bluuebunny/crossref_metadata_2025 huggingface dataset:
Combined infragravity wave and sea‐swell runup over fringing reefs by super typhoon Haiyan
Authors: Shimozono Takenori , Tajima Yoshimitsu , Kennedy Andrew B. , Nobuoka Hisamichi , Sasaki Jun , Sato Shinji
Published: May 2015

Super typhoon Haiyan struck the Philippines on 8 November 2013, marking one of the strongest typhoons at landfall in recorded history. Extreme storm waves attacked the Pacific coast of Eastern Samar where the violent typhoon first made landfall. Our field survey confirmed that storm overwash heights of 6–14 m above mean sea level were distributed along the southeastern coast and extensive inundation occurred in some coastal villages in spite of natural protection by wide fringing reefs. A wave model based on Boussinesq‐type equations is constructed to simulate wave transformation over shallow fringing reefs and validated against existing laboratory data. Wave propagation and runup on the Eastern Samar coast are then reproduced using offshore boundary conditions based on a wave hindcast. The model results suggest that extreme waves on the shore are characterized as a superposition of the infragravity wave and sea‐swell components. The balance of the two components is strongly affected by the reef width and beach slope through wave breaking, frictional dissipation, reef‐flat resonances, and resonant runup amplification. Therefore, flood characteristics significantly differ from site to site due to a large variation of the two topographic parameters on the hilly coast. Strong coupling of infragravity waves and sea swells produces extreme runup on steep beaches fronted by narrow reefs, whereas the infragravity waves become dominant over wide reefs and they evolve into bores on steep beaches.
Liquid‐Filled Valence Tautomeric Microcapsules: A Solid Material with Solution‐Like Behavior
Authors: Vázquez‐Mera Nuria Alexandra , Roscini Claudio , Hernando Jordi , Ruiz‐Molina Daniel
Published: May 2015

The integration of stimuli‐responsive valence tautomeric (VT) molecular systems into solid materials without compromising their functionality is a major bottleneck for the use of these compounds in high‐added value applications. In this work, an innovative, simple, and universal approach is described to tackle this challenge based on the confinement of the active species into liquid‐filled polymeric capsules. A microstructured solid with optimized solution‐like behavior is obtained in this way, whose VT properties can be rationally tuned upon variation of the encapsulated solvent. Incorporation of the resulting capsules into thin films or other matrices of interest allows successful transfer of valence tautomerism from the liquid phase to solid materials, thus paving the way to the fabrication of functional devices based on spin transition compounds.
Deep Cavitand Self‐Assembled on Au NPs‐MWCNT as Highly Sensitive Benzene Sensing Interface
Authors: Clément Pierrick , Korom Saša , Struzzi Claudia , Parra Enrique J. , Bittencourt Carla , Ballester Pablo , Llobet Eduard
Published: May 2015

The unprecedented sensitivity and partial selectivity of quinoxaline‐walled thioether‐legged deep cavitand functionalized multiwall carbon nanotubes toward traces of benzene vapors are presented. The cavitand is grafted onto gold nanoparticle (Au‐NP) decorated oxygen plasma treated multiwall carbon nanotubes (O‐MWCNT) by a self‐assembled monolayer process affording a product referred to as cav‐Au‐MWCNT. The reported technique is suitable for the mass production of hybrid nanomaterials at low cost. The cav‐Au‐MWCNT resistive gas sensor operates at room temperature and shows an outstanding performance toward traces of benzene vapors. The detection of 2.5 ppb of benzene in dry air is demonstrated with a limit of detection (LOD) near 600 ppt. For the first time, it is shown that a CNT nanomaterial can effectively sense the extremely harmful benzene molecule with higher sensitivity than toluene or o‐xylene at the trace levels. The cavitand is well suited for binding benzene, which, being in close proximity to the MWCNT, affects its density of states (DOS) shifting the Fermi level away from the valence band. The binding of benzene is transduced in a diminution of MWCNT conductance. Furthermore, the inclusion of benzene is fully reversible at room temperature, implying that the sensor can operate at very low power consumption.
Ultrabroadband Metasurface for Efficient Light Trapping and Localization: A Universal Surface‐Enhanced Raman Spectroscopy Substrate for “All” Excitation Wavelengths
Authors: Zhang Nan , Liu Kai , Liu Zhejun , Song Haomin , Zeng Xie , Ji Dengxin , Cheney Alec , Jiang Suhua , Gan Qiaoqiang
Published: May 2015

Most reported surface‐enhanced Raman spectroscopy (SERS) substrates can work for individual excitation wavelengths only. Therefore, different substrates have to be used for different excitation wavelengths, which consumes more biological/chemical materials, substrates, and measurement time. Here, an ultrabroadband super absorbing metasurface that can work as a universal substrate for low cost and high performance SERS sensing is reported. Due to broadband light trapping and localized field enhancement, this structure can work for almost “all” available laser lines from 450 to 1100 nm. This predicted feature is validated by SERS experiment using five different excitation laser lines, obtaining a high enhancement factor of 5.3 × 107 and very good uniformity over large areas.
Kinetic study of reactions of aniline and benzoyl chloride in a microstructured chemical system
Authors: Wang Peijian , Wang Kai , Zhang Jisong , Luo Guangsheng
Published: May 2015

The reaction between aniline and benzoyl chloride is well known for producing high performance polymers and chemicals. But the fast main reaction and reversible consecutive side reaction make process rather complicated and no thorough kinetics study has ever been reported before. A microstructured chemical system, consisting of a micromixer, preheat exchange coiled capillaries, a delay loop, and a microhydrolyzer, was designed to carry out this reaction using N‐methyl‐2‐pyrrolidone as the solvent. A kinetic model was established, and the values of kinetic constants, pre‐exponential factors and activation energies of each reaction as well as their confidence intervals were acquired. With this model each substance concentration vs. residence time were obtained to help understand reaction process and further optimize operating conditions. Compared to earlier reports on this reaction, this microstructured chemical system provides more accurate parameters and can develop a reliable platform for kinetic study of similar chemical reactions. © 2015 American Institute of Chemical Engineers AIChE J, 61: 3804–3811, 2015
The aggressive peripheral T‐cell lymphomas: 2015
Authors: Armitage James O.
Published: May 2015

Background: T‐cell lymphomas make up approximately 10%–15% of lymphoid malignancies. The frequency of these lymphomas varies geographically, with the highest incidence in parts of Asia.

Diagnosis: The diagnosis of aggressive peripheral T‐cell lymphoma (PTCL) is usually made using the World Health Organization classification. The ability of hematopathologists to reproducibly diagnosis aggressive PTCL is lower than that for aggressive B‐cell lymphomas, with a range of 72%–97% for the aggressive PTCLs.

Risk Stratification: Patients with aggressive PTCL are staged using the Ann Arbor Classification. Although somewhat controversial, positron emission tomography scans seem to be useful as they are in aggressive B‐cell lymphomas. The most commonly used prognostic index is the International Prognostic Index. The specific subtype of aggressive PTCL is an important risk factor, with the best survival seen in anaplastic large‐cell lymphoma—particularly young patients with the anaplastic lymphoma kinase positive subtype.

Risk‐Adapted Therapy: Anaplastic large‐cell lymphoma is the only subgroup to have a good response to a CHOP‐like regimen. Angioimmunoblastic T‐cell lymphoma has a prolonged disease‐free survival in only ∼20% of patients, but younger patients who have an autotransplant in remission seem to do better. PTCL‐not otherwise specified is not one disease. Anthracycline‐containing regimens have disappointing results, and a new approach is needed. Natural killer/T‐cell lymphoma localized to the nose and nasal sinuses seems to be best treated with radiotherapy‐containing regimens. Enteropathy‐associated PTCL and hepatosplenic PTCL are rare disorders with a generally poor response to therapy, although selected patients with enteropathy‐associated PTCL seem to benefit from intensive therapy. Am. J. Hematol. 90:666–673, 2015. © 2015 Wiley Periodicals, Inc.
Vagotomy and subsequent risk of Parkinson's disease
Authors: Svensson Elisabeth , Horváth‐Puhó Erzsébet , Thomsen Reimar W. , Djurhuus Jens Christian , Pedersen Lars , Borghammer Per , Sørensen Henrik Toft
Published: May 2015

Objective

Parkinson's disease (PD) may be caused by an enteric neurotropic pathogen entering the brain through the vagal nerve, a process that may take over 20 years. We investigated the risk of PD in patients who underwent vagotomy and hypothesized that truncal vagotomy is associated with a protective effect, whereas superselective vagotomy has a minor effect.

Methods

We constructed cohorts of all patients in Denmark who underwent vagotomy during 1977–1995 and a matched general population cohort by linking Danish registries. We used Cox regression to compute hazard ratios (HRs) for PD and corresponding 95% confidence intervals (CIs), adjusting for potential confounders.

Results

Risk of PD was decreased in patients who underwent truncal (HR = 0.85; 95% CI = 0.56–1.27; follow‐up of >20 years: HR = 0.58; 95% CI: 0.28–1.20) compared to superselective vagotomy. Risk of PD was also decreased after truncal vagotomy when compared to the general population cohort (overall adjusted HR = 0.85; 95% CI: 0.63–1.14; follow‐up >20 years, adjusted HR = 0.53; 95% CI: 0.28–0.99). In patients who underwent superselective vagotomy, risk of PD was similar to the general population (HR = 1.09; 95% CI: 0.84–1.43; follow‐up of >20 years: HR = 1.16; 95% CI: 0.80–1.70). Statistical precision of risk estimates was limited. Results were consistent after external adjustment for unmeasured confounding by smoking.

Interpretation

Full truncal vagotomy is associated with a decreased risk for subsequent PD, suggesting that the vagal nerve may be critically involved in the pathogenesis of PD. Ann Neurol 2015;78:522–529
Abnormal synaptic Ca2+ homeostasis and morphology in cortical neurons of familial hemiplegic migraine type 1 mutant mice
Authors: Eikermann‐Haerter Katharina , Arbel‐Ornath Michal , Yalcin Nilufer , Yu Esther S. , Kuchibhotla Kishore V. , Yuzawa Izumi , Hudry Eloise , Willard Carli R. , Climov Mihail , Keles Fatmagul , Belcher Arianna M. , Sengul Buse , Negro Andrea , Rosen Isaac A. , Arreguin Andrea , Ferrari Michel D. , van den Maagdenberg Arn M. J. M. , Bacskai Brian J. , Ayata Cenk
Published: May 2015

Objective

Migraine is among the most common and debilitating neurological conditions. Familial hemiplegic migraine type 1 (FHM1), a monogenic migraine subtype, is caused by gain‐of‐function of voltage‐gated CaV2.1 calcium channels. FHM1 mice carry human pathogenic mutations in the α1A subunit of CaV2.1 channels and are highly susceptible to cortical spreading depression (CSD), the electrophysiologic event underlying migraine aura. To date, however, the mechanism underlying increased CSD/migraine susceptibility remains unclear.

Methods

We employed in vivo multiphoton microscopy of the genetically encoded Ca2+‐indicator yellow cameleon to investigate synaptic morphology and [Ca2+]i in FHM1 mice. To study CSD‐induced cerebral oligemia, we used in vivo laser speckle flowmetry and multimodal imaging. With electrophysiologic recordings, we investigated the effect of the CaV2.1 gating modifier tert‐butyl dihydroquinone on CSD in vivo.

Results

FHM1 mutations elevate neuronal [Ca2+]i and alter synaptic morphology as a mechanism for enhanced CSD susceptibility that we were able to normalize with a CaV2.1 gating modifier in hyperexcitable FHM1 mice. At the synaptic level, axonal boutons were larger, and dendritic spines were predominantly of the mushroom type, which both provide a structural correlate for enhanced neuronal excitability. Resting neuronal [Ca2+]i was elevated in FHM1, with loss of compartmentalization between synapses and neuronal shafts. The percentage of calcium‐overloaded neurons was increased. Neuronal [Ca2+]i surge during CSD was faster and larger, and post‐CSD oligemia and hemoglobin desaturation were more severe in FHM1 brains.

Interpretation

Our findings provide a mechanism for enhanced CSD susceptibility in hemiplegic migraine. Abnormal synaptic Ca2+ homeostasis and morphology may contribute to chronic neurodegenerative changes as well as enhanced vulnerability to ischemia in migraineurs. Ann Neurol 2015;78:193–210
Rayleigh‐wave Resonance Analysis: a Methodological Test on a Viking Age Pit House
Authors: Wilken Dennis , Wunderlich Tina , Majchczack Bente , Andersen Jasmin , Rabbel Wolfgang
Published: May 2015

Seismic surface‐waves may show amplitude resonances at certain frequencies depending on the thickness and elastic parameters of near‐surface layers. We investigate if resonance frequencies of Rayleigh‐waves, (seismic surface‐waves polarized in the vertical plane) can be used to prospect archaeological remains of small‐scale buildings such as pit houses. Our test site is a newly detected Viking age village on the island of Föhr (north Germany) where we concentrated on one typical pit house. The results from resonance analysis are compared with magnetic data, ground penetrating radar (GPR) and classical seismic refraction measurements. The method of Rayleigh‐wave resonance mapping used in this paper is based on the idea that Rayleigh‐wave oscillations on top of anthropogenic structures will show different resonances than on undisturbed soil. We perform spectral analysis of these oscillations to provide information related to the seismic site response. We process single vertical component recordings and map the change in resonance frequency that can be related to the archaeological objects. The test showed that the pit house can be mapped by Rayleigh‐wave resonance analysis with a horizontal resolution of ~0.6 m. Corresponding computations of the depth of the pit house agree with the results from GPR, magnetic modelling and refraction seismics. A modelling study helped to understand the connection between subsoil shear‐wave velocity model and the signal generated by the pit house. The progress of seismic field measurement is slow compared to GPR and magnetometry. However, since seismic methods are based on elastic subsoil parameters, it can be applied in cases where magnetic contrasts are low or GPR fails because of high electromagnetic wave absorption. Copyright © 2015 John Wiley & Sons, Ltd.
Actual drawing of histological images improves knowledge retention
Authors: Balemans Monique C.M. , Kooloos Jan G.M. , Donders A. Rogier T. , Van der Zee Catharina E.E.M.
Published: May 2015

Medical students have to process a large amount of information during the first years of their study, which has to be retained over long periods of nonuse. Therefore, it would be beneficial when knowledge is gained in a way that promotes long‐term retention. Paper‐and‐pencil drawings for the uptake of form‐function relationships of basic tissues has been a teaching tool for a long time, but now seems to be redundant with virtual microscopy on computer‐screens and printers everywhere. Several studies claimed that, apart from learning from pictures, actual drawing of images significantly improved knowledge retention. However, these studies applied only immediate post‐tests. We investigated the effects of actual drawing of histological images, using randomized cross‐over design and different retention periods. The first part of the study concerned esophageal and tracheal epithelium, with 384 medical and biomedical sciences students randomly assigned to either the drawing or the nondrawing group. For the second part of the study, concerning heart muscle cells, students from the previous drawing group were now assigned to the nondrawing group and vice versa. One, four, and six weeks after the experimental intervention, the students were given a free recall test and a questionnaire or drawing exercise, to determine the amount of knowledge retention. The data from this study showed that knowledge retention was significantly improved in the drawing groups compared with the nondrawing groups, even after four or six weeks. This suggests that actual drawing of histological images can be used as a tool to improve long‐term knowledge retention. Anat Sci Educ. © 2015 American Association of Anatomists.
Binding studies of the anti‐retroviral drug, efavirenz to calf thymus DNA using spectroscopic and voltammetric techniques
Authors: Sadeghi Marzieh , Bayat Maryam , Cheraghi Shekofeh , Yari Khirollah , Heydari Rouhollah , Dehdashtian Sara , Shamsipur Mojtaba
Published: May 2015

Interactions between efavirenz (EFZ) with calf thymus DNA (CT‐DNA) were investigated in vitro under stimulated physiological conditions using multispectroscopic techniques, cyclic voltammetry viscosity measurement, and gel electrophoresis. Methylene blue and acridine orange dyes were used as spectral probes by fluorescence spectroscopy. Hypochromicity was observed in ultra‐violet (UV) absorption band of EFZ. Considerable fluorescence enhancement of EFZ was observed in the presence of increasing amounts of DNA solution and the binding constants (Kf) and corresponding numbers of binding sites (n) were calculated at different temperatures. Thermodynamic parameters including enthalpy change (ΔH) and entropy change (ΔS) were calculated to be –304.78 kJ mol–1 and –924.52 J mol–1 K–1 according to the van ’t Hoff equation, which indicated that reaction is predominantly enthalpically driven. In addition, UV/vis absorption titration of DNA bases confirmed that EFZ interacted with guanine and cytosine preferentially. Gel electrophoresis of DNA with EFZ demonstrated that EFZ also has the ability to cleave supercoiled plasmid DNA. Circular dichroism study showed stabilization of the right‐handed B form of CT‐DNA. All results suggest that EFZ interacts with CT‐DNA via an intercalative mode of binding. Copyright © 2015 John Wiley & Sons, Ltd.
Microtiter plate tests for segregation of bioluminescent bacteria
Authors: Šimkus Remigijus , Meškienė Rita , Ledas Žilvinas , Baronas Romas , Meškys Rolandas
Published: May 2015

It has been recently shown that bioluminescence imaging can be usefully applied to provide new insights into bacterial self‐organization. In this work we employ bioluminescence imaging to record images of nutrient rich liquid cultures of the lux‐gene reporter Escherichia coli in microtiter plate wells. The images show that patterns of inhomogenous bioluminescence form along the three‐phase contact lines. The paper analyzes the dependencies of the average number of luminous aggregates (clouds) on various environmental factors. In particular, our results show that optimal (neutral) pH and high aeration rates determine the highest mean number of clouds, and that spatiotemporal patterns do not form in the pH buffered suspensions. In addition, a sigmoidal (switch‐like) dependence of the number of aggregates on the rate of aeration was observed. The obtained bioluminescence imaging data was interpreted by employing the Keller–Segel–Fisher (KSF) model of chemotaxis and logistic growth, adapted to systems of metabolically flexible (two‐state) bacteria. The modified KSF model successfully simulated the observed switch‐like responses. The results of the microtiter plate tests and their simulations indicate that the segregation of bacteria with different activities proceeds in the three‐phase contact line region. Copyright © 2015 John Wiley & Sons, Ltd.
Blue excitable green emitting Ce3+ doped CaS phosphor for w‐LEDs
Authors: Suresh K. , Poornachandra Rao Nannapaneni V. , Murthy K. V. R.
Published: May 2015

CaS:Ce3+ is an efficient green‐emitting (535 nm) phosphor, excitable with blue light (450–470 nm) and was synthesized via a solid‐state reaction method by heating under a reducing atmosphere. The luminescent properties, photoluminescent (PL) excitation and emission of the phosphor were analyzed by spectrofluorophotometry. The excitation and emission peaks of the CaS:Ce3+ phosphor lay in the visible region, which made them relevant for light‐emitting diode (LED) application for the generation of white light. Judd‐Oflet parameters were calculated and revealed that green light emitted upon blue illumination. The prepared phosphor had strong blue absorption at 470 nm and a broad green emission band range from 490–590 nm with the peak at 537 nm. The characteristics of the CaS:Ce3+ phosphor make it suitable for use as a wavelength tunable green emitting phosphor for three band white LEDs pumped by a blue LED (470 nm). The Commission International de l'Eclairage co‐ordinates were calculated by a spectrophotometric method using the spectral energy distribution (0.304, 0.526) and confirm the green emission. The potential application of this phosphor is as a phosphor‐converted white light‐emitting diode. Copyright © 2015 John Wiley & Sons, Ltd.
Hepatic, gastric and intestinal first‐pass effects of vitexin‐2′′‐O‐rhamnoside in rats by ultra‐high‐performance liquid chromatography
Authors: Gao Yucong , Du Yang , Ying Zheming , Leng Aijing , Zhang Wenjie , Meng Yihan , Li Cuiyu , Xu Liang , Ying Xixiang , Kang Tingguo
Published: May 2015

Previous research in our laboratory found that the absolute bioavailability of vitexin‐2′′‐O‐rhamnoside (VR) was quite low at 4.89%. A rapid and sensitive UHPLC method using hesperidin as an internal standard was therefore developed and validated to investigate the reasons for this by determining VR in rat plasma after administering intravenously, intraportally (5 mg/kg), intraduodenally and intragastrically (40 mg/kg) to the rat model of the hepatic, gastric and intestinal first‐pass effects. As only a high intestinal first‐pass effect of VR was found, that is, there existed a low bioavailability of VR (2.40%), inhibitors of P‐glycoprotein (P‐gp) and cytochrome P450 3A (CYP3A), including verapamil, cyclosporin A and midazolam, and absorption enhancers, including bile salts and borneol, combined with VR, were instilled into duodenum to evaluate the effects on bioavailability of VR. The results demonstrated that area under the concentration–time curve (AUC) values of VR slightly increased after administration of verapamil, cyclosporin A and midazolam, indicating that CYP3A and P‐gp do not play an important role in the first‐pass effect in the intestine. AUC values of VR significantly increased after administering bile salts or borneol, indicating that the low bioavailability of VR was mainly related to its poor absorption in the intestine. Copyright © 2015 John Wiley & Sons, Ltd.
A combination of solid‐phase extraction and dispersive solid‐phase extraction effectively reduces the matrix interference in liquid chromatography–ultraviolet detection during pyraclostrobin analysis in perilla leaves
Authors: Farha Waziha , Rahman Md. Musfiqur , Abd El‐Aty A. M. , Jung Da‐I. , Kabir Md. Humayun , Choi Jeong‐Heui , Kim Sung‐Woo , Jeong Im So , Lee Young‐Jun , Shin Ho‐Chul , Kwon Chan‐Hyeok , Son Young‐Wook , Lee Kang‐Bong , Shim Jae‐Han
Published: May 2015

Perilla leaves contain many interfering substances; thus, it is difficult to protect the analytes during identification and integration. Furthermore, increasing the amount of sample to lower the detection limit worsens the situation. To overcome this problem, we established a new method using a combination of solid‐phase extraction and dispersive solid‐phase extraction to analyze pyraclostrobin in perilla leaves by liquid chromatography with ultraviolet absorbance detection. The target compound was quantitated by external calibration with a good determination coefficient (R2 = 0.997). The method was validated (in triplicate) with three fortification levels, and 79.06– 89.10% of the target compound was recovered with a relative standard deviation <4. The limits of detection and quantification were 0.0033 and 0.01 mg/kg, respectively. The method was successfully applied to field samples collected from two different areas at Gwangju and Muan. The decline in the resiudue concentrations was best ascribed to a first‐order kinetic model with half‐lives of 5.7 and 4.6 days. The variation between the patterns was attributed to humidity. Copyright © 2015 John Wiley & Sons, Ltd.
Inflammation and depression: combined use of selective serotonin reuptake inhibitors and NSAIDs or paracetamol and psychiatric outcomes
Authors: Köhler Ole , Petersen Liselotte , Mors Ole , Gasse Christiane
Published: May 2015

Background

Nonsteroidal anti‐inflammatory drugs (NSAIDs) and paracetamol have been shown to yield the potential of adjunctive antidepressant treatment effects to selective serotonin reuptake inhibitors (SSRIs); however, when investigating treatment effects of concomitant use, simultaneous evaluation of potential adverse events is important. The objective was thus to investigate treatment effectiveness and safety aspects of concomitant SSRI use with NSAIDs or paracetamol.

Methods

Within a 25% random sample of the Danish population, we identified all incident SSRI users between 1997 and 2006 (N = 123,351). Effectiveness and safety measures were compared between periods of SSRI use only and periods of combined SSRI and NSAID or paracetamol use by applying Cox regression.

Results

Among 123,351 SSRI users (follow‐up: 53,697.8 person‐years), 21,666 (17.5%) used NSAIDs and 10,232 (8.3%) paracetamol concomitantly. Concomitant NSAID use increased the risk of any psychiatric contact [Hazard rate ratio (95%‐confidence interval): 1.22 (1.07; 1.38)] and with depression [1.31 (1.11; 1.55)]. Low‐dose acetylsalicylic acid reduced the risk of psychiatric contact in general [0.74 (0.56; 0.98)] and with depression [0.71 (0.50; 1.01)]. Ibuprofen reduced the risk of psychiatric contacts [0.76 (0.60; 0.98)]. Concerning safety, paracetamol was associated with increased mortality [3.18 (2.83; 3.58)], especially cardiovascular [2.51 (1.93; 3.28)]. Diclofenac [1.77 (1.22; 2.55)] and the selective COX‐2 inhibitors [1.75 (1.21; 2.53)] increased mortality risks.

Conclusions

Concomitant use of SSRIs and NSAIDs occurred frequently, and effectiveness and safety outcomes varied across individual NSAIDs. Especially low‐dose acetylsalicylic acid may represent an adjunctive antidepressant treatment option. The increased mortality risk of concomitant use of paracetamol needs further investigation.
Random mutagenesis and selection of organic solvent‐stable haloperoxidase from Streptomyces aureofaciens
Authors: Yamada Ryosuke , Higo Tatsutoshi , Yoshikawa Chisa , China Hideyasu , Yasuda Masahiro , Ogino Hiroyasu
Published: May 2015

Haloperoxidases are useful oxygenases involved in halogenation of a range of water‐insoluble organic compounds and can be used without additional high‐cost cofactors. In particular, organic solvent‐stable haloperoxidases are desirable for enzymatic halogenations in the presence of organic solvents. In this study, we adopted a directed evolution approach by error‐prone polymerase chain reaction to improve the organic solvent‐stability of the homodimeric BPO‐A1 haloperoxidase from Streptomyces aureofaciens. Among 1,000 mutant BPO‐A1 haloperoxidases, an organic solvent‐stable mutant OST48 with P123L and P241A mutations and a high active mutant OST959 with H53Y and G162R mutations were selected. The residual activity of mutant OST48 after incubation in 40% (v/v) 1‐propanol for 1 h was 1.8‐fold higher than that of wild‐type BPO‐A1. In addition, the OST48 mutant showed higher stability in methanol, ethanol, dimethyl sulfoxide, and N,N‐dimethylformamide than wild‐type BPO‐A1 haloperoxidase. Moreover, after incubation at 80°C for 1 h, the residual activity of mutant OST959 was 4.6‐fold higher than that of wild‐type BPO‐A1. Based on the evaluation of single amino acid‐substituted mutant models, stabilization of the hydrophobic core derived from P123L mutation and increased numbers of hydrogen bonds derived from G162R mutation led to higher organic solvent‐stability and thermostability, respectively. © 2015 American Institute of Chemical Engineers Biotechnol. Prog., 31:917–924, 2015
Identifying low‐level sequence variants via next generation sequencing to aid stable CHO cell line screening
Authors: Zhang Sheng , Bartkowiak Lisa , Nabiswa Bernard , Mishra Pratibha , Fann John , Ouellette David , Correia Ivan , Regier Dean , Liu Junjian
Published: May 2015

Developing stable Chinese hamster ovary (CHO) cell lines for biotherapeutics is an irreversible process and therefore, key quality attributes, such as sequence variants, must be closely monitored during cell line development (CLD) to avoid delay in the developmental timeline, and more importantly, to assure product safety and efficacy. Sequence variants, defined as unintended amino acid substitution in recombinant protein primary structure, result from alteration at either the DNA or the protein level. Here, for the first time, we report the application of transcriptome sequencing (RNAseq) in an IgG1 monoclonal antibody (mAb) CLD campaign to detect, identify, and eliminate cell lines containing low‐level point mutations in recombinant coding sequence. Among the top eleven mAb producers chosen from transfectant, clone or subclone stages, three of the cell lines contained either missense or nonsense point mutations at a low level of less than 2%. Subsequent LC/MS/MS characterization detected ∼3% sequence variants with an amino acid change from Ser to Leu at residue 117 in the heavy chain of transfectants 11 and 27. This substitution is consistent with the RNAseq finding of a C/T mutation located at 407 base pair (TCA→TTA) in the heavy chain coding sequence. Here we demonstrate that RNAseq is a rapid and highly sensitive method to identify low‐level genetic mutation de novo corresponding to the amino acid substitution that elicits sequence variant(s). Its implementation in CLD constitutes an early and effective step in identifying desired CHO expression cell lines. © 2015 American Institute of Chemical Engineers Biotechnol. Prog., 31:1077–1085, 2015
Percutaneous closure of patent ductus arteriosus in children using amplatzer duct occluder II: Relationship between PDA type and risk of device protrusion into the descending aorta
Authors: Masri Samer , El Rassi Issam , Arabi Mariam , Tabbakh Anas , Bitar Fadi
Published: May 2015

Objectives

To compare the efficacy and safety of Amplatzer Duct Occluder II (ADOII) among the various patent ductus arteriosus (PDA) types, and to assess the association between development of aortic obstruction and the PDA type in terms of measurable parameters as the device angulation and distance of upper end protrusion into the aortic lumen.

Methods

Retrospective cohort study involving 50 consecutive subjects who underwent ADO II device closure of PDA.

Results

The median age and weight at intervention were 13 months (5.5 months to 18 years) and 11 (6–67) kg respectively. The median smallest ductal diameter by angiography was 3.2 (1.9–5.4) mm. Thirty two patients had type A PDA, 5 had type C, 5 had type D, and 8 had type E. Residual shunt was seen in only 1 patient who had a tubular PDA and resolved within 2 months of the procedure. No device embolization or pulmonary side protrusion were noted. There was a 16% aortic protrusion rate. The median distance of protrusion of the upper end of the device into the aortic lumen was 3.1 (0–9) mm and the median angle formed between the aortic end of the device and the PDA take‐off was 10.4 (0–80.6) degrees. These latter parameters of aortic obstruction were significantly higher in the non‐conical PDA group as compared to the conical PDA. Nevertheless, there was no significant coarctation due to aortic retention disc protrusion.

Conclusion

Device closure of PDA using the ADO II is a safe procedure for chosen types of PDA. We demonstrated a novel technique for objective assessment of device protrusion into the descending aorta based on measurable parameters. ADOII device closure of non‐conical PDAs warrants closer follow ups. © 2015 Wiley Periodicals, Inc.
Balloon valvuloplasty for congenital aortic stenosis: Multi‐center safety and efficacy outcome assessment
Authors: Torres Alejandro , Vincent Julie A. , Everett Allen , Lim Scott , Foerster Susan R. , Marshall Audrey C. , Beekman Robert H. , Murphy Joshua , Trucco Sara M. , Gauvreau Kimberlee , Holzer Ralf , Bergersen Lisa , Porras Diego
Published: May 2015

Objective

To describe contemporary outcomes of balloon aortic valvuloplasty (BAVP) performed in 22 US centers. Background: BAVP constitutes first‐line therapy for congenital aortic stenosis (cAS) in many centers.

Methods

We used prospectively‐collected data from two active, multi‐institutional, pediatric cardiac catheterization registries. Acute procedural success was defined, for purposes of this review, as a residual peak systolic gradient ≤ 35 mm Hg and no more than mild aortic regurgitation (AR) for patients with isolated cAS. For patients with mixed aortic valve disease, a residual peak systolic gradient ≤ 35 mm Hg without worsening of AR was considered successful outcome.

Results

In 373 patients with a median age of 8 months (1 day to 40 years of age) peak systolic gradient had a median of 59 [50, 71] mm Hg pre‐BAVP and 22 [15, 30] mm Hg post‐BAVP (P < 0.001). Procedural success was achieved in 160 patients (71%). The factors independently associated with procedural success were: first time intervention (OR = 2.0 (1.0, 4.0) P = 0.04), not‐prostaglandin dependent, (OR=3.5 (1.5, 8.1); P = 0.003), and isolated cAS (absence of AR) (OR = 2.1 (1.1–3.9); P = 0.03). Twenty percent of patients experienced adverse events, half of which were of high severity. There was no procedural mortality. Neonatal status was the only factor associated with increased risk of high severity adverse events (OR 3.7; 95% CI 1.5–9.0).

Conclusion

In the current era, BAVP results in procedural success (gradient reduction with minimal increase in AR) in 71% of patients treated at US centers where BAVP is considered first‐line therapy relative to surgery. © 2015 Wiley Periodicals, Inc.
Variability in utilization of drug eluting stents in United States: Insights from nationwide inpatient sample
Authors: Panaich Sidakpal S. , Badheka Apurva O. , Arora Shilpkumar , Patel Nileshkumar J. , Thakkar Badal , Patel Nilay , Singh Vikas , Chothani Ankit , Deshmukh Abhishek , Agnihotri Kanishk , Jhamnani Sunny , Lahewala Sopan , Manvar Sohilkumar , Panchal Vinaykumar , Patel Achint , Patel Neil , Bhatt Parth , Savani Chirag , Patel Jay , Savani Ghanshyambhai T. , Solanki Shantanu , Patel Samir , Kaki Amir , Mohamad Tamam , Elder Mahir , Kondur Ashok , Cleman Michael , Forrest John K. , Schreiber Theodore , Grines Cindy
Published: May 2015

Objectives

We studied the trends and predictors of drug eluting stent (DES) utilization from 2006 to 2011 to further expound the inter‐hospital variability in their utilization.

Background

We queried the Healthcare Cost and Utilization Project's Nationwide Inpatient Sample (NIS) between 2006 and 2011 using ICD‐9‐CM procedure code, 36.06 (bare metal stent) or 36.07 (drug eluting stents) for Percutaneous Coronary Intervention (PCI). Annual hospital volume was calculated using unique identification numbers and divided into quartiles for analysis.

Methods and Results

We built a hierarchical two level model adjusted for multiple confounding factors, with hospital ID incorporated as random effects in the model. About 665,804 procedures (weighted n = 3,277,884) were analyzed. Safety concerns arising in 2006 reduced utilization DES from 90% of all PCIs performed in 2006 to a nadir of 69% in 2008 followed by increase (76% of all stents in 2009) and plateau (75% in 2011). Significant between‐hospital variation was noted in DES utilization irrespective of patient or hospital characteristics. Independent patient level predictors of DES were (OR, 95% CI, P‐value) age (0.99, 0.98–0.99, <0.001), female(1.12, 1.09–1.15, <0.001), acute myocardial infarction(0.75, 0.71–0.79, <0.001), shock (0.53, 0.49–0.58, <0.001), Charlson Co‐morbidity index (0.81,0.77–0.86, <0.001), private insurance/HMO (1.27, 1.20–1.34, <0.001), and elective admission (1.16, 1.05–1.29, <0.001). Highest quartile hospital (1.64, 1.25–2.16, <0.001) volume was associated with higher DES placement.

Conclusion

There is significant between‐hospital variation in DES utilization and a higher annual hospital volume is associated with higher utilization rate of DES. © 2015 Wiley Periodicals, Inc.
Influence of pseudo‐resistance on the effect of renal denervation on 24‐hour ambulatory blood pressure levels
Authors: Lambert Thomas , Nahler Alexander , Reiter Christian , Gammer Verena , Blessberger Hermann , Kammler Jürgen , Grund Michael , Saleh Karim , Schwarz Stefan , Steinwender Clemens
Published: May 2015

Background

Renal denervation (RDN) is a promising treatment option in addition to medical antihypertensive treatment in patients suffering from resistant hypertension. Despite the growing interest in RDN, the negative result of the Symplicity HTN‐3 trial led to a debate on the efficacy of RDN.

Methods

We systematically investigated the effects of RDN, evaluated by 24‐hr ambulatory blood pressure measurements (ABPM), in a consecutive series of patients with resistant hypertension, which was defined by a mean office systolic blood pressure (SBP) >160 mm Hg (>150 mm Hg in patients with diabetes). Patients with a mean 24‐hr SBP of less than 130 mm Hg at baseline were classified as pseudo‐resistant, while all other patients were classified as true‐resistant. After six months, we analyzed the response rates in true‐resistant and in pseudo‐resistant patients, respectively, by the means of 24‐hr ABPM. Thereby, patients with a reduction of more than 5 mm Hg in 24‐hr SBP were classified as responders.

Results

RDN was performed in 106 patients. By 24‐hr ABPM, 20 patients (18.9%) were classified as pseudo‐resistant patients. In this cohort, we only found two responders (response rate 10%) six months after RDN. By contrast, in true‐resistant patients, the response rate was almost 60% and the mean BP reduction was −18.6/−9 mm Hg in 24‐hr ABPM.

Conclusions

We found a significant BP reduction in almost 60% of patients with true‐resistant hypertension, but only in 10% in patients with pseudo‐resistant hypertension. According to our results, patient selection seems to be crucial for acceptable response rates after RDN. © 2015 Wiley Periodicals, Inc.
Fluidized‐Bed Chemical Vapor Deposition of Silicon on Very Dense Tungsten Powder
Authors: Vanni Florence , Montaigu Mélanie , Caussat Brigitte , Ablitzer Carine , Iltis Xavière , Brothier Méryl
Published: May 2015

A very dense tungsten powder was coated by silicon from silane using the fluidized‐bed chemical vapor deposition process. A reactor of reduced diameter was developed in order to decrease the weight of powders treated. Results show that the fluidization of this powder is possible in this reactor, but with non‐optimal gas solid contact induced by the high powder density. Important disturbances of the fluidized‐bed temperatures appeared in the presence of silane, due to a partial bed defluidization related to the cohesive nature of the deposit. These disturbances are clearly exacerbated by the exceptional density of the particles. This is probably why a powder agglomeration has been unavoidable when the bed temperature was too low and/or the silane inlet concentration too high. However, a set of operating parameters could be found, allowing a uniform and continuous coating of the whole powder surface.
Process Intensification Tools in the Small‐Scale Pharmaceutical Manufacturing of Small Molecules
Authors: Mitic Aleksandar , Gernaey Krist V.
Published: May 2015

The chemical process industry is paying significant attention to the intensification of processes with the main aim of achieving increased productivity, improved economic status, and enhanced sustainability. The pharmaceutical industry is moving in the same direction and, therefore, dozens of processes are in a state of change. However, it is important to note that not all processes can be intensified easily, such as slow chemical reactions, processes with solids, slurries, and on the like. This review summarizes applications of promising tools for achieving process intensification in the small‐scale pharmaceutical manufacturing of so‐called small molecules. The focus is on microwave radiation, microreactors, ultrasounds, and meso‐scale tubular reactors.
Numerische Berechnung physikalischer Schäumungsprozesse auf unterschiedlichen Größenskalen
Authors: Gruber Florian , Piesche Manfred
Published: May 2015

Eine Simulationsmethode zur numerischen Berechnung physikalischer Schaumbildungsprozesse wird vorgestellt. Ein Mikroskalenmodell ermöglicht die Vorhersage der zeitlichen Änderung des Schaumvolumens, indem der Wachstumsvorgang einer einzelnen Schaumblase in Abhängigkeit der gegebenen Prozessbedingungen beschrieben wird. Zur Darstellung der dreidimensionalen Schaumexpansion auf der Makroskala wird die berechnete Wachstumsdynamik innerhalb eines Simulationsmodells auf Basis der Finite‐Volumen‐Methode eingebunden. Das Berechnungsverfahren wird anhand diskontinuierlicher und kontinuierlicher Schäumversuche validiert.
Patient‐reported outcomes enhance understanding of the impact of pazopanib in soft tissue sarcoma
Authors: Gotay Carolyn
Published: May 2015

The primary conclusion of this study—that increased progression‐free survival is associated with more symptoms but not with compromised global health‐related quality of life (global health status)—has important implications. A more fine‐grained approach is necessary to understand more about why patients rate their global health status as they do and how they interpret and explain their symptom experience.
Randomized clinical control study of locoregional therapy combined with arsenic trioxide for the treatment of hepatocellular carcinoma
Authors: Wang Hui , Liu Ying , Wang Xiu , Liu Donghui , Sun Zhiqiang , Wang Chun , Jin Gang , Zhang Beiguang , Yu Shilong
Published: May 2015

BACKGROUND

The objective of this study was to determine the efficacy and safety of locoregional therapy (LRT) combined with arsenic trioxide (As2O3) treatment in primary hepatocellular carcinoma (HCC) patients.

METHODS

One hundred twenty‐five primary HCC patients were recruited for a randomized controlled study. Patients were randomly divided into group A (n = 61) and group B (n = 64). All patients received transarterial chemoembolization. Group A patients were given As2O3 at 10 mg/d for 4 courses (21 days per course) with a 2‐week interval between courses. Survival times, therapeutic responses, extrahepatic metastases, and adverse events were recorded.

RESULTS

A better therapeutic response was found in group A patients, as shown by higher objective response rate (ORR) and clinical benefit rate (CBR) values in group A versus group B (ORR, 81.96% [95% confidence interval (CI), 72.32%‐91.62%] vs 59.37% [95% CI, 47.34%‐71.41%], χ2 = 7.650, P < .05; CBR, 95.08% [95% CI, 89.66%‐100.00%] vs 81.25% [95% CI, 71.69%‐90.81%], χ2 = 5.659, P < .05). There were fewer patients with extrahepatic metastases in group A versus group B (group A, 6 cases or 9.84% [95% CI, 2.36%‐17.31%]; group B, 12 cases or 18.75% [95% CI, 9.19%‐28.31%]). The survival rate for group A patients was significantly higher than that for group B patients (P < .05). No significant differences were found between the 2 groups in terms of hematology or digestive system, liver, or kidney dysfunction except for facial and limb edema.

CONCLUSIONS

LRT combined with As2O3 treatment prevents extrahepatic metastasis and prolongs the survival time for primary HCC patients. Cancer 2015;121:2917–2925. © 2015 American Cancer Society.
Digital gene expression profiling of a series of cytologically indeterminate thyroid nodules
Authors: Giannini Riccardo , Torregrossa Liborio , Gottardi Stefano , Fregoli Lorenzo , Borrelli Nicla , Savino Mauro , Macerola Elisabetta , Vitti Paolo , Miccoli Paolo , Basolo Fulvio
Published: May 2015

BACKGROUND

Fine‐needle aspiration cytology (FNAC) has been widely accepted as the most crucial step in the preoperative assessment of thyroid nodules. Testing for the expression of specific genes should improve the accuracy of FNAC diagnosis, especially when it is performed in samples with indeterminate cytology.

METHODS

In total, 69 consecutive FNACs that had both cytologic and histologic diagnoses were collected, and expression levels of 34 genes were determined in RNA extracted from FNAC cells by using a custom digital mRNA counting assay. A supervised k‐nearest neighbor (K‐nn) learning approach was used to build a 2‐class prediction model based on a subset of 27 benign and 26 malignant FNAC samples. Then, the K‐nn models were used to classify the 16 indeterminate FNAC samples.

RESULTS

Malignant and benign thyroid nodules had different gene expression profiles. The K‐nn approach was able to correctly classify 10 FNAC samples as benign, whereas only 1 sample was grouped in the malignant class. Two malignant FNAC samples were incorrectly classified as benign, and 3 of 16 samples were unclassified.

CONCLUSIONS

Although the current data will require further confirmation in a larger number of cases, the preliminary results indicate that testing for specific gene expression appears to be useful for distinguishing between benign and malignant lesions. The results from this study indicate that, in indeterminate FNAC samples, testing for cancer‐specific gene expression signatures, together with mutational analyses, could improve diagnostic accuracy for patients with thyroid nodules. Cancer (Cancer Cytopathol) 2015;123:461–70. © 2015 American Cancer Society.
Fractional‐order switching type control law design for adaptive sliding mode technique of 3D fractional‐order nonlinear systems
Authors: Yin Chun , Cheng Yuhua , Zhong Shou‐Ming , Bai Zhanbing
Published: May 2015

In this article, an adaptive sliding mode technique based on a fractional‐order (FO) switching type control law is designed to guarantee robust stability for a class of uncertain three‐dimensional FO nonlinear systems with external disturbance. A novel FO switching type control law is proposed to ensure the existence of the sliding motion in finite time. Appropriate adaptive laws are shown to tackle the uncertainty and external disturbance. The calculation formula of the reaching time is analyzed and computed. The reachability analysis is visualized to show how to obtain a shorter reaching time. A stability criteria of the FO sliding mode dynamics is derived based on indirect approach to Lyapunov stability. Effectiveness of the proposed control scheme is illustrated through numerical simulations. © 2015 Wiley Periodicals, Inc. Complexity 21: 363–373, 2016