bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of Two Commercial Susceptibility Test Methods for Determination of Daptomycin MICs
Authors: Jorgensen James H. , Crawford Sharon A.
Published: June 2006

Daptomycin is a lipopeptide antibiotic with activity against several important gram-positive bacterial pathogens, including drug-resistant staphylococci and enterococci. Because the mechanism of action of daptomycin is calcium-dependent depolarization of the cell membrane, susceptibility testing requires medium supplemented with a physiological level of calcium. This study assessed two Food and Drug Administration-cleared commercial test devices for determination of daptomycin MICs, Etest and JustOne. A collection of 220 selected isolates, including
Staphylococcus aureus
, coagulase-negative staphylococci,
Enterococcus faecalis
,
E. faecium
,
E. avium
,
E. durans
,
E. casseliflavus
, and
E. gallinarum
, were tested by both methods. Included in the collection were 22
S. aureus
and 14
Enterococcus
sp. isolates that were recovered from patients and were nonsusceptible on the basis of the daptomycin MICs. As the reference method for comparison, all isolates were tested by the Clinical and Laboratory Standards Institute broth microdilution method incorporating cation-adjusted Mueller-Hinton broth with 50 μg/ml calcium. Daptomycin MICs agreed, within 1 twofold dilution, for 97% of the isolates by Etest and for 100% by JustOne. However, daptomycin MICs determined by Etest were 1 dilution lower than the reference MICs for 65% of the
Enterococcus
sp. isolates tested. This resulted in 28.5% very major (VM) errors (4/14) with enterococci (all
E. faecium
) but none (0/22) with staphylococci. Use of JustOne yielded MICs that were 1 dilution lower than the reference MICs for 69% of the staphylococci and 25% of the enterococci. This resulted in 13.6% VM errors (3/22) with staphylococci and 14.3% VM errors (2/14) with enterococci. The manufacturer-recommended JustOne inoculum preparation resulted in mean colony counts of only 5 × 10
4
to 1 × 10
5
CFU/ml in the wells of the strip. Increasing the inoculum to 3 × 10
5
to 4 × 10
5
CFU/ml eliminated two of five VM errors upon retesting. No major interpretive errors occurred with either device. In summary, daptomycin MICs generated by the Etest or JustOne method generally agreed within 1 dilution of the reference daptomycin MICs. However, both devices produced slightly lower MICs that resulted in some VM errors.
Human Metapneumovirus Infection in a Hematopoietic Stem Cell Transplant Recipient with Relapsed Multiple Myeloma and Rapidly Progressing Lung Cancer
Authors: Huck B. , Egger M. , Bertz H. , Peyerl-Hoffman G. , Kern W. V. , Neumann-Haefelin D. , Falcone V.
Published: June 2006

Human metapneumovirus (HMPV) was isolated from a 63-year-old multiple myeloma patient who had undergone hematopoietic stem cell transplantation and who presented with lower respiratory tract infection several weeks prior to the diagnosis of lung cancer. The isolate was phylogenetically and biologically characterized and compared to HMPV prototypes and recent pediatric isolates. Remarkably, it belonged to the novel genomic subgroup A2b.
Chimeric Antigens ofToxoplasma gondii: Toward Standardization of Toxoplasmosis Serodiagnosis Using Recombinant Products
Authors: Beghetto Elisa , Spadoni Andrea , Bruno Luca , Buffolano Wilma , Gargano Nicola
Published: June 2006

We have evaluated the diagnostic utility of six antigenic regions of theToxoplasma gondii MIC2,MIC3,M2AP,GRA3,GRA7, andSAG1gene products, assembled in recombinant chimeric antigens by genetic engineering, in order to replace the soluble, whole-cell tachyzoite extract in serological assays. Serum samples from 100 adults with acquiredT. gondiiinfection and from 30 infants born to mothers with primary toxoplasmosis contracted during pregnancy, of whom 20 were congenitally infected, were included. Immunoglobulin G (IgG) and IgM antibodies against epitopes carried by chimeric antigens were measured by performing parallel enzyme immunoassays (recombinant enzyme-linked immunosorbent assays [Rec-ELISAs]), and the results obtained by standard commercial assays with the whole-cellToxoplasmaantigen and assays with the chimeric antigens were compared. Our results demonstrate that IgG and IgM Rec-ELISAs with individual chimeric antigens have performance characteristics comparable to those of the corresponding commercial assays. Furthermore, we show that IgM-capture assays based on chimeric antigens improve the ability to diagnose congenital toxoplasmosis postnatally compared with the ability to diagnose congenital toxoplasmosis by the use of standard assays. The use of recombinant chimeric antigens is effective in distinguishingT. gondii-infected individuals fromT. gondii-uninfected individuals and shows that immunoassays based on recombinant products could provide the basis for standardized commercial tests for the serodiagnosis of toxoplasmosis.
Comparison of the BACTEC 9240 and BacT/Alert Blood Culture Systems for Detection of Bacterial Contamination in Platelet Concentrates
Authors: Riedel Stefan , Siwek Gregory , Beekmann Susan E. , Richter Sandra S. , Raife Thomas , Doern Gary V.
Published: June 2006

The BACTEC 9240 blood culture system with a standard aerobic medium, Plus Aerobic/F, was compared to the BacT/Alert system with a platelet-specific medium, BPA, as a means for detecting bacterial contamination of platelet preparations. One hundred thirteen platelet units seeded with low levels of different bacteria were examined with both systems. In 93 instances, growth was detected first in the BACTEC system; in 12 cases, growth registered first in the BacT/Alert system. Among all comparisons, growth was detected, on average, 1.7 h sooner with the BACTEC system. The differences in length of time to detection were statistically significant.
Blinded Comparison of Repetitive-Sequence PCR and Multilocus Sequence Typing for Genotyping Methicillin-Resistant
Staphylococcus aureus
Isolates from a Children's Hospital in St. Louis, Missouri
Authors: Liao Robert S. , Storch Gregory A. , Buller Richard S. , Orscheln Rachel C. , Mardis Elaine R. , Armstrong Jon R. , Dunne W. Michael
Published: June 2006

We performed a blinded study to compare repetitive-sequence PCR and multilocus sequence typing for genotyping hospital- and community-acquired methicillin-resistant
Staphylococcus aureus
(MRSA). The MRSA strains that were sequence type 8 (ST8), staphylococcal cassette chromosome
mec
(SCC
mec
) type IV, and Panton-Valentine leukocidin-positive clustered separately from those that were ST5 and SCC
mec
type II.
Geographical Distribution of the Herpes Simplex Virus Type 1 BgK
L
Variant in Japan Suggests Gradual Dispersion of the Virus from Shikoku Island to the Other Islands
Authors: Ozawa Shigeru , Eda Hiroyuki , Hayashi Kozaburo ,   the Cooperation Group for HSV-1 RFLP Variant Study, Yoshino Kamesaburo , Yanagi Kazuo
Published: June 2006

Restriction endonuclease fragment length polymorphism (RFLP) is useful for the epidemiological study of herpes simplex virus type 1 (HSV-1). We report here the identification of a major BglII RFLP variant of HSV-1, designated BgK
L
, found in 27.0% of 636 HSV-1 clinical isolates. We have also established its geographic distribution in Japan. BgK
L
has an unusually large BglII K fragment. SalI cleavage analyses showed that 97% of BgK
L
variant isolates lack both the SalI C-J and the F-J cleavage sites and have an unusually large SalI D or E fragment, and 91% of the BgK
L
variants lack both SalI G and H fragments. Furthermore, 96% of BgK
L
isolates have an unusually small KpnI M fragment. Therefore, BgK
L
is a marker for these five mutations in most HSV-1 isolates and is a useful HSV-1 RFLP marker. The BgK
L
variant was found in 59% of HSV-1 isolates from Shikoku Island, 44% of HSV-1 isolates from the Chugoku region of Honshu Island, 31% of HSV-1 isolates from Kyushu Island, 0% of HSV-1 isolates from Okinawa Island, 49% of HSV-1 isolates from Osaka, 27% of HSV-1 isolates from Shiga, 13% of HSV-1 isolates from the Chubu Region, and 9% of HSV-1 isolates from the Tohoku Region of Honshu Island. Differences in the frequency of BgK
L
between the Shikoku-Chugoku-Osaka area (49%) and Kyushu, between Kyushu and Okinawa, between the Shikoku-Chugoku-Osaka area and Shiga, and between Shiga and Tohoku are all statistically significant. The BgK
L
frequency decreases in a geographical gradient suggest that this HSV-1 variant was dispersed from Shikoku to the surrounding regions and then to more distant regions. The BgK
L
frequency in Tokyo was similar to the nationwide average. These are the first data to suggest a geographic and demographic dispersion pattern of HSV-1. Implications for the epidemiology and diversification of HSV-1 are discussed.
Nontypeable
Haemophilus influenzae
as a Cause of Spontaneous Bacterial Peritonitis
Authors: Musher Daniel M. , Nichol Aran Cunningham , Rueda Adriana M.
Published: June 2006

Haemophilus influenzae
rarely causes spontaneous bacterial peritonitis. We describe a typical case of spontaneous bacterial peritonitis in which the causative organism was identified as nontypeable
H. influenzae
, biotype III. Infection progressed despite the presence of adequate serum bactericidal antibody, probably due to the absence of complement in ascites fluid.
Chronic Q Fever in the United States
Authors: Karakousis Petros C. , Trucksis Michele , Dumler J. Stephen
Published: June 2006

Infections due to
Coxiella burnetii
, the causative agent of Q fever, are uncommon in the United States. Cases of chronic Q fever are extremely rare and most often manifest as culture-negative endocarditis in patients with underlying valvular heart disease. We describe a 31-year-old farmer from West Virginia with a history of congenital heart disease and recurrent fevers for 14 months who was diagnosed with Q fever endocarditis based on an extremely high antibody titer against
Coxiella burnetii
phase I antigen. Despite treatment with doxycycline, he continued to have markedly elevated
Coxiella burnetii
phase I antibody titers for 10 years after the initial diagnosis. To our knowledge, this case represents the longest follow-up period for a patient with chronic Q fever in the United States. We review all cases of chronic Q fever reported in the United States and discuss important issues pertaining to epidemiology, diagnosis, and management of this disease.
Molecular Analysis of
Clostridium difficile
PCR Ribotype 027 Isolates from Eastern and Western Canada
Authors: MacCannell Duncan R. , Louie Thomas J. , Gregson Dan B. , Laverdiere Michel , Labbe Annie-Claude , Laing Felicia , Henwick Scott
Published: June 2006

The prevalence and characteristics of PCR ribotype 027 strains of
Clostridium difficile
have come into question following recent outbreaks in Eastern Canada and elsewhere. In order to determine the distribution of this strain in other regions in Canada, we screened a bank of 1,419 isolates recovered from three different Canadian health regions between 2000 and 2004. Among isolates from a Montreal area hospital, PCR ribotype 027 strains represented 115/153 strains (75.2%) from 2003 to 2004, but ribotype 027 strains were absent in 2000 and 2001. In Calgary, by contrast, ribotype 027 rates have remained relatively stable over 4 years of surveillance, representing 51/685 (7.4%) hospital isolates and 62/373 (16.6%) strains from the community (
P
< 0.001). PCR ribotype 027 accounted for 8/135 (5.9%) hospital isolates in the Fraser Health Region in 2004. repetitive extragenic palindromic PCR was used to subtype a random selection of 027 isolates from each region. All 10 of the isolates from Quebec were of a single subtype, which was also dominant among isolates from Alberta (8/10 isolates) and British Columbia (6/8 isolates). Comparative sequencing of the
tcdC
repressor gene confirmed the documented 18-bp deletion and identified a second, single-base-pair deletion at position 117. Both deletions were conserved across all three provinces and were identified in a United Kingdom reference strain. The presence of a frameshift in the early portion of the
tcdC
gene implies serious functional disruption and may contribute to the hypervirulence of the 027 phenotype. PCR ribotype 027 strains appear to be widely distributed, to predate the Montreal outbreak, and to have measurable community presence in Western Canada.
Identification of
Campylobacter fetus
Subspecies by Phenotypic Differentiation and PCR
Authors: Schulze Frank , Bagon Audrey , Müller Wolfgang , Hotzel Helmut
Published: June 2006

The species
Campylobacter fetus
is divided into the subspecies
C. fetus
subsp.
venerealis
and
C. fetus
subsp.
fetus
, which differ in their epidemiologies and clinical importance. The differences between these subspecies make accurate distinction between the two essential. First, the value of seven key tests for the traditional differentiation of
C. fetus
was investigated. Afterwards, the results of the phenotypic differentiation and PCR were compared to address the question of the reliability of this PCR assay. Altogether, 103
C. fetus
isolates were investigated, including the type strains of
C. fetus
subsp.
fetus
and
C. fetus
subsp.
venerealis
. Depending on the result of the glycine tolerance test, the isolates could be separated into 81
C. fetus
subsp.
venerealis
isolates (glycine intolerant) and 22
C. fetus
subsp.
fetus
isolates (glycine tolerant). For all
C. fetus
subsp.
venerealis
strains tested, the results of the selenite reduction assay and sensitivity to metronidazole and cefoperazone completely agreed with the results of the glycine tolerance test (correspondence, 100%). Seventy-three
C. fetus
subsp.
venerealis
isolates did not grow at 42°C (correspondence, 90.1%), but eight isolates showed a faintly discernible, flat, dark gray growth. For 22
C. fetus
subsp.
fetus
isolates, the results of additional phenotypic tests only partly agreed with the results of the glycine tolerance test. For
C. fetus
subsp.
fetus
the results of the glycine tolerance test showed a relatively good correspondence with those of the selenite reduction assay (correspondence, 81.8%), assays for cefoperazone resistance (correspondence, 86.4%), and assays for growth at 42°C (correspondence, 81.8%). The results of the glycine tolerance test and PCR completely agreed for the 103
C. fetus
isolates tested. We conclude that at present the traditional phenotypic characterization of
C. fetus
subspecies under strongly defined conditions remains indispensable, but this PCR assay constitutes a valuable adjunctive technique for the confirmation of phenotypic results.
Efficient Tracing of Global Isolates of
Yersinia pestis
by Restriction Fragment Length Polymorphism Analysis Using Three Insertion Sequences as Probes
Authors: Torrea Gabriela , Chenal-Francisque Viviane , Leclercq Alexandre , Carniel Elisabeth
Published: June 2006

Yersinia pestis
is the etiologic agent of plague, a disease that is transmitted from rodent to rodent and from rodent to humans by fleabites. Multiple copies of three insertion sequences (IS
100
, IS
285
, and IS
1541
) are scattered over the
Y. pestis
genome. The genomic instability generated by these insertion sequences (IS) creates a polymorphism of the hybridizing restriction fragments (restriction fragment length polymorphism [RFLP]) which can be used to subtype this relatively clonal species. The aim of this work was to evaluate and compare the potential of the three IS-RFLP techniques, individually or in combination, to define clusters of strains according to their focus of origin. The analysis of 61
Y. pestis
isolates of worldwide origin indicated that no satisfactory strain clustering was observed with each IS-RFLP used individually. In contrast, the combination of the three IS-RFLP data (3IS-RFLP) resulted in both an efficient strain discrimination (
D
= 0.999) and a robust clustering of the isolates according to their biovar and geographical origin. This geographical clustering was observed even within the Orientalis group, although these strains had only a short period of time (one century) to diverge from the original clone that spread globally. Therefore, 3IS-RFLP is a technique that may be useful for addressing epidemiological problems and forensic issues. When plague reemerges after several decades of silence in a quiescent focus, it may help in determining whether the disease was reimported or reactivated. It may also be of value to identify the origin of a strain when plague cases appear in a previously plague-free region. Finally, this technique could be useful for the tracing of a
Y. pestis
isolate that has been used as a biological terrorism threat.
Prevalence of Noroviruses and Sapoviruses in Swine of Various Ages Determined by Reverse Transcription-PCR and Microwell Hybridization Assays
Authors: Wang Qiu-Hong , Souza Menira , Funk Julie A. , Zhang Wei , Saif Linda J.
Published: June 2006

Noroviruses (NoVs) and sapoviruses (SaVs) are emerging enteric pathogens that cause diarrhea in humans and animals. Porcine genogroup II (GII) NoVs replicate in pigs, but their pathogenesis is undefined. The porcine SaV/GIII/Cowden/80/US strain causes diarrhea and intestinal lesions in pigs. Recently, genetically diverse porcine NoVs (genotypes 11, 18, and 19 within GII) and SaVs comprising at least two genogroups (GIII and GVI?/JJ681-like) and two unclassified strains (G?/QW19 and G?/LL26) were identified; however, their prevalence has not been reported. To investigate the prevalence of porcine NoVs and SaVs, 621 fecal samples were collected from swine of various ages from seven swine farms and one slaughterhouse in three states in the United States. Fecal samples were tested by reverse transcription-PCR and microwell hybridization assays with porcine NoV- and SaV-specific primers and probes, respectively. Porcine GII NoVs were detected exclusively from finisher pigs with an overall prevalence of 20%. Porcine GIII SaVs were detected in 62% of pigs, with the highest prevalence in postweaning pigs and lowest in nursing pigs. Porcine GVI?/JJ681-like SaVs and the G?/QW19-like SaVs were detected infrequently in pigs. The G?/LL26-like SaVs were detected mainly in younger pigs. Because some porcine NoVs and SaVs are genetically or antigenically related to human strains and recombinants within NoVs or SaVs occur for human and pig strains, the high prevalence and subclinical infection rate of these viruses in pigs raise questions of whether pigs may be reservoirs for human strains or for the emergence of new human and porcine recombinants.
Adverse reproductive outcomes among male painters with occupational exposure to organic solvents
Authors: Hooiveld M , Haveman W , Roskes K , Bretveld R , Burstyn I , Roeleveld N
Published: June 2006

Objectives:To assess the risks of reproductive disorders and birth defects in offspring of male painters with exposure to organic solvents, and to determine the shape of the dose-response relationship.

Methods:Random samples of painters and carpenters were drawn from workers affiliated with the Dutch Trade Union for Construction Workers, the Netherlands, 2001. Information on reproductive outcomes, occupational exposures, and lifestyle habits was retrospectively obtained through self-administered questionnaires filled in by 398 painters exposed to organic solvents in paints, thinners, and cleansers in the period of three months before the last pregnancy, and 302 carpenters with little or no exposure to solvents. A statistical model was used to estimate quantitative exposure measures.

Results:Workers employed as painters at three months before pregnancy had an increased risk (odds ratio 6.2, 95% CI 1.4 to 27.9) of congenital malformations in offspring compared to carpenters. There was a positive exposure-response trend with increasing exposure to organic solvents based on quantitative model predicted exposure estimates using toluene as a marker. There was some indication of an increased risk of functional developmental disorders in offspring among painters with intermediate and high model predicted exposure. The risk of low birth weight children seemed to be slightly increased among painters as well. Results for other reproductive outcomes (time to pregnancy, spontaneous abortion, and preterm birth) did not show increased risks.

Conclusion:This study showed a positive association between paternal occupational exposure to organic solvents and congenital malformations in offspring. However, the small numbers of cases, especially when examining different exposure levels, as well as the self-reported nature of exposure and outcome variables, may hamper interpretation of the results.
QUANTUM DOT COMPUTING GATES
Authors: CHEN GOONG , DIAO ZIJIAN , KIM JONG U. , NEOGI ARUP , URTEKIN KERIM , ZHANG ZHIGANG
Published: June 2006

Semiconductor quantum dots are a promising candidate for future quantum computer devices. Presently, there are three major proposals for designing quantum computing gates based on quantum dot technology: (i) electrons trapped in microcavity; (ii) spintronics; (iii) biexcitons. We survey these designs and show mathematically how, in principle, they will generate 1-bit rotation gates as well as 2-bit entanglement and, thus, provide a class of universal quantum gates. Some physical attributes and issues related to their limitations, decoherence and measurement are also discussed.
ON THE POTENTIAL INFLUENCE OF QUANTUM NOISE ON MEASURING EFFECTIVENESS IN CLINICAL TRIALS
Authors: JANZING DOMINIK , BETH THOMAS
Published: June 2006

To test the effectiveness of a drug, the medical researcher can instruct two randomly selected groups of patients to take the drug or not to take it. Each group should comply with the instructions exactly or else the causal effect cannot be identified satisfactorily. This holds true even when those who do not comply are identified afterwards, since latent factors such as patient's personality can influence both his decision and his physical response. However, one can still give bounds on the effectiveness of the drug depending on the rate of compliance. They are described by 16 inequalities. Remarkably, the proofs for these bounds given in the literature rely on models that represent all relevant latent factors influencing patient's behavior by hidden classical variables. In a strong analogy to the violation of Bell's inequality, half of the inequalities fail if patient behavior is influenced by latent quantum processes (e.g. in his nervous system). Quantum effects could fake an increase in the recovery rate by about 13%, although the drug would hurt as many patients as it would help if everyone took it. We show that the other eight inequalities remain true even in the quantum case. We do not present a realistic model showing the above effect. We only point out that the physics of decision-making could be relevant for the causal interpretation of every-day life statistical data. Our derivation of the remaining eight inequalities suggests how to avoid problematic hidden-variable models in classical causal reasoning by representing all latent factors by quantum systems.
ENTANGLEMENT-ASSISTED ORIENTATION IN SPACE
Authors: BRUKNER ČASLAV , PAUNKOVIĆ NIKOLA , RUDOLPH TERRY , VEDRAL VLATKO
Published: June 2006

We demonstrate that quantum entanglement can help separated individuals in making decisions if their goal is to find each other in the absence of any communication between them. We derive a Bell-like inequality that the efficiency of every classical solution for our problem has to obey, and demonstrate its violation by the quantum efficiency. This proves that no classical strategy can be more efficient than the quantum one.
AN ECONOMICAL PROTOCOL FOR TELEPORTING M-QUNIT ENTANGLEMENT
Authors: AN NGUYEN BA
Published: June 2006

We propose a protocol to teleport a type of unknown M-quNit entanglement using a single maximally entangled quNit pair as a quantum channel. The faithful teleportation is possible at the expense of consuming local resources together with additional bi-quNit operations at the receiving site. Although the full set of measurement outcomes at the sending site consists of M + 1 Nits, the classical data necessary to rebuild the original teleported state at the receiving site can be managed so that a message of only two Nits suffices. The proposed protocol is economical in the sense that the cost of both quantum nonlocal resource and classical communication is minimal and does not depend on M.
Developmental regulation of the activation of signaling components leading to translation initiation in skeletal muscle of neonatal pigs
Authors: Suryawan Agus , Escobar Jeffery , Frank Jason W. , Nguyen Hanh V. , Davis Teresa A.
Published: June 2006

The rapid growth of neonates is driven by high rates of skeletal muscle protein synthesis. This high rate of protein synthesis, which is induced by feeding, declines with development. Overnight-fasted 7- and 26-day-old pigs either remained fasted or were refed, and the abundance and phosphorylation of growth factor- and nutrient-induced signaling components that regulate mRNA translation initiation were measured in skeletal muscle and liver. In muscle, but not liver, the activation of inhibitors of protein synthesis, phosphatase and tensin homolog deleted on chromosome 10, protein phosphatase 2A, and tuberous sclerosis complex 1/2 increased with age. Serine/threonine phosphorylation of the insulin receptor and insulin receptor substrate-1, which downregulates insulin signaling, and the activation of AMP-activated protein kinase, an inhibitor of protein synthesis, were unaffected by age and feeding in muscle and liver. Activation of positive regulators of protein synthesis, mammalian target of rapamycin (mTOR), ribosomal protein S6 kinase 1 (S6K1), and eIF4E-binding protein-1 (4E-BP1) decreased with age in muscle but not liver. Feeding enhanced mTOR, S6K1, and 4E-BP1 activation in muscle, and this response decreased with age. In liver, activation of S6K1 and 4E-BP1, but not mTOR, was increased by feeding but was unaffected by age. Raptor abundance and the association between raptor and mTOR were greater in 7- than in 26-day-old pigs. The results suggest that the developmental decline in skeletal muscle protein synthesis is due in part to developmental regulation of the activation of growth factor and nutrient-signaling components.
Adrenomedullin inhibits insulin exocytosis via pertussis toxin-sensitive G protein-coupled mechanism
Authors: Sekine Nobuo , Takano Koji , Kimata-Hayashi Nako , Kadowaki Takashi , Fujita Toshiro
Published: June 2006

Direct effects of adrenomedullin on insulin secretion from pancreatic β-cells were investigated using a differentiated insulin-secreting cell line INS-1. Adrenomedullin (1–100 pM) inhibited insulin secretion at both basal (3 mM) and high (15 mM) glucose concentrations, although this inhibitory effect was not observed at higher concentrations of adrenomedullin. The inhibition of glucose-induced insulin secretion by adrenomedullin was restored with 12-h pretreatment with 1 μg/ml pertussis toxin (PTX), suggesting that this effect could be mediated by PTX-sensitive G proteins. Cellular glucose metabolism evaluated by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide colorimetric assay was not affected by adrenomedullin at concentrations that inhibited insulin secretion. Moreover, electrophysiological studies revealed that 10 pM adrenomedullin had no effect on membrane potential, voltage-gated calcium currents, or cytosolic calcium concentration induced by 15 mM glucose. Finally, insulin release induced by cAMP-raising agents, such as forskolin plus 3-isobutyl-1-methylxanthine or the calcium ionophore ionomycin, was significantly inhibited by 10 and 100 pM adrenomedullin. In conclusion, adrenomedullin at picomolar concentrations directly inhibited insulin secretion from β-cells. This effect is likely due to the inhibition of insulin exocytosis through the activation of PTX-sensitive G proteins.
Plasma kisspeptin is raised in patients with gestational trophoblastic neoplasia and falls during treatment
Authors: Dhillo Waljit S. , Savage Philip , Murphy Kevin G. , Chaudhri Owais B. , Patterson Michael , Nijher Gurjinder M. , Foggo Vanessa M. , Dancey Garin S. , Mitchell Hugh , Seckl Michael J. , Ghatei Mohammad A. , Bloom Stephen R.
Published: June 2006

Kisspeptin is a 54-amino acid peptide, encoded by the anti-metastasis gene KiSS-1, that activates G protein-coupled receptor 54 (GPR54). The kisspeptin-GPR54 system is critical to normal reproductive development. KiSS-1 gene expression is increased in the human placenta in normal and molar pregnancies. Circulating kisspeptin is dramatically increased in normal pregnancy, but levels in GTN have not previously been reported. The present study was designed to determine whether plasma kisspeptin levels are altered in patients with malignant GTN. Thirty-nine blood samples were taken from 11 patients with malignant GTN at presentation during and after chemotherapy. Blood was also sampled from nonpregnant and pregnant volunteers. Plasma kisspeptin IR and hCG concentrations were measured. Plasma kisspeptin IR concentration in nonpregnant ( n = 16) females was <2 pmol/l. Plasma kisspeptin IR in females was 803 ± 125 pmol/l in the first trimester of pregnancy ( n = 13), 2,483 ± 302 pmol/l in the third trimester of pregnancy ( n = 7), and <2 pmol/l on day 15 postpartum ( n = 7). Plasma kisspeptin IR and hCG concentrations in patients with malignant GTN were elevated at presentation and fell during and after treatment with chemotherapy in each patient (mean plasma kisspeptin IR: prechemotherapy 1,363 ± 1,076 pmol/l vs. post-chemotherapy <2 pmol/l, P < 0.0001; mean plasma hCG: prechemotherapy 227,191 ± 152,354 U/l vs. postchemotherapy 2 U/l, P < 0.0001). Plasma kisspeptin IR strongly positively correlated with plasma hCG levels ( r2= 0.99, P < 0.0001). Our results suggest that measurement of plasma kisspeptin IR may be a novel tumor marker in patients with malignant GTN.
Oxytocin receptor binding in the hypothalamus during gestation in rats
Authors: Bealer Steven L. , Lipschitz David L. , Ramoz Gina , Crowley William R.
Published: June 2006

Central oxytocin receptors (OTR) may be involved in adaptations of the brain oxytocin (OT) system during gestation, which are critical for systemic release of OT during parturition and lactation. We used quantitative autoradiography to determine changes in OTR binding in numerous brain sites during the course of gestation in the rat. Furthermore, to evaluate the importance of ovarian steroids in mediating pregnancy-related changes in OTR binding, we measured binding in ovariectomized animals treated with progesterone and/or estrogen, and in pregnant animals treated with exogenous progesterone during late gestation. We found that OTR binding was significantly increased in the paraventricular nucleus (PVN) and supraoptic nucleus (SON) by midgestation ( day 15) compared with control. In addition, there was a further significant increase in OTR binding in these nuclei by late gestation ( day 20). The bed nucleus of the stria terminalis (BNST) and the medial preoptic area (MPOA) also showed significant gestation-associated increases in OTR binding, which were similar during mid- and late pregnancy. Treatment with exogenous progesterone throughout pregnancy did not alter the increase in OTR binding characteristic of late gestation in any of these brain sites. Finally, estrogen treatment in ovariectomized animals resulted in increased OTR binding in the SON, BNST, and MPOA, but not the PVN. These data demonstrate that OTR binding in the hypothalamus is increased during mid- and late-gestation, compared with ovariectomized control animals, which may be mediated by increased estradiol.
Angiotensin II mediates downregulation of aquaporin water channels and key renal sodium transporters in response to urinary tract obstruction
Authors: Jensen Anja M. , Li Chunling , Praetorius Helle A. , Nørregaard Rikke , Frische Sebastian , Knepper Mark A. , Nielsen Søren , Frøkiær Jørgen
Published: June 2006

The renin-angiotensin system is well known to be involved in the pathophysiological changes in renal function after obstruction of the ureter. Previously, we demonstrated that bilateral ureteral obstruction (BUO) is associated with dramatic changes in the expression of both renal sodium transporters and aquaporin water channels (AQPs). We now examined the effects of the AT1-receptor antagonist candesartan on the dysregulation of AQPs and key renal sodium transporters in rats subjected to 24-h BUO and followed 2 days after release of BUO (BUO-2R). Consistent with previous observations, BUO-2R resulted in a significantly decreased expression of AQP1, -2, and -3 compared with control rats. Concomitantly, the rats developed polyuria and reduced urine osmolality. Moreover, expression of the type 2 Na-phosphate cotransporter (NaPi-2) and type 1 bumetanide-sensitive Na-K-2Cl cotransporter (NKCC2) was markedly reduced, consistent with postobstructive natriuresis. Candesartan treatment from the onset of obstruction attenuated the reduction in GFR (3.1 ± 0.4 vs. 1.7 ± 0.3 ml·min−1·kg−1) and partially prevented the reduction in the expression of AQP2 (66 ± 21 vs. 13 ± 2%, n = 7; P < 0.05), NaPi-2 (84 ± 6 vs. 57 ± 10%, n = 7; P < 0.05), and NKCC2 (89 ± 12 vs. 46% ± 11, n = 7; P < 0.05). Consistent with this, candesartan treatment attenuated the increase in urine output (58 ± 4 vs. 97 ± 5 μl·min−1·kg−1, n = 7; P < 0.01) and the reduction in sodium reabsorption (433 ± 62 vs. 233 ± 45 μmol·min−1·kg−1, n = 7; P < 0.05) normally found in rats subjected to BUO. Moreover, candesartan treatment attenuated induction of cyclooxygenase 2 (COX-2) expression in the inner medulla, suggesting that COX-2 induction in response to obstruction is regulated by ANG II. In conclusion, candesartan prevents dysregulation of AQP2, sodium transporters, and development of polyuria seen in BUO. This strongly supports the view that candesartan protects kidney function in response to urinary tract obstruction.
Nonperforming Debts in Chinese Enterprises: Patterns, Causes, and Implications for Banking Reform
Authors: Xiao Geng
Published: June 2006

Given the domination of bank financing, nonperforming debts (NPDs) in large Chinese enterprises are a proxy for nonperforming loans (NPLs) in China's major banks. Using a firm-level survey of more than 20,000 large and medium-sized industrial enterprises conducted by the National Bureau of Statistics of China, this paper estimates both the level and ratio of NPDs across ownership type, industry, and region for the period 1995–2002. The results show that NPD ratios have been falling since 2000 as a result of the rapid expansion of better-performing non-state enterprises (NSEs), the improved performance of state-owned enterprises (SOEs), and the exit of poor-performing enterprises (which has been facilitated by asset management companies and other merger and acquisition activities). SOEs, however, are still much more likely than NSEs to generate NPDs. This paper provides useful tools and sector information for assessing enterprise debt risks and draws lessons for banking reform in China.
Extratropical Atmosphere–Ocean Variability in CCSM3
Authors: Alexander Michael , Yin Jeffrey , Branstator Grant , Capotondi Antonietta , Cassou Christophe , Cullather Richard , Kwon Young-oh , Norris Joel , Scott James , Wainer Ilana
Published: June 2006

Extratropical atmosphere–ocean variability over the Northern Hemisphere of the Community Climate System Model version 3 (CCSM3) is examined and compared to observations. Results are presented for an extended control integration with a horizontal resolution of T85 (1.4°) for the atmosphere and land and ∼1° for the ocean and sea ice.

Several atmospheric phenomena are investigated including storms, clouds, and patterns of variability, and their relationship to both tropical and extratropical SST anomalies. The mean storm track, the leading modes of storm track variability, and the relationship of the latter to tropical and midlatitude sea surface temperature (SST) anomalies are fairly well simulated in CCSM3. The positive correlations between extratropical SST and low-cloud anomalies in summer are reproduced by the model, but there are clear biases in the relationship between clouds and the near-surface meridional wind. The model accurately represents the circulation anomalies associated with the jet stream waveguide, the Pacific–North American (PNA) pattern, and fluctuations associated with the Aleutian low, including how the latter two features are influenced by the El Niño–Southern Oscillation (ENSO). CCSM3 has a reasonable depiction of the Pacific decadal oscillation (PDO), but it is not strongly connected to tropical Pacific SSTs as found in nature. There are biases in the position of the North Atlantic Oscillation (NAO) and other Atlantic regimes, as the mean Icelandic low in CCSM3 is stronger and displaced southeastward relative to observations.

Extratropical ocean processes in CCSM3, including upper-ocean mixing, thermocline variability, and extratropical to tropical flow within the thermocline, also influence climate variability. As in observations, the model includes the “reemergence mechanism” where seasonal variability in mixed layer depth (MLD) allows SST anomalies to recur in consecutive winters without persisting through the intervening summer. Remote wind stress curl anomalies drive thermocline variability in the Kuroshio–Oyashio Extension region, which influences SST, surface heat flux anomalies, and the local wind field. The interior ocean pathways connecting the subtropics to the equator in both the Pacific and Atlantic are less pronounced in CCSM3 than in nature or in ocean-only simulations forced by observed atmospheric conditions, and the flow from the subtropical North Atlantic does not appear to reach the equator through either the western boundary or interior pathways.
Assessing Snow Albedo Feedback in Simulated Climate Change
Authors: Qu Xin , Hall Alex
Published: June 2006

In this paper, the two factors controlling Northern Hemisphere springtime snow albedo feedback in transient climate change are isolated and quantified based on scenario runs of 17 climate models used in the Intergovernmental Panel on Climate Change Fourth Assessment Report. The first factor is the dependence of planetary albedo on surface albedo, representing the atmosphere's attenuation effect on surface albedo anomalies. It is potentially a major source of divergence in simulations of snow albedo feedback because of large differences in simulated cloud fields in Northern Hemisphere land areas. To calculate the dependence, an analytical model governing planetary albedo was developed. Detailed validations of the analytical model for two of the simulations are shown, version 3 of the Community Climate System Model (CCSM3) and the Geophysical Fluid Dynamics Laboratory global coupled Climate Model 2.0 (CM2.0), demonstrating that it facilitates a highly accurate calculation of the dependence of planetary albedo on surface albedo given readily available simulation output. In all simulations it is found that surface albedo anomalies are attenuated by approximately half in Northern Hemisphere land areas as they are transformed into planetary albedo anomalies. The intermodel standard deviation in the dependence of planetary albedo on surface albedo is surprisingly small, less than 10% of the mean. Moreover, when an observational estimate of this factor is calculated by applying the same method to the satellite-based International Satellite Cloud Climatology Project (ISCCP) data, it is found that most simulations agree with ISCCP values to within about 10%, despite further disagreements between observed and simulated cloud fields. This suggests that even large relative errors in simulated cloud fields do not result in significant error in this factor, enhancing confidence in climate models. The second factor, related exclusively to surface processes, is the change in surface albedo associated with an anthropogenically induced temperature change in Northern Hemisphere land areas. It exhibits much more intermodel variability. The standard deviation is about ⅓ of the mean, with the largest value being approximately 3 times larger than the smallest. Therefore this factor is unquestionably the main source of the large divergence in simulations of snow albedo feedback. To reduce the divergence, attention should be focused on differing parameterizations of snow processes, rather than intermodel variations in the attenuation effect of the atmosphere on surface albedo anomalies.
A Characterization of Tropical Transient Activity in the CAM3 Atmospheric Hydrologic Cycle
Authors: Rasch Philip J. , Stevens Mark J. , Ricciardulli Lucrezia , Dai Aiguo , Negri Andrew , Wood Robert , Boville Byron A. , Eaton Brian , Hack James J.
Published: June 2006

The Community Atmosphere Model version 3 (CAM3) is the latest generation of a long lineage of general circulation models produced by a collaboration between the National Center for Atmospheric Research (NCAR) and the scientific research community. Many aspects of the hydrological cycle have been changed relative to earlier versions of the model. It is the goal of this paper to document some aspects of the tropical variability of clouds and the hydrologic cycle in CAM3 on time scales shorter than 30 days and to discuss the differences compared to the observed atmosphere and earlier model versions, with a focus on cloud-top brightness temperature, precipitation, and cloud liquid water path. The transient behavior of the model in response to changes in resolution to various numerical methods used to solve the equations for atmospheric dynamics and transport and to the underlying lower boundary condition of sea surface temperature and surface fluxes has been explored.

The ratio of stratiform to convective rainfall is much too low in CAM3, compared to observational estimates. It is much higher in CAM3 (10%) than the Community Climate Model version 3 (CCM3; order 1%–2%) but is still a factor of 4–5 too low compared to observational estimates. Some aspects of the model transients are sensitive to resolution. Higher-resolution versions of CAM3 show too much variability (both in amplitude and spatial extent) in brightness temperature on time scales of 2–10 days compared to observational estimates. Precipitation variance is underestimated on time scales from a few hours to 10 days, compared to observations over ocean, although again the biases are reduced compared to previous generations of the model. The diurnal cycle over tropical landmasses is somewhat too large, and there is not enough precipitation during evening hours. The model tends to produce maxima in precipitation and liquid water path that are a few hours earlier than that seen in the observations over both oceans and land.
Climate Sensitivity of Moderate- and Low-Resolution Versions of CCSM3 to Preindustrial Forcings
Authors: Otto-Bliesner Bette L. , Tomas Robert , Brady Esther C. , Ammann Caspar , Kothavala Zav , Clauzet Gabriel
Published: June 2006

Preindustrial (PI) simulations of the Community Climate System Model version 3 (CCSM3) at two resolutions, a moderate and a low resolution, are described and compared to the standard controls for present-day (PD) simulations. Because of computational efficiency, the moderate- and low-resolution versions of CCSM3 may be appropriate for climate change studies requiring simulations of the order of hundreds to thousands of years. The PI simulations provide the basis for comparison for proxy records that represent average late Holocene conditions.

When forced with PI trace gases, aerosols, and solar irradiance estimates, both resolutions have a global cooling of 1.2°–1.3°C, increased sea ice in both hemispheres, and less precipitation near the equator and at midlatitudes as compared to simulations using PD forcing. The response to PI forcings differs in the two resolutions for North Atlantic meridional overturning circulation (MOC), the Antarctic Circumpolar Current (ACC), and ENSO. The moderate-resolution CCSM3 has enhanced ACC, North Atlantic MOC, and tropical Pacific ENSO variability for PI forcings as compared to PD. The low-resolution CCSM3 with more extensive sea ice and colder climate at high northern latitudes in the PD simulation shows less sensitivity of the North Atlantic MOC to PI forcing. ENSO variability and the strength of the ACC do not increase with PI forcing in the low-resolution CCSM3.
Ocean Chlorofluorocarbon and Heat Uptake during the Twentieth Century in the CCSM3
Authors: Gent Peter R. , Bryan Frank O. , Danabasoglu Gokhan , Lindsay Keith , Tsumune Daisuke , Hecht Matthew W. , Doney Scott C.
Published: June 2006

An ensemble of nine simulations for the climate of the twentieth century has been run using the Community Climate System Model version 3 (CCSM3). Three of these runs also simulate the uptake of chlorofluorocarbon-11 (CFC-11) into the ocean using the protocol from the Ocean Carbon Model Intercomparison Project (OCMIP). Comparison with ocean observations taken between 1980 and 2000 shows that the global CFC-11 uptake is simulated very well. However, there are regional biases, and these are used to identify where too much deep-water formation is occurring in the CCSM3. The differences between the three runs simulating CFC-11 uptake are also briefly documented.

The variability in ocean heat content in the 1870 control runs is shown to be only a little smaller than estimates using ocean observations. The ocean heat uptake between 1957 and 1996 in the ensemble is compared to the recent observational estimates of the secular trend. The trend in ocean heat uptake is considerably larger than the natural variability in the 1870 control runs. The heat uptake down to 300 m between 1957 and 1996 varies by a factor of 2 across the ensemble. Some possible reasons for this large spread are discussed. There is much less spread in the heat uptake down to 3 km. On average, the CCSM3 twentieth-century ensemble runs take up 25% more heat than the recent estimate from ocean observations. Possible explanations for this are that the model heat uptake is calculated over the whole ocean, and not just in the regions where there are many observations and that there is no parameterization of the indirect effects of aerosols in CCSM3.
CCSM–CAM3 Climate Simulation Sensitivity to Changes in Horizontal Resolution
Authors: Hack James J. , Caron Julie M. , Danabasoglu G. , Oleson Keith W. , Bitz Cecilia , Truesdale John E.
Published: June 2006

The latest version of the Community Climate System Model (CCSM) Community Atmosphere Model version 3 (CAM3) has been released to allow for numerical integration at a variety of horizontal resolutions. One goal of the CAM3 design was to provide comparable large-scale simulation fidelity over a range of horizontal resolutions through modifications to adjustable coefficients in the parameterized treatment of clouds and precipitation. Coefficients are modified to provide similar cloud radiative forcing characteristics for each resolution. Simulations with the CAM3 show robust systematic improvements with higher horizontal resolution for a variety of features, most notably associated with the large-scale dynamical circulation. This paper will focus on simulation differences between the two principal configurations of the CAM3, which differ by a factor of 2 in their horizontal resolution.