bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic landscape of RASopathies in Chinese: Three decades' experience in Hong Kong
Authors: Yu Kris P. T. , Luk Ho‐Ming , Leung Gordon K. C. , Mak Christopher C. Y. , Cheng Shirley S. W. , Hau Edgar W. L. , Chan David K. H. , Lam Stephen T. S. , Tong Tony M. F. , Chung Brian H. Y. , Lo Ivan F. M.
Published: March 2019

RASopathies are a group of genetic disorders due to dysregulation of the RAS‐MAPK signaling pathway, which is important in regulating cell growth, proliferation, and differentiation. These include Noonan syndrome (NS), Noonan syndrome with multiple lentigines (NSML), cardiofaciocutaneous (CFC) syndrome, and Costello syndrome (CS), clinical manifestations include growth retardation, developmental delay, cardiac defects, and specific dysmorphic features. There were abundant publications describing the genotype and phenotype from the Western populations. However, detailed study of RASopathies in Chinese population is lacking. We present here the largest cohort of RASopathies ever reported in Chinese populations, detailing the mutation spectrum and clinical phenotypes of these patients. The Clinical Genetic Service, Department of Health, and Queen Mary Hospital are tertiary referral centers for genetic disorders in Hong Kong. We retrospectively reviewed all the genetically confirmed cases of RASopathies, including NS, NSML, CFC syndrome, and CS, over the past 29 years (from 1989 to 2017). Analyses of the mutation spectrum and clinical phenotypes were performed. One hundred and ninety‐one ethnic Chinese patients with genetically confirmed RASopathies were identified, including 148 patients with NS, 23 NSML, 12 CFC syndrome, and eight CS. We found a lower incidence of hypertrophic cardiomyopathy in individuals with NSML (27.3%), and NS caused by RAF1 mutations (62.5%). Another significant finding was for those NS patients with myeloproliferative disorder, the mutations fall within Exon 3 of PTPN11 but not only restricted to the well‐known hotspots, that is, p.Asp61 and p.Thr731, which suggested that re‐evaluation of the current tumor surveillance recommendation maybe warranted.
Synthesis of Fluoromethyl‐Substituted Cyclopentanones via Radical Fluorination and 1,2‐Alkyl Migration Cascade of Alkenyl Cyclobutanols
Authors: Kim Yubin , Kim Dae Young
Published: March 2019

A radical fluorination/1,2‐alkyl migration cascade process of alkenyl cyclobutanols was developed in this study. This approach provides a mild and convenient access to the synthesis of fluoromethyl‐substituted cyclopentanone derivatives from the coupling reaction of alkenyl cyclobutanols with Selectfluor as the fluorine radical source.
Orthogonally Photocontrolled Non‐Autonomous DNA Walker
Authors: Škugor Marko , Valero Julián , Murayama Keiji , Centola Mathias , Asanuma Hiroyuki , Famulok Michael
Published: March 2019

There is considerable interest in developing progressively moving devices on the nanoscale, with the aim of using them as parts of programmable therapeutics, smart materials, and nanofactories. Present here is an entirely light‐induced DNA walker based on orthogonal photocontrol. Implementing two azobenzene derivatives, S‐DM‐Azo and DM‐Azo, enabled precise coordination of strand displacement reactions that powered a biped walker and guided it along a defined track in a non‐autonomous way. This unprecedented type of molecular walker design offers high precision control over the movement in back‐and‐forth directions as desired, and is regulated solely by the sequence of the irradiation wavelengths. This concept may open new avenues for advancing non‐autonomous progressive molecular motors, ultimately facilitating their application at the nanoscale.
Quaternization of Vinyl/Alkynyl Pyridine Enables Ultrafast Cysteine‐Selective Protein Modification and Charge Modulation
Authors: Matos Maria J. , Navo Claudio D. , Hakala Tuuli , Ferhati Xhenti , Guerreiro Ana , Hartmann David , Bernardim Barbara , Saar Kadi L. , Compañón Ismael , Corzana Francisco , Knowles Tuomas P. J. , Jiménez‐Osés Gonzalo , Bernardes Gonçalo J. L.
Published: March 2019

Quaternized vinyl‐ and alkynyl‐pyridine reagents were shown to react in an ultrafast and selective manner with several cysteine‐tagged proteins at near‐stoichiometric quantities. We have demonstrated that this method can effectively create a homogenous antibody–drug conjugate that features a precise drug‐to‐antibody ratio of 2, which was stable in human plasma and retained its specificity towards Her2+ cells. Finally, the developed warhead introduces a +1 charge to the overall net charge of the protein, which enabled us to show that the electrophoretic mobility of the protein may be tuned through the simple attachment of a quaternized vinyl pyridinium reagent at the cysteine residues. We anticipate the generalized use of quaternized vinyl‐ and alkynyl‐pyridine reagents not only for bioconjugation, but also as warheads for covalent inhibition and as tools to profile cysteine reactivity.
Metal‐Free Tandem Rearrangement/Lactonization: Access to 3,3‐Disubstituted Benzofuran‐2‐(3H)‐ones
Authors: Santi Micol , Ould Darren M. C. , Wenz Jan , Soltani Yashar , Melen Rebecca L. , Wirth Thomas
Published: March 2019

A novel metal‐free synthesis of 3,3‐disubstituted benzofuran‐2‐(3H)‐ones through reacting α‐aryl‐α‐diazoacetates with triarylboranes is presented. Initially, triarylboranes were successfully investigated in α‐arylations of α‐diazoacetates, however in the presence of a heteroatom in the ortho position, the boron enolate intermediate undergoes an intramolecular rearrangement to form a quaternary center. The intermediate cyclizes to afford valuable 3,3‐disubstituted benzofuranones in good yields.
Fatty Acids, the Unsaponifiable Matter, and Polyphenols as Criteria to Distinguish Pistacia atlantica Unripe Fruit Oil
Authors: Bentireche Fatna , Guenane Hamid , Yousfi Mohamed
Published: March 2019

This study aimed to determine the effect of the maturation degree on the chemical composition of Pistacia atlantica fruits oil. A total number of 21 samples of fruits at three stages of maturation (unripe, middle maturity, and ripe fruits) were used in this study. Thus, the fatty acid composition was studied; the percentage of the unsaponifiable matter (w/w) and its anti‐DPPH (2,2‐diphenyl‐1‐picrylhydrazyl) activity were assessed. The total phenolic compound content was also evaluated. The obtained results indicated, for the first time, that unripe fruits oil was characterized by richness in linoleic acid (31.63% ± 3.64%), in unsaponifiable matter (9.29% ± 6.19% w/w), and in phenolic compounds (2.51 mg per 100 g oil). For ripe fruit oil, these values were similar to those of some seed oils (22.41% ± 3.66%, 2.98% ± 1.71% w/w, and 0.13 mg per 100 g oil, respectively). Data analysis by principal component analysis showed that linoleic acid percentage and the unsaponifiable fraction percentage could constitute good markers for these fruits. These two parameters associated with a high level of phenolic compounds seem to distinguish and value the oil of P. atlantica unripe fruits. Thus, the findings revealed that the unripe fruits, rich in bioactive molecules such as unsaturated fatty acids and phenolic compounds, would be the optimal stage of harvesting time. Based on this, we could integrate this natural bioresource in industrial applications.
Composite multilayer films based on polyelectrolytes and in situ‐formed carbon nanostructures with enhanced photoluminescence and conductivity properties
Authors: Ermakov Alexey V. , Prikhozhdenko Ekaterina S. , Demina Polina A. , Gorbachev Ilya A. , Vostrikova Anna M. , Sapelkin Andrei V. , Goryacheva Irina Y. , Sukhorukov Gleb B.
Published: March 2019

We report a facile route for the fabrication of thin composite films based on polyelectrolytes and carbon nanostructures. Composite films were made by layer‐by‐layer assembly of polyelectrolyte multilayers utilizing embedded dextran sulfate (Dex) solution as a carbon source. Raman measurements indicate the formation of carbon nanostructures from the Dex precursor over the whole film. Formation of these nanostructures results in enhanced photoluminescence and an increase in conductivity by two orders of magnitude to about 0.055 S cm−1. The latter corresponds to the level of wide‐gap semiconductors, in contrast to the initial insulating polyelectrolyte film. A distinct peak of photoluminescence of the films is found in the blue region at the wavelength of 450 nm. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 136, 47718.
Imaging a medieval shipwreck with the new PingPong 3D marine reflection seismic system
Authors: Wilken Dennis , Wunderlich Tina , Hollmann Hannes , Schwardt Michaela , Rabbel Wolfgang , Mohr Clemens , Schulte‐Kortnack Detlef , Nakoinz Oliver , Enzmann Jonas , Jürgens Fritz , Wilkes Feiko
Published: March 2019

We present a new three‐dimensional (3D) marine seismic data acquisition system, named PingPong, developed for archaeological prospection in shallow water. Prospection targets for the system are ancient harbour sites and sedimented remains of shipwrecks. The prospection of such targets often means working at the transition from land to water, in areas of only a few meters of water depth and hardly accessible waters. An acquisition system for such environments needs to meet specific demands, especially low draught and marginal weight besides the requirements of archaeological prospection, meaning decimetre resolution and 3D imaging capabilities, together with fast multichannel acquisition to be able to cover large areas. We explain the properties of the PingPong system and show its imaging capabilities using the case study of a sedimented medieval shipwreck. The study area is located at the innermost part of the Baltic fjord Schlei, Germany. In 2014, divers found a wreck in this area, mostly covered by mud. Findings and two timbers, dated by dendrochronology, indicated that the wreck is a Scandinavian transport ship dating to the middle of the twelfth century and related to Schleswig, which is located 2 km northwest of the study area.

We show that the PingPong system is able to image the major remains of the wooden wreck at the seafloor and underneath. The acquired seismic datacube has a resolution of 0.15 m. It shows a number of distinct reflections that can clearly be assigned to the shipwreck, helping to understand the overall condition of the wreck. The reflections originate from one half the ship's hull, which is tilted to the side. The reflections concentrate in the first metre below the seafloor and correlate well with the results from the diving prospection.
The IgG2 Isotype of Anti–Transcription Intermediary Factor 1γ Autoantibodies Is a Biomarker of Cancer and Mortality in Adult Dermatomyositis
Authors: Aussy Audrey , Fréret Manuel , Gallay Laure , Bessis Didier , Vincent Thierry , Jullien Denis , Drouot Laurent , Jouen Fabienne , Joly Pascal , Marie Isabelle , Meyer Alain , Sibilia Jean , Bader‐Meunier Brigitte , Hachulla Eric , Hamidou Mohammed , Huë Sophie , Charuel Jean‐Luc , Fabien Nicole , Viailly Pierre‐Julien , Allenbach Yves , Benveniste Olivier , Cordel Nadège , Boyer Olivier ,   the OncoMyositis Study Group
Published: March 2019

Objective

Anti–transcription intermediary factor 1γ (anti‐TIF1γ) antibodies are the main predictors of cancer in dermatomyositis (DM). Yet, a substantial proportion of anti‐TIF1γ–positive DM patients do not develop cancer. This study was undertaken to identify biomarkers to better evaluate the risk of cancer and mortality in DM.

Methods

This multicenter study was conducted in adult anti‐TIF1γ–positive DM patients from August 2013 to August 2017. Anti‐TIF1γ autoantibody levels and IgG subclasses were identified using a newly developed quantitative immunoassay. Age, sex, DM signs and activity, malignancy, and creatine kinase (CK) level were recorded. Risk factors were determined by univariate and multivariate analysis according to a Cox proportional hazards regression model.

Results

Among the 51 adult patients enrolled (mean ± SD age 61 ± 17 years; ratio of men to women 0.65), 40 (78%) had cancer and 21 (41%) died, with a mean ± SD survival time of 10 ± 6 months. Detection of anti‐TIF1γ IgG2 was significantly associated with mortality (P = 0.0011) and occurrence of cancer during follow‐up (P < 0.0001), with a 100% positive predictive value for cancer when the mean fluorescence intensity of anti‐TIF1γ IgG2 was >385. None of the patients developed cancer after 24 months of follow‐up. Univariate survival analyses showed that mortality was also associated with age >60 years (P = 0.0003), active DM (P = 0.0042), cancer (P = 0.0031), male sex (P = 0.011), and CK level >1,084 units/liter (P = 0.005). Multivariate analysis revealed that age >60 years (P = 0.015) and the presence of anti‐TIF1γ IgG2 (P = 0.048) were independently associated with mortality.

Conclusion

Our findings indicate that anti‐TIF1γ IgG2 is a potential new biomarker of cancer that should be helpful in identifying the risk of mortality in anti‐TIF1γ–positive DM patients.
Assessing a hyperarousal hypothesis of insomnia in adults with autism spectrum disorder
Authors: Baker Emma K. , Richdale Amanda L. , Hazi Agnes , Prendergast Luke A.
Published: March 2019

This study aimed to investigate the relationship between sleep, psychopathology (anxiety, depression and presleep arousal) symptoms, and cortisol in adults with autism spectrum disorder (ASD). The sample composed of 29 adults with ASD (51.7% males) and 29 control adults (51.7% males) aged 21–44 years. Thirteen adults with ASD were medicated for a comorbid diagnosis of anxiety and/or depression (ASD‐Med), while the remaining 16 adults with ASD were not medicated for such diagnoses (ASD‐Only). Participants completed a questionnaire battery, 14‐day sleep/wake diary and 14‐day actigraphy assessment. On one day during the data collection period, participants collected five saliva samples, hourly, prior to sleep and two morning samples; immediately upon waking and 30 min thereafter for the analysis of cortisol. Cortisol 1 hr prior to habitual sleep onset time was associated with poorer sleep efficiency in both ASD groups and increased wake after sleep onset duration (ASD‐Only). Higher subjective somatic arousal was also associated with increased sleep onset latency, regardless of group, and poorer sleep efficiency in the ASD‐Only group. ASD‐Only participants had significantly greater reductions in evening cortisol concentrations compared to both ASD‐Med and control participants. No significant group differences were found for the cortisol awakening response. Findings suggest a hyperarousal hypothesis of insomnia in adults with ASD. Moreover, the low cortisol levels observed in ASD‐Only adults suggest dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis. Longitudinal studies exploring the interplay between insomnia, anxiety and HPA axis regulation across the lifespan in those with ASD are warranted. Autism Res 2019, 12: 897–910. © 2019 International Society for Autism Research, Wiley Periodicals, Inc.

Lay Summary

Both objective (cortisol) and subjective (somatic) physiological arousal were associated with poor sleep quality in adults on the autism spectrum. Adults with autism spectrum disorder (ASD) who were not medicated for a comorbid diagnosis of anxiety and/or depression also had dampened cortisol secretion, suggesting a dysregulation of the hypothalamic pituitary axis. Longitudinal studies investigating the relationship between sleep, psychopathology symptoms and physiological arousal in autistic individuals are warranted. Autism Res 2019. © 2019 International Society for Autism Research, Wiley Periodicals, Inc.
PEGylated PAMAM dendrimers loading oxaliplatin with prolonged release and high payload without burst effect
Authors: Ho Minh Nhat , Bach Long Giang , Nguyen Dai Hai , Nguyen Cong Hao , Nguyen Cuu Khoa , Tran Ngoc Quyen , Nguyen Ngoc Vinh , Hoang Thi Thai Thanh
Published: March 2019

Oxaliplatin (OXA) was coupled to PEGylated polyamidoamine dendrimers of fourth generation (G4‐PEG@OXA) in the comparison to PEGylated ones of odd generation (G3.5‐PEG@OXA). Proton nuclear magnetic resonance and Fourier‐transform infrared spectroscopy were used to confirm the successful incorporation of OXA as well as the synthesis of carrier systems. Both two types of carrier systems exhibited in sphere nanoparticle shape with size of less than 100 nm that was in the range being able to cause toxicity on cancer cells. The average drug loading efficiency (DLE) of G4‐PEG@OXA was obtained at 84.63% that was higher than DLE of G3.5‐PEG of 75.69%. The release kinetic of G4‐PEG@OXA and G3.5‐PEG@OXA did not show any burst release phenomenon while free OXA was released over 40% at the first hour. The sustainable release of OXA was achieved when it was encapsulated in these carriers, but the G4 generation liberated OXA (3.4%‐6.4%) slower than G3.5 one (11.9%‐22.8%). The in vitro cytotoxicities of G4‐PEG@OXA were evaluated in HeLa cell lines using resazurin assay and live/dead staining test. Although the free OXA showed a rather moderate killing ability, the G4‐PEG@OXA still displayed the low viability of HeLa that was better to the result of G3.5‐PEG@OXA due to released OXA amount. The benefit of this system was to overcome the burst release phenomenon to minimize OXA toxicity without compromising its efficiency.
Silver‐based surface enhanced Raman spectroscopy devices for detection of organophosphorus pesticides traces
Authors: Dias Soares Juliana M. , de Oliveira Helinando P.
Published: March 2019

The detection of traces of substances by surface‐sensitive techniques such as surface enhanced Raman spectroscopy (SERS) explores the interaction of adsorbed molecules on plasmonic surfaces to improve the limit of detection of analytes. This article is an overview about recent development in SERS substrates applied in the detection of organophosphorus pesticides on plasmonic surfaces (arrays of metal nanoparticles). The morphology, roughness, chemical functionalization degree, and aggregation level of plasmonic centers are some of the critical parameters to be controlled in the optimization of SERS signal from specific analytes.
Hormonal therapy in uterine sarcomas
Authors: Zang Yuqin , Dong Mengting , Zhang Kai , Gao Chao , Guo Fei , Wang Yingmei , Xue Fengxia
Published: March 2019

Uterine sarcomas (USs) are a group of rare but aggressive uterine malignancies, accounting for only 1% of the malignant tumors of female reproductive organs. Due to the high rate of recurrence and metastasis, the prognosis of USs is poor. Given the high mortality rate and limited clinical benefit of surgery and adjuvant chemoradiotherapy, hormonal therapy has shown good prospects in recent years. Hormonal agents include progestins, aromatase inhibitors (AIs), and gonadotropin‐releasing hormone analogue (GnRH‐a). According to the literature, hormonal therapy has been confirmed effective for recurrent, metastatic or unresectable low‐grade endometrial stromal sarcoma (LGESS) and hormone receptor positive (ER+/PR+) uterine leiomyosarcoma (uLMS) with favorable tolerance and compliance. Besides, hormonal therapy can also be used in patients with early‐staged disease who desire to preserve fertility. However, due to the rarity of USs, the rationale of hormonal therapy is generally extrapolated from data of hormone‐sensitive breast cancer, and present studies of hormonal therapy in USs were almost limited to case reports and small‐sized retrospective studies. Therefore, further systematic researches and standardized clinical trials are needed to establish the optimal hormonal therapy regimen of USs. Herein, we reviewed the existing studies related to the hormonal therapy in USs in order to provide reference for clinical management in specific settings.
The prognostic significance of chromosome 17 abnormalities in patients with myelodysplastic syndrome treated with 5‐azacytidine: Results from the Hellenic 5‐azacytidine registry
Authors: Diamantopoulos Panagiotis , Koumbi Dafni , Kotsianidis Ioannis , Pappa Vasiliki , Symeonidis Argiris , Galanopoulos Athanasios , Zikos Panagiotis , Papadaki Helen A. , Panayiotidis Panayiotis , Dimou Maria , Hatzimichael Eleftheria , Vassilopoulos George , Delimpasis Susan , Mparmparousi Despoina , Papageorgiou Sotirios , Variami Eleni , Kyrtsonis Marie‐Christine , Megalakaki Aekaterini , Kotsopoulou Maria , Repousis Panagiotis , Adamopoulos Ioannis , Kontopidou Flora , Christoulas Dimitrios , Kourakli Alexandra , Tsokanas Dimitrios , Konstantinos Papoutselis Menelaos , Kyriakakis Georgios , Viniou Nora‐Athina ,   the Hellenic MDS study group
Published: March 2019

In patients with myelodysplastic syndrome (MDS), the prognostic significance of chromosome 17 abnormalities has not yet been fully elucidated, except for isochromosome 17q that has been characterized as an intermediate risk abnormality in the Revised International Prognostic Scoring System (IPSS‐R). To further characterize the prognostic significance of chromosome 17 abnormalities we analyzed the hematologic and prognostic characteristics of 548 adult patients with MDS treated with 5‐azacytidine through the Hellenic 5‐azacytidine registry and found 32 patients with a chromosome 17 abnormality (6 with i[17q], 15 with ‐17, 3 with add[17p] and the rest with other rarer abnormalities, mostly translocations). The presence of a chromosome 17 abnormality was correlated with poor prognostic features (high IPSS, IPSS‐R, and WPSS scores) and a low overall survival rate (15.7 vs 36.4 months for patients without chromosome 17 abnormalities, Kaplan–Meier, Log Rank P < 0.00001), but these results were confounded by the fact that most (92.3%) of the cases with a chromosome 17 abnormality (with the exception of i(17q) that was found in all cases as an isolated abnormality) were found in the context of a complex karyotype. Nevertheless, one should not ignore the contribution of chromosome 17 abnormalities to the prognostic significance of a complex karyotype since 33.8% of complex karyotypes encompassed a chromosome 17 abnormality.
Age‐related AMP‐activated protein kinase alterations: From cellular energetics to longevity
Authors: Morgunova Galina V. , Klebanov Alexander A.
Published: March 2019

5’ adenosine monophosphate‐activated protein kinase (AMPK) is a key regulator of energy in the cell, which allows the cell/organism to survive with deficit of ATP. Since AMPK is involved in the adaptation to caloric restriction, the role of age‐related changes in AMPK activity in both the aging organism and the aging cell is actively investigated in gerontology. Studies on yeast, worms, flies, rodents, and primates have demonstrated an important effect of this regulator on key signalling pathways involved in the aging process. In some cases, researchers conclude that AMPK promotes aging. However, in our opinion, in such cases, we observe a disturbance in the adaptive ability because of the prolonged cell/organism presence in stressful conditions because the functional capacity of any adaptation system is limited. Interestingly, AMPK can regulate metabolic processes in noncell‐autonomous manner. The main effects of AMPK activation in the cell are realized in restriction of proliferation and launching autophagy. In tissues of an aging organism, the ability of AMPK to respond to energy deficit decreases; this fact is especially critical for organs that contain postmitotic cells. In this review, we have tried to consider the involvement of AMPK in age‐related changes in the cell and in the organism.
Epoxide‐Mediated Stevens Rearrangements of α‐Amino‐Acid‐Derived Tertiary Allylic, Propargylic, and Benzylic Amines: Convenient Access to Polysubstituted Morpholin‐2‐ones
Authors: Jin You‐Xiang , Yu Bang‐Kui , Qin Si‐Ping , Tian Shi‐Kai
Published: March 2019

A new strategy has been established for the synthesis of polysubstituted morpholin‐2‐ones through Stevens rearrangements of tertiary amines via in situ activation with epoxides. A range of α‐amino acid‐derived tertiary allylic, propargylic, and benzylic amines reacted with epoxides in the presence of zinc halide catalysts to afford structurally diverse allyl‐, allenyl‐, and benzyl‐substituted morpholin‐2‐ones, respectively, in moderate‐to‐good yields with high regioselectivity. The process involves [2,3]‐ and [1,2]‐Stevens rearrangements of quaternary ammonium ylide intermediates and constitutes a very convenient method to prepare polysubstituted morpholin‐2‐ones through tandem formation of C−N, C−O, and C−C bonds. Moreover, replacing epoxides with aziridines permitted the synthesis of polysubstituted piperazin‐2‐ones.
Linderazulen aus einer invasiven Pflanze
Authors: Keltsch Nils , Munzert Viola , Zeller Klaus‐Peter , Siehl Hans‐Ullrich , Berger Stefan , Sicker Dieter
Published: March 2019

Linderazulen, ein kristallines Azulenderivat, sieht wegen des annelierten Furanrings violett aus und nicht blau wie viele andere Azulene. Linderazulen kommt in der Natur in Hornkorallen vor. Einige Pflanzen bilden farblose sesquiterpenoide Vorstufen des Linderazulens. Ihr Abbau kann zu Linderazulen als Aromat führen, z. B. bei einer Wasserdampfdestillation. Die chromatografische Isolierung von Linderazulen in winziger Menge aus dem durch Wasserdampfdestillation erhaltenen ätherischen Öl von Samen der Stängelumfassenden Gelbdolde wird beschrieben. Dieser attraktive Doldenblütler ist eine invasive Pflanze. Der gesamte Spektrensatz von Linderazulen wird beschrieben und interpretiert. Dieser 30. Beitrag beendet die Reihe zur Isolierung und Spektroskopie von Naturstoffen. Er basiert auf einer Vertiefungsarbeit und ergänzt die Kapitel des Buchs “Classics in Spectroscopy” von S. Berger und D. Sicker (Wiley‐VCH 2009).
Isomeric Carborane Neuromuscular Blocking Agents
Authors: Goswami Lalit N. , Olds Tyson J. , Monk Terri G. , Johnson Quinn L. , Dilger James P. , Shanawaz Mohammed A. , Jalisatgi Satish S. , Hawthorne M. Frederick , Kracke George R.
Published: March 2019

We synthesized a family of neuromuscular blocking agents (NMB) based on decamethonium, but containing a carborane cluster in the methylene chain between the two quaternary ammonium groups. The carborane cluster isomers o‐NMB, m‐NMB, and p‐NMB were tested in animals for neuromuscular block and compared with agents used clinically: rocuronium and decamethonium. All three isomers caused reversible muscle weakness in mice as determined by grip strength and inverted screen tests, with a potency rank of p‐NMB > rocuronium > decamethonium > m‐NMB > o‐NMB. The mechanism of action of the compounds was determined by using the in vitro rat phrenic nerve hemi‐diaphragm preparation and electrophysiologic measurements in cells. Neostigmine reversed hemi‐diaphragm weakness caused by the three isomers and rocuronium, but not succinylcholine. In electrophysiologic recordings of currents through acetylcholine receptor channels, the carborane compounds did not activate channel activity but did inhibit channel activation by acetylcholine. These results demonstrate that the carborane neuromuscular blocking agents are non‐depolarizers in contrast to the depolarizing action of the parent compound.
Dicyanodistyrylthiophene‐Based Emissive Chiral Photoswitches: Effect of the Position of the Cyano Group on Reversible Photoisomerization and Fatigue Resistance
Authors: Lin Siyang , Li Juntao , Krishna Bisoyi Hari , Juan Ao , Guo Jinbao , Li Quan
Published: March 2019

Emissive chiral molecular switches with reversible and tunable attributes are promising materials for both fundamental studies and device applications. In this study, we have developed two novel chiral fluorescent photoswitches bearing one dicyanodistyrylthiophene as the emissive scaffold and bridged binaphthyl moieties as chiral entities. The position of the cyano group in these photoswitches 1 and 2 is varied and its effect on the photochemical properties of the light‐driven chiral molecular switches is investigated. Experimental and molecular simulation studies indicate that both of these two regio‐isomeric dicyanodistyrylthiophene photoswitches initially exist in (Z,Z) configuration and exhibit partial reversible Z/E photoisomerization and variation of fluorescence intensity upon blue and UV light irradiations in solution as well as in a room‐temperature liquid‐crystal (LC) matrix. The helical twisting power (HTP) values of the switches in inducing cholesteric LCs (Ch−LCs) depend on the position of the cyano group, being higher for switch 1 than switch 2. However, the switch 2 doped Ch−LC system shows a better photoresponsive behavior and pronounced fatigue resistance, while the Ch−LC system fabricated using switch 1 undergoes a considerable degradation in performance after several switching cycles, which might be due to photodissociation of switch 1 with the cyano group close to the thiophene ring upon light irradiation. Finally, simultaneous phototuning of both the reflection band and fluorescence intensity in a Ch−LC sample doped with 14.0 wt % switch 2 is demonstrated. These results provide a route for designing chiral fluorescent photoswitches with reversible photoisomerization characteristics.
Rational Design of a Composite Electrode to Realize a High‐Performance All‐Solid‐State Battery
Authors: Kim KyungSu , Park Jesik , Jeong Goojin , Yu Ji‐Sang , Kim Yong‐Chan , Park Min‐Sik , Cho Woosuk , Kanno Ryoji
Published: March 2019

A potential solid electrolyte for realizing all‐solid‐state battery (ASB) technology has been discovered in the form of Li10GeP2S12 (LGPS), a lithium superionic conductor with a high ionic conductivity (≈12 mS cm−1). Unfortunately, the achievable Li+ conductivity of LGPS is limited in a sheet‐type composite electrode owing to the porosity of this electrode structure. For the practical implementation of LGPS, it is crucial to control the pore structures of the composite electrode, as well as the interfaces between the active materials and solid‐ electrolyte particles. Herein, the addition of an ionic liquid, N‐methyl‐N‐butylpyrrolidinium bis(trifluoromethylsulfonyl)imide ([Py14][TFSI]), is proposed as a pore filler for constructing a highly reliable electrode structure using LGPS. [Py14][TFSI] is coated onto the surface of LGPS powder through a wet process and a sheet‐type composite electrode is prepared using a conventional casting procedure. The [Py14][TFSI]‐embedded composite electrode exhibits significantly improved reversible capacity and power characteristics. It is suggested that pore‐filling with [Py14][TFSI] is effective for increasing contact areas and building robust interfaces between the active materials and solid‐electrolyte particles, leading to the generation of additional Li+ pathways in the composite electrode of ASBs.
Expandable interleaved high voltage gain boost DC‐DC converter with low switching stress
Authors: Saadatizadeh Zahra , Chavoshipour Heris Pedram , Babaei Ebrahim , Sadikoglu Fahreddin
Published: March 2019

In this paper, an interleaved DC‐DC step‐up boost converter with high voltage conversion ratio and low voltage stresses on switches and diodes is proposed. The proposed converter has low average current passing through the diodes and switches and low input current ripple as a feature of interleaved converters. The voltage gain of the proposed converter can be increased by adding more diode‐capacitor modules; therefore, the proposed converter has expandable structure. In addition, by implementing more diode‐capacitor modules, the switching stresses would be more decreased. Also, to evaluate the performance of the proposed converter, it is compared with other similar presented circuits in the literature. The proposed converter is not only able to provide higher voltage gain but also has lower voltage stresses on switches and diodes. Consequently, switches and diodes with low voltage ratings can be selected. Theoretical analysis is provided in this study for each operation mode and the average current through the switches, diodes and inductors, voltage stresses on switches and diodes, voltage gain, and input current ripple are calculated. Finally, to demonstrate the accuracy performance of the proposed converter, a 450‐W prototype is implemented practically.
Using deep learning to combine static and dynamic power analyses of cryptographic circuits
Authors: Xu Jiming , Heys Howard M.
Published: March 2019

Side‐channel attacks have shown to be efficient tools in breaking cryptographic hardware. Many conventional algorithms have been proposed to perform side‐channel attacks exploiting the dynamic power leakage. In recent years, with the development of processing technology, static power has emerged as a new potential source for side‐channel leakage. Both types of power leakage have their advantages and disadvantages. In this work, we propose to use the deep neural network technique to combine the benefits of both static and dynamic power. This approach replaces the classifier in template attacks with our proposed long short‐term memory network schemes. Hence, instead of deriving a specific probability density model for one particular type of power leakage, we gain the ability of combining different leakage sources using a structural algorithm. In this paper, we propose three schemes to combine the static and dynamic power leakage. The performance of these schemes is compared using simulated test circuits designed with a 45‐nm library.
A Framework for Assessing Scientific Merit in Ethical Review of Clinical Research
Authors: Binik Ariella , Hey Spencer Phillips
Published: March 2019

Ethics guidelines and commentary suggest that a central function of research ethics committees is to assess the scientific merit of the protocols they review. However, some commentators object to this role, and evidence suggests that the assessment of scientific merit is a significant source of confusion and animosity between ethics committees and clinical investigators. In this essay, we argue that ethics committees should assess the scientific value and validity of research protocols and that new decision‐making tools are needed to help them do so in a systematic, transparent, and reliable way. We present a novel ethical framework that can assist in this task.
Anticipatory Waivers of Consent for Pediatric Biobanking
Authors: Hartsock Jane A. , Schwartz Peter H. , Waltz Amy C. , Ott Mary A.
Published: March 2019

As pediatric biobank research grows, additional guidance will be needed about whether researchers should always obtain consent from participants when they reach the legal age of majority. Biobanks struggle with a range of practical and ethical issues related to this question. We propose a framework for the use of anticipatory waivers of consent that is empirically rooted in research that shows that children and adolescents are often developmentally capable of meaningful deliberation about the risks and benefits of participation in research. Accordingly, bright‐line legal concepts of majority or competency do not accurately capture the emerging capacity for autonomous decision‐making of many pediatric research participants and unnecessarily complicate the issues about contacting participants at the age of majority to obtain consent for the continued or first use of their biospecimens that were obtained during childhood. We believe the proposed framework provides an ethically sound balance between the concern for potential exploitation of vulnerable populations, the impetus for the federal regulations governing research with children, and the need to conduct valuable research in the age of genomic medicine.
A trial to evaluate the effect of the sodium–glucose co‐transporter 2 inhibitor dapagliflozin on morbidity and mortality in patients with heart failure and reduced left ventricular ejection fraction (DAPA‐HF)
Authors: McMurray John J.V. , DeMets David L. , Inzucchi Silvio E. , Køber Lars , Kosiborod Mikhail N. , Langkilde Anna M. , Martinez Felipe A. , Bengtsson Olof , Ponikowski Piotr , Sabatine Marc S. , Sjöstrand Mikaela , Solomon Scott D. ,   on behalf of the DAPA‐HF Committees and Investigators
Published: March 2019

Background

Sodium–glucose co‐transporter 2 (SGLT2) inhibitors have been shown to reduce the risk of incident heart failure hospitalization in individuals with type 2 diabetes who have, or are at high risk of, cardiovascular disease. Most patients in these trials did not have heart failure at baseline and the effect of SGLT2 inhibitors on outcomes in individuals with established heart failure (with or without diabetes) is unknown.

Design and methods

The Dapagliflozin And Prevention of Adverse‐outcomes in Heart Failure trial (DAPA‐HF) is an international, multicentre, parallel group, randomized, double‐blind, study in patients with chronic heart failure, evaluating the effect of dapagliflozin 10 mg, compared with placebo, given once daily, in addition to standard care, on the primary composite outcome of a worsening heart failure event (hospitalization or equivalent event, i.e. an urgent heart failure visit) or cardiovascular death. Patients with and without diabetes are eligible and must have a left ventricular ejection fraction ≤ 40%, a moderately elevated N‐terminal pro B‐type natriuretic peptide level, and an estimated glomerular filtration rate ≥ 30 mL/min/1.73 m2. The trial is event‐driven, with a target of 844 primary outcomes. Secondary outcomes include the composite of total heart failure hospitalizations (including repeat episodes), and cardiovascular death and patient‐reported outcomes. A total of 4744 patients have been randomized.

Conclusions

DAPA‐HF will determine the efficacy and safety of the SGLT2 inhibitor dapagliflozin, added to conventional therapy, in a broad spectrum of patients with heart failure and reduced ejection fraction.
Gem‐Difluorination of Triazole Alkyl Functionalized Amino Pyrazoles by Selectfluor to Access 4,4‐Difluoro‐pyrazol‐3‐ones/Pyrazol‐3‐imines
Authors: Srikanth Reddy Narra , Ravi Kumar Nagiri , Krishna Swaroop Desireddy , Punna Nagender , Jitender Dev Gaddameedi , Jagadeesh Babu Nanubolu , Narsaiah Banda
Published: March 2019

We have successfully accomplished gem‐difluorination of triazole alkyl functionalized amino pyrazoles in the presence of Selectfluor under dry condition and obtained 4,4‐difluoro pyrazol‐3‐imines derivatives in high yield. However, in the presence of water, 4,4‐difluoro pyrazol‐3‐one derivatives were afforded.
Direct Determination of Bacterial Cell Viability Using Carbon Nanotubes Modified Screen‐printed Electrodes
Authors: Hassan Rabeay Y. A. , Wollenberger Ulla
Published: March 2019

For the early detection of bacterial infection, there is a need for rapid, sensitive, and label‐free assays. Thus, in this study, nanostrucured microbial electrochemical platform is designed to monitor the viability and cell growth of S. aureus. Using multi‐walled carbon nanotube modified screen‐printed electrodes (MWCNTs/SPE), the cyclic voltammetric measurements showed only one irreversible oxidation peak at 600 mV vs Ag/AgCl that accounts for the viable and metabolically active bacterial cells. The assay was optimized and the secreted metabolites, in the extracellular matrix, were directly detected. The peak current showed a positive correlation with viable cell numbers ranging from OD600 nm of 0.1 to 1.1, indicating that the activity of live cells can be quantified. Consequently, responses of viable and non‐viable cells of S. aureus to the effects of antibiotic and respiratory chain inhibitors were determined. Thus, the proposed nanostructure‐based bacterial sensor provides a reasonable and reliable way for real‐time monitoring of live‐dead cell functions, and antibacterial profiling.
Experimental study of ash formation under O2/CO2 combustion
Authors: Haibo Wu , Yi Zhang , Liao Haiyan , Yu Xuehai , Liu Zhaohui
Published: March 2019

Oxy‐fuel combustion technology has been recognized as the most promising technology for controlling CO2 emission in coal‐fired boilers. The slagging characteristics of oxy‐fuel combustion (O2/CO2) are very different from those of air combustion (O2/N2). In this paper, an ash sample collection of Shenhua coal with high Ca and Fe content was carried out in a muffle furnace and a tubular furnace under different conditions. The ash melting point, X‐ray diffraction (XRD) and scanning electron microscopy (SEM) were used for characterization. The characteristics of Shenhua coal ash slagging in different atmospheres were studied, and the mineral transformation trend was obtained. It was concluded that the melting point of the ash samples under oxy‐fuel combustion was lower than that under an air atmosphere, and the slagging tendency was enhanced under conditions of high oxygen combustion. Under oxy‐fuel combustion, CaCO3 was found. This did not occur under an air atmosphere. The atmosphere has no obvious effect on the crystal minerals of Fe. The decrease in high melting point oxide, the formation of carbonate, and the increase in glass state and sulfate under an oxy‐fuel atmosphere all make the ash melting point lower than under an air atmosphere. © 2019 Society of Chemical Industry and John Wiley & Sons, Ltd.
Impact of three dementia‐related behaviors on caregiver depression: The role of rejection of care, aggression, and agitation
Authors: Choi Scott Seung W. , Budhathoki Chakra , Gitlin Laura N.
Published: March 2019

Objective

The relationship of specific dementia‐related behaviors to caregiver depression and moderating factors is unclear. We examined the role of rejection of care, aggression, and agitation to caregiver depression and if social support and mastery independently moderated associations.

Methods

The method used was a cross‐sectional, secondary analysis using baseline data from two community‐based clinical trials. We examined frequency of occurrence of presenting behaviors and their combinations in persons with dementia. Multiple logistic regression analyses examined associations between nonoverlapping behavioral clusters (agitation alone, agitation + rejection, agitation + aggression, and agitation + rejection + aggression) and caregiver depression. Multiple logistic regression with interaction terms was also used to investigate whether social support or caregiver mastery moderated the relationship between behavioral symptom clusters and caregiver depression.

Results

Three of four symptom clusters (all three behaviors [adjusted odds ratio (AOR) = 2.22; 95% CI, 1.02‐4.83], agitation + rejection of care [AOR = 2.55; 95% CI, 1.06‐6.13], and agitation + aggression [AOR = 2.63; 95% CI, 1.17‐5.89]) had a positive association with caregiver depression, whereas agitation alone was not significantly associated with caregiver depression. Neither social support nor mastery significantly moderated the relationship between these three behavioral clusters and caregiver depression.

Conclusion

Caregiver depression was associated with different combinations of behaviors but not with agitation alone. These results have implications for intervention development and identifying caregivers at risk for depression. Level of social support and mastery does not appear to moderate impact on caregiver depression.
Radiative flow of Maxwell nanofluid containing gyrotactic microorganism and energy activation with convective Nield conditions
Authors: Waqas Hassan , Khan Sami U. , Shehzad Sabir A. , Imran M.
Published: March 2019

On the account of industrial and technological applications, the enhancement of energy by inserting nanoparticles is a hot topic in the present century. Therefore, the current analysis presents a theoretical analysis regarding the flow of electrically conducted Maxwell nanofluid over a stretching surface in the presence of the gyrotactic microorganism. In addition, the influence of thermal conductivity and Arrhenius activation energy are considered. By using the apposite transformation, the system of contemporary partial differential expressions is first converted into nonlinear ordinary differential system. The set of these transmuted equations is solved with the help of the shooting method. Reliable results are obtained for the velocity profile, temperature, motile microorganism density and concentration. It is evaluated that by increasing the value of bioconvection Peclet and Lewis numbers, the microorganism distribution exhibited diminishing behavior. These results may be useful in improving the efficiency of heat transfer devices and microbial fuel cells.
Improvement of surface run‐off in the hydrological model ParFlow by a scale‐consistent river parameterization
Authors: Schalge Bernd , Haefliger Vincent , Kollet Stefan , Simmer Clemens
Published: March 2019

We propose an improvement of the overland‐flow parameterization in a distributed hydrological model, which uses a constant horizontal grid resolution and employs the kinematic wave approximation for both hillslope and river channel flow. The standard parameterization lacks any channel flow characteristics for rivers, which results in reduced river flow velocities for streams narrower than the horizontal grid resolution. Moreover, the surface areas, through which these wider model rivers may exchange water with the subsurface, are larger than the real river channels potentially leading to unrealistic vertical flows. We propose an approximation of the subscale channel flow by scaling Manning's roughness in the kinematic wave formulation via a relationship between river width and grid cell size, following a simplified version of the Barré de Saint‐Venant equations (Manning–Strickler equations). The too large exchange areas between model rivers and the subsurface are compensated by a grid resolution‐dependent scaling of the infiltration/exfiltration rate across river beds. We test both scaling approaches in the integrated hydrological model ParFlow. An empirical relation is used for estimating the true river width from the mean annual discharge. Our simulations show that the scaling of the roughness coefficient and the hydraulic conductivity effectively corrects overland flow velocities calculated on the coarse grid leading to a better representation of flood waves in the river channels.
Nuclear orphan receptor NR2F6 confers cisplatin resistance in epithelial ovarian cancer cells by activating the Notch3 signaling pathway
Authors: Li Han , Zhang Weijing , Niu Chunhao , Lin Chuyong , Wu Xianqiu , Jian Yunting , Li Yue , Ye Liping , Dai Yuhu , Ouyang Ying , Chen Jueming , Qiu Jiaqi , Song Libing , Zhang Yanna
Published: March 2019

The primary challenge facing treatment of epithelial ovarian cancer (EOC) is the high frequency of chemoresistance, which severely impairs the quality of life and survival of patients with EOC. Our study aims to investigate the mechanisms by which upregulation of NR2F6 induces chemoresistance in EOC. The biological roles of NR2F6 in EOC chemoresistance were explored in vitro by Sphere, MTT and AnnexinV/PI assay, and in vivo using an ovarian cancer orthotopic transplantation model. Bioinformatics analysis, luciferase assay, CHIP and IP assays were performed to identify the mechanisms by which NR2F6 promotes chemoresistance in EOC. The expression of NR2F6 was significantly upregulated in chemoresistant EOC tissue, and NR2F6 expression was correlated with poorer overall survival. Moreover, overexpression of NR2F6 promotes the EOC cancer stem cell phenotype; conversely, knockdown of NR2F6 represses the EOC cancer stem cell phenotype and sensitizes EOC to cisplatin in vitro and in vivo. Our results further demonstrate that NR2F6 sustains activated Notch3 signaling, resulting in chemoresistance in EOC cells. Notably, NR2F6 acts as an informative biomarker to identify the population of EOC patients who are likely to experience a favorable objective response to gamma‐secretase inhibitors (GSI), which inhibit Notch signaling. Therefore, concurrent inhibition of NR2F6 and treatment with GSI and cisplatin‐based chemotherapy may be a novel therapeutic approach for NR2F6‐overexpressing EOC. In summary, we have, for the first time, identified an important role for NR2F6 in EOC cisplatin resistance. Our study suggests that GSI may serve as a potential targeted treatment for patients with NR2F6‐overexpressing EOC.