bluuebunny/crossref_metadata_2025 huggingface dataset:
SigCS base: an integrated genetic information resource for human cerebral stroke
Authors: Park Young-Kyu , Bang Ok Sun , Cha Min-Ho , Kim Jaeheup , Cole John W , Lee Doheon , Kim Young Joo
Published: December 2011

Background

To understand how stroke risk factors mechanistically contribute to stroke, the genetic components regulating each risk factor need to be integrated and evaluated with respect to biological function and through pathway-based algorithms. This resource will provide information to researchers studying the molecular and genetic causes of stroke in terms of genomic variants, genes, and pathways.

Methods

Reported genetic variants, gene structure, phenotypes, and literature information regarding stroke were collected and extracted from publicly available databases describing variants, genome, proteome, functional annotation, and disease subtypes. Stroke related candidate pathways and etiologic genes that participate significantly in risk were analyzed in terms of canonical pathways in public biological pathway databases. These efforts resulted in a relational database of genetic signals of cerebral stroke, SigCS base, which implements an effective web retrieval system.

Results

The current version of SigCS base documents 1943 non-redundant genes with 11472 genetic variants and 165 non-redundant pathways. The web retrieval system of SigCS base consists of two principal search flows, including: 1) a gene-based variant search using gene table browsing or a keyword search, and, 2) a pathway-based variant search using pathway table browsing. SigCS base is freely accessible at http://sysbio.kribb.re.kr/sigcs.

Conclusions

SigCS base is an effective tool that can assist researchers in the identification of the genetic factors associated with stroke by utilizing existing literature information, selecting candidate genes and variants for experimental studies, and examining the pathways that contribute to the pathophysiological mechanisms of stroke.
SNP-PRAGE: SNP-based parametric robust analysis of gene set enrichment
Authors: Lee Jaehoon , Ahn Soyeon , Oh Sohee , Weir Bruce , Park Taesung
Published: December 2011

Background

The current genome-wide association (GWA) analysis mainly focuses on the single genetic variant, which may not reveal some the genetic variants that have small individual effects but large joint effects. Considering the multiple SNPs jointly in Genome-wide association (GWA) analysis can increase power. When multiple SNPs are jointly considered, the corresponding SNP-level association measures are likely to be correlated due to the linkage disequilibrium (LD) among SNPs.

Methods

We propose SNP-based parametric robust analysis of gene-set enrichment (SNP-PRAGE) method which handles correlation adequately among association measures of SNPs, and minimizes computing effort by the parametric assumption. SNP-PRAGE first obtains gene-level association measures from SNP-level association measures by incorporating the size of corresponding (or nearby) genes and the LD structure among SNPs. Afterward, SNP-PRAGE acquires the gene-set level summary of genes that undergo the same biological knowledge. This two-step summarization makes the within-set association measures to be independent from each other, and therefore the central limit theorem can be adequately applied for the parametric model.

Results & conclusions

We applied SNP-PRAGE to two GWA data sets: hypertension data of 8,842 samples from the Korean population and bipolar disorder data of 4,806 samples from the Wellcome Trust Case Control Consortium (WTCCC). We found two enriched gene sets for hypertension and three enriched gene sets for bipolar disorder. By a simulation study, we compared our method to other gene set methods, and we found SNP-PRAGE reduced many false positives notably while requiring much less computational efforts than other permutation-based gene set approaches.
Ryanodine receptors, a family of intracellular calcium ion channels, are expressed throughout early vertebrate development
Authors: Wu Houdini HT , Brennan Caroline , Ashworth Rachel
Published: December 2011

Background

Calcium signals ([Ca2+]i) direct many aspects of embryo development but their regulation is not well characterised. Ryanodine receptors (RyRs) are a family of intracellular Ca2+ release channels that control the flux of Ca2+ from internal stores into the cytosol. RyRs are primarily known for their role in excitation-contraction coupling in adult striated muscle and ryr gene mutations are implicated in several human diseases. Current evidence suggests that RyRs do not have a major role to play prior to organogenesis but regulate tissue differentiation.

Findings

The sequences of the five zebrafish ryr genes were confirmed, their evolutionary relationship established and the primary sequences compared to other vertebrates, including humans. RyRs are differentially expressed in slow (ryr1a), fast (ryr3) and both types (ryr1b) of developing skeletal muscle. There are two ryr2 genes (ryr2a and ryr2b) which are expressed exclusively in developing CNS and cardiac tissue, respectively. In addition, ryr3 and ryr2a mRNA is detectable in the initial stages of development, prior to embryonic axis formation.

Conclusions

Our work reveals that zebrafish ryr genes are differentially expressed throughout the developing embryo from cleavage onwards. The data suggests that RyR-regulated Ca2+ signals are associated with several aspects of embryonic development, from organogenesis through to the differentiation of the musculoskeletal, cardiovascular and nervous system. These studies will facilitate further work to explore the developmental function of RyRs in each of these tissue types.
Advanced glycation endproducts are increased in rheumatoid arthritis patients with controlled disease
Authors: de Groot Lodewijk , Hinkema Helmy , Westra Johanna , Smit Andries J , Kallenberg Cees GM , Bijl Marc , Posthumus Marcel D
Published: December 2011

Introduction

Advanced glycation end products (AGEs) are produced and can accumulate during chronic inflammation, as might be present in patients with rheumatoid arthritis (RA). AGEs are involved in the development of cardiovascular disease. The aim of this study is to evaluate whether AGEs are increased in patients with long-standing RA and whether AGE accumulation is related to disease activity, disease severity and measures of (premature) atherosclerosis, such as endothelial activation, endothelial dysfunction and intima media thickness (IMT).

Methods

In a cross-sectional study, 49 consecutive RA patients with longstanding disease (median disease duration of 12.3 years (range 9.3 to 15.1)), receiving standard of care, were included and compared with 49 age- and sex-matched healthy controls (HC). AGEs were determined by skin autofluorescence. Disease activity was evaluated by the Disease Activity Score of 28 joints (DAS-28) score and joint damage by modified Sharp-v.d. Heijde score. Endothelial activation (soluble vascular cellular adhesion molecule-1) sVCAM-1, von Willebrand factor (vWF), thrombomodulin), endothelial dysfunction (determined by small artery elasticity (SAE)) and IMT were measured and related to AGE accumulation.

Results

AGEs were increased in RA patients (median 2.4 arbitrary units (a.u.), range 1.6 to 4.2) compared to HC (2.2, 1.3 to 3.8). RA patients had a DAS-28 score of 2.9 (0.8 to 6.9) and a modified Sharp-v.d. Heijde score of 19 (0 to 103). sVCAM-1 and vWF levels were higher in RA patients. SAE was significantly decreased in RA (3.9 ml/mmHg (1.4 to 12.2) vs. 6.1 in HC (1.7 to 12.9). IMT did not differ between the two groups. Combining both groups' AGEs correlated with vWF, sVCAM-1 and IMT, and was inversely related to SAE. In RA, AGEs had an inverse relation with SAE, but did not relate to disease activity or radiological damage. In multivariate analysis for both groups, smoking, glucose levels, vWF, SAE and male gender were significantly related to the formation of AGEs.

Conclusions

AGEs were increased in RA patients with long-standing disease and without signs of premature atherosclerosis. AGEs were related to endothelial activation and endothelial dysfunction. This supports the hypothesis that in RA AGEs may be an early marker of cardiovascular disease.
High-throughput RNA interference screening using pooled shRNA libraries and next generation sequencing
Authors: Sims David , Mendes-Pereira Ana M , Frankum Jessica , Burgess Darren , Cerone Maria-Antonietta , Lombardelli Cristina , Mitsopoulos Costas , Hakas Jarle , Murugaesu Nirupa , Isacke Clare M , Fenwick Kerry , Assiotis Ioannis , Kozarewa Iwanka , Zvelebil Marketa , Ashworth Alan , Lord Christopher J
Published: December 2011

RNA interference (RNAi) screening is a state-of-the-art technology that enables the dissection of biological processes and disease-related phenotypes. The commercial availability of genome-wide, short hairpin RNA (shRNA) libraries has fueled interest in this area but the generation and analysis of these complex data remain a challenge. Here, we describe complete experimental protocols and novel open source computational methodologies, shALIGN and shRNAseq, that allow RNAi screens to be rapidly deconvoluted using next generation sequencing. Our computational pipeline offers efficient screen analysis and the flexibility and scalability to quickly incorporate future developments in shRNA library technology.
MicroRNA profiling reveals age-dependent differential expression of nuclear factor κB and mitogen-activated protein kinase in adipose and bone marrow-derived human mesenchymal stem cells
Authors: Pandey Amitabh C , Semon Julie A , Kaushal Deepak , O'Sullivan Regina P , Glowacki Julie , Gimble Jeffery M , Bunnell Bruce A
Published: December 2011

Introduction

Mesenchymal stem cells (MSCs) play a central role in mediating endogenous repair of cell and tissue damage. Biologic aging is a universal process that results in changes at the cellular and molecular levels. In the present study, the role of microRNA (miRNA) in age-induced molecular changes in MSCs derived from adipose tissue (ASCs) and bone marrow (BMSCs) from young and old human donors were investigated by using an unbiased genome-wide approach.

Methods

Human ASCs and BMSCs from young and old donors were cultured, and total RNA was isolated. The miRNA fraction was enriched and used to determine the expression profile of miRNA in young and old donor MSCs. Based on miRNA expression, differences in donor MSCs were further investigated by using differentiation assays, Western blot, immunocytochemistry, and bioinformatics.

Results

Biologic aging demonstrated reduced osteogenic and adipogenic potential in ASCs isolated from older donors, whereas cell size, complexity, and cell-surface markers remained intact with aging. Analysis of miRNA profiles revealed that small subsets of active miRNAs changed secondary to aging. Evaluation of miRNA showed significantly decreased levels of gene expression of inhibitory kappa B kinase (IκB), interleukin-1α, inducible nitric oxide synthase (iNOS), mitogen-activated protein kinase/p38, ERK1/2, c-fos, and c-jun in MSCs from older donors by both bioinformatics and Western blot analysis. Nuclear factor kappa B (NF-κB), myc, and interleukin-4 receptor mRNA levels were significantly elevated in aged cells from both the adipose and bone marrow depots. Immunocytochemistry showed nuclear localization in young donors, but a cytosolic predominance of phosphorylated NF-κB in ASCs from older donors. Western blot demonstrated significantly elevated levels of NF-κB subunits, p65 and p50, and AKT.

Conclusions

These findings suggest that differential expression of miRNA is an integral component of biologic aging in MSCs.
M-ficolin and leukosialin (CD43): new partners in neutrophil adhesion
Authors: Moreno-Amaral Andrea N , Gout Evelyne , Danella-Polli Claudia , Tabarin Fanny , Lesavre Philippe , Pereira-da-Silva Gabriela , Thielens Nicole M , Halbwachs-Mecarelli Lise
Published: December 2011

M-ficolin specificity for sialylated ligands prompted us to investigate its interactions with the main membrane sialoprotein of human neutrophils, CD43. rM-ficolin bound CD43 and prevented the access of anti-CD43 mAb. Moreover, rM-ficolin reacted exclusively with CD43 on Western blots of neutrophil lysate. We confirmed that M-ficolin is secreted by fMLP-activated neutrophils, and this endogenous M-ficolin also binds to CD43 and competes with anti-CD43 mAb. Anti-CD43 antibody cross-linking or fMLP resulted in M-ficolin and CD43 colocalization on polarized neutrophils. The binding of rM-ficolin to resting neutrophils induced cell polarization, adhesion, and homotypic aggregation as anti-CD43 mAb. The M-ficolin Y271F mutant, unable to bind sialic acid, neither reacted with neutrophils nor modulated their functions. Finally, rM-ficolin activated the lectin complement pathway on neutrophils. These results emphasize a new function of M-ficolin, different from ficolin pathogen recognition, i.e., a participation to neutrophil adhesion potentially important in early inflammation, as nanomolar agonist concentrations are sufficient to mobilize M-ficolin to the neutrophil surface. This multivalent lectin could then endow the antiadhesive CD43, essentially designed to prevent leukocyte aggregation in the blood flow, with new adhesive properties and explain, at least in part, dual-adhesive/antiadhesive roles of CD43 in neutrophil recruitment.
Growth Hormone Stimulates Transcription of the Fibroblast Growth Factor 21 Gene in the Liver through the Signal Transducer and Activator of Transcription 5
Authors: Yu Jie , Zhao Lidan , Wang Aihua , Eleswarapu Satyanarayana , Ge Xiaomei , Chen Daiwen , Jiang Honglin
Published: December 2011

Fibroblast growth factor 21 (FGF21) is a recently discovered metabolic regulator. Interestingly, FGF21 is also known to inhibit Janus kinase 2 (JAK2)-signal transducer and activator of transcription 5 (STAT5) signaling from the GH receptor in the liver, where FGF21 mRNA is predominantly expressed. In this study, we tested the hypothesis that FGF21 gene expression in the liver is controlled by GH through STAT5. We found that GH injection to cattle increased FGF21 mRNA expression in the liver. Mapped by a 5′-rapid amplification of cDNA ends assay, transcription of the FGF21 gene in the bovine liver was mainly initiated from a nucleotide 24 bp downstream of a TATA box. The bovine FGF21 promoter contains three putative STAT5-binding sites. EMSA confirmed the ability of them to bind to liver STAT5 protein from GH-injected cattle. Chromatin immunoprecipitation assays demonstrated that GH administration increased the binding of STAT5 to the FGF21 promoter in the liver. Cotransfection analyses showed that GH induced reporter gene expression from the FGF21 promoter in a STAT5-dependent manner. GH also stimulated FGF21 mRNA expression in cultured mouse hepatocytes. These data together indicate that GH directly stimulates FGF21 gene transcription in the liver, at least in part, through STAT5. This finding, together with the fact that FGF21 inhibits GH-induced JAK2-STAT5 signaling in the liver, suggests a novel negative feedback loop that prevents excessive JAK2-STAT5 signaling from the GH receptor in the liver.
Dragging and Confirming
Authors: Kotzen Matthew
Published: December 2011

This essay addresses the question of when evidence for a stronger claim H1 also constitutes evidence for a weaker claim H2. Although the answer “Always” is tempting, it is false on a natural Bayesian conception of evidence. This essay first describes some prima facie counterexamples to this answer and surveys some weaker answers and rejects them. Next, it proposes an answer, which appeals to the “Dragging Condition.” After explaining and arguing for its use of the Dragging Condition, the essay argues that the Dragging Condition provides a general account of, and solution to, the counterexamples with which the essay began. The essay briefly discusses the relevance of the Dragging Condition to the recently much-discussed topic of “transmission failure” in epistemology, applies the Dragging Condition to the problem of “bootstrapping” in epistemology, and discusses three important objections to the view defended in the essay.
Where Love and Resentment Meet: Strawson's Intrapersonal Defense of Compatibilism
Authors: Shabo Seth
Published: December 2011

In his seminal essay “Freedom and Resentment,” P. F. Strawson drew attention to the role of such emotions as resentment, moral indignation, and guilt in our moral and personal lives. According to Strawson, these reactive attitudes are at once constitutive of moral blame and inseparable from ordinary interpersonal relationships. On this basis, he concluded that relinquishing moral blame isn't a real possibility for us, given our commitment to personal relationships. If well founded, this conclusion puts the traditional free-will debate in a new light. In particular, insofar as incompatibilists believe that we can or should forgo moral blame if determinism is true, their stance may seem out of touch with our emotional reality. This essay examines Strawson's claim that the reactive attitudes are inseparable from ordinary interpersonal relationships. Strawson says surprisingly little to support this intriguing claim, and thus far no argument for it has emerged in the literature. This essay's aim is to remedy this. Specifically, it sets out an argument for a suitably formulated version of the inseparability claim, an argument that appeals to the relationship between the reactive attitudes and other elements of our emotional lives. It then shows how this argument helps to answer an important recent challenge to Strawson's position. If this essay is right, there is good reason to doubt that the reforms envisaged by some incompatibilists, reforms to our blame-related practices, are a real possibility for us.
A minor role of WNK3 in regulating phosphorylation of renal NKCC2 and NCC co-transporters in vivo
Authors: Oi Katsuyuki , Sohara Eisei , Rai Tatemitsu , Misawa Moko , Chiga Motoko , Alessi Dario R. , Sasaki Sei , Uchida Shinichi
Published: December 2011

Mutations in WNK1 and WNK4 kinase genes have been shown to cause a human hereditary hypertensive disease, pseudohypoaldosteronism type II (PHAII). We previously discovered that WNK kinases phosphorylate and activate OSR1/SPAK kinases that regulate renal SLC12A family transporters such as NKCC2 and NCC, and clarified that the constitutive activation of this cascade causes PHAII. WNK3, another member of the WNK kinase family, was reported to be a strong activator of NCC/NKCC2 when assayed in Xenopus oocytes, suggesting that WNK3 also plays a major role in regulating blood pressure and sodium reabsorption in the kidney. However, it remains to be determined whether WNK3 is in fact involved in the regulation of these transporters in vivo. To clarify this issue, we generated and analyzed WNK3 knockout mice. Surprisingly, phosphorylation and expression of OSR1, SPAK, NKCC2 and NCC did not decrease in knockout mouse kidney under normal and low-salt diets. Similarly, expression of epithelial Na channel and Na/H exchanger 3 were not affected in knockout mice. Na+ and K+ excretion in urine in WNK3 knockout mice was not affected under different salt diets. Blood pressure in WNK3 knockout mice was not lower under normal diet. However, lower blood pressure was observed in WNK3 knockout mice fed low-salt diet. WNK4 and WNK1 expression was slightly elevated in the knockout mice under low-salt diet, suggesting compensation for WNK3 knockout by these WNKs. Thus, WNK3 may have some role in the WNK-OSR1/SPAK-NCC/NKCC2 signal cascade in the kidney, but its contribution to total WNK kinase activity may be minimal.
Molecular architecture of heparin and heparan sulfate: Recent developments in solution structural studies
Authors: Mulloy Barbara , Khan Sanaullah , Perkins Stephen J.
Published: December 2011

The study of the relationship between the complex structures and numerous physiological functions of the glycosaminoglycans (GAGs) heparin and heparan sulfate (HS) has continued to thrive in the past decade. Though it is clear that the monosaccharide sequences of these polysaccharides must determine their ability to modulate the action of growth factors, morphogens, chemokines, cytokines, and many other extracellular proteins, the exact details of this dependence still prove elusive. Sequence determines the 3D structure of GAGs at more than one level; detailed sequences of highly sulfated regions may influence affinity for specific proteins in some cases, but in addition attention has been called to the importance of the length and spacing of these highly sulfated sequences, which are separated by unsulfated domains. Within the sulfated “S-domains”, the internal dynamics of the conformationally flexible iduronate pyranose ring have continued to interest NMR spectroscopists and molecular modelers. New studies of the relative degrees of flexibility of sulfated and unsulfated domains lead to an overall model of heparin/HS in which protein-binding, highly sulfated S-domains with well-defined conformations are separated by more flexible NA-domains.
Promotion of Non-Rapid Eye Movement Sleep and Activation of Reticular Thalamic Neurons by a Novel MT2Melatonin Receptor Ligand
Authors: Ochoa-Sanchez Rafael , Comai Stefano , Lacoste Baptiste , Bambico Francis Rodriguez , Dominguez-Lopez Sergio , Spadoni Gilberto , Rivara Silvia , Bedini Annalida , Angeloni Debora , Fraschini Franco , Mor Marco , Tarzia Giorgio , Descarries Laurent , Gobbi Gabriella
Published: December 2011

Melatonin activates two brain G-protein coupled receptors, MT1and MT2, whose differential roles in the sleep–wake cycle remain to be defined. The novel MT2receptor partial agonist,N-{2-[(3-methoxyphenyl) phenylamino] ethyl} acetamide (UCM765), is here shown to selectively promote non-rapid eye movement sleep (NREMS) in rats and mice. The enhancement of NREMS by UCM765 is nullified by the pharmacological blockade or genetic deletion of MT2receptors. MT2, but not MT1, knock-out mice show a decrease in NREMS compared to the wild strain. Immunohistochemical labeling reveals that MT2receptors are localized in sleep-related brain regions, and notably the reticular thalamic nucleus (Rt). Microinfusion of UCM765 in the Rt promotes NREMS, and its systemic administration induces an increase in firing and rhythmic burst activity of Rt neurons, which is blocked by the MT2antagonist 4-phenyl-2-propionamidotetralin. Since developing hypnotics that increase NREMS without altering sleep architecture remains a medical challenge, MT2receptors may represent a novel target for the treatment of sleep disorders.
Searching for Presynaptic NMDA Receptors in the Nucleus Accumbens
Authors: Huang Yanhua H. , Ishikawa Masago , Lee Brian R. , Nakanishi Nobuki , Schlüter Oliver M. , Dong Yan
Published: December 2011

The nucleus accumbens shell (NAc) is a key brain region mediating emotional and motivational learning. In rodent models, dynamic alterations have been observed in synaptic NMDA receptors (NMDARs) within the NAc following incentive stimuli, and some of these alterations are critical for acquiring new emotional/motivational states. NMDARs are prominent molecular devices for controlling neural plasticity and memory formation. Although synaptic NMDARs are predominately located postsynaptically, recent evidence suggests that they may also exist at presynaptic terminals and reshape excitatory synaptic transmission by regulating presynaptic glutamate release. However, it remains unknown whether presynaptic NMDARs exist in the NAc and contribute to emotional and motivational learning. In an attempt to identify presynaptically located NMDARs in the NAc, the present study uses slice electrophysiology combined with pharmacological and genetic tools to examine the physiological role of the putative presynaptic NMDARs in rats. Our results show that application of glycine, the glycine-site agonist of NMDARs, potentiated presynaptic release of glutamate at excitatory synapses on NAc neurons, whereas application of 5,7-dichlorokynurenic acid or 7-chlorokynurenic acid, the glycine-site antagonists of NMDARs, produced the opposite effect. However, these seemingly presynaptic NMDAR-mediated effects could not be prevented by application ofd-APV, the glutamate-site NMDAR antagonist, and were still present in the mice in which NMDAR NR1 or NR3 subunits were genetically deleted. Thus, rather than suggesting the existence of presynaptic NMDARs, our results support the idea that an unidentified type of glycine-activated substrate may account for the presynaptic effects appearing to be mediated by NMDARs.
Dynamic Reconfiguration of Structural and Functional Connectivity Across Core Neurocognitive Brain Networks with Development
Authors: Uddin Lucina Q. , Supekar Kaustubh S. , Ryali Srikanth , Menon Vinod
Published: December 2011

Brain structural and functional development, throughout childhood and into adulthood, underlies the maturation of increasingly sophisticated cognitive abilities. High-level attentional and cognitive control processes rely on the integrity of, and dynamic interactions between, core neurocognitive networks. The right fronto-insular cortex (rFIC) is a critical component of a salience network (SN) that mediates interactions between large-scale brain networks involved in externally oriented attention [central executive network (CEN)] and internally oriented cognition [default mode network (DMN)]. How these systems reconfigure and mature with development is a critical question for cognitive neuroscience, with implications for neurodevelopmental pathologies affecting brain connectivity. Using functional and effective connectivity measures applied to fMRI data, we examine interactions within and between the SN, CEN, and DMN. We find that functional coupling between key network nodes is stronger in adults than in children, as are causal links emanating from the rFIC. Specifically, the causal influence of the rFIC on nodes of the SN and CEN was significantly greater in adults compared with children. Notably, these results were entirely replicated on an independent dataset of matched children and adults. Developmental changes in functional and effective connectivity were related to structural connectivity along these links. Diffusion tensor imaging tractography revealed increased structural integrity in adults compared with children along both within- and between-network pathways associated with the rFIC. These results suggest that structural and functional maturation of rFIC pathways is a critical component of the process by which human brain networks mature during development to support complex, flexible cognitive processes in adulthood.
Experimental and Numerical Investigations of Ferrocene-Doped Propene Flames
Authors: Staude Susanne , Bergmann Ulf , Atakan Burak
Published: December 2011

Ferrocene-doped low-pressure, laminar, premixed propene/oxygen/argon flames of different stoichiometries were investigated experimentally using laser induced fluorescence (LIF) and the results were compared with numerical simulations. The influence of ferrocene on the flame temperature proved to be minimal both in the measurement and in the simulation. The measured flame temperatures were 100–250 K below the adiabatic flame temperature, as expected. However, the modeled flame temperatures were around 450 K below the measurements. It is assumed that the reason for this lies in the incorrect modeling of the flame speed since systematic errors in the LIF measurements should be small, as discussed in the paper. Iron atom concentrations were also measured using LIF. The results show the influence of the stoichiometry on the iron atom concentration, which is also reproduced by the model. The majority of the added iron was observed to exist as atomic iron in the flame. As more oxygen becomes available in leaner flames, iron will tend to form more FeO so that the iron atom concentration decreases with decreasing equivalence ratio.
The Effect of Carbon–Carbon Double Bonds on the Combustion Chemistry of Small Fatty Acid Esters
Authors: Yang Bin , Westbrook Charles K. , Cool Terrill A. , Hansen Nils , Kohse-Höinghaus Katharina
Published: December 2011

Environmentally friendly biodiesel is a mixture of saturated and unsaturated methyl (or ethyl) esters of long-chain fatty acids. To experimentally examine the effect of C=C double bonds on the combustion chemistry of fatty acid esters, low-pressure premixed laminar flames of four small esters have been studied using flame-sampling molecular-beam mass spectrometry. Mole fraction profiles of reactants, products, and well-identified stable and reactive combustion intermediates in flames of the saturated species methyl propanoate (CH3CH2COOCH
3) and its isomer ethyl acetate (CH3COOCH2CH
3) have been compared with results from flames of the unsaturated fuels methyl propenoate (CH2CHCOOCH
3) and vinyl acetate (CH3COOCHCH
2) flames. A total of eight flames have been studied, with two fuel-rich flame conditions investigated (fuel-equivalence ratios φ=1.2 and 1.56) for each fuel. In addition, the underlying oxidation chemistry at these premixed flame conditions has been investigated using a detailed chemical kinetic reaction mechanism, which is largely based on a previously proposed model for saturated esters [B. Yang et al., Phys. Chem. Chem. Phys. 13 (2011) 7205]. The combined results provide a detailed understanding of the similarities and differences between the combustion of saturated vs. unsaturated esters. Meanwhile, the isomeric and stoichiometric effects on their combustion chemistry are also addressed. In this paper, experimental and modeling details are discussed with a special focus on the different reaction pathways.
PLIF Thermometry Based on Measurements of Absolute Concentrations of the OH Radical
Authors: Heinze Johannes , Meier Ulrich , Behrendt Thomas , Willert Chris , Geigle Klaus-Peter , Lammel Oliver , Lückerath Rainer
Published: December 2011

A method for measurements of planar temperature distributions based on planar laser-induced fluorescence (PLIF) of the OH radiacal is described. The technique was developed specifically for the application in lean combustion systems, where OH equilibrium concentrations are largely independent on equivalence ratio and a function of temperature only. It is thus possible to derive a temperature information from measurements of absolute OH concentration, which can be obtained from a combined PLIF/absorption measurement.

This paper discusses the basics of the method, and describes validation experiments in high pressure laminar premixed flames which were performed to asses its applicability and accuracy. Therefore, we compared our LIF based results with CARS measurements performed in the same flames. Finally, an example for the application in a lean gas turbine model combustor is discussed.
Diode Laser Induced Fluorescence for Gas-Phase Diagnostics
Authors: Burns Iain S. , Kaminski Clemens F.
Published: December 2011

We highlight the capabilities and potential of diode laser induced fluorescence for measurements in gas-phase reacting flows. Many applications of diode lasers in practical sensing are based on absorption spectroscopy. Fluorescence-based diagnostics possess similar advantages in terms of practicality and implementation-cost but additionally are capable of achieving excellent spatial resolution. Diode laser fluorescence instruments have been employed for high-sensitivity trace gas monitoring in applications ranging from plasma physics to atmospheric chemistry. This article begins by describing the UV-visible diode laser technology used to perform fluorescence. The principles of diode laser induced fluorescence are then reviewed and a comparison is made with absorption spectroscopy. Examples are given of concentration measurements of both atomic and molecular trace gases. Recent work on using diode laser induced atomic fluorescence for precision measurements of flame temperature is also reviewed. We conclude by a discussion of future opportunities for diode laser fluorescence spectroscopy drawing attention to interesting potential target species as well as novel application areas, such as monitoring of synthesis processes for nanomaterials.
Response of Bacillus thuringiensis Al Hakam Endospores to Gas Dynamic Heating in a Shock Tube
Authors: McCartt A. Daniel , Gates Sean D. , Jeffries Jay B. , Hanson Ronald K. , Joubert Lydia M. , Buhr Tony L.
Published: December 2011

Experiments were conducted in a gas-driven shock tube to investigate shock wave-induced damage to Bacillus
thuringiensis Al Hakam endospores over a wide range of post-shock temperatures in non-oxidative gas environments. The results were compared with previous studies on B. atrophaeus and B. subtilis and demonstrate that B. thuringiensis Al Hakam exhibited a qualitatively similar response to rapid shock heating, even though this strain has a significantly different endospore structure. B.
thuringiensis Al Hakam endospores were nebulized into an aqueous aerosol, which was loaded into the Stanford aerosol shock tube, and subjected to shock waves of controlled strength. Endospores experienced uniform test temperatures between 500 and 1000 K and pressures ranging from 2 atm to 7 atm for approximately 2.5 ms. During this process the bio-aerosol was monitored using in situ time-resolved laser absorption and scattering diagnostics. Additionally, shock-treated bio-aerosol samples were extracted for ex situ analysis including viability plating, flow cytometry and scanning electron microscopy (SEM) imaging. B. thuringiensis Al Hakam endospores lost the ability to form colonies at post-shock temperatures above 500 K while significant breakdown in morphology was observed only for post-shock temperatures above 700 K. While viability loss and endospore morphological deterioration adhere to a similar framework across all endospore species studied, phenomena unique to B. thuringiensis Al Hakam were noted in the SEM images and optical extinction data. This initial characterization of the response of B. thuringiensis Al Hakam spores treated with shock/blast waves shows that these methods have potential for spore inactivation and detection.
Numerical Analysis of Thermoacoustic Instabilities Using LES and Computational Aeroacoustics
Authors: Klewer Christian , Ketelheun Anja , Janicka Johannes
Published: December 2011

Many technical combustion devices are susceptible to thermoacoustic instabilities. A deeper understanding of this transient phenomenon as well as the underlying physical processes is desirable. In this context, a turbulent enclosed flame is investigated numerically within this work by means of a hybrid LES/CAA (Large Eddy Simulation/Computational Aero Acoustics) approach as a step towards a numerical prediction of combustion instability. A thermoacoustically stable as well as a thermoacoustically unstable operating point are investigated. The LES computations reveal good overall agreement between simulation and experimental data. However, the recirculation zone, which is created by a backward facing step, is underestimated for the unstable case. The amplitudes as well as the frequencies of the simulated acoustic pressure are in good agreement with experimental data for the stable case. Considering the unstable case, the frequency of the oscillation is captured accurately, while the amplitudes are underpredicted.
On the Temperature Dependence of the Thermal Electron Attachment to SF
6
, SF
5
Cl, and POCl
3
Authors: Troe Hans-Jürgen , Marowsky Gerd , Shuman Nicholas S. , Miller Thomas M. , Viggiano Albert A.
Published: December 2011

A simplified model for electron attachment to neutral molecules, separating electron--phonon coupling (or intramolecular vibrational redistribution, IVR) factors into an electronic and a vibrational contribution, is tested by comparison with experimental results for the nondissociative electron attachments to SF6, SF5Cl, and POCl3. It is shown that the experimental results can approximately be reproduced by the fit of two parameters, one of them characterizing the dependence of the IVR factor on the electron energy and one accounting for an effective threshold energy for overlap of vibrational wave functions on anionic and neutral potential energy surfaces. After fitting these parameters, temperature dependences over wide ranges of conditions can be represented. Likewise, kinetic modeling of dissociative processes of the highly excited anions produced by attachment is facilitated.
Comparison of Neurocognitive Functions after Beating-Heart Mitral Valve Replacement without Aorta Cross-Clamping and after Standard Mitral Valve Replacement with Cardioplegic Arrest
Authors: Kervan Umit , Cicekcioglu Ferit , Tuluce Hicran , Ozen Anil , Babaroglu Seyhan , Karakas Sibel , Katircioglu Salih Fehmi
Published: December 2011

Background: The aim of this study was to compare the postoperative long-term neurocognitive functions of patients who under-went beating-heart mitral valve replacement on cardiopulmonary bypass (CPB) without aorta cross-clamping with those of patients who underwent mitral valve replacement via the classic method.

Methods: The study group included 25 randomly selected patients who underwent beating-heart mitral valve surgery. During the same period, 25 patients were randomly selected as controls to undergo mitral valve replacement procedures via the standard ascending aorta-cannulation technique. The clinical and postoperative (2 months) neurocognitive functional data of both groups were compared.

Results: Neurologic deficit was observed in neither group during the postoperative period. There were no statistically significant differences between the control and the study groups with respect to Hospital Anxiety and Depression Scale (HADS) results (HADS: anxiety, P = .653; HADS: depression, P = .225), in the right hemispheric cognitive function test results (Raven's Standard Progressive Matrices [RSPM] and Line Orientation Test [LOT] tests: RSPM, P = .189), and in the left hemispheric cognitive function test results (the Ray Auditory Verbal Learning [RAVL] and Stroop Color-Word Test [SCWT] tests: SCWT 1 time, P = .300; SCWT 2 time, P = .679; SCWT 3 time, P = .336; SCWT 4 time, P = .852; SCWT 5 time, P = .416; RAVL total verbal learning, P = .167; RAVL immediate recall, P = .791; RAVL distraction trial, P = .199; RAVL retention, P = .174; RAVL delayed recall, P = .111; RAVL recognition, P = .282; SCWT 4 mistake, P = .306; SCWT 4 reform, P = .066; SCWT 5 mistake, P = .236; SCWT 5 reform, P = .301).

Conclusions: The technique of mitral valve replacement with normothermic CPB without cross-clamping of the aorta may be safely used for the majority of patients requiring mitral valve replacement without causing deterioration in neurocognitive functions.
"Removal without Replacement" Strategy for Uncontrolled Prosthetic Tricuspid Valve Endocarditis Associated with Abortion Sepsis
Authors: Karabulut Ahmet , Surgit Ozgur , Akgul Ozgur , Bakir Ihsan
Published: December 2011

Isolated tricuspid valve (TV) endocarditis associated with abortion is a rare entity with a poor prognosis. We report the case of a 22-year-old woman with a diagnosis of isolated prosthetic TV endocarditis secondary to recurrent abortion. The patient had progressed to multiorgan failure and disseminated intravascular coagulation during her clinical course. Because of the high operative risk and uncontrolled infection, we performed an unusual surgical approach that has not previously been reported. Resection of infected valvular tissue without replacement of the prosthesis led to a rapid convalescence period and complete cure.
Off-Pump Coronary Artery Bypass Grafting in a Low-Volume Center
Authors: Saha Kamales Kumar , Deval Mandar , Jagdale Lukash , Sahani Preetam
Published: December 2011

Background: The advantages of off-pump coronary artery bypass grafting (OPCAB) are well documented; however, the conversion of OPCAB to cardiopulmonary bypass (CPB) is associated with higher morbidity and mortality. This issue is of particular concern in low-volume centers or centers that are beginning to use OPCAB. We present an OPCAB methodology that uses a maximum number of arterial grafts.

Methods: We routinely use OPCAB in every patient unless there is another associated condition. We used the following methods to improve the safety of OPCAB: (1) maintaining normothermia, (2) routine use of a pulmonary artery catheter, (3) routine use of a femoral arterial line, (4) routine use of a cell saver, and (5) complete revascularization.

Results: We included 173 consecutive patients in the study. All patients underwent OPCAB without any conversion to CPB. Hemodynamic compromise in 5 patients (2.89%) required insertion of an intra-aortic balloon pump (IABP). OPCAB was completed in all 5 patients after IABP insertion. Blood transfusions (BTs) were avoided in 55 patients (31.8%), and 68 patients (39.3%) required ?2 units of blood.

Conclusion: The OPCAB technique is still evolving. Low-volume centers have higher rates of conversion to CPB. Hypotension due to an impaired left ventricular function can be successfully treated by using an IABP. Although blood loss can be managed with BTs, use of a cell saver helps to reduce the number of BTs. We conclude that our technique of total arterial OPCAB using a cell saver can be safely performed in a low-volume center.
Transcatheter Aortic Valve Implantation and Simultaneous Closure of Ostium Secundum Atrial Septal Defect
Authors: Pasic Miralem , Berger Felix , D'Ancona Giuseppe , Dreysse Stephan , Buz Semih , Drews Thorsten , Hetzer Roland , Unbehaun Axel , Kukucka Marian
Published: December 2011

We were faced with a difficult question: how to treat a high-risk patient with severe aortic valve stenosis and a secundum atrial septal defect (ASD II). An 85-year-old woman with progressive dyspnea and pedal edema and in New York Heart Association class IV was treated with concomitant transapical aortic valve implantation and transcatheter closure of the ASD II. The combined procedure and postoperative course were completely uneventful. At 2 years after the clinical follow-up, the patient is doing well. This case report demonstrates, for the first time, the feasibility, safety, and effectiveness of simultaneous application of 2 transcatheter methods�aortic valve implantation and closure of an ASD II. As surgeons, we should consider percutaneous treatment of combined structural heart disease in patients at high risk for conventional surgery.
Glutamine Is Cardioprotective in Patients with Ischemic Heart Disease following Cardiopulmonary Bypass
Authors: Lomivorotov Vladimir V. , Efremov Sergey M. , Shmirev Vladimir A. , Ponomarev Dmitry N. , Lomivorotov Vladimir N. , Karaskov Alexander M.
Published: December 2011

Background: The aim of the present study was to investigate the cardioprotective effects of the perioperative use of N(2)-L-alanyl-L-glutamine (GLN) in patients with ischemic heart disease (IHD) who undergo their operations under cardiopulmonary bypass (CPB).

Methods: This double-blind, placebo-controlled, randomized study included 50 patients who underwent cardiac surgery with CPB. Exclusion criteria were a left ventricular ejection fraction <50%, diabetes mellitus, <3 months since the onset of myocardial infarction, and emergency surgery. Patients in the study group (n = 25) received 0.4 g/kg GLN (Dipeptiven, 20% solution) per day. Patients in the control group (n = 25) were administered a placebo (0.9% NaCl). The primary end point was the dynamics of troponin I at the following stages: (1) prior to anesthesia, (2) 30 minutes after CPB, (3) 6 hours after CPB, (4) 24 hours after surgery, and (5) 48 hours after surgery. Secondary end points included measurements of hemodynamics with a Swan-Ganz catheter.

Results: On the first postoperative day after the surgery, the median troponin I level was significantly lower in the study group than in the placebo group: 1.280 ng/mL (interquartile range [IQR], 0.840-2.230 ng/mL) versus 2.410 ng/mL (IQR, 1.060-6.600 ng/mL) (P = .035). At 4 hours after cardiopulmonary bypass (CPB), the median cardiac index was higher in the patients in the study group: 2.58 L/min per m2 (IQR, 2.34-2.91 L/min per m2) versus 2.03 L/min per m2 (IQR, 1.76-2.32 L/min per m2) (P = .002). The median stroke index also was higher in the patients who received GLN: 32.8 mL/m2 (IQR, 27.8-36.0 mL/m2) versus 26.1 mL/m2 (IQR, 22.6-31.8 mL/m2) (P = .023). The median systemic vascular resistance index was significantly lower in the study group than in the placebo group: 1942 dyn�s/cm5 per m2 (IQR, 1828-2209 dyn�s/cm5 per m2) versus 2456 dyn�s/cm5 per m2 (IQR, 2400-3265 dyn�s/cm5 per m2) (P = .001).

Conclusion: Perioperative administration of GLN during the first 24 hours has cardioprotective effects in IHD patients following CPB. This technique enhances the troponin concentration at 24 hours after surgery and is associated with improved myocardial function.
A QTL Study for Regions Contributing toArabidopsis thalianaRoot Skewing on Tilted Surfaces
Authors: Vaughn Laura M , Masson Patrick H
Published: December 2011

Plant root systems must grow in a manner that is dictated by endogenous genetic pathways, yet sensitive to environmental input. This allows them to provide the plant with water and nutrients while navigating a heterogeneous soil environment filled with obstacles, toxins, and pests. Gravity and touch, which constitute important cues for roots growing in soil, have been shown to modulate root architecture by altering growth patterns. This is illustrated by Arabidopsis thaliana roots growing on tilted hard agar surfaces. Under these conditions, the roots are exposed to both gravity and touch stimulation. Consequently, they tend to skew their growth away from the vertical and wave along the surface. This complex growth behavior is believed to help roots avoid obstacles in nature. Interestingly, A. thaliana accessions display distinct growth patterns under these conditions, suggesting the possibility of using this variation as a tool to identify the molecular mechanisms that modulate root behavior in response to their mechanical environment. We have used the Cvi/Ler recombinant inbred line population to identify quantitative trait loci that contribute to root skewing on tilted hard agar surfaces. A combination of fine mapping for one of these QTL and microarray analysis of expression differences between Cvi and Ler root tips identifies a region on chromosome 2 as contributing to root skewing on tilted surfaces, potentially by modulating cell wall composition.
Translational Genomics in Legumes Allowed Placing In Silico 5460 Unigenes on the Pea Functional Map and Identified Candidate Genes in Pisum sativum L.
Authors: Bordat Amandine , Savois Vincent , Nicolas Marie , Salse Jérome , Chauveau Aurélie , Bourgeois Michael , Potier Jean , Houtin Hervé , Rond Céline , Murat Florent , Marget Pascal , Aubert Grégoire , Burstin Judith
Published: December 2011

To identify genes involved in phenotypic traits, translational genomics from highly characterized model plants to poorly characterized crop plants provides a valuable source of markers to saturate a zone of interest as well as functionally characterized candidate genes. In this paper, an integrated view of the pea genetic map was developed. A series of gene markers were mapped and their best reciprocal homologs were identified on M. truncatula, L. japonicus, soybean, and poplar pseudomolecules. Based on the syntenic relationships uncovered between pea and M. truncatula, 5460 pea Unigenes were tentatively placed on the consensus map. A new bioinformatics tool, http://www.thelegumeportal.net/pea_mtr_translational_toolkit, was developed that allows, for any gene sequence, to search its putative position on the pea consensus map and hence to search for candidate genes among neighboring Unigenes. As an example, a promising candidate gene for the hypernodulation mutation nod3 in pea was proposed based on the map position of the likely homolog of Pub1, a M. truncatula gene involved in nodulation regulation. A broader view of pea genome evolution was obtained by revealing syntenic relationships between pea and sequenced genomes. Blocks of synteny were identified which gave new insights into the evolution of chromosome structure in Papillionoids and Eudicots. The power of the translational genomics approach was underlined.