bluuebunny/crossref_metadata_2025 huggingface dataset:
Promotion of Oxygen Reduction with Both Amorphous and Crystalline MnOx through the Surface Engineering of La0.8Sr0.2MnO3‐δ Perovskite
Authors: Yu Jing , Chen Dengjie , Saccoccio Mattia , Lam Kwunyu , Ciucci Francesco
Published: January 2018

Surfaces play a key role in catalysis. Surfaces can be modified in a number of ways, for example by depositing nanoparticles or with functional coating layers. Here, the surface of La0.8Sr0.2MnO3‐δ (LSMO) is treated with diluted HNO3. This process leads to the preferential formation of MnOx/LSMO on the surface, leading to the exposure of Mn cations at the surface of LSMO. The electrocatalytic activity of the MnOx/LSMO heterostructure towards the oxygen reduction reaction (ORR) is shown to increase when it is compared to the untreated LSMO. Thanks to the formation of MnOx at the surface, the resulting MnOx/LSMO possesses 1) a relatively high specific surface area and a mesoporous structure, 2) a higher coverage of Mn4+/Mn3+ cations at the surface, and 3) a high concentration of highly oxidative oxygen species. This work develops a facile strategy (i. e. HNO3 treatment) for improving the ORR activity of perovskite oxides in alkaline solution at room temperature.
Ionisierende Strahlung mit dem Smartphone messen
Authors: Kuhn Jochen , Schäfer Matthias , Hauck Bernhard , Ulber Roland
Published: January 2018

Durch ihre vielseitige Ausstattung lassen sich Smartphones als mobile Minilabore für vielseitige Messungen einsetzen. Der Beitrag beschreibt, wie sich Smartphones und Tablet‐PCs zur Messung von ionisierender Strahlung verwenden lassen. Die dem Experiment zugrundeliegenden physikalischen Zusammenhänge können mit einer für den schulischen Physikunterricht hinreichenden Genauigkeit bestätigt werden, wobei die gewonnenen Daten vergleichbar zu denen eines schulüblichen Geiger‐Müller‐Zählrohres sind. Mittlerweile zeigen erste Untersuchungsergebnisse, dass auch das Lernen gefördert werden kann, wenn diese Medien als mobile Mini‐Labore eingesetzt werden.
Visible Light Promoted β‐C—H Alkylation of β‐Ketocarbonyls via a β‐Enaminyl Radical Intermediate
Authors: Wang Dehong , Zhang Long , Luo Sanzhong
Published: January 2018

A 5πe carbonyl activation mode is reported on the basis of photo‐induced single‐electron‐transfer (SET) oxidation of a secondary enamine. The resultant β‐enaminyl radical intermediate was trapped by a wide range of Michael acceptors, producing β‐alkylation products of β‐ketocarbonyls in a highly efficient manner.
The risk of malignancy of atypical urothelial cells of undetermined significance in patients treated with chemohyperthermia or electromotive drug administration
Authors: Pierconti Francesco , Rossi Esther Diana , Straccia Patrizia , Fadda Guido , Larocca Luigi Maria , Bassi Pier Francesco , Sacco Emilio , Schinzari Giovanni
Published: January 2018

BACKGROUND

Chemohyperthermia (C‐HT) or electromotive drug administration (EMDA) are alternative therapies to radical cystectomy in patients with non‐muscle‐invasive bladder cancer who do not respond to intravesical therapy with bacille Calmette‐Guérin.

METHODS

The authors investigated a group of 87 patients with a diagnosis of high‐grade non‐muscle‐invasive bladder carcinoma or carcinoma in situ. Of these, 45 patients received EMDA of mitomycin (EMDA/MMC) and 42 patients were treated with C‐HT and mitomycin therapy (C‐HT/MMC). In accordance with the Paris System for Reporting Urinary Cytology, a cytological diagnosis was made and patients with diagnoses of atypical urothelial cells (AUC), suspicious high‐grade urothelial carcinoma (SHGUC), or high‐grade urothelial carcinoma also underwent histological bladder biopsies.

RESULTS

In accordance with the Paris System for Reporting Urinary Cytology, the AUC cases may have cytological features of SHGUC present on atypical degenerated cells. In analyzing the AUC group without the SHGUC cases diagnosed on the basis of degenerated urothelial cells, the authors found a significant association between the AUC category and a negative histological biopsy. The SHGUC group, including cases with a SHGUC diagnosis rendered on degenerated urothelial cells, was associated with high‐grade urothelial carcinoma or carcinoma in situ (P =  .0269 for patients treated with EMDA/MMC and P =  .0049 for patients treated with C‐HT/MMC).

CONCLUSIONS

In the urine samples from patients treated with EMDA/MMC or C‐HT/MMC, a diagnosis of SHGUC could be made even on degenerated urothelial cells when considering cellular degeneration as a “physiological” consequence of the treatment that involves either normal or neoplastic cells. Cancer Cytopathol 2018;126:200‐6. © 2018 American Cancer Society.
Investigation of Microalgal Carotenoid Content Using Coherent Anti‐Stokes Raman Scattering (CARS) Microscopy and Spontaneous Raman Spectroscopy
Authors: Legesse Fisseha Bekele , Rüger Jan , Meyer Tobias , Krafft Christoph , Schmitt Michael , Popp Jürgen
Published: January 2018

The yield of high‐value products, such as pigments that could be extracted from microalgae, is affected by various nutritional and physical factors. Consequently, there is a need for fast visualization techniques that investigate the responses of individual microalgal cells to changing environmental conditions without introducing perturbations. Here, we apply CARS microscopy to map the distribution of pigments in the diatoms Ditylum brightwellii and Stephanopyxis turris and report their relative change in response to varying light cycles using a marker‐based watershed analysis of the acquired images. Simultaneously, the underlying specific pigment composition alterations are revealed using Raman microspectroscopy at 785 nm excitation. In regards to assessing the chemical content of microalgae, these methods present themselves as viable alternatives to the standard techniques currently in use because of their non‐disruptive nature and the wealth of complementary information that could be obtained from them.
Role of Thin Sn Layer for Low Temperature Al‐Al Thermo‐compression Bonding of Wafer‐Level Hermetic Sealing
Authors: SATOH SHIRO , FUKUSHI HIDEYUKI , ESASHI MASAYOSHI , TANAKA SHUJI
Published: January 2018

This paper reports low temperature hermetic wafer bonding using Al/Sn/Al/Sn/Al as a bonding layer. The Al surface of the bonding layer was oxidized in air, but hermetic sealing was demonstrated without surface treatment at 370 °C to 390 °C, which was lower than the maximum temperature of complementary metal oxide semiconductor (CMOS) backend process (400 °C). For the successfully sealed samples, the bonding layer was considerably compressed and squeezed, and the remaining thickness was only <16% of the initial one, that is, the reduction rate was >84%. On the other hand, the samples without Sn layers inserted, that is, using a pure Al bonding layer, were not hermetically sealed at similar temperatures, showing the reduction rate smaller than 70%. A clear correlation between the reduction rate and the yield of hermetic sealing was observed. Taking account of analytical results and Al‐Sn phase diagram, it is suggested that Al‐Sn liquid phase in Al grain boundaries enhances the grain slip deformation of the bonding layer and fractionates the surface Al oxide layer during the bonding process. The function of Sn for Al‐Al bonding suggested in this paper is useful for wafer‐level hermetic micro electro mechanical systems (MEMS) packaging at low temperature.
Coupled Analysis by Viscoelastic Body with Rigid Body for Design of MRE Soft Actuator
Authors: MURAO SHUNTA , MITSUFUJI KENTA , HIRATA KATSUHIRO , MIYASAKA FUMIKAZU
Published: January 2018

The magneto rheological elastomer (MRE) is composed of silicone elastomers and ferromagnetic powders that are responsible for its ferromagnetic and viscoelastic properties. The shape and the stiffness of the MRE change depending on the magnetic field. Therefore, it is expected to be used for artificial muscle or damping material. We developed a coupled analysis method by combining the moving particle semi‐implicit/simulation (MPS) method with the finite element method (FEM) for the design of the MRE actuator. However, this method does not take into account a rigid body. Therefore, when analyzing the coil embedded in the MRE, it was difficult to calculate parameters such as the coil rotation and position. Therefore, this paper presents a numerical method for MRE actuator analysis by coupling MPS method with FEM to arrive at a calculation method for a rigid body. The numerical algorithm is described and the calculated results are shown.
ZIF‐11/Matrimid® mixed matrix membranes for efficient CO2, CH4, and H2 separations
Authors: Yumru Ahenk Burcu , Safak Boroglu Mehtap , Boz Ismail
Published: January 2018

Zeolitic imidazolate framework ZIF‐11 particles were prepared and mixed with Matrimid® 5218 polyimide, from 0 to 40 wt. % loadings. The ZIF‐11 particles and the Matrimid® 5218 polyimide matrix were studied using differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), X‐Ray diffraction (XRD), infrared spectroscopy (FT‐IR), and scanning electron microscopy (SEM) techniques. Surface and cross‐sectional scanning electron microscopy images of the mixed matrix membranes (MMMs) were taken to examine the dispersion of particles in the polymer matrix. No visible agglomeration between ZIF‐11 particles and the polymer matrix was spotted, even at 40 wt. % ZIF‐11 loading. Mixed matrix membranes were described by the measured permeabilities of H2, CO2 and CH4 gases. Ideal gas selectivities were determined. Permeability of all gases increased with increasing ZIF‐11 percentages. The permeabilities for all gases decreased at 40 wt. % loading, and the CO2/CH4, and H2/CH4 selectivities were increased. © 2018 Society of Chemical Industry and John Wiley & Sons, Ltd.
In Situ Probing Intracellular Drug Release from Redox‐Responsive Micelles by United FRET and AIE
Authors: Wang Xuelin , Li Juanjuan , Yan Qi , Chen Yanrui , Fan Aiping , Wang Zheng , Zhao Yanjun
Published: January 2018

Redox‐responsive micelles are versatile nanoplatforms for on‐demand drug delivery, but the in situ evaluation of drug release is challenging. Fluorescence resonance energy transfer (FRET) technique shows potential for addressing this, while the aggregation‐caused quenching effect limits the assay sensitivity. The aim of the current work is to combine aggregation‐induced emission (AIE) probe with FRET to realize drug release assessment from micelles. Tetraphenylethene (TPE) is selected as AIE dye and curcumin (Cur) is chosen as the model drug as well as FRET receptor. The drug is covalently linked to a block copolymer via the disulfide bond linker and TPE is also chemically linked to the polymer via an amide bond; the obtained amphiphilic polymer conjugate self‐assembles into micelles with a hydrodynamic size of ≈125 nm. Upon the supplement of glutathione or tris(2‐carboxyethyl)phosphine) trigger (10 × 10−3m), the drug release induces the fluorescence increase of both TPE and Cur. Accompanied with the FRET decay, absorption enhancement and particle size increase are observed. The same phenomenon is observed in MCF‐7 cells. The FRET–AIE approach can be a useful addition to the spectrum of available methods for monitoring drug release from stimuli‐responsive nanomedicine.
MRI quantification of human fetal O2 delivery rate in the second and third trimesters of pregnancy
Authors: Rodríguez‐Soto Ana E. , Langham Michael C. , Abdulmalik Osheiza , Englund Erin K. , Schwartz Nadav , Wehrli Felix W.
Published: January 2018

Purpose

The purpose of this study was to estimate fetal O2 delivery rate in vivo across a range of gestational ages. Toward this, a calibration equation for T2‐based oximetry was derived.

Methods

Umbilical cord blood of varying hematocrit (Hct) and oxygen saturation (HbO2) levels was prepared and T2 measured using a T2‐prepared balanced steady‐state free‐precession sequence at 1.5 T. The relationship between blood R2 = 1/T2, HbO2 and Hct was established based on the model
. Experimental R2, HbO2, and Hct levels were fit to the model‐yielding values of k,
and
(R2 of plasma and erythrocytes). Umbilical vein T2 measured in vivo was then converted to HbO2, yielding—together with blood flow rate—the fetal O2 delivery rate in 22 pregnancies (gestational age 30 ± 3 weeks).

Results

Constants derived from the fit (R2 = 0.94) were k = 83.1 s−1,
, and
. The
and k were found to be larger than those obtained for adult blood, likely the result of differences in dominant hemoglobin type. Data suggest that the use of adult blood calibration could entail errors up 10% in fetal blood HbO2. The average umbilical vein blood flow rate (89.5 ± 17.2 mL/min/kg), HbO2 (84 ± 7%,), and fetal O2 delivery rate (15.1 ± 3.8 mL O2/min/kg) were independent of gestational age. The fetal O2 delivery rate agreed well with the results obtained with invasive methods at term.

Conclusion

The present work describes strategies for measuring umbilical vein blood flow rate and HbO2 in vivo and estimates fetal O2 delivery rate noninvasively with quantitative MRI during the second and third trimesters of pregnancy. Magn Reson Med 80:1148–1157, 2018. © 2018 International Society for Magnetic Resonance in Medicine.
British Society for Rheumatology guideline on gout
Authors: Chaplin Steve
Published: January 2018

The British Society for Rheumatology published a revised and updated guideline on the management of gout in July 2017, the first in a decade. This article summarises the main recommendations of the new guideline.
Putting prescribing to the test
Authors: Delvin David
Published: January 2018

Doctors are under increasing pressure to prescribe a little something to help nervous patients through their driving test, but Dr Delvin wonders whether there really is anything safe and effective that can be offered.
Asymmetric Resistive Switching Effect in Au/Nb:SrTiO3 Schottky Junctions
Authors: Li Jiachen , Yang Guang , Wu Yonghui , Zhang Weifeng , Jia Caihong
Published: January 2018

Asymmetric resistive switching processes are observed in Au/Nb:SrTiO3 (NSTO) Schottky junctions. The SET transition from high‐ to low‐resistance state occurs at 10 ns under +2 to +5 V bias, while the RESET transition from low‐ to high‐ resistance state occurs at 104 to 107 ns under −2 to −5 V bias. A model of electron trapping/detrapping coupled with the migration of oxygen vacancies toward/away from Au/NSTO Schottky junction interface is proposed to understand this fast SET and slow RESET process. This fast SET and slow RESET switch may have potential applications in some special regions.
How is agile development currently being used in regulated embedded domains?
Authors: Diebold Philipp , Theobald Sven
Published: January 2018

Background

Agile development shows benefits for software‐developing companies, eg, shorter time to market or stronger customer connections. Nonetheless, agile methods and practices are most often adapted to a specific context. Especially in regulated domains such as automotive, avionics, or medical, domain‐specific constraints need to be considered, and hence, Agile is often used only partially or not at all.

Objective

The goal of this study was to identify the state of the practice in using agile development as part of the development process in regulated embedded domains.

Method

We conducted a study using a combination of a series of interviews and an online questionnaire as data collection methods.

Results

The responses of 50 participants showed that Agile, mostly in the form of an adapted form of Scrum, has already arrived in those domains, but mainly in noncritical projects and/or early project phases. This means there is further improvement potential, which was also confirmed by the participants regarding future usage.

Conclusions

The results of our state‐of‐the‐practice study provide a good stage for future work, especially for new approaches bringing more “agility” into regulated embedded domains.
Thermal Expansion Behaviors of Li3AsW7O25: A Case Study for Comparative Debye Temperature for a Large Polyatomic Unit Cell
Authors: Mangir Murshed M. , Zhao Pei , Huq Ashfia , Gesing Thorsten M.
Published: January 2018

The thermal expansion behavior of Li3AsW7O25 has been studied. The temperature‐dependent development of crystal structural parameters was obtained from Rietveld refinement using neutron time of flight powder diffraction data. Modeling of the lattice thermal expansion was carried out using a Grüneisen first‐order approximation for the zero‐pressure equation of state, where the temperature‐dependent vibrational energy was calculated taking the Debye‐Einstein‐Anharmonicity approach. Temperature‐dependent Raman spectra shed light on some selective modes with unusual anharmonicity. Debye temperatures were calculated using three different theoretical approaches, namely, thermal expansion, mean‐squared isotropic atomic displacement parameter and heat capacity. Similarities as well as discrepancies between the numerical values obtained from different theoretical approaches are discussed.
Synthesis and anticancer activities of fatty acid analogs of podophyllotoxin
Authors: Mustafa Jamal , Khan Shabana I. , Ma Guoyi , Walker Larry A. , Khan Ikhlas A.
Published: January 2018

Derivatives of podophyllotoxin were prepared by coupling 10 FA with the C4‐α‐hydroxy function of podophyllotoxin. The coupling reactions between FA and podophyllotoxin were carried out by dicyclohexylcarbodiimide in the presence of a catalytic amount of dimethylaminopyridine to produce quantitative yields of desired products. FA incorporated were the following: 10‐hydroxydecanoic, 12‐hydroxydodecanoic, 15‐hydroxypentadecanoic, 16‐hydroxyhexadecanoic, 12‐hydroxyoctadec‐Z‐9‐enoic, eicosa‐Z‐5,8,11,14‐tetraenoic, eicosa‐Z‐8,11, 14‐trienoic, eicosa‐Z‐11,14‐dienoic, eicosa‐Z‐11‐enoic, and eicosanoic acids. Spectroscopic studies confirmed the formation of the desired products. New molecules were investigated for their in vitro anticancer activity against a panel of human cancer cell lines including SK‐MEL, KB, BT‐549, SK‐OV‐3 (solid tumors), and HL‐60 (human leukemia) cells. Most of the analogs were cytotoxic against cancerous cells, whereas no effect was observed against normal cells, unlike the parent compound podophyllotoxin, the use of which is limited due to its severe side effects.
Fifty years with bile acids and steroids in health and disease
Authors: Sjövall Jan
Published: January 2018

Cholesterol and its metabolites, e.g., steroid hormones and bile acids, constitute a class of compounds of great biological importance. Their chemistry, biochemistry, and regulation in the body have been intensely studied for more than two centuries. The author has studied aspects of the biochemistry and clinical chemistry of steroids and bile acids for more than 50 years, and this paper, which is an extended version of the Schroepfer Medal Award lecture, reviews and discusses part of this work. Development and application of analytical methods based on chromatography and mass spectrometry (MS) have been a central part of many projects, aiming at detailed characterization and quantification of metabolic profiles of steroids and bile acids under different conditions. In present terminology, much of the work may be termed steroidomics and cholanoidomics. Topics discussed are bile acids in human bile and feces, bile acid production, bacterial dehydroxylation of bile acids and steroids during the enterohepatic circulation, profiles of steroid sulfates in plasma of humans and other primates, development of neutral and ion‐exchanging lipophilic derivatives of Sephadex for sample preparation and group separation of steroid and bile acid conjugates, profiles of steroids and bile acids in human urine under different conditions, hydroxylation of bile acids in liver disease, effects of alcohol‐induced redox changes on steroid synthesis and metabolism, alcohol‐induced changes of bile acid biosynthesis, compartmentation of bile acid synthesis studied with 3H‐labeled ethanol, formation and metabolism of sulfated metabolites of progesterone in human pregnancy, abnormal patterns of these in patients with intrahepatic cholestasis of pregnancy corrected by ursodeoxycholic acid, inherited and acquired defects of bile acid biosynthesis and their treatment, conjugation of bile acids and steroids with N‐acetylglucosamine, sulfate‐glucuronide double conjugates of hydroxycholesterols, extrahepatic 7α‐hydroxylation and 3‐dehydrogenation of hydroxycholesterols, and extrahepatic formation of C27 bile acids. The final part discusses analysis of free and sulfated steroids in brain tissue by capillary liquid chromatography‐electrospray MS and suggests a need for reevaluation of the function of steroid sulfates in rat brain.
The Young Macpherson on the Transition into Socialism and the Rise of Fascism
Authors: Dahlquist Karl
Published: January 2018

Given the renewed interest in C. B. Macpherson's political theory in a time of late neo-liberalism, the aim of this article is to complement existing scholarship with a detailed account of his early thought on the transition into socialism. Against the prevailing view, I suggest that the young Macpherson outlined a theory of transition, on which the actualization of his democratic vision depended. I trace how he investigated the nature of the state in the 1930s and early 1940s and asked whether a socialist movement could gain control of state institutions and shape their policies to establish an economic democracy that could serve as a defence against fascism. As a democratic socialist, he agonized over the idea that a forcible revolution and unconstitutional measures were likely required to establish socialism. To paint my intellectual portrait, I make use of archival material from the time that has yet to be commented on.
Segal's Spectral Sequence in Twisted Equivariant K-theory for Proper and Discrete Actions
Authors: Bárcenas Noé , Espinoza Jesús , Uribe Bernardo , Velásquez Mario
Published: January 2018

We use a spectral sequence developed by Graeme Segal in order to understand the twisted G-equivariant K-theory for proper and discrete actions. We show that the second page of this spectral sequence is isomorphic to a version of Bredon cohomology with local coefficients in twisted representations. We furthermore explain some phenomena concerning the third differential of the spectral sequence, and recover known results when the twisting comes from finite order elements in discrete torsion.
Images of Equality and Freedom: the Representation of Chinese American Men, America Today Magazine, and the Cultural Cold War in Asia
Authors: YEH CHIOU-LING
Published: January 2018

This article analyzesAmerica Today, a United States Information Service publication circulated to Southeast Asian Chinese between 1949 and 1952. Although the federal government had no intention of lifting immigration restrictions, the magazine promoted the idea that the United States provided humanitarian assistance and abundant opportunities to Chinese immigrants as well as their American-born Chinese counterparts to achieve upward mobility, form a conjugal family, and enjoy patriarchal authority. The stories demonstrated an attempt to inspire Chinese male readers in Southeast Asia to support the United States and the “free world,” rather than Communism and the People's Republic of China.
The dynamics of episodic memory functions
Authors: Berntsen Dorthe
Published: January 2018

There is no doubt that episodic memory serves communicative functions, but Mahr & Csibra (M&C) overlook that this is not the only function served by memories of past events. Autobiographical memory research has identified several other functions, including purely directive functions. The functionality of episodic memory is not stable across situations; it varies dynamically with the demands of the retrieval context.
The communicative function of destination memory
Authors: El Haj Mohamad , Miller Ralph
Published: January 2018

Mahr & Csibra's (M&C's) proposal that episodic memory has a role in communicative interaction is innovative. However, the model would be strengthened by the inclusion of the construct of destination memory. Destination memory refers to the ability to remember to whom one has sent information. Research has demonstrated that this ability is essential for communicative efficacy and daily interactions with others.
Autonoesis and reconstruction in episodic memory: Is remembering systematically misleading?
Authors: Michaelian Kourken
Published: January 2018

Mahr & Csibra (M&C) view autonoesis as being essential to episodic memories and construction as being essential to the process of episodic remembering. These views imply that episodic memory is systematically misleading, not because it often misinforms us about the past, but rather because it often misinforms us about how it informs us about the past.
Developmental roots of episodic memory
Authors: Nelson Katherine
Published: January 2018

Two arguments imply that Mahr & Csibra's (M&C's) functional theory is insufficient as an explanation of episodic memory: (1) The developmental course supports a different social cultural division of episodic and semantic memory, and (2) the existence of long-term autobiographical memory is not explained in the functional theory but can be seen in a broader cultural framework.
A new kinetostatic model for humanoid robots using screw theory
Authors: Toscano Gustavo S. , Simas Henrique , Castelan Eugênio B. , Martins Daniel
Published: January 2018

This study presents a new kinetostatic model for humanoid robots (HRs). Screw theory, together with Assur virtual chains and Davies' method, provides the required tools for the proposal of both the kinematic and static parts of the kinetostatic model. Our kinetostatic model is able to estimate the forces and couples generated at the axes of each joint of the robot, as well as one unknown contact condition between the robot and the environment around it. The proposed model is also very versatile and free of fixed coordinates and, therefore, it allows for an estimate of a great amount of information on the HR. Some results, obtained from computer simulation, are presented to validate the versatility of the proposed technique.
General Assembly of the Church of Scotland
Authors: Lingiah Jason
Published: January 2018

The General Assembly met in Edinburgh from 20 to 26 May with the Rt Revd Dr Derek Browning, Minister of Morningside in the Presbytery of Edinburgh, installed as Moderator. This year's Lord High Commissioner to the General Assembly was the Princess Royal.
Prevalence and risk factors associated with non-attendance in neurodevelopmental follow-up clinic among infants with CHD
Authors: Loccoh Eméfah C. , Yu Sunkyung , Donohue Janet , Lowery Ray , Butcher Jennifer , Pasquali Sara K. , Goldberg Caren S. , Uzark Karen
Published: January 2018

Background

Neurodevelopmental impairment is increasingly recognised as a potentially disabling outcome of CHD and formal evaluation is recommended for high-risk patients. However, data are lacking regarding the proportion of eligible children who actually receive neurodevelopmental evaluation, and barriers to follow-up are unclear. We examined the prevalence and risk factors associated with failure to attend neurodevelopmental follow-up clinic after infant cardiac surgery.

Methods

Survivors of infant (<1 year) cardiac surgery at our institution (4/2011-3/2014) were included. Socio-demographic and clinical characteristics were evaluated in neurodevelopmental clinic attendees and non-attendees in univariate and multivariable analyses.

Results

A total of 552 patients were included; median age at surgery was 2.4 months, 15% were premature, and 80% had moderate–severe CHD. Only 17% returned for neurodevelopmental evaluation, with a median age of 12.4 months. In univariate analysis, non-attendees were older at surgery, had lower surgical complexity, fewer non-cardiac anomalies, shorter hospital stay, and lived farther from the surgical center. Non-attendee families had lower income, and fewer were college graduates or had private insurance. In multivariable analysis, lack of private insurance remained independently associated with non-attendance (adjusted odds ratio 1.85, p=0.01), with a trend towards significance for distance from surgical center (adjusted odds ratio 2.86, p=0.054 for ⩾200 miles).

Conclusions

The majority of infants with CHD at high risk for neurodevelopmental dysfunction evaluated in this study are not receiving important neurodevelopmental evaluation. Efforts to remove financial/insurance barriers, increase access to neurodevelopmental clinics, and better delineate other barriers to receipt of neurodevelopmental evaluation are needed.
Tracing the Path of Gas Atoms from Earth to the Final Frontier
Authors: Witman Sarah
Published: January 2018

Scientists capture the first complete image of Earth’s luminous geocorona and prove its ecliptic north–south symmetry.
Novel therapeutic strategy for cervical cancer harboring FGFR3-TACC3 fusions
Authors: Tamura Ryo , Yoshihara Kosuke , Saito Tetsuya , Ishimura Ryosuke , Martínez-Ledesma Juan Emmanuel , Xin Hu , Ishiguro Tatsuya , Mori Yutaro , Yamawaki Kaoru , Suda Kazuaki , Sato Seiya , Itamochi Hiroaki , Motoyama Teiichi , Aoki Yoichi , Okuda Shujiro , Casingal Cristine R. , Nakaoka Hirofumi , Inoue Ituro , Verhaak Roel G. W. , Komatsu Masaaki , Enomoto Takayuki
Published: January 2018

We previously found that therapeutic targetable fusions are detected across various cancers. To identify therapeutic targetable fusion in uterine cervical cancer, for which no effective gene targeted therapy has yet been clinically applied, we analyzed RNA sequencing data from 306 cervical cancer samples. We detected 445 high confidence fusion transcripts and identified four samples that harbored FGFR3-TACC3 fusion as an attractive therapeutic target. The frequency of FGFR3-TACC3-fusion-positive cervical cancer is also 1.9% (2/103) in an independent cohort. Continuous expression of the FGFR3-TACC3 fusion transcript and protein induced anchorage-independent growth in the cervical epithelial cell line established from the ectocervix (Ect1/E6E7) but not in that from endocervix (End1/E6E7). Injection of FGFR3-TACC3 fusion-transfected-Ect1/E6E7 cells subcutaneously into NOG mice generated squamous cell carcinoma xenograft tumors, suggesting the association between FGFR3-TACC3 fusion and squamous cell carcinogenesis. Transfection of a FGFR3-TACC3 fusion transcript into four cervical cancer cell lines (SiHa, ME180, HeLa, and Ca Ski) induced activation of the MAPK pathway and enhancement of cell proliferation. Transcriptome analysis of the FGFR3-TACC3 fusion-transfected cell lines revealed that an IL8-triggered inflammatory response was increased, via activation of FGFR3–MAPK signaling. Continuous expression of FGFR3-TACC3 fusion led to activation of the PI3K–AKT pathway only in the two cell lines that harbored PIK3CA mutations. Sensitivity to the FGFR inhibitor, BGJ398, was found to depend on PIK3CA mutation status. Dual inhibition of both FGFR and AKT showed an obvious synergistic effect in cell lines that harbor mutant PIK3CA. Additionally, TACC3 inhibitor, KHS101, suppressed FGFR3-TACC3 fusion protein expression and showed antitumor effect against FGFR3-TACC3 fusion-transfected cell lines. FGFR3-TACC3 fusion-positive cancer has frequent genetic alterations of the PI3K/AKT pathway and selection of appropriate treatment based on PI3K/AKT pathway status should be required.
Targeted reduction of the EGFR protein, but not inhibition of its kinase activity, induces mitophagy and death of cancer cells through activation of mTORC2 and Akt
Authors: Katreddy Rajasekhara Reddy , Bollu Lakshmi Reddy , Su Fei , Xian Na , Srivastava Shivangi , Thomas Rintu , Dai Yubing , Wu Bing , Xu Yunlu , Rea Michael A. , Briggs James M. , Zhang Qingyuan , Lu Xiongbin , Huang Gangxiong , Weihua Zhang
Published: January 2018

The oncogenic epidermal growth factor receptor (EGFR) is commonly overexpressed in solid cancers. The tyrosine kinase activity of EGFR has been a major therapeutic target for cancer; however, the efficacy of EGFR tyrosine kinase inhibitors to treat cancers has been challenged by innate and acquired resistance at the clinic. Accumulating evidence suggests that EGFR possesses kinase-independent pro-survival functions, and that cancer cells are more vulnerable to reduction of EGFR protein than to inhibition of its kinase activity. The molecular mechanism underlying loss-of-EGFR-induced cell death remains largely unknown. In this study, we show that, unlike inhibiting EGFR kinase activity that is known to induce pro-survival non-selective autophagy, downregulating EGFR protein, either by siRNA, or by a synthetic EGFR-downregulating peptide (Herdegradin), kills prostate and ovarian cancer cells via selective mitophagy by activating the mTORC2/Akt axis. Furthermore, Herdegradin induced mitophagy and inhibited the growth of orthotopic ovarian cancers in mice. This study identifies anti-mitophagy as a kinase-independent function of EGFR, reveals a novel function of mTORC2/Akt axis in promoting mitophagy in cancer cells, and offers a novel approach for pharmacological downregulation of EGFR protein as a potential treatment for EGFR-positive cancers.
HNRNPH1 is required for rhabdomyosarcoma cell growth and survival
Authors: Li Yanfeng , Bakke Jesse , Finkelstein David , Zeng Hu , Wu Jing , Chen Taosheng
Published: January 2018

Rhabdomyosarcoma (RMS) is an aggressive and difficult to treat cancer characterized by a muscle-like phenotype. Although the average 5-y survival rate is 65% for newly diagnosed RMS, the treatment options for metastatic disease are limited in efficacy, with the 5-y survival rate plummeting to 30%. Heterogenous nuclear ribonucleoprotein H1 (HNRNPH1) is an RNA-binding protein that is highly expressed in many cancers, including RMS. To determine the role HNRNPH1 plays in RMS tumorigenesis, we investigated its expression and effect on growth in three cellular models of RMS: RD, RH30, and RH41 cells. Upon knockdown of HNRNPH1, growth of all cell lines was reduced, most likely through a combination of apoptosis and cell cycle arrest. We then recapitulated this finding by performing in vivo xenograft studies, in which knockdown of HNRNPH1 resulted in a reduction of tumor formation and growth. We used RNA sequencing to identify changes in gene expression after HNRNPH1 knockdown and found altered splicing of some oncogenes. Our data contribute to understanding the role of HNRNPH1 in RMS development.
Statuses of food-derived glutathione in intestine, blood, and liver of rat
Authors: Yamada Hiroaki , Ono Shinn , Wada Sayori , Aoi Wataru , Park Eun Young , Nakamura Yasushi , Sato Kenji
Published: January 2018

Oral administration of glutathione has been demonstrated to reduce exercise-induced fatigue and improve liver function, although glutathione can be synthesized in the liver. However, little is known about the underlying mechanism of this effect. To address this, the status of food-derived glutathione in the intestine, blood, and liver was examined. Glutathione-1-13C or N-acetyl-cysteine-1-13C (NAC) was orally administered to rats (50 mg/kg). Food-derived glutathione contents within tissues were estimated by subtracting endogenous glutathione-1-13C from the total glutathione-1-13C. Food-derived glutathione was present in rat intestines and livers (approximately 60 and 300 μmol/kg, respectively, 120 min after ingestion) in electrochemically reduced form, while all food-derived glutathione in the blood plasma was conjugated with proteins and low-molecular-weight thiol compounds. However, no significant amounts of NAC-derived glutathione were detected in the blood plasma. These findings indicate that food-derived glutathione is directly absorbed in its electrochemically reduced form in the intestine, is then transported in the blood in bound forms, and is finally deposited into the liver in reduced form. Therefore, upon entering the bloodstream, food-derived glutathione binds to thiol compounds and releases hydrogen atom; subsequently, it does the reverse upon incorporation into the liver, which might impact the physiological redox condition. With respect to food-derived glutathione and cysteine-containing peptides, this study provides new insights on their modes of transportation and mechanisms of action.
Low Altitude Solar Magnetic Reconnection, Type III Solar Radio Bursts, and X-ray Emissions
Authors: Cairns I. H. , Lobzin V. V. , Donea A. , Tingay S. J. , McCauley P. I. , Oberoi D. , Duffin R. T. , Reiner M. J. , Hurley-Walker N. , Kudryavtseva N. A. , Melrose D. B. , Harding J. C. , Bernardi G. , Bowman J. D. , Cappallo R. J. , Corey B. E. , Deshpande A. , Emrich D. , Goeke R. , Hazelton B. J. , Johnston-Hollitt M. , Kaplan D. L. , Kasper J. C. , Kratzenberg E. , Lonsdale C. J. , Lynch M. J. , McWhirter S. R. , Mitchell D. A. , Morales M. F. , Morgan E. , Ord S. M. , Prabu T. , Roshi A. , Shankar N. Udaya , Srivani K. S. , Subrahmanyan R. , Wayth R. B. , Waterson M. , Webster R. L. , Whitney A. R. , Williams A. , Williams C. L.
Published: January 2018

Type III solar radio bursts are the Sun’s most intense and frequent nonthermal radio emissions. They involve two critical problems in astrophysics, plasma physics, and space physics: how collective processes produce nonthermal radiation and how magnetic reconnection occurs and changes magnetic energy into kinetic energy. Here magnetic reconnection events are identified definitively in Solar Dynamics Observatory UV-EUV data, with strong upward and downward pairs of jets, current sheets, and cusp-like geometries on top of time-varying magnetic loops, and strong outflows along pairs of open magnetic field lines. Type III bursts imaged by the Murchison Widefield Array and detected by the Learmonth radiospectrograph and STEREO B spacecraft are demonstrated to be in very good temporal and spatial coincidence with specific reconnection events and with bursts of X-rays detected by the RHESSI spacecraft. The reconnection sites are low, near heights of 5–10 Mm. These images and event timings provide the long-desired direct evidence that semi-relativistic electrons energized in magnetic reconnection regions produce type III radio bursts. Not all the observed reconnection events produce X-ray events or coronal or interplanetary type III bursts; thus different special conditions exist for electrons leaving reconnection regions to produce observable radio, EUV, UV, and X-ray bursts.
Activated forms of astrocytes with higher GLT-1 expression are associated with cognitive normal subjects with Alzheimer pathology in human brain
Authors: Kobayashi Eiji , Nakano Masako , Kubota Kenta , Himuro Nobuaki , Mizoguchi Shougo , Chikenji Takako , Otani Miho , Mizue Yuka , Nagaishi Kanna , Fujimiya Mineko
Published: January 2018

Although the cognitive impairment in Alzheimer’s disease (AD) is believed to be caused by amyloid-β (Aβ) plaques and neurofibrillary tangles (NFTs), several postmortem studies have reported cognitive normal subjects with AD brain pathology. As the mechanism underlying these discrepancies has not been clarified, we focused the neuroprotective role of astrocytes. After examining 47 donated brains, we classified brains into 3 groups, no AD pathology with no dementia (N-N), AD pathology with no dementia (AD-N), and AD pathology with dementia (AD-D), which represented 41%, 21%, and 38% of brains, respectively. No differences were found in the accumulation of Aβ plaques or NFTs in the entorhinal cortex (EC) between AD-N and AD-D. Number of neurons and synaptic density were increased in AD-N compared to those in AD-D. The astrocytes in AD-N possessed longer or thicker processes, while those in AD-D possessed shorter or thinner processes in layer I/II of the EC. Astrocytes in all layers of the EC in AD-N showed enhanced GLT-1 expression in comparison to those in AD-D. Therefore these activated forms of astrocytes with increased GLT-1 expression may exert beneficial roles in preserving cognitive function, even in the presence of Aβ and NFTs.
Endoscopic non-ablative fractional laser therapy in an orthotopic colon tumour model
Authors: Yoo Su Woong , Oh Gyungseok , Safi Abdul Mohaimen , Hwang Soonjoo , Seo Young-Seok , Lee Kyung-Hwa , Kim Young L. , Chung Euiheon
Published: January 2018

Colorectal cancer is one of the leading causes of cancer-related deaths. Although several therapeutic management strategies are available at the early colon cancer stages, such as endoscopic mucosal or submucosal dissection, associated complications often include bleeding or bowel perforations. As an alternative approach, we investigated endoscopic non-ablative fractional laser (eNAFL) irradiation as a minimally invasive therapeutic modality for the treatment of early-stage colorectal cancer. By implanting SL4-DsRed colon cancer cells into the colons of the C57BL/6 mice, we developed an orthotopic colon tumour mouse model and demonstrated the early-stage tumour growth delay following the eNAFL irradiation. Additionally, we evaluated the temperature changes in the eNAFL-irradiated area using numerical simulations, and induced inflammation using histological analysis. Our results indicate a minimal thermal damage confined to the irradiated spot, sparing the adjacent tissue and alteration in the tumour microenvironment. eNAFL irradiation may be clinically useful as a minimally invasive therapeutic intervention at the early stage of tumourigenesis. In future, an optimal eNAFL therapeutic dose should be determined, in order to increase the efficacy of this approach.
A dynamic allosteric pathway underlies Rad50 ABC ATPase function in DNA repair
Authors: Boswell Zachary K. , Rahman Samiur , Canny Marella D. , Latham Michael P.
Published: January 2018

The Mre11-Rad50 protein complex is an initial responder to sites of DNA double strand breaks. Many studies have shown that ATP binding to Rad50 causes global changes to the Mre11-Rad50 structure, which are important for DNA repair functions. Here we used methyl-based NMR spectroscopy on a series of mutants to describe a dynamic allosteric pathway within Rad50. Mutations result in changes in the side chain methyl group chemical environment that are correlated with altered nanosecond timescale dynamics. We also observe striking relationships between the magnitude of chemical shift perturbations and Rad50 and Mre11 activities. Together, these data suggest an equilibrium between a ground state and an “active” dimerization competent state of Rad50 that has locally altered structure and dynamics and is poised for ATP-induced dimerization and eventual ATP hydrolysis. Thus, this sparsely populated intermediate is critical for Mre11-Rad50-directed DNA double strand break repair.
Fingerprint analysis of Huolingshengji Formula and its neuroprotective effects in SOD1G93A mouse model of amyotrophic lateral sclerosis
Authors: Zhou Qinming , Wang Youjie , Zhang Jingjing , Shao Yaping , Li Song , Wang Yuan , Cai Huaibin , Feng Yi , Le Weidong
Published: January 2018

Amyotrophic lateral sclerosis (ALS) is a fatal neurological disease characterized by progressive loss of motor neurons. There are no definitive pathogenic mechanisms and effective treatments for ALS now. Traditional Chinese medicine (TCM) plays an important role in Chinese health care system. Huolingshengji Formula (HLSJ) is a TCM formula which is applied for treating flaccid syndrome. Our previous clinical study has indicated that HLSJ may have therapeutic effects in ALS patients. In the present study, we analyzed the chemical profile of HLSJ by the high-performance liquid chromatographic (HPLC) fingerprint analysis. And we investigated the therapeutic effects and neuroprotective mechanisms of HLSJ against ALS in SOD1G93A mouse model. Eleven typical peaks were identified by the fingerprint analysis of HLSJ, and the HPLC method had good precision, repeatability and stability. Consistent with our clinical studies, HLSJ significantly prolonged the lifespan, extended the disease duration, and prevented the motor neuron loss in the anterior horn of the lumbar spinal cords in SOD1G93A ALS model mice. Additionally, HLSJ alleviated the atrophy of the gastrocnemius muscles and ameliorated the apoptotic and inflammatory levels in the spinal cords of SOD1G93A mice. Collectively, our study indicated that HLSJ might be a novel candidate for the treatment of ALS.
Birth weight and body mass index z-score in childhood brain tumors: A cross-sectional study
Authors: Wang Kuan-Wen , de Souza Russell J. , Fleming Adam , Johnston Donna L. , Zelcer Shayna M. , Rassekh Shahrad Rod , Burrow Sarah , Thabane Lehana , Samaan M. Constantine
Published: January 2018

Children with brain tumors (CBT) are at higher risk of cardiovascular disease and type 2 diabetes compared to the general population, in which birth weight is a risk factor for these diseases. However, this is not known in CBT. The primary aim of this study was to explore the association between birth weight and body mass measures in CBT, compared to non-cancer controls. This is a secondary data analysis using cross-sectional data from the CanDECIDE study (n = 78 CBT and n = 133 non-cancer controls). Age, sex, and birth weight (grams) were self-reported, and confirmed through examination of the medical records. Body mass index (BMI) was calculated from height and weight measures and reported as kg/m2. BMI z-scores were obtained for subjects under the age of 20 years. Multivariable linear regression was used to evaluate the relationship between birth weight and BMI and BMI z-score, adjusted for age, sex, puberty, and fat mass percentage. Higher birth weight was associated with higher BMI and BMI z-score among CBT and controls. In conclusion, birth weight is a risk factor for higher body mass during childhood in CBT, and this may help the identification of children at risk of future obesity and cardiometabolic risk.
Characterization of Conformational Ensembles of Protonated N-glycans in the Gas-Phase
Authors: Re Suyong , Watabe Shigehisa , Nishima Wataru , Muneyuki Eiro , Yamaguchi Yoshiki , MacKerell Alexander D. , Sugita Yuji
Published: January 2018

Ion mobility mass spectrometry (IM-MS) is a technique capable of investigating structural changes of biomolecules based on their collision cross section (CCS). Recent advances in IM-MS allow us to separate carbohydrate isomers with subtle conformational differences, but the relationship between CCS and atomic structure remains elusive. Here, we characterize conformational ensembles of gas-phase N-glycans under the electrospray ionization condition using molecular dynamics simulations with enhanced sampling. We show that the separation of CCSs between isomers reflects folding features of N-glycans, which are determined both by chemical compositions and protonation states. Providing a physicochemical basis of CCS for N-glycans helps not only to interpret IM-MS measurements but also to estimate CCSs of complex glycans.