47 research outputs found
New Limit on Axion-Dark-Matter using Cold Neutrons
We report on a search for axion-like dark matter using a Ramsey-type
apparatus for cold neutrons. A hypothetical axion-gluon-coupling would manifest
in a neutron electric dipole moment signal oscillating in time. Twenty-four
hours of data have been analyzed in a frequency range from 23 Hz to 1 kHz,
and no significant oscillating signal has been found. The usage of present
axion and dark-matter models allowed excluding the coupling of axions to gluons
in the mass range from to eV with a
best sensitivity of GeV
(95% C.L.)
Serotonin-3 Receptors in the Posterior Ventral Tegmental Area Regulate Ethanol Self-Administration of Alcohol-Preferring (P) Rats
Several studies indicated the involvement of serotonin-3 (5-HT
3
) receptors in regulating alcohol-
drinking behavior. The objective of this study was to determine the involvement of 5-HT
3
receptors within the ventral tegmental area (VTA) in regulating ethanol self-administration by
alcohol-preferring (P) rats. Standard two-lever operant chambers were used to examine the effects
of 7 consecutive bilateral micro-infusions of ICS205-930 (ICS), a 5-HT
3
receptor antagonist,
directly into the posterior VTA on the acquisition and maintenance of 15% (v/v) ethanol self-
administration. P rats readily acquired ethanol self-administration by the 4
th
session. The three
highest doses (0.125, 0.25 and 1.25 ug) of ICS prevented acquisition of ethanol self-
administration. During the acquisition post-injection period, all rats treated with ICS demonstrated
higher responding on the ethanol lever, with the highest dose producing the greatest effect. In
contrast, during the maintenance phase, the 3 highest doses (0.75, 1.0 and 1.25 ug) of ICS
significantly increased responding on the ethanol lever; following the 7-day dosing regimen,
responding on the ethanol lever returned to control levels. Micro-infusion of ICS into the posterior
VTA did not alter the low responding on the water lever, and did not alter saccharin (0.0125%
w/v) self-administration.. Micro-infusion of ICS into the anterior VTA did not alter ethanol self-
administration. Overall, the results of this study suggest that 5-HT
3
receptors in the posterior VTA
of the P rat may be involved in regulating ethanol self-administration. In addition, chronic operant
ethanol self-administration, and/or repeated treatments with a 5-HT
3
receptor antagonist may alter
neuronal circuitry within the posterior VTA
The James Webb Space Telescope Mission
Twenty-six years ago a small committee report, building on earlier studies,
expounded a compelling and poetic vision for the future of astronomy, calling
for an infrared-optimized space telescope with an aperture of at least .
With the support of their governments in the US, Europe, and Canada, 20,000
people realized that vision as the James Webb Space Telescope. A
generation of astronomers will celebrate their accomplishments for the life of
the mission, potentially as long as 20 years, and beyond. This report and the
scientific discoveries that follow are extended thank-you notes to the 20,000
team members. The telescope is working perfectly, with much better image
quality than expected. In this and accompanying papers, we give a brief
history, describe the observatory, outline its objectives and current observing
program, and discuss the inventions and people who made it possible. We cite
detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space
Telescope Overview, 29 pages, 4 figure
31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two
Background
The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd.
Methods
We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background.
Results
First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001).
Conclusions
In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival
The design of the MEG II experiment
The MEG experiment, designed to search for the μ+→e+γ decay, completed data-taking in 2013 reaching a sensitivity level of 5.3×10−13 for the branching ratio. In order to increase the sensitivity reach of the experiment by an order of magnitude to the level of 6×10−14, a total upgrade, involving substantial changes to the experiment, has been undertaken, known as MEG II. We present both the motivation for the upgrade and a detailed overview of the design of the experiment and of the expected detector performance.ISSN:1434-6044ISSN:1434-605
Measurement of the radiative decay of polarized muons in the MEG experiment
ISSN:1434-6044ISSN:1434-605