bluuebunny/crossref_metadata_2025 huggingface dataset:
Device level communication libraries for high‐performance computing in Java
Authors: Taboada Guillermo L. , Touriño Juan , Doallo Ramón , Shafi Aamir , Baker Mark , Carpenter Bryan
Published: June 2011

Since its release, the Java programming language has attracted considerable attention from the high‐performance computing (HPC) community because of its portability, high programming productivity, and built‐in multithreading and networking support. As a consequence, several initiatives have been taken to develop a high‐performance Java message‐passing library to program distributed memory architectures, such as clusters. The performance of Java message‐passing applications relies heavily on the communications performance. Thus, the design and implementation of low‐level communication devices that support message‐passing libraries is an important research issue in Java for HPC. MPJ Express is our Java message‐passing implementation for developing high‐performance parallel Java applications. Its public release currently contains three communication devices: the first one is built using the Java New Input/Output (NIO) package for the TCP/IP; the second one is specifically designed for the Myrinet Express library on Myrinet; and the third one supports thread‐based shared memory communications. Although these devices have been successfully deployed in many production environments, previous performance evaluations of MPJ Express suggest that the buffering layer, tightly coupled with these devices, incurs a certain degree of copying overhead, which represents one of the main performance penalties. This paper presents a more efficient Java message‐passing communications device, based on Java Input/Output sockets, that avoids this buffering overhead. Moreover, this device implements several strategies, both in the communication protocol and in the HPC hardware support, which optimizes Java message‐passing communications. In order to evaluate its benefits, this paper analyzes the performance of this device comparatively with other Java and native message‐passing libraries on various high‐speed networks, such as Gigabit Ethernet, Scalable Coherent Interface, Myrinet, and InfiniBand, as well as on a shared memory multicore scenario. The reported communication overhead reduction encourages the upcoming incorporation of this device in MPJ Express (http://mpj‐express.org). Copyright © 2011 John Wiley & Sons, Ltd.
Comparison of segmentation algorithms for fluorescence microscopy images of cells
Authors: Dima Alden A. , Elliott John T. , Filliben James J. , Halter Michael , Peskin Adele , Bernal Javier , Kociolek Marcin , Brady Mary C. , Tang Hai C. , Plant Anne L.
Published: June 2011

The analysis of fluorescence microscopy of cells often requires the determination of cell edges. This is typically done using segmentation techniques that separate the cell objects in an image from the surrounding background. This study compares segmentation results from nine different segmentation techniques applied to two different cell lines and five different sets of imaging conditions. Significant variability in the results of segmentation was observed that was due solely to differences in imaging conditions or applications of different algorithms. We quantified and compared the results with a novel bivariate similarity index metric that evaluates the degree of underestimating or overestimating a cell object. The results show that commonly used threshold‐based segmentation techniques are less accurate than k‐means clustering with multiple clusters. Segmentation accuracy varies with imaging conditions that determine the sharpness of cell edges and with geometric features of a cell. Based on this observation, we propose a method that quantifies cell edge character to provide an estimate of how accurately an algorithm will perform. The results of this study will assist the development of criteria for evaluating interlaboratory comparability. Published 2011 Wiley‐Liss, Inc.
The role of glutamate in my professional life: From molecular neuroplasticity to the relief of suffering
Authors: Irwin Scott A.
Published: June 2011

This invited address is offered in celebration of the career of Dr. William T. Greenough, especially the mentorship aspect of this illustrious career. It details how glutamate has been a thread throughout my professional career, including in my training with Bill. Our investigations of the role of metabotropic glutamate receptors in synaptic plasticity, specifically in relation to the fragile‐X mental retardation protein, are described. I then discuss how glutamate has played a role in my current professional life as a psychiatrist working in palliative care. Finally, I end with some words about how the training I received from Bill has had, and continues to have, an impact on my professional development. © 2011 Wiley Periodicals, Inc. Dev Psychobiol 53:482–488, 2011.
Evidence that angiogenesis lags behind neuron and astrocyte growth in experience‐dependent plasticity
Authors: Wallace Christopher S. , Withers Ginger S. , Farnand Alex , Lobingier Braden T. , McCleery Ellen J.
Published: June 2011

Bill Greenough's work on the cell biology of information storage suggests that we cannot understand the mechanism of long‐term memory without understanding the series of cellular transactions that drive coordinated structural changes in neurons, glia, and blood vessels. Here, we show that after 4 days of differential housing, neuropil of EC cortex has expanded significantly, but the vasculature has not, resulting in a dilution of the blood supply. Significant growth of neurons and astrocytes has been reported within this time period, suggesting expression of synaptic plasticity might involve temporally coordinated genomic responses by both neurons and glia. Given that astrocytes appear to couple neuronal and vascular growth during development, we hypothesize that they may also mediate the onset of angiogenesis in response to neural demand in the EC brain. Further, these results may imply that a neuron's capacity for plasticity could be constrained by the rate of vascular expansion. © 2011 Wiley Periodicals, Inc. Dev Psychobiol 53:435–442, 2011.
In vitro approaches to studying the metabolism of new psychoactive compounds
Authors: Peters Frank T. , Meyer Markus R.
Published: June 2011

In the last two decades, a large number of new drugs from several drug classes have appeared on the illicit drug market. While some of these compounds have meanwhile been scheduled as controlled substances, the majority of them are (still) sold as so‐called ‘legal highs’, mostly via the Internet. At the time they appear on the market the metabolism of these drugs is generally unknown. Therefore, it must be studied in order to obtain data necessary for analytical method development as well as toxicological risk assessment. In vitro metabolism studies of new designer drugs can be performed for identification and structure elucidation of new designer drug metabolites or to assess the qualitative and quantitative involvement of certain enzymes in the metabolism of a particular drug. In this review, the value of the following enzyme preparations for in vitro metabolism studies of new designer drugs will be discussed: liver microsomes, recombinant cDNA‐expressed enzymes, liver cytosol, S9 mix, and hepatocytes. This will cover the major metabolic enzymes: cytochrome P450 monooxygenases, flavin‐monooxygenases, monoamine oxidases, UDP‐glucuronyltransferases, sulfotransferases, and catechol‐O‐methyltransferases. Important analytical aspects such as the value of mass spectrometric techniques will also be covered. Copyright © 2011 John Wiley & Sons, Ltd.
Development and validation of an LC‐UV method for the determination of sulfonamides in animal feeds
Authors: Kumar P. , Companyó R.
Published: June 2011

A simple LC‐UV method was developed for the determination of residues of eight sulfonamides (sulfachloropyridazine, sulfadiazine, sulfadimidine, sulfadoxine, sulfamethoxypyridazine, sulfaquinoxaline, sulfamethoxazole, and sulfadimethoxine) in six types of animal feed. C18, Oasis HLB, Plexa and Plexa PCX stationary phases were assessed for the clean‐up step and the latter was chosen as it showed greater efficiency in the clean‐up of interferences. Feed samples spiked with sulfonamides at 2 mg/kg were used to assess the trueness (recovery %) and precision of the method. Mean recovery values ranged from 47% to 66%, intra‐day precision (RSD %) from 4% to 15% and inter‐day precision (RSD %) from 7% to 18% in pig feed. Recoveries and intra‐day precisions were also evaluated in rabbit, hen, cow, chicken and piglet feed matrices. Calibration curves with standards prepared in mobile phase and matrix‐matched calibration curves were compared and the matrix effects were ascertained. The limits of detection and quantification in the feeds ranged from 74 to 265 µg/kg and from 265 to 868 µg/kg, respectively. Copyright © 2011 John Wiley & Sons, Ltd.
Alkali‐like myosin light chain‐1 (myl1) is an early marker for differentiating fast muscle cells in zebrafish
Authors: Burguière A. C. , Nord H. , von Hofsten J.
Published: June 2011

During myogenesis, muscle precursors become divided into either fast‐ or slow‐twitch fibres, which in the zebrafish occupy distinct domains in the embryo. Genes encoding sarcomeric proteins specific for fast or slow fibres are frequently used as lineage markers. In an attempt to identify and evaluate early definitive markers for cells in the fast‐twitch pathway, we analysed genes encoding proteins contributing to the fast sarcomeric structures. The previously uncharacterized zebrafish alkali‐like myosin light chain gene (myl1) was found to be expressed exclusively in cells in the fast‐twitch pathway initiated at an early stage of fast fibre differentiation. Myl1 was expressed earlier, and in a more fibre type restricted manner, than any of the previously described and frequently used fast myosin light and heavy chain and troponin muscle markers mylz2, mylz3, tnni2, tnnt3a, fMyHC1.3. In summary, this study introduces a novel marker for early differentiating fast muscle cells. Developmental Dynamics 240:1856–1863, 2011. © 2011 Wiley‐Liss, Inc.
The Prx1 limb enhancers: Targeted gene expression in developing zebrafish pectoral fins
Authors: Hernández‐Vega Amayra , Minguillón Carolina
Published: June 2011

Limbs represent an excellent model to study the induction, growth, and patterning of several organs. A breakthrough to study gene function in various tissues has been the characterization of regulatory elements that allow tissue‐specific interference of gene function. The mouse Prx1 promoter has been used to generate limb‐specific mutants and overexpress genes in tetrapod limbs. Although zebrafish possess advantages that favor their use to study limb morphogenesis, there is no driver described suitable for specifically interfering with gene function in developing fins. We report the generation of zebrafish lines that express enhanced green fluorescent protein (EGFP) driven by the mouse Prx1 enhancer in developing pectoral fins. We also describe the expression pattern of the zebrafish prrx1 genes and identify three conserved non‐coding elements (CNEs) that we use to generate fin‐specific EGFP reporter lines. Finally, we show that the mouse and zebrafish regulatory elements may be used to modify gene function in pectoral fins. Developmental Dynamics 240:1977–1988, 2011. © 2011 Wiley‐Liss, Inc.
Does the European Pollutant Release and Transfer Register Enable Us to Understand the Environmental Performance of Firms?
Authors: Fikru Mahelet Getachew
Published: June 2011

The study explores a new micro environmental data set, the European Pollutant Release and Transfer Register (E‐PRTR), by identifying limitations and potential strengths. We find that reporting requirements exclude on‐site abatement through end‐of‐the‐pipe techniques and cleaner technologies causing underestimation of firms' actual abatement. In addition, the lack of a mandatory section on production volume and firm size hinders data normalization and the use of control variables in economic analysis. Addressing the above limitations can make the E‐PRTR more usable for policy‐makers, environmentalists and academicians. Furthermore, the paper proposes a normalization procedure based on calculating how much beyond the threshold a firm has abated or emitted; and normalized values are used to approximate the environmental performance of firms. Analysis based on a sample of manufacturing firms suggests that industrial facilities in Europe have performed well in terms of abating a higher percentage of their gross pollution. Copyright © 2011 John Wiley & Sons, Ltd and ERP Environment.
Interleukin‐17‐educated monocytes suppress cytotoxic T‐cell function through B7‐H1 in hepatocellular carcinoma patients
Authors: Zhao Qiyi , Xiao Xiao , Wu Yan , Wei Yi , Zhu Ling‐Yan , Zhou Jia , Kuang Dong‐Ming
Published: June 2011

Substantial evidence indicates that inflammation is a critical component of tumor progression. The proinflammatory IL‐17‐producing cells have recently been detected in tumors, but the effect of IL‐17 on antigen‐presenting cells in tumors is presently unknown. We recently found that B7‐H1+ macrophages (Mφs) were enriched predominantly in the peritumoral stroma of hepatocellular carcinomas (HCCs). Here, we found a positive correlation between IL‐17‐producing cells and B7‐H1‐expressing Mφs in the same area. The B7‐H1+ monocytes/Mφs from HCC tissues expressed significantly more HLA‐DR, CD80, and CD86 than B7‐H1– cells. Accordingly, IL‐17 could activate monocytes to express B7‐H1 in a dose‐dependent manner. Although culture supernatants derived from hepatoma cells also induced B7‐H1 expression on monocytes, IL‐17 additionally increased hepatoma‐mediated B7‐H1 expression. Autocrine inflammatory cytokines released from IL‐17‐activated monocytes stimulated B7‐H1 expression. Moreover, these IL‐17‐exposed monocytes effectively suppressed cytotoxic T‐cell immunity in vitro; the effect could be reversed by blocking B7‐H1 on those monocytes. Consistent with this, cytotoxic T cells from HCC tissues expressed significant B7‐H1 receptor programmed death 1 (PD‐1) and exhibited an exhausted phenotype. These data reveal a fine‐tuned collaborative action between different stromal cells to counteract T‐cell responses in tumors. Such IL‐17‐mediated immune tolerance should be considered for the rational design of effective immune‐based anti‐cancer therapies.
Alternate pathways for Bcl6‐mediated regulation of B cell to plasma cell differentiation
Authors: Alinikula Jukka , Nera Kalle‐Pekka , Junttila Sini , Lassila Olli
Published: June 2011

The transcription factor Bcl6 regulates germinal center formation and differentiation of B cells into high‐affinity antibody‐producing plasma cells. The direct double‐negative regulatory circuit between Bcl6 and Blimp‐1 is well established. We now reveal alternative mechanisms for Bcl6‐mediated regulation of B‐cell differentiation to plasma cells and show with DT40 cells that Bcl6 directly promotes the expression of Bach2, a known suppressor of Blimp‐1. Moreover, Bcl6 suppresses Blimp‐1 expression through direct binding to the IRF4 gene, as well as by promoting the expression of MITF, a known suppressor of IRF4. We also provide evidence that Bcl6 is needed for the expression of AID and UNG, the indispensable proteins for somatic hypermutation and class‐switch recombination, and UNG appears to be a direct Bcl6 target. Our findings reveal a complex regulatory network in which Bcl6 acts as a key element dictating the transition of DT40 B cells to plasma cells.
Characterization of cocoa butter substitutes, milk fat and cocoa butter mixtures
Authors: Wang Fengyan , Liu Yuanfa , Jin Qingzhe , Meng Zong , Wang Xingguo
Published: June 2011

The melting properties and polymorphic behavior of binary and ternary blends of cocoa butter substitutes (CBS), cocoa butter (CB), and milk fat (MF) were studied by using pulsed nuclear magnetic resonance (NMR), differential scanning calorimetry (DSC), and X‐ray diffractometry (XRD). Hydrogenated palm kernel stearin (HPKS) and hydrogenated palm kernel olein (HPKO) were chosen as the two CBS feedstock fats. Both CBS/CB binary blends displayed significant eutectic behaviors. Multiple melting peaks and eutectic effects were observed at 30–50% addition levels of CB to HPKS. The range was broader in HPKO/CB blends. Dilution effect was observed in both CBS/MF blends while slight monotectic effect was also observed in HPKO/MF blends. Ternary phase diagrams and melting curves showed that eutectic effects existed in both ternary blends and the degree of interaction depended on the content of CB and MF. XRD results showed that when pure fat component in each blend exceeded 80%, its polymorphism dominated in the ternary blends. However, when CBS/CB or MF /CB were added at a comparative content (blends D and F), both β and β′ form existed.

Practical applications: Phase properties of fat blends may have significant effects on the sensory characteristics and physical properties of the final products, such as hardness, brittleness, and the bloom formation. This study evaluates the melting properties and the polymorphic characteristics of fat blends of constituents with potential use in the manufacture of confectionery products. A comprehensive analysis of binary and ternary fat blends was conducted in order to provide a guide for compound chocolate production formulation.
Effects of microcapsule constitution on the quality of microencapsulated walnut oil
Authors: Calvo Patricia , Castaño Ángel Luis , Hernández María Teresa , González‐Gómez David
Published: June 2011

The encapsulation is a process by which small particles of core products are packaged within a wall material to form microcapsules. One of the most useful processes for drying thermosensitive substances that are unstable in aqueous solutions is the freeze‐drying technique (lyophilization), which involves conversion of liquid oils in the form of an emulsion into dry powders. In this paper, the chemical composition of walnut oil and microencapsulation conditions (microcapsule wall material composition) have been evaluated in order to assess the influence of the microencapsulation process on the quality and shelf‐life of microencapsulated walnut oil. Highest encapsulation yield was achieved when maltodextrin, carboxymethylcellulose, and lecithin were used as encapsulation agents and the ratio of oil–wall material was 1:1.5. Under these conditions all the oil was encapsulated. The presence of protein constituents in the microcapsule wall material extended the shelf‐life of the microencapsulated walnut oil regardless of the use of antioxidant additives.
Predicting the equilibrium bed slope in natural streams using a stochastic model for incipient sediment motion
Authors: Ferro Vito , Porto Paolo
Published: June 2011

In this paper, a method to predict the equilibrium bed slope in natural streams based on the incipient motion criterion is proposed. The method is based on the criterion suggested by Gessler to simulate the grain size distribution of the armour coat using the concept of critical shear stress of a sediment mixture. In particular, a different expression of the probability for a single particle size to be part of the armour coat is firstly proposed; then, a simple two‐steps criterion is suggested to estimate the safety factor required by the proposed approach. The method is applied in three different Italian regions (Calabria, Basilicata, and Tuscany) and required several field campaigns involving the survey of 251 stream reaches upstream of grade‐control structures. The area including five Calabrian streams is firstly used to test the suitability of the two‐steps approach. In this area, considering the detailed information about the particle size of bed material, the effect of using a simplified grain size distribution for each torrent is also checked. The method is then applied within the two additional areas (Basilicata and Tuscany) in order to check the geographic influence on the prediction of the stable longitudinal profile. A comparison between measured and estimated values of the equilibrium bed slope showed a good agreement for the Calabrian streams, where the number of the investigated stream reaches is greater, and satisfactory results for the torrents located in Basilicata and Tuscany where the field data set is more limited. The overall results encourage the extension of the proposed method to additional field data and suggest the use of this approach by hydraulic designers in order to stabilize the longitudinal profile of natural streams. Copyright © 2011 John Wiley & Sons, Ltd.
Interactions of cadmium and zinc impact their toxicity to the earthworm Aporrectodea caliginosa
Authors: Qiu Hao , Vijver Martina G , Peijnenburg Willie J.G.M
Published: June 2011

Individual and binary mixture effects of Cd and Zn on mortality of the earthworm Aporrectodea caliginosa were investigated in one soil type. Mutual, systemic interactions of Cd and Zn were assessed over a broad range of concentration combinations. Exposures were expressed as measured total concentrations in soil, porewater concentrations, and CaCl2-extractable concentrations. The Cd-Zn and Zn-Cd interactions in soil were estimated by comparing partition coefficients (Kd) of one metal in the presence and absence of the second metal. Simple patterns of mixture toxicity (additive, antagonistic, or synergistic) were evaluated by the toxic unit approach. The more complex patterns (dose ratio dependent or dose level dependent) were quantified by the MIXTOX model. The partitioning of Cd and Zn between soil and pore water was affected neither by their concentration nor presence of the other metal, and metal partitioning remained linear at all exposure levels tested. The effect of the Cd and Zn mixtures on mortality of A. caliginosa was mainly antagonistic, and the magnitude of antagonism (1.1– 2.7 toxic units) was dependent upon both the relative concentrations of Cd and Zn and the concentration magnitudes. Interactions of both metals occurred at the organism level and were manifested in terms of effects (28-d median lethal concentrations). The present study highlights the importance of identifying the relative influence of various interactions from external exposure to internal assimilation in evaluating mixture toxicity. Environ. Toxicol. Chem. 2011;30:2084–2093. © 2011 SETAC
Selective BOLD responses to individual finger movement measured with fMRI at 3T
Authors: Olman Cheryl A. , Pickett Kristen A. , Schallmo Michael‐Paul , Kimberley Teresa J.
Published: June 2011

Although the gross somatotopic organization of the posterior bank of the precentral gyrus is well established, a fine scale organization of the representations of the digits of the hand has not been fully characterized. Previous neuroimaging studies have failed to find clear evidence for a specificity of digit representations in motor cortex, but rather report a distributed network of control. Reported here are the results of two experiments; in Experiment 1 a sequential finger tapping task produced strong blood oxygen level dependent (BOLD) responses in the contralateral precentral gyrus, but there was a lack of specificity for distinguishing individual representations. A randomly ordered task did accomplish this goal. In the second experiment, a randomly ordered finger‐tapping task was used and the findings demonstrated BOLD responses in clusters of voxels specific to movement of a single digit. The region of interest defined for each digit comprised several noncontiguous clusters. A “selectivity index” was developed to quantify the magnitude of the BOLD response to the movement of a specific digit, relative to BOLD response associated with movement of other digits. Strong evidence of BOLD selectivity (albeit not exclusivity) was found in the hemisphere contralateral to the cued digit; however, there was no evidence for an orderly spatial topography. These findings demonstrate that a selectivity of activation is quantifiable, supports a theory of noncontiguous distribution of control, and provides a method for comparing between healthy and impaired populations and investigating changes following training or intervention. Hum Brain Mapp, 2011. © 2011 Wiley‐Liss, Inc.
Engagement of amygdala in third‐person view of face‐to‐face interaction
Authors: Kujala Miiamaaria V. , Carlson Synnöve , Hari Riitta
Published: June 2011

Humans often watch interactions between other people without taking part in the interaction themselves. Strikingly little is, however, known about how gestures and expressions of two interacting humans are processed in the observer's brain, since the study of social cues has mostly focused on the perception of solitary humans. To investigate the neural underpinnings of the third‐person view of social interaction, we studied brain activations of subjects who observed two humans either facing toward or away from each other. Activations within the amygdala, posterior superior temporal sulcus (pSTS), and dorsomedial prefrontal cortex (dmPFC) were sensitive to the interactional position of the observed people and distinguished humans facing toward from humans facing away. The amygdala was most sensitive to face‐to‐face interaction and did not differentiate the humans facing away from the pixelated control figures, whereas the pSTS dissociated both human stimuli from the pixel figures. The results of the amygdala reactivity suggest that, in addition to regulating interpersonal distance towards oneself, the amygdala is involved in the assessment of the proximity between two other persons. Hum Brain Mapp, 2012. © 2011 Wiley Periodicals, Inc.
Neurodegeneration in friedreich's ataxia is associated with a mixed activation pattern of the brain. A fMRI study
Authors: Ginestroni Andrea , Diciotti Stefano , Cecchi Paolo , Pesaresi Ilaria , Tessa Carlo , Giannelli Marco , Nave Riccardo Della , Salvatore Elena , Salvi Fabrizio , Dotti Maria Teresa , Piacentini Silvia , Soricelli Andrea , Cosottini Mirco , De Stefano Nicola , Mascalchi Mario
Published: June 2011

Friedreich's ataxia (FRDA) is associated with a distributed pattern of neurodegeneration in the spinal cord and the brain secondary to selective neuronal loss. We used functional MR Imaging (fMRI) to explore brain activation in FRDA patients during two motor‐sensory tasks of different complexity, i.e. continuous hand tapping and writing of “8” figure, with the right dominant hand and without visual feedback. Seventeen FRDA patients and two groups of age‐matched healthy controls were recruited. Task execution was monitored and recorded using MR‐compatible devices. Hand tapping was correctly performed by 11 (65%) patients and writing of the “8” by 7 (41%) patients. After correction for behavioral variables, FRDA patients showed in both tasks areas of significantly lower activation in the left primary sensory‐motor cortex and right cerebellum. Also left thalamus and right dorsolateral prefrontal cortex showed hypo‐activation during hand tapping. During writing of the “8” task FRDA patients showed areas of higher activation in the right parietal and precentral cortex, globus pallidus, and putamen. Activation of right parietal cortex, anterior cingulum, globus pallidus, and putamen during writing of the “8” increased with severity of the neurological deficit. In conclusion fMRI demonstrates in FRDA a mixed pattern constituted by areas of decreased activation and areas of increased activation. The decreased activation in the primary motor cortex and cerebellum presumably reflects a regional neuronal damage, the decreased activation of the left thalamus and primary sensory cortex could be secondary to deafferentation phenomena, and the increased activation of right parietal cortex and striatum might have a possible compensatory significance. Hum Brain Mapp, 2012. © 2011 Wiley Periodicals, Inc
Disruption of limbic white matter pathways in mild cognitive impairment and Alzheimer's disease: A DTI/FDG‐PET Study
Authors: Bozoki Andrea C. , Korolev Igor O. , Davis Nathan C. , Hoisington Lori A. , Berger Kevin L.
Published: June 2011

Background: Alzheimer's disease (AD) and mild cognitive impairment (MCI) affect the limbic system, causing medial temporal lobe (MTL) atrophy and posterior cingulate cortex (PCC) hypometabolism. Additionally, diffusion tensor imaging (DTI) studies have demonstrated that MCI and AD involve alterations in cerebral white matter (WM) integrity. Objectives: To test if (1) patients with MCI and AD exhibit decreases in the integrity of limbic WM pathways; (2) disconnection between PCC and MTL, manifested as disruption of the cingulum bundle, contributes to PCC hypometabolism during incipient AD. Methods: We measured fractional anisotropy (FA) and volume of the fornix and cingulum using DTI in 23 individuals with MCI, 21 with mild‐to‐moderate AD, and 16 normal control (NC) subjects. We also measured PCC metabolism using 18F‐fluorodeoxyglucose positron emission tomography (FDG‐PET) in AD and MCI patients. Results: Fornix FA and volume were reduced in MCI and AD to a similar extent. Descending cingulum FA was reduced in AD while volume was reduced in MCI and even more so in AD. Both FA and volume of the fornix and descending cingulum reliably discriminated between NC and AD. Fornix FA and descending cingulum volume also reliably discriminated between NC and MCI. Only descending cingulum volume reliably discriminated between MCI and AD. In the combined MCI‐AD cohort, PCC metabolism directly correlated with both FA and volume of the descending cingulum. Conclusions: Disruption of limbic WM pathways is evident during both MCI and AD. Disconnection of the PCC from MTL at the cingulum bundle contributes to PCC hypometabolism during incipient AD. Hum Brain Mapp, 2012. © 2011 Wiley Periodicals, Inc
Hypoxia-inducible factor 1 alpha–activated angiopoietin-like protein 4 contributes to tumor metastasis via vascular cell adhesion molecule-1/integrin β1 signaling in human hepatocellular carcinoma
Authors: Li Hong , Ge Chao , Zhao Fangyu , Yan Mingxia , Hu Chen , Jia Deshui , Tian Hua , Zhu Miaoxin , Chen Taoyang , Jiang Guoping , Xie Haiyang , Cui Ying , Gu Jianren , Tu Hong , He Xianghuo , Yao Ming , Liu Yongzhong , Li Jinjun
Published: June 2011

Angiopoietin-like protein 4 (ANGPTL4) plays complex and often contradictory roles in vascular biology and tumor metastasis, but little is known about its function in hepatocellular carcinoma (HCC) metastasis. In the present study, we showed that hypoxia-inducible factor 1α (HIF-1α) directly up-regulates ANGPTL4, and its stableness positively correlates with ANGPTL4 expression in HCC tissue. Overexpression of ANGPTL4 significantly increased HCC cell transendothelial migration

in vitro

and intrahepatic and distal pulmonary metastasis

in vivo,

whereas silencing ANGPTL4 expression or treatment with a neutralizing antibody specific for ANGPTL4 protein resulted in a reduced transendothelial migration. We also found that serum ANGPTL4 is higher in HCC patients, compared to healthy control, and correlates with intrahepatic metastasis and histological grade. Further, secreted ANGPTL4 promotes transendothelial migration and metastasis of HCC cells

in vitro

and

in vivo

through the up-regulation of vascular cell adhesion molecule-1 (VCAM-1) of human umbilical vein endothelial cells and the activation of the VCAM-1/integrin β1 axis.

Conclusion: ANGPTL4

is a target gene of HIF-1α and acts as an important regulator in the metastasis of HCC. Serum ANGPTL4 correlates with tumor progression and metastasis and might be used to indicate prognosis in HCC patients. (HEPATOLOGY 2011 54:910–919;)
Prolonged hepatomegaly in mice that cannot inactivate bacterial endotoxin
Authors: Shao Baomei , Kitchens Richard L. , Munford Robert S. , Rogers Thomas E. , Rockey Don C. , Varley Alan W.
Published: June 2011

Transient hepatomegaly often accompanies acute bacterial infections. Reversible, dose-dependent hepatomegaly also occurs when animals are given intravenous infusions of bacterial lipopolysaccharide (LPS). We found that recovery from LPS-induced hepatomegaly requires a host enzyme, acyloxyacyl hydrolase (AOAH), that inactivates LPS. When we challenged

Aoah

−/− mice with low doses of LPS or Gram-negative bacteria, their livers remained enlarged (as much as 80% above normal) many weeks longer than did the livers of

Aoah

+/+ animals. When compared with livers from LPS-primed

Aoah

+/+ mice, LPS-primed

Aoah

−/− livers had (1) more numerous and larger Kupffer cells, (2) intrasinusoidal leukocyte aggregates and activated sinusoidal endothelial cells, and (3) sustained production of interleukin (IL)-10 and messenger RNAs (mRNAs) for tumor necrosis factor (TNF), IL-10, and IRAK-M. Depleting Kupffer cells decreased the liver enlargement by ≈40%, whereas depletion of neutrophils, dendritic cells, natural killer (NK) cells, NK-T cells, or B cells had no effect. Pretreatment with dexamethasone almost completely prevented prolonged hepatomegaly in

Aoah

−/− mice, whereas neutralizing TNF or interleukin-1β was only partially effective. In contrast, an antagonistic antibody to the IL-10 receptor increased LPS-induced hepatomegaly by as much as 50%. Conclusion: our findings suggest that persistently active LPS induces Kupffer cells to elaborate mediators that promote the accumulation of leukocytes within enlarged sinusoids. Large increases in IL-10 and several other modulatory molecules are unable to prevent prolonged hepatomegaly in mice that cannot inactivate LPS. The striking findings in this mouse model should encourage studies to find out how AOAH contributes to human liver physiology and disease. (HEPATOLOGY 2011;)
Both innate and adaptive immunity mediate protective immunity against hepatitis C virus infection in chimpanzees
Authors: Barth Heidi , Rybczynska Jolanta , Patient Romuald , Choi Youkyung , Sapp Ronda K. , Baumert Thomas F. , Krawczynski Kris , Liang Jake T.
Published: June 2011

Understanding the immunological correlates associated with protective immunity following hepatitis C virus (HCV) reexposure is a prerequisite for the design of effective HCV vaccines and immunotherapeutics. In this study we performed a comprehensive analysis of innate and adaptive immunity following HCV reexposure of two chimpanzees that had previously recovered from HCV-JFH1 infection. One of the chimpanzees, CH10274, became protected from active viremia by repeated challenges with homologous HCV-JFH1 and developed neutralizing antibodies, but was later infected with high-level viremia by a heterologous challenge with the HCV H77 virus that persisted for more than 1 year. The other chimpanzee, CH10273, was protected from a similar, heterologous H77 challenge without any evidence of neutralizing antibodies. Peripheral HCV-specific T-cell responses were present in both chimpanzees after challenges and, interestingly, the overall magnitude of response was lower in uninfected CH10273, which, however, exhibited a more robust CD8+ T-cell response. CH10273 showed higher hepatic expression of CD8 and CD56 (natural killer) markers than CH10274 did shortly after inoculation with H77. The heightened T-cell response was associated with an enhanced hepatic production of interferons (both type I and II) and interferon-stimulated genes (ISGs) in CH10273. Therefore, protection or clearance of HCV reinfection upon heterologous rechallenge depends on the activation of both intrahepatic innate and cellular immune responses. Furthermore, our results suggest that serum neutralizing antibodies may contribute to early control of viral replication and spread after homologous HCV rechallenges but may not be sufficient for a long-term protective immunity. Conclusion: Our study shows that protective immunity against HCV reinfection is orchestrated by a complex network of innate and adaptive immune responses. (Hepatology 2011;)
One‐Pot, Four‐Component Synthesis of Fully Substituted 1,3,4‐Oxadiazole Derivatives from (Isocyanoimino)triphenylphosphorane, a Primary Amine, an Aromatic Carboxylic Acid, and Chloroacetone
Authors: Ramazani Ali , Zeinali Nasrabadi Fatemeh , Ahmadi Yavar
Published: June 2011

The 1 : 1 imine intermediate 7 generated by the addition of a primary amine 2 to chloroacetone (1) is trapped by (isocyanoimino)triphenylphosphorane (4) in the presence of an aromatic carboxylic acid 3 and leads to the formation of the corresponding iminophosphorane intermediate 9 (Scheme 2). The 1,3,4‐oxadiazole derivatives 5 are then formed via an intramolecular aza‐Wittig reaction of the iminophosphorane intermediate 9. The reactions were completed under neutral conditions at room temperature. The fully substituted 1,3,4‐oxadiazole derivatives 5 were produced in high yields (Table).
Indium(III) Chloride‐Catalyzed Conversion of {[(Benzyloxy)carbonyl]amino}‐Substituted Sulfones with 2‐[(Trimethylsilyl)oxy]furan: A Facile Access to γ‐Butenolactone Derivatives Containing a Protected Amino Group
Authors: Das Biswanath , Sudhakar Chithaluri , Reddy Parigi Raghavendar , Kashanna Jajula
Published: June 2011

Treatment of {[(benzyloxy)carbonyl]amino}‐substituted sulfones 1 with 2‐[(trimethylsilyl)oxy]furan (2) in the presence of InCl3 as a catalyst at room temperature produced the γ‐butenolactone derivatives 3 and 4 containing a protected amino group (Scheme 1). The products were formed in high yields (81–92%) within 3–10 h favoring the anti‐isomer 3.
Three New Sesquiterpene Pyridine Alkaloids from Euonymus fortunei
Authors: Da Yang Ying , Yang Guang Zhong , Liao Mao Chuan , Mei Zhi Nan
Published: June 2011

Three new macrocyclic β‐dihydroagarofuran‐type sesquiterpene pyridine alkaloids, fortuneines A (1), B (2), and C (3), together with the four known alkaloids wilfornine E (4), aquifoliunine E‐I (5), euoverrine B (6), and euojaponine I (7), were isolated from the aerial parts of Euonymus fortunei. Their structures were elucidated by spectroscopic methods, including HR‐ESI‐MS, 1H‐ and 13C‐NMR, DEPT, 1H,1H‐COSY, HSQC, HMBC, and ROESY. This is the first isolation of the above sesquiterpene pyridine alkaloids from this plant, except for compound 6.
Palladium Nanoparticles on Graphite Oxide as Catalyst for SuzukiMiyaura, MizorokiHeck, and Sonogashira Reactions
Authors: Rumi Luigi , Scheuermann Gil M. , Mülhaupt Rolf , Bannwarth Willi
Published: June 2011

Pd2+‐Exchanged graphite oxide (GO) serves as a precatalyst for the formation of Pd‐nanoparticles which are then deposited on the highly functionalized carbonaceous support. This versatile, air‐stable, and ligand‐free system was applied successfully to SuzukiMiyaura couplings of some aryl chlorides and to the MizorokiHeck as well as the Sonogashira reaction showing relatively high activities and good selectivities. Like with other ligand‐free supported systems, the reaction proceeded dominantly by a homogeneous mechanism, but attack of an aryl iodide to Pd‐nanoparticles can be excluded as substantial contribution to the entire catalytic process. Beside its straightforward preparation and its stability in air, the system combines the advantages of both homogeneous and heterogeneous catalysis.
People's policies for the health of the poor globally
Authors: Govender Veloshnee , Mooney Gavin
Published: June 2011

In this paper, we argue that the dominant role played by governments of the developed countries in global health policies is a critical but often an ignored factor in contributing to the lack of progress in global health. The solution to this challenge lies in efforts to ‘democratise’ global decision making and to argue for a greater say of the poor globally in policies affecting them. Although there are potentially many ways to achieve this, the paper proposes ‘communitarian claims’ as one way to have the voice of people globally involved and to make decisions about how best to allocate resources globally. It is argued that such claims can be advanced at a practical level through ‘citizens’ juries' as evident from the experience in Australia. That experience and with increasing evidence from elsewhere, there is a strong indication from communities of desires for a very different set of values to underpin healthcare than the Australian and other governments, in partnership with global institutions, deliver. Copyright © 2011 John Wiley & Sons, Ltd.
Trophic magnification factors: Considerations of ecology, ecosystems, and study design
Authors: Borgå Katrine , Kidd Karen A , Muir Derek CG , Berglund Olof , Conder Jason M , Gobas Frank APC , Kucklick John , Malm Olaf , Powell David E
Published: June 2011

Recent reviews by researchers from academia, industry, and government have revealed that the criteria used by the Stockholm Convention on persistent organic pollutants under the United Nations Environment Programme are not always able to identify the actual bioaccumulative capacity of some substances, by use of chemical properties such as the octanol–water partitioning coefficient. Trophic magnification factors (TMFs) were suggested as a more reliable tool for bioaccumulation assessment of chemicals that have been in commerce long enough to be quantitatively measured in environmental samples. TMFs are increasingly used to quantify biomagnification and represent the average diet-to-consumer transfer of a chemical through food webs. They differ from biomagnification factors, which apply to individual species and can be highly variable between predator–prey combinations. The TMF is calculated from the slope of a regression between the chemical concentration and trophic level of organisms in the food web. The trophic level can be determined from stable N isotope ratios (δ15N). In this article, we give the background for the development of TMFs, identify and discuss impacts of ecosystem and ecological variables on their values, and discuss challenges and uncertainties associated with contaminant measurements and the use of δ15N for trophic level estimations. Recommendations are provided for experimental design, data treatment, and statistical analyses, including advice for users on reporting and interpreting TMF data. Interspecies intrinsic ecological and organismal properties such as thermoregulation, reproductive status, migration, and age, particularly among species at higher trophic levels with high contaminant concentrations, can influence the TMF (i.e., regression slope). Following recommendations herein for study design, empirical TMFs are likely to be useful for understanding the food web biomagnification potential of chemicals, where the target is to definitively identify if chemicals biomagnify (i.e., TMF > or < 1). TMFs may be less useful in species- and site-specific risk assessments, where the goal is to predict absolute contaminant concentrations in organisms in relation to threshold levels. Integr Environ Assess Manag 2012;8:64–84. © 2011 SETAC
Versican V1 isoform regulates cell‐associated matrix formation and cell behavior differentially from aggrecan in Swarm rat chondrosarcoma cells
Authors: Wasa Junji , Nishida Yoshihiro , Shinomura Tamayuki , Isogai Zenzo , Futamura Naohisa , Urakawa Hiroshi , Arai Eisuke , Kozawa Eiji , Tsukushi Satoshi , Ishiguro Naoki
Published: June 2011

Versican, a large chondroitin sulfate proteoglycan that binds hyaluronan and is composed of large extracellular matrix aggregates, has been shown to correlate with tumor progression. No studies have examined the roles of versican in chondrosarcoma nor compared them to those of aggrecan. In clinical specimens of human chondromatous tumors, versican expression was significantly increased in malignant tumors, moreover, as the tumor grade increased. To clarify the roles of versican in chondrosarcoma, versican splicing variant 1, variant 3 or only GFP was stably transfected to Swarm rat chondrosarcoma cells with Trap‐In System. Forced expression of versican V1 isoform in Swarm rat chondrosarcoma cells induced a marked increase of cell‐associated matrix compared to V3‐, GFP‐ transfected or RCS cells. Versican was immunolocalized in a fashion similar to that of hyaluronan and more diffusively than aggrecan. Anchor‐dependent and ‐independent growth was not affected by versican isoform expression, whereas cell motility and migration were significantly enhanced by V1 isoform transfection. Tumors formed in vivo with V1‐transfected cells exhibited more myxomatous area and included more spindle shaped cells. These results support the concept that versican has the capacity to form more extensive cell‐associated matrix than aggrecan, and the prominent matrix formation alters the cell behavior of chondrosarcoma more aggressively. These observations suggest that versican expression may serve as a marker of tumor grade determination in chondrosarcoma and possibly help to decide on therapeutic targets in higher grades of chondrosarcoma.
Occupation and risk of upper aerodigestive tract cancer: The ARCAGE study
Authors: Richiardi Lorenzo , Corbin Marine , Marron Manuela , Ahrens Wolfgang , Pohlabeln Hermann , Lagiou Pagona , Minaki Ploumitsa , Agudo Antonio , Castellsague Xavier , Slamova Alena , Schejbalova Miriam , Kjaerheim Kristina , Barzan Luigi , Talamini Renato , Macfarlane Gary J. , Macfarlane Tatiana V. , Canova Cristina , Simonato Lorenzo , Conway David I. , McKinney Patricia A. , Sneddon Linda , Thomson Peter , Znaor Ariana , Healy Claire M. , McCartan Bernard E. , Benhamou Simone , Bouchardy Christine , Hashibe Mia , Brennan Paul , Merletti Franco
Published: June 2011

We investigated the association between occupational history and upper aerodigestive tract (UADT) cancer risk in the ARCAGE European case–control study. The study included 1,851 patients with incident cancer of the oral cavity, oropharynx, hypopharynx, larynx or esophagus and 1,949 controls. We estimated odds ratios (OR) and 95% confidence intervals (CI) for ever employment in 283 occupations and 172 industries, adjusting for smoking and alcohol. Men (1,457 cases) and women (394 cases) were analyzed separately and we incorporated a semi‐Bayes adjustment approach for multiple comparisons. Among men, we found increased risks for occupational categories previously reported to be associated with at least one type of UADT cancer, including painters (OR = 1.74, 95% CI: 1.01–3.00), bricklayers (1.58, 1.05–2.37), workers employed in the erection of roofs and frames (2.62, 1.08–6.36), reinforced concreters (3.46, 1.11–10.8), dockers (2.91, 1.05–8.05) and workers employed in the construction of roads (3.03, 1.23–7.46), general construction of buildings (1.44, 1.12–1.85) and cargo handling (2.60, 1.17–5.75). With the exception of the first three categories, risks both increased when restricting to long duration of employment and remained elevated after semi‐Bayes adjustment. Increased risks were also found for loggers (3.56, 1.20–10.5) and cattle and dairy farming (3.60, 1.15–11.2). Among women, there was no clear evidence of increased risks of UADT cancer in association with occupations or industrial activities. This study provides evidence of an association between some occupational categories and UADT cancer risk among men. The most consistent findings, also supported by previous studies, were obtained for specific workers employed in the construction industry.
Histone deacetylase inhibition as an anticancer telomerase‐targeting strategy
Authors: Rahman Ruman , Grundy Richard
Published: June 2011

Aberrant epigenetic regulation of gene expression contributes to tumor initiation and progression. Studies from a plethora of hematologic and solid tumors support the use of histone deacetylase inhibitors (HDACi) as potent anticancer agents. The mechanism(s) of HDACi‐induced cancer growth inhibition and cell death are complex and incompletely elucidated. Here, we discuss erroneous epigenetic regulation of hTERT transcription in cancer cells and propose that alleviation of an improper acetylation–deacetylation balance at the hTERT promoter, is one mode by which HDACi induces anticancer effects. We conclude with some pertinent questions and future perspectives arising from the recent impetus in HDACi preclinical and early clinical studies, with particular attention to the cancer stem cell therapeutic paradigm and its relevance to tumor resistance.