bluuebunny/crossref_metadata_2025 huggingface dataset:
Electrothermal stability of uniform arrays of one‐port elements
Authors: Storti‐Gajani Giancarlo , Premoli Amedeo , Brambilla Angelo
Published: January 2009

Power electronic elements are often built employing arrays of devices designed to evenly share high currents over a large number of single devices. In some situations, mismatch in current sharing can occur causing temperature differences between elements of the array. These differences can trigger electrothermal instability phenomena and even device destruction. In this paper, we consider the electrothermal dynamic behavior of arrays composed of identical one‐port elements. We first introduce a simplified model of the thermal paths and of the elements composing the array that allows the analysis of the behavior of the electrothermal system. Then, we investigate from a mathematical standpoint dynamic effects governing current sharing and possible situations causing hot spots with consequent device destruction. These results are compared with simulations of detailed non‐linear models confirming predictions given by the simplified model. Copyright © 2008 John Wiley & Sons, Ltd.
A terminal‐controlled vertical handover decision scheme in IEEE 802.21‐enabled heterogeneous wireless networks
Authors: Wu Jung‐Shyr , Yang Shun‐Fang , Hwang Bor‐Jiunn
Published: January 2009

The seamless internetworking among heterogeneous networks is in great demand to provide ‘always‐on’ connectivity services with quality of service (QoS) provision, anywhere at anytime. The integration of wireless‐fidelity (Wi‐Fi) and wireless metropolitan area networks (WiMAX) networks can combine their best features to provide ubiquitous access, while mediating the weakness of both networks. While it is challenging to obtain optimized handover decision‐based dynamic QoS information, users can improve their perceived QoS by using the terminal‐controlled handover decision in a single device equipped with multiple radio interfaces. The IEEE 802.21 aims at providing a framework that defines media‐independent handover (MIH) mechanism that supports seamless handover across heterogeneous networks. In this paper, an multiple attributes decision making‐based terminal‐controlled vertical handover decision scheme using MIH services is proposed in the integrated Wi‐Fi and WiMAX networks to provide ‘always‐on’ connectivity QoS services. The simulation results show that the proposed scheme provides smaller handover times and lower dropping rate than the RSS‐based and cost function‐based vertical handover schemes. Copyright © 2009 John Wiley & Sons, Ltd.
Characterization of dendritic spines in the Drosophila central nervous system
Authors: Leiss Florian , Koper Ewa , Hein Irina , Fouquet Wernher , Lindner Jana , Sigrist Stephan , Tavosanis Gaia
Published: January 2009

Dendritic spines are a characteristic feature of a number of neurons in the vertebrate nervous system and have been implicated in processes that include learning and memory. In spite of this, there has been no comprehensive analysis of the presence of spines in a classical genetic system, such as Drosophila, so far. Here, we demonstrate that a subset of processes along the dendrites of visual system interneurons in the adult fly central nervous system, called LPTCs, closely resemble vertebrate spines, based on a number of criteria. First, the morphology, size, and density of these processes are very similar to those of vertebrate spines. Second, they are enriched in actin and devoid of tubulin. Third, they are sites of synaptic connections based on confocal and electron microscopy. Importantly, they represent a preferential site of localization of an acetylcholine receptor subunit, suggesting that they are sites of excitatory synaptic input. Finally, their number is modulated by the level of the small GTPase dRac1. Our results provide a basis to dissect the genetics of dendritic spine formation and maintenance and the functional role of spines. © 2009 Wiley Periodicals, Inc. Develop Neurobiol, 2009
Large‐scale rainfall simulation over shallow caves on karst shrublands
Authors: Gregory Lucas , Wilcox Bradford P. , Shade Bev , Munster Clyde , Owens Keith , Veni George
Published: January 2009

Within semi‐arid landscapes, karst areas are among the most productive in terms of water supply—largely because of the high rates of groundwater recharge compared with those of other semi‐arid areas. Recharge rates in karst regions may be affected by the type of vegetation cover. Understanding the interactions between recharge and vegetation is important at many levels, but the complex nature of karst hydrology makes this endeavour challenging. This paper presents the results of a set of hillslope‐scale rainfall simulation experiments conducted within a juniper–oak woodland and over a shallow karst cave that was instrumented for drip‐rate monitoring. The variables measured during these experiments include the amounts and timing of cave recharge, surface runoff, stemflow, and throughfall. The findings of this study provide insights into the importance of canopy interception during runoff‐producing events, the nature and relative magnitude of rapid recharge, and the interplay between recharge and surface runoff. Key findings of the study were (1) for simulated rainstorms of around 50 mm, between 0 and 23% of the water applied was intercepted (depending on cloud conditions), and 4–9% of the water reaching the ground surface came from stemflow (which was highest under the wettest conditions); (2) surface runoff accounted for approximately 3% of the water applied; and (3) recharge accounted for between 8 and 17% of the water applied and typically reached its maximum level within 20 min of rainfall cessation, declining rapidly thereafter. Copyright © 2009 John Wiley & Sons, Ltd.
Direct Aza‐Diels–Alder Reaction in Water Catalyzed by Layered α‐Zirconium Hydrogen Phosphate and Sodium Dodecyl Sulfate
Authors: Costantino Umberto , Fringuelli Francesco , Orrù Mara , Nocchetti Morena , Piermatti Oriana , Pizzo Ferdinando
Published: January 2009

The direct aza‐Diels–Alder reaction between 2‐cyclohexen‐1‐one (1) and benzaldimines 2 in water is reported for the first time. The reaction occurs at 30 °C, is catalyzed by layered α‐zirconium hydrogen phosphate (α‐ZrP) and requires the presence of sodium dodecyl sulfate (SDS). The reaction yield is excellent, the reaction is faster and the exo diastereoselectivity is higher than when organic solvent is used. The one‐pot, three‐component version of the reaction and the recycling of both the catalyst and the aqueous mother liquor in toto (water, α‐ZrP and SDS) have also been investigated. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Symbolic threat and social dominance among liberals and conservatives: SDO reflects conformity to political values
Authors: Morrison Kimberly Rios , Ybarra Oscar
Published: January 2009

Three studies tested the effects of symbolic threat to group values and strength of ingroup (political party) identification on social dominance orientation (SDO), a measure of tolerance for social hierarchies. In Studies 1 and 3, conservative participants were made to feel as though their group's values were either threatened or not threatened by liberals prior to completing the SDO measure. In Studies 2 and 3, liberal participants were made to feel as though their group's values were either threatened or not threatened by conservatives prior to completing the SDO measure. Results demonstrated that high ingroup (political party) identification was associated with high SDO scores for threatened conservatives, and with low SDO for threatened liberals. These findings suggest that in response to symbolic threat, SDO can shift in directions consistent with protecting the ingroup's identity. Copyright © 2009 John Wiley & Sons, Ltd.
Interference from Trace Copper in Electrochemical Investigations Employing Carboxylic Acid Terminated Thiol Modified Gold Electrodes
Authors: Qu Xiaohu , Bond Alan M. , Martin Lisandra L.
Published: January 2009

Unexpectedly, electrochemistry at variable chain length carboxylic acid terminated alkylthiol self‐assembled monolayers (SAMs) on gold electrodes gives rise to a Faradaic process in buffered aqueous electrolyte solution. In particular, the three‐carbon chain length, 3‐mercaptopropionic acid (MPA), exhibits a chemically reversible process with a mid‐point potential of 175 mV vs. Ag/AgCl under conditions of cyclic voltammetry. This process is associated with the presence of trace (parts per billion) amounts of copper(II) ions present in the chemical reagents used to prepare the aqueous electrolyte and also from the gold electrode itself. The carboxylic acid moiety on the SAM concentrates Cu2+ ions by coordination and this surface confined layer is then reduced. Methods to minimize the interference of Cu2+ ions at carboxylic acid terminated SAM are discussed and caution with respect to the interpretation of protein electrochemistry is recommended when using carboxylic acid functionalized SAMs to provide biocompatible electrochemical transduction surfaces, unless a metal free environment can be obtained.
Psychiatric disorder as a first manifestation of cancer: A 10‐year population‐based study
Authors: Benros Michael E. , Laursen Thomas M. , Dalton Susanne O. , Mortensen Preben B.
Published: January 2009

To investigate the possibility that psychiatric symptoms could be caused by a yet undetected cancer or be part of a paraneoplastic syndrome, nationwide population‐based registers were linked including the Danish Psychiatric Central Register and the Danish Cancer Registry. Data were analysed as a cohort study using survival analysis techniques and incidence rate ratios (IRRs) were used as measures of relative risk. A total of 4,320,623 persons were followed in the 10‐year period 1994–2003, resulting in 37,581,600 person‐years at risk, 202,144 persons with a first‐time psychiatric contact, and 208,995 persons diagnosed with cancer. During the first month after a first‐time psychiatric contact, the incidence of all forms of cancer was elevated; IRR: 2.61 (95% CI, 2.31–2.95). Particularly the incidence of brain tumours was elevated; IRR: 18.85 (95% CI, 14.52–24.48), but also the incidence of lung cancer; IRR: 2.98 (95% CI, 2.16–4.12), and especially small‐cell lung cancer; IRR: 6.13 (95% CI, 3.39–11.07) was elevated. The elevated IRR for most cancers decreased towards unity within the first 3 months, except for brain tumours, for which the IRR remained significantly elevated during the first 9 months. One of every 63 patients above 50 years of age was diagnosed with malignant cancer within 1 year of first‐time psychiatric contact. These results indicate an increased incidence of cancer, especially for brain tumours and small‐cell lung cancer, in the first months after a first‐time contact to a psychiatric hospital. Clinicians should be aware that first‐onset psychiatric symptoms could be a sign of a yet undetected cancer. © 2009 UICC
Localization of nuclear cathepsin L and its association with disease progression and poor outcome in colorectal cancer
Authors: Sullivan Shane , Tosetto Miriam , Kevans David , Coss Alan , Wang Laimun , O'Donoghue Diarmuid , Hyland John , Sheahan Kieran , Mulcahy Hugh , O'Sullivan Jacintha
Published: January 2009

Previous in vitro studies have identified a nuclear isoform of Cathepsin L. The aim of this study was to examine if nuclear Cathepsin L exists in vivo and examine its association with clinical, pathological and patient outcome data. Cellular localization (nuclear and cytoplasmic) and expression levels v of Cathespin L in 186 colorectal cancer cases using immunohistochemistry. The molecular weight and activity of nuclear and cytoplasmic Cathepsin L in vivo and in vitro were assessed by Western blotting and ELISA, respectively. Epithelial nuclear staining percentage (p = 0.04) and intensity (p = 0.006) increased with advancing tumor stage, whereas stromal cytoplasmic staining decreased (p = 0.02). Using multivariate statistical analysis, survival was inversely associated with staining intensity in the epithelial cytoplasm (p = 0.01) and stromal nuclei (p = 0.007). In different colorectal cell lines and in vivo tumors, pro‐ and active Cathepsin L isoforms were present in both the cytoplasm and nuclear samples, with pro‐Cathepsin L at 50 kDa and active Cathepsin L at 25 kDa. Purified nuclear and cytoplasmic fractions from cell lines and tumors showed active Cathepsin L activity. The identification of nuclear Cathepsin L may play an important prognostic role in colorectal disease progression and patient outcome. Moreover, these findings suggest that altering active nuclear Cathepsin L may significantly influence disease progression. © 2009 UICC
Management of familial hypertriglyceridemia during pregnancy with plasma exchange
Authors: Sivakumaran Praveen , Tabak Steven W. , Gregory Kimberly , Pepkowitz Samuel H. , Klapper Ellen B.
Published: January 2009

Hypertriglyceridemia‐induced pancreatitis is a serious complication of familial dyslipidemias. Hormonal influences during pregnancy can compromise otherwise controlled lipid levels in women with familial hypertriglyceridemia and predispose to pancreatitis leading to increased morbidity in both mother and fetus. We report the successful use of therapeutic plasma exchange (TPE) in the management of hypertriglyceridemia during pregnancy resulting in avoidance of pancreatitis and delivery of a healthy term infant. Thirteen TPEs were performed from 19 to 36 weeks gestation to maintain tight control of triglyceride levels. J. Clin. Apheresis, 2009. © 2009 Wiley‐Liss, Inc.
Kaempferol induces apoptosis in two different cell lines via Akt inactivation, Bax and SIRT3 activation, and mitochondrial dysfunction
Authors: Marfe Gabriella , Tafani Marco , Indelicato Manuela , Sinibaldi‐Salimei Paola , Reali Valentina , Pucci Bruna , Fini Massimo , Russo Matteo Antonio
Published: January 2009

Kaempferol (3,4′,5,7‐tetrahydroxyflavone) is a flavonoid with anti‐ and pro‐oxidant activity present in various natural sources. Kaempferol has been shown to posses anticancer properties through the induction of the apoptotic program. Here we report that treatment of the chronic myelogenous leukemia cell line K562 and promyelocitic human leukemia U937 with 50 µM kaempferol resulted in an increase of the antioxidant enzymes Mn and Cu/Zn superoxide dismutase (SOD). Kaempferol treatment induced apoptosis by decreasing the expression of Bcl‐2 and increasing the expressions of Bax. There were also induction of mitochondrial release of cytochrome c into cytosol and significant activation of caspase‐3, and ‐9 with PARP cleavage. Kaempferol treatment increased the expression and the mitochondria localization of the NAD‐dependent deacetylase SIRT3. K562 cells stably overexpressing SIRT3 were more sensitive to kaempferol, whereas SIRT3 silencing did not increase the resistance of K562 cells to kaempferol. Inhibition of PI3K and de‐phosphorylation of Akt at Ser473 and Thr308 was also observed after treating both K562 and U937 cells with kaempferol. In conclusion our study shows that the oxidative stress induced by kaempferol in K562 and U937 cell lines causes the inactivation of Akt and the activation of the mitochondrial phase of the apoptotic program with an increase of Bax and SIRT3, decrease of Bcl‐2, release of cytochrome c, caspase‐3 activation, and cell death. J. Cell. Biochem. 106: 643–650, 2009. © 2009 Wiley‐Liss, Inc.
Inactivation of 14‐3‐3 σ by promoter methylation correlates with metastasis in nasopharyngeal carcinoma
Authors: Yi Bin , Tan Shuang‐Xiang , Tang Can‐E , Huang Wei‐Guo , Cheng Ai‐Lan , Li Cui , Zhang Peng‐Fei , Li Mao‐Yu , Li Jian‐Ling , Yi Hong , Peng Fang , Chen Zhu‐Chu , Xiao Zhi‐Qiang
Published: January 2009

14‐3‐3 σ, the downstream target of p53, is a negative regulator of cell cycle G2‐M phase checkpoint in response to DNA damage. Our previous comparative proteomics study showed that 14‐3‐3 σ was downregulated or lost in nasopharyngeal carcinoma (NPC) tissue compared with non‐cancerous nasopharyngeal epithelial tissue (NNET). In this study, we further investigated for the epigenetic mechanism of 14‐3‐3 σ inactivation. Methylation‐specific PCR showed 14‐3‐3 σ promoter methylation in 100% of analyzed NPC cell lines (4/4) but not in immortalized human nasopharyngeal epithelial cell line NP69. Treatment of the four NPC cell lines with the methyltransferase inhibitor 5‐aza‐2′‐dC resulted in the demethylation and upregulation of 14‐3‐3 σ. In tissues, 14‐3‐3 σ promoter methylation occurred at a higher frequency in NPC, 63/75 (84%), compared to adjacent NNET, 7/25 (28%), and fully methylated 14‐3‐3 σ promoter was detected in NPC but not in any of adjacent NNET. RT‐PCR, Western blotting, and immunohistochemistry showed that 14‐3‐3 σ expression was downregulated or lost in NPC with methylation, and there was a negative correlation between the expression levels and methylation statuses of 14‐3‐3 σ gene. In addition, the patients with methylated 14‐3‐3 σ presented a higher frequency of lymph node and distant metastasis, and an advanced clinical stage, and overexpression of 14‐3‐3 σ in NPC cell line 5‐8F with high metastatic potential was able to inhibit its in vitro invasive ability. Our data are the first to show that 14‐3‐3 σ is frequently inactivated by promoter methylation in NPC and this aberrant methylation correlates with lymph node and distant metastasis. J. Cell. Biochem. 106: 858–866, 2009. © 2009 Wiley‐Liss, Inc.
Differential expression of nuclear matrix proteins during the differentiation of human neuroblastoma SK‐N‐SH cells induced by retinoic acid
Authors: Liang Ying , Li Qi‐Fu , Zhang Xiu‐Yan , Shi Song‐Lin , Jing Guang‐Jun
Published: January 2009

To investigate the alteration of nuclear matrix proteins (NMPs) during the differentiation of neuroblastoma SK‐N‐SH cells induced by retinoic acid (RA), differentiation markers were detected by immunocytochemistry and NMPs were selectively extracted and subjected to two‐dimensional gel electrophoresis analysis. Immunocytochemical observation demonstrated that the expression of neuronal markers was up‐regulated in SK‐N‐SH cells following RA treatment. Meanwhile, 52 NMPs (41 of which were identified) changed significantly during SK‐N‐SH differentiation; four of these NMPs were further confirmed by immunoblotting. This study suggests that the differentiation of neuroblastoma cells was accompanied by the altered expression of neuronal markers and NMPs. The presence of some differentially expressed NMPs was related to the proliferation and differentiation of neuroblastomas. Our results may help to reveal the relationship between NMPs and neuroblastoma carcinogenesis and reversion, as well as elucidate the regulatory principals driving neural cell proliferation and differentiation. J. Cell. Biochem. 106: 849–857, 2009. © 2009 Wiley‐Liss, Inc.
Expression profiles of SV40‐immortalization‐associated genes upregulated in various human cancers
Authors: Jung Hyun Min , Choi Seong‐Jun , Kim Jin Kyeoung
Published: January 2009

Immortalization is an early and essential step of human carcinogenesis which is associated with alterations in gene expression and regulation. Suppression subtractive hybridization (SSH) was successfully performed to identify immortalization‐associated genes upregulated in SV40‐immortalized lung fibroblasts. We identified 116 known genes which were related to diverse functions, with 32.8% relevant for cell cycle or proliferation indicating the potential involvement of these genes in immortalization. We chose eight known genes located on the overrepresented chromosomes of non‐small‐cell lung cancers (NSCLCs). ASPM, RFC4, C3orf26, BXDC2, C15orf44, AURKA, C20orf77, and RBMX were upregulated in immortalized cells, cancer cells, and non‐small‐cell lung cancer (NSCLC) tissues. We additionally cloned two novel genes (CHA‐V‐97 and CHA‐V‐165) which showed similar upregulated expression patterns in cells and tissues examined. Identification and further characterization of these genes may provide insights of novel players for immortalization and human carcinogenesis. J. Cell. Biochem. 106: 703–713, 2009. © 2009 Wiley‐Liss, Inc.
Hypoxia or in situ normoxia: The stem cell paradigm
Authors: Ivanovic Zoran
Published: January 2009

Although O2 concentrations are considerably lowered in vivo, depending on the tissue and cell population in question (some cells need almost anoxic environment for their maintenance) the cell and tissue cultures are usually performed at atmospheric O2 concentration (20–21%). As an instructive example, the relationship between stem cells and micro‐environmental/culture oxygenation has been recapitulated. The basic principle of stem cell biology, “the generation‐age hypothesis,” and hypoxic metabolic properties of stem cells are considered in the context of the oxygen‐dependent evolution of life and its transposition to ontogenesis and development. A hypothesis relating the self‐renewal with the anaerobic and hypoxic metabolic properties of stem cells and the actual O2 availability is elaborated (“oxygen stem cell paradigm”). Many examples demonstrated that the cellular response is substantially different at atmospheric O2 concentration when compared to lower O2 concentrations which better approximate the physiologic situation. These lower O2 concentrations, traditionally called “hypoxia” represent, in fact, an in situ normoxia, and should be used in experimentation to get an insight of the real cell/cytokine physiology. The revision of our knowledge on cell/cytokine physiology, which has been acquired ex vivo at non physiological atmospheric (20–21%) O2 concentrations representing a hyperoxic state for most primate cells, has thus become imperious. J. Cell. Physiol. 219: 271–275, 2009. © 2009 Wiley‐Liss, Inc.
Thermal killing of human colon cancer cells is associated with the loss of eukaryotic initiation factor 5A
Authors: Gosslau Alexander , Jao David Li‐en , Butler Renee , Liu Alice Y.‐C. , Chen Kuang Yu
Published: January 2009

Heat‐induced cell death appears to be a cell‐specific event. Chronic heat stress was lethal to human colon cancer cells (Caco‐2, HT29, and HCT116), but not to normal diploid fibroblasts and other cancer cells (BJ‐T, WI38, HeLa, ovarian 2008, WI38VA). Acute heat stress (45–51°C, 30 min) caused cell death of colon cancer cells during recovery at physiological temperature. Thermal killing of Caco‐2 cells was not mediated via oxidative stress since Caco‐2 cells were much more resistant than HeLa and other cancer cells to H2O2‐induced cell death. Acute heat stress caused a striking loss of eukaryotic initiation factor 5A (eIF5A) in colon cancer cells, but not in HeLa and other normal or transformed human fibroblasts. The heat‐induced loss of eIF5A is likely to be due to changes in the protein stability. The half‐life of eIF5A was changed from >20 h to less than 30 min during the acute heat stress. Sequence analysis of the eIF5A gene from Caco‐2 and HeLa cells did not reveal any difference, suggesting that the change in stability in Caco‐2 cells was not due to any eIF5A mutation. Pretreatment of cells with protease inhibitors such as phenylmethyl sulfonyl fluoride (PMSF) partially blocked the heat‐induced loss of eIF5A and prevented heat‐induced cell death. In light of the essential role of eIF5A in cell survival and proliferation, our results suggest that the stability of eIF5A may have an important role in determining the fate of the particular cell type after severe heat stress. J. Cell. Physiol. 219: 485–493, 2009. © 2009 Wiley‐Liss, Inc.
Immunomodulatory properties of human periodontal ligament stem cells
Authors: Wada Naohisa , Menicanin Danijela , Shi Songtao , Bartold P. Mark , Gronthos Stan
Published: January 2009

Tissue engineering utilizing periodontal ligament stem cells (PDLSCs) has recently been proposed for the development of new periodontal regenerative therapies. Although the use of autologous PDLSC transplantation eliminates the potential of a significant host immune response against the donor cells, it is often difficult to generate enough PDLSCs from one donor source due to the variation of stem cell potential between donors and disease state of each patient. In this study, we examined the immunomodulatory properties of PDLSCs as candidates for new allogeneic stem cell‐based therapies. Human PDLSCs displayed cell surface marker characteristics and differentiation potential similar to bone marrow stromal stem cells (BMSSCs) and dental pulp stem cells (DPSCs). PDLSCs, BMSSCs, and DPSCs inhibited peripheral blood mononuclear cell (PBMNC) proliferation stimulated with mitogen or in an allogeneic mixed lymphocyte reaction (MLR). Interestingly, gingival fibroblasts (GFs) also suppressed allogeneic PBMNC proliferation under both assay conditions. PDLSCs, BMSSCs, DPSCs, and GFs exhibited non‐cell contact dependent suppression of PBMNC proliferation in co‐cultures using transwells. Furthermore, conditioned media (CM) derived from each cell type pretreated with IFN‐γ partially suppressed PBMNC proliferation when compared to CMs without IFN‐γ stimulation. In all of these mesenchymal cell types cultured with activated PBMNCs, the expression of TGF‐β1, hepatocyte growth factor (HGF) and indoleamine 2, 3‐dioxygenase (IDO) was upregulated while IDO expression was upregulated following stimulation with IFN‐γ. These results suggest that PDLSCs, BMSSCs, DPSCs, and GFs possess immunosuppressive properties mediated, in part, by soluble factors, produced by activated PBMNCs. J. Cell. Physiol. 219: 667–676, 2009. © 2009 Wiley‐Liss, Inc.
Fast and sensitive liquid chromatography/electrospray mass spectrometry method to study ocular penetration of EDL‐155, a novel antitumor agent for retinoblastoma in rats
Authors: Ramagiri Suma , Ma Fei , Kosanam Hari , Wang XiangDi , Patil Renukadevi , Miller Duane D. , Geisert Eldon , Yates Charles R.
Published: January 2009

Our group has used the tetrahydroisoquinoline derivative EDL‐155 to treat glioblastoma in animal models and it is currently being evaluated in the treatment of ocular cancers. The purpose of this study was to develop a rapid and sensitive liquid chromatography and tandem mass spectrometry (LC‐MS/MS) method to study the plasma and vitreous humor disposition of EDL‐155 in rats. Animals received a single periocular injection of EDL‐155 (20 mg/kg). Animals were sacrificed at specified times (5, 60, 120, 240 and 360 min) and plasma and vitreous humor samples were obtained. EDL‐155 was isolated by protein precipitation and the extracts were analyzed by reversed‐phase high‐pressure liquid chromatography (HPLC) with MS/MS detection. A structurally similar analog was used as internal standard (IS). The chromatographic run time was 3.5 min per injection. The mass spectrometer was operated in positive‐ion, multiple reaction monitoring (MRM) mode. The mass transitions monitored were m/z332.2 → 167.2 (EDL‐155) and m/z391.2 → 200.2 (IS). The lower limit of quantification (LLOQ) was 0.1 ng/ml in both vitreous humor and plasma. The method was validated for selectivity, linearity, accuracy and precision in rat vitreous humor and partially validated for accuracy and precision in rat plasma. The ion suppression, recovery and stability of the analyte in the biological matrix were also tested. The assay was rapid, sensitive and robust enough to support EDL‐155 ocular penetration studies in a rodent model of intraocular cancer. Application of this method revealed that EDL‐155 was rapidly passed into the vitreous humor following periocular administration. Further, vitreous humor exposure exceeded systemic exposure by approximately sevenfold. High local concentrations coupled with minimal systemic exposure supports further testing of EDL‐155 as localized therapy for intraocular cancers. Copyright © 2009 John Wiley & Sons, Ltd.
Potential of long capillary monolithic columns for the analysis of protein digests
Authors: van de Meent Michiel H. M. , de Jong Gerhardus J.
Published: January 2009

The gain in separation efficiency for protein digests using long monolithic columns has been evaluated for a LC‐MS system with capillary monolithic columns of different lengths (150 and 750 mm). A mixture of BSA, α‐casein and β‐casein tryptic digests was used as a test sample. Peak capacity and productivity (peak capacity per unit time) were determined from base peak chromatograms and MS/MS data were used for protein identification by MASCOT database searching. Peak capacity and protein identification scores were higher for the long column. Analyses with similar gradient slope for the two columns produced ratios of the peak capacities that were slightly higher than the expected value of the square root of the column length ratio. Peak capacity ratios varied from 2.7 to 4.0 for four different gradient slopes, while protein identification scores were 2–4 times higher for the long column. Similar values were obtained for the productivity of both columns and the highest productivity was obtained at gradient times of 45 and 75 min for the short and long column, respectively. The use of long monolithic columns improves peptide separation and increases reliability of protein identification for complex digests, especially if longer gradients are chosen.
Poly(N,N‐dimethylacrylamide‐co‐4‐(ethyl)‐morpholine methacrylamide) copolymer as coating for CE
Authors: Bernal José , Sánchez‐Hernández Laura , Elvira Carlos , Velasco Diego , Ibáñez Elena , Cifuentes Alejandro
Published: January 2009

In this work, a new physically adsorbed coating for CE is presented. This coating is based on a poly(N,N‐dimethylacrylamide‐co‐4‐(ethyl)‐morpholine methacrylamide) (DMA/MAEM) copolymer synthesized in our laboratory. It is demonstrated that the direction and magnitude of the EOF in CE can be modulated by varying the composition of the DMA/MAEM copolymer and the type and pH of the BGE. Moreover, the DMA/MAEM coating provides %RSDn = 5 values for migration times lower than 0.9% for the same capillary and day, whereas the %RSDn = 25 obtained for the interday assay was lower than 2.9%. The stability of the coating procedure is also tested between capillaries obtaining %RSDn = 15 values lower than 2.9%, demonstrating that this physically adsorbed copolymer gives rise to a stable and reproducible coating in CE. Finally, the usefulness of this new cationic copolymer as CE coating is demonstrated through different applications. Namely, it is demonstrated that the CE separation of basic proteins, nucleotides and organic acids is achieved in a fast and easy way by using the DMA/MAEM coated capillary. The use of fused bare silica capillaries did not allow the separation of these compounds under the same analytical conditions. These results demonstrate that this type of coating in CE provides the option of using BGEs that are useless when utilized together with bare silica capillaries making wider the application and possibilities of this analytical technique.
Effect of quasi‐interpenetrating network of polyacrylamide and poly(N,N‐dimethylacrylamide) on separation of dsDNA fragments and basic protein using CE
Authors: Song Weihua , Zhou Dan , Peng Shuhua , Wang Yanmei
Published: January 2009

Quasi‐interpenetrating network (quasi‐IPN) of linear polyacrylamide (LPA) with low molecular mass and poly(N,N‐dimethylacrylamide) (PDMA), which is shown to uniquely combine the superior sieving ability of LPA with the coating ability of PDMA, has been synthesized for application in dsDNA and basic protein separation by CE. The performance of quasi‐IPN on dsDNA separation was determined by polymer concentration, electric field strength, LPA molecular masses and different acrylamide (AM) to N,N‐dimethylacrylamide (DMA) ratio. The results showed that all fragments in Φ×174/HaeIII digest were achieved with a 30 cm effective capillary length at –6 kV at an appropriate polymer solution concentration in bare silica capillaries. Furthermore, EOF measurement results showed that quasi‐IPN exhibited good capillary coating ability, via adsorption from aqueous solution, efficiently suppressing EOF. The effect of the buffer pH values on the separation of basic proteins was investigated in detail. The separation efficiencies and analysis reproducibility demonstrated the good potentiality of quasi‐IPN matrix for suppressing the adsorption of basic proteins onto the silica capillary wall. In addition, when quasi‐IPN was used both as sieving matrix and dynamic coating in bare silica capillaries, higher peak separation efficiencies, and better migration time reproducibility were obtained.
Sensitivity enhancement in tandem liquid chromatographic mass spectrometric assays by summation of two transition ion pairs – perspectives
Authors: Srinivas Nuggehally R.
Published: January 2009

The introduction of tandem liquid chromatographic mass spectrometric assays has boosted the sensitivity of the bioanalytical determination for the scores of analytes as compared to other conventional modes of detection [1–6]. Additionally, many intelligent variants such as improved ionization potential, suitable adduct formation, and/or identification of a precursor ion, switching of modality of detection (+ve to –ve and vice versa), and derivatization steps (to aid fragmentation and/or impart ionization property) within tandem mass spectrometric assays have further aided in improving the sensitivity. Some researchers have also expressed thoughts of using matrix effects in a beneficial manner so that there may be ion enhancement for improving the sensitivity of the assay.
Outcome of minimally invasive management of salivary calculi in 4,691 patients
Authors: Iro Heinrich , Zenk Johannes , Escudier Michael P. , Nahlieli Oded , Capaccio Pasquale , Katz Philippe , Brown Jackie , McGurk Mark
Published: January 2009

Objective:

To evaluate the application of minimally invasive techniques in the management of salivary stones.

Background:

The incidence of salivary calculi is 60 cases/million/year, with most stones situated in the mid or proximal duct. The current treatment of these stones is adenectomy. This paper reports the results of minimally invasive methods of stone removal that avoid gland excision.

Methods:

Observational study of 5,528 consecutive patients treated by lithotripsy, endoscopy, basket retrieval, and /or surgery in five centers from 1990 to 2004 inclusive. A total of 567cases were excluded, leaving 4,691 patients (parotid n = 1,165, submandibular n = 3,526) for analysis.

Results:

Salivary calculi were eliminated in 3,775/4,691 (80.5%) of cases and partly cleared in 782/4,691 (16.7%). Salivary glands were removed in 134/4,691 (2.9%) of patients with symptoms in whom treatment failed.

Conclusions:

Minimally invasive techniques move treatment of salivary calculi to an outpatient or a day case setting. They are reliable ways of both retrieving stones and eliminating symptoms, and mean that the gland rarely has to be removed. Laryngoscope, 2009
CT analysis after distraction osteogenesis in Pierre Robin Sequence
Authors: Roy Saswata , Munson Patrick D. , Zhao Linping , Holinger Lauren D. , Patel Pravin K.
Published: January 2009

Objectives/Hypothesis:

Early mandibular lengthening by distraction osteogenesis provides an alternative to traditional methods of airway management in infants with Pierre Robin sequence (PRS). Little evidence in the medical literature quantitatively demonstrates the changes in skeletal, soft tissue, and hypopharyngeal spaces with mandibular distraction.

Study Design:

Prospective analysis of a cohort of three patients with PRS.

Methods:

We reviewed a series of infants with PRS and severe upper airway obstruction who underwent mandibular distraction. The infants underwent mandibular lengthening with the same internal, unidirectional distraction osteogenesis device. Standardized serial computed tomography (CT) scans were obtained according to established protocol. Computed tomography data were extracted and analyzed with medical image analysis software for mandibulo‐maxillary arch harmony, symmetry, hypopharyngeal airway volume, geniohyoid distance, distraction osteogenesis bone volume, and mandibular length.

Results:

Mandibulo‐maxillary alveolar ridge distances were corrected to 0.5 mm after distraction. Clinical examination showed good arch harmony without open‐bite or cross‐bite deformities. Mandibular ramus was lengthened by 19.5%; the body, 43.4%. After distraction, total mandibular length was increased by 26.2%; hypopharyngeal airway volume, 192%; posterior distance from pharyngeal wall to tongue base, 198.9%; and geniohyoid distance, 14.1%.

Conclusions:

Unidirectional internal microdistractors can achieve good mandibulo‐maxillary arch harmony. Hypopharyngeal airway volume increases substantially, with an even greater increase in distance between tongue base and posterior pharyngeal wall. As the distal mandibular segment is distracted, the hyoid moves anteriorly, with minor increase in geniohyoid relationship. Internal mandibular microdistraction devices represent a substantial advance in airway obstruction management in infants with micrognathia. Laryngoscope, 2009
Video rigid laryngeal endoscopy compared to laryngeal mirror examination: An assessment of patient comfort and clinical visualization
Authors: Dunklebarger Joshua , Rhee Diane , Kim Seungwon , Ferguson Berrylin
Published: January 2009

Objectives:

To determine whether there are differences in patient preference and extent of laryngeal visualization between video rigid (30 degree endoscope) laryngoscopy (VRL) and laryngeal mirror examination (LME).

Study Design:

A prospective comparison by patients undergoing laryngeal examination by both VRL and LME conducted by two examiners experienced in both mirror and rigid video endoscopy.

Methods:

Forty‐three patients had laryngeal examination by both VRL and LME in alternating order. Patients were instructed to observe their exam on a monitor screen during the rigid exam. At the conclusioon of both laryngeal examinations, patients were asked to rank comfort and level of gagging on a 1 to 10 scale for both VRL and LME, as well as preference between the two methods and whether seeing their laryngeal examination on the video screen was helpful. The extent of laryngeal visualization by the clinician was recorded for each examination.

Results:

Patient comfort level was greater with VRL (P < .001) and gagging was significantly less with VRL (P < .001) compared to LME. VRL provided a more complete examination of the larynx by the clinician (P < .001) compared to LME. Patient preference significantly favored VRL (79.1%) compared to LME (18.4%) and 2.3% had no preference (P < .001) A total of 83.7% found visualization of laryngeal exam on the monitor during the VRL helpful.

Conclusions:

VRL is superior to LME for most patients based on comfort, extent of laryngeal examination by the clinician, and patient preference. The majority of patients found visualization of their laryngeal examination during VRL to be helpful. Laryngoscope, 2009
Middle ear pressure change as a function of body position
Authors: Cinamon Udi , Russo Eyal , Levy Dalia
Published: January 2009

Objective:

To verify and assess immediate middle ear (ME) pressure changes as a function of body position.

Study Design:

A prospective clinical trail.

Patients and Methods:

Twenty‐six adult volunteers having 52 normal, healthy ears had tympanometric ME pressures measured in an upright and recumbent positions. Recordings were obtained immediately after positioning and after 3 minutes. The main outcome measure was the pressure difference between upright and recumbent measurements, that is, positional ME pressure change.

Results:

All ME pressure recordings were within (−)100 to (+)55 mmH2O. An instant and significant (P < .001) pressure elevation was recorded in all ears once position changed from upright to recumbent. The average pressure increment was 19 mmH2O. Once a recumbent ear was repositioned upright it demonstrated an immediate pressure drop and regaining the initial ME pressure. Assuming the volume of a normal ME cleft as 8 mL and following Boyle's law, an ME volume alteration of about 17 μL was required to induce such pressure change.

Conclusions:

Positional pressure changes were within the range of normal daily ME pressure variations. The instantaneous pressure changes and reversibility may be explained by filling and emptying of blood vessels within the ME cleft, following gravity causing an alteration of the aerated volume. Individual differences of pressure change may follow variability of ME cleft volume, its surface, and vessel density. Laryngoscope, 2009
Mitomycin C and the endoscopic treatment of laryngotracheal stenosis: Are two applications better than one?
Authors: Smith Marshall E. , Elstad Mark
Published: January 2009

Objectives/Hypothesis:

Endoscopic treatment of laryngotracheal stenosis by airway dilation, despite short‐term improvement, is often associated with long‐term relapse. Mitomycin‐C (MMC) inhibits fibroblast proliferation and synthesis of extracellular matrix proteins, and thereby modulates wound healing and scarring. MMC application at the time of endoscopic dilation and laser surgery has been suggested to improve outcomes, but this has not been studied in a rigorous manner. This study examines the hypothesis that two topical applications of MMC given 3–6 weeks apart will result in decreased scarring/restenosis of the airway, when compared to a single topical application.

Study Design:

A randomized, prospective, double‐blind, placebo‐controlled clinical trial.

Methods:

Twenty‐six patients with laryngotracheal stenosis due to idiopathic subglottic stenosis, postintubation stenosis, or Wegener's granulomatosis entered a protocol to receive three endoscopic CO2 laser and dilation procedures over a 3‐month interval. At the first procedure, after radial CO2 laser incision and airway dilation, all patients received topical application of MMC (0.5 mg/mL) to the airway lesion. One month later, a second endoscopic incision and dilation was performed and the patients were randomized to either a second application of mitomycin‐C or to application of saline placebo. A third dilation procedure was performed 2 months later, without MMC application. Patients were followed for up to 5 years for relapse of airway stenosis with clinical symptoms sufficient to require a subsequent procedure.

Results:

The relapse rates at 1, 3, and 5 years were 7%, 36%, and 69% for patients treated with two applications of MMC compared to 33%, 58%, and 70% for patients treated with one application of MMC. The median interval to relapse was 3.8 years in the two‐application group, compared with 2.4 years in the one‐application group.

Conclusions:

This prospective randomized double‐blind placebo‐controlled trial suggests that, in the endoscopic management of laryngotracheal stenosis, two applications of MMC given 3–4 weeks apart after airway radial incision and dilation reduces the restenosis rate for 2 to 3 years after treatment when compared to a single application. However, restenosis and delayed symptom recurrence continues so that at 5 years the relapse rates are the same. Thus, MMC may postpone, but does not prevent, the recurrence of symptomatic stenosis in the majority of patients. Laryngoscope, 2009
Thermal effects of mobile phones on facial nerves and surrounding soft tissue
Authors: Acar Gul Ozbilen , Yener H. Murat , Savrun Feray Karaali , Kalkan Tunaya , Bayrak Ibrahim , Enver Ozgun
Published: January 2009

Objective:

To investigate the possible thermal effects of microwaves from mobile phones on facial nerves (FN) and surrounding soft tissue.

Study Design:

A prospective study.

Methods:

We studied FN conduction rate and compound muscle action potentials (CMAP) on 12 rabbits before exposure to radiofrequency radiation (RFR) emitted from a mobile phone. Also, the temperature change in the soft tissues around the FN was investigated by a four channel Luxtron fiber optic system. A mobile phone with 1900 MHz frequency was placed over the ipsilateral ear of the rabbit for 25 minutes, and FN and surrounding tissues were exposed to a 1.5 watts pulse modulated (217 packets/s) electromagnetic field. During exposure to RFR, immediately after turning off the mobile phone, and 25 minutes after the exposure temperature change in the surrounding tissue of the FN was recorded and compared to preexposure values. Additionally, another recording regarding the FN functions was done and the data were compared to preexposure values.

Results:

The average temperature of the surrounding soft tissues was 0.39 K higher than the preexposure values during the exposure and immediately after turning off the mobile phone, and decreased to normal levels 25 minutes after the exposure, which was statistically significant. The amplitudes of FN CMAP after radiofrequency radiation exposure were significantly smaller than the preexposure amplitudes and the amplitudes were normal in the 25 minute measurement.

Conclusion:

The RFR emitted from a mobile phone can cause temporary FN dysfunction that can be due to temporary temperature increase in the soft tissue around the FN. Laryngoscope, 2009
Poor radiotherapy compliance predicts persistent regional disease in advanced head/neck cancer
Authors: Patel Urjeet A. , Patadia Monica O. , Holloway Nathaniel , Rosen Fred
Published: January 2009

Objective:

To determine if poor compliance to chemoradiation results in an increased rate of persistent neck disease.

Study Design:

Retrospective, cohort study in an urban, tertiary‐care medical center.

Methods:

The study included patients with N+ stage III/IV squamous cell carcinoma of the upper aerodigestive tract treated with curative‐intent chemoradiation, who underwent subsequent planned neck dissection. Main outcome measure was persistent regional disease evidenced by identifiable carcinoma in neck dissection specimens. Variables including age, gender, race, primary site, initial T, N staging, imaging results, and treatment compliance were assessed and correlated to positive neck dissection pathology.

Results:

Of 40 patients, 18 (45%) had persistent carcinoma in neck dissection specimens while 22 (55%) demonstrated complete response in the neck. There were 14 patients (35%) who were poorly compliant to radiotherapy (≥14 days treatment interruption) and the remaining 26 patients (65%) were considered compliant (<14 missed days). Only 23% of compliant patients had positive pathology while 79% of noncompliant patients had positive pathology (hazard ratio: 9.9). Noncompliance was the only variable that had a statistically significant correlation to positive pathology results (P = .002). Multivariate logistic regression showed all other variables to be insignificant in predicting pathology.

Conclusions:

This study found that poorly compliant patients are at significantly higher risk of persistent neck disease. Poor compliance may help identify patients who will most benefit from neck dissection after chemoradiation. This variable was more predictive than pretreatment variables and posttreatment CT scan. Further studies investigating patterns of failure after chemoradiotherapy in the poorly compliant patient population are warranted. Laryngoscope, 2009