bluuebunny/crossref_metadata_2025 huggingface dataset:
Stability of Bovine Spongiform Encephalopathy Prions: Absence of Prion Protein Degradation by Bovine Gut Microbiota
Authors: Böhnlein C. , Groschup M. H. , Maertlbauer E. , Pichner R. , Gareis M.
Published: February 2012

Bovine spongiform encephalopathy (BSE) is transmitted by the oral route. However, the impacts of anaerobic fermentation processes in cattle on the stability of BSE‐associated prion protein (PrPSc) are still unresolved. In this study, experiments were designed to assess the ability of complex ruminal and colonic contents of bovines to degrade BSE‐derived PrPSc. No significant decrease in PrPSc levels in BSE brain homogenates was detected by Western blotting after up to 66 h of co‐incubation with intestinal fluids. These results indicate that BSE‐associated PrPSc survive gastrointestinal digestion processes in cattle and might be excreted via faeces.
Hydroelastic Modal Analysis of the Perforated Cylindrical Shell in SMART
Authors: Choi Youngin , Lim Seungho , Park Kyoung-Su , Park No-Cheol , Park Young-Pil , Jeong Kyeong-Hoon , Park Jin-Seok
Published: February 2012

The System-integrated Modular Advanced ReacTor (SMART) developed by KAERI includes components like a core, steam generators, coolant pumps, and a pressurizer inside the reactor vessel. Though the integrated structure improves the safety of the reactor, it can be excited by an earthquake and pump pulsations. It is important to identify dynamic characteristics of the reactor internals considering fluid-structure interaction caused by inner coolant for preventing damage from the excitations. Thus, the finite element model is constructed to identify dynamic characteristics and natural frequencies and mode shapes are extracted from this finite element model.
The SPES3 Facility for Testing an Integral Layout SMR: BDBE Simulation Analysis
Authors: Ferri Roberta , Achilli Andrea , Congiu Cinzia , Cattadori Gustavo , Bianchi Fosco , Meloni Paride , Monti Stefano , Luce Alfredo , Ricotti Marco Enrico , Papini Davide , Grgic´ Davor
Published: February 2012

The SPES3 facility is being built at the SIET laboratories, in the frame of an R&D program on Nuclear Fission, led by ENEA and funded by the Italian Ministry of Economic Development. The facility is based on the IRIS reactor design, an advanced medium size, integral layout, pressurized water reactor, based on the proven technology of PWR with an innovative configuration and safety features suitable to cope with Loss of Coolant Accidents through a dynamic coupling of the primary and containment systems. SPES3 is suitable to test the plant response to postulated Design and Beyond Design Basis Events, providing experimental data for code validation and plant safety analysis. It reproduces the primary, secondary and containment systems of the reactor with 1:100 volume scale, full elevation, prototypical fluid and thermal-hydraulic conditions. A design-calculation feedback process, based on the comparison between IRIS and SPES3 simulations, performed respectively by FER, with GOTHIC and RELAP5 coupled codes, and by SIET, with RELAP5 code, led to reduce the differences in the two plants behaviour, versus a 2-inch equivalent DVI line DEG break, considered the most challenging LOCA for the IRIS plant. Once available the final design of SPES3, further calculations were performed to investigate Beyond Design Basis Events, where the intervention of the Passive Containment Condenser is fundamental for the accident recovery. Sensitivity analyses showed the importance of the PCC actuation time, to limit the containment pressure, to reach an early pressure equalization between the primary and containment systems and to allow passive water transfer from the containment to the RPV, enhanced by the ADS Stage-II opening.
Recalibrating Intellectual Property Rights to Enhance Translational Research Collaborations
Authors: Bubela Tania , FitzGerald Garret A. , Gold E. Richard
Published: February 2012

New collaborative models of therapeutic research and development require active governance of intellectual property rights to enable sharing.
Phytosphingosine-1-Phosphate Is a Signaling Molecule Involved in Miconazole Resistance in Sessile Candida albicans Cells
Authors: Vandenbosch Davy , Bink Anna , Govaert Gilmer , Cammue Bruno P. A. , Nelis Hans J. , Thevissen Karin , Coenye Tom
Published: February 2012

Previous research has shown that 1% to 10% of sessile
Candida albicans
cells survive treatment with high doses of miconazole (a fungicidal imidazole). In the present study, we investigated the involvement of sphingolipid biosynthetic intermediates in this survival. We observed that the
LCB4
gene, coding for the enzyme that catalyzes the phosphorylation of dihydrosphingosine and phytosphingosine, is important in governing the miconazole resistance of sessile
Saccharomyces cerevisiae
and
C. albicans
cells. The addition of 10 nM phytosphingosine-1-phosphate (PHS-1-P) drastically reduced the intracellular miconazole concentration and significantly increased the miconazole resistance of a hypersusceptible
C. albicans
heterozygous
LCB4/lcb4
mutant, indicating a protective effect of PHS-1-P against miconazole-induced cell death in sessile cells. At this concentration of PHS-1-P, we did not observe any effect on the fluidity of the cytoplasmic membrane. The protective effect of PHS-1-P was not observed when the efflux pumps were inhibited or when tested in a mutant without functional efflux systems. Also, the addition of PHS-1-P during miconazole treatment increased the expression levels of genes coding for efflux pumps, leading to the hypothesis that PHS-1-P acts as a signaling molecule and enhances the efflux of miconazole in sessile
C. albicans
cells.
No Decrease in Susceptibility to NVC-422 in Multiple-Passage Studies with Methicillin-Resistant Staphylococcus aureus, S. aureus, Pseudomonas aeruginosa, and Escherichia coli
Authors: D'Lima Louisa , Friedman Lisa , Wang Lu , Xu Ping , Anderson Mark , Debabov Dmitri
Published: February 2012

Twenty-five serial passages of
Escherichia coli
,
Pseudomonas aeruginosa
, and
Staphylococcus aureus
and 50 passages of methicillin-resistant
Staphylococcus aureus
resulted in no significant increase in NVC-422 MICs, while ciprofloxacin MICs increased 256-fold for
E. coli
and 32-fold for
P. aeruginosa
and
S. aureus
. Mupirocin, fusidic acid, and retapamulin MICs for MRSA increased 64-, 256-, and 16-fold, respectively. No cross-resistance to NVC-422 was observed with mupirocin-, fusidic acid-, and retapamulin-resistant strains.
Comparison of the Clinical Characteristics and Outcomes Associated with Vancomycin-Resistant Enterococcus faecalis and Vancomycin-Resistant E. faecium Bacteremia
Authors: Hayakawa Kayoko , Marchaim Dror , Martin Emily T. , Tiwari Namita , Yousuf Adnan , Sunkara Bharath , Pulluru Harish , Kotra Harikrishna , Hasan Asma , Bheemreddy Suchitha , Sheth Puja , Lee Dae-Won , Kamatam Srinivasa , Bathina Pradeep , Nanjireddy Priyanka , Chalana Indu K. , Patel Satyam , Kumar Sarwan , Vahia Amit , Ku Kimberly , Yee Victoria , Swan Jessie , Pogue Jason M. , Lephart Paul R. , Rybak Michael J. , Kaye Keith S.
Published: February 2012

In published studies, cohorts of patients with bacteremia due to vancomycin-resistant
Enterococcus
(VRE) have predominantly been infected with
Enterococcus faecium
. Little is known about the epidemiology and outcomes associated with bacteremia due to VR
Enterococcus faecalis
. A retrospective study of isolates obtained from January 2008 to October 2010 was conducted at Detroit Medical Center (DMC). Unique patients with blood cultures positive for VRE were reviewed. Outcomes were analyzed using logistic regression. During the study period, 105 cases of bacteremia due to VR
E. faecalis
and 197 cases of bacteremia due to VR
E. faecium
were identified. The mean age in the study cohort was 61.5 ± 15 years; 162 subjects (53.6%) were male. After controlling for a propensity score, bacteremia due to VR
E. faecalis
was associated with >2-fold-lower in-hospital mortality than bacteremia due to VR
E. faecium
. Interestingly, bacteremia due to VR
E. faecalis
was associated with longer hospital stay after VRE isolation, although total length of stay was similar for groups with VR
E. faecalis
and VR
E. faecium
. Bacteremia due to VR
E. faecalis
was associated with a >2-fold-lower risk for mortality than bacteremia due to VR
E. faecium
, possibly due to the availability of β-lactam therapeutics for treatment of VR
E. faecalis
.
Mannheimia haemolytica and Its Leukotoxin Cause Macrophage Extracellular Trap Formation by Bovine Macrophages
Authors: Aulik Nicole A. , Hellenbrand Katrina M. , Czuprynski Charles J.
Published: February 2012

Human and bovine neutrophils release neutrophil extracellular traps (NETs), which are protein-studded DNA matrices capable of extracellular trapping and killing of pathogens. Recently, we reported that bovine neutrophils release NETs in response to the important respiratory pathogen
Mannheimia haemolytica
and its leukotoxin (LKT). Here, we demonstrate macrophage extracellular trap (MET) formation by bovine monocyte-derived macrophages exposed to
M. haemolytica
or its LKT. Both native fully active LKT and noncytolytic pro-LKT (produced by an
lktC
mutant of
M. haemolytica
) stimulated MET formation. Confocal and scanning electron microscopy revealed a network of DNA fibrils with colocalized histones in extracellular traps released from bovine macrophages. Formation of METs required NADPH oxidase activity, as previously demonstrated for NET formation. METs formed in response to LKT trapped and killed a portion of the
M. haemolytica
cells. Bovine alveolar macrophages, but not peripheral blood monocytes, also formed METs in response to
M. haemolytica
cells. MET formation was not restricted to bovine macrophages. We also observed MET formation by the mouse macrophage cell line RAW 264.7 and by human THP-1 cell-derived macrophages, in response to
Escherichia coli
hemolysin. The latter is a member of the repeats-in-toxin (RTX) toxin family related to the
M. haemolytica
leukotoxin. This study demonstrates that macrophages, like neutrophils, can form extracellular traps in response to bacterial pathogens and their exotoxins.
Comparative Genomics of Enterococci: Variation in Enterococcus faecalis, Clade Structure in E. faecium, and Defining Characteristics of
E
.
gallinarum
and
E
.
casseliflavus
Authors: Palmer Kelli L. , Godfrey Paul , Griggs Allison , Kos Veronica N. , Zucker Jeremy , Desjardins Christopher , Cerqueira Gustavo , Gevers Dirk , Walker Suzanne , Wortman Jennifer , Feldgarden Michael , Haas Brian , Birren Bruce , Gilmore Michael S.
Published: February 2012

The enterococci are Gram-positive lactic acid bacteria that inhabit the gastrointestinal tracts of diverse hosts. However,
Enterococcus faecium
and
E. faecalis
have emerged as leading causes of multidrug-resistant hospital-acquired infections. The mechanism by which a well-adapted commensal evolved into a hospital pathogen is poorly understood. In this study, we examined high-quality draft genome data for evidence of key events in the evolution of the leading causes of enterococcal infections, including
E. faecalis
,
E. faecium
,
E
.
casseliflavus
, and
E
.
gallinarum
. We characterized two clades within what is currently classified as
E. faecium
and identified traits characteristic of each, including variation in operons for cell wall carbohydrate and putative capsule biosynthesis. We examined the extent of recombination between the two
E. faecium
clades and identified two strains with mosaic genomes. We determined the underlying genetics for the defining characteristics of the motile enterococci
E
.
casseliflavus
and
E
.
gallinarum
. Further, we identified species-specific traits that could be used to advance the detection of medically relevant enterococci and their identification to the species level.

IMPORTANCE
The enterococci, in particular, vancomycin-resistant enterococci, have emerged as leading causes of multidrug-resistant hospital-acquired infections. In this study, we examined genome sequence data to define traits with the potential to influence host-microbe interactions and to identify sequences and biochemical functions that could form the basis for the rapid identification of enterococcal species or lineages of importance in clinical and environmental samples.
MAGNETIC PROPERTIES AND MAGNETOCALORIC EFFECT OF HYDROGEN TREATED Gd-BASED BULK METALLIC GLASS
Authors: ZHENG Q. , FU H. , WANG M. X.
Published: February 2012

The metallic glass Gd 52.5 Co 18.5 Al 28 Zr 1 preserves the amorphous structure after hydrogenation at 473 K for 48 h. The absorption of hydrogen leads to the reduction of the magnetic transition temperature due to the expansion of the interatomic distance. The magnetic anisotropy is introduced and the coercivity and remanence are 352 Oe and 12.5 emu/g at 1.8 K, respectively. The maxima of magnetic entropy changes are 11.3 and 7.5 J/kg K with the magnetic field changes of 0 to 70 kOe and 0 to 50 kOe, respectively. The decline of the magnetic entropy changes can be attributed to the disappearance of the collinear ferromagnetic characteristics and the difficulty of saturation for the magnetization after hydrogenation.
CORRELATION-BASED MULTIDIMENSIONAL SCALING FOR UNSUPERVISED SUBSPACE LEARNING
Authors: HE GUANGHUI , ZHANG LINGFENG , SHANG ZHAOWEI
Published: February 2012

Multidimensional scaling (MDS) has been applied in many applications such as dimensionality reduction and data mining. However, one of the drawbacks of MDS is that it is only defined on "training" data without clear extension to out-of-sample points. Furthermore, since that MDS is based on Euclidean distance (which is a dissimilarity measure), it is not suitable for detecting the nonlinear manifold structure embedded in the similarities between data points. In this paper, we extend MDS to the correlation measure space, named correlation MDS (CMDS). CMDS employs an explicit nonlinear mapping between the input and reduced space while MDS using an implicit mapping. As a result, CMDS can directly provide prediction for new samples. In addition, correlation is a similarity measure, CMDS method can effectively capture the nonlinear manifold structure of data embedded in the similarities between the data points. Theoretical analysis also shows that CMDS has some properties similar to kernel methods and can be extended to feature space. The effectiveness of the approach provided in this paper are demonstrated by extensive experiments on various datasets, in comparison with serval existing algorithms.
PERSPECTIVES ON GLOBALIZATION AND DEVELOPMENT — AN INTRODUCTION TO THE SPECIAL ISSUE
Authors: REINERT KENNETH A.
Published: February 2012

This Special Issue of the Journal of International Commerce, Economics and Policy is dedicated to investigating specific topics in the realm of globalization and development. The papers in this issue address capital flows, aid, migration, ideas, trade, and policy. They aim to provide a nuanced approach to analyzing the potential links between globalization processes and development.
Groundwater flood or groundwater-induced flood?
Authors: Robins N. S. , Finch J. W.
Published: February 2012

A number of ‘groundwater flood’ events have been recorded over the Chalk aquifer in southern England since the 1994 occurrence at Chichester, Sussex. Reporting of this event and subsequent groundwater floods indicates that there are two types of groundwater flood event. Type 1 is the true groundwater flood in which the water table elevation rises above the ground elevation, and Type 2 occurs when intense groundwater discharge via bourne springs and highly permeable shallow horizons discharges to surface waters and causes overbank flooding. It is recommended that a Type 1 event be referred to as a true ‘groundwater flood’ and Type 2 simply as a ‘groundwater-induced flood’. Such differentiation will provide a clearer picture for the environmental regulator, the planner and the insurance industry to apply to their own work.
Chlorofluorocarbons as tracers of landfill leachate in surface and groundwater
Authors: Foley A. E. , Atkinson T. C. , Zhao Y.
Published: February 2012

The widespread use of chlorofluorocarbons (CFCs) as refrigerants, aerosols and foam insulation gases has led to their ubiquitous presence in modern landfills. Landfill leachates may have concentrations of CFC11, CFC12 and CFC113 thousands of times higher than in uncontaminated surface and groundwaters. Such great disparity offers a means of using CFCs as tracers of environmental contamination by landfill leachate. The threshold at which diluted leachate can be detected is around 0.1–1%, compared with 10–50% for conventional indicators such as COD, Cl
−
or NH
4
+
. A single, systematic survey may establish the extent and pattern of a leachate plume, whereas conventional indicators must rely on monitoring continued over many years to establish trends rising above background. This paper presents results from just such a survey conducted at a landfill site in Yorkshire, England. There were clear impacts on surface water courses and shallow groundwater, whereas an upward hydraulic gradient protected deeper groundwater beneath the site. Selective degradation of CFC11 was observed in groundwaters.
The idea idea
Authors: Denning Peter J.
Published: February 2012

What if practices rather than ideas are the main source of innovation?
Simplified integration of Prolog with RDBMS
Authors: Berghel H. L.
Published: February 2012

In this paper we describe several advantages of integrating the declarative, logic-based language, Prolog, with conventional relational database management systems. We then explain a file conversion procedure which can be used to exchange information between systems. The result is a research environment in which the user can derive maximum benefit from both Prolog and relational database systems.
Identification of hypertrophy- and heart failure-associated genes by combining in vitro and in vivo models
Authors: Lu Bo , Yu Hongjuan , Zwartbol Maarten , Ruifrok Willem P. , van Gilst Wiek H. , de Boer Rudolf A. , Silljé Herman H. W.
Published: February 2012

Heart failure (HF) is a complex disease involving multiple changes including cardiomyocyte hypertrophy (growth). Here we performed a set of screens in different HF and hypertrophy models to identify differentially expressed genes associated with HF and/or hypertrophy. Hypertensive Ren2 rats and animals with postmyocardial infarction (post-MI) HF were used as in vivo HF models, and neonatal rat cardiomyocytes treated with hypertrophy inducing hormones phenylephrine, endothelin-1, and isoproterenol were used as in vitro models. This combined approach revealed a robust set of genes that were differentially expressed both in vitro and in vivo. This included known genes like NPPA (ANP) and FHL1, but also novel genes not previously associated with hypertrophy/HF. Among these are PTGIS, AKIP1, and Dhrs7c, which could constitute interesting targets for further investigations. We also identified a number of in vivo specific genes and these appeared to be enriched for fibrosis, wounding, and stress responses. Therefore a number of novel genes within this in vivo specific list could be related to fibroblasts or other noncardiomyocytes present in the heart. We also observed strong differences between the two HF rat models. For example KCNE1 was strongly upregulated in Ren2, but not in post-MI HF rats, suggesting possible etiology-specific differences. Moreover, Gene Ontology analysis revealed that genes involved in fatty acid oxidation were specifically down regulated in the post-MI group only. Together these results show that combining multiple models, both in vivo and in vitro, can provide a robust set of hypertrophy/HF-associated genes. Moreover it provides insight in the differences between the different etiology models and neurohormonal effects.
Toll-Like Receptor 7 Agonist Therapy with Imidazoquinoline Enhances Cancer Cell Death and Increases Lymphocytic Infiltration and Proinflammatory Cytokine Production in Established Tumors of a Renal Cell Carcinoma Mouse Model
Authors: Kauffman Eric C. , Liu Huixian , Schwartz Michael J. , Scherr Douglas S.
Published: February 2012

Imidazoquinolines are synthetic toll-like receptor 7 and 8 agonists and potent dendritic cell activators with established anticancer activity. Here we test the hypothesis that imidazoquinoline hasin vivoefficacy within established renal cell carcinoma (RCC) tumors. Immunocompetent mice bearing syngeneic RCC xenografts were treated with imidazoquinoline or placebo at two separate time points. Harvested tumors were assayed by TUNEL/caspase-3/Ki67 immunostains to evaluate cell death/apoptosis/proliferation, and CD3/B220/CD45 immunostains to evaluate T-cell lymphocyte/B-cell lymphocyte/pan-leukocyte tumor infiltration. ELISA measurement of tumor and serum levels of proinflammatory cytokines, IL-6 and MCP-1, was performed. A single imidazoquinoline dose significantly decreased RCC tumor growth by 50% and repeat dosing compounded the effect, without observed weight loss or other toxicity. Tumor immunostaining revealed significant increases in cell death and apoptosis without changes in cell proliferation, supporting induction of apoptosis as the primary mechanism of tumor growth suppression. Imidazoquinoline treatment also significantly enhanced peritumoral aggregation and intratumoral infiltration by T-cell lymphocytes, while increasing intratumoral (but not serum) levels of proinflammatory cytokines. In conclusion, imidazoquinoline treatment enhances T-cell lymphocyte infiltration and proinflammatory cytokine production within established mouse RCC tumors, while suppressing tumor growth via induction of cancer cell apoptosis. These findings support a therapeutic role for imidazoquinoline in RCC.
Stromal-Cell-Derived Factor-1 (SDF-1)/CXCL12 as Potential Target of Therapeutic Angiogenesis in Critical Leg Ischaemia
Authors: Ho Teik K. , Shiwen X. , Abraham D. , Tsui J. , Baker D.
Published: February 2012

In the Western world, peripheral vascular disease (PVD) has a high prevalence with high morbidity and mortality. In a large percentage of these patients, lower limb amputation is still required. Studies of ischaemic skeletal muscle disclosed evidence of endogenous angiogenesis and adaptive skeletal muscle metabolic changes in response to hypoxia. Chemokines are potent chemoattractant cytokines that regulate leukocyte trafficking in homeostatic and inflammatory processes. More than 50 different chemokines and 20 different chemokine receptors have been cloned. The chemokine stromal-cell-derived factor-1 (SDF-1 aka CXCL12) is a constitutively expressed and inducible chemokine that regulates multiple physiological processes, including embryonic development and organ homeostasis. The biologic effects of SDF-1 are mediated by chemokine receptor CXCR4, a 352 amino acid rhodopsin-like transmembrane-specific G protein-coupled receptor (GPCR). There is evidence that the administration of SDF-1 increases blood flow and perfusion via recruitment of endothelial progenitor cells (EPCs). This review will focus on the role of the SDF-1/CXCR4 system in the pathophysiology of PVD and discuss their potential as therapeutic targets for PVD.
Antiangiogenic Effects and Therapeutic Targets ofAzadirachta indicaLeaf Extract in Endothelial Cells
Authors: Mahapatra Saswati , Young Charles Y. F. , Kohli Manish , Karnes R. Jeffrey , Klee Eric W. , Holmes Michael W. , Tindall Donald J. , Donkena Krishna Vanaja
Published: February 2012

Azadirachta indica(common name: neem) leaves have been found to possess immunomodulatory, anti-inflammatory and anti-carcinogenic properties. The present study evaluates anti-angiogenic potential of ethanol extract of neem leaves (EENL) in human umbilical vein endothelial cells (HUVECs). Treatment of HUVECs with EENL inhibited VEGF induced angiogenic responsein vitroandin vivo. Thein vitroproliferation, invasion and migration of HUVECs were suppressed with EENL. Nuclear fragmentation and abnormally small mitochondria with dilated cristae were observed in EENL treated HUVECs by transmission electron microscopy. Genome-wide mRNA expression profiling after treatment with EENL revealed differentially regulated genes. Expression changes of the genes were validated by quantitative real-time polymerase chain reaction. Additionally, increase in the expression of HMOX1, ATF3 and EGR1 proteins were determined by immunoblotting. Analysis of the compounds in the EENL by mass spectrometry suggests the presence of nimbolide, 2′,3′-dehydrosalannol, 6-desacetyl nimbinene and nimolinone. We further confirmed antiproliferative activity of nimbolide and 2′,3′-dehydrosalannol in HUVECs. Our results suggest that EENL by regulating the genes involved in cellular development and cell death functions could control cell proliferation, attenuate the stimulatory effects of VEGF and exert antiangiogenic effects. EENL treatment could have a potential therapeutic role during cancer progression.
Effect of the Phosphorus Gettering on Si Heterojunction Solar Cells
Authors: Park Hyomin , Tark Sung Ju , Kim Chan Seok , Park Sungeun , Kim Young Do , Son Chang-Sik , Lee Jeong Chul , Kim Donghwan
Published: February 2012

To improve the efficiency of crystalline silicon solar cells, should be collected the excess carrier as much as possible. Therefore, minimizing the recombination both at the bulk and surface regions is important. Impurities make recombination sites and they are the major reason for recombination. Phosphorus (P) gettering was introduced to reduce metal impurities in the bulk region of Si wafers and then to improve the efficiency of Si heterojunction solar cells fabricated on the wafers. Resistivity of wafers was measured by a four-point probe method. Fill factor of solar cells was measured by a solar simulator. Saturation current and ideality factor were calculated from a dark current density-voltage graph. External quantum efficiency was analyzed to assess the effect of P gettering on the performance of solar cells. Minority bulk lifetime measured by microwave photoconductance decay increases from 368.3 to 660.8 μs. Open-circuit voltage and short-circuit current density increase from 577 to 598 mV and 27.8 to 29.8 mA/cm2, respectively. The efficiency of solar cells increases from 11.9 to 13.4%. P gettering will be feasible to improve the efficiency of Si heterojunction solar cells fabricated on P-doped Si wafers.
Arterial Spin Labeling (ASL) fMRI: Advantages, Theoretical Constrains and Experimental Challenges in Neurosciences
Authors: Borogovac Ajna , Asllani Iris
Published: February 2012

Cerebral blood flow (CBF) is a well-established correlate of brain function and therefore an essential parameter for studying the brain at both normal and diseased states. Arterial spin labeling (ASL) is a noninvasive fMRI technique that uses arterial water as an endogenous tracer to measure CBF. ASL provides reliable absolute quantification of CBF with higher spatial and temporal resolution than other techniques. And yet, the routine application of ASL has been somewhat limited. In this review, we start by highlighting theoretical complexities and technical challenges of ASL fMRI for basic and clinical research. While underscoring the main advantages of ASL versus other techniques such as BOLD, we also expound on inherent challenges and confounds in ASL perfusion imaging. In closing, we expound on several exciting developments in the field that we believe will make ASL reach its full potential in neuroscience research.
In Situ Raman Spectroscopy of COOH-Functionalized SWCNTs Trapped with Optoelectronic Tweezers
Authors: Pauzauskie Peter J. , Jamshidi Arash , Zaug Joseph M. , Baker Sarah , Han T. Y.-J. , Satcher Joe H. , Wu Ming C.
Published: February 2012

Optoelectronic tweezers (OETs) were used to trap and deposit aqueous dispersions of carboxylic-acid-functionalized single-walled carbon nanotube bundles. Dark-field video microscopy was used to visualize the dynamics of the bundles both with and without virtual electrodes, showing rapid accumulation of carbon nanotubes when optical virtual electrodes are actuated. Raman microscopy was used to probe SWCNT materials following deposition onto metallic fiducial markers as well as during trapping. The local carbon nanotube concentration was observed to increase rapidly during trapping by more than an order of magnitude in less than one second due to localized optical dielectrophoresis forces. This combination of enrichment and spectroscopy with a single laser spot suggests a broad range of applications in physical, chemical, and biological sciences.
History and Mechanism for Treatment of Intracerebral Hemorrhage with Scalp Acupuncture
Authors: Liu Zhe , Guan Ling , Wang Yan , Xie Cheng-Long , Lin Xian-Ming , Zheng Guo-Qing
Published: February 2012

Intracerebral hemorrhage (ICH) is an important public health problem with high rates of mortality, morbidity, and disability, but no clinically proven treatment strategy is available to date. Scalp acupuncture (SA) refers to a therapy for treating diseases by needling and stimulating the specific areas of the scalp. The evidence from clinical studies suggested that SA therapy may produce significant benefits for patients with acute ICH. However, the therapeutic mechanisms are yet not well addressed. Therefore, in this paper, we provide a comprehensive overview on the history and mechanisms of SA therapy on acute ICH. Although SA has been practiced for thousands of years in China and could date back to 5 BC, SA therapy for acute ICH develops only in the recent 30 years. The possible mechanisms associated with the therapeutic effects of SA on ICH include the influence on hematoma, brain edema, and blood brain barrier, the products released from haematoma, the immune and inflammatory reaction, focal perihemorrhagic hypoperfusion and hemorheology, neuroelectrophysiology, and so on. At last, the existence of instant effect of SA on acute ICH and its possible mechanisms are presented.
Treatment With OPN-305, a Humanized Anti–Toll-Like Receptor-2 Antibody, Reduces Myocardial Ischemia/Reperfusion Injury in Pigs
Authors: Arslan Fatih , Houtgraaf Jaco H. , Keogh Brian , Kazemi Kushan , de Jong Renate , McCormack William J. , O'Neill Luke A.J. , McGuirk Peter , Timmers Leo , Smeets Mirjam B. , Akeroyd Lars , Reilly Mary , Pasterkamp Gerard , de Kleijn Dominique P.V.
Published: February 2012

Background—

Toll-like receptor (TLR)-2 is an important mediator of innate immunity and ischemia/reperfusion-induced cardiac injury. We have previously shown that TLR2 inhibition reduces infarct size and improves cardiac function in mice. However, the therapeutic efficacy of a clinical grade humanized anti-TLR2 antibody, OPN-305, in a large-animal model remained to be addressed.

Methods and Results—

Pigs (n=38) underwent 75 minutes ischemia followed by 24 hours of reperfusion. Saline or OPN-305 (12.5, 6.25, or 1.56 mg/kg) was infused intravenously 15 minutes before reperfusion. Cardiac function and geometry were assessed by echocardiography. Infarct size was calculated as the percentage of the area at risk and by serum Troponin-I levels. Flow cytometry analysis revealed specific binding of OPN-305 to porcine TLR2. In vivo, OPN-305 exhibited a secondary half-life of 8±2 days. Intravenous administration of OPN-305 before reperfusion significantly reduced infarct size (45% reduction,
P
=0.041) in a dose-dependent manner. In addition, pigs treated with OPN-305 exhibited a significant preservation of systolic performance in a dose-dependent fashion, whereas saline treatment completely diminished the contractile performance of the ischemic/reperfused myocardium.

Conclusions—

OPN-305 significantly reduces infarct size and preserves cardiac function in pigs after ischemia/reperfusion injury. Hence, OPN-305 is a promising adjunctive therapeutic for patients with acute myocardial infarction.
Urinary Bisphenol A Concentration and Risk of Future Coronary Artery Disease in Apparently Healthy Men and Women
Authors: Melzer David , Osborne Nicholas J. , Henley William E. , Cipelli Riccardo , Young Anita , Money Cathryn , McCormack Paul , Luben Robert , Khaw Kay-Tee , Wareham Nicholas J. , Galloway Tamara S.
Published: February 2012

Background—

The endocrine-disrupting chemical bisphenol A (BPA) is widely used in food and beverage packaging. Higher urinary BPA concentrations were cross-sectionally associated with heart disease in National Health and Nutrition Examination Survey (NHANES) 2003–2004 and NHANES 2005–2006, independent of traditional risk factors.

Methods and Results—

We included 758 incident coronary artery disease (CAD) cases and 861 controls followed for 10.8 years from the European Prospective Investigation of Cancer–Norfolk UK. Respondents aged 40 to 74 years and free of CAD, stroke, or diabetes mellitus provided baseline spot urine samples. Urinary BPA concentrations (median value, 1.3 ng/mL) were low. Per-SD (4.56 ng/mL) increases in urinary BPA concentration were associated with incident CAD in age-, sex-, and urinary creatinine–adjusted models (n=1919; odds ratio=1.13; 95% confidence interval, 1.02–1.24;
P
=0.017). With CAD risk factor adjustment (including education, occupational social class, body mass index category, systolic blood pressure, lipid concentrations, and exercise), the estimate was similar but narrowly missed 2-sided significance (n=1744; odds ratio=1.11; 95% confidence interval, 1.00–1.23;
P
=0.058). Sensitivity analyses with the fully adjusted model, excluding those with early CAD (<3-year follow-up), body mass index >30, or abnormal renal function or with additional adjustment for vitamin C, C-reactive protein, or alcohol consumption, all produced similar estimates, and all showed associations at
P
≤0.05.

Conclusions—

Associations between higher BPA exposure (reflected in higher urinary concentrations) and incident CAD during >10 years of follow-up showed trends similar to previously reported cross-sectional findings in the more highly exposed NHANES respondents. Further work is needed to accurately estimate the prospective exposure-response curve and to establish the underlying mechanisms.
Uric Acid Level and Elevated Blood Pressure in US Adolescents
Authors: Loeffler Lauren F. , Navas-Acien Ana , Brady Tammy M. , Miller Edgar R. , Fadrowski Jeffrey J.
Published: February 2012

Uric acid is associated with cardiovascular disease and cardiovascular disease risk factors in adults, including chronic kidney disease, coronary artery disease, stroke, diabetes mellitus, preeclampsia, and hypertension. We examined the association between uric acid and elevated blood pressure in a large, nationally representative cohort of US adolescents, a population with a relatively low prevalence of cardiovascular disease and cardiovascular disease risk factors. Among 6036 adolescents 12 to 17 years of age examined in the 1999–2006 National Health and Nutrition Examination Survey, the mean age was 14.5 years, 17% were obese (body mass index: ≥95th percentile), and 3.3% had elevated blood pressure. Mean serum uric acid level was 5.0 mg/dL, and 34% had a uric acid level ≥5.5 mg/dL. In analyses adjusted for age, sex, race/ethnicity, and body mass index percentile, the odds ratio of elevated blood pressure, defined as a systolic or diastolic blood pressure ≥95th percentile for age, sex, and height, for each 0.1-mg/dL increase in uric acid level was 1.38 (95% CI: 1.16–1.65). Compared with <5.5 mg/dL, participants with a uric acid level ≥5.5 mg/dL had a 2.03 times higher odds of having elevated blood pressure (95% CI: 1.38–3.00). In conclusion, increasing levels of serum uric acid are associated with elevated blood pressure in healthy US adolescents. Additional prospective studies and clinical trials are needed to determine whether uric acid is merely a marker in a complex metabolic pathway or causal of hypertension and, thus, a potential screening and therapeutic target.
Acute Reversal of Endothelial Dysfunction in the Elderly After Antioxidant Consumption
Authors: Wray D. Walter , Nishiyama Steven K. , Harris Ryan A. , Zhao Jia , McDaniel John , Fjeldstad Anette S. , Witman Melissa A.H. , Ives Stephen J. , Barrett-O'Keefe Zachary , Richardson Russell S.
Published: February 2012

Aging is associated with a pro-oxidant state and a decline in endothelial function. Whether acute, enteral antioxidant treatment can reverse this decrement in vascular function is not well known. Flow-mediated vasodilation and reactive hyperemia were evaluated after consumption of either placebo or an oral antioxidant cocktail (vitamin C, 1000 mg; vitamin E, 600 IU; α-lipoic acid, 600 mg) in 87 healthy volunteers (42 young: 25±1 years; 45 older: 71±1 years) using a double-blind, crossover design. Blood velocity and brachial artery diameter (ultrasound Doppler) were assessed before and after 5-minute forearm circulatory arrest. Serum markers of lipid peroxidation, total antioxidant capacity, endogenous antioxidant activity, and vitamin C were assayed, and plasma nitrate, nitrite, and 3-nitrotyrosine were determined. In the placebo trial, an age-related reduction in brachial artery vasodilation was evident (young: 7.4±0.6%; older: 5.2±0.4%). After antioxidant consumption, flow-mediated vasodilation improved in older subjects (placebo: 5.2±0.4%; antioxidant: 8.2±0.6%) but declined in the young (placebo: 7.4±0.6%; antioxidant: 5.8±0.6%). Reactive hyperemia was reduced with age, but antioxidant administration did not alter the response in either group. Together, these data demonstrate that antioxidant consumption acutely restores endothelial function in the elderly while disrupting normal endothelium-dependent vasodilation in the young and suggest that this age-related impairment is attributed, at least in part, to free radicals.
Differential Effects of Nebivolol and Metoprolol on Insulin Sensitivity and Plasminogen Activator Inhibitor in the Metabolic Syndrome
Authors: Ayers Katie , Byrne Loretta M. , DeMatteo Anthony , Brown Nancy J.
Published: February 2012

Early-generation β-blockers lower blood pressure and reduce cardiovascular morality in coronary artery disease and congestive heart failure but worsen glucose homeostasis and fibrinolytic balance. Nebivolol is a third-generation β-blocker that increases the bioavailability of nitric oxide. We compared the effect of nebivolol (5 mg/d) and the β
1
-selective antagonist metoprolol (100 mg/d) on glucose homeostasis and markers of fibrinolysis in 46 subjects with metabolic syndrome. Subjects underwent a frequently sampled IV glucose tolerance test after 3-week washout and placebo treatment and after randomized treatment with study drug. After 12-week treatment, nebivolol and metoprolol equivalently decreased systolic blood pressure, diastolic blood pressure, and heart rate. Neither drug affected β-cell function, disposition index, or acute insulin response to glucose. Metoprolol significantly decreased the insulin sensitivity index. In contrast, nebivolol did not affect insulin sensitivity, and the decrease in sensitivity was significantly greater after metoprolol than after nebivolol (−1.5±2.5×10
−4
×min
−1
per milliunit per liter versus 0.04±2.19×10
−4
×min
−1
per milliunit per liter after nebivolol;
P=
0.03). Circulating plasminogen activator inhibitor also increased after treatment with metoprolol (from 9.8±6.8 to 12.3±7.8 ng/mL) but not nebivolol (from 10.8±7.8 to 10.5±6.2 ng/mL;
P=
0.05 versus metoprolol). Metoprolol, but not nebivolol, increased F
2
-isoprostane concentrations. In summary, treatment with metoprolol decreased insulin sensitivity and increased oxidative stress and the antifibrinolytic plasminogen activator inhibitor 1 in patients with metabolic syndrome, whereas nebivolol lacked detrimental metabolic effects. Large clinical trials are needed to compare effects of nebivolol and the β
1
receptor antagonist metoprolol on clinical outcomes in patients with hypertension and the metabolic syndrome.
Incremental Reduction in Risk of Death Associated With Use of Guideline‐Recommended Therapies in Patients With Heart Failure: A Nested Case‐Control Analysis of IMPROVE HF
Authors: Fonarow Gregg C. , Albert Nancy M. , Curtis Anne B. , Gheorghiade Mihai , Liu Yang , Mehra Mandeep R. , O'Connor Christopher M. , Reynolds Dwight , Walsh Mary N. , Yancy Clyde W.
Published: February 2012

Background

Several therapies are guideline‐recommended to reduce mortality in patients with heart failure (HF) and reduced left ventricular ejection fraction, but the incremental clinical effectiveness of these therapies has not been well studied. We aimed to evaluate the individual and incremental benefits of guideline‐recommended HF therapies associated with 24‐month survival.

Methods and Results

We performed a nested case‐control study of HF patients enrolled in IMPROVE HF. Cases were patients who died within 24 months and controls were patients who survived to 24 months, propensity‐matched 1:2 for multiple prognostic variables. Logistic regression was performed, and the attributable mortality risk from incomplete application of each evidence‐based therapy among eligible patients was calculated. A total of 1376 cases and 2752 matched controls were identified. β‐Blocker and cardiac resynchronization therapy were associated with the greatest 24‐month survival benefit (adjusted odds ratio for death 0.42, 95% confidence interval (CI), 0.34–0.52; and 0.44, 95% CI, 0.29–0.67, respectively). Angiotensin‐converting enzyme inhibitors/angiotensin receptor blockers, implantable cardioverter‐defibrillators, anticoagulation for atrial fibrillation, and HF education were also associated with benefit, whereas aldosterone antagonist use was not. Incremental benefits were observed with each successive therapy, plateauing once any 4 to 5 therapies were provided (adjusted odds ratio 0.31, 95% CI, 0.23–0.42 for 5 or more versus 0/1,
P
<0.0001).

Conclusions

Individual, with a single exception, and incremental use of guideline‐recommended therapies was associated with survival benefit, with a potential plateau at 4 to 5 therapies. These data provide further rationale to implement guideline‐recommended HF therapies in the absence of contraindications to patients with HF and reduced left ventricular ejection fraction.
Impact of Tropical SST on Stratospheric Planetary Waves in the Southern Hemisphere
Authors: Lin Pu , Fu Qiang , Hartmann Dennis L.
Published: February 2012

The impact of tropical sea surface temperature (SST) on stratospheric planetary waves in the Southern Hemisphere (SH) is investigated in austral spring using observed SST and reanalysis data for the past three decades. Maximum covariance analysis indicates that the tropical SST and the SH stratospheric planetary wave activity are primarily coupled through two modes. The leading two modes show the La Niña–like and the central-Pacific El Niño–like SST anomalies in their positive polarities, respectively, which each are related to enhanced stratospheric planetary wave activity. These two modes also introduce phase shifts to the stratospheric stationary planetary waves: a westward shift is seen for La Niña and an eastward shift for warm SST anomalies is seen in the central Pacific. The Eliassen–Palm fluxes associated with the two modes indicate that the anomalous stratospheric wave activity originates in the troposphere and propagates upward over the mid–high latitudes, so that the linkages between tropical SST and extratropical tropospheric circulation appear to play a key role. Furthermore, the observed circulation anomaly patterns for the two modes change rapidly from spring to summer, consistent with a sharp seasonal transition in the SH basic state. Similar SST and circulation anomaly patterns associated with the two modes are simulated in chemistry–climate models.
MMP Activity in the Hybrid Layer Detected with in situ Zymography
Authors: Mazzoni A. , Nascimento F.D. , Carrilho M. , Tersariol I. , Papa V. , Tjäderhane L. , Di Lenarda R. , Tay F.R. , Pashley D.H. , Breschi L.
Published: February 2012

Dentinal proteases are believed to play an important role in the degradation of hybrid layers (HL). This study investigated the HL gelatinolytic activity by in situ zymography and functional enzyme activity assay. The hypotheses were that HLs created by an etch-and-rinse adhesive exhibit active gelatinolytic activity, and MMP-2 and -9 activities in dentin increase during adhesive procedures. Etched-dentin specimens were bonded with Adper Scotchbond 1XT and restored with composite. Adhesive/dentin interface slices were placed on microscope slides, covered with fluorescein-conjugated gelatin, and observed with a multi-photon confocal microscope after 24 hrs. Human dentin powder aliquots were prepared and assigned to the following treatments: A, untreated; B, etched with 10% phosphoric acid; or C, etched with 10% phosphoric acid and mixed with Scotchbond 1XT. The MMP-2 and -9 activities of extracts of dentin powder were measured with functional enzyme assays. Intense and continuous enzyme activity was detected at the bottom of the HL, while that activity was more irregular in the upper HL. Both acid-etching and subsequent adhesive application significantly increased MMP-2 and -9 activities (p < 0.05). The results demonstrate, for the first time, intrinsic MMP activity in the HL, and intense activation of matrix-bound MMP activity with both etching and adhesive application.
When I’s Meet
Authors: Pinel Elizabeth C. , Long Anson E.
Published: February 2012

Believing one shares a subjective experience with another (i.e., I-sharing) fosters connections among strangers and alters perceptions of the ingroup and outgroup. In this article, the authors ask whether I-sharing also fosters liking for members of a salient outgroup. Study 1 establishes that I-sharing promotes liking for the other sex, even among people with salient social identities. Study 2 shows that I-sharing promotes liking for a member of the sexual orientation outgroup, whether it occurs before or after group memberships get revealed. Study 3 focuses on salient race categories and looks at the effects of I-sharing versus value-sharing as a function of shared group membership. For those high in existential isolation, I-sharing trumps value-sharing, regardless of the I-sharer’s social identity. I-sharing may offer a way of improving attitudes toward outgroup members that still enables people to embrace their differing social identities.
Secondary Transfer Effects of Intergroup Contact
Authors: Schmid Katharina , Hewstone Miles , Küpper Beate , Zick Andreas , Wagner Ulrich
Published: February 2012

This article examines so-called secondary transfer effects of intergroup contact, a phenomenon whereby positive intergroup contact experiences can influence attitudes not only toward encountered (primary) outgroups but also toward other (secondary) outgroups that were not initially involved in the intergroup encounter. The current study relies on a unique cross-sectional sample of the general population drawn from eight European countries (N = 7,042) to examine the relationship between intergroup contact with immigrants and attitudes toward primary (immigrants) and secondary (homosexuals and Jews) outgroups. Results showed that intergroup contact was not only directly related with primary outgroup attitudes but also indirectly associated with secondary outgroup attitudes, via attitude generalization. These relationships occurred primarily for individuals low in social dominance orientation. Findings are discussed in terms of their contribution to understanding secondary transfer effects of contact as well as the role of social dominance orientation as a moderator of such effects.