bluuebunny/crossref_metadata_2025 huggingface dataset:
Ovarian cancer side population defines cells with stem cell-like characteristics and Mullerian Inhibiting Substance responsiveness
Authors: Szotek Paul P. , Pieretti-Vanmarcke Rafael , Masiakos Peter T. , Dinulescu Daniela M. , Connolly Denise , Foster Rosemary , Dombkowski David , Preffer Frederic , MacLaughlin David T. , Donahoe Patricia K.
Published: July 2006

The recent identification of “side population” (SP) cells in a number of unrelated human cancers and their normal tissue sources has renewed interest in the hypothesis that cancers may arise from somatic stem/progenitor cells. The high incidence of recurrence attributable to multidrug resistance and the multiple histologic phenotypes indicative of multipotency suggests a stem cell-like etiology of ovarian cancer. Here we identify and characterize SP cells from two distinct genetically engineered mouse ovarian cancer cell lines. Differential efflux of the DNA-binding dye Hoechst 33342 from these cell lines defined a human breast cancer-resistance protein 1-expressing, verapamil-sensitive SP of candidate cancer stem cells.In vivo, mouse SP cells formed measurable tumors sooner than non-SP (NSP) cells when equal numbers were injected into the dorsal fat pad of nude mice. The presence of Mullerian Inhibiting Substance (MIS) signaling pathway transduction molecules in both SP and NSP mouse cells led us to investigate the efficacy of MIS against these populations in comparison with traditional chemotherapies. MIS inhibited the proliferation of both SP and NSP cells, whereas the lipophilic chemotherapeutic agent doxorubicin more significantly inhibited the NSP cells. Finally, we identified breast cancer-resistance protein 1-expressing verapamil-sensitive SPs in three of four human ovarian cancer cell lines and four of six patient primary ascites cells. In the future, individualized therapy must incorporate analysis of the stem cell-like subpopulation of ovarian cancer cells when designing therapeutic strategies for ovarian cancer patients.
Documenting the heroin shortage in New South Wales
Authors: DAY CAROLYN , DEGENHARDT LOUISA , HALL WAYNE
Published: July 2006

Australian heroin markets have recently undergone dramatic change, sparking debate about the nature of such markets. This study aimed to determine the onset, peak and decline of the heroin shortage in New South Wales (NSW), using the most appropriate available methods to detect market level changes. The parameters of the heroin shortage were determined by reviewing: reports of heroin users about availability and price (derived from the existing literature and the Illicit Drug Reporting System); qualitative interviews with injecting drug users, and health and law enforcement professionals working in the illicit drug field; and examining data on heroin seizures over the past decade. There was a marked reduction in heroin supply in NSW in early 2001. An increase in the price of heroin occurred in 2001, whereas it had decreased steadily since 1996. A reduction in purity also occurred, as reported by drug users and heroin seizures. The peak period of the shortage appears to have been January to April 2001. The market appears to have stabilised since that time, although it has not returned to pre‐2001 levels: heroin prices have decreased in NSW for street grams, but not to former levels, and the price of ‘caps’ (street deals) remain elevated. Heroin purity in NSW has remained low, with perhaps a 10% increase above the lowest recorded levels. These data support the notion that the heroin market in NSW underwent significant changes, which appear to have involved a lasting shift in the nature of the market.
Drinking‐driving fatalities and consumption of beer, wine and spirits
Authors: MANN ROBERT E. , ZALCMAN ROSELY FLAM , ASBRIDGE MARK , SUURVALI HELEN , GIESBRECHT NORMAN
Published: July 2006

Drinking‐driving is a leading cause of preventable morbidity and mortality in Canada. The purpose of this paper was to examine factors that influenced drinking driver deaths in Ontario. We examined the impact of per capita consumption of total alcohol, and of beer, wine and spirits separately, on drinking‐driving deaths in Ontario from 1962 to 1996, as well as the impact of the introduction of Canada's per se law and the founding of People to Reduce Impaired Driving Everywhere‐Mothers Against Drunk Driving (PRIDE‐MADD) Canada. We utilised time‐series analyses with autoregressive integrated moving average (ARIMA) modelling. As total alcohol consumption increased, drinking driving fatalities increased. The introduction of Canada's per se law, and of PRIDE‐MADD Canada, acted to reduce drinking driving death rates. Among the specific beverage types, only consumption of beer had a significant impact on drinking driver deaths. Several factors were identified that acted to increase and decrease drinking driver death rates. Of particular interest was the observation of the impact of beer consumption on these death rates. In North America, beer is taxed at a lower rate than other alcoholic beverages. The role of taxation policies as determinants of drinking‐driving deaths is discussed.
Investigating parental preferences regarding the development and implementation of a parent‐directed drug‐related educational intervention: an exploratory study
Authors: BEATTY SHELLEY E. , CROSS DONNA S.
Published: July 2006

Strengthening parents' capacity to reduce children's risk of alcohol, tobacco and other drug‐related harm is recognised as an important public health strategy in Australia, but engaging parents' involvement in these training programs is known to be challenging. This study utilised a self‐complete questionnaire and structured small group discussions with parents in order to identify their needs in terms of communicating with their children about drinking alcohol and smoking cigarettes. It also investigated their preferences regarding the nature of a parent drug education intervention as well as strategies to recruit and actively engage them in parent‐directed interventions. Parents identified numerous barriers to their participation in such programs and reported any intervention targeting them should be able to be completed in their home, be non‐judgemental, easy to read, time‐efficient, easy to use, fun, colourful and interactive. Parents recommended practical communication skills (such as how to talk with children, how to raise the topic and what topics to talk about) be addressed in the intervention. They also recommended a range and combination of strategies to promote and maintain parent involvement, such as providing small rewards for the children of parents who participate. Despite some limitations, the findings of this study contribute important practical knowledge regarding how to recruit, engage and retain higher percentages of parents in parent training programs.
The role of working memory in the carry operation of mental arithmetic: Number and value of the carry
Authors: Imbo Ineke , Vandierendonck André , De Rammelaere Stijn
Published: July 2006

Two experiments were conducted to investigate the role of phonological and executive working-memory components in the carry operation in mental arithmetic. We manipulated the number of carry operations, as previous research had done, but also the value that had to be carried. Results of these experiments show that in addition to the number of carry operations, the value of the carry is also an important variable determining the difficulty of arithmetical sums. Furthermore, both variables (number and value) interacted with each other in such a way that the combination of multiple carries and values of carries larger than one resulted in more difficult problems irrespective of the presence of a working-memory load. The findings with respect to working-memory load suggest that mainly the central executive is important in handling the number of carry operations as well as the value that has to be carried. The implications of the present findings for our views on mental arithmetic and its reliance on working memory are discussed.
Tests for a Simple Tree Order Restriction with Application to Dose–Response Studies
Authors: Peddada Shyamal D. , Haseman Joseph K. , Tan Xiaofeng , Travlos Greg
Published: July 2006

We propose ‘Dunnett-type’ test procedures to test for simple tree order restrictions on the means of p independent normal populations. The new tests are based on the estimation procedures that were introduced by Hwang and Peddada and later by Dunbar, Conaway and Peddada. The procedures proposed are also extended to test for ‘two-sided’ simple tree order restrictions. For non-normal data, nonparametric versions based on ranked data are also suggested. Using computer simulations, we compare the proposed test procedures with some existing test procedures in terms of size and power. Our simulation study suggests that the procedures compete well with the existing procedures for both one-sided and two-sided simple tree alternatives. In some instances, especially in the case of two-sided alternatives or for non-normally distributed data, the gains in power due to the procedures proposed can be substantial.
A New
d,l
-Endopeptidase Gene Product, YojL (Renamed CwlS), Plays a Role in Cell Separation with LytE and LytF in
Bacillus subtilis
Authors: Fukushima Tatsuya , Afkham Anahita , Kurosawa Shin-ichirou , Tanabe Taichi , Yamamoto Hiroki , Sekiguchi Junichi
Published: July 2006

A new peptidoglycan hydrolase,
Bacillus subtilis
YojL (
c
ell
w
all-
l
ytic enzyme associated with cell
s
eparation, renamed CwlS), exhibits high amino acid sequence similarity to LytE (CwlF) and LytF (CwlE), which are associated with cell separation. The N-terminal region of CwlS has four tandem repeat regions (LysM repeats) predicted to be a peptidoglycan-binding module. The C-terminal region exhibits high similarity to the cell wall hydrolase domains of LytE and LytF at their C-terminal ends. The C-terminal region of CwlS produced in
Escherichia coli
could hydrolyze the linkage of
d
-γ-glutamyl-
meso
-diaminopimelic acid in the cell wall of
B. subtilis
, suggesting that CwlS is a
d,l
-endopeptidase. β-Galactosidase fusion experiments and Northern hybridization analysis suggested that the
cwlS
gene is transcribed during the late vegetative and early stationary phases. A
cwlS
mutant exhibited a cell shape similar to that of the wild type; however, a
lytE lytF cwlS
triple mutant exhibited aggregated microfiber formation. Moreover, immunofluorescence microscopy showed that FLAG-tagged CwlS was localized at cell separation sites and cell poles during the late vegetative phase. The localization sites are similar to those of LytF and LytE, indicating that CwlS is involved in cell separation with LytF and LytE. These specific localizations may be dependent on the LysM repeats in their N-terminal domains. The roles of CwlS, LytF, and LytE in cell separation are discussed.
YeeI, a Novel Protein Involved in Modulation of the Activity of the Glucose-Phosphotransferase System in
Escherichia coli
K-12
Authors: Becker Ann-Katrin , Zeppenfeld Tim , Staab Ariane , Seitz Sabine , Boos Winfried , Morita Teppei , Aiba Hiroji , Mahr Kerstin , Titgemeyer Fritz , Jahreis Knut
Published: July 2006

The membrane-bound protein EIICB
Glc
encoded by the
ptsG
gene is the major glucose transporter in
Escherichia coli
. This protein is part of the phosphoenolpyruvate:glucose-phosphotransferase system, a very important transport and signal transduction system in bacteria. The regulation of
ptsG
expression is very complex. Among others, two major regulators, the repressor Mlc and the cyclic AMP-cyclic AMP receptor protein activator complex, have been identified. Here we report identification of a novel protein, YeeI, that is involved in the regulation of
ptsG
by interacting with Mlc. Mutants with reduced activity of the glucose-phosphotransferase system were isolated by transposon mutagenesis. One class of mutations was located in the open reading frame
yeeI
at 44.1 min on the
E. coli
K-12 chromosome. The
yeeI
mutants exhibited increased generation times during growth on glucose, reduced transport of methyl-α-
d
-glucopyranoside, a substrate of EIICB
Glc
, reduced induction of a
ptsG-lacZ
operon fusion, and reduced catabolite repression in lactose/glucose diauxic growth experiments. These observations were the result of decreased
ptsG
expression and a decrease in the amount of EIICB
Glc
. In contrast, overexpression of
yeeI
resulted in higher expression of
ptsG
, of a
ptsG-lacZ
operon fusion, and of the autoregulated
dgsA
gene. The effect of a
yeeI
mutation could be suppressed by introducing a
dgsA
deletion, implying that the two proteins belong to the same signal transduction pathway and that Mlc is epistatic to YeeI. By measuring the surface plasmon resonance, we found that YeeI (proposed gene designation,
mtfA
) directly interacts with Mlc with high affinity.
The Plasmid RK2 Replication Initiator Protein (TrfA) Binds to the Sliding Clamp β Subunit of DNA Polymerase III: Implication for the Toxicity of a Peptide Derived from the Amino-Terminal Portion of 33-Kilodalton TrfA
Authors: Kongsuwan Kritaya , Josh Peter , Picault Marc J. , Wijffels Gene , Dalrymple Brian
Published: July 2006

The broad-host-range plasmid RK2 is capable of replication and stable maintenance within a wide range of gram-negative bacterial hosts. It encodes the essential replication initiation protein TrfA, which binds to the host initiation protein, DnaA, at the plasmid origin of replication (
oriV
). There are two versions of the TrfA protein, 44 and 33 kDa, resulting from alternate in-frame translational starts. We have shown that the smaller protein, TrfA-33, and its 64-residue amino-terminal peptide (designated T1) physically interact with the
Escherichia coli
β sliding clamp (β
2
). This interaction appears to be mediated through a QLSLF peptide motif located near the amino-terminal end of TrfA-33 and T1, which is identical to the previously described eubacterial clamp-binding consensus motif. T1 forms a stable complex with β
2
and was found to inhibit plasmid RK2 replication in vitro. This specific interaction between T1 and β
2
and the ability of T1 to block DNA replication have implications for the previously reported cell lethality caused by overproduction of T1 (P. D. Kim, T. M. Rosche, and W. Firshein, Plasmid 43:214-222, 2000). The toxicity of T1 was suppressed when wild-type T1 was replaced with mutant T1, carrying an LF deletion in the β-binding motif. Previously, T1 toxicity has been shown to be suppressed by Hda, an intermediate regulatory protein which helps prevent overinitiation in
E. coli
through its interaction with the initiator protein, DnaA, and β
2
. Our results support a model in which T1 toxicity is caused by T1 binding to β
2
, especially when T1 is overexpressed, preventing β
2
from interacting with host replication proteins such as Hda during the early events of chromosome replication.
Crystal Structure of TDP-Fucosamine Acetyltransferase (WecD) from
Escherichia coli
, an Enzyme Required for Enterobacterial Common Antigen Synthesis
Authors: Hung Ming-Ni , Rangarajan Erumbi , Munger Christine , Nadeau Guy , Sulea Traian , Matte Allan
Published: July 2006

Enterobacterial common antigen (ECA) is a polysaccharide found on the outer membrane of virtually all gram-negative enteric bacteria and consists of three sugars,
N
-acetyl-
d
-glucosamine,
N
-acetyl-
d
-mannosaminuronic acid, and 4-acetamido-4,6-dideoxy-
d
-galactose, organized into trisaccharide repeating units having the sequence →3)-α-
d
-Fuc4NAc-(1→4)-β-
d
-ManNAcA-(1→4)-α-
d
-GlcNAc-(1→. While the precise function of ECA is unknown, it has been linked to the resistance of Shiga-toxin-producing
Escherichia coli
(STEC) O157:H7 to organic acids and the resistance of
Salmonella enterica
to bile salts. The final step in the synthesis of 4-acetamido-4,6-dideoxy-
d
-galactose, the acetyl-coenzyme A (CoA)-dependent acetylation of the 4-amino group, is carried out by TDP-fucosamine acetyltransferase (WecD). We have determined the crystal structure of WecD in apo form at a 1.95-Å resolution and bound to acetyl-CoA at a 1.66-Å resolution. WecD is a dimeric enzyme, with each monomer adopting the GNAT
N
-acetyltransferase fold, common to a number of enzymes involved in acetylation of histones, aminoglycoside antibiotics, serotonin, and sugars. The crystal structure of WecD, however, represents the first structure of a GNAT family member that acts on nucleotide sugars. Based on this cocrystal structure, we have used flexible docking to generate a WecD-bound model of the acetyl-CoA-TDP-fucosamine tetrahedral intermediate, representing the structure during acetyl transfer. Our structural data show that WecD does not possess a residue that directly functions as a catalytic base, although Tyr208 is well positioned to function as a general acid by protonating the thiolate anion of coenzyme A.
Characterization of the Global Transcriptional Responses to Different Types of DNA Damage and Disruption of Replication in
Bacillus subtilis
Authors: Goranov Alexi I. , Kuester-Schoeck Elke , Wang Jue D. , Grossman Alan D.
Published: July 2006

DNA damage and perturbations in DNA replication can induce global transcriptional responses that can help organisms repair the damage and survive. RecA is known to mediate transcriptional responses to DNA damage in several bacterial species by inactivating the repressor LexA and phage repressors. To gain insight into how
Bacillus subtilis
responds to various types of DNA damage, we measured the effects of DNA damage and perturbations in replication on mRNA levels by using DNA microarrays. We perturbed replication either directly with
p
-hydroxyphenylazo-uracil (HPUra), an inhibitor of DNA polymerase, or indirectly with the DNA-damaging reagents mitomycin C (MMC) and UV irradiation. Our results indicate that the transcriptional responses to HPUra, MMC, and UV are only partially overlapping.
recA
is the major transcriptional regulator under all of the tested conditions, and LexA appears to directly repress the expression of 63 genes in 26 operons, including the 18 operons previously identified as LexA targets. MMC and HPUra treatments caused induction of an integrative and conjugative element (ICE
Bs1
) and resident prophages (PBSX and SPβ), which affected the expression of many host genes. Consistent with previous results, the induction of these mobile elements required
recA
. Induction of the phage appeared to require inactivation of LexA. Unrepaired UV damage and treatment with MMC also affected the expression of some of the genes that are controlled by DnaA. Furthermore, MMC treatment caused an increase in origin-proximal gene dosage. Our results indicate that different types of DNA damage have different effects on replication and on the global transcriptional profile.
Uropathogenic
Escherichia coli
Strains Generally Lack Functional Trg and Tap Chemoreceptors Found in the Majority of
E. coli
Strains Strictly Residing in the Gut
Authors: Lane M. Chelsea , Lloyd Amanda L. , Markyvech Tiffany A. , Hagan Erin C. , Mobley Harry L. T.
Published: July 2006

The prevalence and function of four chemoreceptors, Tsr, Tar, Trg, and Tap,
were determined for a collection of uropathogenic, fecal-commensal, and
diarrheagenic
Escherichia coli
strains.
tar
and
tsr
were present or functional in nearly all isolates.
However,
trg
and
tap
were significantly less
prevalent or functional among the uropathogenic
E. coli
strains (both in 6% of strains) than among fecal-commensal strains
(both in ≥50% of strains) or diarrheal strains (both in≥
75% of strains) (
P
<
0.02).
Role of Histone-Like Proteins H-NS and StpA in Expression of Virulence Determinants of Uropathogenic
Escherichia coli
Authors: Müller Claudia M. , Dobrindt Ulrich , Nagy Gábor , Emödy Levente , Uhlin Bernt Eric , Hacker Jörg
Published: July 2006

The histone-like protein H-NS is a global regulator in
Escherichia coli
that has been intensively studied in nonpathogenic strains. However, no comprehensive study on the role of H-NS and its paralogue, StpA, in gene expression in pathogenic
E. coli
has been carried out so far. Here, we monitored the global effects of H-NS and StpA in a uropathogenic
E. coli
isolate by using DNA arrays. Expression profiling revealed that more than 500 genes were affected by an
hns
mutation, whereas no effect of StpA alone was observed. An
hns stpA
double mutant showed a distinct gene expression pattern that differed in large part from that of the
hns
single mutant. This suggests a direct interaction between the two paralogues and the existence of distinct regulons of H-NS and an H-NS/StpA heteromeric complex.
hns
mutation resulted in increased expression of alpha-hemolysin, fimbriae, and iron uptake systems as well as genes involved in stress adaptation. Furthermore, several other putative virulence genes were found to be part of the H-NS regulon. Although the lack of H-NS, either alone or in combination with StpA, has a huge impact on gene expression in pathogenic
E. coli
strains, its effect on virulence is ambiguous. At a high infection dose,
hns
mutants trigger more sudden lethality due to their increased acute toxicity in murine urinary tract infection and sepsis models. At a lower infectious dose, however, mutants lacking H-NS are attenuated through their impaired growth rate, which can only partially be compensated for by the higher expression of numerous virulence factors.
Electrolysis stimulates creatine transport and transporter cell surface expression in incubated mouse skeletal muscle: potential role of ROS
Authors: Derave Wim , Straumann Nadine , Olek Robert A. , Hespel Peter
Published: July 2006

Electrical field stimulation of isolated, incubated rodent skeletal muscles is a frequently used model to study the effects of contractions on muscle metabolism. In this study, this model was used to investigate the effects of electrically stimulated contractions on creatine transport. Soleus and extensor digitorum longus muscles of male NMRI mice (35–50 g) were incubated in an oxygenated Krebs buffer between platinum electrodes. Muscles were exposed to [14C]creatine for 30 min after either 12 min of repeated tetanic isometric contractions (contractions) or electrical stimulation of only the buffer before incubation of the muscle (electrolysis). Electrolysis was also investigated in the presence of the reactive oxygen species (ROS) scavenging enzymes superoxide dismutase (SOD) and catalase. Both contractions and (to a lesser degree) electrolysis stimulated creatine transport severalfold over basal. The amount of electrolysis, but not contractile activity, induced (determined) creatine transport stimulation. Incubation with SOD and catalase at 100 and 200 U/ml decreased electrolysis-induced creatine transport by ∼50 and ∼100%, respectively. The electrolysis effects on creatine uptake were completely inhibited by β-guanidino propionic acid, a competitive inhibitor of (creatine for) the creatine transporter (CRT), and were accompanied by increased cell surface expression of CRT. Muscle glucose transport was not affected by electrolysis. The present results indicate that electrical field stimulation of incubated mouse muscles, independently of contractions per se, stimulates creatine transport by a mechanism that depends on electrolysis-induced formation of ROS in the incubation buffer. The increased creatine uptake is paralleled by an increased cell surface expression of the creatine transporter.
Effects of galanin-like peptide on luteinizing hormone secretion in the rat: sexually dimorphic responses and enhanced sensitivity at male puberty
Authors: Castellano J. M. , Navarro V. M. , Fernández-Fernández R. , Roa J. , Vigo E. , Pineda R. , Steiner R. A. , Aguilar E. , Pinilla L. , Tena-Sempere M.
Published: July 2006

Reproductive function is exquisitely sensitive to adequacy of nutrition and fuel reserves, through mechanisms that are yet to be completely elucidated. Galanin-like peptide (GALP) has recently emerged as another neuropeptide link that couples reproduction and metabolism. However, although the effects of GALP on luteinizing hormone (LH) secretion have been studied, no systematic investigation on how these responses might differ along sexual maturation and between sexes has been reported. Moreover, the influence of metabolic status and potential interplay with other relevant neurotransmitters controlling LH secretion remain ill defined. These facets of GALP physiology were addressed herein. Intracerebral injection of GALP to male rats induced a dose-dependent increase in serum LH levels, the magnitude of which was significantly greater in pubertal than in adult males. In contrast, negligible LH responses to GALP were detected in pubertal or adult female rats at diestrus. Neonatal androgen treatment to females failed to “masculinize” the pattern of LH response to GALP. In addition, metabolic stress by short-term fasting did not prevent but rather amplified LH responses to GALP in pubertal males, whereas these responses were abrogated by pharmacological inhibition of nitric oxide synthesis. We conclude that the ability of GALP to evoke LH secretion is sexually differentiated, with maximal responses at male puberty, a phenomenon which was not reverted by manipulation of sex steroid milieu during the critical neonatal period and was sensitive to metabolic stress. This state of LH hyperresponsiveness may prove relevant for the mechanisms relaying metabolic status to the reproductive axis in male puberty.
Feedforward Inhibitory Connections From Multiple Thalamic Cells to Multiple Regular-Spiking Cells in Layer 4 of the Somatosensory Cortex
Authors: Inoue Tsuyoshi , Imoto Keiji
Published: July 2006

Thalamocortical (TC) cells in the ventrobasal thalamus make direct excitatory connections with regular-spiking (RS) cells in layer 4 of the somatosensory cortex, but also make disynaptic feedforward inhibitory connections with the RS cells by layer 4 fast-spiking (FS) cells. In this study, we investigated connection rules of the feedforward inhibitory circuit from multiple TC cells to multiple RS cells, at the level of synaptic potentials. Using thalamocortical brain slices of young mice (postnatal days 12–16), we made simultaneous patch-clamp recordings from three adjacent cortical cells (two RS cells and one FS cell), combined with minimal stimulation of presumed single TC fibers. We found that nearly all (97%) of TC fibers, which generated excitatory inputs onto RS cells, also generated divergent excitatory inputs onto adjacent FS cells. Some 44% of TC fibers generated divergent excitatory inputs onto adjacent pairs of RS cells. We then combined the triple patch-clamp recording with multisite (two to three) minimal stimulation of single TC fibers and found that 86% of FS cells received convergent inputs from all of the stimulated TC fibers. We also found that 68% of FS cells generated divergent inhibitory inputs onto adjacent pairs of RS cells. The results indicate that spikes in TC cells, which excite RS cells, also excite adjacent FS cells with high fidelity. The results also indicate that FS cells receive convergent excitatory inputs from multiple TC cells and then send divergent inhibitory outputs to multiple RS cells.
Transcriptional response to persistent β2-adrenergic receptor signaling reveals regulation of phospholamban, which alters airway contractility
Authors: McGraw Dennis W. , Fogel Kevin M. , Kong Sue , Litonjua Augusto A. , Kranias Evangelia G. , Aronow Bruce J. , Liggett Stephen B.
Published: July 2006

β2-Adrenergic receptors (β2AR) are expressed on airway smooth muscle cells and act to relax the airway on activation by β-agonists. These agents are utilized for treating asthma but are associated with adverse outcomes. To ascertain the effects of persistent β2AR activation on gene expression, cultured airway smooth muscle cells derived from wild-type (WT) and transgenic mice overexpressing β2AR were subjected to DNA microarray analysis; 319 genes were increased and 164 were decreased. Differential expression was observed in genes from 22 Gene Ontology Slim categories, including those associated with ion transport and calcium ion binding. A 60% decrease ( P = 0.008) in phospholamban (PLN), an intracellular Ca2+concentration ([Ca2+]i)-handling protein that is at a signaling nodal point in cardiomyocytes, was observed in β2AR-overexpressing cells and confirmed at the protein level. To isolate the physiological effect of decreased PLN in airway smooth muscle, airway contraction and relaxation responses were studied in WT and PLN−/−mice. PLN−/−mice had a markedly reduced constrictive response to methacholine. In contrast, the bronchodilatory effect of β-agonist was not different between WT and PLN−/−mice. These results revealed an unanticipated therapeutic effect of β-agonists, PLN downregulation, which acts to decrease airway hyperreactivity. Thus agents that inhibit PLN may act synergistically with the bronchodilating action of β-agonists. A number of other genes related to [Ca2+]iare also differentially regulated by β2AR activity, some of which may act to oppose, or augment, the efficacy of chronic β-agonists. These genes or pathways may also represent additional targets in the treatment of asthma and related obstructive lung diseases.
In-Hospital Mortality and Time from Onset of Symptoms of Acute Myocardial Infarction in 540 Patients Undergoing Primary Coronary Angioplasty
Authors: Dilmanian Hajir , Aronow Wilbert S. , Das Manisha , Pucillo Anthony L. , Weiss Melvin B. , Kalapatapu Kumar , Monsen Craig E.
Published: July 2006

The time from the onset of symptoms of acute myocardial infarction to primary coronary angioplasty was 18 ± 23 h in 386 men and 19 ± 24 h in 154 women (p not significant) and 14 ± 19 h in 27 blacks, 19 ± 23 h in 493 whites, and 13 ± 11 h in 20 patients of different races (p not significant). In-hospital mortality was 6% in 144 patients aged ≧70 years and 1% in 396 patients <70 years (p < 0.005). In-hospital mortality was 2% in 386 men and 4% in 154 women (p not significant). In-hospital mortality was 2% in 493 whites, 4% in 27 blacks, and 0% in 20 patients of other races (p not significant). In-hospital mortality was 6% in 143 patients with a left ventricular ejection fraction (LVEF) <40% and 1% in 397 patients with a LVEF ≧40% (p < 0.005). In-hospital mortality was 5% in 223 patients with a glomerular filtration rate (GFR) <90 ml/min and 1% in 317 patients with a GFR ≧90 ml/min (p < 0.005).
Fibronectin binding proteins contribute to the adherence of Staphylococcus aureus to intact endothelium in vivo
Authors: Sinha Bhanu , Preissner Klaus , Menger Michael , Kerdudou Sylvain , Laschke Matthias , Herrmann Mathias
Published: July 2006

Staphylococcal adhesins mediate attachment to matrix proteins and endothelial cells in vitro, yet, their role in primary adherence to the physiologic vessel wall has not been studied in vivo, and complex endocarditis models yielded ambiguous results. Recently, we developed a hamster model to study interaction kinetics of S. aureus with intact microvasculature using intravital fluorescence microscopy (Laschke et al. J Infect Dis 2005; 191: 435-43) providing the basis for this study. S. aureus Cowan 1 wild type (WT) log phase cells adhered to postcapillary venules to a significantly larger extent compared to stationary phase staphylococci, a finding in congruence with the fact that the staphylococcal adhesin repertoire largely depends on the growth phase. In comparison, the adherence rate of the fnbA deleted mutant (DU5895) to the vessel wall was significantly reduced to approximately 40% of WT. These DU5895 attachment rates were similar to those of an S. carnosus strain (TM300). In contrast, upon heterologous complementation of TM300 with either fnbA and fnbB, adherence of these transformants to the microvasculature increased, an increase found to be significant for fnbA transformant single cocci and clusters at 30 and 60 min when compared to S. carnosus TM300 WT. In conclusion, these results demonstrate that staphylococcal FnBPs significantly contribute to primary interaction with intact endothelium under physiologic conditions. Accordingly, this attribution of staphylococcal FnBPs providea rationale for novel intervention strategies such as the use of anti-FnBP antibodies in endovascular S. aureus disease.
Platelet activation and high tissue factor level predict acute stent thrombosis in pig coronary arteries: Prothrombogenic response of drug-eluting or bare stent implantation within the first 24 hours
Authors: Strehblow Christoph , Sperker Wolfgang , Hevesi Akos , Garamvölgyi Rita , Petrási Zsolt , Pavo Noemi , Ferdinandy Péter , Csonka Csaba , Csont Tamás , Sylvén Christer , Declerck Paul , Imre Pavo , Wojta Johann , Glogar Dietmar , Huber Kurt , Gyöngyösi Mariann
Published: July 2006

Increased thrombogenicity of drug-eluting stents (DESs) has recently been reported.The aim of the present study was to investigate the prothrombogenic effect of DESs and Bare stents, and determine factors predictive of acute stent thrombosis (AST) in preclinical experiments using new stent design or coating.Circulating preand post-stenting parameters of platelet activation (mean platelet volume, MPV; platelet distribution width, platelet large cell ratio), thrombin activation (thrombin-antithrombin complex, TAT and prothrombin fragments, F1+2), tissue factor antigen (TF-ag) and -activity (TF-act) and plasminogen activator inhibitor-1 (PAI-1) were measured in 141 consecutive pigs. Stent implantations were performed after pretreatment with aspirin and clopidogrel with unfractionated heparin anticoagulation. Nineteen pigs (groups AST-DES, n=12; and AST-Bare, n=7) died mean 6.3 ± 2.9 h after stent implantation from AST.The remaining 122 control (C) pigs (groups C-DES,n=76,and C-Bare,n=46) survived the 1-month follow-up. Non-significantly elevated levels of post-stent F1+2 and TAT were measured in AST groups. Post-stenting MPV was increased significantly in the groups ASTDES and AST-Bare as compared with the groups C-DES and C-Bare (11.73 ± 1.12 and 11.6 ± 0.68 vs. 8.85 ± 0.78 and 9.04 ± 0.81 fL; p<0.001), similarly toTF-ag (189.1± 87.5 and 127 ± 34.9 vs. 42.5 ± 24.6 and 35.3 ± 37.6 pg/ml; p<0.001, respectively),TF-act (3.23 ± 0.95 and 2.73 ± 1.68 vs. 1.43 ± 1.12 and 1.61 ± 1.31 pM; p<0.01, respectively) and PAI-1 (99.1 ± 15.8 and 99 ± 14.7 vs.53.4 ± 40.2 and 46.9 ± 42.4 ng/ml;p<0.01,respectively).Multivariate analysis revealed elevated post-stenting plasma levels of TF-ag (p=0.016) and MPV (p=0.001) as independent risk factors for developing AST within the first 24 h in a porcine coronary stent model.
Issues of Culture and Identity in Contemporary France: The Problem of Reconciling a Colonial Past with a Present Reality
Authors: Adamson Kay
Published: July 2006

In July 2004, a young woman claimed that she had been attacked on the Paris urban railway system by four Maghrebins and two Africans and that the discovery that she might be Jewish had intensified the character of the attack. For a number of days, the French media were dominated by the case and leading politicians condemned it. The events drew attention to a number of issues concerning culture and identity in contemporary France and the role played in constituting this identity of history and memory. However, it also displayed how the constitution of identity is a selective process in which different elements may be dealt with, either in different ways or omitted altogether. This article explores how in attempting to come to terms with the legacies of anti-Semitism, other areas of history and memory have been neglected, including the legacy of France’s colonial empire, and, in particular, her relationship with Algeria.
Pharmacokinetic Interactions of Concomitant Administration of Febuxostat and NSAIDs
Authors: Khosravan Reza , Wu Jing‐Tao , Joseph‐Ridge Nancy , Vernillet Laurent
Published: July 2006

To evaluate the effect of febuxostat on the pharmacokinetics of indomethacin and naproxen and vice versa, 2 multiple‐dose, 3‐period crossover studies were performed in healthy subjects. In study 1, subjects received febuxostat 80 mg once daily, indomethacin 50 mg twice daily, or both. In study 2, subjects received febuxostat 80 mg, naproxen 500 mg twice daily, or both. Twenty‐four‐hour blood samples were collected on day 5 in study 1 and day 7 in study 2. In study 1, 90% confidence intervals of geometric mean ratios for maximum plasma concentration (Cmax) and area under the curve (AUC) were within the 0.80 to 1.25 no‐effect range for febuxostat and indomethacin. In study 2, 90% confidence intervals for febuxostat Cmax and AUC extended above that range, with increases of 28% and 40% in Cmax and AUC24, respectively. However, 90% confidence intervals for naproxen Cmax and AUC were within the 0.80 to 1.25 range. Febuxostat had no effect on the plasma pharmacokinetics of indomethacin and naproxen. Similarly, indomethacin had no effect on the plasma pharmacokinetics of febuxostat. Although naproxen caused an increase in plasma exposure to febuxostat, this increase is not expected to be clinically significant. Therefore, based on the plasma pharmacokinetic data in healthy subjects, febuxostat may be administered with indomethacin or naproxen with no dose adjustments for febuxostat, indomethacin, or naproxen.
Effect of Drospirenone on Serum Potassium and Drospirenone Pharmacokinetics in Women With Normal or Impaired Renal Function
Authors: Schürmann Rolf , Blode Hartmut , Benda Norbert , Cronin Maureen , Küfner Andreas
Published: July 2006

This open‐label study investigated whether drospirenone, a novel progestin with antimineralocorticoid properties, increases the risk for hyperkalemia in subjects with renal impairment. Women with normal renal function and mild or moderate renal impairment were given drospirenone 3 mg/d for 14 days. Mean serum potassium concentrations did not significantly change during steady‐state drospirenone treatment. No difference in drospirenone effects on serum potassium concentrations in subjects with renal insufficiency versus subjects with normal renal function was found. Steady‐state pharmacokinetics was similar in subjects with normal renal function and mild renal impairment, whereas, due to results from 1 subject, drospirenone exposure was slightly higher in the moderate renal impairment group. Given the reported tolerability of drospirenone, this small increase in serum drospirenone is not expected to be clinically significant. In conclusion, this study demonstrated that drospirenone has no significant effect on serum potassium levels in patients with mild to moderate renal insufficiency.
Jewish Christianity, Israel’s Stumbling and the Sonderweg Reading of Paul
Authors: Donaldson Terence L.
Published: July 2006

The Sonderweg reading of Paul posits two distinct categories within Paul’s sociology of salvation. In Lloyd Gaston’s words: ‘Had all Israel followed Paul’s example, we could have had an Israel loyal to the righteousness of God expressed in the Torah alongside a gentile church loyal to the righteousness of God expressed in Jesus Christ and his fulfillment of the promises to Abraham’ (Gaston 1979: 66). In this bifurcated construction of covenantal reality, Jewish Christianity appears to be an anomaly. What to make of Israelites who are also ‘loyal to the righteousness of God expressed in Jesus Christ’? Are they doubly blessed or only misguided? Is such dual loyalty even possible or is it categorically excluded? The purpose of this article is to study the place of Jewish Christianity in the Sonderweg reading of Paul (Gaston, Gager, Stowers), the epistle to the Romans in particular. The conclusion is that, while Paul does not envisage a Sonderweg for Israel, he nevertheless assigns his own people a Sonderplatz within God’s single program of salvation.
Exploring the Reference Point in Prospect Theory: Gambles for Length of Life
Authors: van Osch Sylvie M. C. , van den Hout Wilbert B. , Stiggelbout Anne M.
Published: July 2006

Attitude toward risk is an important factor determining patient preferences. Risk behavior has been shown to be strongly dependent on the perception of the outcome as either a gain or a loss. According to prospect theory, the reference point determines how an outcome is perceived. However, no theory on the location of the reference point exists, and for the health domain, there is no direct evidence for the location of the reference point. This article combines qualitative with quantitative data to provide evidence of the reference point in life-year certainty equivalent (CE) gambles and to explore the psychology behind the reference point. The authors argue that goals (aspirations) in life influence the reference point. While thinking aloud, 45 healthy respondents gave certainty equivalents for life-year CE gambles with long and short durations of survival. Contrary to suggestions from the literature, qualitative data argued that the offered certainty equivalent most frequently served as the reference point. Thus, respondents perceived life-year CE gambles as mixed. Framing of the question and goals set in life appeared to be important factors behind the psychology of the reference point. On the basis of the authors' quantitative and qualitative data, they argue that goals alter the perception of outcomes as described by prospect theory by influencing the reference point. This relationship is more apparent for the near future as opposed to the remote future, as goals are mostly set for the near future.
Fabrication and Characterization of High Temperature Resin/Carbon Nanofiber Composites
Authors: Ghose Sayata , Watson Kent A. , Working Dennis C. , Siochi Emilie J. , Connell John W. , Criss Jim M.
Published: July 2006

Multifunctional composites present a route to structural weight reduction. Nanoparticles such as carbon nanofibers (CNF) provide a compromise as a lower cost nanosize reinforcement that yields a desirable combination of properties. Blends of PETI-330 and CNFs were prepared and characterized to investigate the potential of CNF composites as a high-performance structural medium. Dry mixing techniques were employed and the effect of CNF loading level on melt viscosity was determined. The resulting powders were characterized for degree of mixing, thermal and rheological properties. Based on the characterization results, samples containing 30 and 40 wt.% CNF were scaled up to approximately 300 g and used to fabricate moldings 10.2 cm ′ 15.2 cm ′ 0.32 cm thick. The moldings were fabricated by injecting the mixtures at 260-280°C into a stainless steel tool followed by curing for 1 h at 371°C. The tool was designed to impart high shear during the injection process in an attempt to achieve some alignment of CNFs in the flow direction. Moldings were obtained that were subsequently characterized for thermal, mechanical and electrical properties. The degree of dispersion and alignment of CNFs were investigated using high-resolution scanning electron microscopy. The preparation and preliminary characterization of PETI-330/CNF composites are discussed.
The Diffusion of the Internet and Rural Development
Authors: Jinqiu Zhao , Xiaoming Hao , Banerjee Indrajit
Published: July 2006

This study explores the applicability of the diffusion of innovations theory to internet development in rural China by examining internet diffusion and usage patterns in two rural areas of China's Gansu Province. Its ethnographic research design allowed the researchers to interact with the rural people under study and obtain first-hand data on their adoption and usage of the internet. The results show that in the context of rural China, where the local economy and infrastructure can hardly sustain such an advanced technology as the internet, the diffusion and usage of the internet are determined not much by the will of individuals, but by the change agency. As the weakest social class in terms of their share and control of social resources, Chinese farmers as individuals do not play an important role in the adoption of the internet, which tends to be the result of organizational initiatives.
An Experience of Group Work with Parents of Children and Adolescents with Gender Identity Disorder
Authors: Di Ceglie Domenico , Thümmel Elizabeth Coates
Published: July 2006

This article gives an account of an experience of group work with parents and carers who had children or adolescents with gender identity disorder (GID). The history of this intervention within the context of a service for children with gender identity problems is outlined. The limited literature on the subject is reviewed. Group meetings were held monthly for 6 months, facilitated by two therapists (the authors). Selection criteria for group participants, the aims of the group and the methodology for achieving those aims are described. Some information about the group's composition is provided. The structure and content of the group sessions are outlined together with details of some group interactions. Finally, we present the results of an evaluation of the intervention through feedback questionnaires and discuss the value for the children and young people of running such groups.
Feasibility Study of an Express Assessment Protocol for the Indoor Air Quality of Air-conditioned Offices
Authors: Hui P. S. , Wong L. T. , Mui K. W.
Published: July 2006

It is costly to sample all major toxic pollutants in community air. Sampling should be conducted based on an assessment strategy and monitoring planning. Assessment methods that rely on monitoring some representative pollutants have been proposed variously at different times. In Hong Kong, the Environmental Protection Department (HKEPD) launched an Indoor Air Quality (IAQ) certification scheme to grade the IAQ in workplaces as “Excellent” or “Good” by measuring the levels of 12 indoor environmental parameters, i.e. carbon dioxide (CO2), carbon monoxide (CO), respirable suspended particulates (RSP), nitrogen dioxide (NO2), ozone (O3), formaldehyde (HCHO), total volatile organic compounds (TVOC), radon (Rn), airborne bacteria count (ABC), temperature (T), relative humidity (RH) and air velocity (V). The present study proposes an Express Assessment Protocol (EAP) to quantify IAQ problems by assessing the “dominant” contributors to unacceptable IAQ prior to any detailed assessment for benchmark purposes. To aid this, a comprehensive measurement of the 12 stated indoor environmental parameters was performed in some Hong Kong offices. The results were used to identify the dominant contributors and assess the performance of the proposed protocol in identifying the associated IAQ problems in an office environment. Comparing the results with the parameter measurements in the certification scheme they showed that for the “Excellent” IAQ level, 96% (94 to 98% for 95% confidence interval (CI)) of the “unacceptable” offices (414 samples) could be identified from the measurements of TVOC, RSP and HCHO; while those that achieved the “Good” level, 93% (90 to 97% for 95% CI) of them (201 samples) could be identified from the measurements of TVOC, ABC, RH, HCHO and O3. The EAP would be a useful tool for policymakers, building owners and professionals to quantify IAQ problems in offices and to make improved decisions based on resources and manpower management for efficient mitigation actions.
Applications of Rhetorical Structure Theory
Authors: Taboada Maite , Mann William C.
Published: July 2006

Rhetorical Structure Theory (RST) is a theory of text organization that has led to areas of application beyond discourse analysis and text generation, its original goals. In this article, we review the most important applications in several areas: discourse analysis, theoretical linguistics, psycholinguistics, and computational linguistics. We also provide a list of resources useful for work within the RST framework. The present article is a complement to our review of the theoretical aspects of the theory (Taboada and Mann, 2006).