bluuebunny/crossref_metadata_2025 huggingface dataset:
Saccharin‐Based μ‐Oxo Imidoiodane: A Readily Available and Highly Reactive Reagent for Electrophilic Amination
Authors: Yoshimura Akira , Koski Steven R. , Fuchs Jonathan M. , Saito Akio , Nemykin Victor N. , Zhdankin Viktor V.
Published: February 2015

Three new saccharin‐based hypervalent iodine compounds were prepared by the reaction of saccharine with (diacetoxyiodo)arenes or acetoxybenziodoxole. Structures of these new imidoiodanes were established by X‐ray crystallography. The saccharin‐based μ‐oxo‐bridged imidoiodane readily reacts with silyl enol ethers under mild conditions to give the corresponding α‐aminated carbonyl compounds in moderate yields.
Role of a 12‐Lead Electrocardiogram in the Diagnosis of Cardiac Tamponade as Diagnosed by Transthoracic Echocardiography in Patients With Malignant Pericardial Effusion
Authors: Argula Rahul G. , Negi Smita I. , Banchs Jose , Yusuf Syed Wamique
Published: February 2015

Background

Few studies have looked at the utility of the 12‐lead electrocardiogram (ECG) in diagnosing cardiac tamponade in malignant pericardial effusion (PE). The aim of this study was to determine the sensitivity (Se), specificity (Sp), positive predictive value (PPV), and negative predictive value (NPV) of 12‐lead ECG in diagnosing cardiac tamponade in PE.

Hypothesis

Abnormalities on a 12 lead ECG can be used to diagnose or exclude cardiac tamponade in patients with malignant PE.

Methods

Using echocardiography as the gold standard for diagnosis of cardiac tamponade, we determined the Se, Sp, PPV, and NPV for individual and combinations of the 3 ECG abnormalities (low‐voltage complexes, electrical alternans, and sinus tachycardia).

Results

For PEs of all sizes, the Se, Sp, PPV, and NPV for detecting cardiac tamponade were: low‐voltage complexes (56%, 74%, 81%, 46%), electrical alternans (23%, 98%, 95%, 39%), and sinus tachycardia (76%, 60%, 79%, 56%), respectively. Presence of all 3 and any of the 3 ECG abnormalities had a Se, Sp, PPV, and NPV of 8%, 100%, 100%, 36% and 89%, 47%, 77%, 69%, respectively, for cardiac tamponade. The odds ratios for cardiac tamponade in PE were 3.7 (95% confidence interval [CI]: 1.65‐8.30) for low‐voltage complexes, 12.3 (95% CI: 1.58‐95.17) for electrical alternans, and 4.9 (95% CI: 2.22‐10.80) for sinus tachycardia. Presence of any of 3 ECG abnormalities had an odds ratio of 7.3 (95% CI: 2.9‐18.1) for cardiac tamponade.

Conclusions

In malignant PE, combination of ECG abnormalities can supplement clinical examination in the diagnosis of echocardiographic cardiac tamponade. Due to its low NPV, 12‐lead ECG cannot be used as a screening tool to exclude cardiac tamponade with malignant PE.
p‐Nitrophenol Removal by Bauxite Ore Assisted Ozonation and its Catalytic Potential
Authors: Chen Chunmao , Chen Hongshuo , Yu Ji , Han Chao , Yan Guangxu , Guo Shaohui
Published: February 2015

The catalytic ozonation process (COP) has attracted wide attention in the treatment of recalcitrant organic contaminants because of its high efficiency and easy operation. In this study, the bauxite ore (BO) was used as a heterogeneous catalyst to catalyze ozonation of p‐nitrophenol in water. Calcined BO (CBO) assisted COP (CBO–COP) exhibited a higher degradation and mineralization performance for p‐nitrophenol in comparison with raw BO assisted COP and single ozonation process (SOP). The CBO–COP was dominated by hydroxyl radical mediated oxidation on the CBO surface, following a pseudo‐first order kinetics with a reaction rate constant of 0.1944 min−1 at 298.15 K and an activation energy of 6.476 kJ mol−1. The reaction rate constants increased by about 76% at 298.15 K and 45% at 308.15 K and activation energy decreased by approximately 70% in CBO–COP compared to those in SOP. p‐Nitrophenol in CBO–COP was first transformed into 4‐nitrocatechol, pyrocatechol, hydroquinone, phenol p‐benzoquinone, and o‐benzoquinone, and then into benzoquinone, maleic acid, fumaric acid, acetic anhydride, acetic acid, formic acid, or directly mineralized to carbon dioxide and water. The results demonstrated the catalytic potential of BO for ozonation of recalcitrant organic contaminants considering low cost and earth‐abundant reserves.
Interfacial Nanobubbles on Atomically Flat Substrates with Different Hydrophobicities
Authors: Wang Xingya , Zhao Binyu , Ma Wangguo , Wang Ying , Gao Xingyu , Tai Renzhong , Zhou Xingfei , Zhang Lijuan
Published: February 2015

The dependence of the morphology of interfacial nanobubbles on atomically flat substrates with different wettability ranges was investigated by using PeakForce quantitative nanomechanics. Interfacial nanobubbles were formed and imaged on silicon nitride (Si3N4), mica, and highly ordered pyrolytic graphite (HOPG) substrates that were partly covered by reduced graphene oxide (rGO). The contact angles and sizes of those nanobubbles were measured under the same conditions. Nanobubbles with the same lateral width exhibited different heights on the different substrates, with the order Si3N4≈mica>rGO>HOPG, which is consistent with the trend of the hydrophobicity of the substrates.
A Silver‐Free, Reflective Substrate Electrode for Electron Extraction in Top‐Illuminated Organic Photovoltaics
Authors: Tyler Martin S. , Hutter Oliver S. , Walker Dr Marc , Hatton Dr Ross A.
Published: February 2015

The choice of metals suitable as the reflective substrate electrode for top‐illuminated organic photovoltaics (OPVs) is extremely limited. Herein, we report a novel substrate electrode for this class of OPV architecture based on an Al | Cu | AlOx triple‐layer structure, which offers a reflectivity comparable to that of Al over the wavelength range 400–900 nm, a work function suitable for efficient electron extraction in OPVs and high stability towards oxidation. In addition to demonstrating the advantage of this composite electrode over Al in model top‐illuminated OPVs, we also present the results of a photoelectron spectroscopy study, which show that an oxidised 0.8 nm Al layer deposited by thermal evaporation onto an Al | Cu reflective substrate electrode is sufficient to block oxidation of the underlying Cu by air or during deposition of a ZnO1−x electron‐transport layer. This is remarkable given that the self‐limiting oxide thickness on Al metal is greater than 2 nm.
The future is now: Model‐based clinical trial design for Alzheimer's disease
Authors: Romero K , Ito K , Rogers JA , Polhamus D , Qiu R , Stephenson D , Mohs R , Lalonde R , Sinha V , Wang Y , Brown D , Isaac M , Vamvakas S , Hemmings R , Pani L , Bain LJ , Corrigan B ,   Alzheimer's Disease Neuroimaging Initiative* for the Coalition Against Major Diseases**
Published: February 2015

Failures in trials for Alzheimer's disease (AD) may be attributable to inadequate dosing, population selection, drug inefficacy, or insufficient design optimization. The Coalition Against Major Diseases (CAMD) was formed in 2008 to develop drug development tools (DDT) to expedite drug development for AD and Parkinson's disease.1 CAMD led a process that successfully advanced a clinical trial simulation (CTS) tool for AD through the formal regulatory review process at the US Food and Drug Administration (FDA) and European Medicines Agency (EMA).
Physiologically based pharmacokinetic modeling in drug discovery and development: A pharmaceutical industry perspective
Authors: Jones HM , Chen Y , Gibson C , Heimbach T , Parrott N , Peters SA , Snoeys J , Upreti VV , Zheng M , Hall SD
Published: February 2015

The application of physiologically based pharmacokinetic (PBPK) modeling has developed rapidly within the pharmaceutical industry and is becoming an integral part of drug discovery and development. In this study, we provide a cross pharmaceutical industry position on “how PBPK modeling can be applied in industry” focusing on the strategies for application of PBPK at different stages, an associated perspective on the confidence and challenges, as well as guidance on interacting with regulatory agencies and internal best practices.
Pharmacogenetics of pregnancy‐induced changes in efavirenz pharmacokinetics
Authors: Olagunju A , Bolaji O , Amara A , Else L , Okafor O , Adejuyigbe E , Oyigboja J , Back D , Khoo S , Owen A
Published: February 2015

Pregnancy‐induced physiological changes alter many drugs' pharmacokinetics. We investigated pregnancy‐induced changes in efavirenz pharmacokinetics in 25 pregnant and 19 different postpartum women stratified from 211 HIV‐positive women in whom a preliminary pharmacogenetic study had been undertaken. Despite significant changes in CL/F during pregnancy (42.6% increase; P = 0.023), median (range) Cmin was 1,000 ng/mL (429–5,190) with no significant change in Cmax (P = 0.072). However, when stratified for CYP2B6 516G>T (rs3745274) genotype, efavirenz AUC0‐24, Cmax and Cmin were 50.6% (P = 0.0013), 17.2% (P = 0.14), and 61.6% (P = 0.0027) lower during pregnancy (n = 8) compared with postpartum (n = 6) in 516G homozygotes, with values of 25,900 ng.h/mL (21,700–32,600), 2,640 ng/mL (1,260–3,490), and 592 ng/mL (429–917), respectively, and CL/F was 100% higher (P = 0.0013). No changes were apparent in CYP2B6 516 heterozygotes (14 pregnant vs. 7 postpartum). The clinical implications of these findings warrant further investigation.
Measurement of Vector Magnetic Properties of a Nonoriented Electrical Steel Sheet under Shear Stress
Authors: Kai Yuichiro , Enokizono Masato , Kido Yukihito
Published: February 2015

It is well known that the magnetic properties of electrical steel sheets are influenced strongly by mechanical stress. We have measured the residual stress distribution with an X‐ray stress measurement device and clarified not only the tensile and compressive stress but also the shear stress in a rotating machine core. In particular, the influence of the shear stress on the magnetic properties has not previously been reported. We attempt to develop a new system for measurement of vector magnetic properties under shear stress. This paper presents a mechanism for applying shear stress and the measured vector magnetic properties of nonoriented electrical steel sheet under shear stress. These results indicate that the difference in the vector magnetic properties of the nonoriented electrical steel sheets depended on the shear stress.
Permanent Magnet Motor Torsional Resonance Noise Reduction by Rotor Skew Phase Adjustment
Authors: Arata Masanori , Takahashi Norio , Mochizuki Motoyasu , Araki Takashi , Hanai Takashi
Published: February 2015

Hybrid Vehicles (HEVs) and Electric Vehicles (EVs) improve drive efficiency and reduce CO2 emissions by regenerative braking and operating the engine under optimum conditions. It is desirable to decrease the motor size and increase the maximum torque to minimize driving units. For these purposes, motors employing permanent magnets are now commonly used. The motor driving systems of HEVs and EVs must operate over variable speed ranges of up to 1:5. Over this large range, smooth, silent operation is desirable and important. The skew method is often adopted to ensure a smooth start and stop and silent operation by reducing torque ripple. However, this method possibly causes noise and motor vibration. This paper describes the mechanism of torsional resonance noise and vibrations arising from the skew method and a countermeasure to decrease them by optimizing the skew phase distribution on the rotating axis.
PDM Control Method for a Matrix Converter Converting Several‐Hundred‐kHz Single‐Phase Input to Commercial Frequency Three‐Phase Output
Authors: Nakata Yuki , Itoh Jun‐Ichi
Published: February 2015

This paper discusses pulse density modulation (PDM) control methods for a single‐phase to three‐phase matrix converter (MC) in high‐frequency applications. The proposed circuit is used as an interface converter for a wireless power transfer system. This converter can input a frequency of several hundred kilohertz and output a low frequency, that is, 50 Hz or 60 Hz, for a commercial power grid. The proposed circuit implements zero voltage switching (ZVS) operation by using PDM control methods and obtains high efficiency. In this paper, two PDM control strategies are compared: delta–sigma conversion and the PDM pattern generation method based on space vector modulation (SVM), which is proposed here. Also, the experimental results obtained with the proposed system will be presented and discussed. The total harmonic distortions (THDs) of the output voltage with delta–sigma conversion and the PDM pattern generation method based on SVM are found to be 5.96% and 2.15%, respectively. In addition, the maximum efficiencies with delta–sigma conversion and the PDM control based on SVM are 93.4% and 97.3%, respectively. From the results, the validity of the PDM control based on SVM has been confirmed for improvement of the output waveforms and reduction of the switching loss.
Controlled Synthesis of Phase‐Pure Zeolitic Imidazolate Framework Co‐ZIF‐9
Authors: Öztürk Zafer , Hofmann Jan P. , Lutz Martin , Mazaj Matjaž , Logar Nataša Zabukovec , Weckhuysen Bert M.
Published: February 2015

The synthesis of phase‐pure Co‐ZIF‐9, an important cobalt‐based zeolitic imidazolate framework, could be achieved by modification of the reported synthesis procedure through pH adjustment of the starting synthesis mixture. The phase‐pure Co‐ZIF‐9 material obtained has been characterized by a combination of UV/Vis, FTIR, and Raman spectroscopy as well as by thermogravimetric analysis (TGA) and XRD and possesses a lower overall crystallinity. This can be explained by the addition of the base for the pH adjustment method. On the basis of these findings, a synthesis pathway for the formation of the secondary phase, cobalt formate, is proposed along with its relationship to the flexibility of the coordination environment of cobalt ions. The crystal structures of both phases have been determined by single‐crystal X‐ray crystallography, and the resolved structures also reflect the coordination flexibility of the framework cobalt ions.
Further Insight into Uranium and Thorium Metaphosphate Chemistry and the Effect of Nd3+ Incorporation into Uranium(IV) Metaphosphate
Authors: Yu Na , Klepov Vladislav V. , Neumeier Stefan , Depmeier Wulf , Bosbach Dirk , Suleimanov Evgeny V. , Alekseev Evgeny V.
Published: February 2015

A tetragonal modification of uranium polymetaphosphate U(PO3)4, a mixed U4+/Nd3+ polymetaphosphate “(U0.62Nd0.38)(PO3)4”, and two new tetraphosphates, Th(P4O12) and U(P4O12), were synthesized. The structures of the obtained materials were characterized by X‐ray diffraction and Raman spectroscopy. The presence of Nd in (U0.62Nd0.38)(PO3)4 was proven by energy‐dispersive X‐ray spectroscopy (EDX), and the measured degree of substitution for U agrees well with the X‐ray crystallography results; however, the mechanism of the necessary charge compensation could not be identified. The cation arrangements in the crystal structures of thorium and uranium polymetaphosphates have been studied in terms of Voronoi–Dirichlet polyhedra. Different conformations of the tetraphosphate polyanions were observed in the crystal structures of Th(P4O12) and U(P4O12). The Raman spectrum of a single crystal of Th(P4O12) was recorded, and the bands were assigned.
Three Alkali Metal Lead Orthophosphates – Syntheses, Crystal Structures and Properties of APbPO4 (A = K, Rb, Cs)
Authors: Huang Shengshi , Jing Qun , Han Jian , Pan Shilie , Wu Hongping , Yang Zhihua
Published: February 2015

Three alkali metal lead orthophosphates, APbPO4 (A = K, Rb, Cs), have been synthesized by conventional solid‐state reaction. The single‐crystal X‐ray structural analyses revealed that they crystallize in the same space group, Pnma (No. 62), but they are not all isostructural. APbPO4 (A = K, Rb) are isostructural, and the three‐dimensional (3D) structure of RbPbPO4 (representative) consists of [Pb1|Rb1O4]∞ chains connected with isolated PO4 tetrahedra, the Pb2|Rb2 atoms filling the pore space. The 3D structure of CsPbPO4 consists of another kind of chains, [PbO4]∞, connected with isolated PO4 tetrahedra, and the Cs atoms reside in the channel. Thermal, IR spectroscopy, and UV/Vis/NIR diffuse reflectance spectroscopy analyses have also been performed. In addition, first‐principle theoretical studies were carried out to aid in the understanding of the electronic structures and the projected density of states of CsPbPO4.
Intercalative Ion‐Exchange Route to Amino Acid Layered Double Hydroxide Nanohybrids and Their Sorption Properties
Authors: Choi Goeun , Yang Jae‐Hun , Park Ga‐Young , Vinu Ajayan , Elzatahry Ahmad , Yo Chul Hyun , Choy Jin‐Ho
Published: February 2015

Invited for the cover of this issue is the group of Jin‐Ho Choy at the Department of Chemistry and Nano Science, Ewha Womans University, Republic of Korea. The cover image shows that the present nanohybrid “Pac‐Man” cleans up the earth after an emission of greenhouse gas that threatens to cause global warming.
Influence of genotype on the fatty acids composition of virgin olive oils from advanced selections obtained by crosses between Arbequina, Picual, and Frantoio cultivars along the ripening process
Authors: Sánchez de Medina Verónica , Calderón‐Santiago Mónica , El Riachy Milad , Priego‐Capote Feliciano , Luque de Castro María Dolores
Published: February 2015

The aim of this research was to study the influence of the ripening stage of olive fruits and genotype on the composition of esterified fatty acids (EFAs) and non esterified FAs (NEFAs) in virgin olive oils (VOOs) from advanced selections obtained by crosses between Arbequina, Picual, and Frantoio cultivars. For this purpose, a method based on gas chromatography with flame ionization detection (GC–FID) was used to estimate the percent of each type of FAs. Principal Component Analysis was applied to find clustering of samples attending to the ripening stages. Discrimination was observed for VOOs associated to early and advanced ripening stages according to the concentration of FAs. The contribution of ripening and genotype to explain the variability in the concentration of EFAs and NEFAs was evaluated by ANOVA. Linoleic acid was the FA most influenced by the genotype. The highest genetic variability in FAs composition was observed in the ripening stage in which the fruit color is reddish or light violet, since five EFAs (palmitic, palmitoleic, oleic, linoleic, and linolenic) were significant to explain this effect. Therefore, the interval that lasts this ripening stage is the most appropriate to compare Arbequina, Frantoio, and Picual genotypes in olive breeding programs according to FAs composition.

Practical applications: The composition of fatty acids (FAs) is one of the most critical aspects that affect the quality of VOOs, which has been related to balance of the concentrations of saturated, monounsaturated, and polyunsaturated FAs. The results of this study can be used to improve olive oil quality by olive breeding programs.

() Dark green to yellow or yellowish–green skin (RI 0–1); () yellowish with reddish spots (RI 2); () reddish or light violet to black (RI 3–4).
Enhanced Catalytic Activity for Biodiesel Synthesis using an Acid‐Tolerant Calcium/Magnesium/Aluminum‐Oxide Hybrid with Improved Hydrophobicity and Dispersibility
Authors: Fan Mingming , Han Qiuju , Zhang Pingbo , Jiang Pingping
Published: February 2015

To increase the activity of the CaO catalyst for biodiesel synthesis, CaO–MgO–Al2O3 was prepared by coprecipitation. CaO, CaO–MgO, and CaO–MgO–Al2O3 were investigated with regard to their dispersibility, hydrophobicity, and thermal stability. The additions of MgO and Al2O3 had a beneficial effect on the activity of the resulting CaO–MgO–Al2O3 catalyst, showing a biodiesel yield of 97.7 % because of the improvements in dispersibility and hydrophobicity. CaO–MgO–Al2O3 gave better acid resistance and better reusability, which is important for potential application in biodiesel production.
Thermal degradation and fire performance of plywood treated with expanded vermiculite
Authors: Wang Fei , Gao Zhenzhong , Zheng Min , Sun Jin
Published: February 2015

The new flame‐retardant plywood was manufactured by adding expanded vermiculite (EVMT) in the adhesive and by surface treatment as a flame‐retardant coating. The study discussed the effect of EVMT to the limited oxygen index values of samples. The thermal degradation process of plywood samples has been investigated by thermal analysis. The result showed that EVMT increased all the limited oxygen index values of the treated samples and decreased the thermal activation energy at a high degree of degradation. Scanning electron microscope (FEI, Holland, The Netherlands) images showed that EVMT could form a protective coating, which improved the flame retardancy of plywood. Copyright © 2015 John Wiley & Sons, Ltd.
Effect of stress and peripheral immune activation on astrocyte activation in transgenic bioluminescent Gfap‐luc mice
Authors: Biesmans Steven , Acton Paul D. , Cotto Carlos , Langlois Xavier , Ver Donck Luc , Bouwknecht Jan A. , Aelvoet Sarah‐Ann , Hellings Niels , Meert Theo F. , Nuydens Rony
Published: February 2015

Neuroinflammation and the accompanying activation of glial cells is an important feature of many neurodegenerative conditions. It is known that factors such as peripheral infections and stress can influence immune processes in the brain. However, the effect of these stressors on astrocyte activation in vivo remains elusive. In this study, transgenic Gfap‐luc mice expressing the luciferase gene under the transcriptional control of the glial fibrillary acidic protein promoter were used to quantify the kinetics of in vivo astrocyte activation following immune challenges relevant to clinical inflammation. It was found that astrocytes respond rapidly to peripheral immune activation elicited by either bacterial lipopolysaccharide (LPS) or the viral mimetic polyinosinic:polycytidylic acid (poly(I:C)). By measuring bioluminescence and 18‐kDa translocator protein radioligand binding in the same animal it was observed that LPS induces both astrocyte as well as microglial activation at 6 h post‐administration. Furthermore, the astrocyte response decreased upon repeated systemic LPS injections, indicating development of tolerance to the LPS challenge. Finally, restraining Gfap‐luc mice for 1 h daily on 5 consecutive days did not affect brain bioluminescence, thereby indicating that sub‐chronic stress does not influence astrocyte activation under unchallenged conditions. However, stressed animals showed a reduced response to a subsequent systemic LPS injection, suggesting that the immune system is compromised in these animals. Here, we demonstrate that Gfap‐luc mice can be used to study astrocyte activation in response to stimuli relevant for clinical inflammation and that this approach may provide a more complete characterization of existing and novel models of neuroinflammation. GLIA 2015;63:1126–1137
Downstaging of hepatocellular cancer before liver transplant: Long‐term outcome compared to tumors within Milan criteria
Authors: Yao Francis Y. , Mehta Neil , Flemming Jennifer , Dodge Jennifer , Hameed Bilal , Fix Oren , Hirose Ryutaro , Fidelman Nicholas , Kerlan Robert K. , Roberts John P.
Published: February 2015

We report on the long‐term intention‐to‐treat (ITT) outcome of 118 patients with hepatocellular carcinoma (HCC) undergoing downstaging to within Milan/United Network for Organ Sharing T2 criteria before liver transplantation (LT) since 2002 and compare the results with 488 patients listed for LT with HCC meeting T2 criteria at listing in the same period. The downstaging subgroups include 1 lesion >5 and ≤8 cm (n = 43), 2 or 3 lesions at least one >3 and ≤5 cm with total tumor diameter ≤8 cm (n = 61), or 4‐5 lesions each ≤3 cm with total tumor diameter ≤8 cm (n = 14). In the downstaging group, 64 patients (54.2%) had received LT and 5 (7.5%) developed HCC recurrence. Two of the five patients with HCC recurrence had 4‐5 tumors at presentation. The 1‐ and 2‐year cumulative probabilities for dropout (competing risk) were 24.1% and 34.2% in the downstaging group versus 20.3% and 25.6% in the T2 group (P = 0.04). Kaplan‐Meier's 5‐year post‐transplant survival and recurrence‐free probabilities were 77.8% and 90.8%, respectively, in the downstaging group versus 81% and 88%, respectively, in the T2 group (P = 0.69 and P = 0.66, respectively). The 5‐year ITT survival was 56.1% in the downstaging group versus 63.3% in the T2 group (P = 0.29). Factors predicting dropout in the downstaging group included pretreatment alpha‐fetoprotein ≥1,000 ng/mL (multivariate hazard ratio [HR]: 2.42; P = 0.02) and Child's B versus Child's A cirrhosis (multivariate HR: 2.19; P = 0.04). Conclusion: Successful downstaging of HCC to within T2 criteria was associated with a low rate of HCC recurrence and excellent post‐transplant survival, comparable to those meeting T2 criteria without downstaging. Owing to the small number of patients with 4‐5 tumors, further investigations are needed to confirm the efficacy of downstaging in this subgroup. (Hepatology 2015;61:1968–1977)
Induced pluripotent stem cells model personalized variations in liver disease resulting from α1‐antitrypsin deficiency
Authors: Tafaleng Edgar N. , Chakraborty Souvik , Han Bing , Hale Pamela , Wu Wanquan , Soto‐Gutierrez Alejandro , Feghali‐Bostwick Carol A. , Wilson Andrew A. , Kotton Darrell N. , Nagaya Masaki , Strom Stephen C. , Roy‐Chowdhury Jayanta , Stolz Donna B. , Perlmutter David H. , Fox Ira J.
Published: February 2015

In the classical form of α1‐antitrypsin deficiency (ATD), aberrant intracellular accumulation of misfolded mutant α1‐antitrypsin Z (ATZ) in hepatocytes causes hepatic damage by a gain‐of‐function, “proteotoxic” mechanism. Whereas some ATD patients develop severe liver disease (SLD) that necessitates liver transplantation, others with the same genetic defect completely escape this clinical phenotype. We investigated whether induced pluripotent stem cells (iPSCs) from ATD individuals with or without SLD could model these personalized variations in hepatic disease phenotypes. Patient‐specific iPSCs were generated from ATD patients and a control and differentiated into hepatocyte‐like cells (iHeps) having many characteristics of hepatocytes. Pulse‐chase and endoglycosidase H analysis demonstrate that the iHeps recapitulate the abnormal accumulation and processing of the ATZ molecule, compared to the wild‐type AT molecule. Measurements of the fate of intracellular ATZ show a marked delay in the rate of ATZ degradation in iHeps from SLD patients, compared to those from no liver disease patients. Transmission electron microscopy showed dilated rough endoplasmic reticulum in iHeps from all individuals with ATD, not in controls, but globular inclusions that are partially covered with ribosomes were observed only in iHeps from individuals with SLD. Conclusion: iHeps model the individual disease phenotypes of ATD patients with more rapid degradation of misfolded ATZ and lack of globular inclusions in cells from patients who have escaped liver disease. The results support the concept that “proteostasis” mechanisms, such as intracellular degradation pathways, play a role in observed variations in clinical phenotype and show that iPSCs can potentially be used to facilitate predictions of disease susceptibility for more precise and timely application of therapeutic strategies. (Hepatology 2015;62:147‐157)
Hydrodynamic characteristics of rill flow on steep slopes
Authors: Peng Wenying , Zhang Zhuodong , Zhang Keli
Published: February 2015

Rill erosion is a dominant sediment source on sloping lands. However, the amount of soil loss from rills on steep slopes is vastly more than that on gentle slopes because of differences in rill shape and hydraulic patterns. The aims of this paper are to determine the hydrodynamic characteristics of rills and the friction coefficients in steep slope conditions and to propose modifications of some hydraulic parameters used in soil loss prediction models. A series of inflow experiments was conducted on loess slopes. The results show that the geometric and hydraulic properties of rill on the steep loess slopes, which are characterized by the mean width of cross sections, mean velocity and mean depth of flow, are related to discharge and slope gradient in power functions. However, the related exponents to discharge are 0.26, 0.48 and 0.26, respectively, which are different from the exponents derived in previous studies, which were conducted on gentle slopes. The Manning roughness coefficient ranged from 0.035 to 0.071, with an average of 0.0536, and the Darcy–Weisbach friction coefficients varied from 0.4 to 1.9. The roughness coefficients are closely related to the Reynolds numbers and flow volumes; however, the correlations vary with slope gradient. The roughness coefficients are directly proportional to the Reynolds number and the flow volume on steep slopes, in contrast with the roughness coefficients found on gentle slopes, which decrease as the Reynolds number and flow volume increase. This difference is caused by the interactions among the hydraulics of the flow, the shape of the rills and the sediment concentrations on steep slopes. The results indicate that parameters used in models to predict rill erosion have to be modified according to slope gradient. Copyright © 2015 John Wiley & Sons, Ltd.
Circulating CUDR, LSINCT‐5 and PTENP1 long noncoding RNAs in sera distinguish patients with gastric cancer from healthy controls
Authors: Dong Lei , Qi Peng , Xu Mi‐Die , Ni Shu‐Juan , Huang Dan , Xu Qing‐Hua , Weng Wei‐Wei , Tan Cong , Sheng Wei‐Qi , Zhou Xiao‐Yan , Du Xiang
Published: February 2015

The examination of circulating nucleic acids (CNAs) is an emerging noninvasive diagnostic technique. However, it is unclear if serum long noncoding RNAs (lncRNAs) represent a novel marker to detect gastric cancer (GC). In this study, we measured 39 candidate cancer‐associated lncRNAs by reverse transcription and quantitative polymerase chain reaction (RT‐qPCR) in sera from 110 patients with GC, 106 age‐ and sex‐matched healthy subjects and 15 patients with gastric peptic ulcer, markers were validated and assessed by RT‐qPCR. The correlation of the expression levels of the candidate serum lncRNAs with clinical parameters of GC patients was performed. A three‐lncRNA signature, including CUDR, LSINCT‐5 and PTENP1, was identified that may be potential diagnostic marker for GC. The areas under the receiver operating characteristic (ROC) curve for this serum three‐lncRNA signature were 0.920 and 0.829 for the two sets of serum samples. Moreover, a risk model for the serum three‐lncRNA signature demonstrated that healthy samples can be distinguished from early GC samples. Three‐lncRNA signature in serum was identified as diagnostic marker for GC. This work may facilitate the detection of GC and serve as the basis for further studies of the clinical value of serum lncRNAs in maintaining surveillance and forecasting prognosis.
Chemical Glycosylation by Single Electron Transfer
Authors: Nokami Toshiki , Itoh Toshiyuki , Mong Kwok‐Kong Tony
Published: February 2015

Oligosaccharides play important roles in nature; however, chemical synthesis of oligosaccharides is still difficult and not carried out in a fully automated manner. Among various methods, the activation of glycosyl donors by single electron transfer using electrochemical and photochemical methods has several benefits. In particular, electrochemical oxidation is a powerful method to activate glycosyl donors, including thioglycosides, which are one of the most popular class of glycosyl donors in modern chemical glycosylations. This review article covers the pioneering works of electrochemical glycosylations, other chemical glycosylations achieved by single electron transfer, and our recent approach to the automated solution‐phase synthesis of oligosaccharides based on the electrochemical method.
Tea waste: an effective and economic substrate for oyster mushroom cultivation
Authors: Yang Doudou , Liang Jin , Wang Yunsheng , Sun Feng , Tao Hong , Xu Qiang , Zhang Liang , Zhang Zhengzhu , Ho Chi‐Tang , Wan Xiaochun
Published: February 2015

BACKGROUND

Tea waste is the residue that remains after tea leaves have been extracted by hot water to obtain water‐soluble components. The waste contains a re‐usable energy substrate and nutrients which may pollute the environment if they are not dealt with appropriately. Other agricultural wastes have been widely studied as substrates for cultivating mushrooms. In the present study, we cultivated oyster mushroom using tea waste as substrate. To study the feasibility of re‐using it, tea waste was added to the substrate at different ratios in different experimental groups. Three mushroom strains (39, 71 and YOU) were compared and evaluated. Mycelia growth rate, yield, biological efficiency and growth duration were measured.

RESULTS

Substrates with different tea waste ratios showed different growth and yield performance. The substrate containing 40–60% of tea waste resulted in the highest yield.

CONCLUSION

Tea waste could be used as an effective and economic substrate for oyster mushroom cultivation. This study also provided a useful way of dealing with massive amounts of tea waste. © 2015 Society of Chemical Industry
Racial disparities in laryngeal cancer treatment and outcome: A population‐based analysis of 24,069 patients
Authors: Shin Jacob Y. , Truong Minh T.
Published: February 2015

Objectives

To determine the impact of race on laryngeal preservation strategies and overall survival (OS) for laryngeal squamous cell carcinoma (SCC).

Study Design

Retrospective, national cancer database analysis.

Methods

Data were extracted from the Surveillance, Epidemiology, and End Results database. Chi‐square test, Kaplan‐Meier method, and Cox regression models were employed in SPSS 20.0 (Armonk, NY: IBM Corp.) for data analyses.

Results

A total of 24,069 patients with laryngeal SCC were identified. Of these, 18,166 (75.5%) patients were white, 3,475 (14.4%) were black, 1,608 (6.7%) were Hispanic, and 820 (3.4%) were Asian. Compared with other races, black patients were more likely to be diagnosed at a younger age (P < 0.001), undergo lymph node dissection (P < 0.001), have nodal metastasis (P < 0.001), be with advanced stage disease (P < 0.001), and be unmarried (P < 0.001). Black patients with T1 to T2 and T3 disease were more likely to undergo total laryngectomy as compared with white patients (T1–2: 8.2% vs. 4.3%; P < 0.001; T3: 28.4% vs. 24.3%; P = 0.023). For patients with T4 disease, however, rates of primary radiotherapy among black patients were higher (40.5% vs. 35.7%; P = 0.015).

The 5‐year OS for white, black, Hispanic, and Asian patients were 60.6%, 52.7%, 59.5% and 65.7% (P < 0.001). This significant 5‐year OS difference by race persisted regardless of age, gender, year of diagnosis, primary treatment, nodal status, or tumor grade. On multivariate analysis, race remained an independent prognostic factor for OS.

Conclusions

Race is an independent prognostic factor for OS. Further studies are warranted to evaluate causes for racial disparities and discrepancies in OS and laryngeal preservation strategies.

Level of Evidence

2c. Laryngoscope, 125:1667–1674, 2015
Elliptic Yang–Mills flow theory
Authors: Janner Rémi , Swoboda Jan
Published: February 2015

We lay the foundations of a Morse homology on the space of connections on a principal G‐bundle over a compact manifold Y, based on a newly defined gauge‐invariant functional on . While the critical points of correspond to Yang–Mills connections on P, its L2‐gradient gives rise to a novel system of elliptic equations. This contrasts previous approaches to a study of the Yang–Mills functional via a parabolic gradient flow. We carry out the analytical details of our programme in the case of a compact two‐dimensional base manifold Y. We furthermore discuss its relation to the well‐developed parabolic Morse homology over closed surfaces. Finally, an application of our elliptic theory is given to three‐dimensional product manifolds .
Simulation of fatigue crack growth in welded joints
Authors: Beier H. T. , Schork B. , Bernhard J. , Tchoffo Ngoula D. , Melz T. , Oechsner M. , Vormwald M.
Published: February 2015

This paper gives an overview on recent research results of the Darmstadt group inside a project called integral fracture mechanics based determination of the fatigue strength of weldments (IBESS). Purpose of this project is the fracture mechanics based simulation of Wöhler‐curves (S‐N‐curves) of welded joints. Part of this project is the investigation of initial defects and imperfections of welded joints. Metallographic and fractographic investigations have been done to derive a definition of an initial crack situation. Also investigations of the crack growth of multiple short cracks were performed on the basis of thermographic and fractographic studies. Another part of integral fracture mechanics based determination of the fatigue strength of weldments gives attention to the stability of the residual stress field in a welded joint due to the transient plastic deformation behaviour under cyclic loading. Numerical simulations using Döring's material model have been done to investigate the effect of a cyclic loading on a residual stress field in an uncracked and a cracked situation.
Integration of structural health monitoring sensors with aerospace, composite materials and structures
Authors: Foote P. D.
Published: February 2015

Structural health monitoring (SHM) technology offers potential to enhance or even supplant current structural inspection processes that are performed manually. Sensors that are permanently attached to a structure perform the inspection task rather than the application of an instrument probe or transducer that is manually scanned. Structures made from composite material can include during their manufacture the sensor components necessary for structural health monitoring. In this way, the sensors become an intimate part of the structure and are protected from potentially damaging external environments. To achieve this embedment however a number of challenges need to be faced from manufacturing through to design. This paper explores some of the examples of structural health monitoring technology suitable for embedment, the problems associated with embedment and some examples of how some key challenges have been overcome.
Cerebral Iron Accumulation Is Not a Major Feature of FA2H/SPG35
Authors: Marelli Cecilia , Salih Mustafa A. , Nguyen Karine , Mallaret Martial , Leboucq Nicolas , Hassan Hamdy H. , Drouot Nathalie , Labauge Pierre , Koenig Michel
Published: February 2015

Mutations in the fatty‐acid 2‐hydroxylase (FA2H) gene cause an autosomal recessive spastic paraplegia (SPG35), often associating with cerebellar ataxia; cerebral MRI may show iron accumulation in the basal ganglia, leading to the inclusion of SPG35 among the causes of neurodegeneration with brain iron accumulation. This finding was initially considered strongly relevant for diagnosis, although its frequency is not yet established. We found 5 novel patients (from two families) with mutations in the FA2H gene: none of them showed cerebral iron accumulation (T2‐weighted images performed in all; T2 gradient‐echo in 2); notably, in 1 case, iron accumulation was absent even after 18 years from disease onset on both T2 gradient‐echo and susceptibility‐weight MRI sequences. Cerebral iron accumulation is not a prominent feature in SPG35 and is not always dependent on disease duration; its absence should not discourage from evoking this diagnosis.
A longitudinal study of magnetic resonance spectroscopy Huntington's disease biomarkers
Authors: Sturrock Aaron , Laule Corree , Wyper Katy , Milner Ruth A. , Decolongon Joji , Santos Rachelle Dar , Coleman Allison J. , Carter Kimberley , Creighton Susan , Bechtel Natalie , Bohlen Stefan , Reilmann Ralf , Johnson Hans J. , Hayden Michael R. , Tabrizi Sarah J. , Mackay Alex L. , Leavitt Blair R.
Published: February 2015

Putaminal metabolites examined using cross‐sectional magnetic resonance spectroscopy (MRS) can distinguish pre‐manifest and early Huntington's Disease (HD) individuals from controls. An ideal biomarker, however, will demonstrate longitudinal change over short durations. The objective here was to evaluate longitudinal in vivo brain metabolite profiles in HD over 24 months. Eighty‐four participants (30 controls, 25 pre‐manifest HD, 29 early HD) recruited as part of TRACK‐HD were imaged at baseline, 12 months, and 24 months using 3T MRS of left putamen. Automated putaminal volume measurement was performed simultaneously. To quantify partial volume effects, spectroscopy was performed in a second, white matter voxel adjacent to putamen in six subjects. Subjects underwent TRACK‐HD motor assessment. Statistical analyses included linear regression and one‐way analysis of variance (ANOVA). At all time‐points N‐acetyl aspartate and total N‐acetyl aspartate (NAA), neuronal integrity markers, were lower in early HD than in controls. Total NAA was lower in pre‐manifest HD than in controls, whereas the gliosis marker myo‐inositol (MI) was robustly elevated in early HD. Metabolites were stable over 24 months with no longitudinal change. Total NAA was not markedly different in adjacent white matter than putamen, arguing against partial volume confounding effects in cross‐sectional group differences. Total NAA correlations with disease burden score suggest that this metabolite may be useful in identifying neurochemical responses to therapeutic agents. We demonstrate almost consistent group differences in putaminal metabolites in HD‐affected individuals compared with controls over 24 months. Future work establishing spectroscopy as an HD biomarker should include multi‐site assessments in large, pathologically diverse cohorts. © 2015 International Parkinson and Movement Disorder Society
A 32‐channel combined RF and B0 shim array for 3T brain imaging
Authors: Stockmann Jason P. , Witzel Thomas , Keil Boris , Polimeni Jonathan R. , Mareyam Azma , LaPierre Cristen , Setsompop Kawin , Wald Lawrence L.
Published: February 2015

Purpose

We add user‐controllable direct currents (DC) to the individual elements of a 32‐channel radio‐frequency (RF) receive array to provide B0 shimming ability while preserving the array's reception sensitivity and parallel imaging performance.

Methods

Shim performance using constrained DC current (±2.5A) is simulated for brain arrays ranging from 8 to 128 elements. A 32‐channel 3‐tesla brain array is realized using inductive chokes to bridge the tuning capacitors on each RF loop. The RF and B0 shimming performance is assessed in bench and imaging measurements.

Results

The addition of DC currents to the 32‐channel RF array is achieved with minimal disruption of the RF performance and/or negative side effects such as conductor heating or mechanical torques. The shimming results agree well with simulations and show performance superior to third‐order spherical harmonic (SH) shimming. Imaging tests show the ability to reduce the standard frontal lobe susceptibility‐induced fields and improve echo planar imaging geometric distortion. The simulation of 64‐ and 128‐channel brain arrays suggest that even further shimming improvement is possible (equivalent to up to 6th‐order SH shim coils).

Conclusion

Including user‐controlled shim currents on the loops of a conventional highly parallel brain array coil is feasible with modest current levels and produces improved B0 shimming performance over standard second‐order SH shimming. Magn Reson Med 75:441–451, 2016. © 2015 Wiley Periodicals, Inc.
Whole‐exome DNA sequence analysis of Brca2‐ and Trp53‐deficient mouse mammary gland tumours
Authors: Francis Jeffrey C , Melchor Lorenzo , Campbell James , Kendrick Howard , Wei Wenbin , Armisen‐Garrido Javier , Assiotis Ioannis , Chen Lina , Kozarewa Iwanka , Fenwick Kerry , Swain Amanda , Smalley Matthew J , Lord Christopher J , Ashworth Alan
Published: February 2015

Germline mutations in the tumour suppressor BRCA2 predispose to breast, ovarian and a number of other human cancers. Brca2‐deficient mouse models are used for preclinical studies but the pattern of genomic alterations in these tumours has not yet been described in detail. We have performed whole‐exome DNA sequencing analysis of mouse mammary tumours from Blg–Cre Brca2f/f Trp53f/f animals, a model of BRCA2‐deficient human cancer. We also used the sequencing data to estimate DNA copy number alterations in these tumours and identified a recurrent copy number gain in Met, which has been found amplified in other mouse mammary cancer models. Through a comparative genomic analysis, we identified several mouse Blg–Cre Brca2f/f Trp53f/f mammary tumour somatic mutations in genes that are also mutated in human cancer, but few of these genes have been found frequently mutated in human breast cancer. A more detailed analysis of these somatic mutations revealed a set of genes that are mutated in human BRCA2 mutant breast and ovarian tumours and that are also mutated in mouse Brca2‐null, Trp53‐null mammary tumours. Finally, a DNA deletion surrounded by microhomology signature found in human BRCA1/2‐deficient cancers was not common in the genome of these mouse tumours. Although a useful model, there are some differences in the genomic landscape of tumours arising in Blg–Cre Brca2f/f Trp53f/f mice compared to human BRCA‐mutated breast cancers. Therefore, this needs to be taken into account in the use of this model. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Cardiac conduction effects with olanzapine
Authors: Lam Y. W. Francis
Published: February 2015

Cardiac conduction delays, including prolongation of the electrocardiographic QT interval, are known to occur with both typical and atypical antipsychotics. The following case report describes an elderly patient in whom the occurrence of torsades de pointes, a potentially fatal type of arrhythmia, appeared to be associated with the use of olanzapine in the setting of hypokalemia.
The Joint Work of Connecting Multiple (Re)presentations in Science Classrooms
Authors: JORNET ALFREDO , ROTH WOLFF‐MICHAEL
Published: February 2015

The aim of this study is to advance current understanding of the transactional processes that characterize students’ sense‐making practices when they are confronted with multiple representations of scientific phenomena. Data for the study are derived from a design experiment that involves a technology‐rich, inquiry‐based sequence of activities. We draw on interaction analysis to examine the work by means of which a group of upper secondary school students make sense of a number of different ways in which a physical phenomenon—a phase transition—is presented to them. Our analytical perspective, grounded in a cultural‐historical framework, involves scrutinizing how the different materials emerge and evolve as signifiers for something other than themselves during teacher–student and student–student transactions. This approach allows us to trace the emergence of students’ interpretations of the relations between phenomena and their diverse presentations without committing to any preconceived notion of what these presentations stand for. We describe how students’ bodily and pragmatic actions become reified in conceptual terms and how these relate to lived‐in experiences rather than to formal underlying concepts. Findings are discussed with regard to the central role of body and praxis in research on learning science with multiple representations.