bluuebunny/crossref_metadata_2025 huggingface dataset:
The Reaction of Amino Acids and Proteins with Diazonium Compounds. I. A Spectrophotometric Study of Azo-Derivatives of Histidine and Tyrosine.
Authors: Higgins HG , Fraser D
Published: September 2006

The coupling in alkaline solution of free
histidine and tyrosine with p-diazobenzene-sulphonic acid has been studied as a
basis for quantitative investigation of the behaviour of proteins in the
presence of diazonium compounds. Both mono- and bisazo- derivatives may be
formed with each amino acid, the wavelengths of maximum absorption being 380
and 490 mμ respectively for histidine and 325 and 480 mμ respectively
for tyrosine ; the wavelength displacements on accepting a second diazonium
group are comparable to effects reported for similarly conjugated systems. When
appropriate corrections are made for other absorbing components, the
extinctions at 490 mμ and the initial histidine concentrations up to the
(bis) equivalent of diazonium compound conform to Beer's law, showing that
bis(azobenzenesu1phonic acid)histidine is formed exclusively under these conditions.
At higher histidine concentrations mono(azobenzenesulphonic acid)histidine is
formed in increasing proportions. Even at low initial tyrosine concentrations
both mono- and bis(azobenzenesulphonic acid)-tyrosine are formed, although
mono-coupling is again favoured more as the concentration increases. No direct
reaction between histidine and the nitrous acid used in the formation of the
diazonium compound could be detected spectrophotometrically, but diazotization
of tyrosine appears to reduce the propensity for bis-coupling to some extent.
If urea is incorporated in the system to destroy excess nitrous acid, a yellow
compound having maximum absorption at 430 mμ is formed between
p-diazo-benzenesulphonic acid and the urea.
Colouring Matters of Australian Plants. II. Naphthoquinones from Diospyros hebecarpa A. Cunn
Authors: Cooke RG , Dowd H
Published: September 2006

Ether extraction of Diospyros hebecarpa A.
Cunn. yields plumbagin, and two new compounds which are shown to be 5-hydroxy-7-methyl-1,4-naphthoquinone
and 1,4-diketo-5-hydroxy-7-methyl-1,2,3,4-tetrahydronaphthalene. The
ultraviolet absorption spectra of these and related compounds are recorded, and
the synthesis of 1,4,5-tri-methoxy-7-methylnaphthalene is described.
Alkaloids of the Australian Rutaceae: Pentaceras australis Hook. F. III. Identification of 4-Methylthiocanthin-6-one
Authors: Nelson ER , Price JR
Published: September 2006

The alkaloid C15H10OSN2
occurring in the bark of Pentaceras australis Hook. f. is shown to be
4-methylthiocanthin-6-one. The lactam ring is opened by alcoholic alkali giving
2-methylthio-2-(1'-β-carbolyl)acrylic acid, followed by the elimination of
methyl mercaptan and recyclization to 4-hydroxycanthin-6-one. Confirmation of
the relation- ship of the alkaloid to canthinone is provided by (i) the
ultraviolet absorption spectra, (ii) the formation of methyl mercaptan and
4,5-dihydrocanthine by treatment with zinc and hydrochloric acid, and (iii) the
formation, by treatment with Raney nickel, of canthinone,
4,5-dihydrocanthinone, or the methyl or ethyl esters of β-carbolylpropionic
acid, depending on the conditions employed. The alkaloid has been synthesized
from β-carboline-1-carboxylic acid by conversion of the acid chloride with
malonic ester, followed by cyclization, to 4-hydroxycanthinone, thence to
4-chlorocanthinone which with potassium methyl mercaptide yields
4-methylthiocanthinone. The low basicity of the alkaloid is discussed,
particularly in relation to the basicity of 4-methoxy- canthinone.
The Thermal Conductivity of Organic Vapours: The Influence of Molecular Interaction
Authors: Vines RG
Published: September 2006

A study has been made of the thermal
conductivities of a number of simple organic vapours at various pressures and
temperatures. The measurements indicate that the variation of conductivity with
pressure is a function of gas imperfection ; for substances with appreciable
dipole interaction the effect is large, but for other substances where gas
imperfection involves only van der Waals forces, the effect is much less. In
all cases it is probable that the change in specific beat of the vapour with
pressure is the main cause of the observed conductivity variation.
Colouring matters of Australian Plants. III. Synthesis of 7-Methyljuglone and related compounds
Authors: Cooke RG , Dowd H
Published: September 2006

The structures previously assigned to two constituents
of Diospyros hebecarpa A. Cunn. are confirmed by the synthesis of
5-hydroxy-7-methyl-l,4-naphthoquinone and its conversion to
1,4-diketo-5-hydroxy-7-methyl-1,2,3,4-tetrahydronaphthalene. By an independent
route 5-methoxy-7-methyl-l,4-naphthoquinone has also been prepared, and has
been converted to 1,4,5-trimethoxy-7-methylnaphthalene.
The Alkaloids of Cryptocasrya bowiei (Hook.) Druce
Authors: Ewing J , Hughes GK , Ritchie E , Taylor WC
Published: September 2006

Two closely related water-soluble
alkaloids cryptaustoline and cryptowoline iodides have been isolated from the
bark of Cryptocarya bowiei (Hook.) Druce. Both have been shown to be
derivatives of dibenzo[b,g]pyrrocoline. This constitutes the first isolation of
substances containing this nucleus from natural sources.
The chemicial consitituents of Australian Zanthoxylum species. II. The Constituents of Z. brachyacanthum F. Muell., Z. veneficum F.M. Bail., and Z. suberosum C.T. White
Authors: Cannon JR , Hughes GK , Ritchie E , Taylor WC
Published: September 2006

The known substances l-α-canadine methiodide, β-homochelidonine,
chelerythrine, isocorydine methiodide (a new alkaloid), lupeol, and hesperidin
have been isolated from both Z. brachyacanthum F. Muell. and Z. veneficum F. M.
Bail. and it is suggested that these two species are identical. From Z.
suberosum C.T. White the recently discovered alkaloid, canthin-6-one, was
isolated.
Synthesis and Some Reactions of 1-(Trimethoxymethyl)cyclohexene
Authors: Bourke DG , Collins DJ
Published: September 2006

1-( Trimethoxymethyl ) cyclohexene (11) was synthesized in three steps from N-methyl-N-phenylcyclohex-1-ene-1-carboxamide (8). Reaction of the α,β -unsaturated ortho ester (11) with sodium hydride and N- methylaniline gave a 1:1 mixture of methyl cyclohex-1-ene-1-carboxylate (15) and N,N- dimethylaniline . Treatment of (11) with 3-methoxyphenol gave 1-[ dimethoxy (3'-methoxyphenoxy)methyl] cyclohexene (10) which underwent thermolysis at 250° to give 1,3-dimethoxybenzene (16) and methyl cyclohex-1-ene-1-carboxylate (15).
New Antibiotic Uperin Peptides From the Dorsal Glands of the Australian Toadlet Uperoleia mjobergii
Authors: Bradford AM , Bowie JH , Tyler MJ , Wallace JC
Published: September 2006

The dorsal glandular extract of the toadlet Uperoleia mjobergii contains more than 20 peptides. We report the amino acid sequences of the seven major peptides: these were determined by a combination of mass spectrometry and automated Edman sequencing. Three of these peptides have 19 amino acid residues and belong to the uperin 2 group of peptides [e.g. uperin 2.6, Gly Ile Leu Asp Ile Ala Lys Lys Leu Val Gly Gly Ile Arg Asn Val Leu Gly Ile (OH)], while the other four have 17 residues and are classified as uperins 3 [e.g. Uperin 3.4, Gly Val Gly Asp Leu Ile Arg Lys Ala Val Ala Ala Ile Lys Asn Ile Val (NH2)]. Several of these cationic peptides have been synthesized in order for bioassays to be carried out: they show significant antibiotic activity against a range of Gram-positive microorganisms. A major skin peptide from the related species Uperoleia inundata is a powerful neuropeptide named uperin 1.1 ([Ala2] uperolein ): no corresponding neuropeptide is detected in the skin glands of Uperoleia mjobergii.
Tetradentate (N2O2) Chelate Complexes of the Group 13 Elements Having a Ligand-Metal Stoichiometry of 1:2
Authors: Atwood DA , Jegier JA , Remington MP , Rutherford D
Published: September 2006

In this paper are reported Acen and Salean complexes of the Group 13 elements in a ligand-to-metal stoichiometry of 1:2. These are unconventional by comparison to previously reported examples (with these ligands ) which are predominantly of a 1:1 and 1:3 stoichiometry. The Acen complex, Acen (BPh2)2 (1) (where AcenH2 is N,N'- bis (2-hydroxy(methyl) benzylidene ) ethylenediamine ('common' name)) was isolated as a minor side-product in the synthesis of [ AcenAl ( MeOH )2] BPh4. In a different type of reaction the monomeric SaleanHAl (Al(NMe2)3) (2) (where SaleanH4 is N,N'-bis(2-hydroxybenzy1) ethylenediamine ('common' name)) is isolated. Crystal data for (1): triclinic, Pī , a 9.701(3), b 11.116(1), c 11.393(2) Ǻ, α 62.84(1), β 78.99(1), γ 79.94(1)°, V 1067.6(4), Z 21 with 1032 reflections with F > 6.0σ(F), R = 0.0725. Crystal data for (2): orthorhombic, P 212121, a 12.432(3), b 12.574(2), c 20.024(4) Ǻ, V 3130.3(11), Z 4, with 855 reflections with F > 5.0σ(F), R=0.1044.
Synthesis of Peptide Derivatives of Mimosine. I. L-Mimosylglycine
Authors: Roblot G , Fehrentz JA , Wylde R , Martinez J
Published: September 2006

A successful synthesis of L- mimosylglycine is described. This peptide could be an antagonist of an active fragment of an enkephalin. The structure of this novel peptide has been elucidated by exhaustive n.m.r. methods.
Three restricted forms of Epstein–Barr virus latency counteracting apoptosis in c-myc-expressing Burkitt lymphoma cells
Authors: Kelly Gemma L. , Milner Anne E. , Baldwin Gouri S. , Bell Andrew I. , Rickinson Alan B.
Published: September 2006

Epstein–Barr virus (EBV), a human herpesvirus, transforms B cell growth
in vitro
through expressing six virus-coded Epstein–Barr nuclear antigens (EBNAs) and two latent membrane proteins (LMPs). In many EBV-associated tumors, however, viral antigen expression is more restricted, and the aetiological role of the virus is unclear. For example, endemic Burkitt lymphoma (BL) classically presents as a monoclonal, c-myc-translocation-positive tumor in which every cell carries EBV as an EBNA1-only (Latency I) infection; such homogeneity among EBV-positive cells, and the lack of EBV-negative comparators, hampers attempts to understand EBV's role in BL pathogenesis. Here, we describe an endemic BL that was unusually heterogeneous at the single-cell level and, in early passage culture, yielded a range of cellular clones, all with the same c-myc translocation but differing in EBV status. Rare EBV-negative cells were isolated alongside EBV-positive cells displaying one of three forms of restricted latency: (
i
) conventional Latency I expressing EBNA1 only from a WT virus genome, (
ii
) Wp-restricted latency expressing EBNAs 1, 3A, 3B, 3C, and -LP only from an EBNA2-deleted genome, and (
iii
) a previously undescribed EBNA2
+
/LMP1
−
latency in which all six EBNAs are expressed again in the absence of the LMPs. Interclonal comparisons showed that each form of EBV infection was associated with a specific degree of protection from apoptosis. Our work suggests that EBV acts as an antiapoptotic rather than a growth-promoting agent in BL by selecting among three transcriptional programs, all of which, unlike the full virus growth-transforming program, remain compatible with high c-myc expression.
Detoxification of superoxide without production of H
2
O
2
: Antioxidant activity of superoxide reductase complexed with ferrocyanide
Authors: Molina-Heredia Fernando P. , Houée-Levin Chantal , Berthomieu Catherine , Touati Danièle , Tremey Emilie , Favaudon Vincent , Adam Virgile , Nivière Vincent
Published: September 2006

The superoxide radical O
2
·̅
is a toxic by-product of oxygen metabolism. Two O
2
·̅
detoxifying enzymes have been described so far, superoxide dismutase and superoxide reductase (SOR), both forming H
2
O
2
as a reaction product. Recently, the SOR active site, a ferrous iron in a [Fe
2+
(N-His)
4
(S-Cys)] pentacoordination, was shown to have the ability to form a complex with the organometallic compound ferrocyanide. Here, we have investigated in detail the reactivity of the SOR–ferrocyanide complex with O
2
·̅
by pulse and γ-ray radiolysis, infrared, and UV-visible spectroscopies. The complex reacts very efficiently with O
2
·̅
. However, the presence of the ferrocyanide adduct markedly modifies the reaction mechanism of SOR, with the formation of transient intermediates different from those observed for SOR alone. A one-electron redox chemistry appears to be carried out by the ferrocyanide moiety of the complex, whereas the SOR iron site remains in the reduced state. Surprisingly, the toxic H
2
O
2
species is no longer the reaction product. Accordingly,
in vivo
experiments showed that formation of the SOR–ferrocyanide complex increased the antioxidant capabilities of SOR expressed in an
Escherichia coli sodA sodB recA
mutant strain. Altogether, these data describe an unprecedented O
2
·̅
detoxification activity, catalyzed by the SOR–ferrocyanide complex, which does not conduct to the production of the toxic H
2
O
2
species.
Identification of class I MHC-associated phosphopeptides as targets for cancer immunotherapy
Authors: Zarling Angela L. , Polefrone Joy M. , Evans Anne M. , Mikesh Leann M. , Shabanowitz Jeffrey , Lewis Sarah T. , Engelhard Victor H. , Hunt Donald F.
Published: September 2006

Alterations in phosphorylation of cellular proteins are a hallmark of malignant transformation. Degradation of these phosphoproteins could generate cancer-specific class I MHC-associated phosphopeptides recognizable by CD8
+
T lymphocytes. In a comparative analysis of phosphopeptides presented on the surface of melanoma, ovarian carcinoma, and B lymphoblastoid cells, we find 5 of 36 that are restricted to the solid tumors and common to both cancers. Differential presentation of these peptides can result from differential phosphorylation of the source proteins. Recognition of the peptides on cancer cells by phosphopeptide-specific CD8
+
T lymphocytes validates the potential of these phosphopeptides as immunotherapeutic targets.
Poly(ADP-ribose) polymerase-2 contributes to the fidelity of male meiosis I and spermiogenesis
Authors: Dantzer Françoise , Mark Manuel , Quenet Delphine , Scherthan Harry , Huber Aline , Liebe Bodo , Monaco Lucia , Chicheportiche Alexandra , Sassone-Corsi Paolo , de Murcia Gilbert , Ménissier-de Murcia Josiane
Published: September 2006

Besides the established central role of poly(ADP-ribose) polymerase-1 (Parp-1) and Parp-2 in the maintenance of genomic integrity, accumulating evidence indicates that poly(ADP-ribosyl)ation may modulate epigenetic modifications under physiological conditions. Here, we provide
in vivo
evidence for the pleiotropic involvement of Parp-2 in both meiotic and postmeiotic processes. We show that Parp-2-deficient mice exhibit severely impaired spermatogenesis, with a defect in prophase of meiosis I characterized by massive apoptosis at pachytene and metaphase I stages. Although

Parp-2
−/−

spermatocytes exhibit normal telomere dynamics and normal chromosome synapsis, they display defective meiotic sex chromosome inactivation associated with derailed regulation of histone acetylation and methylation and up-regulated X- and Y-linked gene expression. Furthermore, a drastically reduced number of crossover-associated Mlh1 foci are associated with chromosome missegregation at metaphase I. Moreover,

Parp-2
−/−

spermatids are severely compromised in differentiation and exhibit a marked delay in nuclear elongation. Altogether, our findings indicate that, in addition to its well known role in DNA repair, Parp-2 exerts essential functions during meiosis I and haploid gamete differentiation.
Genome-wide functional analysis of human cell-cycle regulators
Authors: Mukherji Mridul , Bell Russell , Supekova Lubica , Wang Yan , Orth Anthony P. , Batalov Serge , Miraglia Loren , Huesken Dieter , Lange Joerg , Martin Christopher , Sahasrabudhe Sudhir , Reinhardt Mischa , Natt Francois , Hall Jonathan , Mickanin Craig , Labow Mark , Chanda Sumit K. , Cho Charles Y. , Schultz Peter G.
Published: September 2006

Human cells have evolved complex signaling networks to coordinate the cell cycle. A detailed understanding of the global regulation of this fundamental process requires comprehensive identification of the genes and pathways involved in the various stages of cell-cycle progression. To this end, we report a genome-wide analysis of the human cell cycle, cell size, and proliferation by targeting >95% of the protein-coding genes in the human genome using small interfering RNAs (siRNAs). Analysis of >2 million images, acquired by quantitative fluorescence microscopy, showed that depletion of 1,152 genes strongly affected cell-cycle progression. These genes clustered into eight distinct phenotypic categories based on phase of arrest, nuclear area, and nuclear morphology. Phase-specific networks were built by interrogating knowledge-based and physical interaction databases with identified genes. Genome-wide analysis of cell-cycle regulators revealed a number of kinase, phosphatase, and proteolytic proteins and also suggests that processes thought to regulate G
1
-S phase progression like receptor-mediated signaling, nutrient status, and translation also play important roles in the regulation of G
2
/M phase transition. Moreover, 15 genes that are integral to TNF/NF-κB signaling were found to regulate G
2
/M, a previously unanticipated role for this pathway. These analyses provide systems-level insight into both known and novel genes as well as pathways that regulate cell-cycle progression, a number of which may provide new therapeutic approaches for the treatment of cancer.
Prediction of protein orientation upon immobilization on biological and nonbiological surfaces
Authors: Talasaz AmirAli H. , Nemat-Gorgani Mohsen , Liu Yang , Ståhl Patrik , Dutton Robert W. , Ronaghi Mostafa , Davis Ronald W.
Published: September 2006

We report on a rapid simulation method for predicting protein orientation on a surface based on electrostatic interactions. New methods for predicting protein immobilization are needed because of the increasing use of biosensors and protein microarrays, two technologies that use protein immobilization onto a solid support, and because the orientation of an immobilized protein is important for its function. The proposed simulation model is based on the premise that the protein interacts with the electric field generated by the surface, and this interaction defines the orientation of attachment. Results of this model are in agreement with experimental observations of immobilization of mitochondrial creatine kinase and type I hexokinase on biological membranes. The advantages of our method are that it can be applied to any protein with a known structure; it does not require modeling of the surface at atomic resolution and can be run relatively quickly on readily available computing resources. Finally, we also propose an orientation of membrane-bound cytochrome
c
, a protein for which the membrane orientation has not been unequivocally determined.
Deterministic hydrodynamics: Taking blood apart
Authors: Davis John A. , Inglis David W. , Morton Keith J. , Lawrence David A. , Huang Lotien R. , Chou Stephen Y. , Sturm James C. , Austin Robert H.
Published: September 2006

We show the fractionation of whole blood components and isolation of blood plasma with no dilution by using a continuous-flow deterministic array that separates blood components by their hydrodynamic size, independent of their mass. We use the technology we developed of deterministic arrays which separate white blood cells, red blood cells, and platelets from blood plasma at flow velocities of 1,000 μm/sec and volume rates up to 1 μl/min. We verified by flow cytometry that an array using focused injection removed 100% of the lymphocytes and monocytes from the main red blood cell and platelet stream. Using a second design, we demonstrated the separation of blood plasma from the blood cells (white, red, and platelets) with virtually no dilution of the plasma and no cellular contamination of the plasma.
Aging may be a conditional strategic choice and not an inevitable outcome for bacteria
Authors: Watve Milind , Parab Sweta , Jogdand Prajakta , Keni Sarita
Published: September 2006

Aging is known in all organisms that have different somatic and reproductive cells or in unicellular organisms that divide asymmetrically. Bacteria that divide symmetrically were believed to be immune to natural aging. The demonstration of functionally asymmetric division and aging in
Escherichia coli
recently has challenged this belief and led to the suggestion that aging might be inevitable for all life forms. We modeled the effects of symmetric and asymmetric division in bacteria to examine selective advantages of the alternative strategies of division. Aging of cell components was modeled by using a modified Leslie matrix framework. The model suggests that asymmetric division accompanied by aging and death of some cells results in a higher growth rate but a reduced growth yield. Symmetric division with or without gradual replacement of the old components, on the other hand, slows down the growth rate but may increase growth yield over a wide range of conditions. Thus, aging and immortality can be selected under different sets of conditions, and this selection may also lead to a tradeoff between growth rate and growth yield.
Formation of functional centromeric chromatin is specified epigenetically in
Candida albicans
Authors: Baum Mary , Sanyal Kaustuv , Mishra Prashant K. , Thaler Nathaniel , Carbon John
Published: September 2006

In the pathogenic yeast
Candida albicans
, the 3-kb centromeric DNA regions (
CEN
) of each of the eight chromosomes have different and unique DNA sequences. The centromeric histone CaCse4p (CENP-A homolog) occurs only within these 3-kb
CEN
regions to form specialized centromeric chromatin. Centromere activity was maintained on small chromosome fragments derived
in vivo
by homologous recombination of a native chromosome with linear DNA fragments containing a telomere and a selectable marker. An
in vivo
derived 85-kb truncated chromosome containing the 3-kb
CEN7
locus on 69 kb of chromosome 7 DNA was stably and autonomously maintained in mitosis, indicating that preexisting active
CEN
chromatin remains functional through many generations. This same 85-kb chromosome fragment, isolated as naked DNA (devoid of chromatin proteins) from
C. albicans
and reintroduced back into
C. albicans
cells by standard DNA transformation techniques, was unable to reform functional
CEN
chromatin and was mitotically unstable. Comparison of active and inactive
CEN
chromatin digested with micrococcal nuclease revealed that periodic nucleosome arrays are disrupted at active centromeres. Chromatin immunoprecipitation with antibodies against CaCse4p confirmed that
CEN
7 introduced into
C. albicans
cells as naked DNA did not recruit CaCse4p or induce its spread to a duplicate region only 7 kb away from active
CEN7
chromatin. These results indicate that CaCse4p recruitment and centromere activation are epigenetically specified and maintained in
C. albicans.
Carbon monoxide differentially inhibits TLR signaling pathways by regulating ROS-induced trafficking of TLRs to lipid rafts
Authors: Nakahira Kiichi , Kim Hong Pyo , Geng Xue Hui , Nakao Atsunori , Wang Xue , Murase Noriko , Drain Peter F. , Wang Xiaomei , Sasidhar Madhu , Nabel Elizabeth G. , Takahashi Toru , Lukacs Nicholas W. , Ryter Stefan W. , Morita Kiyoshi , Choi Augustine M.K.
Published: September 2006

Carbon monoxide (CO), a byproduct of heme catabolism by heme oxygenase (HO), confers potent antiinflammatory effects. Here we demonstrate that CO derived from HO-1 inhibited Toll-like receptor (TLR) 2, 4, 5, and 9 signaling, but not TLR3-dependent signaling, in macrophages. Ligand-mediated receptor trafficking to lipid rafts represents an early event in signal initiation of immune cells. Trafficking of TLR4 to lipid rafts in response to LPS was reactive oxygen species (ROS) dependent because it was inhibited by diphenylene iodonium, an inhibitor of NADPH oxidase, and in gp91phox-deficient macrophages. CO selectively inhibited ligand-induced recruitment of TLR4 to lipid rafts, which was also associated with the inhibition of ligand-induced ROS production in macrophages. TLR3 did not translocate to lipid rafts by polyinosine-polycytidylic acid (poly(I:C)). CO had no effect on poly(I:C)-induced ROS production and TLR3 signaling. The inhibitory effect of CO on TLR-induced cytokine production was abolished in gp91phox-deficient macrophages, also indicating a role for NADPH oxidase. CO attenuated LPS-induced NADPH oxidase activity in vitro, potentially by binding to gp91phox. Thus, CO negatively controlled TLR signaling pathways by inhibiting translocation of TLR to lipid rafts through suppression of NADPH oxidase–dependent ROS generation.
Synergy between the pre–T cell receptor and Notch: cementing the αβ lineage choice
Authors: Guidos Cynthia J.
Published: September 2006

Notch1 signaling suppresses B cell development and promotes T lineage commitment in thymus-seeding hematopoietic progenitors. Notch1 is also activated in early T cell progenitors, but the functions of these later Notch signals have not been clearly defined. Recent studies reveal that Notch signaling is not essential for pre–T cell receptor (TCR) expression or γδ lineage choice. Rather, pre-TCR signaling enhances progenitor competitiveness for limiting Notch ligands, leading to preferential expansion of TCRβ-bearing progenitors.
Ghys-like models for Lavaurs and simple entire maps
Authors: Chéritat Arnaud
Published: September 2006

We provide a new geometric construction of pre-models (à la Ghys) for Lavaurs maps, from which we deduce that their Siegel disk is a Jordan curve running through a critical point, which was not known before. The construction turns out to work also for a class of entire maps, very specific, nonetheless including cases where no pre-models were known.
Peptide length-based prediction of peptide–MHC class II binding
Authors: Chang Stewart T. , Ghosh Debashis , Kirschner Denise E. , Linderman Jennifer J.
Published: September 2006

Motivation: Algorithms for predicting peptide–MHC class II binding are typically similar, if not identical, to methods for predicting peptide–MHC class I binding despite known differences between the two scenarios. We investigate whether representing one of these differences, the greater range of peptide lengths binding MHC class II, improves the performance of these algorithms.

Results: A non-linear relationship between peptide length and peptide–MHC class II binding affinity was identified in the data available for several MHC class II alleles. Peptide length was incorporated into existing prediction algorithms using one of several modifications: using regression to pre-process the data, using peptide length as an additional variable within the algorithm, or representing register shifting in longer peptides. For several datasets and at least two algorithms these modifications consistently improved prediction accuracy.

Availability:  

Contact:  linderma@umich.edu
Modelling interaction sites in protein domains with interaction profile hidden Markov models
Authors: Friedrich Torben , Pils Birgit , Dandekar Thomas , Schultz Jörg , Müller Tobias
Published: September 2006

Motivation: Due to the growing number of completely sequenced genomes, functional annotation of proteins becomes a more and more important issue. Here, we describe a method for the prediction of sites within protein domains, which are part of protein–ligand interactions. As recently demonstrated, these sites are not trivial to detect because of a varying degree of conservation of their location and type within a domain family.

Results: The developed method for the prediction of protein–ligand interaction sites is based on a newly defined interaction profile hidden Markov model (ipHMM) topology that takes structural and sequence data into account. It is based on a homology search via a posterior decoding algorithm that yields probabilities for interacting sequence positions and inherits the efficiency and the power of the profile hidden Markov model (pHMM) methodology. The algorithm enhances the quality of interaction site predictions and is a suitable tool for large scale studies, which was already demonstrated for pHMMs.

Availability: The MATLAB-files are available on request from the first author.

Contact:  tobias.mueller@biozentrum.uni-wuerzburg.de

Supplementary information:
Incidence and Characteristics of Facial Nerve Stimulation in Children With Cochlear Implants
Authors: Cushing Sharon L. , Papsin Blake C. , Gordon Karen A.
Published: September 2006

Objectives: Electrical stimulation from a cochlear implant can spread beyond the auditory nerve. The aims of this study were to accurately measure facial nerve stimulation in pediatric implant users and to determine the characteristics and incidence of this unwanted activity. Part A consisted of a prospective study of a randomized sample of 44 pediatric implant users. Part B consisted of a retrospective analysis of 121 children with previously recorded electrically evoked auditory brainstem responses (EABR).

Study Design and Methods: Responses were evoked by 3 electrodes along the implant array in three groups of children: 1) postmeningitic, 2) abnormal cochlea, and 3) neither. Intraoperative measures were obtained under anesthesia; all other recordings were completed in awake children.

Results: Intraoperative recordings revealed large nonauditory responses in a number of channels, including the midline EABR. Under paralysis, these responses disappeared, and clear EABRs were recorded. Similarly, prospective postoperative electromyographic (EMG) responses from the facial nerve were found in more than 59% (26 of 44) of experienced implant users (Nucleus 24): 31% of postmeningitic children (4 of 13), 80% of those with abnormal cochlea (8 of 10), and 66% of those with neither (14 of 21). Retrospective analysis of previously recorded postoperative EABRs demonstrated facial nerve stimulation in 35% (42 of 121). In most cases, facial nerve stimulation occurred when levels were perceptually loud but comfortable.

Conclusions: 1) Facial nerve potentials can be recorded using EMG in a large proportion of cochlear implant users at high levels of stimulation. 2) The EABR can be obscured in the presence of facial nerve stimulation and care should be taken to distinguish it from the EMG response, particularly when auditory brainstem activity is in question. 3) Use of surface EMG provides an additional objective measure to ensure the safe and comfortable use of cochlear implants.
Quality of Life of Patients With Otitis Media and Caregivers: A Multicenter Study
Authors: Lee Jeanne , Witsell David L. , Dolor Rowena J. , Stinnett Sandra , Hannley Maureen
Published: September 2006

Objective: The objective of this study was to determine the quality of life of otitis media (OM) patients and their caregivers.

Study Design: A cross‐sectional study was conducted at 11 otolaryngology and five pediatric clinics in the United States between July 1998 and August 1999. All patients, regardless of primary complaint, completed a demographic survey, OM‐6 survey, and Child Health Questionaire‐PF28 survey by proxy. Physicians completed an International Classification of Diseases, 9th Revision diagnosis sheet for each patient.

Methods: Analysis, including Spearman rank correlation, was restricted to study patients with active OM.

Results: A total of 1,001 patients with active OM were identified: 503 OM with effusion, 267 acute OM, and 258 recurrent acute OM. Median patient age was 2 years (interquartile range, 1–5). Mean caretaker age was 32.6 years (standard deviation, 7.4). There was moderate correlation between OM frequency and physical suffering (r = 0.50; P < .001) and caregiver concerns (r = 0.45; P < .001). Moderate correlation was found between percentage of time with fluid in the ears and caregiver concerns (r = 0.46; P < .001) and physical suffering (r = 0.43; P < .001). OM patients over 5 years of age scored significantly worse than healthy children ages 5 to 7 years in almost all areas of global health, including physical functioning and impact on caretaker's personal time and emotions.

Conclusion: The global quality of life of patients with OM over 5 years of age is worse than that of healthy children of similar age. Physical suffering and caregiver concerns are associated with frequent OM or effusion duration. Hopefully, these results will direct the focus of future outcomes studies.
Evaluation of Culture and Antibiotic Use in Patients With Pharyngitis
Authors: Rufener Justin B. , Yaremchuk Kathleen L. , Payne Spencer C.
Published: September 2006

Objectives: The objectives of this study were to evaluate practice patterns for treatment of patients with pharyngitis with regard to testing for group A beta hemolytic streptococcal (GABHS) infection, frequency of antibiotic use, and appropriate choice of antibiotics.

Study Design: The authors conducted a retrospective review of billing data for 10,482 office visits for pharyngitis.

Methods: The 2004 billing database for a tertiary institution was queried for outpatient visits for pharyngitis or tonsillitis, group A Streptococcus tests (GAST), and antibiotic prescriptions filled after the visit. Patients were separated by age group and analyzed for the proportion of patients that received a GAST and proportion prescribed an antibiotic. Antibiotic prescriptions were also analyzed to determine whether they were appropriate for treatment of GABHS.

Results: A total of 68.7% of all patients and 82.2% of pediatric patients were tested for GAST. A total of 47.1% of adult patients and 44.9% of pediatric patients received an antibiotic. For adult patients for whom GAST was obtained, 48.6% were prescribed an antibiotic versus 53.6% of those not tested. Streptococcus testing was a significant predictor of antibiotic use (P < .0001), whereas age was not (P = .22). A total of 82.1% of all antibiotics prescribed were recommended for treatment of GABHS.

Conclusions: Most patients seen for pharyngitis were tested for GABHS, but pediatric patients were tested more frequently than adults. Patients who received a GAST were less likely to receive antibiotics. The rates experienced in our tertiary academic institution are higher than previously quoted for community practice. When antibiotics were prescribed, they were usually appropriate for the treatment of GABHS based on current recommendations.
Topical Pimecrolimus 1% for the Treatment of Pruritic External Auditory Canals
Authors: Djalilia Hamid R. , Memar Omid
Published: September 2006

Objectives/Hypothesis: To understand the role and efficacy of topical pimecrolimus in the treatment of refractory pruritis of the external auditory canals (EACs).

Study Design: Retrospective chart review.

Methods: Thirty‐six patients with pruritic EACs who had failed conventional therapy with topical and systemic medications were treated with topical pimecrolimus 1% for a period of 3 months. Baseline and follow‐up evaluation of the degree of pruritis among other variables was performed. A control group of 19 patients was instructed on aural toilet alone and was not treated with topical pimecrolimus 1%.

Results: Of the 36 patients who were treated with topical pimecrolimus for their pruritic EACs, 34 patients had resolution of their symptoms. There was evidence of return of cerumen production in 86% of patients. In the control group, 16% of patients had improvement of their symptoms with aural toilet. This difference was statistically significant (χ2, P < .0001).

Conclusions: Topical pimecrolimus appears to be more efficacious than aural toilet in the treatment of pruritic ears for chronic use without side effects.
Delayed Extrusion of Hydroxyapatite after Transpetrosal Reconstruction
Authors: Krishnamoorthy Kumaresh , Pensa Myles L. , Samy Ravi N.
Published: September 2006

Objectives:To review the long‐term results of hydroxyapatite closure of transpetrosal defects.

Study Design:Retrospective chart review.

Methods:One hundred seventy‐seven patients were followed for more than 5 years. After surgical management by way of transpetrosal routes, hydroxyapatite was placed after medial wound closure with abdominal fat and before a three‐layered lateral soft tissue closure.

Results:Among this group of patients, three (1.7%) cerebrospinal fluid (CSF) leaks were encountered. None of these required re‐operation. Delayed extrusion of hydroxyapatite with concomitant superficial wound infections have occurred in seven (4%) patients. All required operative re‐intervention.

Conclusions:Hydroxyapatite has proven to be an effective material in the closure of skull base defects. Nevertheless, delayed extrusion of this agent can occur, resulting in the potential for morbidity and the need for operative re‐intervention.
Clinical Evaluation of Parkinson's‐Related Dysphonia
Authors: Sewall Gregory K. , Jiang Jack , Ford Charles N.
Published: September 2006

Objectives: Nearly one third of patients with idiopathic Parkinson's disease (IPD) cite dysphonia, characterized subjectively as causing a harsh and breathy voice, as their most debilitating deficit. Medical or behavioral treatments may lead to voice improvement. The purpose of this study was 1) to determine whether vocal fold injection of Cymetra (micronized form of collagen, elastin, proteoglycans; Lifecell Co.) is associated with changes in dysphonic voice characteristics in subjects with IPD, as judged perceptually using a standard instrument Consensus Auditory‐Perceptual Evaluation of Voice (CAPE‐V), and (2) which acoustic and aerodynamic measurements of voice are most reflective of any observed perceptual changes in voice.

Study Design: Prospective clinical evaluation of patients with Parkinson's‐related dysphonia (PRD).

Methods: Six patients with PRD were evaluated before treatment for the presence of dysphonia and glottal gap. All subjects underwent transoral vocal fold collagen injection using topical anesthesia in the otolaryngology clinic as part of their clinical care. At the initial clinic visit, and 10 to14 days after vocal fold collagen injection, patients were asked to complete the Voice Handicap Index (VHI), a questionnaire concerning voice‐related quality of life, and perceptual analyses of voice quality were performed. In addition, patients underwent acoustic (pitch/loudness range, maximum phonation time [MPT], and aerodynamic phonation threshold pressure [PTP]) voice analysis.

Results: Five of six subjects had self‐perceived improvements in voice after treatment, as determined by the VHI (range, +8 to −24). All five subjects who completed testing demonstrated decreased PTP (range, −1.3 to −2.7, P = .002). Five of six subjects demonstrated statistically significant improvements in MPT (range, −2–16 s, P = .05). Five of six subjects had improved pitch range (−26–343 Hz), whereas all subjects had increased intensity range (0.6–23 db) after injection.

Conclusions: Transoral collagen injection in patients with PRD is safe, well tolerated, and is an effective temporary method of subjectively improving voice and speech in selected patients with IPD. Reduction of glottal gap with collagen improves MPT and subglottal PTP. The resulting gain of vocal efficiency may reduce vocal fatigue and provide a useful adjunct to voice therapy for PRD.
Endoscopic Techniques in Resection of Anterior Skull Base/Paranasal Sinus Malignancies
Authors: Buchmann Luke , Larsen Christopher , Pollack Ania , Tawfik Ossama , Sykes Kevin , Hoover Larry A.
Published: September 2006

Objective: The objective of this study was to examine the role of endoscopic approaches to the resection of anterior skull base and paranasal sinus malignancies at one tertiary care medical center.

Study Design: The authors conducted a retrospective chart review over a period of 17 years.

Methods: Patients undergoing anterior skull base resections for malignancies over a 17‐year period were reviewed. Data were collected on each patient with respect to the pathology of the tumor and approach used as well as demographic and follow‐up information.

Results: A total of 78 patients were treated at a tertiary care medical center for malignancies of the paranasal sinuses and anterior skull base. The most common diagnosis was squamous cell carcinoma occurring in 33% of the cases. The remaining pathologies included esthesioneuroblastoma (23%), adenoid cystic carcinoma (15%), melanoma (3%), sinonasal undifferentiated carcinoma (3%), lymphoma (5%), nasopharyngeal carcinoma (4%), and other tumor types (14%). Endoscopic techniques were used extensively in this population of patients. Combined approaches using a sublabial/transmaxillary approach and coronal approaches were used when indicated and complemented the endoscopic approach. A majority of patients were without evidence of disease at the end of this review. Using endoscopic techniques allowed for acceptable cosmetic results and facial incisions were used minimally.

Conclusion: With complete endoscopic surgical resection followed by radiation therapy, local recurrence, morbidity, and cosmetic deformity have been minimized. The microscopic view provided by endoscopic techniques, with or without complementary approaches, allows for complete tumor removal.
A New Generation Videokymography for Routine Clinical Vocal Fold Examination
Authors: Qiu Qingjun , Schutte Harm K.
Published: September 2006

Objective: This study aims to introduce a new‐generation videokymographic system, which provides simultaneous laryngoscopic and kymographic image, for routine clinical vocal fold examination.

Study Design: The authors explored a new imaging method for diagnosis and evaluation of voice disorders.

Methods: The new‐generation videokymographic system includes two charge‐coupled device image sensors, a color area image sensor, and a monochromic high‐speed line‐scan image sensor. The high‐speed line‐scan image sensor is used to capture the kymogram, and the color area image sensor is used to obtain the laryngoscopic image. The two images can be displayed simultaneously on a video monitor or stored in a standard video recorder. Three subjects with nonpathologic voice were investigated in detail with the new videokymographic system.

Results: The high‐quality laryngoscopic image and kymogram can be used directly for clinical purposes with no further postprocessing. The scan position of the kymogram is always indicated in the laryngoscopic image, which provides feedback for the operator to easily locate the expected scanning position. All varieties of vocal fold vibration, including irregular vibrations, phonation onset and offset, can be observed with the presented method. The continuous kymogram of the vocal fold vibration can be retrieved from a kymographic image sequence for quantitative analysis.

Conclusions: The new‐generation videokymography provides a simple, quick means to investigate vocal fold vibration, especially for voice disorders. It can emerge as an important tool for routine clinical vocal fold examination.
Neck Management in Patients Undergoing Postradiotherapy Salvage Laryngeal Surgery for Recurrent/Persistent Laryngeal Cancer
Authors: Farrag Tarik Y. , Lin Frank R. , Cummings Charles W. , Koch Wayne M. , Flint Paul W. , Califano Joseph A. , Broussard Jennifer , Bajaj Gopal , Tufano Ralph P.
Published: September 2006

Objective: To determine a plan for the management of cervical lymph nodes in patients undergoing salvage laryngeal surgery (SLS) for recurrent/persistent laryngeal cancer after primary radiotherapy (RT).

Study Design: Retrospective chart review.

Methods: Charts of 51 consecutive patients who had salvage total or supracricoid laryngectomy with or without neck dissection for recurrent/persistent laryngeal squamous cell carcinoma after primary RT from 1988 to 2005 in our institution were reviewed. No patients received concomitant or neo‐adjuvant chemotherapy. Thirty‐four patients underwent SLS along with unilateral or bilateral neck dissection, whereas 17 patients underwent the SLS without neck dissection. Reports of preRT and preSLS staging of the primary tumor and the neck, recorded using the TNM system, were reviewed. Reports of the final histopathologic examination for the excised laryngeal cancer and cervical lymph nodes were reviewed.

Results: Thirty‐four patients underwent SLS with unilateral or bilateral neck dissection. The preRT staging of the primary tumor for those 34 patients showed that 32 (94%) were staged T‐1 (14) and T‐2 (18), whereas the preSLS staging of the primary tumor for those 34 patients showed that 29 (85%) were staged T‐3 and T‐4. The postSLS final histopathologic examination of the excised lymph nodes in those 34 patients demonstrated that 30 (88%) did not have any evidence of nodal metastasis. On comparing patients with and without nodal metastasis (on their postSLS final histopathology), we found that the preSLS neck staging, based on computed tomographic (CT) scanning of the neck, was significantly associated with the negative/positive postSLS status of nodal metastasis (P = .006). Of 29 patients staged preSLS as N‐0, 28 (97%) patients did not have nodal metastasis on their postSLS final pathology (negative predictive value = 97%, confidence interval, 82.2–99.9). PreRT neck staging, preRT and preSLS staging of the primary tumor, along with laryngeal subsite involvement (supraglottis, glottis, subglottis) did not significantly correlate with the status of neck metastasis on final postSLS histopathology (P = .68, 0.78, 0.49, and 0.42, respectively). None of the 34 patients had any neck tumor recurrence in the postSLS follow‐up period (median, 3 yr). In addition, all 17 patients who underwent SLS without neck dissection were staged N‐0 both before RT as well as preSLS, and none developed neck disease in the postSLS follow‐up period (median, 2.5 yr).

Conclusion: Management of the neck in patients undergoing salvage total or supracricoid laryngectomy for laryngeal cancer recurrence/persistence after primary RT should be based on the preSLS CT staging of the neck. Patients staged N‐0 preSLS are not likely to harbor occult nodal metastasis and therefore may not require elective neck dissection.
Contour and Paired‐Point Registration in a Model for Image‐Guided Surgery
Authors: Knott P Daniel , Batra Pete S. , Butler Robert S. , Citardi Martin J.
Published: September 2006

Objectives/Hypothesis: This study assesses target registration error (TRE) of contour‐based registration (CBR) and paired‐point registration (PPR) for endoscopic sinus surgery.

Study Design: The experimental registration model consisted of a replica of a human head (Sawbones #1345‐27; Pacific Research Laboratories, Vashon, WA). Twelve surface fiducial markers were affixed to the simulated skin on the model, and titanium screws were placed in the regions of the anterior ethmoid (AE) and sphenoid face (SF). An axial computed tomography scan (1‐mm slice thickness) was then obtained.

Methods: Registration was then performed on the InstaTrak 3500 Plus (GE Surgical Navigation & Visualization, Lawrence, MA) with the standard PPR protocol with 12 points and CBR protocol with 500, 250, 125, 50, and 4 points. TRE was then calculated at the AE and SF targets.

Results: Target registration error was significantly lower for paired‐point registration compared with contour‐based registration (AE, 0.5 mm vs. 1.5 mm, P < .0001; SF, 0.8 mm vs. 1.5 mm, P < .0001). Among contour‐based registration protocols, target registration error at the sphenoid face was lowest with 50 points (1.5 mm, P < .02). At the anterior ethmoid, contour‐based registration with 50 points produced a lower target registration error than contour‐based registration with 125 points (1.5 vs. 1.8 mm, P < .01). Other target registration error values for CBR were similar at both regions. The target registration error interquartile range was lowest with CBR‐125 at both regions.

Conclusions: Paired‐point registration provided significantly lower target registration error. Contour‐based registration with 125 points (and possibly as few as 50 points) produces clinically acceptable target registration error. This registration model elucidates important concepts about registration for surgical navigation for sinus surgery.