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We describe a comprehensive pulsar monitoring campaign for the Large Area Telescope (LAT) on the Fermi Gamma-ray Space Telescope(formerly GLAST). The detection and study of pulsars in gamma rays give insights into the populations of neutron stars and supernova rates in the Galaxy, into particle acceleration mechanisms in neutron star magnetospheres, and into the “engines” driving pulsar wind nebulae. LAT's unprecedented sensitivity between 20 MeV and 300 GeV together with its 2.4 sr field-of-view makes detection of many gamma-ray pulsars likely, justifying the monitoring of over two hundred pulsars with large spin-down powers. To search for gamma-ray pulsations from most of these pulsars requires a set of phase-connected timing solutions spanning a year or more to properly align the sparse photon arrival times. We describe the choice of pulsars and the instruments involved in the campaign. Attention is paid to verifications of the LAT pulsar software, using for example giant radio pulses from the Craband from PSR B1937+21recorded at Nançay, and using X-ray data on PSR J0218+4232from XMM-Newton. We demonstrate accuracy of the pulsar phase calculations at the microsecond level.

The idea of possible involvement of the aryl hydrocarbon receptor (AhR) in transplant tolerance can be traced back >30 years, when very low doses of dioxin—the most potent AhR ligand—were found to markedly reduce the generation of cytotoxic T lymphocytes in response to alloantigen challenge in vivo. AhR is a ligand‐activated transcription factor that is activated by dioxins and other environmental pollutants. We now know that AhR can bind a broad variety of activating ligands that are disparate in nature, including endogenous molecules and those formed in the gut from food and bacterial products. Consequently, in addition to its classical role as a toxicological signal mediator, AhR is emerging as a transcription factor involved in the regulation of both innate and adaptive immune responses in various immune cell types, including lymphocytes and antigen‐presenting cells (APCs). Allograft rejection is mostly a T cell–mediated alloimmune response initiated by the recognition of alloantigens presented by donor and recipient APCs to recipient CD4+and CD8+T cells. Based on those findings, AhR may function as a critical sensor of outside and inside environments, leading to changes in the immune system that may have relevance in transplantation. Data described in this minireview identify AhR as a novel target for immunomodulation that may hold great promise in the treatment of transplant rejection and achievement of tolerance.

We present a new grid of LTE model atmospheres for weakly magnetic ($B\la10^{10}$G) neutron stars, using opacity and equation of state data from the OPAL project and employing a fully frequency- and angle-dependent radiation transfer. We discuss the differences from earlier models, including a comparison with a detailed NLTE calculation. We suggest heating of the outer layers of the neutron star atmosphere as an explanation for the featureless X-ray spectra of RX J1856.5–3754 and RX J0720.4–3125 recently observed with Chandraand XMM.

We describe a comprehensive pulsar monitoring campaign for the Large Area Telescope (LAT) on the Fermi Gamma-ray Space Telescope (formerly GLAST). The detection and study of pulsars in gamma rays give insights into the populations of neutron stars and supernova rates in the Galaxy, into particle acceleration mechanisms in neutron star magnetospheres, and into the ?engines? driving pulsar wind nebulae. LAT's unprecedented sensitivity between 20?MeV and 300?GeV together with its 2.4?sr field-of-view makes detection of many gamma-ray pulsars likely, justifying the monitoring of over two hundred pulsars with large spin-down powers. To search for gamma-ray pulsations from most of these pulsars requires a set of phase-connected timing solutions spanning a year or more to properly align the sparse photon arrival times. We describe the choice of pulsars and the instruments involved in the campaign. Attention is paid to verifications of the LAT pulsar software, using for example giant radio pulses from the Crab and from PSR?B1937+21 recorded at Nan?ay, and using X-ray data on PSR?J0218+4232 from XMM-Newton. We demonstrate accuracy of the pulsar phase calculations at the microsecond level.

Summary. Males of Polistes dominulus perform antennal vibrations and grasping of female antennae during pre-copulatory and copulatory phases. Male antennation plays a relevant role in mating success. In several antennomeres of males of P. dominulus and Vespa crabro, a further species in which we observed male antennation, we found secretory cells of class 1 and 3 associated to the same release site. In P. dominulus, class 3 cells with ampulla-like reservoirs and class 1 cells release their secretion through hairless multiporous areas. In V. crabro, tyloid-like structures are associated with large apodemes. The as yet unidentified secretion of these glands may act as a contact or low-volatile sex pheromone during courtship behaviour.

Summary A first description of the structural organization of two exocrine glands associated with the mandibles of queens of the obligatory slave-making ant Polyergus rufescens is reported. The mandibular gland consists of clustered bicellular secretory units connected by means of cuticular ducts to a big reservoir. The reservoir continues in a duct that opens proximally on the mandible cuticle. Intramandibular glands are isolated bicellular secretory units connected to the external pores through a cuticular duct. No reservoir has been observed. In both cases the secretory cells belong to the 3 rd class. Functional aspects of the investigated glands are discussed taking also into account for the parasitic habit of this slave-making species.

Intracellular Ca2+signals elicited by nucleotide agonists were investigated in primary cultures of rat cardiac microvascular endothelial cells using the fura-2 technique. UTP increased the intracellular [Ca2+] in 94% of the cells, whereas 2MeSATP was active in 32%. The rank order of potency was ATP = UTP > 2MeSATP and the maximal response to 2MeSATP was lower compared to UTP and ATP. ATP and UTP showed strong homologous and heterologous desensitization. ATP fully inhibited the 2MeSATP response, while UTP abolished 2MeSATP-elicited transients in 25% of cells. 2MeSATP did not desensitize the UTP or ATP response. Adenosine 2′,5′-diphosphate inhibited the response to 2MeSATP, while it did not modify the response to ATP and UTP. 2MeSATP was more sensitive to suramin than UTP and ATP. These results indicate that P2Y1and P2Y2receptors may be coexpressed in CMEC. Nucleotide-induced Ca2+signals lacked a sustained plateau and were almost independent from extracellular Ca2+. ATP and UTP elicited Ca2+transients longer than 2MeSATP-evoked transients. The kinetics of Ca2+responses was not affected by bath solution stirring or ectonucleotidase inhibition. Furthermore, the nonhydrolyzable ATP analogue AMP-PNP induced Ca2+signals similar to those elicited by ATP and UTP. These results suggest that the distinct kinetics of nucleotide-evoked Ca2+responses do not depend on the activity of ectonucleotidases or ATP autocrine stimulation. The possibility that Ca2+signals with different time courses may modulate different cellular responses is discussed.

Mechanical properties of the vascular smooth muscle from normal and dystrophin-deficient (mdx) mice were examined. Changes in resting and developed tensions in response to stretch were recorded in isolated portal vein. The vascular segments were elongated in 5 % increments of the 'in situ' length (Lr) up to 1 30Lr. The resting length-tension curves in male mdxmice were similar to normal mice, while a marked decrease in the slope of the curve was noted in female mdx mice. These findings were not affected by atropine, phentolamine, tetrodotoxin or [Ca2+] in the surrounding media. At Lr, the tension of isolated portal vein was characterized by spontaneous synchronized uniform force waves in normal mouse. In contrast, in mdxmouse portal veins an irregular motor pattern characterized by desynchronized force waves with a decrease of amplitude and an increase in frequency was recorded. Extension of the length of the portal vein segment did not increase the spontaneous phasic activity developed in female mdx mice although this was noted with male mdx mice and normal mice. Experiments with chemical depolarizing agents indicated that spontaneous myogenic excitation activated the great majority of vascular smooth muscle cells in normal mouse portal vein, whereas in mdx mice only a reduced number of these cells were excited suggesting that in the mdx mouse the intercellular electronic coupling is altered. In conclusion this study provides the first description of the mechanical activities of portal vein longitudinal muscle and shows that in mdx mice the motor activity is severely disrupted.

Mechanical properties of the vascular smooth muscle from normal and dystrophin‐deficient (mdx) mice were examined. Changes in resting and developed tensions in response to stretch were recorded in isolated portal vein. The vascular segments were elongated in 5% increments of the ‘in situ’length (Lr) up to 1·30Lr. The resting length‐tension curves in male mdxmice were similar to normal mice, while a marked decrease in the slope of the curve was noted in female mdxmice. These findings were not affected by atropine, phentolamine, tetrodotoxin or [Ca2+] in the surrounding media. At Lr, the tension of isolated portal vein was characterized by spontaneous synchronized uniform force waves in normal mouse. In contrast, in mdxmouse portal veins an irregular motor pattern characterized by desynchronized force waves with a decrease of amplitude and an increase in frequency was recorded. Extension of the length of the portal vein segment did not increase the spontaneous phasic activity developed in female mdxmice although this was noted with male mdxmice and normal mice. Experiments with chemical depolarizing agents indicated that spontaneous myogenic excitation activated the great majority of vascular smooth muscle cells in normal mouse portal vein, whereas in mdxmice only a reduced number of these cells were excited suggesting that in the mdxmouse the intercellular electronic coupling is altered. In conclusion this study provides the first description of the mechanical activities of portal vein longitudinal muscle and shows that in mdxmice the motor activity is severely disrupted.

A single form of cholinesterase was detected in the parasitic nematode Parascaris equorum and purified from a low-salt Triton X-100 extract of whole animals by affinity chromatography on an edrophonium–Sepharose matrix. Based on gel-filtration chromatography, sedimentation analysis and SDS–PAGE, such a cholinesterase is an amphiphilic globular (G2) dimer (125–129 kDa, 6·1 S). It includes some hydrophobic domain other than phosphatidylinositol, which gives auto-aggregation, detergent interaction and also anchors the molecule to the cell membrane. The enzyme, probably functional in cholinergic neurotransmission, is an acetylcholinesterase showing a fairly low substrate specificity with thiocholine esters. Electrostatic interactions seem to play a major role in the catalytic activity. Studies with inhibitors gave complete inhibition with 1 mM eserine, low sensitivity for procainamide and for tetra(monoisopropyl)pyrophosphortetramide as well as higher inhibition with edrophonium chloride and 1,5-bis(4allyldimethylammoniumphenyl)-pentan-3-one dibromide. The enzyme also showed excess-substrate inhibition with acetylthiocholine. No cross-hybridization occurred between the gene(s) encoding acetylcholinesterase in P. equorum and ace-1 from the free-living nematode Caenorhabditis elegans. The expression of a single cholinesterase form in P. equorum, unusual in free-living nematodes, could be due to parasitic life adaptation with resulting reduction of locomotor activity.

5-Fluorouracil (5-FU) is still the most effective cytotoxic agent for the treatment of human colorectal cancer. Response rates, however, vary between 5-20%. One attempt to improve the effect of 5-FU is through biomodulation. We have previously found the somatostatin analogue, SMS 201.995 (Sandostatin, Sandoz), to inhibit both the in-vitro and in-vivo growth of some human colon cancer cell lines. It may act specifically by means of receptors on the surface of tumour cells, or by reducing the concentration of some growth factors. We report that, when 5-FU at 0.125 and 0.25 @mg/ml was combined with SMS 201.995 at 10^-^1^2 x 2 to 10^-^8 x 2M, an enhanced inhibition of in-vitro growth of two human colorectal cancer cell lines (C170 and LIM 1215) was achieved. Effects were measured using [3H]-thymidine uptake and by a colorimetric assay of cellular respiration (MTT, Promega, Sydney). SMS 201.995 alone has minimal inhibitory effects, whilst 5-FU alone shows inhibition as low as 39.6% of control. When 5-FU was then combined with SMS 201.995, a 10-30% inhibition occurred compared to the 5-FU control. The combination of 5-FU and SMS 201.995 may be a useful method of improving response to human colorectal cancer therapy.

Toxoplasma gondii infection was investigated in 14 AIDS patients with neurological involvement who showed clinical and computer tomographic scan signs suggestive of toxoplasmic encephalitis or extraneuronal localization suggestive of toxoplasmic infection. Blood, lung secretion (bronchoalveolar lavage and/or induced sputum sample) and cerebral spinal fluid (CSF) samples were cultured, and the results compared with the results of direct examination by Giemsa and by immunofluorescence of lung secretions and CSF.Toxoplasma gondii were observed directly in only four patients by immunofluorescence in bronchoalveolar lavage, induced sputum and CSF samples, and in three of these patients by Giemsa staining of bronchoalveolar lavage and CSF smears. In contrast, parasites were detected after 48 h in blood cultures from 11 of the 14 AIDS patients, in CSF cultures from eight of them and also in cultures of bronchoalveolar lavage and induced sputum from the six patients with respiratory and radiological features indicative of lung tissue damage. The findings indicate the value of tissue culture for diagnosis of toxoplasmosis as well as for monitoring the effects of treatment and also indicate that culture of induced sputum could be a powerful tool in establishing the incidence of pulmonary toxoplasmosis in AIDS patients.

Irradiated sporangiospores of Rhizopus stoloniferexcreted pectolytic enzymes, which hydrolyzed pectin and macerated potato tuber discs, into the suspending medium. Pectin glycosidase, but not pectin methylesterase, activity developed regardless of the amount of radiation the spores had received, unless the dose exceeded about 1 megarad. The ability to produce pectolytic enzymes was found to be more radiation-resistant than the potential for colony formation or the ability to germinate. Spores made incapable, through irradiation, of forming colonies continued to produce pectolytic enzymes after a 6-day period following irradiation treatment.

Context.Pulsars PSR J0248+6021 (with a rotation period P= 217 ms and spin-down power Ė= 2.13  ×  1035erg s-1) and PSR J2240+5832 (P= 140 ms, Ė= 2.12  ×  1035erg s-1) were discovered in 1997 with the Nançay radio telescope during a northern Galactic plane survey, using the Navy-Berkeley Pulsar Processor (NBPP) filter bank. The GeV gamma-ray pulsations from both were discovered using the Fermi Large Area Telescope.

Context.Globular clusters with their large populations of millisecond pulsars (MSPs) are believed to be potential emitters of high-energy gamma-ray emission. The observation of this emission provides a powerful tool to assess the millisecond pulsar population of a cluster, is essential for understanding the importance of binary systems for the evolution of globular clusters, and provides complementary insights into magnetospheric emission processes.

Context.Cosmic rays (CRs) can be studied through the galaxy-wide gamma-ray emission that they generate when propagating in the interstellar medium. The comparison of the diffuse signals from different systems may inform us about the key parameters in CR acceleration and transport.

Context.The flux of gamma rays with energies greater than 100 MeV is dominated by diffuse emission coming from cosmic-rays (CRs) illuminating the interstellar medium (ISM) of our Galaxy through the processes of Bremsstrahlung, pion production and decay, and inverse-Compton scattering. The study of this diffuse emission provides insight into the origin and transport of cosmic rays.

Context. The Large Magellanic Cloud (LMC) is to date the only normal external galaxy that has been detected in high-energy gamma rays. High-energy gamma rays trace particle acceleration processes and gamma-ray observations allow the nature and sites of acceleration to be studied.Aims. We characterise the distribution and sources of cosmic rays in the LMC from analysis of gamma-ray observations.Methods. We analyse 11 months of continuous sky-survey observations obtained with the Large Area Telescope aboard the Fermi Gamma-Ray Space Telescope and compare it to tracers of the interstellar medium and models of the gamma-ray sources in the LMC.Results. The LMC is detected at 33σsignificance. The integrated >100 MeV photon flux of the LMC amounts to (2.6 ±0.2) $\times$10-7ph cm-2s-1which corresponds to an energy flux of (1.6 ±0.1) $\times$10-10erg cm-2s-1, with additional systematic uncertainties of $\la$16%. The analysis reveals the massive star forming region 30 Doradus as a bright source of gamma-ray emission in the LMC in addition to fainter emission regions found in the northern part of the galaxy. The gamma-ray emission from the LMC shows very little correlation with gas density and is rather correlated to tracers of massive star forming regions. The close confinement of gamma-ray emission to star forming regions suggests a relatively short GeV cosmic-ray proton diffusion length. Conclusions. The close correlation between cosmic-ray density and massive star tracers supports the idea that cosmic rays are accelerated in massive star forming regions as a result of the large amounts of kinetic energy that are input by the stellar winds and supernova explosions of massive stars into the interstellar medium.