Dispersive estimates for the Schrödinger equation

In this document we explore the issue of $L^1\to L^\infty$ estimates for the solution operator of the linear Schr\"{o}dinger equation, \begin{align*} iu_t-\Delta u+Vu&=0 &u(x,0)=f(x)\in \mathcal S(\R^n). \end{align*} We focus particularly on the five and seven dimensional cases. We prove that the solution operator precomposed with projection onto the absolutely continuous spectrum of $H=-\Delta+V$ satisfies the following estimate $\|e^{itH} P_{ac}(H)\|_{L^1\to L^\infty} \lesssim |t|^{-\frac{n}{2}}$ under certain conditions on the potential $V$. Specifically, we prove the dispersive estimate is satisfied with optimal assumptions on smoothness, that is $V\in C^{\frac{n-3}{2}}(\R^n)$ for $n=5,7$ assuming that zero is regular, $|V(x)|\lesssim \langle x\rangle^{-\beta}$ and $|\nabla^j V(x)|\lesssim \langle x\rangle^{-\alpha}$, $1\leq j\leq \frac{n-3}{2}$ for some $\beta>\frac{3n+5}{2}$ and $\alpha>3,8$ in dimensions five and seven respectively. We also show that for the five dimensional result one only needs that $|V(x)|\lesssim \langle x\rangle^{-4-}$ in addition to the assumptions on the derivative and regularity of the potential. This more than cuts in half the required decay rate in the first chapter. Finally we consider a problem involving the non-linear Schr\"{o}dinger equation. In particular, we consider the following equation that arises in fiber optic communication systems, \begin{align*} iu_t+d(t) u_{xx}+|u|^2 u=0. \end{align*} We can reduce this to a non-linear, non-local eigenvalue equation that describes the so-called dispersion management solitons. We prove that the dispersion management solitons decay exponentially in $x$ and in the Fourier transform of $x$.

Acute phase proteins and biomarkers for health in chickens

Acute phase proteins (APPs) are proteins synthesised predominantly in the liver, whose plasma concentrations increase (positive APP) or decrease (negative APP) as a result of infection, inflammation, trauma and tissue injury. They also change as a result of the introduction of immunogens such as bacterial lipopolysaccharide (LPS), turpentine and vaccination. While publications on APPs in chickens are numerous, the limited availability of anti-sera and commercial ELISAs has resulted in a lot of information on only a few APPs. Disease is a threat to the poultry industry, as pathogens have the potential to evolve, spread and cause rapid onset of disease that is detrimental to the welfare of birds. Low level, sub-acute disease with non-specific, often undiagnosed causes can greatly affect bird health and growth and impact greatly on productivity and profitability. Developing and validating methods to measure and characterise APPs in chickens will allow these proteins to be used diagnostically for monitoring flock health. Using immune parameters such as APPs that correlate with disease resistance or improvements in production and welfare will allow the use of APPs as selection parameters for breeding to be evaluated. For APPs to be useful parameters on which to evaluate chicken health, information on normal APP concentrations is required. Ceruloplasmin (Cp) and PIT54 concentrations were found to be much lower in healthy birds form commercial production farms than the reported normal values obtained from the literature. These APPs were found to be significantly higher in culled birds from a commercial farm and Cp, PIT54 and ovotransferrin (Ovt) were significantly higher in birds classified as having obvious gait defects. Using quantitative shotgun proteomics to identify the differentially abundant proteins between three pools: highly acute phase (HAP), acute phase (AP) and non-acute phase (NAP), generated data from which a selection of proteins, based on the fold difference between the three pools was made. These proteins were targeted on a individual samples alongside proteins known to be APPs in chickens or other species: serum amyloid A (SAA), C-reactive protein (CRP), Ovt, apolipoprotein A-I (apo-AI), transthyretin (Ttn), haemopexin (Hpx) and PIT54. Together with immunoassay data for SAA, Ovt, alpha-1-acid glycoprotein (AGP) and Cp the results of this research reveal that SAA is the only major APP in chickens. Ovotransferrin and AGP behave as moderate APPs while PIT54 and Cp are minor APPs. Haemopexin was not significantly different between the three acute phase groups. Apolipoprotein AI and Ttn were significantly lower in the HAP and AP groups and as such can be classed as negative APPs. In an effort to identify CRP, multiple anti-sera cross reacting with CRP from other species were used and a phosphorylcholine column known to affinity purify CRP were used. Enriched fractions containing low molecular weight proteins, elutions from the affinity column together with HAP, AP and NAP pooled samples were applied to a Q-Exactive Hybrid Quadrupole–Orbitrap mass spectrometer (Thermo Scientific) for Shotgun analysis and CRP was not identified. It would appear that CRP is not present as a plasma protein constitutively or during an APR in chickens and as such is not an APP in this species. Of the proteins targeted as possible novel biomarkers of the APR in chickens mannan binding lectin associated serine protease-2, α-2-HS-glycoprotein (fetuin) and major facilitator superfamily domain-containing protein 10 were reduced in abundance in the HAP group, behaving as negative biomarkers. Myeloid protein and putative ISG(12)2 were positively associated with the acute phase being significantly higher in the HAP and AP groups. The protein cathepsin D was significantly higher in both HAP and AP compared to the NAP indicating that of all the proteins targeted, this appears to have the most potential as a biomarker of the acute phase, as it was significantly increased in the AP as well as the HAP group. To evaluate APPs and investigate biomarkers of intestinal health, a study using re-used poultry litter was undertaken. The introduction of litter at 12 days of age did not significantly increase any APPs measured using immunoassays and quantitative proteomics at 3, 6 and 10 days post introduction. While no APP was found to be significantly different between the challenged and control groups at anytime point, the APPs AGP, SAA and Hpx did increase over time in all birds. The protein apolipoprotein AIV (apo-AIV) was targeted as a possible APP and because of its reported role in controlling satiety. An ELISA was developed, successfully validated and used to measure apo-AIV in this study. While no significant differences in apo-AIV plasma concentrations between challenged and control groups were identified apo-AIV plasma concentrations did change significantly between certain time points in challenged and control groups. Apoliporotein AIV does not appear to behave as an APP in chickens, as it was not significantly different between acute phase groups. The actin associated proteins villin and gelsolin were investigated as possible biomarkers of intestinal health. Villin was found not to be present in the plasma of chickens and as such not a biomarker target. Gelsolin was found not to be differentially expressed during the acute phase or as a result of intestinal challenge. Finally a proteomic approach was undertaken to investigate gastrocnemius tendon (GT) rupture in broiler chickens with a view of elucidating to and identify proteins associated with risk of rupture. A number of proteins were found to be differentially expressed between tendon pools and further work would enable further detailing of these findings. In conclusion this work has made a number of novel findings and addressed a number of data poor areas. The area of chicken APPs research has stagnated over the last 15 years with publications becoming repetitive and reliant on a small number of immunoassays. This work has sought to characterise the classic APPs in chickens, and use a quantitative proteomic approach to measure and categorise them. This method was also used to take a fresh approach to biomarker identification for both the APR and intestinal health. The development and validation of assays for Ovt and apo-AIV and the shotgun data mean that these proteins can be further characterised in chickens with a view of applying their measurement to diagnostics and selective breeding programs.

Avaliação transcricional de Glutationas -transferases em PEIXE-ZEBRA (Danio rerio) e alterações causadas pela exposição á Microcistina-LR

As Microcistinas são heptapeptídios cíclicos produzidos como metabólitos secundários por diferentes espécies de cianobactérias, sendo relevantes pelo seu potencial hepatotóxico. Peixes apresentam estratégias bioquímicas para detoxificar contaminantes ambientais, incluindo a ativação de enzimas de fase II de biotransformação, que incluem as isoformas de glutationa S-transferase (GST). As GST catalizam a conjugação de glutationa reduzida (GSH) com uma variedade de xenobióticos, incluindo as microcistinas. O presente estudo avaliou os níveis transcricionais de quinze isoformas de GST a fim de identificar isoformas possivelmente envolvidas na detoxificação de contaminantes ambientais como a microcistina-LR (MC-LR) em Danio rerio. A técnica de PCR em tempo real (RT-qPCR) foi utilizada para avaliação dos níveis transcricionais, permitindo análise das GST em diferentes órgãos, abundância e a ativação/repressão das isoformas de GST pela exposição à MC-LR. Foram avaliados os possíveis efeitos causados em brânquia e fígado após exposição por 24 hs às concentrações de 5 µg.L-1 e 50 µg.L-1 de MC-LR. Baseado nos scores de estabilidade para oito genes normalizadores, foram selecionados glicose-6-fosfato desidrogenase (g6pdh), β-actina1 e beta-2-microglobulina (b2m); b2m, alfa-tubulina 1 (tuba) e β- actin1; e tuba, b2m e g6pdh, para normalização dos níveis trancricionais de GST para distribuição órgão-específica, abundância e efeito da MC-LR em brânquia e fígado, respectivamente. A avaliação transcricional da distribuição órgão-específica revelou níveis significativos de gstal e gstk1.1 no fígado; gstp1 e gstp2 em brânquia; mgst3a, gstr1, gstm2, gstm33, gstp1, gstp2 e gstk1.1 no intestino; gstm2, gstm3 e gstal no olho e gstt1a e gsta2.1 no cérebro. Considerando os níveis de transcritos para um dado órgão, gstk1.1, gstal, gstp1 e gstt2 foram mais abundantes nos órgãos de detoxificação, tais como o fígado, brânquias e intestino, enquanto gstt1a e gsta2.1 foram mais abundantes no rim. Em brânquia, gsta2.1 e gstt1b foram reprimidas por 5 µg.L-1 de MC-LR e mgst1.1 foi reprimida em 50 µg.L-1 de MC-LR. No fígado, as isoformas gst2.2 e gstp2 foram reprimidas em ambas as concentrações, gstal foi reprimida em 5 µg.L-1, e gstt1a e gstk1.1 foram reprimidas em 50 µg.L-1 de MC-LR. As isoformas gstal, gstr1, gstp1, mgst3a, gstm1, gstm2 e gstm3 não foram alteradas pela exposição a MC-LR. Os resultados obtidos fornecem informações para a escolha de isoformas específicas de GST possivelmente envolvidas na detoxificação/toxicidade de MC-LR, a serem melhores caracterizadas ao nível protéico e também contribui para a escolha de genes normalizadores a serem utilizados em outros estudos da mesma natureza

Gene expression profile suggests that pigs (Sus scrofa) are susceptible to Anaplasma phagocytophilum but control infection

BACKGROUND Anaplasma phagocytophilum infects a wide variety of hosts and causes granulocytic anaplasmosis in humans, horses and dogs and tick-borne fever in ruminants. Infection with A. phagocytophilum results in the modification of host gene expression and immune response. The objective of this research was to characterize gene expression in pigs (Sus scrofa) naturally and experimentally infected with A. phagocytophilum trying to identify mechanisms that help to explain low infection prevalence in this species. RESULTS For gene expression analysis in naturally infected pigs, microarray hybridization was used. The expression of differentially expressed immune response genes was analyzed by real-time RT-PCR in naturally and experimentally infected pigs. Results suggested that A. phagocytophilum infection affected cytoskeleton rearrangement and increased both innate and adaptive immune responses by up regulation of interleukin 1 receptor accessory protein-like 1 (IL1RAPL1), T-cell receptor alpha chain (TCR-alpha), thrombospondin 4 (TSP-4) and Gap junction protein alpha 1 (GJA1) genes. Higher serum levels of IL-1 beta, IL-8 and TNF-alpha in infected pigs when compared to controls supported data obtained at the mRNA level. CONCLUSIONS These results suggested that pigs are susceptible to A. phagocytophilum but control infection, particularly through activation of innate immune responses, phagocytosis and autophagy. This fact may account for the low infection prevalence detected in pigs in some regions and thus their low or no impact as a reservoir host for this pathogen. These results advanced our understanding of the molecular mechanisms at the host-pathogen interface and suggested a role for newly reported genes in the protection of pigs against A. phagocytophilum.

Macrophage Cell Activation With Acute Apical Abscess Contents Determined By Interleukin-1 Beta And Tumor Necrosis Factor Alpha Production.

This clinical study has investigated the antigenic activity of bacterial contents from exudates of acute apical abscesses (AAAs) and their paired root canal contents regarding the stimulation capacity by levels of interleukin (IL)-1 beta and tumor necrosis factor alpha (TNF-α) throughout the root canal treatment against macrophage cells. Paired samples of infected root canals and exudates of AAAs were collected from 10 subjects. Endodontic contents were sampled before (root canal sample [RCS] 1) and after chemomechanical preparation (RCS2) and after 30 days of intracanal medication with calcium hydroxide + chlorhexidine gel (Ca[OH]2 + CHX gel) (RCS3). Polymerase chain reaction (16S rDNA) was used for detection of the target bacteria, whereas limulus amebocyte lysate was used to measure endotoxin levels. Raw 264.7 macrophages were stimulated with AAA exudates from endodontic contents sampled in different moments of root canal treatment. Enzyme-linked immunosorbent assays were used to measure the levels of TNF-α and IL-1 beta. Parvimonas micra, Porphyromonas endodontalis, Dialister pneumosintes, and Prevotella nigrescens were the most frequently detected species. Higher levels of endotoxins were found in samples from periapical exudates at RCS1 (P < .005). In fact, samples collected from periapical exudates showed a higher stimulation capacity at RCS1 (P < .05). A positive correlation was found between endotoxins from exudates with IL-1 beta (r = 0.97) and TNF-α (r = 0.88) production (P < .01). The significant reduction of endotoxins and bacterial species achieved by chemomechanical procedures (RCS2) resulted in a lower capacity of root canal contents to stimulate the cells compared with that at RCS1 (P < .05). The use of Ca(OH)2 + CHX gel as an intracanal medication (RCS3) improved the removal of endotoxins and bacteria from infected root canals (P < .05) whose contents induced a lower stimulation capacity against macrophages cells at RCS1, RCS2, and RCS3 (P < .05). AAA exudates showed higher levels of endotoxins and showed a greater capacity of macrophage stimulation than the paired root canal samples. Moreover, the use of intracanal medication improved the removal of bacteria and endotoxins from infected root canals, which may have resulted in the reduction of the inflammatory potential of the root canal content.

Differential regulation of PGC-1 alpha expression in rat liver and skeletal muscle in response to voluntary running

Background: The beneficial actions of exercise training on lipid, glucose and energy metabolism and insulin sensitivity appear to be in part mediated by PGC-1 alpha. Previous studies have shown that spontaneously exercised rats show at rest enhanced responsiveness to exogenous insulin, lower plasma insulin levels and increased skeletal muscle insulin sensitivity. This study was initiated to examine the functional interaction between exercise-induced modulation of skeletal muscle and liver PGC-1 alpha protein expression, whole body insulin sensitivity, and circulating FFA levels as a measure of whole body fatty acid (lipid) metabolism. Methods: Two groups of male Wistar rats (2 Mo of age, 188.82 +/- 2.77 g BW) were used in this study. One group consisted of control rats placed in standard laboratory cages. Exercising rats were housed individually in cages equipped with running wheels and allowed to run at their own pace for 5 weeks. At the end of exercise training, insulin sensitivity was evaluated by comparing steady-state plasma glucose (SSPG) concentrations at constant plasma insulin levels attained during the continuous infusion of glucose and insulin to each experimental group. Subsequently, soleus and plantaris muscle and liver samples were collected and quantified for PGC-1 alpha protein expression by Western blotting. Collected blood samples were analyzed for glucose, insulin and FFA concentrations. Results: Rats housed in the exercise wheel cages demonstrated almost linear increases in running activity with advancing time reaching to maximum value around 4 weeks. On an average, the rats ran a mean (Mean +/- SE) of 4.102 +/- 0.747 km/day and consumed significantly more food as compared to sedentary controls (P < 0.001) in order to meet their increased caloric requirement. Mean plasma insulin (P < 0.001) and FFA (P < 0.006) concentrations were lower in the exercise-trained rats as compared to sedentary controls. Mean steady state plasma insulin (SSPI) and glucose (SSPG) concentrations were not significantly different in sedentary control rats as compared to exercise-trained animals. Plantaris PGC-1 alpha protein expression increased significantly from a 1.11 +/- 0.12 in the sedentary rats to 1.74 +/- 0.09 in exercising rats (P < 0.001). However, exercise had no effect on PGC-1 alpha protein content in either soleus muscle or liver tissue. These results indicate that exercise training selectively up regulates the PGC-1 alpha protein expression in high-oxidative fast skeletal muscle type such as plantaris muscle. Conclusion: These data suggest that PGC-1 alpha most likely plays a restricted role in exercise-mediated improvements in insulin resistance (sensitivity) and lowering of circulating FFA levels.

Effect of Laser Phototherapy on the Release of TNF-alpha and MMP-1 by Endodontic Sealer-Stimulated Macrophages

Objective: Our aim was to analyze the effect of laser phototherapy on the secretory activity of macrophages activated by interferon-gamma (IFN-gamma) and lipopolysaccharide (LPS), and stimulated by substances leached from an epoxy resin-based sealer (AH-Plus) and a calcium hydroxide-based sealer (Sealapex). Background Data: Laser phototherapy can modulate the inflammatory process, improving wound healing. This type of therapy could be useful for modulating postoperative symptoms seen after endodontic treatment. Materials and Methods: Cytotoxicity was indirectly assessed by measuring mitochondrial activity. Macrophages were stimulated by the leached substances or not (controls), and the groups were then irradiated or not. The secretion of pro-inflammatory cytokines (TNF-alpha and MMP-1) was analyzed using ELISA. Two irradiations at 6-h intervals were done with an As-Ga-Al diode laser (780 nm, 70 mW, spot size 4.0 mm(2), 3 J/cm(2), for 1.5 sec) in contact mode. Results: The sealers were non-cytotoxic to macrophages. The production of TNF-alpha was significantly decreased by laser phototherapy, regardless of experimental group. The level of secretion of MMP-1 was similar in all groups. Conclusion: Based on the conditions of this study we concluded that in activated macrophages, laser phototherapy impairs the secretion of the pro-inflammatory cytokine TNF-alpha, but has no influence on MMP-1 secretion.

Differential expression of HIF-1 alpha in CD44(+)CD24(-/) (low) breast ductal carcinomas

Background: Cancer stem cell (CSC) hypothesis postulates that tumors are maintained by a self-renewing CSC population that is also capable of differentiating into non-self-renewing cell populations that constitute the bulk of tumor. Stem cells renewal and differentiation can be directly influenced by the oxygen levels of determined tissues, probably by the reduction of oxidative DNA damage in hypoxic regions, thus leading to a friendlier microenvironment, regarding to clonal expansion and for resistance to chemotherapeutic regimens. Furthermore, there have been strong data indicating a pivotal role of hypoxic niche in cancer stem cells development. There are evidence that hypoxia could drive the maintenance of CSC, via HIF-1 alpha expression, but it still to be determined whether hypoxia markers are expressed in breast tumors presenting CD44(+)CD24(-/low) immunophenotype. Methods: Immunohistochemical analysis of CD44(+)CD24(-/low) expression and its relationship with hypoxia markers and clinical outcome were evaluated in 253 samples of breast ductal carcinomas. Double-immunolabeling was performed using EnVision Doublestain System (Dako, Carpinteria, CA, USA). Slides were then scanned into high-resolution images using Aperio ScanScope XT and then, visualized in the software Image Scope (Aperio, Vista, CA, USA). Results: In univariate analysis, CD44(+)CD24(-/low) expression showed association with death due to breast cancer (p = 0.035). Breast tumors expressing CD44(+)CD24(-/low) immunophenotype showed relationship with HIF-1 alpha (p = 0.039) and negativity for HER-2 (p = 0.013). Conclusion: Considering that there are strong evidences that the fraction of a tumour considered to be cancer stem cells is plastic depending upon microenvironmental signals, our findings provide further evidence that hypoxia might be related to the worse prognosis found in CD44(+)CD24(-/low) positive breast tumors.

Intracellular mechanisms of specific beta-adrenoceptor antagonists involved in improved cardiac function and survival in a genetic model of heart failure

beta-blockers, as class, improve cardiac function and survival in heart failure (HF). However, the molecular mechanisms underlying these beneficial effects remain elusive. In the present study, metoprolol and carvedilol were used in doses that display comparable heart rate reduction to assess their beneficial effects in a genetic model of sympathetic hyperactivity-induced HF (alpha(2A)/alpha(2C)-ARKO mice). Five month-old HF mice were randomly assigned to receive either saline, metoprolol or carvedilol for 8 weeks and age-matched wild-type mice (WT) were used as controls. HF mice displayed baseline tachycardia, systolic dysfunction evaluated by echocardiography, 50% mortality rate, increased cardiac myocyte width (50%) and ventricular fibrosis (3-fold) compared with WT. All these responses were significantly improved by both treatments. Cardiomyocytes from HF mice showed reduced peak [Ca(2+)](i) transient (13%) using confocal microscopy imaging. Interestingly, while metoprolol improved [Ca(2+)](i) transient, carvedilol had no effect on peak [Ca(2+)](i) transient but also increased [Ca(2+)] transient decay dynamics. We then examined the influence of carvedilol in cardiac oxidative stress as an alternative target to explain its beneficial effects. Indeed, HF mice showed 10-fold decrease in cardiac reduced/oxidized glutathione ratio compared with WT, which was significantly improved only by carvedilol treatment. Taken together, we provide direct evidence that the beneficial effects of metoprolol were mainly associated with improved cardiac Ca(2+) transients and the net balance of cardiac Ca(2+) handling proteins while carvedilol preferentially improved cardiac redox state. (C) 2008 Elsevier Inc. All rights reserved.

Tick saliva inhibits the chemotactic function of MIP-1 alpha and selectively impairs chemotaxis of immature dendritic cells by down-regulating cell-surface CCR5

Ticks are blood-feeding arthropods that secrete immunomodulatory molecules through their saliva to antagonize host inflammatory and immune responses. As dendritic cells (DCs) play a major role in host immune responses, we studied the effects of Rhipicephalus sanguineus tick saliva on DC migration and function. Bone marrow-derived immature DCs pre-exposed to tick saliva showed reduced migration towards macrophage inflammatory protein (MIP)-1 alpha, MIP-1 beta and regulated upon activation, normal T cell expressed and secreted (RANTES) chemokines in a Boyden microchamber assay. This inhibition was mediated by saliva which significantly reduced the percentage and the average cell-surface expression of CC chemokine receptor CCR5. In contrast, saliva did not alter migration of DCs towards MIP-3 beta, not even if the cells were induced for maturation. Next, we evaluated the effect of tick saliva on the activity of chemokines related to DC migration and showed that tick saliva per se inhibits the chemotactic function of MIP-1 alpha, while it did not affect RANTES, MIP-1 beta and MIP-3 beta. These data suggest that saliva possibly reduces immature DC migration, while mature DC chemotaxis remains unaffected. In support of this, we have analyzed the percentage of DCs on mice 48 h after intradermal inoculation with saliva and found that the DC turnover in the skin was reduced compared with controls. Finally, to test the biological activity of the saliva-exposed DCs, we transferred DCs pre-cultured with saliva and loaded with the keyhole limpet haemocyanin (KLH) antigen to mice and measured their capacity to induce specific T cell cytokines. Data showed that saliva reduced the synthesis of both T helper (Th)1 and Th2 cytokines, suggesting the induction of a non-polarised T cell response. These findings propose that the inhibition of DCs migratory ability and function may be a relevant mechanism used by ticks to subvert the immune response of the host. (c) 2007 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

Effect of alpha prime due to 475 degrees C aging on fracture behavior and corrosion resistance of DIN 1.4575 and MA 956 high performance ferritic stainless steels

The 475 degrees C embrittlement in stainless steels is a well-known phenomenon associated to alpha prime (alpha`) formed by precipitation or spinodal decomposition. Many doubts still remain on the mechanism of alpha` formation and its consequence on deformation and fracture mechanisms and corrosion resistance. In this investigation, the fracture behavior and corrosion resistance of two high performance ferritic stainless steels were investigated: a superferritic DIN 1.4575 and MA 956 superalloy were evaluated. Samples of both stainless steels (SS) were aged at 475 degrees C for periods varying from 1 to 1,080 h. Their fracture surfaces were observed using scanning electron microscopy (SEM) and the cleavage planes were determined by electron backscattering diffraction (EBSD). Some samples were tested for corrosion resistance using electrochemical impedance spectroscopy (EIS) and potentiodynamic polarization. Brittle and ductile fractures were observed in both ferritic stainless steels after aging at 475 degrees C. For aging periods longer than 500 h, the ductile fracture regions completely disappeared. The cleavage plane in the DIN 1.4575 samples aged at 475 degrees C for 1,080 h was mainly {110}, however the {102}, {314}, and {131} families of planes were also detected. The pitting corrosion resistance decreased with aging at 475 degrees C. The effect of alpha prime on the corrosion resistance was more significant in the DIN 1.4575 SS comparatively to the Incoloy MA 956.

Highly efficient palladium-catalyzed Suzuki-Miyaura reactions of potassium aryltrifluoroborates with 5-iodo-1,3-dioxin-4-ones in water: an approach to alpha-aryl-beta-ketoesters

The high efficient palladium-catalyzed Suzuki-Miyaura reactions of potassium aryltrifluoroborates 3 with 5-iodo-1,3-dioxin-4-ones 2a-b in water as only solvent in the presence of n-Bu(4)NOH as base is reported. The respective 5-aryl-1,3-dioxin-4-ones 4a-n were obtained in good to excellent yields. The catalyst system provides high efficiency at low load using electronically diverse coupling partners. The obtained 2,2,6-trimethyl-5-aryl-1,3-dioxin-4-ones were transformed into corresponding alpha-aryl-beta-ketoesters 6 by reaction with an alcohol in the absence of solvent. (C) 2009 Elsevier Ltd. All rights reserved.

Ultrasound-assisted synthesis of functionalized 1,3-enynes by palladium-catalyzed cross-coupling reaction of alpha-styrylbutyltelluride with alkynyltrifluoroborate salts

An ultrasound-assisted synthesis of functionalized 1,3-enyne scaffolds is described and illustrated by palladium-catalyzed cross-coupling of potassium alkynyltrifluoroborate salts and alpha-styrylbutyltellurides. This procedure offers easy access to 1,3-enyne architecture that contains aliphatic and aromatic groups in good to excellent yields.

The contribution of classical (beta(1/2)-) and atypical beta-adrenoceptors to the stimulation of human white adipocyte lipolysis and right atrial appendage contraction by novel beta(3)-adrenoceptor agonists of differing selectivities

The role of beta(3)- and other putative atypical beta-adrenaceptors in human white adipocytes and right atrial appendage has been investigated using CGP 12177 and novel phenylethanolamine and aryloxypropanolamine beta(3)-adrenoceptor (beta(3)AR) agonists with varying intrinsic activities and selectivities for human cloned PAR subtypes. The ability to demonstrate beta(1/2)AR antagonist-insensitive (beta(3) or other atypical beta AR-mediated) responses to CGP 12177 was critically dependent on the albumin batch used to prepare and incubate the adipocytes. Four aryloxypropanolamine selective beta(3)AR agonists (SB-226552, SB-229432, SB-236923, SB-246982) consistently elicited beta(1/2)AR antagonist-insensitive lipolysis. However, a phenylethanolamine (SB-220646) that was a selective full beta(3)AR agonist elicited full lipolytic and inotropic responses that were sensitive to beta(1/2)AR antagonism, despite it having very low efficacies at cloned beta(1)- and beta(2)ARs. A component of the response to another phenylethanolamine selective beta(3)AR agonist (SB-215691) was insensitive to beta(1/2)AR antagonism in some experiments. Because novel aryloxypropanolamine had a beta(1/2)AR antagonist-insensitive inotropic effect, these results establish more firmly that beta(3)ARs mediate lipolysis in human white adipocytes, and suggest that putative 'beta(4)ARs' mediate inotropic responses to CGP 12177. The results also illustrate the difficulty of predicting from studies on cloned beta ARs which beta ARs will mediate responses to agonists in tissues that have a high number of beta(1)- and beta(2)ARs or a low number of beta(3)ARs.

The 1.1 angstrom resolution crystal structure of [Tyr(15)]EpI, a novel alpha-conotoxin from Conus episcopatus, solved by direct methods

Conotoxins are valuable probes of receptors and ion channels because of their small size and highly selective activity. alpha-Conotoxin EpI, a 16-residue peptide from the mollusk-hunting Conus episcopatus, has the amino acid sequence GCCSDPRCNMNNPDY(SO3H)C-NH2 and appears to be an extremely potent and selective inhibitor of the alpha 3 beta 2 and alpha 3 beta 4 neuronal subtypes of the nicotinic acetylcholine receptor (nAChR). The desulfated form of EpI ([Tyr(15)]EpI) has a potency and selectivity for the nAChR receptor similar to those of EpI. Here we describe the crystal structure of [Tyr(15)]EpI solved at a resolution of 1.1 Angstrom using SnB. The asymmetric unit has a total of 284 non-hydrogen atoms, making this one of the largest structures solved de novo try direct methods. The [Tyr(15)]EpI structure brings to six the number of alpha-conotoxin structures that have been determined to date. Four of these, [Tyr(15)]EpI, PnIA, PnIB, and MII, have an alpha 4/7 cysteine framework and are selective for the neuronal subtype of the nAChR. The structure of [Tyr(15)]EpI has the same backbone fold as the other alpha 4/7-conotoxin structures, supporting the notion that this conotoxin cysteine framework and spacing give rise to a conserved fold. The surface charge distribution of [Tyr(15)]EpI is similar to that of PnIA and PnIB but is likely to be different from that of MII, suggesting that [Tyr(15)]EpI and MII may have different binding modes for the same receptor subtype.