bluuebunny/crossref_metadata_2025 huggingface dataset:
Der Koralmtunnel – eine interdisziplinäre Herausforderung
Authors: Harer Gerhard
Published: July 2013

Die Koralmbahn als Teil der internationalen Baltisch‐Adriatischen Achse von Danzig bis Bologna stellt aktuell eine der umfassendsten Bauaufgaben Österreichs dar. Für das Herzstück der Koralmbahn, den 32,9 km langen Koralmtunnel, gilt es auch, Technologien zu revolutionieren und neue einzusetzen – vielfach Themen, die nur durch ein interdisziplinäres Zusammenwirken lösbar sind. Bereits ab den frühen Projektphasen wurden modifizierte Strategien in der Baugrunderkundung entwickelt, Regelausführungen angepasst und wurde besonderes Augenmerk auf die komplexe Bauausführung und Logistik gelegt. Aus Gründen der Verbesserung der Gesamtwirtschaftlichkeit und der Umweltverträglichkeit werden Konzepte, die den Instandhaltungsaufwand verringern oder zur Abfallvermeidung und Ressourcenschonung beitragen, besonders intensiv verfolgt.

The Koralm tunnel – an interdisciplinary challenge

The Koralm railway as a part of the so‐called “Baltic‐Adriatic‐Axis” between Gdánsk and Bologna is currently one of the largest construction works in Austria. The core‐piece of the Koralm railway line is formed by the 32.9 km long Koralm tunnel. For this tunnel it was necessary to revolutionize technologies and to implement new ones. These topics could only be handled in an interdisciplinary interaction. From the early stages of the projects site investigation strategies were adapted, standard design had to be adjusted and special attention was paid to topics in relation with construction sequence and logistics. Due to economically and environmentally favorable effects concepts, which minimize maintenance, refuse and conserve natural resources, were intensively pursued.
Benchmark dose profiles for joint‐action continuous data in quantitative risk assessment
Authors: Deutsch Roland C. , Piegorsch Walter W.
Published: July 2013

Benchmark analysis is a widely used tool in biomedical and environmental risk assessment. Therein, estimation of minimum exposure levels, called benchmark doses (BMDs), that induce a prespecified benchmark response (BMR) is well understood for the case of an adverse response to a single stimulus. For cases where two agents are studied in tandem, however, the benchmark approach is far less developed. This paper demonstrates how the benchmark modeling paradigm can be expanded from the single‐agent setting to joint‐action, two‐agent studies. Focus is on continuous response outcomes. Extending the single‐exposure setting, representations of risk are based on a joint‐action dose–response model involving both agents. Based on such a model, the concept of a benchmark profile—a two‐dimensional analog of the single‐dose BMD at which both agents achieve the specified BMR—is defined for use in quantitative risk characterization and assessment.
Ultra‐performance liquid‐chromatography with tandem mass spectrometry for rapid analysis of pharmacokinetics, biodistribution and excretion of schisandrin after oral administration of Shengmaisan
Authors: Lu Sheng‐wen , Zhang Ai‐hua , Sun Hui , Yan Guang‐li , Han Ying , Wu Xiu‐hong , Wang Xi‐jun
Published: July 2013

This study aimed to investigate the in vivo behaviors of the main components in traditional Chinese medicine (TCM) fomulae. The plasma pharmacokinetics, tissue distribution and excretion of the main component‐schisandrin in rats after oral administration of a classical TCM prescription, shengmaisan (SMS), were studied by a developed and validated UPLC‐MS/MS method. The separation of schisandrin was achieved on a UPLC HSS T3 column with a mobile phase consisting of acetonitrile and water at a flow rate of 0.5 mL/min by linear gradient elution. The MS/MS detection was carried out by monitoring the fragmentation of m/z 415.22 → 384.26 for schisandrin on a triple quadrupole mass spectrometer. The result showed that the method was suitable for the quantification of schisandrin in plasma, tissue and excreta samples with satisfactory selectivity, precision, accuracy, sensitivity, linearity and recovery. Pharmacokinetic results showed a rapid absorption phase with the mean Tmax of 0.17 h and a relatively slow elimination proceeding with a half‐life (T1/2) of 5.24 ± 1.28 h. The tissue distribution showed the maximum concentration distributions of schisandrin after oral administration of SMS were in the order of small intestine > large intestine > lung > liver > kidney > spleen > heart > brain. Only 0.005–0.006% of schisandrin was recovered in feces and was not detected in urine. Copyright © 2013 John Wiley & Sons, Ltd.
Quantification of subcortical gray‐matter vascularization using 7 Tesla time‐of‐flight angiography
Authors: Laurig Mathias , Liu Xinyang , Wyss Michael , Gietl Anton , Jellestad Lena , Nitsch Roger M. , Prüssmann Klaas , Hock Christoph , Unschuld Paul G.
Published: July 2013

Background

The integrity of subcortical brain nuclei is associated with maintenance of regular cognitive performance levels and has been shown to be particularly affected by aging‐related vascular pathology. This study aims to demonstrate applicability of high field strength magnetic resonance angiography at 7 Tesla (7T) for assessment of interindividual variation in subcortical vascularization.

Methods

Two healthy female subjects without known history of cerebrovascular disease or malformation, aged 43 and 86 years, respectively, were administered three‐dimensional (3D) high‐resolution time‐of‐flight (TOF) magnetic resonance angiography at 7T. The FreeSurfer software package was used for automated parcellation and assessment of subcortical volumes. For each volume, mean regional intensities were calculated based on the TOF contrast as a quantitative reflection of regional subcortical gray‐matter vascularization.

Results

While volumes of the subcortical brain region assessed did not differ significantly (30.2 and 27.8 mL, P = 0.78), mean intensities were significantly reduced in the older participant (10%, P = 0.004). Mean intensities could be assessed for each participant for 14 subcortical structures, strongest differences were observable for the left and right Thalamus (T [left, right] = 3.85, 3.82; P [left, right] = 0.002, 0.003).

Conclusions

High‐resolution TOF magnetic resonance angiography may be used in combination with automated volume‐based parcellation to quantify regional subcortical vascularization and to assess interindividual differences. Additional studies are necessary to assess its potential use in clinical trials on cerebrovascular integrity in a context of aging‐related brain change.
Antegrade approach for TAVR with total occlusion of the descending aorta
Authors: Levisay Justin P. , Salinger Michael H. , Feldman Ted
Published: July 2013

The antegrade approach for aortic valve interventions is well known but has not been widely used for transcatheter aortic valve replacement (TAVR) procedures. We encountered a patient with no possibility of retrograde access due to a totally occluded abdominal aorta who had a failed attempt at apical TAVR. We describe antegrade TAVR despite occlusion of the abdominal aorta, with the arterial limb of the requisite veno‐arterial loop created using bilateral arm access, a novel version of the previously described antegrade approach. © 2013 Wiley Periodicals, Inc.
Biosorption of Zinc and Nickel and Its Effect on Growth of Different Spirulina Strains
Authors: Balaji Sundaramoorthy , Kalaivani Thiagarajan , Rajasekaran Chandrasekaran
Published: July 2013

Biosorption of two chosen heavy metals viz. zinc and nickel were tested with selected strains of Spirulina namely S. indica, S. maxima, and S. platensis under laboratory conditions. The selected cyanobacterial strains were cultured in Zarrouk medium treated with zinc and nickel ions at varying concentrations (0.01, 0.05, and 0.1 mM). Biosorption ability of the selected cyanobacterial strains were evaluated in terms of doubling time, chlorophyll content (Chl A, Chl C) and protein content. Data depict that growth was significantly affected by the concentration of selected metals in the culture medium. At a concentration of 0.1 mM, growth of the strains exhibited poor growth due to heavy metal stress. Maximum growth was exhibited by S. maxima at 0.01 mM zinc (6.9 mg/L) and 0.01 mM nickel (17 mg/L). Results indicate that S. maxima can be used as a potential candidate for bioremediation of the major pollutants (zinc and nickel) in the tannery effluent.
Fast Real‐Time NMR Methods for Characterizing Short‐Lived Molecular States
Authors: Rennella Enrico , Brutscher Bernhard
Published: July 2013

The characterization of both the structure and the conformational dynamics of biological macromolecules, namely proteins and nucleic acids, is required for understanding the molecular mechanisms underlying physiological function and disease. Molecular dynamics involves the transient departure from the ground‐state structures to populate short‐lived excited state conformations that can play important functional roles. Real‐time multi‐dimensional NMR spectroscopy represents a unique tool for investigating dynamic molecular processes occurring on time scales of seconds or longer, providing atomic‐resolution information about short‐lived states. In this minireview, we discuss recent progress made in the field of fast real‐time multidimensional NMR. The potential of these new methods is illustrated for several biomolecular systems that have recently been studied by fast real‐time multidimensional NMR.
Work‐Function Modification of Au and Ag Surfaces upon Deposition of Self‐Assembled Monolayers: Influence of the Choice of the Theoretical Approach and the Thiol Decomposition Scheme
Authors: Cornil David , Li Hong , Wood Christopher , Pourtois Geoffrey , Brédas Jean‐Luc , Cornil Jérôme
Published: July 2013

We have characterized theoretically the work‐function modifications of the (111) surfaces of gold and silver upon deposition of self‐assembled monolayers based on methanethiol and trifluoromethanethiol. A comparative analysis is made between the experimental results and those obtained from two widely used approaches based on density functional theory. The contributions to the total work‐function modifications are estimated on the basis of two decomposition schemes of the thiol molecules that have been proposed in the literature. The contributions are found to differ significantly between the two approaches, as do the corresponding adsorption energies.
Siloxane‐Bond Formation Promoted by Lewis Acids: A Nonhydrolytic Sol–Gel Process and the Piers–Rubinsztajn Reaction
Authors: Wakabayashi Ryutaro , Kuroda Kazuyuki
Published: July 2013

Siloxane formation reactions of both the nonhydrolytic sol–gel process and Piers–Rubinsztajn reaction can be integrated as Lewis acid promoted siloxane syntheses without involving silanol groups. The former was developed in the field of inorganic materials chemistry and the latter was initiated in polymer chemistry. We have realized both reactions are quite similar, in terms of 1) the nonhydrolytic reaction, 2) the use of alkoxysilanes, 3) the group‐exchange reactions competing with the siloxane formation, and 4) the proposed reaction mechanisms. This Minireview focuses on the above two reactions. The evolution of both reactions should realize a more sophisticated molecular design of siloxane compounds, which surely contributes to the development of advanced functional materials.
Rev1 is essential in generating G to C transversions downstream of the Ung2 pathway but not the Msh2+Ung2 hybrid pathway
Authors: Krijger Peter HL , Tsaalbi‐Shtylik Anastasia , Wit Niek , van den Berk Paul Cornelius Maria , de Wind Niels , Jacobs Heinz
Published: July 2013

Somatic hypermutation (SHM) and class switch recombination (CSR) of immunoglobulin (Ig) genes are initiated by the enzymatic deamination of cytosine (C) to uracil (U). Uracil‐DNA‐glycosylase (Ung2) converts uracils into apyrimidinic (AP) sites, which is essential for the generation of transversions (TVs) at G/C basepairs during SHM and for efficient DNA break formation during CSR. Besides Ung2, the mismatch repair protein Msh2 and the translesion synthesis (TLS) DNA polymerase (Pol) Rev1 are implicated in SHM and CSR. To further unravel the role of Rev1, we studied WT, Rev1‐deficient, Msh2‐deficient, and Rev1, Msh2 double‐deficient B cells. Loss of Rev1 only slightly reduced CSR. During SHM G/C to C/G TVs are generated in both Ung2‐ and Ung+Msh2‐dependent fashions. We found that Rev1 is essential for the Msh2‐independent generation of these TVs downstream of Ung2‐induced AP sites. In the Ung+Msh2 hybrid pathway, Rev1 is not essential and can be substituted by an alternative TLS Pol, especially when Rev1 is lacking.
Capillary electrophoresis‐mass spectrometry‐based metabolome analysis of serum and saliva from neurodegenerative dementia patients
Authors: Tsuruoka Mayuko , Hara Junko , Hirayama Akiyoshi , Sugimoto Masahiro , Soga Tomoyoshi , Shankle William R. , Tomita Masaru
Published: July 2013

Despite increasing global prevalence, the precise pathogenesis and terms for objective diagnosis of neurodegenerative dementias remain controversial, and comprehensive understanding of the disease remains lacking. Here, we conducted metabolomic analysis of serum and saliva obtained from patients with neurodegenerative dementias (n = 10), including Alzheimer's disease, frontotemporal lobe dementia, and Lewy body disease, as well as from age‐matched healthy controls (n = 9). Using CE‐TOF‐MS, six metabolites in serum (β‐alanine, creatinine, hydroxyproline, glutamine, iso‐citrate, and cytidine) and two in saliva (arginine and tyrosine) were significantly different between dementias and controls. Using multivariate analysis, serum was confirmed as a more efficient biological fluid for diagnosis compared to saliva; additionally, 45 metabolites in total were identified as candidate markers that could discriminate at least one pair of diagnostic groups from the healthy control group. These metabolites possibly provide an objective method for diagnosing dementia‐type by multiphase screening. Moreover, diagnostic‐type‐dependent differences were observed in several tricarboxylic acid cycle compounds detected in serum, indicating that some pathways in glucose metabolism may be altered in dementia patients. This pilot study revealed novel alterations in metabolomic profiles between various neurodegenerative dementias, which would contribute to etiological investigations.
Static coatings for the analysis of intact monoclonal antibody drugs by capillary zone electrophoresis
Authors: Gassner Anne‐Laure , Rudaz Serge , Schappler Julie
Published: July 2013

This work reports on the investigation of the optimal conditions associated with good isoform resolution, minimized adsorption, and acceptable repeatability for the analysis of intact monoclonal antibodies. To this end, various static capillary coatings were evaluated, and major trends were observed. For a positively charged coating, a low EOF mobility value was the main criterion for satisfactory resolution. For neutral coatings, adsorption was the main concern. If the coating does not fully cover the surface silanols, electrostatic interactions tend to decrease protein recovery through irreversible adsorption. The influence of the BGE pH was also investigated, as the resolution of monoclonal antibody isoforms is driven by their charge difference. The nature and concentration of the BGE were proven to be important, as an ampholytic compound such as ε‐aminocaproic acid was found to decrease adsorption compared with ammonium acetate. With the optimal conditions determined during method development, a complete investigation according to four criteria, i.e. migration time, separation efficiency, EOF mobility, and protein recovery, did not present evidence of any adsorption. Finally, the repeatability and intermediate precision were assessed, and low variability was demonstrated with an RSD less than 1.3% for the main peak migration time.
Determination of free amino acids in African gourd seed milks by capillary electrophoresis with light‐emitting diode induced fluorescence and laser‐induced fluorescence detection
Authors: Enzonga Josiane , Ong‐Meang Varravaddheay , Couderc François , Boutonnet Audrey , Poinsot Véréna , Tsieri Michel Mvoula , Silou Thomas , Bouajila Jalloul
Published: July 2013

A CE technique coupled to LIF detection (488 nm) or LED‐induced fluorescence detection (470 nm) has been evaluated to acquire a cheap way to analyze amino acids (AAs) whilst maintaining the best sensitivity. To quantitate AAs in milk of Cucurbitaceae of Sub‐Saharan Africa, they were labeled with FITC. We used an optimized separation buffer composed of 30 mM boric acid buffer adjusted to pH 9.3 with NaOH (1 M) containing 12 mM SDS and 5% ethylene glycol v/v; prior to the injections, the derivatized samples are diluted 100 times. The LOQs in the sample are Arg: 1.1 μM, Ala: 3.5 μM, and Glu 8.9 μM. Cucumeropsis mannii (CM) Naudin and Citrullus lanatus (CL) are vegetable sources rich in proteins and AAs of high quality. Our analyses have led to the identification of 11 AAs in CL and CM milks. Phe, Trp, and Ala are predominant in the two types of lyophilized milks, while Asp and Val demonstrate very low contents. Six essential AAs (Phe, Thr, Val, Trp, Ile, and Leu) are present in both types of extracts, but lysine was not detected, indicating that this AA is missing in gourd milk. These results should be useful in efforts to complement or replace very expensive cow milk or the less‐appreciated soya milk with milk from available local agroressources.
Capillary electrophoresis coupled to evaporative light scattering detection for direct determination of underivatized amino acids: Application to tea samples using carboxyled single‐walled carbon nanotubes for sample preparation
Authors: Bouri Mohamed , Salghi Rachid , Zougagh Mohammed , Ríos Angel
Published: July 2013

An improved and efficient method for the determination of underivatized amino acids based on the use of CE coupled to evaporative light scattering detector (ELSD), involving carbon nanotubes, was successfully developed. Carboxyled single‐walled carbon nanotubes were used for the first time to perform the clean‐up of the analyzed samples, which were afterwards analyzed by CE‐ELSD. White tea samples were used to demonstrate the usefulness of the CE‐ELSD coupled methodology. A suitable interface, based on a triple tube design sprayer, was developed and successfully used for coupling both instruments. Parameters affecting the separation and determination, including the elimination of interferences, were studied and properly optimized. Under the optimized conditions good resolution was achieved for the separation of seven amino acids. The precision of the method, expressed as RSD, was found within the 3.5–5.3% range. The LOD obtained for the proposed method were in the 1.2–2.1 pg range and the LOQ, were in the 2.0–11.5 pg range, with injection pressure of 5 KPa for 20 s (15.3 nL). This method is simple, rapid, and selective compared with other conventional techniques.
Variability of microchip capillary electrophoresis with conductivity detection
Authors: Tantra Ratna , Robinson Kenneth , Sikora Aneta
Published: July 2013

Microfluidic CE with conductivity detection platforms could have an impact on the future development of smaller, faster and portable devices. However, for the purpose of reliable identification and quantification, there is a need to understand the degree of irreproducibility associated with the analytical technique. In this study, a protocol was developed to remove baseline drift problems sometimes observed in such devices. The protocol, which consisted of pre‐conditioning steps prior to analysis, was used to further assess measurement variability from 24 individual microchips fabricated from six separate batches of glass substrate. Results show acceptable RSD percentage for retention time measurements but large variability in their corresponding peak areas (with some microchips having variability of ∼50%). Sources of variability were not related to substrate batch but possibly to a number of factors such as applied voltage fluctuations or variations in microchannel quality, for example surface roughness that will subsequently affect microchannel dimensions.
A joint atmosphere‐ocean inversion for the estimation of seasonal carbon sources and sinks
Authors: Steinkamp K. , Gruber N.
Published: July 2013

We have estimated global surface fluxes of carbon dioxide for the period 1992–1996 using an inverse approach that sequentially considers four constraints: (1) atmospheric CO2, (2) ocean interior DIC (dissolved inorganic carbon) interpreted through an ocean interior inversion and surface ocean pCO2 (partial pressure of CO2), (3) annual prior fluxes for selected land regions, and (4) atmospheric model selection based on vertical transport skill. Estimated fluxes are monthly resolved for each of the 22 Transcom regions over land and ocean. The ocean constraint is particularly valuable, as it does not only add prior information about air‐sea fluxes to the inversion problem but also preserves the regional variance‐covariance structure from the underlying ocean interior inversion. It allows to constrain annual oceanic uptake of 1.8 PgCyr−1 to within 0.2 PgCyr−1, which implies a net annual land uptake of 1.3 (±0.3) PgCyr−1. Furthermore, it leads to a pronounced asymmetry in the seasonal pattern of global land uptake, which was not seen in previous atmosphere‐only inversions. Tropical land is consistently estimated to be a source of carbon, though the source magnitude is reduced as more constraints are applied. With all four constraints, the inversion suggests a net tropical source of 1.1 (±0.9) PgCyr−1, which is comparable to global estimates of deforestation rates in tropical forests and therefore implies an annually balanced tropical land biosphere flux. This balance is not found, however, at the regional level: For the Amazonian region and after accounting for deforestation, we find a biospheric source of 0.6 (±0.5) PgCyr−1. This is at the upper range of estimates from bottom‐up methods, which tend to identify the region as a sink.
Using core complex geometry to constrain fault strength
Authors: Choi Eunseo , Buck W. Roger , Lavier Luc L. , Petersen Kenni Dinesen
Published: July 2013

We present the first model results showing that some core complex detachment faults are strong and that their strength has to be in a narrow range to allow certain extensional structures to develop. The structures we simulate are kilometer‐scale “rider blocks” that are particularly well observed on some oceanic core complexes as well as continental metamorphic core complexes. Previous numerical simulations of lithospheric extension produced the large‐offset, core complex‐forming, normal faults only when the faults were weaker than a given threshold. However, our new, high‐resolution simulations indicate that rider blocks only result when the faults are stronger than a given level. A narrow range of fault weakening, relative to intact surrounding rock, allows for a consecutive series of rider blocks to emerge in a core complex‐like geometry. Our results show that rider blocks develop when the dominant form of weakening is by reduction of fault cohesion while faults that weaken primarily by friction reduction do not form distinct rider blocks.
Ti content in Huguangyan maar lake sediment as a proxy for monsoon‐induced vegetation density in the Holocene
Authors: Shen Ji , Wu Xudong , Zhang Zhaohui , Gong Weiming , He Tong , Xu Xiaomei , Dong Hailiang
Published: July 2013

The provenance of element Ti in Huguangyan maar lake (HGY) sediment has been under debate since Yancheva et al. () proposed its eolian source from the Chinese Loess Plateau (CLP) and applied it as a proxy for Asian winter monsoon. We performed a comprehensive study on Ti‐carrying minerals and Ti fluxes in lake sediments, wall rocks, and loess from the CLP. Here we show that the chemical compositions and morphological features of magnetite, the most important Ti carrier in HGY surface sediments, are identical to those in wall rocks around the lake, but substantially different from those in CLP loess samples. Our calculated modern eolian Ti flux from the CLP is negligible compared to the average total Ti flux to HGY, and Ti flux from catchment erosion can provide enough Ti, indicating Ti in HGY sediment are predominantly from wall rock erosion. Inverse correlation between total organic carbon (TOC) (vegetation density) and Ti/Ca ratio (terrestrial input) in the Holocene suggests monsoon‐induced vegetation density predominates over runoff in controlling Ti input to HGY. S‐ratio represents TOC directly mediated reductive diagenesis of iron oxides (magnetite preservation), rather than anoxic/oxic condition at the bottom water induced by winter monsoon. Our record shows a decreased vegetation density, increased Ti input and weakened reductive diagenesis through the Holocene driven by a weakened summer monsoon.
Impact thermochronology and the age of Haughton impact structure, Canada
Authors: Young Kelsey E. , van Soest Matthijs C. , Hodges Kip V. , Watson E. Bruce , Adams Byron A. , Lee Pascal
Published: July 2013

Most successful efforts to determine the ages of impact events are based on the isotope geochronology of crystalline or glassy impact melts. Studies of impact sites on Earth show that many form without significant melt production, meaning that traditional geochronologic approaches can yield unsatisfying results. We describe here an alternative approach based on theoretical calculations that even brief thermal events related to impact can reset the isotopic systematics of unmelted target rocks. Thermochronometers based on the production of radiogenic 4He in accessory minerals are particularly amenable to complete resetting by impact and should yield robust impact ages if helium systematics are not further disturbed during post‐impact thermal events. We illustrate the utility of this method through a presentation of a new zircon (U‐Th)/He date for the Haughton impact structure, Canada, of 23.5 ± 2.0 Ma.
Sector structure of the interplanetary magnetic field in the nineteenth century
Authors: Vokhmyanin M. V. , Ponyavin D. I.
Published: July 2013

The interplanetary magnetic field (IMF) is the magnetic field of the Sun stretched out by the solar wind. The polarity of the IMF is either positive or negative according to the polarity of the original solar magnetic field. The equivalent ionospheric Disturbance Polar current powered by the azimuthal Y component current system is located at polar latitudes and provides specific geomagnetic variations. It is known that the configuration of this system depends on the polarity of the IMF. Thus, in the absence of direct data in the presatellite era, the IMF sector structure could only be inferred from ground‐based geomagnetic observations (Svalgaard,1968; Mansurov,1969). In this paper the IMF polarities have been reconstructed for the nineteenth century for the first time. It is possible due to the advent of the digitized geomagnetic records in the Helsinki and St. Petersburg observatories. These data have been available since 1844 and 1878, respectively. We assume that the reconstructions are reliable enough to study the solar magnetic field of the past. The polarities inferred for the nineteenth and twentieth centuries display similar sector structures. Seasonal variations of the ratio of positive and negative sectors give clear evidence of solar magnetic field reversals starting from the second half of the nineteenth century.
Human epidermal receptor 2–amplified salivary duct carcinoma: Regression with dual human epidermal receptor 2 inhibition and anti–vascular endothelial growth factor combination treatment
Authors: Falchook Gerald S. , Lippman Scott M. , Bastida Christel C. , Kurzrock Razelle
Published: July 2013

Background

Salivary ductal carcinoma is a rare cancer with poor prognosis and limited treatment options. Human epidermal receptor 2 (HER2)‐directed treatment has been attempted in HER2‐amplified or overexpressed salivary gland malignancies with limited success.

Methods

We report resolution of measurable disease and minimal residual disease in a patient with salivary duct cancer treated with trastuzumab, lapatinib, and bevacizumab, with treatment ongoing for more than 2 years.

Results

This treatment has been tolerated well except for grade 2 diarrhea and mucositis, which required a dose reduction of lapatinib to 1000 mg daily. The response observed was achieved in spite of receiving extensive prior therapy, including trastuzumab and/or chemotherapy for 20 months on which his tumors progressed.

Conclusion

The combination of trastuzumab, lapatinib, and bevacizumab may warrant investigation as a non‐cytotoxic alternative for treatment of HER2‐amplified or overexpressed salivary duct carcinoma and other HER2‐amplified or overexpressed salivary gland tumors, particularly those not responsive to trastuzumab monotherapy. © 2013 Wiley Periodicals, Inc. Head Neck 36: E25–E27, 2014
MicroRNA/gene profiling unveils early molecular changes and nuclear factor erythroid related factor 2 (NRF2) activation in a rat model recapitulating human hepatocellular carcinoma (HCC)
Authors: Petrelli Annalisa , Perra Andrea , Cora Davide , Sulas Pia , Menegon Silvia , Manca Claudia , Migliore Cristina , Kowalik Marta Anna , Ledda-Columbano Giovanna Maria , Giordano Silvia , Columbano Amedeo
Published: July 2013

Studies on gene and/or microRNA (miRNA) dysregulation in the early stages of hepatocarcinogenesis are hampered by the difficulty of diagnosing early lesions in humans. Experimental models recapitulating human hepatocellular carcinoma (HCC) are then used to perform this analysis. We performed miRNA and gene expression profiling to characterize the molecular events involved in the multistep process of hepatocarcinogenesis in the resistant-hepatocyte rat model. A high percentage of dysregulated miRNAs/genes in HCC were similarly altered in early preneoplastic lesions positive for the stem/progenitor cell marker cytokeratin-19, indicating that several HCC-associated alterations occur from the very beginning of the carcinogenic process. Our analysis also identified miRNA/gene-target networks aberrantly activated at the initial stage of hepatocarcinogenesis. Activation of the nuclear factor erythroid related factor 2 (NRF2) pathway and up-regulation of the miR-200 family were among the most prominent changes. The relevance of these alterations in the development of HCC was confirmed by the observation that NRF2 silencing impaired while miR-200a overexpression promoted HCC cell proliferation

in vitro

. Moreover, T3-induced

in vivo

inhibition of the NRF2 pathway accompanied the regression of cytokeratin-19-positive nodules, suggesting that activation of this transcription factor contributes to the onset and progression of preneoplastic lesions towards malignancy. The finding that 78% of genes and 57% of dysregulated miRNAs in rat HCC have been previously associated with human HCC as well underlines the translational value of our results.

Conclusion :

This study indicates that most of the molecular changes found in HCC occur in the very early stages of hepatocarcinogenesis. Among these, the NRF2 pathway plays a relevant role and may represent a new therapeutic target.
Association of severe intrahepatic cholestasis of pregnancy with adverse pregnancy outcomes: A prospective population-based case-control study
Authors: Geenes Victoria , Chappell Lucy C. , Seed Paul T. , Steer Philip J. , Knight Marian , Williamson Catherine
Published: July 2013

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disease, characterized by maternal pruritus and raised serum bile acids. Our objectives were to describe the epidemiology and pregnancy complications associated with severe ICP and to test the hypothesis that adverse perinatal outcomes are increased in these women. A prospective population-based case-control study with national coverage was undertaken using the UK Obstetric Surveillance System (UKOSS). Control data for comparison were obtained from women with healthy pregnancy outcome through UKOSS (n = 2,232), St Mary's Maternity Information System (n = 554,319), and Office for National Statistics (n = 668,195). The main outcome measures investigated were preterm delivery, stillbirth, and neonatal unit admission. In all, 713 confirmed cases of severe ICP were identified, giving an estimated incidence of 9.2 per 10,000 maternities. Women with severe ICP and a singleton pregnancy (n = 669) had increased risks of preterm delivery (164/664; 25% versus 144/2200; 6.5%; adjusted odds ratio [OR] 5.39, 95% confidence interval [CI] 4.17 to 6.98), neonatal unit admission (80/654; 12% versus 123/2192; 5.6%; adjusted OR 2.68, 95% CI 1.97 to 3.65), and stillbirth (10/664; 1.5% versus 11/2205; 0.5%; adjusted OR 2.58, 95% CI 1.03 to 6.49) compared to controls. Seven of 10 stillbirths in ICP cases were associated with coexisting pregnancy complications. These differences remained significant against national data. Risks of preterm delivery, meconium-stained amniotic fluid, and stillbirth rose with increasing maternal serum bile acid concentrations. Conclusion: In the largest prospective cohort study in severe ICP to date, we demonstrate significant increased risks of adverse perinatal outcomes, including stillbirth. Our findings support the case for close antenatal monitoring of pregnancies affected by severe ICP. (HEPATOLOGY 2014;59:1482-1491)
Regulation of FOXO3 by phosphorylation and methylation in hepatitis C virus infection and alcohol exposure
Authors: Tikhanovich Irina , Kuravi Sudhakiranmayi , Campbell Roosevelt V. , Kharbanda Kusum K. , Artigues Antonio , Villar Maria T. , Weinman Steven A.
Published: July 2013

Hepatitis C virus (HCV) infection produces chronic liver injury that is significantly exacerbated by alcohol consumption. While multiple mechanisms contribute to this synergy, a viral-induced loss of antioxidant responses has been shown to play an important role. This study examined the effects of HCV infection and alcohol on the regulation of the transcription factor FOXO3, an important regulator of Mn-superoxide dismutase (SOD2) expression, a tumor suppressor, and a component of the hepatic antioxidant response system. FOXO3 was activated by either HCV or alcohol alone but suppressed by the combination. To understand this paradoxical result, we applied a capillary isoelectric focusing (IEF) method to determine the pattern of FOXO3 posttranslational modifications (PTMs) induced by HCV and alcohol. We observed the presence of multiple different nuclear and cytosolic species of FOXO3 and used antiphosphoserine, acetyl-lysine, methylarginine, and ubiquitin antibodies to identify the PTM patterns present in each species. HCV caused multiple changes including phosphorylation of FOXO3 at S-574, a novel c-Jun N-terminal kinase (JNK) site, which promoted nuclear translocation and transcription. Ethanol suppressed arginine-methylation of FOXO3 promoting nuclear export and degradation of the JNK phosphorylated form. Human liver biopsy samples showed the presence of the HCV-specific form of FOXO3 in HCV-infected livers but not in normal liver or nonalcoholic steatohepatitis.

Conclusion :

The development of this novel IEF method for the simultaneous quantification of differently modified FOXO3 species allowed us to demonstrate how HCV and alcohol combine to modify a complex pattern of FOXO3 PTMs that contribute to pathogenesis. This approach will allow further dissection of the role of protein PTMs in viral liver disease.
Monitoring of tumor response to cisplatin with simultaneous fluorescence and positron emission tomography: a feasibility study
Authors: Liu Fei , Cao Xu , Liu Shuangquan , Zhang Bin , He Wei , Song Jinping , Dai Zhongquan , Zhang Bin , Luo Jianwen , Li Yinghui , Shan Baoci , Bai Jing
Published: July 2013

Dual modality molecular imaging can capture concurrent molecular events and evaluate therapeutic efficacy from uniquely different perspectives based on different molecular targets. In this work, dual modality tomographic imaging, 18F‐fluorodeoxyglucose based positron emission tomography and subsurface fluorescence molecular tomography ([18F]FDG‐PET/subsurface FMT), is proposed to monitor tumor response to cisplatin on a mouse xenograft model in vivo. One mouse was administered with cisplatin (1.0 mg/kg) by intraperitoneal injection once every day for 14 days, and another mouse was administered with saline to serve as the control. Dual modality [18F]FDG‐PET/subsurface FMT imaging was conducted on days 0, 2, 5, 9, 15, and 22. In vivo imaging and quantitative analysis demonstrated the feasibility of [18F]FDG‐PET/subsurface FMT imaging in tracking the changes of [18F]FDG tumor uptake and amount of red fluorescent protein (RFP) synthesized by tumor cells in the same mouse simultaneously. Dual modality [18F]FDG‐PET/subsurface FMT imaging may thus provide a powerful tool for better understanding disease progress and treatment evaluation from different perspectives. (© 2014 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
The Role of Brain Peptides in the Reproduction of Blue Gourami Males (Trichogaster trichopterus)
Authors: Levy Gal , Degani Gad
Published: July 2013

In all vertebrates, reproduction and growth are closely linked and both are controlled by complex hormonal interactions at the brain‐pituitary level. In this study, we focused on the reciprocal interactions between brain peptides that regulate growth and reproductive functions in a teleostei fish (blue gourami Trichogaster trichopterus). An increase in gonadotropin‐releasing hormone 1 (GnRH1) gene expression was detected during ontogeny, and this peptide increased growth hormone (GH) and β follicle‐stimulating hormone (βFSH) gene expression in pituitary cell culture. However, although no change in gonadotropin‐releasing hormone 2 (GnRH2) gene expression during the reproductive cycle or sexual behavior was detected, a stimulatory effect of this peptide on β gonadotropins (βGtH) gene expression was observed. In addition, pituitary adenylate cyclase‐activating polypeptide 38 (PACAP‐38) inhibited GnRH‐analog‐induced βFSH gene expression, and co‐treatment of cells with GnRH‐analog and PACAP‐38 inhibited GnRH‐analog‐stimulatory and PACAP‐38‐inhibitory effects on GH gene expression. These findings together with previous studies were used to create a model summarizing the mechanism of brain peptides (GnRH, PACAP and its related peptide) and the relationship to reproduction and growth through pituitary hormone gene expression during ontogenesis and reproductive stages in blue gourami. J. Exp. Zool. 319A: 461–470, 2013. © 2013 Wiley Periodicals, Inc.
Reduction of the field‐aligned potential drop in the polar cap during large geomagnetic storms
Authors: Kitamura N. , Seki K. , Nishimura Y. , Hori T. , Terada N. , Ono T. , Strangeway R. J.
Published: July 2013

We have studied photoelectron flows and the inferred field‐aligned potential drop in the polar cap during five large geomagnetic storms, which occurred in the periods when the photoelectron observations in the polar cap are available near the apogee of the Fast Auroral SnapshoT satellite (~4000 km) at solar maximum, and the footprint of the satellite paths in the polar cap was under sunlit conditions most of the time. In contrast to the ~20 V potential drop during geomagnetically quiet periods at solar maximum identified by Kitamura et al. (2012), the field‐aligned potential drop frequently became smaller than ~5 V during the main and early recovery phases of the large geomagnetic storms. This result indicates that the acceleration of ions by a field‐aligned potential drop in the polar cap and the lobe region is smaller during the main and early recovery phases of large geomagnetic storms compared to during geomagnetically quiet periods. Since ions with large flux originating from the cusp/cleft ionosphere convect into the polar cap during geomagnetic storms, the net escaping electron number flux should increase to balance the enhanced ion outflows under small field‐aligned current conditions. The magnitude of the field‐aligned potential drop would be reduced to let larger part of photoelectrons escape.
A method for optimizing the cosine response of solar UV diffusers
Authors: Pulli Tomi , Kärhä Petri , Ikonen Erkki
Published: July 2013

Instruments measuring global solar ultraviolet (UV) irradiance at the surface of the Earth need to collect radiation from the entire hemisphere. Entrance optics with angular response as close as possible to the ideal cosine response are necessary to perform these measurements accurately. Typically, the cosine response is obtained using a transmitting diffuser. We have developed an efficient method based on a Monte Carlo algorithm to simulate radiation transport in the solar UV diffuser assembly. The algorithm takes into account propagation, absorption, and scattering of the radiation inside the diffuser material. The effects of the inner sidewalls of the diffuser housing, the shadow ring, and the protective weather dome are also accounted for. The software implementation of the algorithm is highly optimized: a simulation of 109 photons takes approximately 10 to 15 min to complete on a typical high‐end PC. The results of the simulations agree well with the measured angular responses, indicating that the algorithm can be used to guide the diffuser design process. Cost savings can be obtained when simulations are carried out before diffuser fabrication as compared to a purely trial‐and‐error‐based diffuser optimization. The algorithm was used to optimize two types of detectors, one with a planar diffuser and the other with a spherically shaped diffuser. The integrated cosine errors—which indicate the relative measurement error caused by the nonideal angular response under isotropic sky radiance—of these two detectors were calculated to be f2=1.4% and 0.66%, respectively.
Compressed sensing reconstruction for undersampled breath‐hold radial cine imaging with auxiliary free‐breathing data
Authors: Nam Seunghoon , Hong Susie N. , Akçakaya Mehmet , Kwak Yongjun , Goddu Beth , Kissinger Kraig V. , Manning Warren J. , Tarokh Vahid , Nezafat Reza
Published: July 2013

Purpose

To improve compressed sensing (CS) reconstruction of accelerated breath‐hold (BH) radial cine magnetic resonance imaging (MRI) by exploiting auxiliary data acquired between different BHs.

Materials and Methods

Cardiac function is usually assessed using segmented cine acquisitions over multiple BHs to cover the entire left ventricle (LV). Subjects are given a resting period between adjacent BHs, when conventionally no data are acquired and subjects rest in the scanner. In this study the resting periods between BHs were used to acquire additional free‐breathing (FB) data, which are subsequently used to generate a sparsity constraint for each cardiac phase. Images reconstructed using the proposed sparsity constraint were compared with conventional CS using a composite image generated by averaging different cardiac phases. The efficacy of the proposed reconstruction was compared using indices of LV function and blood‐myocardium sharpness.

Results

The proposed method provided accurate LV ejection fraction measurements for 33% and 20% sampled datasets compared with fully sampled reference images, and showed 14% and 11% higher blood‐myocardium border sharpness scores compared to the conventional CS.

Conclusion

The FB data acquired during resting periods can be efficiently used to improve the image quality of the undersampled BH data without increasing the total scan time. J. Magn. Reson. Imaging 2014;39:179–188. © 2013 Wiley Periodicals, Inc.
Influence of a new discrete‐time LQR‐based motion cueing on driving simulator
Authors: Aykent B. , Merienne F. , Paillot D. , Kemeny A.
Published: July 2013

This study proposes a method and an experimental validation to analyze dynamics response of the simulator's cabin and platform with respect to the type of the control used in the hexapod driving simulator. In this article, two different forms of motion platform tracking control are performed as a classical motion cueing algorithm and a discrete‐time linear quadratic regulator (LQR) motion cueing algorithm. For each situation, vehicle dynamics and motion platform level data are registered from the driving simulation software. In addition, the natural frequencies of the roll accelerations are obtained in real‐time by using FFT. The data are denoised by using wavelet 1D transformation. The results show that by using discrete‐time LQR algorithm, the roll acceleration amplitudes that correspond to the natural frequencies and the total roll jerk have decreased at the motion platform level. Also, the natural frequencies have increased reasonably by using the discrete LQR motion cueing (1.5–2.2 Hz) compared with using the classical algorithm (0.4–1.5 Hz) at the motion platform, which is an indicator of motion sickness incidence avoidance. The literature shows that lateral motion (roll, yaw, etc.) in the frequency range of 0.1–0.5 Hz induces motion sickness. Furthermore, using discrete‐time LQR motion cueing algorithm has decreased the sensation error (motion platform–vehicle (cabin) levels) two times in terms of total roll jerk. In conclusion, discrete‐time LQR motion cueing has reduced the simulator sickness more than the classical motion cueing algorithm depending on sensory cue conflict theory. Copyright © 2013 John Wiley & Sons, Ltd.
Effect of quenching rate on the average grain size and martensitic transformation temperature in rapidly solidified polycrystalline Ni50Mn37Sn13 alloy ribbons
Authors: Quintana‐Nedelcos A. , Llamazares J. L. Sánchez , Ríos‐Jara D. , Lara‐Rodríguez A. G. , García‐Fernández T.
Published: July 2013

The present investigation was undertaken to investigate the effect of quenching rate on the microstructure of Ni50Mn50 − xSnx ribbon alloys and its influence on the martensitic starting phase‐transition temperature MS. The study was performed on melt‐spun ribbons of a ferromagnetic shape memory alloy (FSMA) of composition Ni50Mn37Sn13 produced by varying the speed of the rotating copper wheel between 15 and 50 m s−1. The resulting samples have a chemical composition close to the nominal one and at room temperature crystallize in a cubic single‐phase austenite with the highly ordered L21‐type crystal structure without a significant variation in the cell parameter. The average grain size varies between 1.4 and 7.3 µm, while MS increased from 212 to 258 K. Our results suggest that in these materials the average grain size of the parent austenite phase limits the size of the martensite variants, giving rise to its stabilization, while a multivariant transformation mode is maintained.