Fumiyuki , Murate Tatsuyoshi , Masuda Tomohisa , Yamamoto Koichi , Kojima Ryosuke , Nakadai Kazuhiro , Okuno Hiroshi G.
Published: December 2017

Acoustic interactions are important for understanding intra‐ and interspecific communication in songbird communities from the viewpoint of soundscape ecology. It has been suggested that birds may divide up sound space to increase communication efficiency in such a manner that they tend to avoid overlap with other birds when they sing. We are interested in clarifying the dynamics underlying the process as an example of complex systems based on short‐term behavioral plasticity. However, it is very problematic to manually collect spatiotemporal patterns of acoustic events in natural habitats using data derived from a standard single‐channel recording of several species singing simultaneously. Our purpose here was to investigate fine‐scale spatiotemporal acoustic interactions of the great reed warbler. We surveyed spatial and temporal patterns of several vocalizing color‐banded great reed warblers (Acrocephalus arundinaceus) using an open‐source software for robot audition HARK (Honda Research Institute Japan Audition for Robots with Kyoto University) and three new 16‐channel, stand‐alone, and water‐resistant microphone arrays, named DACHO spread out in the bird's habitat. We first show that our system estimated the location of two color‐banded individuals’ song posts with mean error distance of 5.5 ± 4.5 m from the location of observed song posts. We then evaluated the temporal localization accuracy of the songs by comparing the duration of localized songs around the song posts with those annotated by human observers, with an accuracy score of average 0.89 for one bird that stayed at one song post. We further found significant temporal overlap avoidance and an asymmetric relationship between songs of the two singing individuals, using transfer entropy. We believe that our system and analytical approach contribute to a better understanding of fine‐scale acoustic interactions in time and space in bird communities.
Symbioses with nitrogen‐fixing bacteria: nodulation and phylogenetic data across legume genera
Authors: Afkhami Michelle E. , Luke Mahler D. , Burns Jean H. , Weber Marjorie G. , Wojciechowski Martin F. , Sprent Janet , Strauss Sharon Y.
Published: December 2017

How species interactions shape global biodiversity and influence diversification is a central – but also data‐hungry – question in evolutionary ecology. Microbially based mutualisms are widespread and could cause diversification by ameliorating stress and thus allowing organisms to colonize and adapt to otherwise unsuitable habitats. Yet the role of these interactions in generating species diversity has received limited attention, especially across large taxonomic groups. In the massive angiosperm family Leguminosae, plants often associate with root‐nodulating bacteria that ameliorate nutrient stress by fixing atmospheric nitrogen. These symbioses are ecologically‐important interactions, influencing community assembly, diversity, and succession, contributing ~100–290 million tons of N annually to natural ecosystems, and enhancing growth of agronomically‐important forage and crop plants worldwide. In recent work attempting to determine whether mutualism with N‐fixing bacteria led to increased diversification across legumes, we were unable to definitively resolve the relationship between diversification and nodulation. We did, however, succeed in compiling a very large searchable, analysis‐ready database of nodulation data for 749 legume genera (98% of Leguminosae genera; LPWG 2017), which, along with associated phylogenetic information, will provide a valuable resource for future work addressing this question and others. For each legume genus, we provide information about the species richness, frequency of nodulation, subfamily association, and topological correspondence with an additional data set of 100 phylogenetic trees curated for database compatibility. We found 386 legume genera were confirmed nodulators (i.e., all species examined for nodulation nodulated), 116 were non‐nodulating, four were variable (i.e., containing both confirmed nodulators and confirmed non‐nodulators), and 243 had not been examined for nodulation in published studies. Interestingly, data exploration revealed that nodulating legume genera are ~3 × more species‐rich than non‐nodulating genera, but we did not find evidence that this difference in diversity was due to differences in net diversification rate. Our metadata file describes in more detail the structure of these data that provide a foundational resource for future work as more nodulation data become available, and as greater phylogenetic resolution of this ca. 19,500‐species family comes into focus. We release this data set under the Creative Commons 4.0 Attribution‐ShareAlike License (https://creativecommons.org/licenses/by-sa/4.0/). The data may be used, distributed, and reproduced with proper citation of this article.
Predictors and outcomes of heart failure with mid‐range ejection fraction
Authors: Bhambhani Vijeta , Kizer Jorge R. , Lima Joao A.C. , van der Harst Pim , Bahrami Hossein , Nayor Matthew , de Filippi Christopher R. , Enserro Danielle , Blaha Michael J. , Cushman Mary , Wang Thomas J. , Gansevoort Ron T. , Fox Caroline S. , Gaggin Hanna K. , Kop Willem J. , Liu Kiang , Vasan Ramachandran S. , Psaty Bruce M. , Lee Douglas S. , Brouwers Frank P. , Hillege Hans L. , Bartz Traci M. , Benjamin Emelia J. , Chan Cheeling , Allison Matthew , Gardin Julius M. , Januzzi James L. , Levy Daniel , Herrington David M. , van Gilst Wiek H. , Bertoni Alain G. , Larson Martin G. , de Boer Rudolf A. , Gottdiener John S. , Shah Sanjiv J. , Ho Jennifer E.
Published: December 2017

Aims

While heart failure with preserved (HFpEF) and reduced ejection fraction (HFrEF) are well described, determinants and outcomes of heart failure with mid‐range ejection fraction (HFmrEF) remain unclear. We sought to examine clinical and biochemical predictors of incident HFmrEF in the community.

Methods and results

We pooled data from four community‐based longitudinal cohorts, with ascertainment of new heart failure (HF) classified into HFmrEF [ejection fraction (EF) 41–49%], HFpEF (EF ≥50%), and HFrEF (EF ≤40%). Predictors of incident HF subtypes were assessed using multivariable Cox models. Among 28 820 participants free of HF followed for a median of 12 years, there were 200 new HFmrEF cases, compared with 811 HFpEF and 1048 HFrEF. Clinical predictors of HFmrEF included age, male sex, systolic blood pressure, diabetes mellitus, and prior myocardial infarction (multivariable adjusted P ≤ 0.003 for all). Biomarkers that predicted HFmrEF included natriuretic peptides, cystatin‐C, and high‐sensitivity troponin (P ≤ 0.0004 for all). Natriuretic peptides were stronger predictors of HFrEF [hazard ratio (HR) 2.00 per 1 standard deviation increase, 95% confidence interval (CI) 1.81–2.20] than of HFmrEF (HR 1.51, 95% CI 1.20–1.90, P = 0.01 for difference), and did not differ in their association with incident HFmrEF and HFpEF (HR 1.56, 95% CI 1.41–1.73, P = 0.68 for difference). All‐cause mortality following the onset of HFmrEF was worse than that of HFpEF (50 vs. 39 events per 1000 person‐years, P = 0.02), but comparable to that of HFrEF (46 events per 1000 person‐years, P = 0.78).

Conclusions

We found overlap in predictors of incident HFmrEF with other HF subtypes. In contrast, mortality risk after HFmrEF was worse than HFpEF, and similar to HFrEF.
Anti‐inflammatory effects of propranolol in the temporomandibular joint of female rats and its contribution to antinociceptive action
Authors: Zanelatto F.B. , Dias E.V. , Teixeira J.M. , Sartori C.R. , Parada C.A. , Tambeli C.H.
Published: December 2017

Background

β‐Blockers reduce temporomandibular joint (TMJ) pain. We asked whether they also reduce TMJ inflammation and, if so, whether this anti‐inflammatory effect contributes to its analgesic action.

Methods

We measured many parameters of the inflammatory response after co‐administration of the β‐blocker propranolol with the inflammatory agent carrageenan in the TMJ of female rats. We also hypothesized that the activation of β‐adrenoceptors in the TMJ induces nociception mediated, at least in part, by the inflammatory response. To test this hypothesis, we examined the nociceptive response induced by the activation of the β‐adrenoceptors in the TMJ in female rats pretreated with thalidomide and fucoidan.

Results

We found that the co‐administration of propranolol with carrageenan in the TMJ of female rats significantly reduced several parameters of the inflammatory response induced by carrageenan such as plasma extravasation, neutrophil migration and the release of the pro‐inflammatory cytokines TNF‐α, IL‐1β and CINC‐1. Furthermore, the injection of the β‐adrenergic receptor agonist isoproterenol in the TMJ induced nociception that was significantly reduced by thalidomide, fucoidan and by the co‐administration of propranolol but not of the α‐adrenergic receptor antagonist phentolamine.

Conclusions

Propranolol has anti‐inflammatory effects that contribute to its antinociceptive action in the TMJ of females.

Significance

β‐Blockers have an anti‐inflammatory effect on temporomandibular joint (TMJ) that contributes to its analgesic effect. The results of this work suggest that β‐blockers can be used to treat the painful conditions of TMJ, especially when they are associated with an inflammatory process.
Influence of horizontal projection on upward flame spread over XPS thermal insulation material
Authors: An Weiguang , Meng Qingxuan , Pan Rongliang , Zhu Hongya
Published: December 2017

Experimental methods and theoretical analysis are employed to investigate the effects of horizontal projection on upward flame spread over extruded polystyrene thermal insulation material of building façade. The average flame height (Hf) (or area S) drops exponentially as dimensionless projection width (w*) rises, and dropping rates are more significant for wider projection. The decrease of flame area is more remarkable than that of flame height. There exists a low temperature zone which is surrounded by the horizontal projection, the flame, and the façade. The average of maximum temperature (
) of zone below the projection first decreases and then increases as projection width (w) rises. The temperature dropping rate increases exponentially with w*.
of the zone adjoining the surface of extruded polystyrene sample above the projection decreases linearly with w*. For wider projection (w ≥ 10 cm), the average temperature above it first increases and then drops as height rises. The heat flux history could be divided into 4 stages, ie, ignition stage, smoke heat transfer stage, flame heat transfer stage, and attenuation stage. The average heat flux (
) at each stage decreases as w rises. The maximum value is observed at the third stage, where
increases linearly with S.