bluuebunny/crossref_metadata_2025 huggingface dataset:
Deficiency of Neutrophil Bactericidal Activity in Term and Preterm Infants
Authors: Chirico Gaetano , Marconi Massimo , De Amici Mara , Gasparoni Antonella , Mingrat Gabriella , Chiara Alberto , Rondini Giorgio , Ugazio Alberto G.
Published: September 2009

The present longitudinal study of 40 healthy term infants and 20 preterm infants shows that neutrophil bactericidal activity against Staphylococcus aureus and Streptococcus faecalis is transiently but significantly impaired in term infants during the 1st week of life. The deficiency is more severe and prolonged in preterm infants, and may contribute to the neonate’s increased susceptibility to infections.
Effect of Nutrition on Tissue Carnitine Concentrations in Infants of Different Gestational Ages
Authors: Penn Duna , Ludwigs Britta , Schmidt-Sommerfeld Eberhard , Pascu Filon
Published: September 2009

To investigate the effect of nutrition on tissue carnitine concentrations in infants of different gestational ages, specimens of muscle, heart, liver and kidney obtained at autopsy from 62 infants were analyzed for total acid-soluble carnitine content. Immature infants had smaller carnitine tissue reserves than term infants. Parenterally alimented premature infants (> 10 days old) had lower carnitine levels in heart, liver and kidney than those dying within 24 h after birth. Infants who received oral or intravenous carnitine had larger carnitine tissue reserves than those who did not. These data suggest that both gestational age and exogenous carnitine supply affect tissue carnitine reserves.
In vitro Permeability of the Pig Placenta in the Last Third of Gestation
Authors: Michael Kalliope , Ward B.S. , Moore W.M.O.
Published: September 2009

The pig placenta is membranous throughout gestation and is suitable for investigation as a membrane system. The site of maternal-fetal exchange in vivo is used for permeability measurements in vitro and its surface area can be measured morphometrically. Fetal weight, placental weight, placental DNA content, placental macroscopic surface area, epithelio-chorial membrane area and thickness, and permeability in vitro to urea, tritiated water and sodium were measured in eight conceptuses aged between 79 and Ill days. These solutes were selected in order to facilitate comparison with data for sheep. Urea permeability per unit DNA increased throughout the last third of gestation although placental weight and DNA content ceased to increase before term.
The Effects of Arterial Glucose Infusion above the Celiac Axis in the Neonatal Lamb
Authors: Cowett Richard M. , Tenenbaum Denis G. , Fatoba Olu , Oh William
Published: September 2009

Refractory hypoglycemia has been reported in an infant receiving glucose infusion via an umbilical artery catheter (UAC) above the celiac axis. To prove the hypothesis that hypoglycemia resulted from direct glucose infusion to the pancreas, 15 term spontaneously delivered lambs were infused with 5.3 ± 0.1 mg·kg––1·min––1 of glucose via an arterial catheter. In 9 glucose was infused below the celiac, and the glucose production rate (GPR) was derived. After a recovery period, the study was repeated with glucose infused above the celiac. During glucose infusion above the celiac, the plasma glucose concentration was lower than when the infusion was given below the celiac (140 ± 6 vs. 175 ± 11 mg/dl, p < 0.01). There was also a fall in the average GPR (3.7 ± 0.5 vs. 5.5 ± 0.8 mg·kg––1·min––1, p < 0.05). In 6 lambs the study was performed in the reverse sequence (high then low infusion) and no differences were noted in the parameters measured. However, there was a marked heterogeneity in the paired GPR in these lambs. We conclude that direct glucose infusion above the celiac increases glucose delivery to the pancreas. This produces increased insulin delivery to the portal system resulting in suppressed GPR and reduction in plasma glucose concentration. These changes may account for refractory hypoglycemia in infants clinically when glucose is infused above the celiac through a UAC.
Effect of Low-Dose Dopamine Infusion on Prolactin and Thyrotropin Secretion in Preterm Infants with Hyaline Membrane Disease
Authors: Sen I. , Tulassay T. , Kiszel J. , Ruppert F. , Sulyok E. , Ertl T. , Bódis J. , Csömör S.
Published: September 2009

The effect of low-dose (2–4 μg/kg/min) and long-term (≥ 46 h) dopamine infusion on serum prolactin and thyrotropin concentrations was investigated in 8 preterm infants with hyaline membrane disease. Dopamine was administered for systemic hypotension and/or for impending renal failure. Serum prolactin decreased from 1,314.5 ± 422.7 μU/ml to 489.9 ± 464.1 μU/ml (p < 0.005), while serum thyrotropin fell from 3.77 ± 2.27 μU/ml to 1.01 ± 0.25 μU/ml (p < 0.025) during dopamine infusion. Our data indicate that exogenous dopamine exerts an inhibitory effect on the secretion of prolactin and thyrotropin even in the sick preterm neonate. The role of prolactin in fetal lung maturation and in regulation of the neonatal tissue water stores is discussed. The results of the present study are also useful in explaining the renal effects of long-term low-dose dopamine infusion in the sick preterm infant.
Synthesis of C20 and C22 Polyunsaturated Fatty Acids by the Placenta of the Sheep
Authors: Noble R.C. , Shand J.H. , Christie W.W.
Published: September 2009

Incubation in vitro of sheep placental homogenates with [1–14C] oleic, Hnoleic and linolenic acids resulted in extensive amounts of radioactivity becoming associated with C20 and C22 polyunsaturated fatty acid products. The fatty acids of the fetal plasma displayed substantial levels of both C20 and C22 polyunsaturated fatty acids, including the n-9 eicosatrienoic fatty acid associated with essential fatty acid deficiency, but extremely low levels of hnoleic and linolenic acids. A role for the placenta in the provision to the fetus of a range of C20 and C22 polyunsaturated fatty acids derived from C18 fatty acid precursors is implicated.
Iloprost Improves Gas Exchange and Exercise Tolerance in Patients with Pulmonary Hypertension and Chronic Obstructive Pulmonary Disease
Authors: Dernaika Tarek A. , Beavin Mikel , Kinasewitz Gary T.
Published: September 2009

Background: Nonselective systemic vasodilators worsen ventilation perfusion (V/Q) matching and gas exchange in patients with chronic obstructive pulmonary disease (COPD). Inhaled iloprost has the potential to act preferentially in ventilated regions of the lung, thereby reducing pulmonary hypertension (PH) while alveolar ventilation is still maintained. Objectives: To investigate the acute effects of inhaled iloprost on V/Q matching in patients with COPD and PH. Methods: Ten males with COPD and PH on echocardiography were evaluated before and after inhaling 2 doses of iloprost (2.5 µg). Measurements included lung function, arterial blood gas, 6-min walk test (6MWT) as well as ventilatory equivalents for oxygen (VE/VO2) and carbon dioxide (VE/VCO2) taken at baseline, 30 min following each dose of iloprost, and 2 h after the second dose. Results: Mean differences in VE/VCO2 and VE/VO2 were –13.3 (95% CI –36.5 to –2.7; p = 0.002) and –15.0 (95% CI –36.7 to –0.4; p = 0.02), respectively, and the mean change in (A-a) gradient was –3.7 mm Hg (95% CI –6.1 to –1.0; p = 0.01) after a single dose of iloprost, whereas mean improvement in 6MWT was 49.8 m (95% CI 14.8 to 84.7; p = 0.02). Arterial blood gas, venous admixture, dead space fraction and lung functions were maintained after iloprost. The effects of iloprost were reproducible after the second dose. All measurements returned to baseline 2 h after the last dose. No adverse effects on systemic blood pressure or oxygen saturation were seen. Conclusions: Iloprost inhalation was safe in patients with COPD and PH, and was associated with improved V/Q matching and exercise tolerance.
Cross-Sectional Study of the Characteristics of Reported Elder Self-Neglect in a Community-Dwelling Population: Findings from a Population-Based Cohort
Authors: Dong Xin-Qi , Simon Melissa , Evans Denis
Published: September 2009

Background: Elder self-neglect is an important public health issue. However, little is known about the characteristics of self-neglect and its association with social factors among community-dwelling populations. Objectives: (1) To examine the sociodemographic, health-related and psychosocial characteristics of reported elder self-neglect; (2) to examine the association of social network and social engagement with reported self-neglect. Methods: Population-based study conducted from 1993 to 2005 of community-dwelling subjects (n = 9,056) participating in the Chicago Health and Aging Project (CHAP). Subsets of the CHAP subjects (n = 1,812) were identified for suspected self-neglect by the social services agency, which also assessed the severity. This reported group was compared with the unreported group in the CHAP across the sociodemographic, health-related and psychosocial variables. Logistical regressions were used to assess the association of social factors and self-neglect. Results: Older age, women, African-Americans, and those with lower education or lower income were more likely to be reported for self-neglect. Those reported for self-neglect were more likely to have lower levels of cognitive and physical function, nutritional status, psychosocial function and a higher number of medical comorbidities. After adjusting for confounders, lower levels of social network and social engagement were significantly associated with an increased risk of reported self-neglect. Among the reported cases of self-neglect, the study found increased trends of older age, women, African-American, lower income, lower cognitive and physical function, lower social engagement and a higher number of chronic medical conditions with self-neglect severity. Conclusion: Reported self-neglect elders have multiple sociodemographic, health- related and psychosocial characteristics that are different than elders not reported. Lower levels of social network and social engagement were associated with increased risk of self-neglect.
Dynamic Observation of Mechanically-Injured Mouse Femoral Artery Reveals an Antiinflammatory Effect of Renin Inhibitor
Authors: Ino Jun , Kojima Chiari , Osaka Mizuko , Nitta Kosaku , Yoshida Masayuki
Published: September 2009

Objective—

The renin-angiotensin-aldosterone system (RAS) plays a central role in atherosclerosis. To investigate the effects of a direct renin inhibitor aliskiren on vascular inflammation, we conducted leukocyte adhesion assays in vivo and in vitro using a novel real-time imaging system.

Methods and Results—

Aliskiren (10 mg/kg/d) or PBS was administered to C57BL/6 mice (6–7 weeks of age; Oriental Yeast, Tokyo, Japan) for 2 weeks via an osmotic pump. Blood pressure was not significantly changed in the 2 groups throughout the experimental period. A perivascular cuff injury was then introduced to the femoral artery and real-time intravital microscopic observation was conducted 24 hours after injury. The number of adherent leukocytes was elevated in the injured mice without aliskiren (43.8±9.3/10
−2
mm
2
), whereas that was significantly reduced in the mice with aliskiren (18.4±4.4,
P
<0.05). Treatment of human umbilical vein endothelial cells (HUVECs) with aliskiren significantly reduced the adhesion of THP-1 cells to TNF-α–activated HUVECs (
P
<0.05). Interestingly, TNF-α–induced renin activity and angiotensin II production in HUVECs were also blunted by aliskiren. Furthermore, exogenous renin and angiotensin II abrogated the aliskiren-mediated reduction of THP-1 cell adhesion to HUVECs.

Conclusions—

Our in vivo and in vitro findings indicate a pivotal role for renin inhibition in vascular inflammation independent of blood pressure.
Actin-Binding Rho Activating Protein (
Abra
) Is Essential for Fluid Shear Stress-Induced Arteriogenesis
Authors: Troidl Kerstin , Rüding Inka , Cai Wei-Jun , Mücke Yvonne , Grossekettler Leonie , Piotrowska Izabela , Apfelbeck Hanna , Schierling Wilma , Volger Oscar L. , Horrevoets Anton J. , Grote Karsten , Schmitz-Rixen Thomas , Schaper Wolfgang , Troidl Christian
Published: September 2009

Objective—

Arteriogenesis, the development of a collateral circulation, is important for tissue survival but remains functionally defective because of early normalization of fluid shear stress (FSS). Using a surgical model of chronically elevated FSS we showed that rabbits exhibited normal blood flow reserve after femoral artery ligature (FAL). Inhibition of the Rho pathway by Fasudil completely blocked the beneficial effect of FSS. In a genome-wide gene profiling we identified
actin-binding Rho activating protein
(
Abra
), which was highly upregulated in growing collaterals.

Methods and Results—

qRT-PCR and Western blot confirmed highly increased FSS-dependent expression of
Abra
in growing collaterals. NO blockage by L-NAME abolished FSS-generated
Abra
expression as well as the whole arteriogenic process. Cell culture studies demonstrated an Abra-triggered proliferation of smooth muscle cells through a mechanism that requires Rho signaling. Local intracollateral adenoviral overexpression of
Abra
improved collateral conductance by 60% in rabbits compared to the natural response after FAL. In contrast, targeted deletion of
Abra
in CL57BL/6 mice led to impaired arteriogenesis.

Conclusions—

FSS-induced
Abra
expression during arteriogenesis is triggered by NO and leads to stimulation of collateral growth by smooth muscle cell proliferation.
Specification of the Cardiac Conduction System by Transcription Factors
Authors: Hatcher Cathy J. , Basson Craig T.
Published: September 2009

Abstract:

Diseases of the cardiovascular system that cause sudden cardiac deaths are often caused by lethal arrhythmias that originate from defects in the cardiac conduction system. Development of the cardiac conduction system is a complex biological process that can be wrought with problems. Although several genes involved in mature conduction system function have been identified, their association with development of specific subcomponents of the cardiac conduction system remains challenging. Several transcription factors, including homeodomain proteins and T-box proteins, are essential for cardiac conduction system morphogenesis and activation or repression of key regulatory genes. In addition, several transcription factors modify expression of genes encoding the ion channel proteins that contribute to the electrophysiological properties of the conduction system and govern contraction of the surrounding myocardium. Loss of transcriptional regulation during cardiac development has detrimental effects on cardiogenesis that may lead to arrhythmias. Human genetic mutations in some of these transcription factors have been identified and are known to cause congenital heart diseases that include cardiac conduction system malformations. In this review, we summarize the contributions of several key transcription factors to specification, patterning, maturation, and function of the cardiac conduction system. Further analysis of the molecular programs involved in this process should lead to improved diagnosis and therapy of conduction system disease.
Interrater Agreement for Final Infarct MRI Lesion Delineation
Authors: Neumann Anders B. , Jonsdottir Kristjana Y. , Mouridsen Kim , Hjort Niels , Gyldensted Carsten , Bizzi Alberto , Fiehler Jens , Gasparotti Roberto , Gillard Jonathan H. , Hermier Marc , Kucinski Thomas , Larsson Elna-Marie , Sørensen Leif , Østergaard Leif
Published: September 2009

Background and Purpose—

Lesion volume measured on follow-up magnetic resonance imaging (MRI) is commonly used as an outcome parameter in clinical stroke trials. However, few studies have evaluated the optimal sequence choice and the interrater reliability of this outcome measure. The objective of this study was to quantify the geometric interrater agreement for lesion delineation of chronic infarcts on T2-weighted and fluid-attenuated inverse recovery (FLAIR) MRI.

Methods—

In a retrospective study of 14 patients, lesions on 90-day follow-up FLAIR and T2 fast spin echo MRI were outlined by 9 independent, blinded, experienced neuroradiologists. Voxel-wise interrater agreement was measured as (1) the volume of the intersection of individual rater’s lesion outlines relative to the mean lesion volume (overlap ratio) and (2) the Hausdorff distance between the lesion markings.

Results—

Mean patient age was 64.4 years (range, 45 to 79). Lesion volumes on FLAIR were, on average, 2.5 mL greater than were T2 volumes (median;
P
<0.001). We found considerable differences between raters’ lesion markings, but interrater agreement was consistently better on FLAIR than on T2 images, as measured by a greater overlap ratio (
P
<0.0001) and a smaller Hausdorff distance (
P
<0.0001) on FLAIR than on T2.

Conclusions—

FLAIR should be used to quantify follow-up infarct size to minimize interrater variability. Our study suggests that imaging analysis performed by 1 or a few trained readers may be preferred. Future studies should address objective and preferably automated criteria for final lesion delineation.
Identification of a bacteriocin and its cognate immunity factor expressed by Moraxella catarrhalis
Authors: Attia Ahmed S , Sedillo Jennifer L , Hoopman Todd C , Liu Wei , Liu Lixia , Brautigam Chad A , Hansen Eric J
Published: September 2009

Background

Bacteriocins are antimicrobial proteins and peptides ribosomally synthesized by some bacteria which can effect both intraspecies and interspecies killing.

Results

Moraxella catarrhalis strain E22 containing plasmid pLQ510 was shown to inhibit the growth of M. catarrhalis strain O35E. Two genes (mcbA and mcbB) in pLQ510 encoded proteins predicted to be involved in the secretion of a bacteriocin. Immediately downstream from these two genes, a very short ORF (mcbC) encoded a protein which had some homology to double-glycine bacteriocins produced by other bacteria. A second very short ORF (mcbI) immediately downstream from mcbC encoded a protein which had no significant similarity to other proteins in the databases. Cloning and expression of the mcbI gene in M. catarrhalis O35E indicated that this gene encoded the cognate immunity factor. Reverse transcriptase-PCR was used to show that the mcbA, mcbB, mcbC, and mcbI ORFs were transcriptionally linked. This four-gene cluster was subsequently shown to be present in the chromosome of several M. catarrhalis strains including O12E. Inactivation of the mcbA, mcbB, or mcbC ORFs in M. catarrhalis O12E eliminated the ability of this strain to inhibit the growth of M. catarrhalis O35E. In co-culture experiments involving a M. catarrhalis strain containing the mcbABCI locus and one which lacked this locus, the former strain became the predominant member of the culture after overnight growth in broth.

Conclusion

This is the first description of a bacteriocin and its cognate immunity factor produced by M. catarrhalis. The killing activity of the McbC protein raises the possibility that it might serve to lyse other M. catarrhalis strains that lack the mcbABCI locus, thereby making their DNA available for lateral gene transfer.
Applied public health research - falling through the cracks?
Authors: Simmons Rebecca K , Ogilvie David , Griffin Simon J , Sargeant Lincoln A
Published: September 2009

Background

There is a degree of dissonance between the types of evaluative research required by organisations providing or commissioning health care, those recommended by organisations developing evidence-based guidance, and those which research funding bodies are prepared to support.

Methods

We present a case study of efforts to establish a pragmatic but robust evaluation of local exercise referral schemes. We considered the epidemiological, ethical and practical advantages and disadvantages of a number of study designs and applied for research funding based on an uncontrolled design, outlining the difficulties of carrying out a randomised controlled trial to evaluate an existing service.

Results

Our proposal was praised for its relevance and clear patient outcomes, but the application was twice rejected because both funders and reviewers insisted on a randomised controlled trial design, which we had found to be impractical, unacceptable to service users and potentially unethical.

Conclusion

The case study highlights continuing challenges for applied public health research in the current funding climate.
Blockade of Wnt-1 signaling leads to anti-tumor effects in hepatocellular carcinoma cells
Authors: Wei Wei , Chua Mei-Sze , Grepper Susan , So Samuel K
Published: September 2009

Background

Hepatocellular carcinoma (HCC) is an aggressive cancer, and is the third leading cause of cancer death worldwide. Standard therapy is ineffective partly because HCC is intrinsically resistant to conventional chemotherapy. Its poor prognosis and limited treatment options make it critical to develop novel and selective chemotherapeutic agents. Since the Wnt/β-catenin pathway is essential in HCC carcinogenesis, we studied the inhibition of Wnt-1-mediated signaling as a potential molecular target in HCC.

Results

We demonstrated that Wnt-1 is highly expressed in human hepatoma cell lines and a subgroup of human HCC tissues compared to paired adjacent non-tumor tissues. An anti-Wnt-1 antibody dose-dependently decreased viability and proliferation of Huh7 and Hep40 cells over-expressing Wnt-1 and harboring wild type β-catenin, but did not affect normal hepatocytes with undetectable Wnt-1 expression. Apoptosis was also observed in Huh7 and Hep40 cells after treatment with anti-Wnt-1 antibody. In these two cell lines, the anti-Wnt-1 antibody decreased β-catenin/Tcf4 transcriptional activities, which were associated with down-regulation of the endogenous β-catenin/Tcf4 target genes c-Myc, cyclin D1, and survivin. Intratumoral injection of anti-Wnt-1 antibody suppressedin vivotumor growth in a Huh7 xenograft model, which was also associated with apoptosis and reduced c-Myc, cyclin D1, and survivin expressions.

Conclusion

Our results suggest that Wnt-1 is a survival factor for HCC cells, and that the blockade of Wnt-1-mediated signaling may offer a potential pathway-specific therapeutic strategy for the treatment of a subgroup of HCC that over-expresses Wnt-1.
Preclinical characterization of DEKAVIL (F8-IL10), a novel clinical-stage immunocytokine which inhibits the progression of collagen-induced arthritis
Authors: Schwager Kathrin , Kaspar Manuela , Bootz Frank , Marcolongo Roberto , Paresce Erberto , Neri Dario , Trachsel Eveline
Published: September 2009

Introduction

In this article, we present a comparative immunohistochemical evaluation of four clinical-stage antibodies (L19, F16, G11 and F8) directed against splice isoforms of fibronectin and of tenascin-C for their ability to stain synovial tissue alterations in rheumatoid arthritis patients. Furthermore we have evaluated the therapeutic potential of the most promising antibody, F8, fused to the anti-inflammatory cytokine interleukin (IL) 10.

Methods

F8-IL10 was produced and purified to homogeneity in CHO cells and shown to comprise biological active antibody and cytokine moieties by binding assays on recombinant antigen and by MC/9 cell proliferation assays. We have also characterized the ability of F8-IL10 to inhibit arthritis progression in the collagen-induced arthritis mouse model.

Results

The human antibody F8, specific to the extra-domain A of fibronectin, exhibited the strongest and most homogenous staining pattern in synovial biopsies and was thus selected for the development of a fully human fusion protein with IL10 (F8-IL10, also named DEKAVIL). Following radioiodination, F8-IL10 was able to selectively target arthritic lesions and tumor neo-vascular structures in mice, as evidenced by autoradiographic analysis and quantitative biodistribution studies. The subcutaneous administration route led to equivalent targeting results when compared with intravenous administration and was thus selected for the clinical development of the product. F8-IL10 potently inhibited progression of established arthritis in the collagen-induced mouse model when tested alone and in combination with methotrexate. In preparation for clinical trials in patients with rheumatoid arthritis, F8-IL10 was studied in rodents and in cynomolgus monkeys, revealing an excellent safety profile at doses tenfold higher than the planned starting dose for clinical phase I trials.

Conclusions

Following the encouraging preclinical results presented in this paper, clinical trials with F8-IL10 will now elucidate the therapeutic potential of this product and whether the targeted delivery of IL10 potentiates the anti-arthritic action of the cytokine in rheumatoid arthritis patients.
Sepsis-associated microvascular dysfunction measured by peripheral arterial tonometry: an observational study
Authors: Davis Joshua S , Yeo Tsin W , Thomas Jane H , McMillan Mark , Darcy Christabelle J , McNeil Yvette R , Cheng Allen C , Celermajer David S , Stephens Dianne P , Anstey Nicholas M
Published: September 2009

Introduction

Sepsis has a high mortality despite advances in management. Microcirculatory and endothelial dysfunction contribute to organ failure, and better tools are needed to assess microcirculatory responses to adjunctive therapies. We hypothesised that peripheral arterial tonometry (PAT), a novel user-independent measure of endothelium-dependent microvascular reactivity, would be impaired in proportion to sepsis severity and related to endothelial activation and plasma arginine concentrations.

Methods

Observational cohort study in a 350-bed teaching hospital in tropical Australia. Bedside microvascular reactivity was measured in 85 adults with sepsis and 45 controls at baseline and 2-4 days later by peripheral arterial tonometry. Microvascular reactivity was related to measures of disease severity, plasma concentrations of L-arginine (the substrate for nitric oxide synthase), and biomarkers of endothelial activation.

Results

Baseline reactive hyperaemia index (RH-PAT index), measuring endothelium-dependent microvascular reactivity; (mean [95% CI]) was lowest in severe sepsis (1.57 [1.43-1.70]), intermediate in sepsis without organ failure (1.85 [1.67-2.03]) and highest in controls (2.05 [1.91-2.19]); P < 0.00001. Independent predictors of baseline RH-PAT index in sepsis were APACHE II score and mean arterial pressure, but not plasma L-arginine or markers of endothelial activation. Low baseline RH-PAT index was significantly correlated with an increase in SOFA score over the first 2-4 days (r = -0.37, P = 0.02).

Conclusions

Endothelium-dependent microvascular reactivity is impaired in proportion to sepsis severity and suggests decreased endothelial nitric oxide bioavailability in sepsis. Peripheral arterial tonometry may have a role as a user-independent method of monitoring responses to novel adjunctive therapies targeting endothelial dysfunction in sepsis.
T Helper Type 17 Immune Response Plays an Indispensable Role for Development of Iodine-Induced Autoimmune Thyroiditis in Nonobese Diabetic-H2h4 Mice
Authors: Horie Ichiro , Abiru Norio , Nagayama Yuji , Kuriya Genpei , Saitoh Ohki , Ichikawa Tatsuki , Iwakura Yoichiro , Eguchi Katsumi
Published: September 2009

T helper type 1(Th1)/Th2 paradigm has been expanded by discovery of a novel effector T cell (Teff) subset, Th17 cells, which produce a proinflammatory cytokine IL-17. Th17 cells have recently been shown to play a major role in numerous autoimmune diseases that had previously been thought to be Th1-dominant diseases. We here studied the significance of Th17 cells in iodine-induced autoimmune thyroiditis in nonobese diabetic-H2h4 mice, a mouse model of Hashimoto’s thyroiditis in humans, which spontaneously develop antithyroglobulin autoantibodies and intrathyroidal lymphocyte infiltration when supplied with iodine in the drinking water. We observed increased numbers of Th1 and Th17 cells in spleen and accumulation of both types of Teff in the thyroid glands of iodine-fed wild-type mice, indicating that Th17 cells as well as Th1 cells constitute thyroid lesions. Furthermore, the incidence and severity of intrathyroidal lymphocyte infiltration, and the titers of antithyroglobulin autoantibodies were markedly reduced in iodine-treated IL-17−/− mice as compared with wild-type mice. Of interest, IL-17+/− mice showed an intermediate phenotype. Therefore, the present study, together with a previous report demonstrating the importance of Th1, not Th2, immune response for developing thyroiditis using mice deficient for interferon-γ or IL-4, clearly indicates that both Th1 and Th17 cells are critical Teff subsets for the pathogenesis of spontaneous autoimmune thyroiditis in nonobese diabetic-H2h4 mice.
Patched 1 is a crucial determinant of asymmetry and digit number in the vertebrate limb
Authors: Butterfield Natalie C. , Metzis Vicki , McGlinn Edwina , Bruce Stephen J. , Wainwright Brandon J. , Wicking Carol
Published: September 2009

The vertebrate hedgehog receptor patched 1 (Ptc1) is crucial for negative regulation of the sonic hedgehog (Shh) pathway during anterior-posterior patterning of the limb. We have conditionally inactivated Ptc1 in the mesenchyme of the mouse limb using Prx1-Cre. This results in constitutive activation of hedgehog (Hh) signalling during the early stages of limb budding. Our data suggest that variations in the timing and efficiency of Cre-mediated excision result in differential forelimb and hindlimb phenotypes. Hindlimbs display polydactyly (gain of digits) and a molecular profile similar to the Gli3 mutant extra-toes. Strikingly, forelimbs are predominantly oligodactylous (displaying a loss of digits), with a symmetrical, mirror-image molecular profile that is consistent with re-specification of the anterior forelimb to a posterior identity. Our data suggest that this is related to very early inactivation of Ptc1 in the forelimb perturbing the gene regulatory networks responsible for both the pre-patterning and the subsequent patterning stages of limb development. These results establish the importance of the downstream consequences of Hh pathway repression, and identify Ptc1 as a key player in limb patterning even prior to the onset of Shh expression.
Dendrite branching and self-avoidance are controlled by Turtle, a conserved IgSF protein in Drosophila
Authors: Long Hong , Ou Yimiao , Rao Yong , van Meyel Donald J.
Published: September 2009

The dendritic trees of neurons result from specific patterns of growth and branching, and dendrite branches of the same neuron avoid one another to spread over a particular receptive field. Recognition molecules on the surfaces of dendrites influence these patterning and avoidance processes by promoting attractive, repulsive or adhesive responses to specific cues. The Drosophila transmembrane protein Turtle (Tutl) and its orthologs in other species are conserved members of the immunoglobulin superfamily, the in vivo functions of which are unknown. In Drosophila sensory neurons,we show that the tutl gene is required to restrain dendrite branch formation in neurons with simple arbors, and to promote dendrite self-avoidance in neurons with complex arbors. The cytoplasmic tail of Tutl is dispensable for control of dendrite branching, suggesting that Tutl acts as a ligand or co-receptor for an unidentified recognition molecule to influence the architecture of dendrites and their coverage of receptive territories.
A Comparison of Warm Asphalt Binder Aging with Laboratory Aging Procedures
Authors: Gandhi Tejash , Akisetty Chandrakiran , Amirkhanian Serji
Published: September 2009

Warm asphalt has been gaining increasing popularity in recent years; however there are several characteristics about warm asphalt that are still unknown. While several studies have been conducted to study the performance of warm asphalt mixtures, aging characteristics of warm mix asphalt (WMA) binders are not known in great detail. This paper presents the results of a limited study to evaluate the aging characteristics of two WMA binders artificially aged in the rolling thin film oven (RTFO) and the pressure aging vessel and comparing them with binder extracted from freshly prepared and artificially aged warm asphalt mixtures. RTFO aging was performed at 163°C and a lower temperature to simulate warm asphalt aging. Tests on binders aged in the laboratory and binders extracted from freshly mixed and aged mixtures indicated that the WMA binders extracted from WMA mixtures had significantly lower viscosities and G∗/sin δ compared to binders extracted from hot mix asphalt (HMA) and binders aged in the RTFO at 163°C (325°F). This indicates that the lower mixing and compaction temperatures reduce the aging of the warm asphalt binders. Also, binders extracted from WMA had significantly lower creep stiffness values and significantly higher m-values compared to warm asphalt binders aged in the RTFO at 163°C (325°F) and binders extracted from HMA. Binders containing WMA additives did not have higher G∗ sin δ values, indicating that the warm asphalt additives do not negatively affect the fatigue properties of the binders. Gel permeation chromatography analysis indicated that the addition of the warm asphalt additives did not have any significant effect on the %LMS of the binders used in this study.
Distress Evolution in Highway Flexible Pavements: A 5-Year Study at the Korea Highway Corporation Test Road
Authors: Seo Youngguk
Published: September 2009

In Korea, a 7.7 km-long test road was constructed with an aim to better understand the behavior of pavements and to develop a mechanistic-empirical pavement design guide (MEPDG). This two lane highway consisted of asphalt and concrete pavements that were further divided into diverse sections: 33 asphalt sections and 25 concrete sections. Construction of the test road began in 1997 and ended in 2002. It opened to traffic in March 2004. So far, many field tests have been carried out to evaluate the response and performance of pavements. At asphalt sections, the first attempt was made to correlate design parameters with the performance of pavements, and this is the focus of this paper. Performance was characterized by the evolution of failures, such as rutting, cracking, and longitudinal road profile. Design parameters included surface type, base type, base thickness, and anti-frost layer. Field surveys were made with an automatic road analyzer for the 2002–2007 period, and trends in pavement failures were analyzed with respect to individual design parameters. Also, a highway present condition index (HPCI) was adopted to assess the overall performance of individual sections. Findings of this study are being used to validate pavement performance models incorporated into the MEPDG that is scheduled to be released in 2010.
Brinell and Vickers Hardness Measurement Using Image Processing and Analysis Techniques
Authors: Filho Pedro Pedrosa Rebouças , Cavalcante Tarique da Silveira , de Albuquerque Victor Hugo C. , Tavares João Manuel R. S.
Published: September 2009

Mechanical hardness testing is fundamental in the evaluation of the mechanical properties of metallic materials due to the fact that the hardness values allow one to determine the wear resistance of the material involved, as well as the approximate values of its ductility and flow tension, among a number of other key characteristics. As a result, the main objective of the present work has been the development and analysis of a computational methodology capable of determining the Brinell and Vickers hardness values from hardness indentation images, which are based on image processing and analysis algorithms. In order to validate the methodology that has been developed, comparisons of the results resulting from the consideration of ten indentation image samples obtained through the conventional manual hardness measurement approach and a computational methodology have been carried out. This analysis allows one to conclude that the semi-automatic measurement of Vickers and Brinell hardnesses by the computational approach is easier, faster, and less dependent on the operator’s subjectivity.
Ultrasonic Monitoring Technology for Polymer Compounding Extrusion
Authors: Chen Youxing , Wang Zhaoba , Zhao Xia , Jin Yong
Published: September 2009

In order to optimize control of the extrusion process of polymer compounds in the screw extruder, it is necessary to monitor the compounding state in-line. Therefore a polyetheretherketone (PEEK) buffer rod with a cooling device is analyzed and designed. The ultrasound probe, whose performance is tested at high temperature, is composed of a newly developed PEEK buffer rod and ultrasonic transducer. Then the ultrasonic probe is applied for the in-line ultrasonic monitoring of polymer extrusion of low-density polyethylene (LDPE)/CaCO3 compounds and LDPE/BaSO4 compounds. The results show that the attenuation has a relation to the composition of the polymer compounds and filler concentration. The results also indicate that the presented ultrasonic technique may be used for determining the mixing status of polymer/filler systems with multi-probes at different locations inside the extruder barrel during the extrusion processes.
Benchmarking and Performance Modeling of Event-Based SystemsModellierung und Bewertung von Ereignis-basierten Systemen
Authors: Kounev Samuel , Sachs Kai
Published: September 2009

Event-based systems are used increasingly often to build loosely-coupled distributed applications. With their growing popularity and gradual adoption in mission critical areas, the need for novel techniques for benchmarking and performance modeling of event-based systems is increasing. In this article, we provide an overview of the state-of-the-art in this area considering both centralized systems based on message-oriented middleware as well as large-scale distributed publish/subscribe systems. We consider a number of specific techniques for benchmarking and performance modeling, discuss their advantages and disadvantages, and provide references for further information. The techniques we review help to ensure that systems are designed and sized to meet their quality-of-service requirements.
Security in Multi-domain Event-based SystemsSicherheit in ereignis-basierten Mehrdomänensystemen
Authors: Bacon Jean , Eyers David , Singh Jatinder , Shand Brian , Migliavacca Matteo , Pietzuch Peter
Published: September 2009

Event-based systems give the potential for active information sharing. The event-based paradigm, if used for event transport, provides loose coupling between components, many-to-many communication and mutual anonymity of event producers and event consumers. This communication style has been adopted enthusiastically for convenience of programming; particularly for financial processing, healthcare applications and sensor-based systems. But some data is sensitive, and its visibility must be controlled carefully for personal and legal reasons. Our research projects have explored this space for some time, investigating application domains in which the event-based paradigm is appropriate yet where security is an issue. We discuss security issues for multi-domain, event-based systems, considering the requirements of applications and the risk associated with failure. We provide an overview of the state-of-the-art in secure event-based systems: research already carried out, work in progress and issues still to be addressed. This is of relevance to emerging large-scale systems required by government and public bodies for domains such as healthcare, police, transport and environmental monitoring.
Intelligent Medical Image SearchIntelligente Bildsuche in der Medizin
Authors: Zillner Sonja , Huber Martin
Published: September 2009

Due to vast progress of medical image devices, clinicians today rely deeply on images for screening, diagnosis, treatment planning and follow up. However, these medical images are still indexed by keywords and can not be searched and retrieved for their content. In this article we present the project MEDICO that strives to implement intelligent medical image search by means of machine learning algorithms and semantic technologies.
Dynamics of constitutive heterochromatin: two contrasted kinetics of genome restructuring in early cloned bovine embryos
Authors: Pichugin Andrey , Le Bourhis Daniel , Adenot Pierre , Lehmann Gaëtan , Audouard Christophe , Renard Jean-Paul , Vignon Xavier , Beaujean Nathalie
Published: September 2009

Efficient reprograming of the donor cell genome in nuclear transfer (NT) embryos is linked to the ability of the embryos to sustain full-term development. As the nuclear architecture has recently emerged as a key factor in the regulation of gene expression, we questioned whether early bovine embryos obtained from transfer of cultured fibroblasts into enucleated oocytes would adopt an embryo-like nuclear organization. We studied the dynamics of constitutive heterochromatin in the stages prior to embryonic genome activation by distribution analysis of heterochromatin protein CBX1 (HP1), centromeric proteins CENPA and CENPB, and histone H3 three-methylated at lysine 9. Then we applied descriptive, quantitative, and co-localization analyses. A dramatic reorganization of heterochromatic blocks of somatic donor cells was first observed in the late one-cell stage NT embryos. Then at two- and four-cell stages, we found two types of NT embryos: one displaying noncondensed heterochromatin patches similar to IVF embryos, whereas the second type displayed condensed heterochromatin blocks, normally observed in IVF embryos only after the eight-cell stage. These analyses discriminate for the first time two contrasted types of nuclear organization in NT embryos, which may correspond to different functional states of the nuclei. The relationship with the somatic nucleus reprograming efficiency is discussed.
Índice de priorização para avaliar a contenção vegetativa em talude rodoviário de saprolito de gnaisse, na Zona da Mata de Minas Gerais
Authors: Einloft Rosilene , Ruiz Hugo Alberto , Griffith James Jackson , Schaefer Carlos Ernesto Gonçalves R. , Costa Liovando Marciano da
Published: September 2009

O objetivo desse trabalho foi formular um índice de priorização para avaliar a contenção vegetativa em talude rodoviário de declividade acentuada subtrecho entre Viçosa e Araponga (MG), Brasil, a 20º44' latitude S; 42º50' longitude W. Neste trabalho, os tratamentos consistiram de nove consórcios de uma gramínea (Brachiaria brizantha, Brachiaria decumbens ou Brachiaria ruziziensis) e uma leguminosa [mucuna preta (Stizolobium aterrimum), feijão guandu (Cajanus cajan) ou lablabe (Dolichos lab lab)]. Na elaboração do índice, o primeiro passo foi escolher, dentre as características analisadas, aquelas mais apropriadas para a seleção do consórcio no processo de revegetação estabelecendo, consequentemente, uma frequência por meio de uma matriz de ponderação. Ao término do exercício, a frequência com que uma característica foi assinalada, representa a importância individual na resposta global do consórcio aos tratamentos. A nota final de cada consórcio foi dada pelo somatório do produto das frequências multiplicadas pelos valores relativos das características determinadas experimentalmente. Após o cálculo, os índices foram analisados estatisticamente, aplicando-se o teste de agrupamento de Scott-Knott. Da análise do índice conjunto padronizado, pode-se concluir que a mucuna-preta foi a leguminosa mais apropriada no processo de revegetação, dentre as três testadas, com valor médio de 28,03 sobre máximo possível de 30. O feijão-guandu revelou comportamento intermediário (26,52) e o lab lab foi o menos indicado (23,08). As características semelhantes de crescimento das braquiárias permitiram atestar respostas alternativas, dependendo da leguminosa associada. Assim, a Braquiaria brizanta foi a mais adequada para associação com a mucuna-preta, e a Braquiaria decumbens, quando em consórcio com o feijão-guandu.
MicroRNAs and prostate cancer
Authors: Coppola Valeria , De Maria Ruggero , Bonci Désirée
Published: September 2009

Despite much progress in prostate cancer management, new diagnostic, prognostic and therapeutic tools are needed to predict disease severity, choose among the available treatments and establish more effective therapies for advanced prostate cancer. In the last few years, compelling evidence has documented the role of microRNAs as new broad-spectrum oncogenes or tumour suppressor genes, thus their use as diagnostic, prognostic and therapeutic biomolecules is envisaged. This review extensively and critically summarizes the current knowledge about microRNA deregulation in prostate cancer disease, underlining present limits and future perspectives.
Inhibition Performance of a New Series of Mono-/Diamine-Based Corrosion Inhibitors for HCl Solutions
Authors: Al-Taq Ali A. , Ali Shaikh A. , Nasr-El-Din Hisham A.
Published: September 2009

New mono- and diamine compounds were synthesized from dodecylamine and 1,12-dodacanediamine and evaluated as acid corrosion inhibitors for low-carbon steel. The inhibition behavior of these compounds was examined using gravimetric and electrochemical methods (linear polarization and Tafel plot). Weight-loss tests were conducted in 1M HCl at 60°C for six hours. To simulate acid stimulation treatments, other weight-loss tests were conducted using typical acid stimulation concentrations of 4.1 and 7.7M HCl at 60°C for 2 hours. The effects of corrosion inhibitor type, concentration, and acid concentration were investigated.

Aromatic and multiple bonds substituents introduced to mono-and diamine compounds were found to enhance inhibition performance compared to the starting materials (dodecylamine and 1,12-dodacanediamine). This is attributed to the π-electrons present in aromatic and to polymerization of substituents with multiple bonds. Both dodecylamine derivatives with a triple bond or an aromatic substituent exhibited excellent protection in 4.1M HCl. However, the derivative with a triple bond showed the best protection (98%) at 7.7M HCl. This result is very promising and suggests that this corrosion inhibitor has a good potential to be used in acid stimulation treatments conducted in oil and gas wells.
List of Acronyms
Authors: Fu Yongqi
Published: September 2009

Full text available