bluuebunny/crossref_metadata_2025 huggingface dataset:
Two C—P Lyase Operons in
Pseudomonas stutzeri
and Their Roles in the Oxidation of Phosphonates, Phosphite, and Hypophosphite
Authors: White Andrea K. , Metcalf William W.
Published: July 2004

DNA sequencing and analysis of two distinct C—P lyase operons in
Pseudomonas stutzeri
WM88 were completed. The
htxABCDEFGHIJKLMN
operon encodes a hypophosphite-2-oxoglutarate dioxygenase (HtxA), whereas the predicted amino acid sequences of HtxB to HtxN are each homologous to the components of the
Escherichia coli phn
operon, which encodes C—P lyase, although homologs of
E. coli phnF
and
phnO
are absent. The genes in the
htx
operon are cotranscribed based on gene organization, and the presence of the intergenic sequences is verified by reverse transcription-PCR with total RNA. Deletion of the
htx
locus does not affect the ability of
P. stutzeri
to grow on phosphonates, indicating the presence of an additional C—P lyase pathway in this organism. To identify the genes comprising this pathway, a Δ
htx
strain was mutagenized and one mutant lacking the ability to grow on methylphosphonate as the sole P source was isolated. A ca.-10.6-kbp region surrounding the transposon insertion site of this mutant was sequenced, revealing 13 open reading frames, designated
phnCDEFGHIJKLMNP,
which were homologous to the
E. coli phn
genes. Deletion of both the
htx
and
phn
operons of
P. stutzeri
abolishes all growth on methylphosphonate and aminoethylphosphonate. Both operons individually support growth on methylphosphonate; however, the
phn
operon supports growth on aminoethylphosphonate and phosphite, as well. The substrate ranges of both C—P lyases are limited, as growth on other phosphonate compounds, including glyphosate and phenylphosphonate, was not observed.
Construction and Validation of the
Rhodobacter sphaeroides
2.4.1 DNA Microarray: Transcriptome Flexibility at Diverse Growth Modes
Authors: Pappas Christopher T. , Sram Jakub , Moskvin Oleg V. , Ivanov Pavel S. , Mackenzie R. Christopher , Choudhary Madhusudan , Land Miriam L. , Larimer Frank W. , Kaplan Samuel , Gomelsky Mark
Published: July 2004

A high-density oligonucleotide DNA microarray, a genechip, representing the 4.6-Mb genome of the facultative phototrophic proteobacterium,
Rhodobacter sphaeroides
2.4.1, was custom-designed and manufactured by Affymetrix, Santa Clara, Calif. The genechip contains probe sets for 4,292 open reading frames (ORFs), 47 rRNA and tRNA genes, and 394 intergenic regions. The probe set sequences were derived from the genome annotation generated by Oak Ridge National Laboratory after extensive revision, which was based primarily upon codon usage characteristic of this GC-rich bacterium. As a result of the revision, numerous missing ORFs were uncovered, nonexistent ORFs were deleted, and misidentified start codons were corrected. To evaluate
R. sphaeroides
transcriptome flexibility, expression profiles for three diverse growth modes—aerobic respiration, anaerobic respiration in the dark, and anaerobic photosynthesis—were generated. Expression levels of one-fifth to one-third of the
R. sphaeroides
ORFs were significantly different in cells under any two growth modes. Pathways involved in energy generation and redox balance maintenance under three growth modes were reconstructed. Expression patterns of genes involved in these pathways mirrored known functional changes, suggesting that massive changes in gene expression are the major means used by
R. sphaeroides
in adaptation to diverse conditions. Differential expression was observed for genes encoding putative new participants in these pathways (additional photosystem genes, duplicate NADH dehydrogenase, ATP synthases), whose functionality has yet to be investigated. The DNA microarray data correlated well with data derived from quantitative reverse transcription-PCR, as well as with data from the literature, thus validating the
R. sphaeroides
genechip as a powerful and reliable tool for studying unprecedented metabolic versatility of this bacterium.
Evidence that the
algI
/
algJ
Gene Cassette, Required for O Acetylation of
Pseudomonas aeruginosa
Alginate, Evolved by Lateral Gene Transfer
Authors: Franklin Michael J. , Douthit Stephanie A. , McClure Marcella A.
Published: July 2004

Pseudomonas aeruginosa
strains, isolated from chronically infected patients with cystic fibrosis, produce the O-acetylated extracellular polysaccharide, alginate, giving these strains a mucoid phenotype. O acetylation of alginate plays an important role in the ability of mucoid
P. aeruginosa
to form biofilms and to resist complement-mediated phagocytosis. The O-acetylation process is complex, requiring a protein with seven transmembrane domains (AlgI), a type II membrane protein (AlgJ), and a periplasmic protein (AlgF). The cellular localization of these proteins suggests a model wherein alginate is modified at the polymer level after the transport of O-acetyl groups to the periplasm. Here, we demonstrate that this mechanism for polysaccharide esterification may be common among bacteria, since AlgI homologs linked to type II membrane proteins are found in a variety of gram-positive and gram-negative bacteria. In some cases, genes for these homologs have been incorporated into polysaccharide biosynthetic operons other than for alginate biosynthesis. The phylogenies of AlgI do not correlate with the phylogeny of the host bacteria, based on 16S rRNA analysis. The
algI
homologs and the gene for their adjacent type II membrane protein present a mosaic pattern of gene arrangement, suggesting that individual components of the multigene cassette, as well as the entire cassette, evolved by lateral gene transfer. AlgJ and the other type II membrane proteins, although more diverged than AlgI, contain conserved motifs, including a motif surrounding a highly conserved histidine residue, which is required for alginate O-acetylation activity by AlgJ. The AlgI homologs also contain an ordered series of motifs that included conserved amino acid residues in the cytoplasmic domain CD-4; the transmembrane domains TM-C, TM-D, and TM-E; and the periplasmic domain PD-3. Site-directed mutagenesis studies were used to identify amino acids important for alginate O-acetylation activity, including those likely required for (i) the interaction of AlgI with the O-acetyl precursor in the cytoplasm, (ii) the export of the O-acetyl group across the cytoplasmic membrane, and (iii) the transfer of the O-acetyl group to a periplasmic protein or to alginate. These results indicate that AlgI belongs to a family of membrane proteins required for modification of polysaccharides and that a mechanism requiring an AlgI homolog and a type II membrane protein has evolved by lateral gene transfer for the esterification of many bacterial extracellular polysaccharides.
Characterization of NopP, a Type III Secreted Effector of
Rhizobium
sp. Strain NGR234
Authors: Ausmees Nora , Kobayashi Hajime , Deakin William J. , Marie Corinne , Krishnan Hari B. , Broughton William J. , Perret Xavier
Published: July 2004

The type three secretion system (TTSS) encoded by pNGR234
a
, the symbiotic plasmid of
Rhizobium
sp. strain NGR234, is responsible for the flavonoid- and NodD1-dependent secretion of

n

odulation

o

uter

p

roteins (Nops). Abolition of secretion of all or specific Nops significantly alters the nodulation ability of NGR234 on many of its hosts. In the closely related strain
Rhizobium fredii
USDA257, inactivation of the TTSS modifies the host range of the mutant so that it includes the improved
Glycine max
variety McCall. To assess the impact of individual TTSS-secreted proteins on symbioses with legumes, various attempts were made to identify
nop
genes. Amino-terminal sequencing of peptides purified from gels was used to characterize NopA, NopL, and NopX, but it failed to identify SR3, a TTSS-dependent product of USDA257. By using phage display and antibodies that recognize SR3, the corresponding protein of NGR234 was identified as NopP. NopP, like NopL, is an effector secreted by the TTSS of NGR234, and depending on the legume host, it may have a deleterious or beneficial effect on nodulation or it may have little effect.
Interaction between Protein Subunits of the Type IV Secretion System ofBartonella henselae
Authors: Shamaei-Tousi Alireza , Cahill Rachel , Frankel Gad
Published: July 2004

In this study we used the yeast two-hybrid system to identify interactions between protein subunits of thevirBtype IV secretion system ofBartonella henselae. We report interactions between inner membrane and periplasmic proteins, the pilus polypeptide, and the core complex and a novel interaction between VirB3 and VirB5.
Role of
Escherichia coli
DNA Polymerase IV in In Vivo Replication Fidelity
Authors: Kuban Wojciech , Jonczyk Piotr , Gawel Damian , Malanowska Karolina , Schaaper Roel M. , Fijalkowska Iwona J.
Published: July 2004

We have investigated whether DNA polymerase IV (Pol IV; the
dinB
gene product) contributes to the error rate of chromosomal DNA replication in
Escherichia coli
. We compared mutation frequencies in mismatch repair-defective strains that were either
dinB
positive or
dinB
deficient, using a series of mutational markers, including
lac
targets in both orientations on the chromosome. Virtually no contribution of Pol IV to the chromosomal mutation rate was observed. On the other hand, a significant effect of
dinB
was observed for reversion of a
lac
allele when the
lac
gene resided on an F′(
pro-lac
) episome.
Loop Deletions Indicate Regions Important for FhuA Transport and Receptor Functions in
Escherichia coli
Authors: Endriß Franziska , Braun Volkmar
Published: July 2004

Precise deletions of cell surface-exposed loops of FhuA resulted in mutants of
Escherichia coli
with distinct phenotypes. Deletion of loop 3 or 11 inactivated ferrichrome transport activity. Deletion of loop 8 inactivated receptor activity for colicin M and the phages T1, T5, and φ80. The loop 7 deletion mutant was colicin M resistant but fully phage sensitive. The loop 4 deletion mutant was resistant to the TonB-dependent phages T1 and φ80 but fully sensitive to the TonB-independent phage T5. The phenotypes of the deletion mutants revealed important sites for the multiple FhuA transport and receptor activities. The ligand binding sites are nonidentical and are distributed among the entire exposed surface. Presumably, FhuA evolved as a ferrichrome transporter and was subsequently used as a receptor by the phages and colicin M, which selected the same as well as distinct loops as receptor sites.
KERR–ADS BUBBLE SPACETIMES AND TIME-DEPENDENT ADS/CFT CORRESPONDENCE
Authors: GHEZELBASH A. M. , MANN R. B.
Published: July 2004

We compute the boundary stress-energies of time-dependent asymptotically AdS spacetimes in five and seven dimensions, and find that their traces are equal to the respective four- and six-dimensional field-theoretic trace anomalies. This provides good supporting evidence in favor of the AdS/CFT correspondence in time-dependent backgrounds.
EXAMINING THE USE OF CONCEPTUAL GRAPHS IN ADAPTIVE WEB-BASED SYSTEMS THAT AID TERMINOLOGY LEARNING
Authors: BONTCHEVA KALINA , DIMITROVA VANIA
Published: July 2004

This paper discussed the use of Conceptual Graphs (CGs) for implementing tasks employed in web-based educational systems that aid terminology learning. Specifically, we focus on two critical issues in intelligent tutoring - student diagnosis and generation of adaptive explanations. Both tasks are demonstrated in terminological domains where learners have to familiarize themselves with concepts in a specific subject area (e.g. computing, finance, chemistry). Based on CG reasoning, robust and computationally tractable algorithms for student modelling and adaptive explanation generation are defined. Two intelligent systems are presented — STyLE-OLM and HYLITE+. STyLE-OLM is an interactive learner modelling system that extracts extended models of the learners' cognition. HYLITE+ is a natural language generation system that generates adaptive Web pages based on a learner model(LM). The two systems are complementary and have been implemented separately. However, considered together they cover most of the key tasks in adaptive web-based educational hypermedia that aid learning technical terminology. Based on evaluative studies of STyLE-OLM and HYLITE+, the use of CGs for interactive open student modelling and adaptive concept explanations is examined. The applicability of CGs in adaptive web-based systems that aid learning technical terminology is discussed.
DOMAIN KNOWLEDGE ACQUISITION AND PLAN RECOGNITION BY PROBABILISTIC REASONING
Authors: MARAGOUDAKIS MANOLIS , THANOPOULOS ARISTOMENIS , SGARBAS KYRIAKOS , FAKOTAKIS NIKOS
Published: July 2004

This paper introduces a statistical framework for extracting medical domain knowledge from heterogeneous corpora. The acquired information is incorporated into a natural language understanding agent and applied to DIKTIS, an existing web-based educational dialogue system for the chemotherapy of nosocomial and community acquired pneumonia, aiming at providing a more intelligent natural language interaction. Unlike the majority of existing dialogue understanding engines, the presented system automatically encodes semantic representation of a user's query using Bayesian networks. The structure of the networks is determined from annotated dialogue corpora using the Bayesian scoring method, thus eliminating the tedious and costly process of manually coding domain knowledge. The conditional probability distributions are estimated during a training phase using data obtained from the same set of dialogue acts. In order to cope with words absent from our restricted dialogue corpus, a separate offline module was incorporated, which estimates their semantic role from both medical and general raw text corpora, correlating them with known lexical-semantically similar words or predefined topics. Lexical similarity is identified on the basis of both contextual similarity and co-occurrence in conjunctive expressions. The evaluation of the platform was performed against the existing language natural understanding module of DIKTIS, the architecture of which is based on manually embedded domain knowledge.
AN ENSEMBLE OF CLASSIFIERS APPROACH TO USER MODELING ON ADAPTIVE LEARNING COMMUNITIES
Authors: GAUDIOSO ELENA , BOTICARIO JESUS G.
Published: July 2004

Nowadays, web-based distance learning is benefiting from improved communication services. However, the mere fact of setting up an environment for students and lecturers does not guarantee mutual collaboration or successful student learning. This is partly due to the fact that an unique response is given to every user with different background knowledge, different interests, or different skill levels in the use of the services provided. To resolve this situation, adaptive systems provide an adapted response to each user's needs based on a constructed user model containing his/her characteristics. In this paper we will see that the construction of this user model is not trivial. In a user model in a web-based collaborative environment, there are very diverse attributes related with the interaction of the user with the services and the value of these attributes are obtained in very different ways. In addition, as any adaptive system the user model constructed should be explicit and accesible by the user and tutor. We will also see how we dynamically manage the user model in an adaptive learning environment by means of a ensemble of classifiers.
EXACT CONFIDENCE INTERVALS AND JOINT CONFIDENCE REGIONS FOR THE PARAMETERS OF THE WEIBULL DISTRIBUTIONS
Authors: CHEN ZHENMIN
Published: July 2004

The Weibull distribution is widely adopted as a lifetime distribution. One of the characteristics the Weibull distribution possesses is that its cumulative distribution function can be expressed by closed form. Parameter estimation for the Weibull distribution has been discussed by many authors. Various methods have been proposed for constructing confidence intervals and joint confidence regions for the parameters of the Weibull distribution based on censored data. This paper discusses those methods that deal with exact confidence intervals or exact joint confidence regions for the parameters. One of the applications of the joint confidence regions of the parameters is to find confidence bounds for the functions of the parameters. In this paper, confidence bounds for the mean lifetime and reliability function for the Weibull distributions are discussed. Some unresolved problems for the exact confidences and joint confidence regions are mentioned in the discussion section.
VARIABLE SELECTION IN NONPARAMETRIC REGRESSION MODEL
Authors: KULASEKERA K. B. , OLAYA JAVIER
Published: July 2004

A new procedure is proposed for deciding whether a candidate variable is significant in a general nonparametric regression model with independent covariates. A forward selection process is conducted using a formal test of equality of regression curves at each stage. The proposed procedure does not require multidimensional smoothing at any intermediate step. Asymptotic properties are given. Some simulation results and a real application are given.
INFERENCES ON THE PARAMETERS AND SYSTEM RELIABILITY FOR A FAILURE-TRUNCATED POWER LAW PROCESS: A BAYESIAN APPROACH USING A CHANGE-POINT
Authors: RICHARDSON M. G. , BASU A. P.
Published: July 2004

The reliability of a repairable system that is either improving or deteriorating depends on the system's chronological age. If such a system undergoes "minimal repair" at the occurrence of each failure so that the rate of system failures is not disturbed by the repair, then a nonhomogeneous Poisson process (NHPP) may be used to model the "age-dependent" reliability of the system. The power law process (PLP) is a model within the class of NHPP models and is commonly used as a model for describing the failure times of a repairable system. We introduce a new model that is an extension of the PLP model: the power law process change-point model. This model is capable of describing the failure times of particular types of repairable systems that experience a single change in their rates of occurrence of failures. Bayesian inference procedures for this model are developed.
ON PERSISTENCE AND STABILITY OF SOME BIOLOGICAL SYSTEMS WITH CROSS DIFFUSION
Authors: AHMED E. , HEGAZI A. S. , ELGAZZAR A. S.
Published: July 2004

The concept of cross diffusion is applied to some biological systems. The conditions for persistence and Turing instability in the presence of cross diffusion are derived. Many examples including: predator-prey, epidemics (with and without delay), hawk–dove–retaliate and prisoner's dilemma games are given.
GENERATING PRODUCT RECOMMENDATIONS USING FILTER COMBINATION
Authors: RENNEBERG VOLKER , BORGHOFF UWE M.
Published: July 2004

Traditionally, customers spend most of their money for pre-configured "off-the-shelf" products. Simple product variations are offered, but fine-tuning by the customer before the purchase is generally not intended. Why pay for functionality that is not wanted? Why spend money for products that are so rigid and do not satisfy a hundred percent? To remedy these issues, we discuss a possible solution based on recommendations. In our approach, traditional filtering techniques known from recommender systems guide the customer through a sophisticated product personalization process using pipelined filter combination. This process distinguishes between expert customers and novices. An extended example shows the rich capabilities of the proposed solution.
Ochratoxin A increases permeability through tight junctions by removal of specific claudin isoforms
Authors: McLaughlin John , Padfield Philip J. , Burt Julian P. H. , O'Neill Catherine A.
Published: July 2004

On interaction with the intestine, the mycotoxin ochratoxin A is know to cause rapid inflammation, diarrhea, and increased bacterial translocation. All these effects are consistent with a decrease in epithelial barrier function. However, this has not been shown directly. We determined that ochratoxin A is able to reduce the barrier properties of the model intestinal cell line Caco-2. Over 24 h, ochratoxin A reduces the transepithelial electrical resistance of Caco-2 monolayers growing on Transwell filters by ∼40%. At the same time, the permeability of the monolayer is increased with respect to 4- and 10-kDa FITC dextrans, but not to 20- or 40-kDa dextrans. Immunoblotting and immuofluorescence reveal that the decrease in barrier properties is concomitant with disappearance of claudins 3 and 4, but not claudin 1 from Caco-2 cell membranes. These results suggest that ochratoxin A is able to modulate the barrier function of Caco-2 cells by removal of specific claudin isoforms.
Differential regulation of urokinase-type plasminogen activator expression by fluid shear stress in human coronary artery endothelial cells
Authors: Sokabe Takaaki , Yamamoto Kimiko , Ohura Norihiko , Nakatsuka Hideki , Qin Kairong , Obi Syotaro , Kamiya Akira , Ando Joji
Published: July 2004

Atherosclerotic plaques preferentially localize at arterial regions exposed to turbulent low-shear flow. Urokinase-type plasminogen activator (uPA) plays a role in vascular remodeling by facilitating smooth muscle cell migration and proliferation in addition to the proteolysis of extracellular matrix, and the expression of uPA is elevated in atherosclerotic lesions. In this study, we analyzed the effects of laminar and turbulent shear stress on uPA expression in cultured human coronary artery endothelial cells. The application of laminar shear stress (1.5 or 15 dyn/cm2) significantly decreased the amount of uPA mRNA as well as the secretion of uPA protein. In contrast, turbulent shear stress (average intensity, 1.5 dyn/cm2) markedly increased uPA gene expression and protein secretion. Laminar shear stress downregulated uPA gene expression transcriptionally and posttranscriptionally; laminar shear stress activated transcription factor GATA6, which binds to a GATA consensus element located between −692 and −687 bp in the uPA promoter, thereby inhibiting uPA gene transcription. Laminar shear stress also accelerated the degradation of uPA mRNA; the half-life of uPA mRNA decreased to about half of the static control's half-life. Although turbulent shear stress had no effect on the transcription of uPA, it significantly increased uPA mRNA stability; the half-life of uPA mRNA increased by about two times the static control's half-life. Our results suggest that endothelial uPA expression is flow sensitive and differentially regulated by laminar and turbulent shear stress in vitro. We speculate that this effect may contribute to the local nature of atherosclerosis.
Attenuation of lipopolysaccharide anorexia by antagonism of caudal brain stem but not forebrain GLP-1-R
Authors: Grill Harvey J. , Carmody Jill S. , Amanda Sadacca L. , Williams Diana L. , Kaplan Joel M.
Published: July 2004

The central glucagon-like peptide-1 (GLP-1) system has been implicated in the control of feeding behavior. Here we explore GLP-1 mediation of the anorexic response to administration of systemic LPS and address the relative importance of caudal brain stem and forebrain GLP-1 receptor (GLP-1-R) for the mediation of the response. Fourth-intracerebroventricular delivery of the GLP-1-R antagonist exendin-(9–39) (10 μg) did not itself affect food intake in the 24 h after injection but significantly attenuated the otherwise robust (∼60%) reduction in food intake obtained after LPS (100 μg/kg) treatment. This result highlights a role for caudal brain stem GLP-1-R in the mediation of LPS anorexia but does not rule out the possibility that forebrain receptors also contribute to the response. Forebrain contribution was addressed by delivery of the GLP-1-R antagonist to the third ventricle with the caudal flow of cerebrospinal fluid blocked by occlusion of the cerebral aqueduct. Exendin-(9–39) delivery thus limited to forebrain did not attenuate the anorexic response to LPS. These data suggest that LPS anorexia is mediated, in part, by release of the native peptide acting on GLP-1-R within the caudal brain stem.
Retinal Bipolar Cell Input Mechanisms in Giant Danio. II. Patch-Clamp Analysis ofonBipolar Cells
Authors: Wong Kwoon Y. , Cohen Ethan D. , Dowling John E.
Published: July 2004

Glutamate receptors on giant danio retinal on bipolar cells were studied with whole cell patch clamping using a slice preparation. Cone-driven on bipolars (Cbs) and mixed-input on bipolars (Mbs) were identified morphologically. Most Cbs responded to the excitatory amino acid transporter (EAAT) substrate d-aspartate but not to the group III metabotropic glutamate receptor (mGluR) agonist l-(+)-2-amino-4-phosphonobutyric acid (l-AP4) or the AMPA/kainate receptor agonist kainate, suggesting EAATs are the primary glutamate receptors on Cbs. The EAAT inhibitor dl- threo-β-benzyloxyasparate (TBOA) blocked all light-evoked responses of Cbs, suggesting these responses are mediated exclusively by EAATs. Conversely, all Mbs responded to d-aspartate and l-AP4 but not to kainate, indicating they have both EAATs and group III mGluRs (presumably mGluR6). The light responses of Mbs involve both receptors because they could be blocked by TBOA plus (RS)-α-cyclopropyl-4-phosphonophenylglycine (CPPG, a group III mGluR antagonist) but not by either alone. Under dark-adapted conditions, the responses of Mbs to green (rod-selective) stimuli were reduced by CPPG but enhanced by TBOA. In contrast, both antagonists reduced the responses to red (cone-selective) stimuli, although TBOA was more effective. Furthermore, under photopic conditions, TBOA failed to eliminate light-evoked responses of Mbs. Thus on Mbs, rod inputs are mediated predominantly by mGluR6, whereas cone inputs are mediated mainly by EAATs but also by mGluR6 to some extent. Finally, we explored the interactions between EAATs and mGluR6 in Mbs. Responses to d-aspartate were reduced by l-AP4 and vice versa. Therefore mGluR6 and EAATs suppress each other, and this might underlie mutual suppression between rod and cone signals in Mbs.
Semi-Chronic Motorized Microdrive and Control Algorithm for Autonomously Isolating and Maintaining Optimal Extracellular Action Potentials
Authors: Cham Jorge G. , Branchaud Edward A. , Nenadic Zoran , Greger Bradley , Andersen Richard A. , Burdick Joel W.
Published: July 2004

A system was developed that can autonomously position recording electrodes to isolate and maintain optimal quality extracellular signals. The system consists of a novel motorized miniature recording microdrive and a control algorithm. The microdrive was designed for chronic operation and can independently position four glass-coated Pt-Ir electrodes with micrometer precision over a 5-mm range using small (3 mm diam) piezoelectric linear actuators. The autonomous positioning algorithm is designed to detect, align, and cluster action potentials and then command the microdrive to optimize and maintain the neural signal. This system is shown to be capable of autonomous operation in monkey cortical tissue.
Functional Topography of Converging Visual and Auditory Inputs to Neurons in the Rat Superior Colliculus
Authors: Skaliora Irini , Doubell Timothy P. , Holmes Nicholas P. , Nodal Fernando R. , King Andrew J.
Published: July 2004

We have used a slice preparation of the infant rat midbrain to examine converging inputs onto neurons in the deeper multisensory layers of the superior colliculus (dSC). Electrical stimulation of the superficial visual layers (sSC) and of the auditory nucleus of the brachium of the inferior colliculus (nBIC) evoked robust monosynaptic responses in dSC cells. Furthermore, the inputs from the sSC were found to be topographically organized as early as the second postnatal week and thus before opening of the eyes and ear canals. This precocious topography was found to be sculpted by GABAA-mediated inhibition of a more widespread set of connections. Tracer injections in the nBIC, both in coronal slices as well as in hemisected brains, confirmed a robust projection originating in the nBIC with distinct terminals in the proximity of the cell bodies of dSC neurons. Combined stimulation of the sSC and nBIC sites revealed that the presumptive visual and auditory inputs are summed linearly. Finally, whereas either input on its own could manifest a significant degree of paired-pulse facilitation, temporally offset stimulation of the two sites revealed no synaptic interactions, indicating again that the two inputs function independently. Taken together, these data provide the first detailed intracellular analysis of convergent sensory inputs onto dSC neurons and form the basis for further exploration of multisensory integration and developmental plasticity.
On univalent functions defined by a generalized Sălăgean operator
Authors: Al-Oboudi F. M.
Published: July 2004

We introduce a class of univalent functions
Rn(λ, α) defined by a new differential operator
Dnf(z), n ∈ ℕ0 = {0, 1, 2, …}, where
D0f(z) = f(z), D1f(z) = (1 − λ)f(z) + λzf′(z) = Dλf(z), λ ≥ 0, and
Dnf(z) = Dλ(Dn−1f(z)). Inclusion relations,
extreme points of Rn(λ, α), some convolution
properties of functions belonging to Rn(λ, α), and
other results are given.
Spectral properties of the Klein‐Gordon s‐wave equation with spectral parameter‐dependent boundary condition
Authors: Başcanbaz-Tunca Gülen
Published: July 2004

We investigate the spectrum of the differential operator
Lλ defined by the Klein‐Gordon s‐wave equation
y″ + (λ − q(x)) 2y = 0, x ∈ ℝ+ = [0, ∞),
subject to the spectral parameter‐dependent boundary condition
y′(0) − (aλ + b)y(0) = 0 in the space L2(ℝ+), where a ≠ ±i, b are complex
constants, q is a complex‐valued function. Discussing the
spectrum, we prove that Lλ has a finite number of
eigenvalues and spectral singularities with finite multiplicities
if the conditions limx→∞q(x) = 0, ,
ϵ > 0, hold. Finally we show the properties of the
principal functions corresponding to the spectral singularities.
Manipulating dendritic cell biology for the active immunotherapy of cancer
Authors: O'Neill David W. , Adams Sylvia , Bhardwaj Nina
Published: July 2004

Dendritic cells (DCs) are specialized antigen-presenting cells (APCs) that have an unequaled capacity to initiate primary immune responses, including tolerogenic responses. Because of the importance of DCs in the induction and control of immunity, an understanding of their biology is central to the development of potent immunotherapies for cancer, chronic infections, autoimmune disease, and induction of transplantation tolerance. This review discusses recent advances in DC research and the application of this knowledge toward new strategies for the clinical manipulation of DCs for cancer immunotherapy.
Increase in laminin expression in allergic airway remodelling and decrease by dexamethasone
Authors: Christie P.E. , Jonas M. , Tsai C-H. , Chi E.Y. , Henderson W.R.
Published: July 2004

Lung expression of the extracellular matrix protein, laminin, and its receptor, laminin‐1 receptor, were examined in a mouse model of asthma with airway remodelling.

Ovalbumin (OVA) was administered to BALB/c mice, intraperitoneally on days 0 and 14, and intranasally periodically between days 14 and 75.

The mice developed airway eosinophil and mononuclear inflammatory cell infiltration and fibrosis. On day 76, a marked increase in total laminin was seen in the airways of OVA‐treated mice compared to controls by Western blot analysis. The increased laminin expression was detected immunocytochemically in the thickened subepithelial basement membrane and around airways and blood vessels. The OVA‐treated mice showed increased expression of the α1, β1, and γ1 chains of the laminin‐1 isoform in monocytes, macrophages and eosinophils infiltrating the airways. Laminin‐1 receptor expression was increased in inflammatory and endothelial cells in the lungs of OVA‐treated mice compared to controls. Treatment of OVA‐sensitised/challenged mice with dexamethasone reduced airway expression of laminin and laminin‐1 receptor in OVA‐treated mice but not airway hyperresponsiveness to methacholine.

Laminin deposition may be an important component of the airway remodelling observed in chronic allergic lung inflammation and is a process modulated by corticosteroids.
Clinical prognostic indicators of high-grade pre-invasive bronchial lesions
Authors: Moro‐Sibilot D. , Fievet F. , Jeanmart M. , Lantuejoul S. , Arbib F. , Laverrière M.H. , Brambilla E. , Brambilla C.
Published: July 2004

Lung cancer arises from multistep genetic damage of bronchial epithelium, driving multifocal progressive dysplastic lesions. However, the risk of progression of high-grade pre-invasive bronchial lesions to cancer is poorly assessed. The purpose of this study was to better define the parameters that predict the outcome of these lesions.

The current authors prospectively studied 27 patients with 31 histologically proven severe dysplasia (SD) and carcinomain situ(CIS), with repeated bronchoscopy and endobronchial treatment. The influence of respiratory-cancer history, histopathological classification, tobacco consumption, and number of biopsies on the progression rate into cancer was studied.

The actuarial progression rate to cancer was 17% at 1 yr and 63% at 3 yrs. A total of 11 cases of CIS progressed to invasive cancer, 17 were stable or regressed during the study, two with SD regressed and one progressed to invasive cancer. Progression of CIS appeared more frequent in lesions diagnosed as “questionable CIS”. Persistence of smoking did not influence high-grade lesion outcome. The existence of synchronous lung cancer did not seem to impact on progression. The number of biopsies did not influence the outcome.

In conclusion, the current study suggests that the outcome of high-grade pre-invasive lesions is not modified by the number of biopsies performed on these lesions. Careful pathological examination of these lesions and pathological revision seem necessary, since questionable cases have the worse progression rate.
Laser-assisted uvulopalatoplasty for snoring: does it meet the expectations?
Authors: Larrosa F. , Hernandez L. , Morello A. , Ballester E. , Quinto L. , Montserrat J.M.
Published: July 2004

The high prevalence of habitual snoring (35% of the general population) and the increasing demand for an effective treatment have led, in the last decade, to the generalisation of laser-assisted uvulopalatoplasty (LAUP). However, acceptable studies on its effectiveness are lacking.

The present randomised, placebo-controlled study included 25 nonapnoeic and mild obstructive sleep apnoea snorers to evaluate LAUP effectiveness for snoring. Group I received a one-stage LAUP treatment and group II a placebo (simulated snore surgery followed by an oral placebo). Before each treatment and 3 months after, the variables and procedures assessed were: body weight; sleepiness (Epworth sleepiness scale); quality of life (SF‐36); subjective snoring intensity (0–10 analogue scale); objective snoring intensity (average decibel intensity); snoring index (number of snores per hour); and apnoea/hypopnea index.

No differences were observed in body weight, sleepiness, quality of life, subjective and objective intensity, and frequency of snoring, and apnoea/hypopnea index between the groups before and 3 months after treatment.

In conclusion, this study provides evidence of the lack of effectiveness of one-stage laser-assisted uvulopalatoplasty for snoring in nonapnoeic and mild obstructive sleep apnoea patients, with the result that it does not meet the expectations generated by the procedure.
Normal nasal mucociliary clearance in CF children: evidence against a CFTR‐related defect
Authors: McShane D. , Davies J.C. , Wodehouse T. , Bush A. , Geddes D. , Alton E.W.F.W.
Published: July 2004

Studies on mucociliary clearance (MCC) in cystic fibrosis (CF) have produced conflicting results. This study aimed to differentiate primary (ion transport-related) from secondary (inflammatory) causes of delayed MCC in CF.

Nasal MCC was measured in 50 children (CF, primary ciliary dyskinesia (PCD) and no respiratory disease). Nasal lavage fluid was analysed for interleukin (IL)‐8 and tumour necrosis factor‐α. Similar measurements were obtained in adult CF patients with and without chronic sinusitis (CS).

Children with CF had neither delayed MCC nor increased levels of cytokines. Conversely, children with PCD had prolonged MCC times (all >30 min) and significantly raised levels of IL‐8. CS‐positive CF adults had significantly slower MCC than CS‐negative subjects, but IL‐8 levels were low and similar in both groups.

Decreased airway surface liquid and delayed mucociliary clearance are the postulated primary mechanisms in cystic fibrosis. However, the current study reports that cystic fibrosis children have normal nasal mucociliary clearance. Abnormalities appeared in cystic fibrosis adults with symptoms of chronic sinus disease, suggesting a secondary rather than primary phenomenon. Studies to explore this mechanism in the distal, more sparsely-ciliated airways could aid an understanding of pathogenesis and the development of new treatments.
PPAR‐γ agonists as therapy for diseases involving airway neutrophilia
Authors: Birrell M.A. , Patel H.J. , McCluskie K. , Wong S. , Leonard T. , Yacoub M.H. , Belvisi M.G.
Published: July 2004

Peroxisome proliferator-activated receptors (PPARs) are a family of ligand-activated nuclear hormone receptors belonging to the steroid receptor superfamily. Previously, the present authors have shown that PPAR‐γ agonists inhibit the release of inflammatory cell survival factors and induce apoptosisin vitro. The aim of this study was to determine the effect of two structurally different PPAR agonists in anin vivomodel of lipopolysaccharide (LPS)-induced airway inflammation.

Mice were treated with PPAR agonists, rosiglitazone or SB 219994, prior to exposure to aerosolised LPS, and the extent of airway inflammation was assessed 3 h later.

In these experiments, the PPAR ligands inhibited LPS-induced airway neutrophilia and associated chemoattractants/survival factors (keratinocyte-derived chemokine and granulocyte-colony stimulating factor) in the mouse lung.

The present authors postulate that if a peroxisome proliferator-activated receptor agonist has the same effect in man, and neutrophils are important in the progression of respiratory diseases, such as chronic obstructive pulmonary disease, then this class of compounds could be a potential therapy. Furthermore, several peroxisome proliferator-activated receptor‐γ agonists have been shown to be clinically effective for the treatment of type II diabetes, suggesting that any benefit of peroxisome proliferator-activated receptor‐γ ligands in the progression of respiratory diseases, which may involve airway neutrophilia, could be explored relatively quickly.
Comparison of99mTc‐DTPA and urea for measuring cefepime concentrations in epithelial lining fluid
Authors: Bayat S. , Louchahi K. , Verdière B. , Anglade D. , Rahoui A. , Sorin P‐M. , Tod M. , Petitjean O. , Fraisse F. , Grimbert F.A.
Published: July 2004

The efficacy of antimicrobial agents against pulmonary infections depends on their local concentrations in the lung. The aims of the present study were to: 1) compare technetium‐99m diethylenetriaminepenta-acetic acid (99mTc‐DTPA) and urea as markers of epithelial lining fluid (ELF) dilution for measuring ELF concentrations of pharmaceuticals; 2) quantify ELF cefepime concentrations in normal and injured lung; and 3) measure the increase in permeability to cefepime following oleic acid-induced acute lung injury.

A modified bronchoalveolar lavage technique, based on equilibration of infused99mTc-DTPA, was used to measure ELF volume. Cefepime was administered intravenously at steady plasma levels. Six serial bronchoalveolar lavages were performed 5 h after the beginning of infusion.

ELF to plasma cefepime concentration ratios were 95±17 and 100±14.5% in normal and injured lung respectively. When urea was used as marker, cefepime concentration ratios were underestimated at 16.4±2.7 and 73.9±8.4% respectively. Cefepime blood/airspace clearance increased from 3.8±0.7 µL·min−1in controls to 39.8±4.9 µL·min−1in acute lung injury.

It was concluded that: 1) cefepime concentrations in epithelial lining fluid were in equilibrium with those in plasma in both normal and injured lung after 5 h at steady plasma concentrations; 2) epithelial lining fluid cefepime concentration by the urea method was much less underestimated in injuredversusnormal lung; and 3) acute lung injury induces a 10‐fold elevation of cefepime blood/airspace clearance.
Cavitary lung masses in SLE patients: an unusual manifestation of CMV infection
Authors: Najjar M. , Siddiqui A.K. , Rossoff L. , Cohen R.I.
Published: July 2004

The typical radiographical findings of cytomegalovirus pneumonitis are bilateral interstitial infiltrates.

In this study, the current authors describe two patients on corticosteroid treatment for systemic lupus erythematosus, complicated by histologically confirmed cytomegalovirus pneumonitis, presenting as cavitary masses.

This rare presentation of cytomegalovirus pneumonitis broadens the differential diagnosis of cavitary lesions to include cytomegalovirus infection in immunocompromised individuals.
Idiopathic pulmonary haemosiderosis revisited
Authors: Ioachimescu O.C. , Sieber S. , Kotch A.
Published: July 2004

Idiopathic pulmonary haemosiderosis is a rare cause of diffuse alveolar haemorrhage of unknown aetiology. It occurs most frequently in children, has a variable natural history with repetitive episodes of diffuse alveolar haemorrhage, and has been reported to have a high mortality. Many patients develop iron deficiency anaemia secondary to deposition of haemosiderin iron in the alveoli.

Examination of sputum and bronchoalveolar lavage fluid can disclose haemosiderin-laden alveolar macrophages (siderophages), and the lung biopsy shows numerous siderophages in the alveoli, without any evidence of pulmonary vasculitis, nonspecific/granulomatous inflammation, or deposition of immunoglobulins. Contrary to earlier reports, corticosteroids alone or in combination with other immunosuppressive agents may be effective for either exacerbations or maintenance therapy of idiopathic pulmonary haemosiderosis.
Clonal strains ofPseudomonas aeruginosain paediatric and adult cystic fibrosis units
Authors: O'Carroll M.R. , Syrmis M.W. , Wainwright C.E. , Greer R.M. , Mitchell P. , Coulter C. , Sloots T.P. , Nissen M.D. , Bell S.C.
Published: July 2004

Despite recent reports of clonal strains ofPseudomonas aeruginosain cystic fibrosis (CF) units, the need for routine microbiological surveillance remains contentious.

Sputum was collected prospectively from productive patients attending the regional paediatric and adult CF units in Brisbane, Australia. AllP. aeruginosaisolates were typed using pulsed-field gel electrophoresis. Spirometry, anthropometrics, hospitalisations and antibiotic sensitivity data were recorded.

The first 100 sputum samples (first 50 patients at each clinic) harboured 163 isolates ofP. aeruginosa. A total of 39 patients shared a common strain (pulsotype 2), 20 patients shared a strain with at least one other patient and 41 patients harboured unique strains. Eight patients shared a strain identical to a previously reported Australian transmissible strain (pulsotype 1). Compared with the unique strain group, patients harbouring pulsotype 2 were younger and had poorer lung function. Treatment requirements were similar in these two groups, as were the rates of multiresistance.

In conclusion, 59% of patients harboured a clonal strain, supporting the need for routine microbiological surveillance. In contrast to previously described clonal strains, the dominant pulsotype was indistinguishable from nonclonal strains with respect to both colonial morphology and multiresistance. The clinical significance of clonal strains remains uncertain and requires longitudinal study.
Immunokinetics in severe pneumonia due to influenza virus and bacteria coinfection in mice
Authors: Seki M. , Yanagihara K. , Higashiyama Y. , Fukuda Y. , Kaneko Y. , Ohno H. , Miyazaki Y. , Hirakata Y. , Tomono K. , Kadota J. , Tashiro T. , Kohno S.
Published: July 2004

Coinfections of bacteria and influenza are a major cause of excessive mortality during influenza epidemics. However, the mechanism of the synergy between influenza virus and bacteria are poorly understood.

In this study, mice were inoculated with influenza virus, followed 2 days later by inoculation withStreptococcus pneumoniae. The kinetics of viral titres, bacterial numbers and the immune response (cytokine and chemokine production) were also analysed.

Short-term survival correlated with pathological changes in the lungs of infected mice. Influenza virus orS. pneumoniaeinfection alone induced moderate pneumonia; however, severe bronchopneumonia with massive haemorrhage in coinfected mice, which caused death of these mice ∼2 days after inoculation withS. pneumoniae, was noted. Intrapulmonary levels of inflammatory cytokines/chemokines, type‐1 T‐helper cell cytokines and Toll-like receptors, and the related mitogen-activated protein kinase signalling molecules (phosphorylated extracellular signal-regulated kinase ‐1 and ‐2, p38 and c‐Jun N‐terminal kinase), were increased in coinfected mice.

These results suggest that immune mediators, including cytokines and chemokines, through Toll-like receptors/mitogen-activated protein kinase pathways, play important roles in the pathology of coinfection caused by influenza virus andStreptococcus pneumoniae.
Prescribing of clozapine and olanzapine: dosage, polypharmacy and patient ethnicity
Authors: Taylor David M.
Published: July 2004

Aims and Method

The aim of this study was to determine the existence and extent of differences in prescribing practice for patients according to ethnic group, with two widely used atypical antipsychotics, olanzapine and clozapine. All in-patient prescription charts were screened and patients receiving olanzapine and clozapine identified. Dosage, antipsychotic co-prescription and race were recorded, along with demographic details, and evaluated using comparative statistical analysis.

Results

Overall, 1441 prescriptions were screened; 328 patients received olanzapine and 200 clozapine. Details of ethnic origin were available for 287 of those prescribed olanzapine and 188 of those prescribed clozapine. There was no significant difference between ethnic groups in age or gender, for either drug. For clozapine, dosage and extent of antipsychotic co-prescription did not differ significantly between ethnic groups; for olanzapine, there was no significant difference in daily dose between the groups, but co-prescription was significantly more common in Black (33%) than in White patients (20%; P=0.023).

Clinical Implications

Important differences in the prescription of olanzapine and clozapine between ethnic groups are uncommon, but demand further investigation. Larger studies incorporating additional baseline details such as diagnosis and body weight are called for.
Are dedicated research posts of value to psychiatry trainees?
Authors: Strydom Andre , Higgins Nicola
Published: July 2004

Aims

To explore psychiatric trainees' (senior house officers') experience of a dedicated 6-month research post.

Method

A questionnaire survey was conducted by post or e-mail of all previous post-holders of two research posts in a large London training rotation.

Results and Clinical Implications

Twenty of the 28 post-holders completed the questionnaire. Overall, their experiences were positive in terms of research experience, exposure to academic environment and in facilitating future career opportunities. A minority of respondents found supervision to be unsatisfactory. Dedicated research posts are a valuable training opportunity that can complement clinical experience for trainees and foster an interest in research.