bluuebunny/crossref_metadata_2025 huggingface dataset:
Changing product development process through information technology: a Brazilian case
Authors: José Barbin Laurindo Fernando , Monteiro de Carvalho Marly
Published: March 2005

Purpose

Aims to discuss the linking of enhanced performance of the new product development process with the increasing use of IT applications, resulting in a competitive advantage.

Design/methodology/approach

Utilises a case study methodology in a manufacturing company in the Brazilian building materials industry.

Findings

Some evidence of enhancement of new product development could be found, such as a reduction in both development cycle time and development costs. As regards customer satisfaction, the executive perception of improvement in final product quality could be identified, and finally no relationship could be observed between the effects and the number of new products launched.

Originality/value

IT applications are more successful when links with business strategy are stronger. The benefits of IT strategic alignment occurred after the critical success factor method was adopted in both IT and new product development processes.
Neuropsychiatric disturbances in SLE are associated with antibodies against NMDA receptors
Authors: Omdal R. , Brokstad K. , Waterloo K. , Koldingsnes W. , Jonsson R. , Mellgren S. I.
Published: March 2005

To determine whether neuropsychiatric manifestations in patients with systemic lupus erythematosus (SLE) are influenced by antibodies against the human N‐methyl‐d‐aspartate (NMDA) receptor types NR2a or NR2b. A decapeptide was synthesized containing a sequence motif present in the extracellular ligand‐binding domain of NMDA receptors NR2a and NR2b, bound by the monoclonal murine anti‐DNA antibody R4A. In an ELISA with the murine monoclonal R4v as positive control, plasma samples of 57 patients with SLE were examined for the anti‐peptide (anti‐NR2) antibody after the patients had been subjected to comprehensive psychological and cognitive testing. Poor performance on the Visual Paired Associates test (immediate), the Grooved Pegboard test, as well as high scores on the Beck Depression Inventory, and scales D‐2 (depression), Pd‐4 (psychopathic deviate), Sc‐8 (schizophrenia), and Ma‐9 (hypomania) of the MMPI‐2 were significantly associated with elevated levels of anti‐NR2 antibodies. The findings in several domains indicate an association between anti‐NR2 antibodies and depressed mood in addition to decreased short‐time memory and learning. Antibodies to NMDA receptors thus may represent one of several mechanisms for cerebral dysfunction in patients with SLE.
An unusual family with Leber's hereditary optic neuropathy and facioscapulohumeral muscular dystrophy
Authors: Chuenkongkaew W.L. , Lertrit P. , Limwongse C. , Nilanont Y. , Boonyapisit K. , Sangruchi T. , Chirapapaisan N. , Suphavilai R.
Published: March 2005

We performed an observational prospective analysis to study the clinical characteristics as well as a molecular genetic analysis of 17 members of a Thai family who had visual loss and/or muscle weakness. Their blood mitochondrial DNA were examined for the presence of the G11778A Leber's hereditary optic neuropathy (LHON) mutation. Facioscapulohumeral muscular dystrophy (FSHD) DNA analysis was performed in four members who had visual loss. Of 17 family members, the eight members who had the 11778 LHON mutation were all from branch ‘a’. Three of these eight members had FSHD with a 17–27‐kb deletion of a tandem repeat in the 4q35 subtelomere, and two had been clinically diagnosed as FSHD. Four of six examined members in branch ‘b’ showed muscular dystrophy clinically diagnosed as FSHD. No correlation of blood DNA analysis between LHON and FSHD in affected members was found. We describe the first family with FSHD and G11778A LHON in which a mutation in mitochondrial DNA at nucleotide position 11778 of branch ‘a’ was found to be the origin of the mutation.
A1152D mutation of the Na+ channel causes paramyotonia congenita and emphasizes the role of DIII/S4–S5 linker in fast inactivation
Authors: Bouhours Magali , Luce Sandrine , Sternberg Damien , Willer Jean Claude , Fontaine Bertrand , Tabti Nacira
Published: March 2005

Missense mutations in the human skeletal muscle Na+ channel α subunit (hSkM1) are responsible for a number of muscle excitability disorders. Among them, paramyotonia congenita (PC) is characterized by episodes of muscle stiffness induced by cold and aggravated by exercise. We have identified a new PC‐associated mutation, which substitutes aspartic acid for a conserved alanine in the S4–S5 linker of domain III (A1152D). This residue is of particular interest since its homologue in the rat brain type II Na+ channel has been suggested as an essential receptor site for the fast inactivation particle. To identify the biophysical changes induced by the A1152D mutation, we stably expressed hSkM1 mutant or wild‐type (WT) channels in HEK293 (human embryonic kidney) cells, and recorded whole‐cell Na+ currents with the patch‐clamp technique. Experiments were performed both at 21 and 11°C to better understand the sensitivity to cold of paramyotonia. The A1152D mutation disrupted channel fast inactivation. In comparison to the WT, mutant channels inactivated with slower kinetics and displayed a 5 mV depolarizing shift in the voltage dependence of the steady‐state. The other noticeable defect of A1152D mutant channels was an accelerated rate of deactivation from the inactivated state. Decreasing temperature by 10°C amplified the differences in channel gating kinetics between mutant and WT, and unveiled differences in both the sustained current and channel deactivation from the open state. Overall, cold‐exacerbated mutant defects may result in a sufficient excess of Na+ influx to produce repetitive firing and myotonia. In the light of previous reports, our data point to functional as well as phenotypic differences between mutations of conserved S4–S5 residues in domains II and III of the human skeletal muscle Na+ channel.
A Formal Two-Phase Method for Decomposition of Complex Design Problems
Authors: Chen Li , Ding Zhendong , Li Simon
Published: March 2005

This paper presents a formal two-phase decomposition method for complex design problems that are represented in an attribute-component incidence matrix. Unlike the conventional approaches, this method decouples the overall decomposition process into two separate, autonomous function components: dependency analysis and matrix partitioning, which are algorithmically achieved by an extended Hierarchical Cluster Analysis (HCA) and a Partition Point Analysis (PPA), respectively. The extended HCA (Phase 1) is applied to convert the (input) incidence matrix, which is originally unorganized, into a banded diagonal matrix. The PPA (Phase 2) is applied to further transform this matrix into a block-angular matrix according to a given set of decomposition criteria. This method provides both flexibility in the choice of the different settings on the decomposition criteria, and diversity in the generation of the decomposition solutions, both taking place in Phase 2 without resort to Phase 1. These features essentially make this decomposition method effective, especially in its application to re-decomposition. A powertrain design example is employed for illustration and discussion.
Rotor Profiles Synthesis for Lobe Pumps With Given Flow Rate Functions
Authors: Tong Shih-Hsi , Yang Daniel C. H.
Published: March 2005

In this paper we present a complete synthesis procedure for lobe pumps with required flow rate functions. A dimensionless flow rate expression, called the “specific flow rate,” is used for our pump synthesis. This specific flow rate depends only on the pitch and deviation functions of the pump rotor, and it is independent of the individual pump size, neither pumping frequency. Another important design parameter used is the “lobe noncircularity,” which is defined as the ratio of the lobe length to the rotor center distance. It is found that the lobe noncircularity is linearly dependent on the ratio of maximum to minimum flow rate regardless of the type of flow rate function. As a result, our synthesis procedure can be simplified as (1) select a type of desirable flow rate function, (2) from the flow rate function derive the corresponding deviation function, (3) based on the deviation function generate the desired rotor profile, and (4) calculate the real pump size. Another advantage is that by using this method wide classes of lobe pumps can be designed. A detailed design example is presented for illustration. In addition, new lobe profiles are invented based on some typical flow rate functions.
Similarity and Equivalence of Nutating Mechanisms to Bevel Epicyclic Gear Trains for Modeling and Analysis
Authors: Nelson Carl A. , Cipra Raymond J.
Published: March 2005

This paper addresses similarities between various nutating or wobbling mechanisms, in particular kinematic similarities. A case is made for the generalization of these mechanisms into a mechanism “class” having common kinematic characteristics, which is typified by bevel epicyclic gear trains. A similarity index is proposed to describe the quality of kinematic similarity, with the best degree of similarity termed “equivalence.” It is proposed that kinematic analysis of mechanisms belonging to this “class” can be simplified by modeling them as bevel-gear trains, and that static-force, power-flow, and efficiency analyses can also be greatly simplified in the case of “equivalent” mechanisms. Simplified kinematic, force, and efficiency analyses are demonstrated for a unique wobbling speed reducer using this new concept of equivalent geared mechanisms.
Graphical Methods to Locate the Secondary Instant Centers of Single-Degree-of-Freedom Indeterminate Linkages
Authors: Foster David E. , Pennock Gordon R.
Published: March 2005

This paper presents graphical techniques to locate the unknown instantaneous centers of zero velocity of planar, single-degree-of-freedom, linkages with kinematic indeterminacy. The approach is to convert a single-degree-of-freedom indeterminate linkage into a two-degree-of-freedom linkage. Two methods are presented to perform this conversion. The first method is to remove a binary link and the second method is to replace a single link with a pair of links connected by a revolute joint. First, the paper shows that a secondary instant center of a two-degree-of-freedom linkage must lie on a unique straight line. Then this property is used to locate a secondary instant center of the single-degree-of-freedom indeterminate linkage at the intersection of two lines. The two lines are obtained from a purely graphical procedure. The graphical techniques presented in this paper are illustrated by three examples of single-degree-of-freedom linkages with kinematic indeterminacy. The examples are a ten-bar linkage with only revolute joints, the single flier eight-bar linkage, and a ten-bar linkage with revolute and prismatic joints.
An Efficient Weighting Update Method to Achieve Acceptable Consistency Deviation in Analytical Target Cascading
Authors: Michalek Jeremy J. , Papalambros Panos Y.
Published: March 2005

Weighting coefficients are used in analytical target cascading (ATC) at each element of the hierarchy to express the relative importance of (a) matching targets passed from the parent element and (b) maintaining consistency of linking variables and consistency with designs achieved by subsystem child elements. Proper selection of weight values is crucial when the top-level targets are unattainable, for example when “stretch” targets are used. In this case, strict design consistency cannot be achieved with finite weights; however, it is possible to achieve arbitrarily small inconsistencies. This article presents an iterative method for finding weighting coefficients that achieve solutions within user-specified inconsistency tolerances and demonstrates its effectiveness with several examples. The method also led to reduced computational time in the demonstration examples.
Measurement of Thermal Boundary Conductance of a Series of Metal-Dielectric Interfaces by the Transient Thermoreflectance Technique
Authors: Stevens Robert J. , Smith Andrew N. , Norris Pamela M.
Published: March 2005

Measurement of the thermal boundary conductance (TBC) by use of a nondestructive optical technique, transient thermoreflectance (TTR), is presented. A simple thermal model for the TTR is presented with a discussion of its applicability and sensitivity. A specially prepared sample series of Cr, Al, Au, and Pt on four different substrates (Si, sapphire, GaN, and AlN) were tested at room temperature and the TTR signal fitted to the thermal model. The resulting TBC values vary by more than a factor of 3 0.71×108-2.3×108 W/m2 K. It is shown that the diffuse mismatch model (DMM) tended to overpredict the TBC of interfaces with materials having similar phonon spectra, while underpredicting the TBC for interfaces with dissimilar phonon spectra. The DMM only accounts for diffuse elastic scattering. Other scattering mechanisms are discussed which may explain the failure of the DMM at room temperature.
Experimental Study of Heat Transfer in an Evaporating Meniscus on a Moving Heated Surface
Authors: Kandlikar Satish G. , Kuan Wai Keat , Mukherjee Abhijit
Published: March 2005

A stable meniscus is formed by a circular nozzle dispensing water over a heated circular face of a rotating cylindrical copper block. The nozzle is offset from the axis of rotation of the copper block and thus a moving meniscus is formed on the surface. The water flow rate, heater surface temperature, and the speed of rotation are controlled to provide a stable meniscus with continuous evaporation of water without any meniscus breakup. The study provides an important insight into the role of the evaporating liquid-vapor interface and transient heat conduction around a nucleating bubble in pool boiling.
Frost Temperature Relations for Defrosting Sensing System
Authors: Iragorry J. , Tao Y.-X.
Published: March 2005

To develop a better defrosting control system on finned evaporators of a refrigeration system, a study is conducted to better quantify the frosting and defrosting processes by using an infrared thermometer to determine the frost surface temperature. For gradual frost deposition a slow variation in surface emissivity is expected, while the defrosting process is characterized by a sudden change of this property. As an indicator for the defrosting initiation control mechanism, the times at which the IR signals stabilize at different conditions (Reynolds number, cold surface temperature, and ambient temperature) are reported along with the terminal mass concentration of a defined frosting process. On the other hand, the abrupt variation of surface emissivity indicates the termination of the defrosting process. Removable fins are used to measure frost weight, and a video microscope is used to determine the frost thickness. Defrosting initiation time and durations marked by melting, temperature are reported as a function of initial mass concentration and defrosting base surface temperature. The presented results could be used to design a better defrosting control system with better accuracy and energy saving features.
Functional Genomic Analysis of RNA Interference in
C. elegans
Authors: Kim John K. , Gabel Harrison W. , Kamath Ravi S. , Tewari Muneesh , Pasquinelli Amy , Rual Jean-François , Kennedy Scott , Dybbs Michael , Bertin Nicolas , Kaplan Joshua M. , Vidal Marc , Ruvkun Gary
Published: March 2005

RNA interference (RNAi) of target genes is triggered by double-stranded RNAs (dsRNAs) processed by conserved nucleases and accessory factors. To identify the genetic components required for RNAi, we performed a genome-wide screen using an engineered RNAi sensor strain of
Caenorhabditis elegans
. The RNAi screen identified 90 genes. These included Piwi/PAZ proteins, DEAH helicases, RNA binding/processing factors, chromatin-associated factors, DNA recombination proteins, nuclear import/export factors, and 11 known components of the RNAi machinery. We demonstrate that some of these genes are also required for germline and somatic transgene silencing. Moreover, the physical interactions among these potential RNAi factors suggest links to other RNA-dependent gene regulatory pathways.
Azithromycin Exhibits Bactericidal Effects on
Pseudomonas aeruginosa
through Interaction with the Outer Membrane
Authors: Imamura Yoshifumi , Higashiyama Yasuhito , Tomono Kazunori , Izumikawa Koichi , Yanagihara Katsunori , Ohno Hideaki , Miyazaki Yoshitsugu , Hirakata Yoichi , Mizuta Yohei , Kadota Jun-ichi , Iglewski Barbara H. , Kohno Shigeru
Published: March 2005

The aim of the present study was to elucidate the effect of the macrolide antibiotic azithromycin on
Pseudomonas aeruginosa
. We studied the susceptibility to azithromycin in
P. aeruginosa
PAO1 using a killing assay. PAO1 cells at the exponential growth phase were resistant to azithromycin. In contrast, PAO1 cells at the stationary growth phase were sensitive to azithromycin. The divalent cations Mg
2+
and Ca
2+
inhibited this activity, suggesting that the action of azithromycin is mediated by interaction with the outer membranes of the cells, since the divalent cations exist between adjacent lipopolysaccharides (LPSs) and stabilize the outer membrane. The divalent cation chelator EDTA behaved in a manner resembling that of azithromycin; EDTA killed more PAO1 in the stationary growth phase than in the exponential growth phase. A 1-
N
-phenylnaphthylamine assay showed that azithromycin interacted with the outer membrane of
P. aeruginosa
PAO1 and increased its permeability while Mg
2+
and Ca
2+
antagonized this action. Our results indicate that azithromycin directly interacts with the outer membrane of
P. aeruginosa
PAO1 by displacement of divalent cations from their binding sites on LPS. This action explains, at least in part, the effectiveness of sub-MICs of macrolide antibiotics in pseudomonal chronic airway infection.
Phototargeting Oral Black-Pigmented Bacteria
Authors: Soukos Nikolaos S. , Som Sovanda , Abernethy Abraham D. , Ruggiero Karriann , Dunham Joshua , Lee Chul , Doukas Apostolos G. , Goodson J. Max
Published: March 2005

We have found that broadband light (380 to 520 nm) rapidly and selectively kills oral black-pigmented bacteria (BPB) in pure cultures and in dental plaque samples obtained from human subjects with chronic periodontitis. We hypothesize that this killing effect is a result of light excitation of their endogenous porphyrins. Cultures of
Prevotella intermedia
and
P
.
nigrescens
were killed by 4.2 J/cm
2
, whereas
P
.
melaninogenica
required 21 J/cm
2
. Exposure to light with a fluence of 42 J/cm
2
produced 99% killing of
P. gingivalis
. High-performance liquid chromatography demonstrated the presence of various amounts of different porphyrin molecules in BPB. The amounts of endogenous porphyrin in BPB were 267 (
P
.
intermedia
), 47 (
P
.
nigrescens
), 41 (
P
.
melaninogenica
), and 2.2 (
P
.
gingivalis
) ng/mg. Analysis of bacteria in dental plaque samples by DNA-DNA hybridization for 40 taxa before and after phototherapy showed that the growth of the four BPB was decreased by 2 and 3 times after irradiation at energy fluences of 4.2 and 21 J/cm
2
, respectively, whereas the growth of the remaining 36 microorganisms was decreased by 1.5 times at both energy fluences. The present study suggests that intraoral light exposure may be used to control BPB growth and possibly benefit patients with periodontal disease.
Differential Expression of Cytokines and Chemokines in Human Monocytes Induced by Lipid Formulations of Amphotericin B
Authors: Simitsopoulou M. , Roilides E. , Dotis J. , Dalakiouridou M. , Dudkova F. , Andreadou E. , Walsh T. J.
Published: March 2005

The immunomodulatory effects of liposomal amphotericin B (LAMB), amphotericin B lipid complex (ABLC), and amphotericin B colloidal dispersion (ABCD) on mRNA and protein profiles of five cytokines and chemokines expressed by human monocyte-enriched mononuclear leukocytes (MNCs) were comprehensively evaluated by semiquantitative reverse transcription-PCR and enzyme-linked immunosorbent assays; they were compared to those of deoxycholate amphotericin B (DAMB). mRNAs of interleukin-1β (IL-1β), IL-1 receptor antagonist (IL-1ra), tumor necrosis factor alpha (TNF-α), monocyte chemotactic protein 1 (MCP-1), and macrophage inflammatory protein 1β (MIP-1β) were assessed after treatment of MNCs with each drug for 0.5, 2, 6, and 22 h. The cytokine protein profiles were obtained after incubation of MNCs with the drugs for 2 h (TNF-α) or 6 h (all the others). In the mRNA studies, DAMB resulted in an early increase of inflammatory cytokines or chemokines IL-1β, TNF-α, MCP-1, and MIP-1β (2 to 6 h) and in a late increase of anti-inflammatory IL-1ra (22 h). ABCD showed a general similar trend of inflammatory gene up-regulation. LAMB and ABLC decreased or did not affect IL-1β and TNF-α, whereas ABLC additionally decreased MIP-1β. In protein measurement studies, DAMB and ABCD up-regulated production of IL-1β (P< 0.05), decreased the IL-1ra/IL-1β ratio, and up-regulated the production of MCP-1 and MIP-1β. In comparison, LAMB and ABLC down-regulated or did not affect the production of these cytokines/chemokines compared to untreated MNCs; furthermore, ABLC tended to increase the IL-1ra/IL-1β ratio. These studies demonstrate that amphotericin B formulations differentially affect gene expression and release of an array of proinflammatory and anti-inflammatory cytokines that potentially may explain the differences in infusion-related reactions and dose-dependent nephrotoxicity as well as modulation of the host immune response to invasive fungal infections.
In Vitro and In Vivo Activities of Macrolide Derivatives against
Mycobacterium tuberculosis
Authors: Falzari Kanakeshwari , Zhu Zhaohai , Pan Dahua , Liu Huiwen , Hongmanee Poonpilas , Franzblau Scott G.
Published: March 2005

Existing macrolides have never shown definitive clinical efficacy in tuberculosis. Recent reports suggest that ribosome methylation is involved in macrolide resistance in
Mycobacterium tuberculosis
, a mechanism that newer macrolides have been designed to overcome in gram-positive bacteria. Therefore, selected macrolides and ketolides (descladinose) with substitutions at positions 9, 11,12, and 6 were assessed for activity against
M. tuberculosis
, and those with MICs of ≤4 μM were evaluated for cytotoxicity to Vero cells and J774A.1 macrophages. Several compounds with 9-oxime substitutions or aryl substitutions at position 6 or on 11,12 carbamates or carbazates demonstrated submicromolar MICs. For the three macrolide-ketolide pairs, macrolides demonstrated superior activity. Four compounds with low MICs and low cytotoxicity also effected significant reductions in CFU in infected macrophages. Active compounds were assessed for tolerance and the ability to reduce CFU in the lungs of BALB/c mice in an aerosol infection model. A substituted 11,12 carbazate macrolide demonstrated significant dose-dependent inhibition of
M. tuberculosis
growth in mice, with a 10- to 20-fold reduction of CFU in lung tissue. Structure-activity relationships, some of which are unique to
M. tuberculosis
, suggest several synthetic directions for further improvement of antituberculosis activity. This class appears promising for yielding a clinically useful agent for tuberculosis.
Molecular Analysis of Isoniazid-Resistant
Mycobacterium tuberculosis
Isolates from England and Wales Reveals the Phylogenetic Significance of the
ahpC
−46A Polymorphism
Authors: Baker L. V. , Brown T. J. , Maxwell O. , Gibson A. L. , Fang Z. , Yates M. D. , Drobniewski F. A.
Published: March 2005

The present study investigated the prevalence and diagnostic potential of the most commonly reported mutations associated with isoniazid resistance,
katG
315Thr,
katG
315Asn,
inhA
−15T,
inhA
−8A, and the
oxyR
-
ahpC
intergenic region, in a population sample of 202 isoniazid-resistant
Mycobacterium tuberculosis
isolates and 176 randomly selected fully sensitive isolates from England and Wales identified by using a directed oligonucleotide array and limited DNA sequencing. The strains were recovered from patients originating from 29 countries; 41 isolates were multidrug resistant. Mutations affecting
katG
315, the
inhA
promoter, and the
oxyR
-
ahpC
intergenic region were found in 62.7, 21.9, and 30% of 169 genotypically distinct isoniazid-resistant isolates, respectively, whereas they were found in 0, 0, and 8% of susceptible strains, respectively. The frequency of mutation at each locus was unrelated to the resistance profile or previous antituberculous drug therapy. The commonest mutation in the
oxyR
-
ahpC
intergenic region,
ahpC
−46A, was present in 23.7% of isoniazid-resistant isolates and 7.5% of susceptible isolates. This proved to be a phylogenetic marker for a subgroup of
M. tuberculosis
strains originating on the Indian subcontinent, which shared IS
6110
-based restriction fragment length polymorphism and spoligotype features with the Delhi strain and Central Asian strain CAS1; and this marker is strongly associated with isoniazid resistance and the
katG
315Thr mutation. In total, 82.8% of unrelated isoniazid-resistant isolates could be identified by analysis of just two loci:
katG
315 and the
inhA
promoter. Analysis of the
oxyR
-
ahpC
intergenic region, although phylogenetically interesting, does not contribute significantly to further identification of isoniazid-resistant isolates.
Effect of Mupirocin Treatment on Nasal, Pharyngeal, and Perineal Carriage of
Staphylococcus aureus
in Healthy Adults
Authors: Wertheim Heiman F. L. , Verveer Jeroen , Boelens Hélène A. M. , van Belkum Alex , Verbrugh Henri A. , Vos Magreet C.
Published: March 2005

Nasal carriage of
Staphylococcus aureus
is an important risk factor for
S. aureus
infections. Mupirocin nasal ointment is presently the treatment of choice for decolonizing the anterior nares. However, recent clinical trials show limited benefit from mupirocin prophylaxis in preventing nosocomial
S. aureus
infections, probably due to (re)colonization from extranasal carriage sites. Therefore, we studied the effectiveness of mupirocin nasal ointment treatment on the dynamics of
S. aureus
nasal and extranasal carriage. Twenty noncarriers, 26 intermittent carriers, and 16 persistent carriers had nasal, throat, and perineum samples taken 1 day before and 5 weeks after mupirocin treatment (twice daily for 5 days) and assessed for growth of
S. aureus
. The identities of cultured strains were assessed by restriction fragment length polymorphisms of the coagulase and protein A genes. The overall carriage rate (either nasal, pharyngeal, or perineal carrier or a combination) was significantly reduced after mupirocin treatment from 30 to 17 carriers (
P
= 0.003). Of the 17 carriers, 10 (60%) were still colonized with their old strain, 6 (35%) were colonized with an exogenous strain, and 1 (5%) was colonized with both. Two noncarriers became carriers after treatment. The acquisition of exogenous strains after mupirocin treatment is a common phenomenon. The finding warrants the use of mupirocin only in proven carriers for decolonization purposes. Mupirocin is effective overall in decolonizing nasal carriers but less effective in decolonizing extranasal sites.
Comparative Antimicrobial Characterization of LBM415 (NVP PDF-713), a New Peptide Deformylase Inhibitor of Clinical Importance
Authors: Fritsche Thomas R. , Sader Helio S. , Cleeland Roy , Jones Ronald N.
Published: March 2005

LBM415 (NVP PDF-713) is the first member of the peptide deformylase (PDF) inhibitor class being developed for clinical trials as a parenteral and oral agent for treatment of community-acquired respiratory tract disease and serious infections caused by antimicrobial-resistant gram-positive cocci. In this study susceptibility testing results from 1,306 recent clinical isolates selected to overrepresent resistance trends among the species were summarized. All staphylococci (153 strains; MIC at which 90% of isolates were inhibited [MIC90], 2 μg/ml),Streptococcus pneumoniae(170 strains; MIC90, 1 μg/ml), other streptococci (150 strains; MIC90, 1 μg/ml), enterococci (104 strains; MIC90, 4 μg/ml),Moraxella catarrhalis(103 strains; MIC90, 0.5 μg/ml), andLegionella pneumophila(50 strains; MIC90, 0.12 μg/ml) were inhibited at ≤8 μg of LBM415/ml, as were 97% ofHaemophilus influenzaeisolates (300 strains; MIC90, 4 to 8 μg/ml). Among other bacterial groups, 100% of gram-positive and -negative anaerobes, including 22Bacteroidesspp. strains (31 strains total; MIC90, 1 μg/ml), were inhibited by ≤4 μg/ml, whereasEnterobacteriaceae(112 strains) and most nonfermentative bacilli (107 strains) were not inhibited at readily achievable concentrations. The compound was found to have a dominantly bacteriostatic action, and spontaneous single-step mutational rates occurred at low levels (10−6to <10−8). Drug interaction studies failed to identify any class-specific synergistic interactions, nor were antagonistic interactions observed. Variations in broth and agar MIC test conditions demonstrated that, whereas the agar-based method trended towards a 1-log2dilution-higher MIC than the broth method and was inoculum dependent, other variations in incubation environment, medium supplements, pH, or calcium concentration had little influence on LBM415 MIC results. Use of the efflux inhibitor phe-arg-β-naphthylamide showed an average of 1 log2dilution decrease inH.influenzaeMICs, demonstrating the contribution of efflux pumps in influencing susceptibility to PDF inhibitors. The in vitro activity of LBM415 against targeted bacterial species, including resistant subsets, and other laboratory characteristics of this novel compound demonstrate the potential of PDF inhibitors as a new class of antimicrobial agents.
Excision of Nucleoside Analogs from DNA by p53 Protein, a Potential Cellular Mechanism of Resistance to Inhibitors of Human Immunodeficiency Virus Type 1 Reverse Transcriptase
Authors: Bakhanashvili Mary , Novitsky Elena , Rubinstein Ethan , Levy Itzchak , Rahav Galia
Published: March 2005

We investigated the ability of p53 in cytoplasm to excise nucleoside analogs (NAs). A decrease in incorporation of NAs by human immunodeficiency virus type 1 reverse transcriptase and their excision from DNA by p53, provided by the cytoplasmic fraction of LCC2 cells, suggest that p53 in cytoplasm may act as an external proofreader for NA incorporation.
In Vitro Effects of Spectinomycin and Ceftriaxone Alone or in Combination with Other Antibiotics against
Chlamydia trachomatis
Authors: Shang Shuxian , Xia Longqing , Zhong Mingying , Zhang Jinping , Zhao Jianbin , Gong Xiangdong , Mabey David , Wang Qianqiu
Published: March 2005

The in vitro effects of spectinomycin and ceftriaxone, alone or in combination with erythromycin, ofloxacin, and doxycycline, against
Chlamydia trachomatis
were investigated by the checkerboard method and compared by Ridit (reference identical unit) analysis. A combination of spectinomycin with erythromycin or doxycycline was found to be more effective than that of ceftriaxone.
Cloning, Characterization, and Expression Analysis of Hepcidin Gene from Red Sea Bream (
Chrysophrys major
)
Authors: Chen Song-Lin , Xu Mei-Yu , Ji Xiang-Shan , Yu Guo-Cai , Liu Yang
Published: March 2005

A cDNA encoding hepcidin was isolated from a library of cDNA from spleen of red sea bream (
Chrysophrys major
) by expressed sequence tag analysis. The expression of the hepcidin mRNA in various tissues was examined. Challenge of red sea bream with
Escherichia coli
DH5α elevated hepcidin mRNA levels in spleen, gill, liver, and intestine.
Antibiotic Tolerance Induced by Lactoferrin in Clinical
Pseudomonas aeruginosa
Isolates from Cystic Fibrosis Patients
Authors: Andrés María T. , Viejo-Diaz Mónica , Pérez Francisco , Fierro José F.
Published: March 2005

Lactoferrin-induced cell depolarization and a delayed tobramycin-killing effect on
Pseudomonas aeruginosa
cells were correlated. This antibiotic tolerance effect (ATE) reflects the ability of a defense protein to modify the activity of an antibiotic as a result of its modulatory effect on bacterial physiology.
P. aeruginosa
isolates from cystic fibrosis patients showed higher ATE values (≤6-fold) than other clinical strains.
Role of P-Glycoprotein in Distribution of Nelfinavir across the Blood-Mammary Tissue Barrier and Blood-Brain Barrier
Authors: Edwards Jeffrey E. , Alcorn Jane , Savolainen Juoko , Anderson Bradley D. , McNamara Patrick J.
Published: March 2005

As a first approach in understanding the possible efficacy and toxicity of human immunodeficiency virus protease inhibitors during breast feeding, the milk-to-plasma ratio of nelfinavir was determined in lactating rats. The milk-to-plasma ratio of nelfinavir was determined to be 0.56 ± 0.10 (means ± standard deviations). Western blotting indicated that P-glycoprotein is expressed in rat mammary and brain tissue; however, the multidrug-resistant modulator GF120918 showed a significant effect only at the blood-brain barrier and not at the mammary-epithelial tissue barrier.
Presence of Tetracycline Resistance Determinants and Susceptibility to Tigecycline and Minocycline
Authors: Fluit Ad C. , Florijn Alice , Verhoef Jan , Milatovic Dana
Published: March 2005

No relation between the presence of tetracycline resistance determinants
tet
(A) to
tet
(E) and the MICs of tigecycline was observed for
Enterobacteriaceae
, although tetracycline-susceptible isolates were more susceptible overall to tigecycline, whereas the presence of
tet
(M) in
Staphylococcus aureus
was associated with higher MICs of minocycline.
Drug use in English professional football
Authors: Waddington I , Malcolm D , Roderick M , Naik R
Published: March 2005

Objectives:To examine several issues related to drug use in English professional football. More particularly the project sought to gather data on: players’ use of permitted supplements (mineral and vitamin pills and creatine); whether they sought advice, and if so from whom, about their use of supplements; their experience of and attitudes towards drug testing; their views on the extent of the use of banned performance enhancing and recreational drugs in football; and their personal knowledge of players who used such drugs.

Methods:With the cooperation of the Professional Footballers Association (PFA), reply paid postal questionnaires were delivered to the home addresses of all 2863 members of the PFA. A total of 706 questionnaires were returned, a response rate of just under 25%.

Results:Many players use supplements, although almost one in five players does so without seeking qualified professional advice from anyone within the club. Blood tests are rarely used to monitor the health of players. One third of players had not been tested for drugs within the preceding two years, and 60% felt that they were unlikely to be tested in the next year. The use of performance enhancing drugs appears to be rare, although recreational drugs are commonly used by professional footballers: 6% of respondents indicated that they personally knew players who used performance enhancing drugs, and 45% of players knew players who used recreational drugs.

Conclusions:There is a need to ensure that footballers are given appropriate advice about the use of supplements in order to minimise the risk of using supplements that may be contaminated with banned substances. Footballers are tested for drugs less often than many other elite athletes. This needs to be addressed. The relatively high level of recreational drug use is not reflected in the number of positive tests. This suggests that many players who use recreational drugs avoid detection. It also raises doubts about the ability of the drug testing programme to detect the use of performance enhancing drugs.
Methods for injury surveillance in international cricket
Authors: Orchard J W , Newman D , Stretch R , Frost W , Mansingh A , Leipus A
Published: March 2005

Background:The varying methods of cricket injury surveillance have made direct comparison of published studies in this field impossible.

Methods:A consensus regarding definitions and methods to calculate injury rates in cricket was sought between researchers in this field. This was arrived at through a variety of face to face meetings, email communication, and draft reviews between researchers from six of the major cricket playing nations.

Results:It is recommended that a cricket injury is defined as any injury or other medical condition that either (a) prevents a player from being fully available for selection for a major match or (b) during a major match, causes a player to be unable to bat, bowl, or keep wicket when required by either the rules or the team’s captain. Recommended definitions for injury incidence (for matches, training sessions, and seasons) and injury prevalence are also provided. It is proposed that match injury incidence is calculated using a denominator based on a standard time estimated for player exposure in matches, for the purposes of simplicity. This will allow all injury surveillance systems, including those with limited resources, to make calculations according to a standard definition.

Conclusion:The consensus statement presented provides a standard which, if followed, allows meaningful comparison of injury surveillance data from different countries and time periods, which will assist in the possible identification of risk factors for injury in cricket.
The repeatability and criterion related validity of the 20 m multistage fitness test as a predictor of maximal oxygen uptake in active young men
Authors: Cooper S-M , Baker J S , Tong R J , Roberts E , Hanford M
Published: March 2005

Objective:To investigate the repeatability and criterion related validity of the 20 m multistage fitness test (MFT) for predicting maximal oxygen uptake (Vo2max) in active young men.

Methods:Data were gathered from two phases using 30 subjects (x̄±s; age = 21.8±3.6 years, mass = 76.9±10.7 kg, stature = 1.76±0.05 m). MFT repeatability was investigated in phase 1 where 21 subjects performed the test twice. The MFT criterion validity to predict Vo2maxwas investigated in phase 2 where 30 subjects performed a continuous incremental laboratory test to volitional exhaustion to determine Vo2maxand the MFT.

Results:Phase 1 showed non-significant bias between the two applications of the MFT (x̄diff±sdiff = −0.4±1.4 ml kg−1min−1; t = −1.37, p = 0.190) with 95% limits of agreement (LoA) ±2.7 ml kg−1min−1and heteroscedasticity 0.223 (p = 0.330). Log transformation of these data reduced heteroscedasticity to 0.056 (p = 0.808) with bias −0.007±0.025 (t = −1.35, p = 0.190) and LoA±0.049. Antilogs gave a mean bias on the ratio scale of 0.993 and random error (ratio limits) ×/÷1.050. Phase 2 showed that the MFT significantly underpredicted Vo2max(x̄diff±sdiff = 1.8±3.2 ml kg−1min−1; t = 3.10, p = 0.004). LoA were ±6.3 ml kg−1min−1and heteroscedasticity 0.084 (p = 0.658). Log transformation reduced heteroscedasticity to −0.045 (p = 0.814) with LoA±0.110. The significant systematic bias was not eliminated (x̄diff±sdiff = 0.033±0.056; t = 3.20, p = 0.003). Antilogs gave a mean bias of 1.034 with random error×/÷1.116.

Conclusions:These findings lend support to previous investigations of the MFT by identifying that in the population assessed it provides results that are repeatable but it routinely underestimates Vo2maxwhen compared to laboratory determinations. Unlike previous findings, however, these results show that when applying an arguably more appropriate analysis method, the MFT does not provide valid predictions of Vo2max.
Head injuries in youth soccer players presenting to the emergency department
Authors: Pickett W , Streight S , Simpson K , Brison R J
Published: March 2005

Background:There has been recent concern about neuropsychological injuries experienced by soccer players, particularly related to the purposeful heading of the ball. There are few population based analyses examining whether this is a legitimate concern.

Objectives:To explore, using an existing injury surveillance system, one of many parts of this issue: acute injuries requiring emergency medical care experienced by youth soccer players.

Methods:Descriptive epidemiological analysis of emergency department injury surveillance data (1996–2001) for youths aged 10–24 years from the Kingston sites of the Canadian Hospital Injury Reporting and Prevention Program.

Results:A total of 1714 cases of soccer injury were identified (mean 286 a year); 235 (13.7%) involved diagnoses of injuries to the head. Leading mechanical factors resulting in head injury were contact with other players or persons (153/235; 65.1%) and balls (62/235; 26.4%). Heading was reported in 4/62 (6%) of the ball contact injuries, and attempted heading was reported in 15/153 (9.8%) of the cases involving person to person contact. Unspecified head to head contact between players was reported in 39 cases.

Conclusions:Minor head injuries that result in emergency medical treatment do not happen often in youth soccer, and very few can be attributed to the purposeful heading of the ball. Player contact injuries appear to be a more important injury control concern. This study informs one of many aspects of the soccer heading injury debate.
“Pack year” smoking histories: what about patients who use loose tobacco?: Table 1
Authors: Wood D M , Mould M G , Ong S B Y , Baker E H
Published: March 2005

Life time smoking of ready made cigarettes can be readily quantified as “pack years” smoked, but methods for measuring loose tobacco use are less well established. In this study the frequency of loose tobacco use by 247 hospital in-patients was determined; 64% were current or ex-smokers, 41.3% of whom (25.9% of participants) had smoked loose tobacco. A formula was developed for converting loose tobacco use to pack years smoked, based on the weight of tobacco in ready made cigarettes; 12.5 g or half an ounce of loose tobacco was approximately equivalent to one packet of 20 cigarettes. Using a questionnaire it was found that hospital physicians of all grades were able to convert smoking histories of ready made cigarettes, but not loose tobacco, into number of “pack years” smoked.
Reduced intestinal fat absorptive capacity but enhanced susceptibility to diet-induced fatty liver in mice heterozygous for ApoB38.9 truncation
Authors: Lin Xiaobo , Yue Pin , Xie Yan , Davidson Nicholas O. , Sakata Nobuhiro , Ostlund Richard E. , Chen Zhouji , Schonfeld Gustav
Published: March 2005

Fatty liver is prevalent in apolipoprotein B (apoB)-defective familial hypobetalipoproteinemia (FHBL). Similar to humans, mouse models of FHBL produced by gene targeting ( apob+/38.9) manifest low plasma cholesterol and increased hepatic triglycerides (TG) even on a chow diet due to impaired hepatic VLDL-TG secretive capacity. Because apoB truncations shorter than apoB48 are expressed in the intestine, we examined whether FHBL mice may have limited capacity for intestinal dietary TG absorption. In addition, we investigated whether FHBL mice are more susceptible to diet-induced hepatic TG accumulation. Fat absorption capacity was impaired in apoB38.9 mice in a gene dose-dependent manner. Relative fractional fat absorption coefficients for apob+/+, apob+/38.9, and apob38.9/38.9were 1.00, 0.96, and 0.71, respectively. To raise hepatic TG, we fed high-fat (HF) and low-fat (LF) pellets. Hepatic TG level was observed in rank order: HF > LF > chow. On both LF and HF, liver TG level was higher in the apob+/38.9than in apob+/+. Hepatic TG secretion remained impaired in the apob+/38.9on the HF diet. Thus the FHBL mice are more susceptible to diet-induced fatty liver despite relatively reduced intestinal TG absorption capacity on a HF diet.
Lipopolysaccharide-induced changes in mesenteric afferent sensitivity of rat jejunum in vitro: role of prostaglandins
Authors: Wang B. , Glatzle J. , Mueller M. H. , Kreis M. , Enck P. , Grundy D.
Published: March 2005

Bacterial translocation across the intestinal mucosal barrier leads to a macrophage-mediated inflammatory response, visceral hyperalgesia, and ileus. Our aim was to examine how mediators released into mesenteric lymph following LPS treatment influence intestinal afferent sensitivity and the role played by prostanoids in any sensitization. Intestinal lymph was collected from awake rats following treatment with either saline or LPS (5 mg/kg ip). Extracellular multiunit afferent recordings were made from paravascular mesenteric nerve bundles supplying the rat jejunum in vitro following arterial administration of control lymph, LPS lymph, and LPS. Mesenteric afferent discharge increased significantly after LPS lymph compared with control lymph. Peak discharge occurred within 2 min and remained elevated for 5 to 8 min. This response was attenuated by pretreatment with naproxen (10 μM), and restored upon addition of prostaglandin E2 (5 μM) in the presence of naproxen, but AH6809 (5 μM), an EP1/EP2 receptor(s) antagonist, failed to decrease the magnitude of LPS lymph-induced response. LPS itself also stimulated mesenteric afferent discharge but was unaffected by naproxen. TNF-α was significantly increased in LPS lymph compared with control lymph (1,583 ± 197 vs. 169 ± 38 pg/ml, P < 0.01) but exogenous TNF-α failed to evoke any afferent nerve discharge. We concluded that inflammatory mediators released from the gut into mesenteric lymph during endotoxemia have a profound effect on afferent discharge. These mediators influence afferent firing via the release of local prostaglandins.
Transcriptional regulation of inflammatory mediators secreted by human colonic circular smooth muscle cells
Authors: Shi Xuan-Zheng , Sarna Sushil K.
Published: March 2005

We investigated the transcriptional regulation of secretion of pro- and anti-inflammatory mediators by human colonic circular smooth muscle cells (HCCSMC) in response to tumor necrosis factor (TNF)-α. Gene chip array analysis indicated that HCCSMC express a specific panel of 11 cytokines, chemokines, and cell adhesion molecules in a time-dependent manner in response to TNF-α. The chip array data were supported by quantitative analysis of mRNA and protein expressions of interleukin (IL)-6, IL-8, intercellular adhesion molecule (ICAM)-1 and IL-11. The proinflammatory mediators were expressed early, whereas the anti-inflammatory cytokine IL-11 was expressed late after TNF-α treatment. The expression of ICAM-1 on HCCSMC increased lymphocyte adhesion to these cells, which was blocked by pretreatment with antibody to ICAM-1. TNF-α acted on both R1and R2receptors to induce the expression of ICAM-1. Pretreatment of HCCSMC with antisense oligonucleotides to p65 nuclear factor-κB (NF-κB) blocked the expression of ICAM-1, whereas pretreatment with antisense oligonucleotides to p50 NF-κB had little effect. The overexpression of p65 NF-κB enhanced the constitutive expression of ICAM-1, and TNF-α treatment had no further effect. The delayed expression of endogenous IL-11 limited the expression of ICAM-1, and pretreatment of HCCSMC with antisense oligonucleotides to IL-11 enhanced it. We conclude that TNF-α induces gene expression in HCCSMC for programmed synthesis and release of pro- and anti-inflammatory mediators.