bluuebunny/crossref_metadata_2025 huggingface dataset:
Generating and maintaining diversity at the elite level in crop breedingThis article is one of a selection of papers from the conference “Exploiting Genome-wide Association in Oilseed Brassicas: a model for genetic improvement of major OECD crops for sustainable farming”
Authors: Falk Duane E.
Published: November 2010

Most breeding programs develop elite genotypes that are well adapted to the normal range of environmental conditions in the target production region. These elite lines have similar essential alleles for desirable end use characteristics, agronomics, disease resistance, and adaptation in the target region. The genetic makeup of these elite lines is complex. Intermating among the elite lines will often produce new variability through recombination with minimal risk of introducing new undesirable features, and is the source of most new cultivars. Eventually, this variation will be exhausted and new alleles must be introduced into the elite breeding population. Introducing desirable alleles from exotic germplasm may “pollute” the elite gene pool with undesirable alleles. Exotic germplasm may also disrupt essential allele combinations for adaptation, quality, and agronomic performance. New desirable alleles from exotic germplasm can be introgressed into an elite population in a systematic way through limited backcrossing with a minimal disturbance to the finely tuned elite background. Combining recurrent selection within elite germplasm with a systematic introgression from exotic germplasm in the recurrent introgressive population enrichment (RIPE) system has created an open-ended, continually improving, and sustainable elite population breeding system, which is simple, effective, and a regular source of new cultivars.
An alternative approach to a harmony search algorithm for a construction site layout problem
Authors: Gholizadeh Roozbeh , Amiri Gholamrez Ghodrati , Mohebi Benyamin
Published: November 2010

The task of positioning temporary facilities on a construction site has long been recognized as a factor of great influence on the cost of projects. This paper proposes the use of a recently developed harmony search (HS) algorithm to solve the problem of assigning a set of predetermined facilities to a set of preallocated locations within a construction site. Experiments with different parameter settings were conducted, and an alternative approach was used with a modified HS algorithm to overcome shortcomings of the original method. The proposed algorithm shows a rapid convergence to an optimum solution during the early stages of algorithm progress. In addition, comparisons with different variations of the HS algorithm and genetic algorithm (GA) are presented to demonstrate the efficiency of the proposed method and HS methodology in solving facility layout problems.
Design and construction coordination problems and planning for design–build project new users
Authors: Chang Andrew S. , Shen Fang-Ying , Ibbs William
Published: November 2010

Design–build (DB) is adopted as a project delivery method in hopes to improve performance. Previous studies focus on upstream issues such as conditions for adoption and contractor selection, but few address the design and construction coordination issues that are very likely to be encountered in execution by new users. This paper investigates coordination problems arising from design and construction concurrence and solutions by studying five ongoing DB projects and interviewing nine major contract parties. Inconsistent application of the design and construction process and infrequent feedback are two major problems found to have high influence on DB execution. A work unit planning process with five steps is presented in this paper to help better manage the design and construction coordination of a DB project.
Floor response spectra for seismic design of operational and functional components of concrete buildings in Canada
Authors: Shooshtari M. , Saatcioglu M. , Naumoski N. , Foo S.
Published: November 2010

It has been observed during previous earthquakes that the damage to operational and functional components of buildings often result in more injuries, fatalities and property damage than those inflicted by structural damage. Operational and functional components of a building include architectural components, mechanical and electrical equipment, as well as building contents. A rational approach to designing these elements against seismic excitations involves the use of floor design spectra. The development of such design spectra for buildings in Canada constitutes the objective of the paper. This objective was achieved by conducting comprehensive analyses of selected reinforced concrete buildings, with different lateral force resisting systems and building heights, under code compatible earthquake records for an eastern and a western Canadian city. It was observed that the floor response was significantly amplified, especially for buildings with short periods. Generally, the higher floors showed higher amplifications with differences in spectra between the floors being more pronounced in low-rise buildings and shear wall buildings with short fundamental periods. The results provided a large volume of data to generate floor response spectra for the design of operational and functional components of buildings in Canada. The details of the approach and the design spectra are presented in the paper.
Analysis and design for the resilience of shear connections
Authors: Gong Yanglin
Published: November 2010

This paper proposes an approach for quantifying the demands on shear connections under the assumption of an ineffective column. Formulas and an algorithm are developed to evaluate the axial force, axial deformation, rotation, and moment demands on beam-to-column shear connections. The analysis algorithm developed is verified using a solved example found from literature. Parametric studies are conducted to determine important parameters in the connection modeling for resilience design. Furthermore, a detailed procedure indicating how to obtain the properties of an end-plate shear connection for its resilience design is provided. Four end-plate connection examples are employed to illustrate the proposed methodology. Finally, a capacity design concept is introduced for the ductility design of shear connections. This study demonstrates that shear connections should be designed explicitly for its resilience to resist progressive collapse of a girder-and-beam system.
Roughness effects on turbulence characteristics in an open channel flow
Authors: Faruque Md Abdullah Al , Balachandar Ram
Published: November 2010

A comprehensive study was carried out to understand the effect of roughness on the turbulence characteristics of flow in an open channel. To this end, tests were conducted with four different types of bed surface conditions at two different Reynolds number (Re = 47 500 and 31 000). This includes the use of an impermeable smooth bed, impermeable rough bed, permeable sand bed, and an impermeable bed with distributed roughness. The roughness is generated using sand grains of median diameter 2.46 mm. The effect of bed roughness is seen to have penetrated through most of the flow depth, disputing the conventional "wall similarity" hypothesis. The results show that the distributed roughness generates the largest roughness effect. The differences in the characteristics as noted by the velocity triple products exceed 200% between the flow over the smooth and rough beds. Although the same sand grain is used to create the different rough bed conditions, there are differences in turbulence characteristics, which is an indication that specific geometry of the roughness has an influence. A quadrant analysis indicates that roughness increases the contribution of the extreme turbulent events that produce very large instantaneous Reynolds shear stress and consequently influence the flow.
COMPARISON OF SUPPORT VECTOR MACHINES AND BAYESIAN NEURAL NETWORKS PERFORMANCE FOR BREAST TISSUES USING GEOSTATISTICAL FUNCTIONS IN MAMMOGRAPHIC IMAGES
Authors: JUNIOR GERALDO BRAZ , MARTINS LEONARDO DE OLIVEIRA , SILVA ARISTÓFANES CORREA , PAIVA ANSELMO CARDOSO
Published: November 2010

Female breast cancer is a major cause of deaths in occidental countries. Computer-aided Detection (CAD) systems can aid radiologists to increase diagnostic accuracy. In this work, we present a comparison between two classifiers applied to the separation of normal and abnormal breast tissues from mammograms. The purpose of the comparison is to select the best prediction technique to be part of a CAD system. Each region of interest is classified through a Support Vector Machine (SVM) and a Bayesian Neural Network (BNN) as normal or abnormal region. SVM is a machine-learning method, based on the principle of structural risk minimization, which shows good performance when applied to data outside the training set. A Bayesian Neural Network is a classifier that joins traditional neural networks theory and Bayesian inference. We use a set of measures obtained by the application of the semivariogram, semimadogram, covariogram, and correlogram functions to the characterization of breast tissue as normal or abnormal. The results show that SVM presents best performance for the classification of breast tissues in mammographic images. The tests indicate that SVM has more generalization power than the BNN classifier. BNN has a sensibility of 76.19% and a specificity of 79.31%, while SVM presents a sensibility of 74.07% and a specificity of 98.77%. The accuracy rate for tests is 78.70% and 92.59% for BNN and SVM, respectively.
TIMELINESMCC's human interface laboratory
Authors: Curtis Bill
Published: November 2010

Success famously has many parents, and SIGCHI is no exception. A strong paternity claim can be made by Bill Curtis, who garnered funding and organized ACM's sponsorship for the Gaithersburg conference in 1982, during which plans to form SIGCHI were announced. The successful and unexpectedly profitable Gaithersburg meeting provided the model for the first CHI conference, which convened in Boston in December 1983. In this column, Bill discusses his subsequent involvement with the Microelectronics and Computer Technology Corporation. This research enterprise, largely forgotten today, was highly influential in the 1980s, hiring and providing visibility to HCI researchers, many of whom remain active. From 1986 to 1989, I was one of the occupants of that unusual building in Austin, Texas, where the fourth-floor management comprised mainly former intelligence-agency employees, while many researchers on the floors below were there in part to avoid working on Reagan-era Strategic Defense Initiative ("Star Wars") projects.

As Timelines editor, I would like to thank Richard Anderson and Jon Kolko for their unwavering support and assistance, and for the inspiration provided by their dedication to and outstanding stewardship of this magazine.---Jonathan Grudin
KissKissBan
Authors: Ho Chien-Ju , Chang Tao-Hsuan , Lee Jong-Chuan , Hsu Jane Yung-jen , Chen Kuan-Ta
Published: November 2010

In this paper, we propose a competitive human computation game, KissKissBan (KKB), for image annotation. KKB is different from other human computation games since it integrates both collaborative and competitive elements in the game design. In a KKB game, one player, the blocker, competeswith the other two collaborative players, the couples; while the couples try to find consensual descriptions about an image, the blocker's mission is to prevent the couples from reaching consensus. Because of its design, KKB possesses two nice properties over the traditional human computation game. First, since the blocker is encouraged to stop the couples from reaching consensual descriptions, he will try to detect and prevent coalition between the couples; therefore, these efforts naturally form a player-levelcheating-proof mechanism. Second, to evade the restrictions set by the blocker, the couples would endeavor to bring up a more diverse set of image annotations. Experiments hosted on Amazon Mechanical Turk and a gameplay survey involving 17 participants have shown that KKB is a fun and efficient game for collecting diverse image annotations.
Alcohol exposure during late gestation adversely affects myocardial development with implications for postnatal cardiac function
Authors: Goh Joanna M. , Bensley Jonathan G. , Kenna Kelly , Sozo Foula , Bocking Alan D. , Brien James , Walker David , Harding Richard , Black M. Jane
Published: November 2010

Prenatal exposure to high levels of ethanol is associated with cardiac malformations, but the effects of lower levels of exposure on the heart are unclear. Our aim was to investigate the effects of daily exposure to ethanol during late gestation, when cardiomyocytes are undergoing maturation, on the developing myocardium. Pregnant ewes were infused with either ethanol (0.75 g/kg) or saline for 1 h each day from gestational days 95 to 133 (term ∼145 days); tissues were collected at 134 days. In sheep, cardiomyocytes mature during late gestation as in humans. Within the left ventricle (LV), cardiomyocyte number was determined using unbiased stereology and cardiomyocyte size and nuclearity determined using confocal microscopy. Collagen deposition was quantified using image analysis. Genes relating to cardiomyocyte proliferation and apoptosis were examined using quantitative real-time PCR. Fetal plasma ethanol concentration reached 0.11 g/dL after EtOH infusions. Ethanol exposure induced significant increases in relative heart weight, relative LV wall volume, and cardiomyocyte cross-sectional area. Ethanol exposure advanced LV maturation in that the proportion of binucleated cardiomyocytes increased by 12%, and the number of mononucleated cardiomyocytes was decreased by a similar amount. Apoptotic gene expression increased in the ethanol-exposed hearts, although there were no significant differences between groups in total cardiomyocyte number or interstitial collagen. Daily exposure to a moderate dose of ethanol in late gestation accelerates the maturation of cardiomyocytes and increases cardiomyocyte and LV tissue volume in the fetal heart. These effects on cardiomyocyte growth may program for long-term cardiac vulnerability.
Bronchodilation response to deep inspirations in asthma is dependent on airway distensibility and air trapping
Authors: Pyrgos George , Scichilone Nicola , Togias Alkis , Brown Robert H.
Published: November 2010

In healthy individuals, deep inspirations (DIs) have a potent bronchodilatory ability against methacholine (MCh)-induced bronchoconstriction. This is variably attenuated in asthma. We hypothesized that inability to bronchodilate with DIs is related to reduced airway distensibility. We examined the relationship between DI-induced bronchodilation and airway distensibility in 15 asthmatic individuals with a wide range of baseline lung function [forced expired volume in 1 s (FEV1) = 60–99% predicted]. After abstaining from DIs for 20 min, subjects received a single-dose MCh challenge and then asked to perform DIs. The effectiveness of DIs was assessed by the ability of the subjects to improve FEV1. The same subjects were studied by two sets of high-resolution CT scans, one at functional residual capacity (FRC) and one at total lung capacity (TLC). In each subject, the areas of 21–41 airways (0.8–6.8 mm diameter at FRC) were matched and measured, and airway distensibility (increase in airway diameter from FRC to TLC) was calculated. The bronchodilatory ability of DIs was significantly lower in individuals with FEV1 <75% predicted than in those with FEV1 ≥75% predicted (15 ± 11% vs. 46 ± 9%, P = 0.04) and strongly correlated with airway distensibility ( r = 0.57, P = 0.03), but also with residual volume (RV)/TLC ( r = −0.63, P = 0.01). In multiple regression, only RV/TLC was a significant determinant of DI-induced bronchodilation. These relationships were lost when the airways were examined after maximal bronchodilation with albuterol. Our data indicate that the loss of the bronchodilatory effect of DI in asthma is related to the ability to distend the airways with lung inflation, which is, in turn, related to the extent of air trapping and airway smooth muscle tone. These relationships only exist in the presence of airway tone, indicating that structural changes in the conducting airways visualized by high-resolution CT do not play a pivotal role.
Signals mediating skeletal muscle remodeling by resistance exercise: PI3-kinase independent activation of mTORC1
Authors: Philp Andrew , Hamilton D. Lee , Baar Keith
Published: November 2010

For over 10 years, we have known that the activation of the mammalian target of rapamycin complex 1 (mTORC1) has correlated with the increase in skeletal muscle size and strength that occurs following resistance exercise. Initial cell culture and rodent models of muscle growth demonstrated that the activation of mTORC1 is common to hypertrophy induced by growth factors and increased loading. The further observation that high loads increased the local production of growth factors led to the paradigm that resistance exercise stimulates the autocrine production of factors that act on membrane receptors to activate mTORC1, and this results in skeletal muscle hypertrophy. Over the last few years, there has been a paradigm shift. From both human and rodent studies, it has become clear that the phenotypic and molecular responses to resistance exercise occur in a growth factor-independent manner. Although the mechanism of load-induced mTORC1 activation remains to be determined, it is clear that it does not require classical growth factor signaling.
Dietary nitrate supplementation reduces the O2cost of walking and running: a placebo-controlled study
Authors: Lansley Katherine E. , Winyard Paul G. , Fulford Jonathan , Vanhatalo Anni , Bailey Stephen J. , Blackwell Jamie R. , DiMenna Fred J. , Gilchrist Mark , Benjamin Nigel , Jones Andrew M.
Published: November 2010

Dietary supplementation with beetroot juice (BR) has been shown to reduce resting blood pressure and the O2cost of submaximal exercise and to increase tolerance to high-intensity cycling. We tested the hypothesis that the physiological effects of BR were consequent to its high NO3−content per se, and not the presence of other potentially bioactive compounds. We investigated changes in blood pressure, mitochondrial oxidative capacity (Qmax), and physiological responses to walking and moderate- and severe-intensity running following dietary supplementation with BR and NO3−-depleted BR [placebo (PL)]. After control (nonsupplemented) tests, nine healthy, physically active male subjects were assigned in a randomized, double-blind, crossover design to receive BR (0.5 l/day, containing ∼6.2 mmol of NO3−) and PL (0.5 l/day, containing ∼0.003 mmol of NO3−) for 6 days. Subjects completed treadmill exercise tests on days 4 and 5 and knee-extension exercise tests for estimation of Qmax(using31P-magnetic resonance spectroscopy) on day 6 of the supplementation periods. Relative to PL, BR elevated plasma NO2−concentration (183 ± 119 vs. 373 ± 211 nM, P < 0.05) and reduced systolic blood pressure (129 ± 9 vs. 124 ± 10 mmHg, P < 0.01). Qmaxwas not different between PL and BR (0.93 ± 0.05 and 1.05 ± 0.22 mM/s, respectively). The O2cost of walking (0.87 ± 0.12 and 0.70 ± 0.10 l/min in PL and BR, respectively, P < 0.01), moderate-intensity running (2.26 ± 0.27 and 2.10 ± 0.28 l/min in PL and BR, respectively, P < 0.01), and severe-intensity running (end-exercise O2uptake = 3.77 ± 0.57 and 3.50 ± 0.62 l/min in PL and BL, respectively, P < 0.01) was reduced by BR, and time to exhaustion during severe-intensity running was increased by 15% (7.6 ± 1.5 and 8.7 ± 1.8 min in PL and BR, respectively, P < 0.01). In contrast, relative to control, PL supplementation did not alter plasma NO2−concentration, blood pressure, or the physiological responses to exercise. These results indicate that the positive effects of 6 days of BR supplementation on the physiological responses to exercise can be ascribed to the high NO3−content per se.
Prognostic Significance of the Detection of Peripheral Blood CEACAM5mRNA-Positive Cells by Real-Time Polymerase Chain Reaction in Operable Colorectal Cancer
Authors: Vardakis Nikolaos , Messaritakis Ippokratis , Papadaki Chara , Agoglossakis Georgios , Sfakianaki Maria , Saridaki Zacharenia , Apostolaki Stella , Koutroubakis Ioannis , Perraki Maria , Hatzidaki Dora , Mavroudis Dimitris , Georgoulias Vassilis , Souglakos John
Published: November 2010

Purpose: To evaluate the clinical relevance of circulating CEACAM5mRNA-positive cells in patients with operable colorectal cancer (CRC).

Methods: Peripheral blood was obtained from 265 patients with operable CRC before the initiation of adjuvant systemic therapy from 96 normal donors and RNA prepared from the Lovo and ARH-77 CRC and leukemic cell lines, respectively, was used as positive and negative controls. The detection of CEACAM5mRNA-positive cells was done using a real-time PCR assay. The association with known prognostic factors and the effect of CEACAM5mRNA-positive cells on patients' prognosis was investigated.

Results: The analytical detection limit of the method was found to correspond to 0.7 Lovo cell equivalence/5 μg RNA, with a sensitivity of 1 tumor cell/105 normal cells and a specificity of 97%. Ninety-eight (37%) patients had detectable circulating CEACAM5mRNA-positive cells. Detection of CEACAM5mRNA-positive cells was significantly associated with higher relapse rate (P < 0.001), decreased disease-free survival (DFS; P < 0.001), higher death rate (P = 0.017), and decreased median overall survival (P = 0.025). Multivariate analysis revealed that the detection of circulating CEACAM5mRNA-positive cells was an independent prognostic factor for decreased DFS [HR = 3.4; 95% CI: 2.0–5.9; P < 0.001].

Conclusions: Detection of peripheral blood CEACAM5mRNA-positive cells is an adverse prognostic factor correlated with poor clinical outcome in patients with operable CRC. Clin Cancer Res; 17(1); 165–73. ©2010 AACR.
FMNL2 Enhances Invasion of Colorectal Carcinoma by Inducing Epithelial-Mesenchymal Transition
Authors: Li Yufa , Zhu Xiling , Zeng Yuanfeng , Wang Jianmei , Zhang Xiaojing , Ding Yan-qing , Liang Li
Published: November 2010

FMNL2 is a member of diaphanous-related formins that control actin-dependent processes such as cell motility and invasion. Its overexpression in metastatic cell lines and tissues of colorectal carcinoma has been associated with aggressive tumor development in our previous study. But its specific role in cancer is largely unknown. Here we report that FMNL2 is involved in epithelial-mesenchymal transition (EMT) maintenance in human colorectal carcinoma cells. A positive correlation between FMNL2 and vimentin expression and an inverse correlation between FMNL2 and E-cadherin expression were found in colorectal carcinoma cell lines and cancer tissues. Specific knockdown of FMNL2 led to an epithelial-state transition, confirmed by the cobblestone-like phenotype, upregulation of E-cadherin, α-catenin, and γ-catenin, and downregulation of vimentin, snail, slug. Loss of FMNL2 expression lowered the ability of TGF-β to induce cell invasion and EMT, as shown by morphology and the expression levels. Upregulation of vimentin, slug, snail, downregulation of E-cadherin and activation of receptor-Smad3 phosphorylation were observed in M5 and MDCK cells induced by TGF-β, whereas altered expression of these markers was not obvious in FMNL2-depleting M5 cells. High levels of activation of p-MAPK and p-MEK, but not p-PI3K and p-AKT, were observed in SW480/FMNL2+ cells compared with control cells. Treatment with U0126 could abrogate the activation of p-MAPK and p-MEK, whereas LY294002 treatment had no effect on the PI3K/AKT pathway. In conclusion, these findings identify a novel EMT and tumor promoting function for FMNL2, which is involved in TGF-β–induced EMT and colorectal carcinoma cell invasion via Smad3 effectors, or in collaboration with MAPK/MEK pathway. Mol Cancer Res; 8(12); 1579–90. ©2010 AACR.
A Migration Signature and Plasma Biomarker Panel for Pancreatic Adenocarcinoma
Authors: Balasenthil Seetharaman , Chen Nanyue , Lott Steven T. , Chen Jinyun , Carter Jennifer , Grizzle William E. , Frazier Marsha L. , Sen Subrata , Killary Ann McNeill
Published: November 2010

Pancreatic ductal adenocarcinoma is a disease of extremely poor prognosis for which there are no reliable markers of asymptomatic disease. To identify pancreatic cancer biomarkers, we focused on a genomic interval proximal to the most common fragile site in the human genome, chromosome 3p12, which undergoes smoking-related breakage, loss of heterozygosity, and homozygous deletion as an early event in many epithelial tumors, including pancreatic cancers. Using a functional genomic approach, we identified a seven-gene panel (TNC, TFPI, TGFBI, SEL-1L, L1CAM, WWTR1, and CDC42BPA) that was differentially expressed across three different expression platforms, including pancreatic tumor/normal samples. In addition, Ingenuity Pathways Analysis (IPA) and literature searches indicated that this seven-gene panel functions in one network associated with cellular movement/morphology/development, indicative of a “migration signature” of the 3p pathway. We tested whether two secreted proteins from this panel, tenascin C (TNC) and tissue factor pathway inhibitor (TFPI), could serve as plasma biomarkers. Plasma ELISA assays for TFPI/TNC resulted in a combined area under the curve (AUC) of 0.88 and, with addition of CA19-9, a combined AUC for the three-gene panel (TNC/TFPI/CA19-9), of 0.99 with 100% specificity at 90% sensitivity and 97.22% sensitivity at 90% specificity. Validation studies using TFPI only in a blinded sample set increased the performance of CA19-9 from an AUC of 0.84 to 0.94 with the two-gene panel. Results identify a novel 3p pathway–associated migration signature and plasma biomarker panel that has utility for discrimination of pancreatic cancer from normal controls and promise for clinical application. Cancer Prev Res; 4(1); 137–49. ©2010 AACR.
Expression of Transcription Factor GATA-6 in Alveolar Epithelial Cells Is Linked to Neonatal Lung Disease
Authors: Vähätalo Riika , Asikainen Tiina M. , Karikoski Riitta , Kinnula Vuokko L. , White Carl W. , Andersson Sture , Heikinheimo Markku , Myllärniemi Marjukka
Published: November 2010

Background: Premature birth and respiratory distress syndrome (RDS) are risk factors for disturbed lung development and bronchopulmonary dysplasia (BPD). The molecular mechanisms related to prematurity and BPD remain largely unknown. Epithelial expression of the transcription factor GATA-6 has been implicated in normal and abnormal murine lung development. Objectives: The possible involvement of GATA-6 in the normal development and in RDS and BPD was investigated in the human and baboon lung. Methods: Immunohistochemistry was used to study the expression of GATA-6 and thyroid transcription factor 1 in lung specimens from different age groups of human and baboon fetuses and newborns with lung disease. Furthermore, the regulatory role of TGF-β1 in GATA-6 expression was investigated in human pulmonary epithelial cell lines using RT-PCR. Results: GATA-6 expression increased in the developing human airway epithelium along with advancing gestation, but diminished to negligible at birth. In RDS, GATA-6 expression was enhanced at 5–7 days after birth, and decreased thereafter. In BPD, the expression of GATA-6 in alveolar epithelial cells was low. These results were confirmed and extended using an established baboon model of prematurity. The in vitro experiments revealed that TGF-β1 induces GATA-6 and thyroid transcription factor 1 expression in lung epithelial cells. Conclusions: Our results suggest that the expression of GATA-6 at the early stages of the preterm lung may be related to impaired postnatal alveolar development.
Iron Deficiency in Childhood: Causes and Consequences for Child Development
Authors: Grantham-McGregor Sally , Baker-Henningham Helen
Published: November 2010

The main causes of iron deficiency (ID) are briefly discussed, followed by the examination of studies of ID and child cognitive and motor development and behaviour for evidence of a causal link, classifying them by study design. Iron deficiency anaemia (IDA) is associated with many psychosocial and economic disadvantages that can affect child development and could explain the frequently demonstrated relationship between IDA and poor development and behavioural differences. There is evidence of changes to brain function in infants with IDA. Many treatment trials lack statistical power due to small samples, including children without ID in the sampling or iron treatment resulting in little or no differences in iron status between placebo and treated groups. In children with IDA under 3 years, randomized trials indicate that iron supplementation is usually beneficial to motor development, but the effect on mental development is inconsistent. Iron supplementation also has a beneficial effect on cognitive function in school-aged children with IDA. Evidence for a threshold level of ID at which child development is affected is inconsistent, but children with IDA are most likely to benefit from iron supplementation. Possible harmful effects of iron supplementation in iron-replete children on growth and morbidity have to be considered when developing programmes and policy.
Local Expression of C-Reactive Protein Is Associated with Deteriorating Graft Function in Acute and Chronic Failure of Kidney Transplants
Authors: Jabs Wolfram J. , Meier Markus , Lamprecht Peter , Steinhoff Juergen , Nitschke Martin
Published: November 2010

Background: C-reactive protein (CRP) is a key molecule in inflammation and tissue homeostasis and is produced locally by renal tubular epithelial cells. Its significance of expression in contrast to expression of cytotoxic T cell (CTL) markers remains to be elucidated. Methods: By means of real-time PCR, we determined mRNA levels of CRP in 66 renal allograft biopsies with acute allograft failure and in 34 biopsies with chronic dysfunction. Results were compared to expression of CTL components (perforin, granzyme B) and were correlated with histologic diagnoses and outcome. Results: CTL markers were found in most biopsies, and thus were not specific for particular histologies, although expression levels increased significantly with Banff rejection grades. Expression of CRP was highly specific for rejection episodes in acute failure (p < 0.0001) as well as for transplant glomerulopathy or de novo/recurrent glomerulonephritis in chronic failure (p < 0.005). Finally, the presence of CRP expression in renal allografts was associated with a deteriorating 1-year graft function in acute (p < 0.01) as well as chronic allograft dysfunction (p = 0.077). Conclusions: Our data suggest local CRP expression of kidney transplants as an indicator for pathologic entities associated with unfavorable outcomes in the early and late course of kidney transplants.
Una revisión de los beneficios del aporte complementario de nutrientes durante el embarazo: desde hierro y ácido fólico hasta probióticos pasando por ácidos grasos poliinsaturados de cadena larga
Authors: Ramakrishnan Usha
Published: November 2010

En esta revisión se resume el conocimiento actual sobre la eficacia de los aportes complementarios prenatales de nutrientes, desde hierro y ácido fólico (HAF), que representan el patrón asistencial en muchas partes del mundo, hasta los más novedosos como ácidos grasos ω–3 y probióticos, en la mejora de los desenlaces del estado de salud materno-infantil. En ensayos aleatorios controlados se ha demostrado que los aportes complementarios prenatales de HAF reducen el riesgo de anemia y carencia de hierro durante el embarazo y a término, si bien las pruebas a favor de las reducciones del riesgo de bajo peso al nacer (BPN) y parto prematuro (PP) son débiles. No obstante, en estudios recientes se da a entender que los aportes complementarios prenatales de HAF pueden reducir la mortalidad infantil. Por otra parte, se dispone de datos convincentes a favor de que los aportes complementarios de micronutrientes múltiples, que contienen 1 a 2 ingestiones diarias recomendadas de varias vitaminas y minerales, son seguros y reducen el riesgo de BPN en el 19 y el 17% en comparación con un placebo o con la administración sistemática de HAF. También se ha demostrado que los aportes complementarios prenatales de calcio (>1 g/día) reducen significativamente el riesgo de preeclampsia y mortalidad o morbilidad grave materna en el 52 y el 20%, respectivamente. Los aportes complementarios de cinc y aceite de pescado, que contiene ácidos grasos ω–3, pueden también incrementar, en poblaciones seleccionadas, la edad gestacional y reducir el riesgo de PP, pero no de BPN. No obstante, la disponibilidad de datos que apoyen el suministro de aportes complementarios que contengan sólo las vitaminas A y D o antioxidantes como las vitaminas C y E, son limitados. Aunque el efecto protector del ácido fólico durante el periodo periconceptivo consistente en reducir las anomalías congénitas del tubo neural está confirmado, en muy pocos o en ningún ensayo de intervención se han evaluado los efectos independientes de vitaminas B específicas (vitaminas B6, B12 y ácido fólico), ácido docosahexanoico y probióticos durante el embarazo. Tampoco se han explorado los efectos de aportes complementarios prenatales de yodo en zonas con carencia leve a moderada del mismo. Si bien algunos de estos nutrientes pueden no influir sobre desenlaces como PP o BPN, pueden producir beneficios a largo plazo para el estado de salud y el desarrollo de la descendencia.
Can the Diverse Family of Dialysis Adequacy Indices Be Understood as One Integrated System?
Authors: Waniewski Jacek , Debowska Malgorzata , Lindholm Bengt
Published: November 2010

Background: Dialysis adequacy indices are based on the amount of removed solute and systemized into two groups: (1) fractional solute removal (FSR, non-dimensional), and (2) equivalent continuous clearance (ECC, ml/min), which are expressed using appropriate reference method for solute concentration or mass such as: peak, peak average, time average, and treatment time average values. Methods: A review and critical analysis of the recent studies was performed. Results: The indices are mathematically interrelated and depend on kinetic parameters of the treatment, as device clearance, treatment time, solute distribution volume, dialysis frequency. In particular, KT/V and KT can be directly translated to FSR and ECC using the treatment time average reference method. Conclusion: The diverse family of dialysis adequacy indices can be understood as one integrated system and be useful when assessing both standard treatment modalities and newer schedules and modalities (frequent dialysis, hybrid dialysis, dialysis in acute renal failure) of renal replacement therapies.
Early Markers of Choroidal Neovascularization in the Fellow Eye of Patients with Unilateral Exudative Age-Related Macular Degeneration
Authors: Cachulo Luz , Silva Rufino , Fonseca Pedro , Pires Isabel , Carvajal-Gonzalez Santos , Bernardes Rui , Cunha-Vaz José G.
Published: November 2010

Objective: To identify morphological and/or functional early markers of choroidal neovascularization (CNV) development in fellow eyes of patients with exudative age-related macular degeneration (AMD). Design: This is a single-center, prospective, observational, longitudinal 2-year study. Patients: Patients were enrolled with the diagnosis of neovascular AMD in 1 eye and early age-related maculopathy (ARM) in the fellow eye. Intervention or Methods: All patients completed the baseline assessment and were followed up for up to 24 months with repeated ophthalmic and imaging assessments performed at 6-month intervals. Main OutcomeMeasures: Each patient underwent a detailed ocular and medical history, a complete ophthalmologic examination with color fundus photography, fluorescein angiography, indocyanine green angiography (ICG), optical coherence tomography (OCT), fundus autofluorescence (FAF) imaging and retinal leakage analysis (RLA). Results: Sixty-two patients were enrolled in the study. Large or intermediate drusen were present in 100% of the study eyes and hyperpigmentation in 46% (24 eyes). Fifty-two patients completed the 2-year study follow-up. Large soft drusen (>125 µm) were observed in 15 out of 17 eyes (88%) that converted and developed CNV during the study and in 25 out of 35 eyes (71.4%) that did not develop CNV. Among the 17 eyes that developed CNV, 9 (53%) showed abnormal findings before conversion, on ICG. No particular FAF pattern was found to be correlated with conversion to wet AMD. OCT was able to document the presence of intra- or subretinal fluid at the time of conversion in all 17 eyes that developed CNV during the study. Alterations of the blood-retinal barrier were identified by RLA before conversion in 76% of the eyes that converted and 23% of the eyes that did not convert during the study. Conclusions: Characterization of early ARM phenotypes is challenging. By combining different imaging modalities of the macula and correlating this information, we were able to determine the presence of functional macular alterations in the fellow eye of patients with this disease before development of CNV.
D178N, 129Val and N171S, 129Val Genotype in a Family with Creutzfeldt-Jakob Disease
Authors: Appleby Brian S. , Appleby Kristin K. , Hall Ryan C.W. , Wallin Mitchell T.
Published: November 2010

Background: Fatal familial insomnia (FFI) and genetic Creutzfeldt-Jakob disease (CJDD178N,129V) are two phenotypes that share a common point mutation at codon 178 of the prion protein gene (PRNP), but differ in their polymorphism at codon 129 of the mutant allele. A mutation at codon 171 of the PRNP gene has been described in a family with a strong psychiatric history without prion disease. Methods: Clinical and genetic information of a family with CJD was obtained from medical records and family informants. Results: We identified an African-American family with molecular and genetically confirmed CJDD178N,129V that also carried the N171S, 129V polymorphism and had a strong psychiatric clinical presentation. Conclusion: This is a complex family that carries the D178N, 129V and N171S, 129V genotype. This report is the first description of both genotypes occurring within a family with genetic human prion disease.
Prognostic Implication of Plasma Osteopontin Levels in Patients with Chronic Kidney Disease
Authors: Barreto Daniela V. , Lenglet Aurelie , Liabeuf Sophie , Kretschmer Axel , Barreto Fellype C. , Nollet Aude , Slama Michel , Choukroun Gabriel , Brazier Michel , Massy Ziad
Published: November 2010

Aims: To assess (a) plasma osteopontin (pOPN) in a cohort of chronic kidney disease (CKD) patients; (b) the relationship between pOPN and aortic calcification and stiffness, and (c) the association between pOPN and the overall and cardiovascular mortality risk. Methods: pOPN, the abdominal aortic calcification score and pulse wave velocity (PWV) were determined in 94 CKD patients (68 ± 13 years; 60% males; 31% at CKD stages 2–3, 31% at stages 4–5, 38% at stage 5D), prospectively followed for mortality. Results: pOPN was higher in CKD patients than in controls. Interleukin (IL)-6 (r2 = 0.086; p = 0.004), CRP (r2 = 0.046; p = 0.038), iPTH (r2 = 0.065; p = 0.014), albumin (r2 = 0.210; p < 0.0001) and statin use (r2 = 0.038; p = 0.059) were associated with pOPN. There was no association between pOPN and the aortic calcification score or PWV. During follow-up (969 ± 405 days), 32 patients died. In crude analysis, pOPN >167 ng/ml predicted overall and cardiovascular mortality (p = 0.02 and 0.01, respectively), but this effect was lost after adjustment for albumin or IL-6. Conclusions: pOPN is elevated from the early stages of CKD onward. We found no associations between pOPN and the aortic calcification score or the PWV. The positive association between pOPN and clinical outcomes was dependent of the patients’ inflammatory status.
Regulation of Platelet Function by Class B Scavenger Receptors in Hyperlipidemia
Authors: Zimman Alejandro , Podrez Eugene A.
Published: November 2010

Platelets constitutively express class B scavenger receptors CD36 and SR-BI, 2 closely related pattern recognition receptors best known for their roles in lipoprotein and lipid metabolism. The biological role of scavenger receptors in platelets is poorly understood. However, in vitro and in vivo data suggest that class B scavenger receptors modulate platelet function and contribute significantly to thrombosis by sensing pathological or physiological ligands, inducing prothrombotic signaling, and increasing platelet reactivity. Platelet CD36 recognizes a novel family of endogenous oxidized choline phospholipids that accumulate in plasma of hyperlipidemic mice and in plasma of subjects with low high-density lipoprotein levels. This interaction leads to the activation of specific signaling pathways and promotes platelet activation and thrombosis. Platelet SR-BI, on the other hand, plays a critical role in the induction of platelet hyperreactivity and accelerated thrombosis under conditions associated with increased platelet cholesterol content. Intriguingly, oxidized high-density lipoprotein, an SR-BI ligand, can suppress platelet function. These recent findings demonstrate that platelet class B scavenger receptors play roles in thrombosis in dyslipidemia and may contribute to acute cardiovascular events in vivo in hypercholesterolemia.
Platelets
Authors: Bertozzi Cara C. , Hess Paul R. , Kahn Mark L.
Published: November 2010

The field of platelet biology has rapidly expanded beyond the classical role of platelets in preventing blood loss and orchestrating clot formation. Despite the lack of transcriptional ability of these anuclear cell fragments, platelet function is now thought to encompass such diverse contexts as tissue repair, immune activation, primary tumor formation, and metastasis. Recent studies from multiple groups have turned the spotlight on an exciting new role for platelets in the formation of lymphatic vessels during embryonic development. Genetic experiments demonstrate that Podoplanin, a transmembrane protein expressed on lymphatic endothelial cells, engages the platelet C-type lectin-like receptor 2 (CLEC-2) when exposed to blood, leading to SYK-SLP-76-dependent platelet activation. When components of this pathway are disrupted, aberrant vascular connections form, resulting in blood-lymphatic mixing. Furthermore, platelet-null embryos manifest identical blood-lymphatic mixing. The identification of platelets as the critical cell type mediating blood-lymphatic vascular separation raises new questions in our understanding of lymphatic development and platelet biology.
Inherited Human gp91phoxDeficiency Is Associated With Impaired Isoprostane Formation and Platelet Dysfunction
Authors: Pignatelli Pasquale , Carnevale Roberto , Di Santo Serena , Bartimoccia Simona , Sanguigni Valerio , Lenti Luisa , Finocchi Andrea , Mendolicchio Loredana , Soresina Anna Rosa , Plebani Alessandro , Violi Francesco
Published: November 2010

Object—

Platelet isoprostane 8-ISO-prostaglandin F2α (8-iso-PGF2α), a proaggregating molecule, is believed to derive from nonenzymatic oxidation of arachidonic acid. We hypothesized that NADPH is implicated in isoprostane formation and platelet activation.

Methods and Results—

We studied 8-iso-PGF2α in platelets from 8 male patients with hereditary deficiency of gp91phox, the catalytic subunit of NADPH oxidase, and 8 male controls. On stimulation, platelets from controls produced 8-iso-PGF2α, which was inhibited −8% by aspirin and −58% by a specific inhibitor of gp91phox. Platelets from patients with gp91phoxhereditary deficiency had normal thromboxane A2formation but marked 8-iso-PGF2α reduction compared with controls. In normal platelets incubated with a gp91phoxinhibitor or with SQ29548, a thromboxane A2/isoprostane receptor inhibitor, platelet recruitment, an in vitro model of thrombus growth, was reduced by 44% and 64%, respectively; a lower effect (−17%) was seen with aspirin. Moreover, thrombus formation under shear stress (blood perfusion at the wall shear rate of 1500 s−1) was reduced in samples in which isoprostane formation was inhibited by NADPH oxidase inhibitors. In gp91phox-deficient patients, agonist-induced platelet aggregation was within the normal range, whereas platelet recruitment was reduced compared with controls. Incubation of platelets from gp91phox-deficient patients with 8-iso-PGF2α dose-dependently (1 to 100 pmol/L) increased platelet recruitment by mobilizing platelet Ca2+and activating gpIIb/IIIa; a further increase in platelet recruitment was detected by platelet coincubation withl-NAME, an inhibitor of NO synthase.

Conclusion—

This study provides the first evidence that platelet 8-iso-PGF2α maximally derives from gp91phoxactivation and contributes to platelet recruitment via activation of gpIIb/IIIa.
Reduction in Hexokinase II Levels Results in Decreased Cardiac Function and Altered Remodeling After Ischemia/Reperfusion Injury
Authors: Wu Rongxue , Smeele Kirsten M. , Wyatt Eugene , Ichikawa Yoshihiko , Eerbeek Otto , Sun Lin , Chawla Kusum , Hollmann Markus W. , Nagpal Varun , Heikkinen Sami , Laakso Markku , Jujo Kentaro , Wasserstrom J. Andrew , Zuurbier Coert J. , Ardehali Hossein
Published: November 2010

Rationale:

Cardiomyocytes switch substrate utilization from fatty acid to glucose under ischemic conditions; however, it is unknown how perturbations in glycolytic enzymes affect cardiac response to ischemia/reperfusion (I/R). Hexokinase (HK)II is a HK isoform that is expressed in the heart and can bind to the mitochondrial outer membrane.

Objective:

We sought to define how HKII and its binding to mitochondria play a role in cardiac response and remodeling after I/R.

Methods and Results:

We first showed that HKII levels and its binding to mitochondria are reduced 2 days after I/R. We then subjected the hearts of wild-type and heterozygote HKII knockout (HKII
+/−
) mice to I/R by coronary ligation. At baseline, HKII
+/−
mice have normal cardiac function; however, they display lower systolic function after I/R compared to wild-type animals. The mechanism appears to be through an increase in cardiomyocyte death and fibrosis and a reduction in angiogenesis; the latter is through a decrease in hypoxia-inducible factor–dependent pathway signaling in cardiomyocytes. HKII mitochondrial binding is also critical for cardiomyocyte survival, because its displacement in tissue culture with a synthetic peptide increases cell death. Our results also suggest that HKII may be important for the remodeling of the viable cardiac tissue because its modulation in vitro alters cellular energy levels, O
2
consumption, and contractility.

Conclusions:

These results suggest that reduction in HKII levels causes altered remodeling of the heart in I/R by increasing cell death and fibrosis and reducing angiogenesis and that mitochondrial binding is needed for protection of cardiomyocytes.