AGAPE, an experiment to detect MACHO's in the direction of the Andromeda galaxy

The status of the Agape experiment to detect Machos in the direction of the andromeda galaxy is presented.Comment: 4 pages, 1 figure in a separate compressed, tarred, uuencoded uufile. In case ofproblem contact [email protected]

AgapeZ1: a Large Amplification Microlensing Event or an Odd Variable Star Towards the Inner Bulge of M31

AgapeZ1 is the brightest and the shortest duration microlensing candidate event found in the Agape data. It occured only 42" from the center of M31. Our photometry shows that the half intensity duration of the event6 is 4.8 days and at maximum brightness we measure a stellar magnitude of R=18.0 with B-R=0.80 mag color. A search on HST archives produced a single resolved star within the projected event position error box. Its magnitude is R=22.Comment: 4 pages with 5 figure

Spitzer/IRS Imaging and Spectroscopy of the luminous infrared galaxy NGC 6052 (Mrk 297)

We present photometric and spectroscopic data of the interacting starburst galaxy NGC 6052 obtained with the Spitzer Space Telescope. The mid-infrared (MIR) spectra of the three brightest spatially resolved regions in the galaxy are remarkably similar and are consistent with dust emission from young nearly coeval stellar populations. Analysis of the brightest infrared region of the system, which contributes ~18.5 % of the total 16\micron flux, indicates that unlike similar off-nuclear infrared-bright regions found in Arp 299 or NGC 4038/9, its MIR spectrum is inconsistent with an enshrouded hot dust (T > 300K) component. Instead, the three brightest MIR regions all display dust continua of temperatures less than ~ 200K. These low dust temperatures indicate the dust is likely in the form of a patchy screen of relatively cold material situated along the line of sight. We also find that emission from polycyclic aromatic hydrocarbons (PAHs) and the forbidden atomic lines is very similar for each region. We conclude that the ionization regions are self-similar and come from young (about 6 Myr) stellar populations. A fourth region, for which we have no MIR spectra, exhibits MIR emission similar to tidal tail features in other interacting galaxies.Comment: 20 pages in preprint form, estimated 7 pages in ApJ Aeptember 10, 2007, v666n 2 issue, six encapsulated postscript figure

Phase IB study of doxorubicin in combination with the multidrug resistance reversing agent S9788 in advanced colorectal and renal cell cancer.

S9788 is a new triazineaminopiperidine derivate capable of reversing multidrug resistance (MDR) in cells resistant to chemotherapeutic agents such as doxorubicin. It does not belong to a known class of MDR revertants, but its action involves the binding of P-glycoprotein. Thirty-eight evaluable patients with advanced colorectal or renal cell cancer were treated with doxorubicin alone (16 patients) followed after disease progression with combination treatment of doxorubicin plus S9788 (12 patients) or upfront with the combination of doxorubicin plus S9788 (22 patients). S9788 was given i.v. as a loading dose of 56 mg m-2 over 30 min followed by doxorubicin given at 50 mg m-2 as a bolus infusion. Thereafter, a 2-h infusion of S9788 was administered at escalating doses ranging from 24 to 120 mg m-2 in subsequent cohorts of 4-10 patients. Pharmacokinetic analysis demonstrated that concentrations of S9788 that are known to reverse MDR in vitro were achieved in patients at non-toxic doses. Compared with treatment with doxorubicin alone, treatment with the combination of doxorubicin and S9788 produced a significant increase in the occurrence of WHO grade 3-4 granulocytopenia. Treatment with S9788 was cardiotoxic as it caused a dose-dependent and reversible increase in corrected QT intervals as well as clinically non-significant arrhythmias on 24- or 48-h Holter recordings. Although clinically relevant cardiac toxicities did not occur, the study was terminated as higher doses of S9788 may increase the risk of severe cardiac arrhythmias. Twenty-nine patients treated with S9788 plus doxorubicin were evaluable for response, and one patient, who progressed after treatment with doxorubicin alone, achieved a partial response. We conclude that S9788 administered at the doses and schedule used in this study results in relevant plasma concentrations in humans and can safely be administered in combination with doxorubicin

AGAPE: a microlensing search in the direction of M31

A status report of the microlensing search by the pixel method in the direction of M31, on the 2 meter telescope at Pic du Midi is given. Pixels are stable to a level better than 0.5%. Pixel variations as small as 0.02 magnitude can clearly be detected

Variable stars towards the bulge of M31: the AGAPE catalogue

We present the AGAPE astrometric and photometric catalogue of 1579 variable stars in a 14'x10' field centred on M31. This work is the first survey devoted to variable stars in the bulge of M31. The R magnitudes of the objects and the B-R colours suggest that our sample is dominated by red long-period variable stars (LPV), with a possible overlap with Cepheid-like type II stars. Twelve nova candidates are identified. Correlations with other catalogues suggest that 2 novae could be recurrent novae and provide possible optical counterparts for 2 supersoft X-ray sources candidates observed with Chandra.Comment: 11 pages, Latex, accepted for publication in A&

New Diabetic Treatment by Alleviation of Autonomic Nervous System Dysfunction Measured as Periosteal Pressure Sensitivity at Sternum Improves Empowerment, Treatment Satisfaction, and Self-Reported Health of People with Type 2 Diabetes: A Randomized Trial

Sofie Korsgaard Hecquet,1,2,* Søren Ballegaard,1,* Ebbe Eldrup,1,3 Christian Stevns Hansen,1,2 Tine Willum Hansen,2,3 Gitte Sommer Harboe,1 Peter Rossing,2,3 Caroline Sophie Hjelm Pichat,1 Torquil Watt,1 Finn Gyntelberg,4 Nanna Ørsted,1 Jens Oscar Faber1,3 1Department of Medicine, Endocrine Unit, Herlev Gentofte University Hospital, Herlev, Denmark; 2Clinical and Translational Research, Complications Research, Steno Diabetes Center Copenhagen, Herlev, Denmark; 3Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; 4The National Research Center for the Working Environment, Copenhagen, Denmark*These authors contributed equally to this workCorrespondence: Sofie Korsgaard Hecquet, Clinical and Translational Research, Complications Research, Steno Diabetes Center Copenhagen, Borgmester Ib Juuls vej 83, Herlev, Copenhagen, 2730, Denmark, Tel +45 30913413, Email [email protected]: Autonomic nervous system dysfunction (ANSD), for which presently no treatment exists, has a negative impact on prognosis in people with type 2 diabetes (T2D). Periosteal pressure sensitivity (PPS) on sternum may be a measure of autonomic nervous system dysfunction (ANSD). We tested if a non-pharmacological PPS-feedback-guided treatment program based on non-noxious sensory nerve stimulation, known to reduce PPS, changed empowerment, treatment satisfaction, and quality of life in people with T2D, compared to usual treatment.Patients and Methods: Analysis of secondary endpoints in a single center, two-armed, parallel-group, observer-blinded, randomized controlled trial of individuals with T2D. Participants were randomized to non-pharmacological intervention as an add-on to treatment as usual. Endpoints were evaluated by five validated questionnaires: Diabetes specific Empowerment (DES-SF), Diabetes Treatment Satisfaction (DTSQ), quality of life (QOL) (WHO-5), clinical stress signs (CSS), and self-reported health (SF-36). Sample size calculation was based on the primary endpoint HbA1c.Results: We included 144 participants, 71 allocated to active intervention and 73 to the control group. Active intervention compared to control revealed improved diabetes-specific empowerment (p = 0.004), DTSQ (p = 0.001), and SF-36 self-reported health (p=0.003) and tended to improve quality of life (WHO-5) (p = 0.056). The findings were clinically relevant with a Cohen’s effect size of 0.5 to 0.7.Conclusion: This non-pharmacological intervention, aiming to reduce PPS, and thus ANSD, improved diabetes-specific empowerment, treatment satisfaction, and self-reported health when compared to usual treatment. The proposed intervention may be a supplement to conventional treatment for T2D.Keywords: type 2 diabetes, empowerment, autonomic nervous system dysfunction, periosteal pressure sensitivit

Requirement for the N-Terminal Coiled-Coil Domain for Expression and Function, but not Subunit Interaction of, the ADPR-Activated TRPM2 Channel

Transient receptor potential melastatin 2 (TRPM2) proteins form multiple-subunit complexes, most likely homotetramers, which operate as Ca2+-permeable, nonselective cation channels activated by intracellular ADP-ribose (ADPR) and oxidative stress. Each TRPM2 channel subunit is predicted to contain two coiled-coil (CC) domains, one in the N-terminus and the other in the C-terminus. Our recent study has shown that the C-terminal CC domain plays an important, but not exclusive, role in the TRPM2 channel assembly. This study aimed to examine the potential role of the N-terminal CC domain. Domain deletion dramatically reduced protein expression and abolished ADPR-evoked currents but did not alter the subunit interaction. Deletion of both CC domains strongly attenuated the subunit interaction, confirming that the C-terminal CC domain is critical in the subunit interaction. Glutamine substitutions into individual hydrophobic residues at positions a and d in the heptad repeats to disrupt the CC formation had no effect on protein expression, subunit interaction, or ADPR-evoked currents. Mutation of Ile658 to glutamine, which did not perturb the CC formation, decreased ADPR-evoked currents without affecting protein expression, subunit interaction, or membrane trafficking. These results collectively suggest the requirement for the N-terminal CC domain for protein expression and function, but not subunit interaction, of the TRPM2 channel

Induced Pluripotent Stem Cell-Derived Retinal Pigmented Epithelium: A Comparative Study Between Cell Lines and Differentiation Methods

PurposeThe application of induced pluripotent stem cell-derived retinal pigmented epithelium (iPSC-RPE) in patients with retinal degenerative disease is making headway toward the clinic, with clinical trials already underway. Multiple groups have developed methods for RPE differentiation from pluripotent cells, but previous studies have shown variability in iPSC propensity to differentiate into RPE.MethodsThis study provides a comparison between 2 different methods for RPE differentiation: (1) a commonly used spontaneous continuously adherent culture (SCAC) protocol and (2) a more rapid, directed differentiation using growth factors. Integration-free iPSC lines were differentiated to RPE, which were characterized with respect to global gene expression, expression of RPE markers, and cellular function.ResultsWe found that all 5 iPSC lines (iPSC-1, iPSC-2, iPSC-3, iPSC-4, and iPSC-12) generated RPE using the directed differentiation protocol; however, 2 of the 5 iPSC lines (iPSC-4 and iPSC-12) did not yield RPE using the SCAC method. Both methods can yield bona fide RPE that expresses signature RPE genes and carry out RPE functions, and are similar, but not identical to fetal RPE. No differences between methods were detected in transcript levels, protein localization, or functional analyses between iPSC-1-RPE, iPSC-2-RPE, and iPSC-3-RPE. Directed iPSC-3-RPE showed enhanced transcript levels of RPE65 compared to directed iPSC-2-RPE and increased BEST1 expression and pigment epithelium-derived factor (PEDF) secretion compared to directed iPSC-1-RPE. In addition, SCAC iPSC-3-RPE secreted more PEDF than SCAC iPSC-1-RPE.ConclusionsThe directed protocol is a more reliable method for differentiating RPE from various pluripotent sources and some iPSC lines are more amenable to RPE differentiation