bluuebunny/crossref_metadata_2025 huggingface dataset:
Characteristics of δ13CDIC in lakes on the Tibetan Plateau and its implications for the carbon cycle
Authors: Lei Yanbin , Yao Tandong , Sheng Yongwei , Zhang Enlou , Wang Weicai , Li Junli
Published: April 2011

Dissolved inorganic carbon isotope (δ13CDIC) is an important tool to reveal the carbon cycle in lake systems. However, there are only few studies focusing on the spatial variation of δ13CDIC of closed lakes. Here we analyze the characteristics of δ13CDIC of 24 sampled lakes (mainly closed lakes) across the Qiangtang Plateau (QTP) and identify the driving factors for its spatial variation. The δ13CDIC value of these observed lakes varies in the range of − 15·0 to 3·2‰, with an average value of − 1·2‰. The δ13CDIC value of closed lakes is close to the atmospheric isotopic equilibrium value, much higher than that in rivers and freshwater lakes reported before. The high δ13CDIC value of closed lakes is mainly attributed to the significant contribution of carbonate weathering in the catchment and the evasion of dissolved CO2 induced by the strong evaporation of lake water. The δ13CDIC value of closed lakes has a logarithmic correlation with water chemistry (TDS, DIC and pCO2), also suggesting that the evapo‐concentration of lake water can influence the δ13CDIC value. The δ13CDIC value shows two opposite logarithmic correlations with lake size depending on the δ13CDIC range. This study suggests that the δ13C in carbonates in lacustrine sediments can be taken as an indicator of lake volume variation in closed lakes on QTP. Copyright © 2011 John Wiley & Sons, Ltd.
In situ quantification of spatial and temporal variability of hyporheic exchange in static and mobile gravel‐bed rivers
Authors: Rosenberry Donald O. , Klos P. Zion , Neal Andrew
Published: April 2011

Seepage meters modified for use in flowing water were used to directly measure rates of exchange between surface and subsurface water in a gravel‐ and cobble bed river in western Pennsylvania, USA (Allegheny River, Qmean = 190 m3/s) and a sand‐ and gravel‐bed river in Colorado, USA (South Platte River, Qmean = 9·7 m3/s). Study reaches at the Allegheny River were located downstream from a dam. The bed was stable with moss, algae, and river grass present in many locations. Median seepage was + 0·28 m/d and seepage was highly variable among measurement locations. Upward and downward seepage greatly exceeded the median seepage rate, ranging from + 2·26 (upward) to − 3·76 (downward) m/d. At the South Platte River site, substantial local‐scale bed topography as well as mobile bedforms resulted in spatial and temporal variability in seepage greatly in exceedence of the median groundwater discharge rate of 0·24 m/d. Both upward and downward seepage were recorded along every transect across the river with rates ranging from + 2·37 to − 3·40 m/d. Despite a stable bed, which commonly facilitates clogging by fine‐grained or organic sediments, seepage rates at the Allegheny River were not reduced relative to those at the South Platte River. Seepage rate and direction depended primarily on measurement position relative to local‐ and meso‐scale bed topography at both rivers. Hydraulic gradients were small at nearly all seepage‐measurement locations and commonly were not a good indicator of seepage rate or direction. Therefore, measuring hydraulic gradient and hydraulic conductivity at in‐stream piezometers may be misleading if used to determine seepage flux across the sediment‐water interface. Such a method assumes that flow between the well screen and sediment‐water interface is vertical, which appears to be a poor assumption in coarse‐grained hyporheic settings. Copyright © 2011 John Wiley & Sons, Ltd.
Modelling of groundwater flow in heterogeneous porous media by finite element method
Authors: Smaoui Hassan , Zouhri Lahcen , Ouahsine Abdellatif , Carlier Erick
Published: April 2011

The HySuf‐FEM code (Hydrodynamic of Subsurface Flow by Finite Element Method) is proposed in this article in order to estimate the spatial variability of the transmissivity values of the Berrechid aquifer (Morocco).

The calibration of the model is based on the hydraulic head, hydraulic conductivity and recharge. Three numerical tests are used to validate the model and verify its convergence. The first test case consists in using the steady analytical solution of the Poisson equation. In the second, the model has been compared with the hydrogeological system which is characterized by an unconfined monolayer (isotropic layer) and computed by using PMWIN‐MODFLOW software. The third test case is based on the comparison between the results of HySuf‐FEM and the multiple cell balance method in the aquifer system with natural boundaries case.

Good agreement between the Hydrodynamic of Subsurface Flow, the numerical tests and the spatial distribution of the thickening of the hydrogeological system is deduced from the analysis and the interpretations of hydrogeological wells. Copyright © 2011 John Wiley & Sons, Ltd.
Influences of watershed landscape composition and configuration on lake‐water quality in the Yangtze River basin of China
Authors: Liu Wenzhi , Zhang Quanfa , Liu Guihua
Published: April 2011

Lake‐water quality is highly dependent on the landscape characteristics in its respective watershed. In this study, we investigated the relationships between lake‐water quality and landscape composition and configuration within the watershed in the Yangtze River basin of China. Water quality variables, including pH, electrical conductivity (EC), dissolved oxygen (DO), Secchi depth (SD), NO2−, NO3−, NH4+, TN, TP, chemical oxygen demand (CODMn), chlorophyll‐a (Chl‐a), and trophic state index (TSI), were collected from 16 lakes during the period of 2001–2003. Landscape composition (i.e. the percentage of vegetation, agriculture, water, urban, and bare land) and landscape configuration metrics, including number of patches (NP), patch density (PD), largest patch index (LPI), edge density (ED), mean patch area (MPA), mean shape index (MSI), contagion (CONTAG), patch cohesion index (COHESION), Shannon's diversity index (SHDI), and aggregation index (AI), were calculated for each lake's watershed. Results revealed that the percentage of agriculture was negatively related to NO2−, TN, TP, Chl‐a concentrations, and TSI, while the percentage of urban was significantly correlated with EC, NH4+, and CODMn concentrations. Among landscape‐level configuration metrics, only ED showed significant relationships with TN, TP concentrations, and TSI. However, at the class level, the PD, LPI, ED, and AI of agriculture and urban land uses were significantly correlated with two or more water quality variables. This study suggests that, for a given total area, large and clustered agricultural or urban patches in the watershed may have a greater impact on lake‐water quality than small and scattered ones. Copyright © 2011 John Wiley & Sons, Ltd.
Influence of drought and total phosphorus on diel pH in wadeable streams: Implications for ecological risk assessment of ionizable contaminants
Authors: Valenti Theodore W , Taylor Jason M , Back Jeffrey A , King Ryan S , Brooks Bryan W
Published: April 2011

Climatological influences on site-specific ecohydrology are particularly germane in semiarid regions where instream flows are strongly influenced by effluent discharges. Because many traditional and emerging aquatic contaminants, such as pharmaceuticals, are ionizable, we examined diel surface water pH patterns (i.e., change in pH over a 24-h period) at 23 wadeable streams in central Texas, USA, representing a gradient of nutrient enrichment during consecutive summers of 2006 and 2007. The years of our study were characterized by decidedly different instream flows, which likely affected production:respiration dynamics and led to distinctions in diel pH patterns between 2006 and 2007. Site-specific ambient water quality criteria for NH3 and the aquatic toxicity of the model weak base pharmaceutical sertraline were predicted using continuous water quality monitoring data from the sites. Drought conditions of 2006 significantly increased (p < 0.05) diel pH changes compared to high instream flows of 2007,and the magnitude of diel pH variability was most pronounced at nutrient-enriched sites in 2006. Differences in diel pH change patterns between 2006 and 2007 affected predictions of the environmental fate and effects for model weak base pharmaceuticals and NH3. Overall, site-specific diel pH was more variable at some sites than the difference in mean surface water pH between the 2 summers. Diel pH variability affected regulatory criteria, because 20% of the study sites in 2006 experienced greater than 5-fold differences in National Ambient Water Quality Criteria for NH3 over 24-h periods. Our study emphasizes the potential uncertainty that diel pH variability may introduce in site-specific assessments and provides recommendations for environmental assessment of ionizable contaminants. Integr Environ Assess Manag 2011;7:636–647. © 2011 SETAC
Risk aversion, intertemporal substitution, and the term structure of interest rates
Authors: Garcia René , Luger Richard
Published: April 2011

We build and estimate an equilibrium model of the term structure of interest rates based on a recursive utility specification. We contrast it with an arbitrage‐free model, where prices of risk are estimated freely without preference constraints. In both models, nominal bond yields are affine functions of macroeconomic state variables. The equilibrium model accounts for the tent‐shaped pattern and magnitude of coefficients from predictive regressions of excess bond returns on forward rates and the hump‐shaped pattern in the term structure of volatilities, while the reduced‐form no‐arbitrage model does not account for these important features of the yield curve. Copyright © 2011 John Wiley & Sons, Ltd.
Prophylactic role of D‐saccharic acid‐1,4‐lactone in tertiary butyl hydroperoxide induced cytotoxicity and cell death of murine hepatocytes via mitochondria‐dependent pathways
Authors: Bhattacharya Semantee , Chatterjee Srabasti , Manna Prasenjit , Das Joydeep , Ghosh Jyotirmoy , Gachhui Ratan , Sil Parames C.
Published: April 2011

D‐Saccharic acid 1,4‐lactone (DSL) is a derivative of D‐glucaric acid. It is a beta‐glucuronidase inhibitor and possesses anticarcinogenic, detoxifying, and antioxidant properties. In the present study, the protective effects of DSL were investigated against tertiary butyl hydroperoxide (TBHP) induced cytotoxicity and cell death in vitro using murine hepatocytes. Exposure of TBHP caused a reduction in cell viability, enhanced the membrane leakage, and disturbed the intracellular antioxidant machineries in murine hepatocytes. Investigating the signaling mechanism of TBHP‐induced cellular pathophysiology and protective action of DSL, we found that TBHP exposure disrupted mitochondrial membrane potential, facilitated cytochrome c release in the cytosol, and led to apoptotic cell death via mitochondria‐dependent pathways. DSL counteracted these changes and maintained normalcy in hepatocytes. Combining, results suggest that DSL possesses the ability to ameliorate TBHP‐induced oxidative insult, cytotoxicity, and apoptotic cell death probably due to its antioxidant activity and functioning via mitochondria‐dependent pathways. © 2011 Wiley Periodicals, Inc. J Biochem Mol Toxicol 25:341–354 2011; View this article online at wileyonlinelibrary.com. DOI 10.1002/jbt.20393
Parameterization of Org27569: An allosteric modulator of the cannabinoid CB1G protein‐coupled receptor
Authors: Iliff Hadley A. , Lynch Diane L. , Kotsikorou Evangelia , Reggio Patricia H.
Published: April 2011

The cannabinoid CB1receptor is a class A G protein‐coupled receptor (GPCR) that is the most widely expressed GPCR in the brain. Many GPCRs contain allosteric binding sites for endogenous and/or synthetic ligands, which are topographically distinct from the agonist‐binding site that is known as the orthosteric site. While both endogenous and synthetic ligands that act at the CB1orthosteric site have been known for some time, compounds that act at a CB1allosteric site have only recently been discovered. The most studied of these is 5‐chloro‐3‐ethyl‐1H‐indole‐2‐carboxylic acid [2‐(4‐piperidin‐1‐ylphenyl)ethyl]amide (Org27569). Because allosteric ligands are thought to act through conformational changes in the receptor that are transmitted from the allosteric to the orthosteric site, computational studies of the structural and dynamic interactions of Org27569 with the CB1receptor are crucial to achieve a molecular level understanding of the basis of action of this important new class of compounds. To date, such computational studies have not been possible due to the lack of a complete set of molecular mechanics force field parameters for Org27569. Here, we present the development of missing CHARMM force field parameters for Org27569 using previously published methods and the validation and application of these new parameters using normal mode analysis and molecular dynamics simulations combined with experimental infrared measurements. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2011
Empirical prediction of protein pKavalues with residue mutation
Authors: Burger Steven K. , Ayers Paul W.
Published: April 2011

A fast, empirical method, Mut‐pKa, is presented for predicting the pKa values of ionizable residues in proteins based on mutation. The method compares the effect of mutating each residue that may act as a hydrogen bond donor or acceptor for the ionizable residue. The energetic effect of each type of mutation, along with a desolvation measure and the overall background charge, is fit against pKa data for histidine and carboxyl residues. A total of 214 residues from 35 different proteins were used in the dataset. Using 11 parameters for each type of ionizable residue, a root mean squared error (RMSE) of 0.78 and 1.12 pH units were obtained for carboxyl and histidines residues, respectively, using leave one out cross validation (LOOCV). The results were particularly promising for buried residues, which had RMSE values of 0.99 and 1.13 for carboxyl and histidine residues, respectively. A number of desolvation measures were tested. The simplest measure, the number of atoms surrounding the residue, was found to work best. The effect of using dynamics was also studied using short molecular dynamics runs, followed by minimization of the structures. Mut‐pKa has significantly fewer parameters than, but similar performance to, other empirical methods. Because of this and the LOOCV results, we believe the model is robust and that overfitting is not a problem. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2011
Synthesis and antimicrobial activity of new C‐furyl glycosides bearing substituted 1,3,4‐oxadiazoles
Authors: El‐Sayed Wael A. , Abbas Hebat‐Allah S. , Mohamed Ashraf M. , Abdel‐Rahman Adel A.‐H.
Published: April 2011

New 2,5‐disubstituted 1,3,4‐oxadiazole derivatives bearing C‐furyl glycoside moieties and their sugar hydrazone as well as their per‐O‐acetyl derivatives were synthesized starting from ethyl 2‐[5‐(3,4‐dihydroxytetrahydrofuran‐2‐yl)‐2‐methylfuran‐3‐yl]‐2‐oxoacetate. Heterocyclization of the sugar hydrazones using acetic anhydride afforded the corresponding oxadiazoline acyclic C‐nucleosides. The antimicrobial activity evaluation showed that many of the synthesized compounds revealed moderate to high antimicrobial activity. J. Heterocyclic Chem., (2011)
Dendritic EGFP‐STIM1 activation after type I metabotropic glutamate and muscarinic acetylcholine receptor stimulation in hippocampal neuron
Authors: Ng Ai Na , Krogh Morten , Toresson Håkan
Published: April 2011

Several signaling pathways in neurons engage the endoplasmic reticulum (ER) calcium store by triggering calcium release. After release, ER calcium levels must be restored. In many non‐neuronal cell types, this is mediated by store‐operated calcium entry (SOCE), a cellular homeostatic mechanism that activates specialized store‐operated calcium channels (SOC). Although much evidence supports the existence of SOCE in neurons, its importance has been difficult to determine because of the abundance of calcium channels expressed and the lack of SOC‐specific pharmacological agents. We have explored the function of the SOCE‐inducing protein STIM1 in neurons. In EGFP‐STIM1‐expressing hippocampal neurons, the sarco‐ and endoplasmic reticulum calcium ATPase (SERCA) inhibitor thapsigargin caused rapid aggregation (i.e., activation) of STIM1 in soma and dendrites. Upon STIM1 activation by thapsigargin, a dramatic reduction in STIM1 mobility was detected by fluorescence recovery after photobleaching (FRAP). By triggering release of ER calcium with 3,5‐dihydroxyphenylglycine (DHPG) or carbachol (Cch), agonists of type I metabotropic glutamate receptors (mGluR) and muscarinic acetylcholine receptors (mAChR), respectively, STIM1 was activated, and calcium entry (likely to represent SOCE) occurred in dendrites. It is therefore possible that neuronal SOCE is activated by physiological stimuli, some of which may alter the postsynaptic calcium signaling properties. © 2011 Wiley‐Liss, Inc.
Responses to adversarial situations and collective intelligence
Authors: Woolley Anita Williams
Published: April 2011

Responses to threat and adversity, including responses to terrorist threats, are becoming an important influence on social behavior in an increasing number of settings. This paper considers the influence of strategic orientation on the responses individuals and groups may exhibit in adversarial situations, and the consequences of these responses for organizational and societal functioning and collective intelligence. Copyright © 2011 John Wiley & Sons, Ltd.
The low latitude influence on winter rainfall in Victoria, South‐Eastern Australia—II. Relationships with the southern oscillation and Australian region circulation
Authors: Wright W. J.
Published: April 2011

In this companion to Part I (Wright, 1988a) of the study on low latitude influences on Victorian rainfall, northern Victorian winter rainfall variability is shown to be dominated by ‘interacting’ (I) fronts, and both parameters are then related to atmospheric circulation anomalies in the Australian region and the Southern Oscillation. The major circulation features accompanying extreme wet and dry winter months in northern Victoria are identified from composited sea level pressure, 500 h Pa height, and 200 h Pa wind fields. Wet winters are characterized by a vigorous subtropical westerly circulation at middle and upper tropospheric levels, a relatively weak subtropical high pressure belt over Australia, and above normal amplitude of the climatological mean long‐wave trough in western Australian longitudes. The intensity and frequency of I frontal systems influencing southeastern Australia is shown to be strongly related to these features, and to cloudiness over the tropical Indian Ocean northwest of Australia, a major source‐region for cloudbands involved in the interactions.

In turn, above normal trough amplitude and cloudiness, a weak subtropical high pressure belt, and frequent and relatively well‐developed interactions, are all shown to be characteristic of winters in which the Tahiti‐Darwin Southern Oscillation Index (SOI) is positive. Anomalies tend to be in the opposite sense during negative SOI winters, which feature infrequent, generally poorly developed, interactions, and much lighter rainfall. The dual association of these circulation and cloudiness features with both the SOI and northern Victorian rainfall strongly suggests that I fronts provide the well‐known link between the SOI and northern Victorian rainfall. The current results are discussed in relation to results from other recent studies on synoptic associations with anomalous heat‐sources.
The southern oscillation and South African summer rainfall
Authors: Van Heerden Johan , Terblanche Deon E. , Schulze Gerhard C.
Published: April 2011

Using data since 1882 the relationship between summer rainfall over South Africa and the ENSO phenomenon is investigated. A strong association between Warm Events and dry spells, and between Cold Events and wet spells is discussed. The temporal and spatial variability in the relationship is presented. Rainfall during December and March correlates significantly with the previous winter's SOI but rainfall during the mid‐summer months, January and February, shows much weaker correlation. A significant relationship is detected between the summer rainfall and mean monthly geopotentials as well as the 850–500 hPa thermal wind over the central parts of South Africa. Distinctions are made between the dominant rain‐producing systems with regard to these parameters. During January and February, when the SO/rainfall relationship is fairly weak, rainfall develops in a predominantly quasi‐barotropic circulation. On the other hand, during December and March the most significant SO/rainfall correlation coincides with a shift to baroclinic systems. Analysis suggests that a clear signal of the SO can be observed in the phase and amplitude of summertime synoptic‐scale baroclinic systems over the South African region.
An investigation of winds up to 300 hPA over Turkey between 1970 and 1984
Authors: Erdoǧmuş Fevzi
Published: April 2011

Turkish radiosonde data obtained at the meteorological stations in Istanbul, Ankara, and Izmir have been analysed in order to study the winds between 850 hPa and 300 hPa pressure levels between 1970 and 1984. The monthly mean values of both the zonal (ū) and the meridional (v̄) wind velocity components, their variances, σ2u and σ2v, and the monthly mean values of wind direction, α, were statistically determined. The constancy, Q, of the winds was then computed by taking the ratio of the monthly mean resultant wind speed (V̄t) and the monthly mean scalar wind speed (V̄s). The results were interpreted by taking local wind patterns into consideration.
PI3Kγ deletion reduces variability in the in vivo osteolytic response induced by orthopaedic wear particles
Authors: Greenfield Edward M. , Tatro Joscelyn M. , Smith Matthew V. , Schnaser Erik A. , Wu Dianqing
Published: April 2011

Orthopedic wear particles activate a number of intracellular signaling pathways associated with inflammation in macrophages and we have previously shown that the phosphoinositol‐3‐kinase (PI3K)/Akt pathway is one of the signal transduction pathways that mediates the in vitro activation of macrophages by orthopedic wear particles. Since PI3Kγ is primarily responsible for PI3K activity during inflammation, we hypothesized that PI3Kγ mediates particle‐induced osteolysis in vivo. Our results do not strongly support the hypothesis that PI3Kγ regulates the overall amount of particle‐induced osteolysis in the murine calvarial model. However, our results strongly support the conclusion that variability in the amount of particle‐induced osteolysis between individual mice is reduced in the PI3Kγ−/− mice. These results suggest that PI3Kγ contributes to osteolysis to different degrees in individual mice and that the mice, and patients, that are most susceptible to osteolysis may be so, in part, due to an increased contribution from PI3Kγ. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 29:1649–1653, 2011
Late Quaternary tephra layers around Raoul and Macauley Islands, Kermadec Arc: implications for volcanic sources, explosive volcanism and tephrochronology
Authors: Shane Phil , Wright Ian C.
Published: April 2011

A suite of deep‐sea cores were collected along transects up to 100 km across the fore‐arc and back‐arc regions of the predominantly submarine Kermadec arc near Raoul and Macauley islands, southwest Pacific. The cores reveal a macroscopic tephra record extending back >50 ka. This is a significant addition to the dated record of volcanism, previously restricted to fragmented late Holocene records exposed on the two islands. The 27 macroscopic tephra layers display a wide compositional diversity in glass (∼50–78 wt% SiO2). Many tephra layers comprise silicic shards with a subordinate mafic shard population. This could arise from magma mingling and may reflect mafic triggering of the silicic eruptions. Broadly, the glass compositions can be distinguished on diverging high‐K and low‐K trends, most likely arising from different source volcanoes. This distinction is also reflected in the tephra records exposed on Raoul (low‐K) and Macauley (high‐K) islands, the likely source areas. Heterogeneous tephra comprising shards of both high‐ and low‐K affinity, silicic and mafic compositions, and more homogeneous tephra with subordinate outlier shard compositions, are best explained by post‐depositional mixing of separate eruption deposits or contemporaneous eruptions. Evidently, the slow sedimentation rates of the calcareous oozes (∼101–102 mm ka−1) were insufficient to adequately separate and preserve closely spaced eruption deposits. This exemplifies the difficulty in assessing eruption frequencies and magmatic trends, and erecting a tephrostratigraphy, using geochemical fingerprinting in such environments. Despite these difficulties, the ca. 5.7 ka Sandy Bay Tephra erupted from Macauley Island can be correlated over a distance of >100 km, extending east and west of the island, showing that the mostly submerged volcanoes are capable of wide tephra dispersal. Hence there is potential for developing chronostratigraphies for the southwest Pacific beyond the region covered by the extensive rhyolite marker beds from the Taupo Volcanic Zone. Copyright © 2011 John Wiley & Sons, Ltd.
Prognostic impact of dihydropyrimidine dehydrogenase expression on pancreatic adenocarcinoma patients treated with S‐1‐based adjuvant chemotherapy after surgical resection
Authors: Kondo Naru , Murakami Yoshiaki , Uemura Kenichiro , Sudo Takeshi , Hashimoto Yasushi , Nakashima Akira , Ohge Hiroki , Sueda Taijiro
Published: April 2011

Background and Objectives

The aim of this study is to investigate the prognostic value of intratumoral expression of thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), and orotate phosphoribosyltransferase (OPRT) in patients treated with S‐1‐based chemotherapy after surgical resection for pancreatic adenocarcinoma.

Methods

Intratumoral TS, DPD, and OPRT expression was investigated in 106 patients with resected pancreatic adenocarcinoma by immunohistochemistry. Associations between clinicopathological factors, including intratumoral TS, DPD, and OPRT expression, and survival were evaluated by univariate and multivariate analyses.

Results

Of 106 patients, 72 had received S‐1‐based adjuvant chemotherapy (S‐1(+) group), and 34 had not (S‐1(−) group). High TS, DPD, and OPRT expression was observed in 64%, 37%, and 66% of patients, respectively. Among S‐1(+) group patients, survival was significantly better for patients with low DPD expression than for patients with high DPD expression (P = 0.022). Intratumoral DPD expression was the only independent prognostic factor for patients treated with S‐1‐based adjuvant chemotherapy by multivariate analysis (P = 0.037). Intratumoral TS and OPRT expression did not appear to influence survival.

Conclusions

Intratumoral DPD expression may be a relevant predictive marker of survival benefit associated with S‐1‐based adjuvant chemotherapy for pancreatic adenocarcinoma. J. Surg. Oncol. 2011;104:146–154. © 2011 Wiley‐Liss, Inc.
Optimal concentration of hepatocyte growth factor for treatment of the aged rat vocal fold
Authors: Suehiro Atsushi , Wright Harry , Rousseau Bernard
Published: April 2011

Objectives/Hypothesis:

Hepatocyte growth factor (HGF) demonstrates beneficial properties in the treatment of aged vocal folds. However, the optimal concentration of HGF remains unknown. The purpose of the present study was to investigate the effects of HGF concentration on treatment of the aged rat vocal fold.

Study Design:

Prospective animal study.

Methods:

Seventy‐five rats were studied. The rats were divided into five groups and received serial injections of HGF in 10 μL of phosphate‐buffered saline (PBS) at the following concentrations: 10 ng/10 μL, 50 ng/10 μL, 100 ng/10 μL, 200 ng/10 μL, or control (PBS only). Alcian blue staining was performed to investigate hyaluronan (HA), and immunohistochemistry was performed to investigate collagen type I and III. Gene expression of hyaluronic acid synthase (HAS)‐1, ‐2, matrix metalloproteinases (MMP)‐2, ‐9, and procollagen I and III were also investigated using real‐time polymerase chain reaction (RT‐PCR).

Results:

Histologic analyses revealed increased HA and decreased collagen type I in rats receiving injections of HGF at 100 ng/10 μL. Results were supported by RT‐PCR revealing upregulated expression of HAS‐2, decreased expression of procollagen I, and a significant increase of MMP‐9 mRNA in rats receiving HGF at 100 ng/10 μL.

Conclusions:

We report the first in vivo concentration study of HGF for treatment of the aged vocal fold. Results revealed desirable biochemical effects of HGF at 100 ng/10 μL. These data will be used to provide immediate direction to programmatic efforts aimed at examining future applications of HGF for treatment of the aged vocal fold.
The triological society 2011 presidential address
Authors: Berke Gerald S.
Published: April 2011

The Triological Society 2011 Presidential Address was presented at The Triological Society's 2011 Combined Sections Meeting in Scottsdale, Arizona, Thursday January 27–29, 2011, by Gerald Berke, MD. The address captures the president's inspiration for the annual address as the past, present, and future of otolaryngology. A review of the financing and economics of health care in the United States over time is presented, and the future of health care with reference to otolaryngology is discussed. The address focused on the percentage increase in gross domestic product assigned to medical care in the United States owing to the emergence, adoption, and widespread diffusion of new medical technologies and services. It showed that a significant proportion of the expense goes to hospitals and physician/clinical services. It refuted many of the current criticisms of medical care in the United States, pointing out that neonatal death rates in the United States include all gestational ages, but many countries only use full‐term births in their statistics; also, longevity is excellent when deaths due to motor vehicle accidents and homicides are adjusted. Furthermore, survival rates for common malignancies and myocardial infarctions are better in the United States than in many countries. The address related the president's memories of medical care in the United States as an intern and young resident. It went on to discuss the concept of treating diseased organs ex vivo and reimplanting them without systemic side effects within the next 25 years but cautioned that future medical advances may be moderated by a reliance on evidence‐based studies before new technologies can be adopted. Finally, it emphasized physician's altruistic motivations for choosing this profession despite future economic realities in coming years.
Change in epworth sleepiness scale after surgical treatment of obstructive sleep apnea
Authors: Yaremchuk Kathleen , Tacia Brandy , Peterson Edward , Roth Thomas
Published: April 2011

Objectives/Hypothesis:

To evaluate the effect of surgical intervention for obstructive sleep apnea (OSA) on patients' level of excessive daytime sleepiness as determined by the Epworth Sleepiness Scale (ESS). The ESS questionnaire is a validated measure of subjective daytime sleepiness. There have been several studies that have shown that continuous positive airway pressure (CPAP) improves excessive daytime sleepiness in OSA patients as measured by the ESS.

Study Design:

Retrospective case series.

Methods:

This is a study of patients who had uvulopalatopharyngoplasty (UPPP); UPPP and tonsillectomy; or UPPP, tonsillectomy, and radiofrequency ablation of the base of the tongue for OSA between January 2007 and December 2009. Forty patients were identified who met the criteria of having had an ESS evaluation and polysomnography prior to surgery for OSA.

Results:

Across all of the patients there was a mean reduction of their ESS by 5.6 ± 4.1; t = 8.82, P < .001. Only three of the patients did not improve in their ESS scores after surgical treatment for OSA.

Conclusions:

Surgical intervention for OSA significantly improves sleepiness in OSA patients as measured by the ESS. Two meta‐analyses of multiple, randomized, controlled studies showed patients with mild to moderate OSA treated with CPAP demonstrated an improvement in the ESS score of 1.2 points (95% confidence interval, 0.05‐1.9, P = .001) and 2.94 points for patients with mild to severe OSA treated with CPAP. The results of this study show an improvement in ESS after surgery that is substantially higher than previously reported with CPAP for all categories of OSA.
Otologic diagnoses in the elderly
Authors: Lin Harrison W. , Bhattacharyya Neil
Published: April 2011

Objectives/Hypothesis:

To establish the current outpatient workload for otologic conditions in the elderly and to estimate its potential increase based on an anticipated aging population.

Study Design:

Cross‐sectional analysis of a national database.

Methods:

All outpatient clinic visits for patients aged ≥65 years receiving one of six common otologic diagnoses from 2005 to 2007 in the United States were determined from the National Ambulatory Medical Care Survey. The distribution of the visits for these diagnoses across 15 specialties was assessed. The number of visits was projected to the 2020 population based on changes in population demographics predicted by the US Census Bureau.

Results:

An estimated 4.48 ± 0.49 million clinic visits with an otologic issue as a coded diagnosis were conducted in 2005 to 2007 in patients aged ≥65 years. These consisted of 230,000 visits for benign positional paroxysmal vertigo, 263,000 visits for vestibular neuritis, 292,000 visits for Meniere's disease, 1.09 million visits for tinnitus, and 2.85 million visits for sensorineural hearing loss. Otolaryngology, internal medicine, family practice, and neurology managed the most visits, seeing 57.0%, 21.0%, 14.3%, and 2.2% of the cases, respectively. With expected changes in population demographics by 2020, annual clinic visits for an otologic diagnosis will increase from 1.49 ± 0.78 million to 2.14 million visits in the elderly, annualized, including 1.218 million visits to otolaryngology.

Conclusions:

These data quantify the current outpatient otology workload and predict a substantial increase for many specialties, including otolaryngology. Efforts to prepare for this increase including manpower planning and education appear imperative.
Construction of G‐Hilbert schemes
Authors: Blume Mark
Published: April 2011

In this paper we construct G‐Hilbert schemes for finite group schemes G. We find a construction of G‐Hilbert schemes as relative G‐Hilbert schemes over the quotient that does not need the Hilbert scheme of n points, works under more natural assumptions and gives additional information about the morphism from the G‐Hilbert scheme to the quotient. © 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim
Hybrid Steered Molecular Dynamics‐Docking: An Efficient Solution to the Problem of Ranking Inhibitor Affinities Against a Flexible Drug Target.
Authors: Whalen Katie L. , Chang Kevin M. , Spies M. Ashley
Published: April 2011

Existing techniques which attempt to predict the affinity of protein‐ligand interactions have demonstrated a direct relationship between computational cost and prediction accuracy. We present here the first application of a hybrid ensemble docking and steered molecular dynamics scheme (with a minimized computational cost), which achieves a binding affinity rank‐ordering of ligands with a Spearman correlation coefficient of 0.79 and an RMS error of 0.7 kcal/mol. The scheme, termed Flexible Enzyme Receptor Method by Steered Molecular Dynamics (FERM‐SMD), is applied to an in‐house collection of 17 validated ligands of glutamate racemase. The resulting improved accuracy in affinity prediction allows elucidation of the key structural components of a heretofore unreported glutamate racemase inhibitor (Ki=9 µM), a promising new lead in the development of antibacterial therapeutics.
Structure analysis for concrete‐faced rockfill dams based on information entropy theory and finite element method
Authors: Su Huaizhi , Hu Jiang , Wen Zhiping
Published: April 2011

Numerical simulation methods are extensively used to analyze the stress and displacement of concrete‐faced rockfill dams (CFRD). The results of these methods are influenced by fuzzy factors, i.e. geometric features, material properties, loads and boundary conditions, which exist widely in the engineering of CFRD as a kind of commonly uncertain factor. To solve this problem, the information entropy theory and the conventional method of structure analysis, namely, finite element method (FEM), were combined in this work. Information entropy, as an effective tool of measuring uncertainty, was used to represent the uncertainty of CFRD. Based on the model that can transform fuzzy information entropy into random information entropy, fuzzy structure can be transformed into equivalent random structure, then mechanical characteristics of CFRD were analyzed by well‐developed stochastic FEM. As an example, one CFRD was chosen to analyze the structure, and the result shows that this method is effective. Copyright © 2011 John Wiley & Sons, Ltd.
Performance of mixed and enhanced finite elements for strain localization in hypoplasticity
Authors: Trinh B. T. , Hackl K.
Published: April 2011

Displacement and mixed finite element formulations of shear localization in materials are presented. The formulations are based on hypoplastic constitutive laws for soils and the mixed enhanced treatment involving displacement, strain and stress rates as independently varied fields. Included in these formulations are the standard displacement method, the three‐field mixed formulation, the enhanced assumed strain method and the mixed enhanced strain method. Several numerical examples demonstrating the capability and performance of the different finite element formulations are presented. The numerical results are compared with available experimental data for Hostun RF sand and numerical results for Karlsruhe sand on biaxial tests. Copyright © 2011 John Wiley & Sons, Ltd.
Access: insider perk or key to transparency?
Authors: Fallon Jonathan
Published: April 2011

This paper will examine the issue of access in Irish lobbying. Addressing the current situation, the paper outlines why access is important to lobbyists, who currently has it and the various layers and levels that exist in our system. Examining the issue, the paper argues that this currently leads to a perception of lobbying being an insiders' occupation. If lobbying in Ireland is to become accountable, transparent and open, then lobbying activities must be clearly defined, and those who sign up to this must gain from it, and there can be no benefit for those who do not declare lobbying activities. The paper argues that lobbying in the long term should become an accepted and trained profession. Lobbying should therefore move away from being a profession populated by those ‘in the know’ or from a political background and become open to anybody who can qualify and meet the desired ethics and standards. For this to happen, a level playing field must be introduced where lobbyists are not reliant on particular politicians or parties or contacts to make a case. Similar to journalists, lobbyists must be integrated into the political system where they can be monitored and observed and where there is a real and tangible price to be paid for breach of a code. Copyright © 2011 John Wiley & Sons, Ltd.
The rise and fall of social partnership: its impact on interest group lobbying in Ireland
Authors: Stafford Peter
Published: April 2011

This paper explores the dynamics of interest group lobbying in Ireland, and the mechanism of lobbying through social partnership, an institutionalized form of deliberative policy making. Following the resignation of Bertie Ahern as Taoiseach (prime minister) in May 2008 and the collapse of the Irish economy, the influencing and lobbying ability of the social partners has waned, and this paper explores how interest groups amended their lobbying tactics to cope with the rise and fall of social partnership in Ireland. Copyright © 2011 John Wiley & Sons, Ltd.
The evolution of taxi policy in Ireland
Authors: Weir Stephen
Published: April 2011

This paper analyzes the role of interest groups in the setting of taxi policy in Ireland during the 1990s. It uses a simple illustrative game theoretic framework to explain the behavior of the taxi lobby and politicians in determining taxi policy over the decade. It draws on recent theoretical advances that explain the impact of negative incentives (i.e., strikes, blockades, smear campaigns, physical threats, etc.) on the relationship between lobby groups and policymakers and their effect on policy reform. This paper shows that the taxi lobby exerted significant power over policy determination during the decade and that they used both their connections with politicians and strikes and blockades in order to obtain favorable policy outcomes. It further demonstrates that as the decade progressed, the problems of the policy became more obvious to the public and became increasingly costly for politicians in terms of support and credibility. This visibility and the simplicity of the policy solution weakened the taxi lobby's ability to confuse the issue and maintain their favorable policy. It also shows that the taxi lobby's inability to compromise to ameliorate the public's concerns eventually led to the ‘worst possible’ policy outcome from their point of view. Copyright © 2011 John Wiley & Sons, Ltd.
Lobbying in Ireland: a reform agenda
Authors: McGrath Conor
Published: April 2011

This article considers the prospects for lobbying regulation in Ireland following that country's February 2011 general election, which produced a new Fine Gael/Labour Party coalition government. Both these parties had published, prior to the election, legislative proposals, which are analysed here. The government has now committed itself to the introduction of statutory regulation, but the precise terms of such a scheme are yet to be decided. Further reflection on the detail of a regulatory regime would be useful, as would more positive engagement in this debate by lobbyists themselves. The article suggests a number of ways by which proposed lobbying regulation could be enhanced and made more rigorous. Copyright © 2011 John Wiley & Sons, Ltd.
Gentherapie – Was ist das? “Heilen” mit Genen
Authors: Büning Hildegard
Published: April 2011

Durch die zunehmende Aufklärung molekularbiologischer Prinzipien und durch beträchtliche technische Fortschritte vor allem im Bereich der Vektoren und der Isolierung und Kultivierung von Zellen, konnten deutliche therapeutische Effekte in der somatischen Gentherapie erzielt werden. Trotz dieser Erfolge ist die Gentherapie weiterhin eine experimentelle Therapieform. Limitierende Faktoren sind zum einen die hohe Komplexität vieler Erkrankungen und zum anderen die häufig noch unzureichende Effizienz und geringe Spezifität der Vektoren. Eine weitere Herausforderung für den Erfolg gentherapeutischer Ansätze, vor allem im Bereich der monogenetischen und der Infektionserkrankungen, ist das Erzielen eines stabilen Gentransfers mit dauerhafter Expression der transferierten Nukleinsäure bei gleichzeitiger Vermeidung der Insertionsmutagenese. Diese interdisziplinären Herausforderungen werden gemeinsam von Grundlagenforschern und Klinikern in enger Zusammenarbeit mit den regulatorischen Behörden angegangen.
Virale Gentransfer‐Arzneimittel. Therapie mit “entschärften” Humanpathogenen
Authors: Winckler Thomas
Published: April 2011

Somatischer Gentransfer ist eine experimentelle Therapieform, die es ermöglichen soll, durch Gendefekte verursachte Krankheiten kausal zu behandeln. Heute sind Gentherapie‐Studien so angelegt, dass dem Patienten im Sinne einer Substitutionstherapie eine intakte Genkopie zugeführt wird. Im Idealfall kann der Patient das fehlende Protein dann wieder selbst bilden. Das therapeutische Gen wird bestimmten Zellen des Patienten über Vektoren zugeführt, die im Sinne des Arzneimittelgesetzes als Gentransfer‐Arzneimittel bezeichnet werden. Es gibt keinen eindeutig optimalen Gentransfer‐Vektor für jedes Gentherapie‐Problem. Vielmehr muss für jede Therapie der beste Vektor unter Berücksichtigung der spezifischen Stärken und Schwächen verschiedener Vektorsysteme gefunden werden.

Häufig verwendet werden virale Vektoren, die durch ihre natürlichen Infektionsmechanismen die therapeutischen Gene besonders effizient in die Patientenzellen einschleusen. Unter den viralen Gentransfer‐Arzneimitteln gibt es solche, die die genetische Information in ein Chromosom einbauen (z.B. Retroviren) und solche, die extrachromosomal bleiben (z.B. Adenoviren). Man geht davon aus, dass ein “therapeutisches Gen” in das Genom der modifizierten Zellen integriert werden muss, um eine lang anhaltende Expression in sich teilenden Zellen zu ermöglichen.
Nichtvirale Gentransfer‐Arzneimittel. Therapie mit synthetischen Vektoren
Authors: Fischer Dagmar , Fahr Alfred
Published: April 2011

Die Suche nach Alternativen zu viralen Vektoren hat zu einer unglaublichen Zahl von nichtviralen Vektorsystemen geführt. Unterschiedlichste Strukturen auf der Basis von Lipiden, Polymeren und anorganischen Verbindungen wurden auf ihre Eignung als Transfektionssystem für DNA untersucht. Die Euphorie der frühen Studien führte zur Entdeckung immer neuer Verbindungen und Partikelsysteme, aber auch zur Frage, welche dieser Systeme denn nun am besten geeignet sind. Nachfolgend wurden in vielen Untersuchungen Struktur‐Aktivitäts‐Beziehungen etabliert, die die Strukturmerkmale und ihren Einfluss auf biologische und toxikologische Eigenschaften der Trägersysteme systematisch beschreiben.

Der wesentliche Vorteil der nichtviralen Vektoren besteht in der Möglichkeit, zielgerichtet Modifikationen einzubauen und dadurch Verträglichkeit, Effizienz und Stabilität zu verbessern. Für die Zukunft zeichnen sich multifunktionale Systeme ab, die nicht nur mit Wirkstoffen, sondern auch mit Markern zur simultanen Verfolgung der Trägersysteme im Organismus als Theranostics dienen.
Minicircle – Die nächste Generation nicht‐viraler Gentherapie‐Vektoren. Zirkuläre, superspiralisierte Expressionskassetten ersetzen Plasmid‐DNA
Authors: Schleef Martin , Schmeer Marco
Published: April 2011

Klassische Plasmid‐DNA, wie sie in der Gentherapieforschung eingesetzt wird, enthält Sequenzmotive, die lediglich für die Vermehrung der DNA in Bakterienkulturen benötigt werden. Für eine effiziente Genexpression in den Zielzellen sind diese Sequenzbereiche überflüssig und sogar störend. Neuerdings ist die Herstellung entsprechender DNA‐Moleküle möglich, die nur die therapeutisch wirksame Genkassette enthalten.
Wie Genvektoren mit dem richtigen Schlüssel ausgestattet werden. Die Zelloberfläche gezielt ansteuern
Authors: Abel Tobias , Kreppel Florian , Ogris Manfred , Büning Hildegard
Published: April 2011

Essentiell für die Realisierung gentherapeutischer Behandlungsstrategien ist die Verfügbarkeit von geeigneten “Genfähren” (Vektoren). Mit der Optimierung der Vektoren befasst sich ein eigenes Forschungsgebiet, die Vektorologie. Ein Teilbereich der Vektorologie fokussiert auf die Verbesserung der Gentransfereffizienz und ‐spezifität. Hierzu wurde unter anderem die Cell‐surface‐targeting‐Technologie entwickelt, die in diesem Beitrag vorgestellt werden wird.