bluuebunny/crossref_metadata_2025 huggingface dataset:
International Retrospective Analysis of 73 Cases of Invasive Fusariosis Treated with Voriconazole
Authors: Lortholary Olivier , Obenga Gaelle , Biswas Pinaki , Caillot Denis , Chachaty Elisabeth , Bienvenu Anne-Lise , Cornet Muriel , Greene John , Herbrecht Raoul , Lacroix Claire , Grenouillet Frédéric , Raad Issam , Sitbon Karine , Troke Peter
Published: July 2010

The outcomes for 73 invasive fusariosis patients treated with voriconazole were investigated. Patients with proven (
n
= 67) or probable (
n
= 6) infections were identified from the voriconazole clinical database (
n
= 39) and the French National Reference Center for Mycoses and Antifungals database (
n
= 34). Investigator-determined success was a complete or partial response. Survival was determined from day 1 of voriconazole therapy to the last day known alive. Patients were 2 to 79 years old (median, 43 years), and 66% were male. Identified
Fusarium
species (62%) were
F. solani
,
F. moniliforme
,
F. proliferatum
, and
F. oxysporum
. Underlying conditions analyzed included hematopoietic stem cell transplant (HSCT; 18%), hematologic malignancy (HM; 60%), chronic immunosuppression (CI; 12%), or other condition (OC; 10%). Infection sites were brain (5%), disseminated excluding brain (67%), lungs/sinus (15%), and other (12%). Most patients (64%) were or had recently been neutropenic (<500 cells/mm
3
). Therapy duration was 1 to 480 days (median, 57 days), with a 47% success rate. Baseline neutropenia impacted success adversely (
P
≤ 0.03). Success varied by underlying condition (HSCT, 38%; HM, 45%; CI, 44%; OC, 71%) and infection site (brain, 0%; disseminated, 45%; other, 56%; lung/sinus, 64%) (
P
> 0.05). Combination therapy (13 patients) was no better than treatment with voriconazole alone. Overall, 59% of the patients died (49% died of fusariosis), and 90-day survival was 42%. Site of infection influenced survival (
P
= 0.02). Median survival (in days) by species was as follows:
F. solani
, 213;
F. oxysporum
, 112;
Fusarium
spp., 101;
F. proliferatum
, 84;
F. moniliforme
, 76. We conclude that voriconazole is a therapeutic option for invasive fusariosis.
Chemical Validation of Phosphodiesterase C as a Chemotherapeutic Target in
Trypanosoma cruzi
, the Etiological Agent of Chagas' Disease
Authors: King-Keller Sharon , Li Minyong , Smith Alyssa , Zheng Shilong , Kaur Gurpreet , Yang Xiaochuan , Wang Binghe , Docampo Roberto
Published: July 2010

Trypanosoma cruzi
phosphodiesterase (PDE) C (TcrPDEC), a novel and rather unusual PDE in which, unlike all other class I PDEs, the catalytic domain is localized in the middle of the polypeptide chain, is able to hydrolyze cyclic GMP (cGMP), although it prefers cyclic AMP (cAMP), and has a FYVE-type domain in its
N
-terminal region (S. Kunz et al., FEBS J.
272:
6412-6422, 2005). TcrPDEC shows homology to the mammalian PDE4 family members. PDE4 inhibitors are currently under development for the treatment of inflammatory diseases, such as asthma, chronic pulmonary diseases, and psoriasis, and for treating depression and serving as cognitive enhancers. We therefore tested a number of compounds originally synthesized as potential PDE4 inhibitors on
T. cruzi
amastigote growth, and we obtained several useful hits. We then conducted homology modeling of
T. cruzi
PDEC and identified other compounds as potential inhibitors through virtual screening. Testing of these compounds against amastigote growth and recombinant TcrPDEC activity resulted in several potent inhibitors. The most-potent inhibitors were found to increase the cellular concentration of cAMP. Preincubation of cells in the presence of one of these compounds stimulated volume recovery after hyposmotic stress, in agreement with their TcrPDEC inhibitory activity
in vitro
, providing chemical validation of this target. The compounds found could be useful tools in the study of osmoregulation in
T. cruzi
. In addition, their further optimization could result in the development of new drugs against Chagas' disease and other trypanosomiases.
Bioavailability and Efficacy of Levofloxacin against
Francisella tularensis
in the Common Marmoset (
Callithrix jacchus
)
Authors: Nelson Michelle , Lever Mark S. , Dean Rachel E. , Pearce Peter C. , Stevens Daniel J. , Simpson Andrew J. H.
Published: July 2010

Pharmacokinetic and efficacy studies with levofloxacin were performed in the common marmoset (
Callithrix jacchus
) model of inhalational tularemia. Plasma levofloxacin pharmacokinetics were determined in six animals in separate single-dose and multidose studies. Plasma drug concentrations were analyzed using liquid chromatography-tandem mass spectrometry-electrospray ionization. On day 7 of a twice-daily dosing regimen of 40 mg/kg, the levofloxacin half-life, maximum concentration, and area under the curve in marmoset plasma were 2.3 h, 20.9 μg/ml, and 81.4 μg/liter/h, respectively. An efficacy study was undertaken using eight treated and two untreated control animals. Marmosets were challenged with a mean of 1.5 × 10
2
CFU of
Francisella tularensis
by the airborne route. Treated animals were administered 16.5 mg/kg levofloxacin by mouth twice daily, based on the pharmacokinetic parameters, beginning 24 h after challenge. Control animals had a raised core body temperature by 57 h postchallenge and died from infection by day 5. All of the other animals survived, remained afebrile, and lacked overt clinical signs. No bacteria were recovered from the organs of these animals at postmortem after culling at day 24 postchallenge. In conclusion, postexposure prophylaxis with orally administered levofloxacin was efficacious against acute inhalational tularemia in the common marmoset. The marmoset appears to be an appropriate animal model for the evaluation of postexposure therapies.
Comparative
In Vitro
Activity Profiles of Novel Bis-Indole Antibacterials against Gram-Positive and Gram-Negative Clinical Isolates
Authors: Butler Michelle M. , Williams John D. , Peet Norton P. , Moir Donald T. , Panchal Rekha G. , Bavari Sina , Shinabarger Dean L. , Bowlin Terry L.
Published: July 2010

Antimicrobial susceptibilities of 233 Gram-positive and 180 Gram-negative strains to two novel bis-indoles were evaluated. Both compounds were potent inhibitors of Gram-positive bacteria, with MIC
90
values of 0.004 to 0.5 μg/ml. One bis-indole, MBX 1162, exhibited potent activity against all Gram-negative strains, with MIC
90
values of 0.12 to 4 μg/ml, even against high-level-resistant pathogens, and compared favorably to all comparator antibiotics. The bis-indole compounds show promise for the treatment of multidrug-resistant clinical pathogens.
Antimicrobial Mechanism of Action of Transferrins: Selective Inhibition of H
+
-ATPase
Authors: Andrés María T. , Fierro José F.
Published: July 2010

Two bacterial species with different metabolic features, namely,
Pseudomonas aeruginosa
and
Lactococcus lactis
, were used as a comparative experimental model to investigate the antimicrobial target and mechanism of transferrins. In anaerobiosis,
P. aeruginosa
cells were not susceptible to lactoferrin (hLf) or transferrin (hTf). In aerobiosis, the cells were susceptible but O
2
consumption was not modified, indicating that components of the electron transport chain (ETC) were not targeted. However, the respiratory chain inhibitor piericidin A significantly reduced the killing activity of both proteins. Moreover, 2,6-dichlorophenolindophenol (DCIP), a reducing agent that accepts electrons from the ETC coupled to H
+
extrusion, made
P. aeruginosa
susceptible to hLf and hTf in anaerobiosis. These results indicated that active cooperation of the cell was indispensable for the antimicrobial effect. For
L. lactis
cells lacking an ETC, the absence of a detectable transmembrane electrical potential in hLf-treated cells suggested a loss of H
+
-ATPase activity. Furthermore, the inhibition of ATPase activity and H
+
translocation (inverted membrane vesicles) provided direct evidence of the ability of hLf to inhibit H
+
-ATPase in
L. lactis
. Based on these data, we propose that hLf and hTf also inhibit the H
+
-ATPase of respiring
P. aeruginosa
cells. Such inhibition thereby interferes with reentry of H
+
from the periplasmic space to the cytoplasm, resulting in perturbation of intracellular pH and the transmembrane proton gradient. Consistent with this hypothesis, periplasmic H
+
accumulation was prevented by anaerobiosis or by piericidin A or was induced by DCIP in anaerobiosis. Collectively, these results indicate that transferrins target H
+
-ATPase and interfere with H
+
translocation, yielding a lethal effect
in vitro
.
Determination of CEM-101 Activity Tested against Clinical Isolates of
Neisseria meningitidis
from a Worldwide Collection
Authors: Biedenbach Douglas J. , Castanheira Mariana , Jones Ronald N.
Published: July 2010

The activity of CEM-101, a fluoroketolide, was compared to those of 11 other antimicrobial agents using the reference broth microdilution method tested against 103
Neisseria meningitidis
strains, including ciprofloxacin-nonsusceptible isolates with confirmed
gyr
A
(T91I) mutations. Among the tested isolates, 79.6% were serogroup B or C and all isolates were susceptible to ceftriaxone, azithromycin, minocycline, and rifampin. However, penicillin-nonsusceptible strains were observed (15.5%) and susceptibility to trimethoprim-sulfamethoxazole was only 50.5%. CEM-101 was the most active macrolide-like compound (MIC
90
, ≤0.015 μg/ml) compared with MIC
90
s of telithromycin (MIC
90
, 0.03 μg/ml), azithromycin and clarithromycin (MIC
90
, 0.12 μg/ml), and erythromycin (MIC
90
, 0.25 μg/ml). CEM-101 could provide a potent alternative for the prophylaxis of meningococcal disease.
Use of a Mixture of Surrogates for Infectious Bioagents in a Standard Approach to Assessing Disinfection of Environmental Surfaces
Authors: Sabbah Safaa , Springthorpe Susan , Sattar Syed A.
Published: July 2010

We used a mixture of surrogates (
Acinetobacter baumannii
,
Mycobacterium terrae
, hepatitis A virus, and spores of
Geobacillus stearothermophilus
) for bioagents in a standardized approach to test environmental surface disinfectants. Each carrier containing 10 μl of mixture received 50 μl of a test chemical or saline at 22 ± 2°C. Disinfectant efficacy criteria were ≥6 log
10
reduction for the bacteria and the spores and ≥3 log
10
reduction for the virus. Peracetic acid (1,000 ppm) was effective in 5 min against the two bacteria and the spores but not against the virus. Chlorine dioxide (CD; 500 and 1,000 ppm) and domestic bleach (DB; 2,500, 3,500, and 5,000 ppm) were effective in 5 min, except for sporicidal activity, which needed 20 min of contact with either 1,000 ppm of CD or the two higher concentrations of DB.
Identification of
Cryptosporidium
Species and Genotypes in Scottish Raw and Drinking Waters during a One-Year Monitoring Period
Authors: Nichols R. A. B. , Connelly L. , Sullivan C. B. , Smith H. V.
Published: July 2010

We analyzed 1,042
Cryptosporidium
oocyst-positive slides (456 from raw waters and 586 from drinking waters) of which 55.7% contained 1 or 2 oocysts, to determine species/genotypes present in Scottish waters. Two nested PCR-restriction fragment length polymorphism (RFLP) assays targeting different loci (1 and 2) of the hypervariable region of the 18S rRNA gene were used for species identification, and 62.4% of samples were amplified with at least one of the PCR assays. More samples (577 slides; 48.7% from raw water and 51.3% from drinking water) were amplified at locus 1 than at locus 2 (419 slides; 50.1% from raw water and 49.9% from drinking water). PCR at loci 1 and 2 amplified 45.4% and 31.7% of samples containing 1 or 2 oocysts, respectively. We detected both human-infectious and non-human-infectious species/genotype oocysts in Scottish raw and drinking waters.
C
ryptosporidium
andersoni
,
C
ryptosporidium
parvum
, and the
Cryptosporidium
cervine genotype (now
C
ryptosporidium
ubiquitum
) were most commonly detected in both raw and drinking waters, with
C. ubiquitum
being most common in drinking waters (12.5%) followed by
C. parvum
(4.2%) and
C. andersoni
(4.0%). Numerous samples (16.6% total; 18.9% from drinking water) contained mixtures of two or more species/genotypes, and we describe strategies for unraveling their identity. Repetitive analysis for discriminating mixtures proved useful, but both template concentration and PCR assay influenced outcomes. Five novel
Cryptosporidium
spp. (SW1 to SW5) were identified by RFLP/sequencing, and
Cryptosporidium
sp. SW1 was the fourth most common contaminant of Scottish drinking water (3%).
Accidental Selection and Intentional Restoration of Sporulation-DeficientBacillus anthracisMutants
Authors: Sastalla Inka , Rosovitz M. J. , Leppla Stephen H.
Published: July 2010

We demonstrate the frequent accidental enrichment of spontaneous sporulation-deficient mutants ofBacillus anthracison solid medium and identify contributing factors. Mutations inspo0A, encoding the master regulator of sporulation initiation, were found in 38 of 53 mutants. Transductions using bacteriophage CP51 propagated on sporogenic bacteria allowed for the restoration of sporulation phenotypes.
Yersinia enterocolitica
Infection and
tcaA
-Dependent Killing of
Caenorhabditis elegans
Authors: Spanier Britta , Starke Mandy , Higel Fabian , Scherer Siegfried , Fuchs Thilo M.
Published: July 2010

Caenorhabditis elegans
is a validated model to study bacterial pathogenicity. We report that
Yersinia enterocolitica
strains W22703 (biovar 2, serovar O:9) and WA314 (biovar 1B, serovar O:8) kill
C. elegans
when feeding on the pathogens for at least 15 min before transfer to the feeding strain
Escherichia coli
OP50. The killing by
Yersinia enterocolitica
requires viable bacteria and, in contrast to that by
Yersinia pestis
and
Yersinia pseudotuberculosis
strains, is biofilm independent. The deletion of
tcaA
encoding an insecticidal toxin resulted in an OP50-like life span of
C. elegans
, indicating an essential role of TcaA in the nematocidal activity of
Y. enterocolitica
. TcaA alone is not sufficient for nematocidal activity because
E. coli
DH5α overexpressing TcaA did not result in a reduced
C. elegans
life span. Spatial-temporal analysis of
C. elegans
infected with green fluorescent protein-labeled
Y. enterocolitica
strains showed that
Y. enterocolitica
colonizes the nematode intestine, leading to an extreme expansion of the intestinal lumen. By low-dose infection with W22703 or DH5α followed by transfer to
E. coli
OP50, proliferation of
Y. enterocolitica
, but not
E. coli
, in the intestinal lumen of the nematode was observed. The titer of W22703 cells within the worm increased to over 10
6
per worm 4 days after infection while a significantly lower number of a
tcaA
knockout mutant was recovered. A strong expression of
tcaA
was observed during the first 5 days of infection.
Y. enterocolitica
WA314 (biovar 1B, serovar O:8) mutant strains lacking the
yadA
,
inv
,
yopE
, and
irp1
genes known to be important for virulence in mammals were not attenuated or only slightly attenuated in their toxicity toward the nematode, suggesting that these factors do not play a significant role in the colonization and persistence of this pathogen in nematodes. In summary, this study supports the hypothesis that
C. elegans
is a natural host and nutrient source of
Y. enterocolitica
.
APorphyromonas gingivalisMutant Defective in a Putative Glycosyltransferase Exhibits Defective Biosynthesis of the Polysaccharide Portions of Lipopolysaccharide, Decreased Gingipain Activities, Strong Autoaggregation, and Increased Biofilm Formation
Authors: Yamaguchi Mikiyo , Sato Keiko , Yukitake Hideharu , Noiri Yuichiro , Ebisu Shigeyuki , Nakayama Koji
Published: July 2010

The Gram-negative anaerobic bacteriumPorphyromonas gingivalisis a major pathogen in periodontal disease, one of the biofilm-caused infectious diseases. The bacterium possesses potential virulence factors, including fimbriae, proteinases, hemagglutinin, lipopolysaccharide (LPS), and outer membrane vesicles, and some of these factors are associated with biofilm formation; however, the precise mechanism of biofilm formation is still unknown. Colonial pigmentation of the bacterium on blood agar plates is related to its virulence. In this study, we isolated a nonpigmented mutant that had an insertion mutation within the new gene PGN_1251 (gtfB) by screening a transposon insertion library. The gene shares homology with genes encoding glycosyltransferase 1 of several bacteria. ThegtfBmutant was defective in biosynthesis of both LPSs containing O side chain polysaccharide (O-LPS) and anionic polysaccharide (A-LPS). The defect in the gene resulted in a complete loss of surface-associated gingipain proteinases, strong autoaggregation, and a marked increase in biofilm formation, suggesting that polysaccharide portions of LPSs influence attachment of gingipain proteinases to the cell surface, autoaggregation, and biofilm formation ofP. gingivalis.
Effects ofInVitroHIV-1 Infection on Mycobacterial Growth in Peripheral Blood Monocyte-Derived Macrophages
Authors: Pathak Sharad , Wentzel-Larsen Tore , Åsjö Birgitta
Published: July 2010

Coinfection with human immunodeficiency virus type 1 (HIV-1) and opportunistic mycobacteria, especiallyMycobacteriumtuberculosis, is a cause of high morbidity and mortality worldwide. Both mycobacteria and HIV-1 may infect macrophages, and thus, coinfection may generate conditions that reciprocally influence the intracellular replication of the pathogens. Elucidation of the interaction between HIV-1 and mycobacteria in their common target cell is important for understanding pathogenesis in coinfected individuals. In this study, we investigated the effects ofinvitroHIV-1 infection on the growth ofM.tuberculosis,M.avium, andM.paratuberculosisin human peripheral blood monocyte-derived macrophages. Interestingly, HIV-1 infection induced a greater bacterial burden in coinfected cell cultures for all of the mycobacterial species tested and specifically induced accelerated growth ofM.tuberculosiswith a reduced mean generation time. The interaction of HIV-1 andM.tuberculosiswas especially detrimental to the host cell, causing a significant synergistic reduction in macrophage viability. Also, inM.tuberculosis/HIV-1-coinfected cultures, increased levels of interleukin-1β (IL-1β), IL-6, IL-8, and granulocyte-macrophage colony-stimulating factor were observed and viral replication was enhanced. Overall, the present data suggest that HIV-1 infection of macrophages may impair their ability to contain mycobacterial growth. Furthermore, coinfection with HIV-1 andM.tuberculosisseems to give rise to synergistic effects at the cellular level that mutually enhance the replication of both pathogens. This may, in part, contribute to the increased morbidity and mortality seen in coinfected individuals.
Cytotoxicity of the
Bacillus cereus
Nhe Enterotoxin Requires Specific Binding Order of Its Three Exoprotein Components
Authors: Lindbäck Toril , Hardy Simon P. , Dietrich Richard , Sødring Marianne , Didier Andrea , Moravek Maximilian , Fagerlund Annette , Bock Stefanie , Nielsen Carina , Casteel Maximilian , Granum Per Einar , Märtlbauer Erwin
Published: July 2010

This study focuses on the interaction of the three components of the
Bacillus cereus
Nhe enterotoxin with particular emphasis on the functional roles of NheB and NheC. The results demonstrated that both NheB and NheC were able to bind to Vero cells directly while NheA lacked this ability. It was also shown that Nhe-induced cytotoxicity required a specific binding order of the individual components whereby the presence of NheC in the priming step as well as the presence of NheA in the final incubation step was mandatory. Priming of cells with NheB alone and addition of NheA plus NheC in the second step failed to induce toxic effects. Furthermore, in solution, excess NheC inhibited binding of NheB to Vero cells, whereas priming of cells with excess NheC resulted in full toxicity if unbound NheC was removed before addition of NheB. By using mutated NheC proteins where the two cysteine residues in the predicted β-tongue were replaced with glycine (NheC
cys−
) or where the entire hydrophobic stretch was deleted (NheC
hr−
), the predicted hydrophobic β-tongue of NheC was found essential for binding to cell membranes but not for interaction with NheB in solution. All data presented here are compatible with the following model. The first step in the mode of action of Nhe is associated with binding of NheC and NheB to the cell surface and probably accompanied by conformational changes. These events allow subsequent binding of NheA, leading to cell lysis.
Clinical Curative Effect of Acupuncture Therapy on Xerophthalmia
Authors: Gong Lan , Sun Xinghuai , Chapin William J.
Published: July 2010

This study observes changes in symptoms of xerophthalmia pre- and post-acupuncture therapy and compares the results of the acupuncture therapy (AT) group and the artificial tear control (ATC) group. Parallel comparative studies were carried out on 44 patients with xerophthalmia, who were divided into the AT group (n = 20) and the ATC group (n = 24). A 10-session acupuncture therapy program was performed for the AT group while Dextran 70 was used for the ATC group with each course of treatment lasting 21 day. Examinations were made on the day when a patient was chosen to join the study, 1 hour after completion of treatment, and 3 weeks after stopping treatment. There was no statistically significant difference in terms of the reduction of the symptoms and sign score (SSS) 1 hour after completion of treatment between the AT group and the ATC group. Three weeks after completion of treatment, the reduction of SSS for the AT group was larger than that of the ATC group, with the difference achieving statistical significance. Both acupuncture therapy and artificial tear therapy have an immediate positive effect on the symptoms of xerophthalmia, but acupuncture therapy has a longer continuous effect than that of artificial tears.
The Effects of Auricular Acupressure on Weight Loss and Serum Lipid Levels in Overweight Adolescents
Authors: Hsieh Ching Hsiu
Published: July 2010

Auricular acupressure is widely used to reduce body weight. The current study was designed to test the efficacy of auricular acupressure on weight reduction and serum total cholesterol (TC), total triglycerides (TG), high density lipids (HDL) and low density lipids (LDL) in an eight-week, randomized controlled trial of three groups of 84 adolescents aged 18–20 with a body mass index (BMI) of 23 or higher. The control group received tape treatment only and the other two experimental groups were administered acupressure using either Japanese Magnetic Pearls or vaccaria seeds. All three groups were educated on reduced calorie diets, physical activity, weight loss, and lifestyle modification. During the eight-week trial, all participants were seen weekly for 10 min per session. Anthropometric measurements of BMI and TC, TG, HDL, and LDL were performed at weeks 0 and 8 for all participants. Changes in BMI, TC, TG, HDL, and LDL were calculated from baseline to trial completion. BMI was significantly increased in the control group by +0.0457 ( p < 0.0001), it was decreased in the Japanese Magnetic Pearl group by -0.6982 ( p < 0.0001) and the vaccaria seed group by -1.2341 ( p < 0.0001). All three groups showed significant increases in TC, TG, HDL, and LDL.

In conclusion, the current study shows that auricular acupressure employing Japanese Magnetic Pearls or vaccaria seeds can decrease BMI, with the vaccaria seed method showing the greatest reduction. Auricular acupressure did not result in decreased TC, TG, HDL, or LDL in the current eight-week protocol.
Electrical Acupoint Stimulation Changes Body Composition and the Meridian Systems in Postmenopausal Women with Obesity
Authors: Lin Chia-Hsien , Lin Yu-Min , Liu Chi-Feng
Published: July 2010

This study evaluates the effects of electrical stimulation on body composition and the meridian system in postmenopausal women with obesity. Forty-one postmenopausal women were recruited in Taiwan. The body composition was used as a screening test for obesity (percentage of body fat: > 30%, waist circumference: > 80 cm). The experimental group (EG, n = 20) received modulated middle-frequency electrical stimulation treatment for 20 min twice a week for 12 consecutive weeks at the Zusanli (ST36) and Sanyinjiao (SP6) acupoints. The control group (CG, n = 21) did not receive any intervention. The measurements of body composition and the meridian system were recorded for both groups in the pre- and post-study. The results showed that the data of body composition (weight, waist and hip circumference, percentage of body fat, and percentage of lean muscle mass) changed considerably in the EG ( p < 0.05); however, no significant difference was observed in the CG. The left triple burner meridian changed notably in both EG and CG throughout the study ( p < 0.05), however there was no difference between the two groups in the overall mean value, up-down ratio, qi and blood ratio, and yin-yang ratio. Our findings suggest that modulated middle-frequency electrical stimulation could help to improve body composition in postmenopausal women with obesity, potentially providing them with better care and health by integrating Western medicine and traditional Chinese medicine.
Sairei-to Therapy on Alloimmune Recurrent Spontaneous Abortions and Alloimmune-, Autoimmune Complicated Recurrent Spontaneous Abortions
Authors: Kano Takashi , Shimizu Masahiko , Kanda Takayoshi , Hijikata Yasuyo
Published: July 2010

Alloimmune recurrent spontaneous abortion (RSA) cases that could not be treated with lymphocyte transfusion due to medical and social reasons were treated with Sairei-to therapy as an emergency measure and all four cases resulted in live births. This may show that Sairei-to treatment is effective in preventing alloimmune RSA. The efficacy of Sojyutsu-Sairei-to and Byakujyutsu-Sairei-to on autoimmune RSA has already been proven. When they were used in the treatment of alloimmune-, autoimmune complicated RSA, the abortion prevention rates were 65.4% and 82.3% respectively. These results indicate that Sairei-to is effective in the treatment of alloimmune RSA and alloimmune-, autoimmune complicated RSA.
Antidiabetic Effects of Total Flavonoids from Litsea Coreana leve on Fat-Fed, Streptozotocin-Induced Type 2 Diabetic Rats
Authors: Lu Yun-Xia , Zhang Qiu , Li Jun , Sun Yu-Xiu , Wang Ling-Yun , Cheng Wen-Ming , Hu Xiang-Yang
Published: July 2010

This study was initiated to determine the possible antidiabetic effects of total flavonoids of Litsea Coreana leve (TFLC), an alcohol extract from the dried leaves of Litsea Coreana leve, on type 2 diabetic rats. Male Sprague-Dawley rats ( n = 40, 160–180 g) were divided into two groups and fed with normal chow diet (Normal Control group) or high-fat diet (HFD) for a period of 4 weeks. After 4 weeks of dietary manipulation, the HFD-fed rats were injected with 30 mg/kg streptozocin (STZ) to induce diabetes 72 hours after STZ injection. These diabetic rats were randomly divided into 3 groups ( n = 10): Diabetic Control group, Diabetic + TFLC group and Diabetic + PIO group. Diabetic + TFLC group and Diabetic + PIO group were orally administered with 400 mg/kg TFLC or 10 mg/kg pioglitazone (all suspended in 0.5% CMC-Na) respectively for 6 weeks. All rats were examined for body weight, serum and hepatic biochemical indices, content of malondialdehyde (MDA), activities of superoxide dismutase (SOD) and pathological changes in liver and pancreas, as well as protein tyrosine phosphatase 1B (PTP1B) expression in liver. The diabetic rats became obese, insulin resistant, hyperglycemic and hyperlipidemic. Treatment with TFLC showed a significant increase in insulin sensitivity, serum HDL-C level and SOD activities, meanwhile marked decrease in body weight, serum FFA, TC, TG, LDL-C, CRP, MDA content. TFLC also attenuated pathologic alterations in liver and pancreatic islet. Furthermore, TFLC was found to decrease the expression of PTP1B in diabetic rat liver. These results suggested that TFLC could ameliorate hyperglycemia, hyperlipoidemia, inflammation and oxidation stress, as well as insulin resistance of type 2 diabetic rats.
Gingko biloba Extract (EGb 761) Prevents Cerebral Ischemia-Induced p70S6 Kinase and S6 Phosphorylation
Authors: Koh Phil-Ok
Published: July 2010

EGb 761 is an extract of Gingko biloba that exhibits neuroprotective effects against cerebral ischemia. The mammalian target of rapamycin (mTOR) is a critical downstream effector of Akt and a central regulator of ribosomal biogenesis and protein synthesis. We investigated whether EGb 761 regulates Akt downstream targets, including mTOR, p70S6 kinase, and S6 phosphorylation. Adult male rats were treated with vehicle or EGb 761 (100 mg/kg) prior to middle cerebral artery occlusion (MCAO). Brains were collected at 24 hours after MCAO and the cerebral cortex regions were examined. We previously showed that EGb 761 significantly reduces infarct volume and decreases the number of TUNEL-positive cells in the cerebral cortex. Ischemic brain injury induces a decrease in Akt up-stream target, PDK1 phosphorylation. The levels of phospho-mTOR, phospho-p70S6 kinase, and phospho-S6 are subsequently decreased in regions affected by ischemic injury. However, EGb 761 prevented injury-induced decreases in these protein levels. We confirmed that EGb 761 inhibits injury-induced decreases in the number of positive cells for phospho-p70S6 kinase and phospho-S6. The results of this study provide evidence that EGb 761 protects neuronal cells against ischemic brain injury by preventing injury-induced decreases in p70S6 kinase and S6 phosphorylation.
MEAN VALUE ANALYSIS OF SINGLE SERVER RETRIAL QUEUES
Authors: ARTALEJO J. R. , RESING J. A. C.
Published: July 2010

Mean value analysis is an elegant tool for determining mean performance measures in queueing models. In this paper we show how mean value analysis can be applied to retrial queues. First, we illustrate the technique for the standard M/G/1 retrial queue with exponential retrial times. After that we show how the relations can be adapted to obtain mean performance measures in more advanced M/G/1-type retrial queues.
A RUN-BASED ONE-AND-A-HALF-SCAN CONNECTED-COMPONENT LABELING ALGORITHM
Authors: HE LIFENG , CHAO YUYAN , SUZUKI KENJI
Published: July 2010

This paper presents a run- and label-equivalence-based one-and-a-half-scan algorithm for labeling connected components in a binary image. Major differences between our algorithm and conventional label-equivalence-based algorithms are: (1) all conventional label-equivalence-based algorithms scan all pixels in the given image at least twice, whereas our algorithm scans background pixels once and object pixels twice; (2) all conventional label-equivalence-based algorithms assign a provisional label to each object pixel in the first scan and relabel the pixel in the later scan(s), whereas our algorithm assigns a provisional label to each run in the first scan, and after resolving label equivalences between runs, by using the recorded run data, it assigns each object pixel a final label directly. That is, in our algorithm, relabeling of object pixels is not necessary any more. Experimental results demonstrated that our algorithm is highly efficient on images with many long runs and/or a small number of object pixels. Moreover, our algorithm is directly applicable to run-length-encoded images, and we can obtain contours of connected components efficiently.
ANALYSIS OF GENE EXPRESSION DATA USING RPEM ALGORITHM IN NORMAL MIXTURE MODEL WITH DYNAMIC ADJUSTMENT OF LEARNING RATE
Authors: ZHAO XING-MING , CHEUNG YIU-MING , HUANG DE-SHUANG
Published: July 2010

Microarray technology is a useful tool for monitoring the expression levels of thousands of genes simultaneously. Recently, mixture modeling has been used to extract expression signatures from gene expression profiles. In general, two separate steps are utilized to estimate the number of classes and model parameters, respectively. However, such a method is often time-consuming and leads to suboptimal solutions. In this paper, we therefore apply a one-step approach, namely Rival Penalized Expectation-Maximization (RPEM) algorithm, to analyze the gene expression data. The RPEM algorithm is capable of estimating the parameters of normal mixture model, while determining the number of classes automatically at the same time. Furthermore, we speed up the learning procedure of RPEM by proposing a new mechanism to adjust the learning rate dynamically. The numerical results on real gene expression data demonstrate that our proposed method is indeed effective and efficient.
SKELETONIZATION WITH PARTICLE FILTERS
Authors: TANG YUCHUN , BAI XIANG , YANG XINGWEI , LIN LIANG , LIU SHUWEI , LATECKI LONGIN JAN
Published: July 2010

We present a novel method to obtain high quality skeletons of binary shapes. The obtained skeletons are connected and one pixel thick. They do not require any pruning or any other post-processing. The computation is composed of two major parts. First, a small set of salient contour points is computed. We use Discrete Curve Evolution, but any other robust method could be used. Second, particle filters are used to obtain the skeleton. The main idea is that the particles walk along the skeletal paths between pairs of the salient points. We provide experimental results that clearly demonstrate that the proposed method significantly outperforms other well-known methods for skeleton computation. Moreover, we propose an extension of our method to computing skeletons of gray level images and provide promising experimental results.
A VISUAL FRAMEWORK FOR INTERACTION DETECTION IN SOCCER MATCHES
Authors: LEO MARCO , MOSCA NICOLA , SPAGNOLO PAOLO , MAZZEO PIER LUIGI , D'ORAZIO TIZIANA , DISTANTE ARCANGELO
Published: July 2010

In the last decade, soccer video analysis has received a lot of attention from the scientific community. This increasing interest is motivated by the possible applications over a wide spectrum of topics: indexing, summarization, video enhancement, team and players statistics, tactics analysis, referee support, etc. The application of computer vision methodologies in the soccer context requires many problems to be faced: ball and players have to be detected in the images in any light and weather condition, they have to be localized in the field, tracked over time and finally their interactions have to be detected and analyzed. The latter task is fundamental, especially for statistic and referee decision support purposes, but, unfortunately, it has not received adequate attention from the scientific community and a lot of research remains to be done. In this paper a multicamera system is presented to detect the ball player interactions during soccer matches. The proposed method extracts, by triangulation from multiple cameras, the 3D ball and player trajectories and, by estimating the trajectory intersections, detects the ball-player interactions. An inference process is then introduced to determine the player kicking the ball and to estimate the interaction frame. The system was tested during several matches of the Italian first division football championship and experimental results demonstrated that the proposed method is robust and accurate.
AUTOMATIC GEO-REGISTRATION FOR PORT SURVEILLANCE
Authors: CAO XIAOCHUN , WU LIN , RASHEED ZEESHAN , LIU HAIYING , CHOE TAEEUN , GUO FENG , HAERING NIELS
Published: July 2010

This paper proposes a new solution to geo-register the nearly feature-less maritime video feeds. We detect the horizon using sizable or uniformly moving vessels, and estimate the vertical apex using water reflections of the street lamps. The computed horizon and apex provide a metric rectification that removes the affine distortions and reduces the searching space for geo-registration. Geo-registration is obtained by searching the best orientation where the estimated water masks on satellite images and camera views are matched. The proposed solution has the following contributions: first, water and coastlines are used as features for registration between horizontally looking maritime views and satellite images. Second, water reflections are proposed to estimate the vertical vanishing point. Third, we give algorithms for the detection of water areas in both satellite images and camera views. Experimental results and applications on cross camera tracking are demonstrated. We also discuss several observations, as well as limitations of the proposed approach.
EARLY BUFFER PLANNING WITH CONGESTION CONTROL USING BUFFER REQUIREMENT MAP
Authors: JAHANIAN ALI , ZAMANI MORTEZA SAHEB
Published: July 2010

Buffer insertion plays an important role in circuit performance and signal integrity especially in deep submicron technologies. The stage at which buffers are inserted in a design has a large impact on the design quality. Early buffer insertion may cause misestimation due to unknown cell locations whereas buffer insertion after placement may not be very effective because the cell locations have been fixed and buffer resources may be distributed inappropriately.

In this paper, a buffer planning algorithm for floor-placement design flow is presented. This algorithm creates a map of buffer requirements in various regions of the design at the floorplanning stage and then enforces the detailed placer to distribute white spaces with respect to the estimated buffer requirement map.

Experimental results show that the proposed method improves the performance of attempted circuits with fewer buffers. Furthermore, results show that congestion, routability and design convergence are improved and the auxiliary loops are avoided in the proposed design flow. Our analyses and experiments show that the CPU time overhead of this algorithm is very small.
BIFURCATIONS AND CHAOS IN HAMILTONIAN SYSTEMS
Authors: BARRIO R. , BLESA F. , SERRANO S.
Published: July 2010

This paper deals with the use of recent computational techniques in the numerical study of qualitative properties of two degrees of freedom of Hamiltonian systems. These numerical methods are based on the computation of the OFLI2 Chaos Indicator, the Crash Test and exit basins and the skeleton of symmetric periodic orbits. As paradigmatic examples, three classical problems are studied: the Copenhagen and the (n + 1)-body ring problems and the Hénón–Heiles Hamiltonian. All the numerical integrations have been done by using the state-of-the-art numerical library TIDES based on the extended Taylor series method.
FLUCTUATIONS IN NON-EQUILIBRIUM ELECTRON GAS: EFFECT OF QUANTUM STATISTICS
Authors: KATILIUS R. , GANTSEVICH S. V. , KAGAN V. D. , MURADOV M. I.
Published: July 2010

Here we develop a mathematical apparatus to describe quasi-classical fluctuations in a non-equilibrium electron gas with electron-electron collisions. We substantiate the method by deriving, from general principles of quantum kinetics, an equation recently proposed by us for an equal-time electron-electron correlation function. The derivation is performed using the kinetic diagram technique. In degenerate non-equilibrium gas, the theory predicts that there exists a specific equal-time correlation between electrons. Due to the prevalence of small-angle electron-electron scattering, the equation in question takes a rather simple and treatable form (the Coulomb-type electron-electron interaction stands out against the background of all other types of interaction as one that does not generate, in the framework of quasi-classical approach, any direct exchange effects).
THE EFFECTS OF HRM-RELATED MECHANISMS ON COMMUNICATION IN R&D COLLABORATION
Authors: OLANDER HEIDI , HURMELINNA-LAUKKANEN PIA
Published: July 2010

Prior research has shown that the level of communication has an effect on the learning outcomes in R&D alliances and, subsequently, on performance. The level of communication depends on issues such as the systems that enhance knowledge sharing and the factors that deter knowledge flows, such as tacitness of knowledge and (deliberate) barriers set up to limit knowledge transfer. Innovations and value can only be created through sufficiently open knowledge sharing. But on the other hand, too open knowledge sharing might outrun the value gained by innovations if the knowledge lost would leave the knowledge sharing firm vulnerable. Yet, there is still a lack of understanding on which factors are responsible of the level of communication and to what extent. In particular, it has often been forgotten that HRM-related mechanisms are not only functional within firms, but also between firms. Thus, in this study, the HRM-related mechanisms that contribute to both of these areas are examined by using empirical quantitative data gathered from 83 Finnish R&D intensive firms.
USER-INVOLVEMENT AND OPEN INNOVATION: THE CASE OF DECISION-MAKER OPENNESS
Authors: JESPERSEN KRISTINA RISOM
Published: July 2010

The promise of customers as an external resource for new-product development (NPD) has been recognized in theory and practice for a long time. Technological progress has increased the interaction between companies and users. Yet the involvement of users in NPD depends on the ability of decision-makers to act as boundary spanners. There is a cognitive distance between NPD decision-makers and users. The larger this distance is, the more novel information is contained in user inputs. True open innovation requires that these cognitive distant inputs are treated in NPD. We find that decision-maker openness is significant for NPD openness to be true. Successful collaboration in form of innovations builds on involvement of launching and lead users in NPD. Our analyses show that decision-maker openness facilitates the involvement process. Further, low decision-maker openness traps the implementation of open innovation.
AN EMPIRICAL ANALYSIS ON ABSORPTIVE CAPACITY BASED ON LINKAGE WITH ACADEMIA
Authors: SAITO HIROMI , SUMIKURA KOICHI
Published: July 2010

In this paper, we empirically explain how scientific knowledge assimilated from academia affects corporate performance, particularly in the pharmaceutical industry of Japan. We use balanced panel data on 46 pharmaceutical firms in Japan for the period 1992–2005. Then, we introduce a new concept, propensity to capture basic research (PCBR), to index how much scientific knowledge firms have assimilated from universities and public research institutes. We use this index to verify whether absorption of such knowledge influences corporate performance. According to econometric analysis, PCBR is positively significant for patent applications and patent efficiency but not for number of approved drugs. This obviously implies that scientific knowledge assimilated from academia is effective for technological performance in firms. Moreover, the results suggest how R&D is structured in the organizational setup of Japanese pharmaceutical firms.
Investigation of Electrochemical Reactions beneath Paint Using a Combination of Methods
Authors: Sykes John , Xu Yan
Published: July 2010

A Fe-Zn bi-electrode coated with paint was exposed to NaCl solution, so that a well-defined galvanic cell was established with the current directly measured by a zero-resistance ammeter (ZRA). Electrochemical impedance spectroscopy (EIS) was periodically used to monitor coating behaviour for the two electrodes separately or coupled together. Potentiostatic current measurements were also made on each metal at different overpotentials to plot polarization curves. The ohmic potential drop in the paint was corrected using film resistance values determined by EIS. Evans diagrams were thus plotted from the corrected polarization curves to make a quantitative assessment of Mayne's resistance inhibition model.
Corrosion Protection Properties of Various Ligand Modified Organic Inorganic Hybrid Coating on AA 2024-T3
Authors: Padinchare Covilakath Rajath Varma , Cassidy John , Oubaha Mohamed , McDonagh Colette , Colreavy John , Duffy Brendan
Published: July 2010

The inclusion of zirconium precursors in the preparation of organosilane sol-gel coatings has been acknowledged to improve the corrosion protection performance of such coatings on aluminium and steel. Due to the inherent differences in the hydrolysis rates of the silane and zirconium precursors, various ligands were used to control the hydrolysis by decreasing the number of reactive alkoxide group. Hybrid sols were synthesised using 3-(trimethoxysilyl) propylmethacrylate (MAPTMS) and zirconium n-propoxide which was chelated with organic ligands. The selection of ligands included different organic acids, acetyl acetone and 2 2' bipyridyl. The effects of zirconia inclusion on the properties of the coatings were compared on the aerospace alloy AA 2024-T3. Dynamic light scattering (DLS) was used to measure the sol-gel particle diameter, while differential scanning calorimetry (DSC) and atomic force microscopy (AFM) were used to study thermal network stability and the surface morphology of the coating respectively. Potentiodynamic scan (PDS) and electrochemical impedance spectroscopy (EIS) were used to characterize the protective properties of the coatings, while neutral salt spray (NSS) tests were used to evaluate the coatings in an aggressive corrosive environment. The results indicate that acid chelated systems possess better corrosion protection when compared to the other ligands, due to smaller zirconium nanoparticles being formed thereby leading to improved film formation. In particular superior performance was displayed by the coatings involving 3,4 diaminobenzoic acid (DABA) due to inherent anticorrosive properties
Interleukin-10 inhibits the in vivo and in vitro adverse effects of TNF-α on the endothelium of murine aorta
Authors: Zemse Saiprasad M. , Chiao Chin Wei , Hilgers Rob H. P. , Webb R. Clinton
Published: July 2010

TNF-α is a proinflammatory cytokine and is an important mediator of maternal endothelial dysfunction leading to preeclampsia. In this study, we tested whether IL-10 protects against TNF-α-induced endothelial dysfunction in murine aorta. In in vitro experiments, aortic rings of C57BL/6 female mice were incubated in Dulbecco's modified Eagle's medium in the presence of either vehicle (distilled H2O), TNF-α (4 nmol/l), or recombinant mouse IL-10 (300 ng/ml) or in the presence of both TNF-α and IL-10 for 22 h at 37°C. In in vivo experiments C57BL6/IL-10 knockout female mice were treated with saline or TNF-α (220 ng·kg−1·day−1) for 14 days. Aortic rings were isolated from in vitro and in vivo experiments and mounted in a wire myograph (Danish Myotech) and stretched to a tension of 5 mN. Endothelium-dependent relaxation was assessed by constructing cumulative concentration-response curves to acetylcholine (ACh, 0.001–10 μmol/l) during phenylephrine (10 μmol/l)-induced contraction. As a result, overnight exposure of aortic rings to TNF-α resulted in significant blunted maximal relaxing responses ( Emax) to ACh compared with untreated rings (22 ± 4 vs. 82 ± 3%, respectively). IL-10 knockout mice treated with TNF-α showed significant impairment in ACh responses ( Emax) compared with C57BL/6 mice treated with TNF-α (51 ± 3 vs. 72 ± 3%, respectively). Western blot analysis showed that endothelial nitric oxide synthase (eNOS) expression was reduced by TNF-α in in vitro and in vivo experiments, whereas IL-10 restored the eNOS expression. In conclusion, the anti-inflammatory cytokine IL-10 prevents impairment in endothelium-dependent vasorelaxation caused by TNF-α by protecting eNOS expression.