bluuebunny/crossref_metadata_2025_split huggingface dataset:
Core-Collapse Supernovae as Dust Producers
Authors: Kotak Rubina 
Published: June 2008

AbstractAlthough it has long been hypothesised that core-collapse supernovae may produce large quantities of dust, interest in this problem has recently been rekindled given the enormous dust masses inferred at very high redshifts (z ≳ 6), when conventional low-mass dust-producing stars would fail to contribute significantly to the universal dust budget. Emission due to warm dust peaks at mid-IR wavelengths. However, with the notable exception of SN 1987A, supernova studies in the mid-IR have been virtually non-existent until the advent of the Spitzer Space Telescope. On behalf of the Mid-Infrared Supernova Consortium, I briefly discuss recent exciting results from mid-IR studies of core-collapse supernovae using Spitzer and attempt to put the role of supernovae as major dust producers into perspective.
GRBs as Probes of Massive Stars Near and Far
Authors: Fynbo Johan P. U. , Malesani Daniele 
Published: June 2008

AbstractLong-duration gamma-ray bursts are the manifestations of massive stellar death. Due to the immense energy release they are detectable from most of the observable universe. In this way they allow us to study the deaths of single (or binary) massive stars possibly throughout the full timespan massive stars have existed in the Universe. GRBs provide a means to infer information about the environments and typical galaxies in which massive stars are formed. Two main obstacles remain to be crossed before the full potential of GRBs as probes of massive stars can be harvested: i) we need to build more complete and well understood samples in order not to be fooled by biases, and ii) we need to understand to which extent GRBs may be intrinsically biased in the sense that they are only formed by a limited subset of massive stars defined by most likely a restricted metallicity interval. I describe the status of an ongoing effort to build a more complete sample of long-duration GRBs with measured redshifts. Already now we can conclude that the environments of GRB progenitors are very diverse with metallicities ranging from solar to a hundredth solar and extinction ranging from none to AV > 5 mag. We have also identified a sightline with significant escape of Lyman continuum photons and another with a clear 2175 Å extinction bump.
The Connection between Gamma-Ray Bursts and Extremely Metal-Poor Stars as Nucleosynthetic Probes of the Early Universe
Authors: Nomoto K. , Tominaga N. , Tanaka M. , Maeda K. , Umeda H. 
Published: June 2008

AbstractThe connection between the long GRBs and Type Ic Supernovae (SNe) has revealed the interesting diversity: (i) GRB-SNe, (ii) Non-GRB Hypernovae (HNe), (iii) X-Ray Flash (XRF)-SNe, and (iv) Non-SN GRBs (or dark HNe). We show that nucleosynthetic properties found in the above diversity are connected to the variation of the abundance patterns of extremely-metal-poor (EMP) stars, such as the excess of C, Co, Zn relative to Fe. We explain such a connection in a unified manner as nucleosynthesis of hyper-aspherical (jet-induced) explosions of Pop III core-collapse SNe. We show that (1) the explosions with large energy deposition rate, Ėdep, are observed as GRB-HNe and their yields can explain the abundances of normal EMP stars, and (2) the explosions with small Ėdepare observed as GRBs without bright SNe and can be responsible for the formation of the C-rich EMP (CEMP) and the hyper metal-poor (HMP) stars. We thus propose that GRB-HNe and the Non-SN GRBs (dark HNe) belong to a continuous series of BH-forming massive stellar deaths with the relativistic jets of different Ėdep.
Imaging and Spectroscopy with the James Webb Space Telescope
Authors: Sonneborn George 
Published: June 2008

AbstractThe James Webb Space Telescope (JWST) is a large, infrared-optimized space telescope scheduled for launch in 2013. JWST will find the first stars and galaxies that formed in the early universe, connecting the Big Bang to our own Milky Way galaxy. JWST will peer through dusty clouds to see stars forming planetary systems, connecting the Milky Way to our own Solar System. JWST's instruments are designed to work primarily in the infrared range of 1 - 28 μm, with some capability in the visible range. JWST will have a large segmented mirror, ~6.5 m in diameter, and will be diffraction-limited at 2 μm (< 0.1 arcsec resolution). JWST will be placed in an L2 orbit about 1.5 million km from the Earth. The instruments will provide imaging, coronography, and multi-object and integral-field spectroscopy across the 1 - 28 μm wavelength range. The breakthrough capabilities of JWST will enable new studies of massive stars from the Milky Way to the early universe.
Evolution of Massive Stars at Low Metallicity
Authors: Meynet Georges , Walborn Nolan R. , Hunter Ian , Martayan Christophe , van Marle Allard Jan , Marchenko Sergey , Vink Jorick S. , Limongi Marco , Levesque Emily M. , Modjaz Maryam 
Published: June 2008

AbstractThis paper reports the contributions made on the occasion of the Special Session entitled “Evolution of Massive Stars at Low Metallicity” which was held on Sunday, December 9, 2007 in Kauai (USA).
Magnetic Massive Stars
Authors: Townsend Rich , Cohen David H. , Dessart Luc , Hubrig Swetlana , Nazé Yaël , Petit Véronique , ud-Doula Asif , Walborn Nolan R. 
Published: June 2008

AbstractMagnetic fields are unexpected in massive stars, due to the absence of a sub-surface convective dynamo. However, advances in instrumentation over the past three decades have led to their detection in a small but growing subset of these stars. Moreover, complementary theoretical developments have highlighted their potentially significant influence over the structure, evolution and circumstellar environments of massive stars. Here, we summarize a special session convened prior to the main conference, focused on presenting recent developments in the study of massive-star magnetic fields.
Moving towards better predictors of drug‐induced torsades de pointes
Authors: Bass A S , Darpo B , Valentin J‐P , Sager P , Thomas K 
Published: June 2008

Drug‐induced torsades de pointes (TdP) remains a significant public health concern that has challenged scientists who have the responsibility of advancing new medicines through development to the patient, while assuring public safety. As a result, from the point of discovering a new molecule to the time of its registration, significant efforts are made to recognize potential liabilities, including the potential for TdP. With this background, the ILSI (HESI) Proarrhythmia Models Project Committee recognized that there was little practical understanding of the relationship between drug effects on cardiac ventricular repolarization and the rare clinical event of TdP. A workshop was therefore convened at which four topics were considered including: Molecular and Cellular Biology Underlying TdP, Dynamics of Periodicity, Models of TdP Proarrhythmia and Key Considerations for Demonstrating Utility of Pre‐Clinical Models. The series of publications in this special edition has established the background, areas of debate and those that deserve scientific pursuit. This is intented to encourage the research community to contribute to these important areas of investigation in advancing the science and our understanding of drug‐induced proarrhythmia. British Journal of Pharmacology (2008) 154, 1550–1553; doi:fn1; published online 23 June 2008
High‐affinity blockade of voltage‐operated skeletal muscle and neuronal sodium channels by halogenated propofol analogues
Authors: Haeseler G , Karst M , Foadi N , Gudehus S , Roeder A , Hecker H , Dengler R , Leuwer M 
Published: June 2008

Background and purpose:Voltage‐operated sodium channels constitute major target sites for local anaesthetic‐like action. The clinical use of local anaesthetics is still limited by severe side effects, in particular, arrhythmias and convulsions. These side effects render the search for new local anaesthetics a matter of high interest.Experimental approach:We have investigated the effects of three halogenated structural analogues of propofol on voltage‐operated human skeletal muscle sodium channels (NaV1.4) and the effect of one compound (4‐chloropropofol) on neuronal sodium channels (NaV1.2) heterologously expressed in human embryonic kidney cell line 293.Key results:4‐Iodo‐, 4‐bromo‐ and 4‐chloropropofol reversibly suppressed depolarization‐induced whole‐cell sodium inward currents with high potency. The IC50for block of resting channels at −150 mV was 2.3, 3.9 and 11.3 μMin NaV1.4, respectively, and 29.2 μMfor 4‐chloropropofol in NaV1.2. Membrane depolarization inducing inactivation strongly increased the blocking potency of all compounds. Estimated affinities for the fast‐inactivated channel state were 81 nM, 312 nMand 227 nMfor 4‐iodopropofol, 4‐bromopropofol and 4‐chloropropofol in NaV1.4, and 450 nMfor 4‐chloropropofol in NaV1.2. Recovery from fast inactivation was prolonged in the presence of drug leading to an accumulation of block during repetitive stimulation at high frequencies (100 Hz).Conclusions and implications:Halogenated propofol analogues constitute a novel class of sodium channel‐blocking drugs possessing almost 100‐fold higher potency compared with the local anaesthetic and anti‐arrhythmic drug lidocaine. Preferential drug binding to inactivated channel states suggests that halogenated propofol analogues might be especially effective in suppressing ectopic discharges in a variety of pathological conditions.British Journal of Pharmacology(2008)155, 265–275; doi:10.1038/bjp.2008.255; published online 23 June 2008
Hypertension and the absence of EDHF‐mediated responses favour endothelium‐dependent contractions in renal arteries of the rat
Authors: Michel F S , Man G S , Man R Y K , Vanhoutte P M 
Published: June 2008

Background and purpose:Experiments were designed to determine the modulation by nitric oxide (NO) and endothelium‐dependent hyperpolarizations (EDHF‐mediated responses) of endothelium‐dependent contractions in renal arteries of normotensive and hypertensive rats.Experimental approach:Rings, with or without endothelium, of renal arteries of 8‐month‐old Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were suspended in myographs for isometric force recording.Key results:ACh evoked relaxations in preparations contracted with phenylephrine. L‐NAME (inhibitor of NOS) attenuated (WKY) or abolished (SHR) these relaxations. TRAM‐34 plus UCL 1684 (inhibitors of EDHF‐mediated responses) did not decrease the relaxation, except in rings of WKY when L‐NAME was also present. High concentrations of ACh caused a secondary increase in tension, augmented in rings of WKY by L‐NAME or TRAM‐34 plus UCL 1684. The increase in tension was prevented by indomethacin. Under baseline tension, ACh induced endothelium‐dependent contractions, prevented by indomethacin (COX inhibitor) or terutroban (TP receptor antagonist). The calculated endothelium‐dependent contractions were larger in rings of SHR compared with those of WKY. In preparations of SHR, the contractions were augmented by L‐NAME in the presence of SC19220 (EP‐1 receptor antagonist). In arteries of WKY, the endothelium‐dependent contractions were augmented by TRAM‐34 plus UCL 1684. The responses were reduced by SC19220.Conclusions and implications:In the renal artery of the rat, EDCF‐mediated contractions are augmented by hypertension. The endothelium‐dependent contractions are facilitated by NOS inhibition (in the presence of an EP‐1 receptor antagonist) and by the withdrawal of EDHF‐mediated responses.British Journal of Pharmacology (2008) 155, 217–226; doi:10.1038/bjp.2008.256; published online 23 June 2008
PEGylated cholecystokinin is more potent in inducing anorexia than conditioned taste aversion in rats
Authors: Verbaeys I , León‐Tamariz F , Pottel H , Decuypere E , Swennen Q , Cokelaere M 
Published: June 2008

Background and purpose:The physiological involvement of endogenous cholecystokinin (CCK) in the termination of feeding has been challenged by evidence of aversive effects of exogenous CCK8. We previously prolonged the anorectic effect of CCK by conjugation to polyethylene glycol (PEGylation) to produce PEG‐CCK9. In this study, we investigated the ability of different doses of PEG‐CCK9 to induce conditioned taste aversion (CTA) and satiety and identified the receptors involved in CTA induction.Experimental approach:Induction of CTA, measured by the saccharin preference ratio determined in a two‐bottle CTA procedure, and of satiety in adult male Wistar rats after intraperitoneal (i.p.) injection of different doses of PEG‐CCK9 (1, 2, 4, 8, 16 or 32 μg kg−1) was compared. Devazepide (100 μg kg−1) and 2‐NAP (3 mg kg−1), two selective CCK1‐receptor antagonists, were co‐administered i.p. with PEG‐CCK9 (8 μg kg−1) and the CTA effects monitored.Key results:PEG‐CCK9 dose‐dependently induced CTA, with a minimal effective dose of 8 μg kg−1, whereas the minimal effective dose to induce satiety was 1 μg kg−1. The CTA effects of PEG‐CCK9 were completely abolished by i.p. administration of devazepide prior to PEG‐CCK9 treatment and only partially abolished by administration of 2‐NAP.Conclusions and implications:Although PEG‐CCK9‐induced satiety and PEG‐CCK9‐induced CTA both increased with dose, the conjugate was more potent in inducing satiety, suggesting that the anorexia could not be completely attributed to the aversiveness of the drug. As observed with induction of satiety, PEG‐CCK9‐induced CTA was mediated by CCK1‐receptors.British Journal of Pharmacology (2008) 155, 417–423; doi:10.1038/bjp.2008.257; published online 23 June 2008
Effects of pregabalin on visceral pain responses and colonic compliance in rats
Authors: Ravnefjord A , Brusberg M , Larsson H , Lindström E , Martínez V 
Published: June 2008

Background and purpose:Pregabalin, which binds to the α2‐δ subunit of voltage‐gated calcium channels, increased the threshold for pain during colorectal distension (CRD) in irritable bowel syndrome (IBS) patients. We tested the effects of oral pregabalin on the visceral pain‐related viscerosomatic and autonomic cardiovascular responses to CRD and colonic compliance in rats.Experimental approach:The activity of the abdominal musculature (viscerosomatic response), monitored by electromyography and intracolonic manometry, and changes in blood pressure and heart rate, monitored by telemetry, were assessed simultaneously in conscious rats during CRD.Key results:Pregabalin (10–200 μmol kg−1, p.o.) inhibited dose dependently the viscerosomatic response to phasic, noxious CRD (12 distensions at 80 mm Hg). At 200 μmol kg−1, pregabalin also reduced the increase in blood pressure and heart rate associated with noxious CRD. Moreover, pregabalin (200 μmol kg−1, p.o.) reduced the visceromotor response to ascending phasic CRD (10–80 mm Hg) and significantly increased the threshold pressure for response. During phasic CRD (2–20 mm Hg), pregabalin (200 μmol kg−1, p.o.) increased intracolonic volume, resulting in a shift to the left of the pressure–volume relationship curve, indicative of an increase of compliance.Conclusions and implications:Pregabalin reduced the viscerosomatic and autonomic responses associated with CRD‐induced visceral pain and increased colonic compliance in rats. These observations confirm the analgesic activity of pregabalin on visceral pain and support the translational value of the CRD model to humans. Ligands for the α2‐δ subunit might represent interesting compounds for the treatment of visceral pain disorders, such as IBS.British Journal of Pharmacology (2008) 155, 407–416; doi:10.1038/bjp.2008.259; published online 23 June 2008
Antitumour activity of ANG1005, a conjugate between paclitaxel and the new brain delivery vector Angiopep‐2
Authors: Régina A , Demeule M , Ché C , Lavallée I , Poirier J , Gabathuler R , Béliveau R , Castaigne J‐P 
Published: June 2008

Background and purpose:Paclitaxel is highly efficacious in the treatment of breast, head and neck, non‐small cell lung cancers and ovarian carcinoma. For malignant gliomas, paclitaxel is prevented from reaching its target by the presence of the efflux pump P‐glycoprotein (P‐gp) at the blood–brain barrier. We investigated the utilization of a new drug delivery system to increase brain delivery of paclitaxel.Experimental approach:Paclitaxel molecules were conjugated to a brain peptide vector, Angiopep‐2, to provide a paclitaxel–Angiopep‐2 conjugate named ANG1005. We determined the brain uptake capacity, intracellular effects and antitumour properties of ANG1005 in vitro against human tumour cell lines and in vivo in human xenografts. We then determined ANG1005 activity on brain tumours with intracerebral human tumour models in nude mice.Key results:We show by in situ brain perfusion that ANG1005 enters the brain to a greater extent than paclitaxel and bypasses the P‐gp. ANG1005 has an antineoplastic potency similar to that of paclitaxel against human cancer cell lines. We also demonstrate that ANG1005 caused a more potent inhibition of human tumour xenografts than paclitaxel. Finally, ANG1005 administration led to a significant increase in the survival of mice with intracerebral implantation of U87 MG glioblastoma cells or NCI‐H460 lung carcinoma cells.Conclusions and implications:These results demonstrate the antitumour potential of a new drug, ANG1005, and establish that conjugation of anticancer agents with the Angiopep‐2 peptide vector could increase their efficacy in the treatment of brain cancer.British Journal of Pharmacology (2008) 155, 185–197; doi:fn1; published online 23 June 2008
The 5‐HT2antagonist ketanserin is an open channel blocker of human cardiacether‐à‐go‐go‐related gene (hERG) potassium channels
Authors: Tang Q , Li Z‐Q , Li W , Guo J , Sun H‐Y , Zhang X‐H , Lau C‐P , Tse H‐F , Zhang S , Li G‐R 
Published: June 2008

Background and purpose:Ketanserin, a selective 5‐HT receptor antagonist, prolongs the QT interval of ECG in patients. The purpose of the present study was to determine whether ketanserin would block human cardiacether‐à‐go‐go‐related gene (hERG) potassium channels.Experimental approach:Whole‐cell patch voltage‐clamp technique was used to record membrane currents in HEK 293 cells expressing wild type or mutant hERG channel genes.Key results:Ketanserin blocked hERG current (IhERG) in a concentration‐dependent manner (IC50=0.11 μM). The drug showed an open channel blocking property, the block increasing significantly at depolarizing voltages between +10 to +60 mV. Voltage‐dependence for inactivation of hERG channels was negatively shifted by 0.3 μMketanserin. A 2.8 fold attenuation of inhibition by elevation of external K+concentration (from 5.0 to 20 mM) was observed, whereas the inactivation‐deficient mutants S620T and S631A had the IC50s of 0.84±0.2 and 1.7±0.4 μM(7.6 and 15.4 fold attenuation of block). In addition, the hERG mutants in pore helix and S6 also significantly reduced the channel block (2–59 fold) by ketanserin.Conclusions and implications:These results suggest that ketanserin binds to and blocks the open hERG channels in the pore helix and the S6 domain; channel inactivation is also involved in the blockade of hERG channels. Blockade of hERG channels most likely contributes to the prolongation of QT intervals in ECG observed clinically at therapeutic concentrations of ketanserin.British Journal of Pharmacology(2008)155, 365–373; doi:10.1038/bjp.2008.261; published online 23 June 2008
The enigma of nitroglycerin bioactivation and nitrate tolerance: news, views and troubles
Authors: Mayer B , Beretta M 
Published: June 2008

Nitroglycerin (glyceryl trinitrate; GTN) is the most prominent representative of the organic nitrates or nitrovasodilators, a class of compounds that have been used clinically since the late nineteenth century for the treatment of coronary artery disease (angina pectoris), congestive heart failure and myocardial infarction. Medline lists more than 15 000 publications on GTN and other organic nitrates, but the mode of action of these drugs is still largely a mystery. In the first part of this article, we give an overview on the molecular mechanisms of GTN biotransformation resulting in vascular cyclic GMP accumulation and vasodilation with focus on the role of mitochondrial aldehyde dehydrogenase (ALDH2) and the link between the ALDH2 reaction and activation of vascular soluble guanylate cyclase (sGC). In particular, we address the identity of the bioactive species that activates sGC and the potential involvement of nitrite as an intermediate, describe our recent findings suggesting that ALDH2 catalyses direct 3‐electron reduction of GTN to NO and discuss possible reaction mechanisms. In the second part, we discuss contingent processes leading to markedly reduced sensitivity of blood vessels to GTN, referred to as vascular nitrate tolerance. Again, we focus on ALDH2 and describe the current controversy on the role of ALDH2 inactivation in tolerance development. Finally, we emphasize some of the most intriguing, in our opinion, unresolved puzzles of GTN pharmacology that urgently need to be addressed in future studies.British Journal of Pharmacology(2008)155, 170–184; doi:10.1038/bjp.2008.263; published online 23 June 2008
The α1L‐adrenoceptor is an alternative phenotype of the α1A‐adrenoceptor
Authors: Nelson C P 
Published: June 2008

Despite over two decades of research, the molecular identity of the α1L‐adrenoceptor phenotype has remained elusive. In this issue of theBJP, Grayet al.(2008) provide persuasive evidence that thein vivoα1L‐adrenoceptor phenotype requires the expression of the α1A‐adrenoceptor gene. They have shown that in mice lacking the functional α1A‐adrenoceptor gene, α1L‐mediated responses to noradrenaline in prostate smooth muscle are substantially attenuated. These findings support earlier evidence that the α1L‐adrenoceptor profile represents a functional phenotype of the α1A‐adrenoceptor gene product, but additional cell background‐dependent factors must act in concert with the α1A‐adrenoceptor protein to determine whether an α1L‐ or a classical α1A‐adrenoceptor profile is expressed. The challenge remains to establish the nature of these cellular factors and the mechanism(s) by which they influence G‐protein‐coupled receptor pharmacology.British Journal of Pharmacology(2008)155, 1–3; doi:fn1; published online 23 June 2008
Comparative Enumeration Gene Expression
Authors: Varuzza Leonardo , Pereira Carlos 
Published: June 2008

AbstractThis paper is about differential gene expression measured by transcript counting methods such as SAGE or MPSS. It introduces two significance tests for detection of differential expressed tags: frequentist and Bayesian. Under the frequentist view, it is proposed a test that computes the critical level as a function of each tag total frequency. Under the Bayesian view the Full Bayesian Significance Test is used considering the logistic normal distribution. The two proposed significance levels, the frequentist and the Bayesian, are compared for a data set with four libraries. The linking function between them is a Beta distribution function with mean 0.39 and standard deviation 0.30.