bluuebunny/crossref_metadata_2025 huggingface dataset:
Multivariate Phenotype Association Analysis by Marker‐Set Kernel Machine Regression
Authors: Maity Arnab , Sullivan Patrick F. , Tzeng Jun‐ing
Published: August 2012

Genetic studies of complex diseases often collect multiple phenotypes relevant to the disorders. As these phenotypes can be correlated and share common genetic mechanisms, jointly analyzing these traits may bring more power to detect genes influencing individual or multiple phenotypes. Given the advancement brought by the multivariate phenotype approaches and the multimarker kernel machine regression, we construct a multivariate regression based on kernel machine to facilitate the joint evaluation of multimarker effects on multiple phenotypes. The kernel machine serves as a powerful dimension‐reduction tool to capture complex effects among markers. The multivariate framework incorporates the potentially correlated multidimensional phenotypic information and accommodates common or different environmental covariates for each trait. We derive the multivariate kernel machine test based on a score‐like statistic, and conduct simulations to evaluate the validity and efficacy of the method. We also study the performance of the commonly adapted strategies for kernel machine analysis on multiple phenotypes, including the multiple univariate kernel machine tests with original phenotypes or with their principal components. Our results suggest that none of these approaches has the uniformly best power, and the optimal test depends on the magnitude of the phenotype correlation and the effect patterns. However, the multivariate test retains to be a reasonable approach when the multiple phenotypes have none or mild correlations, and gives the best power once the correlation becomes stronger or when there exist genes that affect more than one phenotype. We illustrate the utility of the multivariate kernel machine method through the Clinical Antipsychotic Trails of Intervention Effectiveness antibody study.
Determination of reliability criteria for liver stiffness evaluation by transient elastography
Authors: Boursier Jérôme , Zarski Jean-Pierre , de Ledinghen Victor , Rousselet Marie-Christine , Sturm Nathalie , Lebail Brigitte , Fouchard-Hubert Isabelle , Gallois Yves , Oberti Frédéric , Bertrais Sandrine , Calès Paul
Published: August 2012

Liver stiffness evaluation (LSE) is usually considered as reliable when it fulfills all the following criteria: ≥10 valid measurements, ≥60% success rate, and interquartile range / median ratio (IQR/M) ≤0.30. However, such reliable LSE have never been shown to be more accurate than unreliable LSE. Thus, we aimed to evaluate the relevance of the usual definition for LSE reliability, and to improve reliability by using diagnostic accuracy as a primary outcome in a large population. 1,165 patients with chronic liver disease from 19 French centers were included. All patients had liver biopsy and LSE. 75.7% of LSE were reliable according to the usual definition. However, these reliable LSE were not significantly more accurate than unreliable LSE with, respectively: 85.8% versus 81.5% well-classified patients for the diagnosis of cirrhosis (

P

= 0.082). In multivariate analyses with different diagnostic targets, LSE median and IQR/M were independent predictors of fibrosis staging, with no significant influence of ≥10 valid measurements or LSE success rate. These two reliability criteria determined three LSE groups: “very reliable” (IQR/M ≤0.10), “reliable” (0.10< IQR/M ≤0.30, or IQR/M >0.30 with LSE median <7.1 kPa), and “poorly reliable” (IQR/M >0.30 with LSE median ≥7.1 kPa). The rates of well-classified patients for the diagnosis of cirrhosis were, respectively: 90.4%, 85.8%, and 69.5% (

P

< 10−3). According to these new reliability criteria, 9.1% of LSE were poorly reliable (versus 24.3% unreliable LSE with the usual definition,

P

< 10−3), 74.3% were reliable, and 16.6% were very reliable.

Conclusion
: The usual definition for LSE reliability is not relevant. LSE reliability depends on IQR/M according to liver stiffness median level, defining thus three reliability categories: very reliable, reliable, and poorly reliable LSE. (Hepatology 2013)
Sex bias occurrence of hepatocellular carcinoma in Poly7 molecular subclass is associated with EGFR
Authors: Keng Vincent W. , Sia Daniela , Sarver Aaron L. , Tschida Barbara R. , Fan Danhua , Alsinet Clara , Solé Manel , Lee Wai L. , Kuka Timothy P. , Moriarity Branden S. , Villanueva Augusto , Dupuy Adam J. , Riordan Jesse D. , Bell Jason B. , Silverstein Kevin A.T. , Llovet Josep M. , Largaespada David A.
Published: August 2012

Hepatocellular carcinoma (HCC) is one of the deadliest solid cancers and is the third leading cause of cancer-related death. There is a universal estimated male/female ratio of 2.5, but the reason for this is not well understood. The Sleeping Beauty (SB) transposon system was used to elucidate candidate oncogenic drivers of HCC in a forward genetics screening approach. Sex bias occurrence was conserved in our model, with male experimental mice developing liver tumors at reduced latency and higher tumor penetrance. In parallel, we explored sex differences regarding genomic aberrations in 235 HCC patients. Liver cancer candidate genes were identified from both sexes and genotypes. Interestingly, transposon insertions in the epidermal growth factor receptor (Egfr) gene were common in SB-induced liver tumors from male mice (10/10, 100%) but infrequent in female mice (2/9, 22%). Human single-nucleotide polymorphism data confirmed that polysomy of chromosome 7, locus of EGFR, was more frequent in males (26/62, 41%) than females (2/27, 7%) (P = 0.001). Gene expression–based Poly7 subclass patients were predominantly male (9/9) compared with 67% males (55/82) in other HCC subclasses (P = 0.02), and this subclass was accompanied by EGFR overexpression (P < 0.001). Conclusion: Sex bias occurrence of HCC associated with EGFR was confirmed in experimental animals using the SB transposon system in a reverse genetic approach. This study provides evidence for the role of EGFR in sex bias occurrences of liver cancer and as the driver mutational gene in the Poly7 molecular subclass of human HCC. (Hepatology 2013)
Directly acting drugs prostacyclin or nitroglycerine and endothelin receptor blocker bosentan improve cell engraftment in rodent liver
Authors: Bahde Ralf , Kapoor Sorabh , Bandi Sriram , Bhargava Kuldeep K. , Palestro Christopher J. , Gupta Sanjeev
Published: August 2012

To optimize strategies for liver-directed cell therapy, prevention of initial transplanted cell losses is particularly important for subsequent liver repopulation. After cell transplantation in hepatic sinusoids, perturbations in hepatic microcirculation along with changes in various liver cell types are among the earliest changes. Therefore, for advancing further concepts in cell engraftment we studied vascular and related events in the liver after transplanting syngeneic hepatocytes into dipeptidyl peptidase IV-deficient rats. We treated rats with vascular drugs to define whether deleterious cell transplantation-induced events could be controlled followed by improvements in transplanted cell engraftment and proliferation. We found cell transplantation altered liver gene expression related to vessel tone, inflammation, cell adhesion, thrombosis, or tissue damage/remodeling. This was due to hepatic ischemia, endothelial injury, and activation of neutrophils, Kupffer cells, and hepatic stellate cells. Treatment of rats before cell transplantation with the angiotensin converting enzyme blocker, lisinopril, or angiotensin II receptor blocker, losartan, did not improve cell engraftment. By contrast, direct-acting nitroglycerine or prostacyclin improved cell engraftment and also kinetics of liver repopulation. These drugs lowered hepatic ischemia and inflammation, whereas pretreatment of rats with the dual endothelin-1 receptor blocker, bosentan, improved cell engraftment independently of hepatic ischemia or inflammation, without improving liver repopulation. However, incubation of hepatocytes with bosentan protected cells from cytokine toxicity in vitro and produced superior cell engraftment and proliferation in vivo. Conclusion: Cell transplantation-induced changes in hepatic microcirculation contributed to transplanted cell clearances from liver. Vascular drugs, such as nitroglycerine, prostacyclin, and bosentan, offer opportunities for improving cell therapy results through superior cell engraftment and liver repopulation. Ongoing clinical use of these drugs will permit rapid translation of the findings in people. (Hepatology 2013)
Promotion of liver regeneration by natural killer cells in a murine model is dependent on extracellular adenosine triphosphate phosphohydrolysis
Authors: Graubardt Nadine , Fahrner René , Trochsler Markus , Keogh Adrian , Breu Karin , Furer Cynthia , Stroka Deborah , Robson Simon C. , Slack Emma , Candinas Daniel , Beldi Guido
Published: August 2012

Nucleotides, such as adenosine triphosphate (ATP), are released by cellular injury, bind to purinergic receptors expressed on hepatic parenchymal and nonparenchymal cells, and modulate cellular crosstalk. Liver resection and resulting cellular stress initiate such purinergic signaling responses between hepatocytes and innate immune cells, which regulate and ultimately drive liver regeneration. We studied a murine model of partial hepatectomy using immunodeficient mice to determine the effects of natural killer (NK) cell-mediated purinergic signaling on liver regeneration. We noted first that liver NK cells undergo phenotypic changes post-partial hepatectomy (PH)

in vivo

, including increased cytotoxicity and more immature phenotype manifested by alterations in the expression of CD107a, CD27, CD11b, and CD16. Hepatocellular proliferation is significantly decreased in Rag2/common gamma-null mice (lacking T, B, and NK cells) when compared to wildtype and Rag1-null mice (lacking T and B cells but retaining NK cells). Extracellular ATP levels are elevated post-PH and NK cell cytotoxicity is substantively increased

in vivo

in response to hydrolysis of extracellular ATP levels by apyrase (soluble NTPDase). Moreover, liver regeneration is significantly increased by the scavenging of extracellular ATP in wildtype mice and in Rag2/common gamma-null mice after adoptive transfer of NK cells. Blockade of NKG2D-dependent interactions significantly decreased hepatocellular proliferation.

In vitro

, NK cell cytotoxicity is inhibited by extracellular ATP in a manner dependent on P2Y1, P2Y2, and P2X3 receptor activation.

Conclusion :

We propose that hepatic NK cells are activated and cytotoxic post-PH and support hepatocellular proliferation. NK cell cytotoxicity is, however, attenuated by hepatic release of extracellular ATP by way of the activation of specific P2 receptors. Clearance of extracellular ATP elevates NK cell cytotoxicity and boosts liver regeneration.
Genetic and functional identification of the likely causative variant for cholesterol gallstone disease at the ABCG5/8 lithogenic locus
Authors: von Kampen Oliver , Buch Stephan , Nothnagel Michael , Azocar Lorena , Molina Hector , Brosch Mario , Erhart Wiebke , von Schönfels Witigo , Egberts Jan , Seeger Marcus , Arlt Alexander , Balschun Tobias , Franke Andre , Lerch Markus M. , Mayerle Julia , Kratzer Wolfgang , Boehm Bernhard O. , Huse Klaus , Schniewind Bodo , Tiemann Katharina , Jiang Zhao-Yan , Han Tian-Quan , Mittal Balraj , Srivastava Anshika , Fenger Mogens , Jφrgensen Torben , Schirin-Sokhan Ramin , Tönjes Anke , Wittenburg Henning , Stumvoll Michael , Kalthoff Holger , Lammert Frank , Tepel Jürgen , Puschel Klaus , Becker Thomas , Schreiber Stefan , Platzer Matthias , Völzke Henry , Krawczak Michael , Miquel Juan Francisco , Schafmayer Clemens , Hampe Jochen
Published: August 2012

The sterolin locus (

ABCG5/ABCG8

) confers susceptibility for cholesterol gallstone disease in humans. Both the responsible variant and the molecular mechanism causing an increased incidence of gallstones in these patients have as yet not been identified. Genetic mapping utilized patient samples from Germany (2,808 cases, 2,089 controls), Chile (680 cases, 442 controls), Denmark (366 cases, 766 controls), India (247 cases, 224 controls), and China (280 cases, 244 controls). Analysis of allelic imbalance in complementary DNA (cDNA) samples from human liver (n = 22) was performed using pyrosequencing. Transiently transfected HEK293 cells were used for [3H]-cholesterol export assays, analysis of protein expression, and localization of allelic constructs. Through fine mapping in German and Chilean samples, an ˜250 kB disease-associated interval could be defined for this locus. Lack of allelic imbalance or allelic splicing of the

ABCG5

and

ABCG8

transcripts in human liver limited the search to coding single nucleotide polymorphisms. Subsequent mutation detection and genotyping yielded two disease-associated variants: ABCG5-R50C (

P

= 4.94 × 10−9) and ABCG8-D19H (

P

= 1.74 × 10−10) in high pairwise linkage disequilibrium (

r

2 = 0.95). [3H]-cholesterol export assays of allelic constructs harboring these genetic candidate variants demonstrated increased transport activity (3.2-fold,

P

= 0.003) only for the ABCG8-19H variant, which was also superior in nested logistic regression models in German (

P

= 0.018), Chilean (

P

= 0.030), and Chinese (

P

= 0.040) patient samples.

Conclusion

: This variant thus provides a molecular basis for biliary cholesterol hypersecretion as the mechanism for cholesterol gallstone formation, thereby drawing a link between “postgenomic” and “pregenomic” pathophysiological knowledge about this common complex disorder.
Ethanol facilitates hepatitis C virus replication via up-regulation of GW182 and heat shock protein 90 in human hepatoma cells
Authors: Bukong Terence N. , Hou Wei , Kodys Karen , Szabo Gyongyi
Published: August 2012

Alcohol use and hepatitis C virus (HCV) infection synergize to cause liver damage, and microRNA-122 (miR-122) appears to play a key role in this process. Argonaute 2 (Ago2), a key component of the RNA-induced silencing complex (RISC), has been shown to be important in modulating miR-122 function during HCV infection. However, GW182, a critical component of processing bodies (GW bodies) that is recruited by Ago2 to target messenger RNA (mRNA), has not been assessed in HCV infection. To characterize the role of GW182 in the pathogenesis of HCV infection, we determined its transcription and protein expression in an HCV J6/JFH1 culture system. Transcript and protein levels of GW182 as well as HCV RNA and protein expression increased with alcohol exposure. Specific silencing of mRNA expression by small interfering RNA against GW182 significantly decreased HCV RNA and protein expression. Overexpression of GW182 significantly increased HCV RNA and protein expression in HCV J6/JFH1 infected Huh7.5 cells. Furthermore, GW182 colocalized and coimmunoprecipitated with heat shock protein 90 (HSP90), which increased upon alcohol exposure with and without HCV infection and enhanced HCV gene expression. The use of an HSP90 inhibitor or knockdown of HSP90 decreased GW182 and miR-122 expression and significantly reduced HCV replication. Conclusion: Overall, our results suggest that GW182 protein that is linked to miR-122 biogenesis and HSP90, which has been shown to stabilize the RISC, are novel host proteins that regulate HCV infection during alcohol abuse. (Hepatology 2013)
Distribution of Cyprideis torosa (Ostracoda) in Quaternary Athalassic Sediments in Germany and its Application for Palaeoecological Reconstructions
Authors: Pint Anna , Frenzel Peter , Fuhrmann Roland , Scharf Burkhard , Wennrich Volker
Published: August 2012

Cyprideis torosa (Jones, 1850) is a very common brackish water ostracod of the German coasts, but, despite empty valves are found occasionally in surface sediments of some modern inland waters, C. torosa could not be found living in modern athalassic waters of Germany so far. During interglacial periods, including the Holocene, however, fossils of this species are quite common in Central Germany, at a distance of more than 300 km away from the coasts of the Baltic and North Seas. All 31 Quaternary localities with C. torosa known so far from Germany are documented. C. torosa is an indicator for brackish waters and widely used as index‐fossil in palaeosalinity reconstructions relying on water chemistry bound morphological changes (nodes, sieve‐pores). The comparisons imply a general underestimation of palaeosalinity in oligo‐ to mesohaline athalassic waters if using nodes and sieve‐pores of C. torosa as proxy. A water chemistry (ionic composition) driven morphological response is assumed instead one by salinity only. Palaeosalinity estimations for athalassic waters, relying on morphological variability alone, should therefore be used with caution. Palaeosalinity trends, however, can be detected. Distinguishing thalassic and athalassic sediments with C. torosa is possible by using the associated ostracod fauna as a discriminator. Regarding the ecology and distribution of C. torosa, permanent, brackish, and shallow water bodies under relatively warm conditions are required for its settlement. The source of the salt are brines originating from Zechsteinian or Triassic underground evaporites. Warm and relatively dry climates could enhance the process for such water bodies of becoming salty, a situation present in Holocene Central Germany. The occurrence of C. torosa can therefore be used for palaeoclimatological studies. The most probable migration path of this ostracod species to athalassic waters is by avian transport. (© 2012 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Late Glacial and Holocene Ostracoda of the Gulf of Gdańsk, the Baltic Sea, Poland
Authors: Krzyminska Jarmila , Namiotko Tadeusz
Published: August 2012

To trace environmental changes in water hydrology and salinity in the Late Glacial to Holocene of the Gulf of Gdańsk, a south‐eastern bay of the Baltic Sea within the maritime zone of Poland, the distribution of ostracod valves was studied in 20 sediment cores collected from both the shallow‐ and deep‐water zones (depth 10.9–67.5 m). The studied sediment sequences yielded ca. 3000 valves of 21 ostracod species, of which only five are known to live today in the Gulf, which has a present maximum depth of 118 m and water salinity up to 7–8‰. The majority of the studied sediment layers that contained ostracod valves corresponded to the period of the Late Glacial to Mid‐Holocene and was dominated by non‐marine species, of which the most common were Candona neglecta (present in 17 cores), Cytherissa lacustris (15 cores) and Candona candida (14 cores). By clustering classification five major ostracod assemblage types were recognised in the studied cores. Initial assemblage types dominated mostly by inhabitants of the profundal/sub‐littoral zones of modern oligo‐mesotrophic lakes (C. lacustris and C. neglecta) in some sediment sequences were replaced in stratigraphical order by the assemblages dominated by brackish‐water species (Cyprideis torosa or Cytheromorpha fuscata). The structure and species composition of the distinguished ostracod assemblage types as well as their successional transitions indicate that the studied sediments were deposited initially in the Late Glacial in freshwater lacustrine conditions, and subsequently, during the Holocene marine transgression, covered by marine sands. The present results confirm and consolidate inferences based on previously published data on ostracods from the western part of the Gulf of Gdańsk as well as on other biotic (molluscs, diatoms) and abiotic (seismoacoustic) indices from this area (© 2012 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Correlation of temperature rise and optical coherence tomography characteristics in patient retinal photocoagulation
Authors: Koinzer Stefan , Schlott Kerstin , Portz Lea , Ptaszynski Lars , Baade Alexander , Bever Marco , Saeger Mark , Caliebe Amke , Denner Renè , Birngruber Reginald , Brinkmann Ralf , Roider Johann
Published: August 2012

We conducted a study to correlate the retinal temperature rise during photocoagulation to the afterward detected tissue effect in optical coherence tomography (OCT). 504 photocoagulation lesions were examined in 20 patients. The retinal temperature increase was determined in real‐time during treatment based on thermoelastic tissue expansion which was probed by repetitively applied ns laser pulses. The tissue effect was examined on fundus images and OCT images of individualized lesions. We discerned seven characteristic morphological OCT lesion classes. Their validity was confirmed by increasing visibility and diameters. Mean peak temperatures at the end of irradiation ranged from approx. 60 °C to beyond 100 °C, depending on burn intensity. (© 2012 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Synthesis of Some Novel Pyrazole‐Substituted 9‐Anilinoacridine Derivatives and Evaluation for their Antioxidant and Cytotoxic Activities
Authors: Kalirajan R. , Muralidharan V. , Jubie S. , Gowramma B. , Gomathy S. , Sankar S. , Elango K.
Published: August 2012

This article focuses on the synthesis of new series of pyrazole‐substituted 9‐anilinoacridine derivatives 5a–m and 6a–l. The compounds were confirmed by physical and analytical data. The synthesized compounds when screened for in vitro antioxidant activity showed promising activity for many compounds. The selected compounds were screened for cytotoxic activity showed promising inhibition of HEp‐2 cell line for the compounds 6c, 6e, and 6f.
Polycyclic N‐Heterocyclic Compounds, Part 72: Reaction of N‐([1]Benzofuro (or Benzothieno)[3,2‐d]pyrimidin‐4‐yl)formamidine and N‐(Pyrido[2,3‐d]pyrimidin‐4‐yl)formamidine Derivatives with Hydroxylamine Hydrochloride
Authors: Okuda Kensuke , Tsuchie Kiyoko , Hirota Takashi
Published: August 2012

The reactions of N‐([1]benzofuro[3,2‐d]pyrimidin‐4‐yl)formamidines with hydroxylamine hydrochloride gave rearranged cyclization products via ring cleavage of the pyrimidine component accompanied by a ring closure of the 1,2,4‐oxadiazole to give N‐[2‐([1,2,4]oxadiazol‐5‐yl)[1]benzofuran‐3‐yl)formamide oximes. N‐([1]Benzothieno[3,2‐d]pyrimidin‐4‐yl)formamidines and N‐(pyrido[2,3‐d]pyrimidin‐4‐yl)formamidines with hydroxylamine hydrochloride gave similar results.
Highlight: Stereoselective Cross‐Dehydrogenative Coupling Reactions Based on Sp3 C―H Activation to Give Chiral Heterocyclic Compounds
Authors: Zhang Ming , Zhang Aiqin
Published: August 2012

Stereoselective cross‐dehydrogenative coupling (CDC) reactions based on sp3 C—H activation for functionalization of heterocycles were introduced. It is an efficient, economical and convenient strategy for functionalization of heterocycles.
Isomeric 3‐Isoxadiazolylcoumarins and Their Derivatives
Authors: Detistov Oleksandr S. , Orlov Valeriy D. , Zhuravel' Irina O.
Published: August 2012

Here, we represent preparative methods of synthesis of isomeric 3‐isoxadiazolylcoumarins and their derivatives. Two new synthetic methods have been developed for 3‐[1,2,4‐oxadiazol‐5‐yl]coumarins I. The first method is based on a three‐component condensation of coumarin‐;3‐carboxylic acids, 1,1′‐carbonyldiimidazole, and amidoximes. The second method essentially uses the interaction of 5‐cyanomethyl‐1,2,4‐oxadiazoles with salicylic aldehydes. General approach for preparation of 3‐[1,2,4‐oxadiazol‐3‐yl]coumarins II has been worked out. Moreover, aforementioned synthetic ways open the way for the synthesis of 2‐iminoderivatives III and IV not described before, those were diversified by reaction of nucleophilic substitution of 2‐imino group with a numerous amino compounds.
The Course of Case Linkage Never Did Run Smooth: A New Investigation to Tackle the Behavioural Changes in Serial Car Theft
Authors: Davies Kari , Tonkin Matthew , Bull Ray , Bond John W.
Published: August 2012

This study aimed to investigate the case linkage principles, behavioural consistency and distinctiveness, with a sample of serial car thieves. Target selection, acquisition, and disposal behaviours, as well as geographical and temporal behaviours, were examined. The effects of temporal proximity and offender expertise were also investigated as moderating factors of behavioural consistency. As in previous case linkage research, geographical and some target selection behaviours were able to predict whether crime pairs are linked or unlinked at a statistically significant level. Crucially, it was also found that temporal behaviours demonstrate a significant capability to predict linkage status, a variable which has never before been applied to the prediction of linkage in serial car theft. Furthermore, it was demonstrated that changing the operationalisation of the behavioural domains can affect the results obtained. No support was found for the moderation of behavioural consistency on the basis of temporal proximity or expertise. Overall, the results support previous case linkage studies, furthering their practical applicability within the criminal justice system. Copyright © 2012 John Wiley & Sons, Ltd.
When does centrality matter? Scientific productivity and the moderating role of research specialization and cross‐community ties
Authors: Rotolo Daniele , Messeni Petruzzelli Antonio
Published: August 2012

The present study addresses the ongoing debate concerning academic scientific productivity. Specifically, given the increasing number of collaborations in academia and the crucial role networks play in knowledge creation, we investigate the extent to which building social capital within the academic community represents a valuable resource for a scientist's knowledge‐creation process. We measure the social capital in terms of structural position within the academic collaborative network. Furthermore, we analyse the extent to which an academic scientist's research specialization and ties that cross‐community boundaries act as moderators of the aforementioned relationship. Empirical results derived from an analysis of an Italian academic community from 2001 to 2008 suggest academic scientists that build social capital by occupying central positions in the community outperform their more isolated colleagues. However, scientific productivity declines beyond a certain threshold value of centrality, hence revealing the existence of an inverted U‐shaped relationship. This relationship is negatively moderated by the extent to which an academic focuses research activities in few scientific knowledge domains, whereas it is positively moderated by the number of cross‐community ties established. Copyright © 2012 John Wiley & Sons, Ltd.
Rapid determination of alkylphenols in aqueous samples by in situ acetylation and microwave‐assisted headspace solid‐phase microextraction coupled with gas chromatography–mass spectrometry
Authors: Wu Yu‐Pei , Wang Yu‐Chen , Ding Wang‐Hsien
Published: August 2012

A rapid and solvent‐free procedure for the determination of 4‐tert‐octylphenol and 4‐nonylphenol isomers in aqueous samples is described. The method involves in‐situ acetylation and microwave‐assisted headspace solid‐phase microextraction prior to their determination using gas chromatography–ion trap mass spectrometry operated in the selected ion storage mode. The dual experimental protocols to evaluate the effects of various derivatization and extraction parameters were investigated and the conditions optimized. Under optimized conditions, 300 μL of acetic anhydride mixed with 1 g of potassium hydrogencarbonate and 2 g of sodium chloride in a 20 mL aqueous sample were efficiently extracted by a 65 μm polydimethylsiloxane‐divinylbenzene fiber that was located in the headspace when the system was microwave irradiated at 80 W for 5 min. The limits of quantitation were 5 and 50 ng/L for 4‐tert‐octylphenol and 4‐nonylphenol isomers, respectively. The precision for these analytes, as indicated by relative standard deviations, were less than 8% for both intra‐ and inter‐day analysis. Accuracy, expressed as the mean extraction recovery, was between 74 to 88%. A standard addition method was used to quantitate 4‐tert‐octylphenol and 4‐nonylphenol isomers, and the concentrations ranged from 120 to 930 ng/L in various environmental water samples.
A novel octadecylsilane functionalized graphene oxide/silica composite stationary phase for high performance liquid chromatography
Authors: Liang Xiaojing , Wang Shuai , Liu Shujuan , Liu Xia , Jiang Shengxiang
Published: August 2012

An octadecylsilane functionalized graphene oxide/silica stationary phase was fabricated by assembling graphene oxide onto the silica particles through an amide bond and subsequent immobilization of octadecylsilane. The chromatographic properties of the stationary phase were investigated by reversed‐phase chromatography with alkylbenzenes, polycyclic aromatic hydrocarbons, amines, and phenolic compounds as the analytes. All the compounds achieved good separation on the column. The comparison between a C18 commercial column and the new stationary phase indicated that the existence of π‐electron system of graphene oxide allows π–π interaction between analyte and octadecylsilane functionalized graphene oxide/silica stationary phase except for hydrophobic interaction, while only hydrophobic interaction presented between analyte and C18 commercial column. This suggests that some analytes can be better separated on the octadecylsilane functionalized graphene oxide/silica column.
Angular effect of optical fiber movement on endoscopic laser prostatectomy
Authors: Rajabhandharaks Danop , Kang Hyun Wook , Oh Junghwan
Published: August 2012

Background and Objective

The optimal fiber manipulation during laser prostatectomy has been highlighted as a critical element to achieve desirable clinical outcomes. However, scientific understanding of the physical interplay between fiber movement and ablative tissue response is still lacking. The objective of this study was to quantitatively investigate the effect of angular movement of an optical fiber on tissue ablation performance.

Study Design/Materials and Methods

Porcine kidney was employed as a tissue model in vitro. A 180 W 532 nm surgical laser with 750 µm side‐firing fibers was utilized to mimic clinical laser prostatectomy. The effect of fiber manipulation parameters on the tissue such as irradiance, number of overlapping pulses (OP), and beam path length (BPL) was assessed at various fiber sweeping (rotational) angles ranging from 0° to 120°. Morphological properties of the post‐irradiated tissue were also evaluated in light of ablation depth, coagulative necrosis, and volumetric ablation density (VAD).

Results

As sweeping angle (SA) increased, both laser irradiance and number of OP decreased but BPL increased. Ablation depth was maximized (5.4 ± 1.0 mm) at SAs less than 30° but decreased at higher SAs. The SAs of 15° and 30° demonstrated the minimal thickness of denaturized tissue (0.74 ± 0.14 mm) and VAD (total laser energy/ablation volume (AV) ≈ 4.6 ± 0.46 J/mm3). Decreasing depth and increasing tissue coagulation associated with increasing SA resulted from substantial reduction in both beam irradiance and number of OP, eventually impeding ablation process. Excessive tissue denaturation also occurred when no rotational motion was applied to the fiber possibly due to plume shielding.

Conclusion

Inefficient tissue ablation could lead to adverse post‐operative complications due to unwanted thermal injury to peripheral tissue. A SA of 30° was found to be desirable for effective tissue ablation, and further clinical investigations will validate the current findings. Lasers Surg. Med. 44: 653–663, 2012. © 2012 Wiley Periodicals, Inc.
Photodynamic therapy with systemic meta‐tetrahydroxyphenylchlorin in the treatment of anal intraepithelial neoplasia, grade 3
Authors: van der Snoek Eric M. , den Hollander Jan C. , Aans Jan B. , Sterenborg Henricus J.C.M. , van der Ende Marchina E. , Robinson Dominic J.
Published: August 2012

Background and Objective

Anal cancer and preneoplastic anal lesions (anal intraepithelial neoplasia, AIN) rising especially in men having sex with men (MSM). There are no widely accepted treatment standards for AIN. Photodynamic therapy (PDT) using the systemic sensitizer meta‐tetrahydroxyphenylchlorin (mTHPC) has the potential to treat the anal area even when the exact borders of the preneoplastic anal lesion cannot easily be visualized.

Study Design/Materials and Methods

In this prospective intervention study, 15 HIV‐positive MSM with AIN 3 were treated in 25 PDT‐sessions using mTHPC intravenously administered at drug doses of 0.075–0.15 mg ml−1 and illumination at 48 hours. The illumination was performed using a custom made applicator using either red light (652 nm) to a measured intended fluence of 10 and 20 J cm−2 and green light (532 nm) to a measured intended fluence of 105, 210, and 340 J cm−2. Red and green illuminations were performed at a (green) equivalent fluence rate of 105 mW cm−2.

Results

Initial complete response was seen in 7/25 (28%) of treatments and another 4/25 (16%) initial partial responses. After an average 8 months, recurrences were detected in 7/11 (64%) of sessions that initially showed response. A total 4/25 (16%) showed persistent complete response 6–15 months after green light illumination. Red light illuminations caused more significant side effects combined with no persistent complete response. Reported side effects were intense pain, bloody and purulent rectal discharge, and anal stricture formation, in one patient.

Conclusion

The results show that the use of systemic mTHPC is partially effective for the treatment of AIN 3. Lasers Surg. Med. 44: 637–644, 2012. © 2012 Wiley Periodicals, Inc.
Evaluation of combined fractional radiofrequency and fractional laser treatment for acne scars in Asians
Authors: Yeung Chi K. , Chan Nicola P.Y. , Shek Samantha Y.N. , Chan Henry H.L.
Published: August 2012

Background and Objectives

Fractionated radiofrequency (RF) induces deep dermal heating and leaves the epidermis less affected. We studied the efficacy and safety of bipolar RF and fractional diode laser followed by fractional RF in Asians with acne scars.

Materials and Methods

Twenty‐four patients (skin types III and IV) with acne scars received up to five treatments of combined fractional 915‐nm laser and bipolar RF using a Matrix IR applicator (Syneron Medical Ltd, Yokneam, Israel) with fluence ranging from 50 to 70 J/cm2, RF at 70–100 J/cm3, double passes followed by full‐face bipolar fractional RF treatment using Matrix RF at energy ranging from 50 to 62 mJ/pin, at 4‐week intervals. Changes in acne scars, skin texture, pore size, pigmentation irregularity, and complications were assessed up to 3 months post‐treatment by standardized photographs obtained with Canfield Visia‐CR system®. Subjective improvement and patient satisfaction were assessed by questionnaire.

Results

Twenty patients (age 27.7 ± 8.4 years) completed the study. Modest but statistically significant improvement was noted in acne scars, with the mean grade decreased by 29% (P < 0.001), and 52% were rated with at least moderate objective global improvement at 3 months. Mean pain score was 2.6 on a scale of 0–4. There were also objective improvements in all secondary endpoints. Post‐inflammatory hyperpigmentation (PIH) occurred mainly over bony areas in 6.5% of all treatments. Subjective improvement was moderate to significant for 36.8% of patients, and 63% reported being satisfied with the treatment results at 3 months despite considerable pain level.

Conclusion

Use of fractional laser with RF followed by fractional RF was shown to be safe and effective for acne scars with modest improvement and low PIH rate comparable to other resurfacing techniques in this Asian case series. Adequate pain control and recduced energy level when treating areas in close proximity to bone are advised. Lasers Surg. Med. 44: 622–630, 2012. © 2012 Wiley Periodicals, Inc.
Disclosure Strategies and Cost of Capital
Authors: Bravo Urquiza Francisco , Abad Navarro María Cristina , Trombetta Marco
Published: August 2012

Theoretically, companies disclosing more voluntary information will benefit from a lower cost of capital, although empirical research provides inconclusive results. Our study aims to analyze the influence of the disclosure of forward‐looking information on the cost of capital, because this information is extremely useful for investors. Results show that only specific information on actions, programs, decisions, and/or quantitative financial information helps toward the reduction of cost of capital. This evidence has direct economic implications, because it enables regulators and managers to focus on those disclosure strategies that are effective in the reduction of cost of capital. Copyright © 2012 John Wiley & Sons, Ltd.
Does the Gender Preference for Competition Affect Job Performance? Evidence from a Real Effort Experiment
Authors: Price Curtis R.
Published: August 2012

Experimental evidence has documented that competition may enhance the performance of male subjects in some tasks when competition is imposed exogenously by the experimenter. This note describes data for a task where a simple agency relationship is established in the laboratory between two groups of agents, managers, and workers. The manager chooses from either the piece rate or tournament payment scheme for the worker. The results show that male performance decreases when the tournament is chosen for them by the manager and also suggests that the gender of the manager may be an important facet of the agency relationship. Copyright © 2012 John Wiley & Sons, Ltd.
Effects of temperature and fatigue on the electromechanical delay components
Authors: Cè Emiliano , Rampichini Susanna , Agnello Luca , Limonta Eloisa , Veicsteinas Arsenio , Esposito Fabio
Published: August 2012

Introduction: Neuromuscular activation can be influenced by both muscle temperature (Tm) and fatigue. Methods: To assess the effects of Tm and fatigue on the electromechanical delay (EMD), 15 participants performed voluntary isometric contractions of different intensities under neutral (TmN), low (TmL), and high (TmH) Tm, before and after a fatiguing exercise. During contraction, electromyogram (EMG), mechanomyogram (MMG), and force (F) were recorded from the biceps brachii muscle. The EMD and the latencies between EMG and MMG (Δt EMG‐MMG, which includes the electrochemical processes of EMD) and between MMG and F (Δt MMG‐F, which includes the mechanical processes of EMD) were calculated. Results: TmL increased only Δt EMG‐MMG, both before and after fatigue. Fatigue lengthened EMD, Δt EMG‐MMG, and Δt MMG‐F under all Tm to a similar extent. Conclusions: While fatigue increased all EMD components, muscle cooling affected only the electrochemical but not the mechanical processes of EMD. Muscle Nerve, 2013
Exact solution for granular flows
Authors: Faccanoni Gloria , Mangeney Anne
Published: August 2012

In this paper, we present the exact solution of the Riemann problem for the nonlinear one‐dimensional so‐called shallow‐water or Saint‐Venant equations with friction proposed by SAVAGE and HUTTER to describe debris avalanches. This model is based on the depth‐averaged thin layer approximation of granular flows over sloping beds and takes into account a Coulomb type friction law with a constant friction coefficient. A particular configuration of the Riemann problem corresponds to a dam of infinite length in one direction from which granular material is released from rest at a given time over an inclined rigid or erodible bed. We solve analytically and numerically the depth‐averaged long‐wave equations derived in a topography‐linked coordinate system for all the possible Riemann problems. The detailed mathematical proof of the derivation of the analytical solutions and the analysis of their structure and properties is intended, first of all, for geophysicists, mathematicians, and physicists because of the possible extension of this study to more complex problems (geometries, friction laws, …). The numerical solution of the first‐order finite‐volume method based on a Godunov‐type scheme is compared with the proposed exact Riemann problem solution. This solution is used to solve the dam‐break problem and analyze the influence of the thickness of the erodible bed on the speed of the granular front. Comparison with existing experimental results shows that, for an erodible bed, the equations lack fundamental physical significance to reproduce the observed dynamics of erosive granular flows. Copyright © 2012 John Wiley & Sons, Ltd.
Molecular characterization of mucinous ovarian tumours supports a stratified treatment approach with HER2 targeting in 19% of carcinomas
Authors: Anglesio Michael S , Kommoss Stefan , Tolcher Mary C , Clarke Blaise , Galletta Laura , Porter Henry , Damaraju Sambasivarao , Fereday Sian , Winterhoff Boris J , Kalloger Steve E , Senz Janine , Yang Winnie , Steed Helen , Allo Ghassan , Ferguson Sarah , Shaw Patricia , Teoman Attila , Garcia Joaquin J , Schoolmeester John K , Bakkum‐Gamez Jamie , Tinker Anna V , Bowtell David D , Huntsman David G , Gilks C Blake , McAlpine Jessica N
Published: August 2012

Mucinous ovarian carcinomas (MCs) typically do not respond to current conventional therapy. We have previously demonstrated amplification of HER2 in 6 of 33 (18.2%) mucinous ovarian carcinomas (MCs) and presented anecdotal evidence of response with HER2‐targeted treatment in a small series of women with recurrent HER2‐amplified (HER2+) MC. Here, we explore HER2 amplification and KRAS mutation status in an independent cohort of 189 MCs and 199 mucinous borderline ovarian tumours (MBOTs) and their association to clinicopathological features. HER2 status was assessed by immunohistochemistry (IHC), FISH, and CISH, and interpreted per ASCO/CAP guidelines, with intratumoural heterogeneity assessment on full sections, where available. KRAS mutation testing was performed with Sanger sequencing. Stage and grade were associated with recurrence on both univariate and multivariate analysis (p < 0.001). Assessment of HER2 status revealed overexpression/amplification of HER2 in 29/154 (18.8%) MCs and 11/176 (6.2%) MBOTs. There was excellent agreement between IHC, FISH, and CISH assessment of HER2 status (perfect concordance of HER2 0 or 1+ IHC with non‐amplified status, and 3+ IHC with amplified status). KRAS mutations were seen in 31/71 (43.6%) MCs and 26/33 (78.8%) MBOTs, and were near mutually exclusive of HER2 amplification. In the 189 MC cases, a total of 54 recurrences and 59 deaths (53 of progressive disease) were observed. Within MCs, either HER2 amplification/overexpression or KRAS mutation was associated with decreased likelihood of disease recurrence (p = 0.019) or death (p = 0.0041) when compared to cases with neither feature. Intratumoural heterogeneity was noted in 26% of HER2‐overexpressing cases. These data support the stratification of MCs for the testing of new treatments, with HER2‐targeted therapy as a viable option for HER2+ advanced or recurrent disease. Further research is required to delineate the molecular and clinical features of the ∼34% of MC cases with neither HER2 amplification nor KRAS mutations.
Vapor phase oxidative synthesis of conjugated polymers and applications
Authors: Bhattacharyya Dhiman , Howden Rachel M. , Borrelli David C. , Gleason Karen K.
Published: August 2012

Since their discovery, electrically conductive polymers have gained immense interest both in the fields of basic and applied research. Despite their vast potential in the fabrication of efficient, flexible, and low‐cost electronic and optoelectronic devices, they are often difficult to process by wet‐chemical methods due to their very low to poor solubility in organic solvents. The use of vapor‐based synthetic routes, in which conductive polymers can be synthesized and deposited as a thin film directly on a substrate from the vapor phase, provides many unique advantages. This article discusses oxidative vapor deposition processes, primarily vapor phase polymerization and oxidative chemical vapor deposition, of conjugated polymers and their applications. The mild operating conditions (near room temperature processing) allow conformal and functional coatings of conjugated polymers on delicate substrates. © 2012 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys, 2012
Slow geminate‐charge‐pair recombination dynamics at polymer: Fullerene heterojunctions in efficient organic solar cells
Authors: Provencher Françoise , Sakowicz Maciej , Brosseau Colin‐Nadeau , Latini Gianluca , Beaupré Serge , Leclerc Mario , Reynolds Luke X. , Haque Saif A. , Leonelli Richard , Silva Carlos
Published: August 2012

We explore charge recombination dynamics at electron donor‐acceptor heterojunctions, formed between a semiconductor polymer (PCDTBT) and a fullerene derivative (PC70BM), by means of combined time‐resolved photoluminescence and transient absorption spectroscopies. Following prompt exciton dissociation across the heterojunction, a subset of bound electron‐hole pairs recombines with a temperature‐independent rate distribution spanning submicrosecond timescales to produce luminescent charge‐transfer excitons (CTX). At 14 K, this slow mechanism is the dominant geminate charge recombination pathway, whereas we also observe CTX emission on subnanosecond timescales at 293 K. We thus find that at these temperatures, a fraction of the initial charge‐pair population is trapped deeply such that they only recombine slowly over a broad distribution of timescales by quantum tunneling. We identify geminate polaron pairs (GPP) as a reservoir of long‐lived localized states that repopulate the CTX up to microsecond timescales. The observation of such distributed geminate‐charge recombination highlights the importance of the molecular nature of specific donor–acceptor electronic interactions in defining the relaxation pathways of trapped GPP. © 2012 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys, 2012
Effects of water freezing on the mechanical properties of nafion membranes
Authors: Teocoli Francesca , Paolone Annalisa , Palumbo Oriele , Navarra Maria Assunta , Casciola Mario , Donnadio Anna
Published: August 2012

Most of the research efforts on Nafion have been devoted to the study of the perfluorinated ionomer membranes at optimal conditions for the desired applications, such as high temperature and low relative humidity for polymer electrolyte membrane fuel cells (PEM FC). In view of the possible changes induced by the freezing of water in the structure of Nafion and considering that in cold start conditions of a PEM FC device, Nafion needs to work also below 273 K, we measured the Young's modulus (Y) and the elastic energy dissipation (tan δ) in the temperature range between 90 and 470 K and the stress–strain curves between 300 and 173 K. The measurements reported here indicate that the mechanical properties of wet Nafion membrane change dramatically with temperature, that is, from a rubber‐like behavior at room temperature to a brittle behavior below 180 K. Moreover, we observed that the freezing of the nanoconfined water is complete only below 180 K, as indicated by a large increase of the Young's modulus. Between 180 and 300 K, the large values of tan δ suggest the occurrence of friction between the liquid water bound to the walls of the hydrophilic domains and the solid ice residing in the center of channels. © 2012 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys, 2012