Myc controls a distinct transcriptional program in fetal thymic epithelial cells that determines thymus growth

Interactions between thymic epithelial cells (TEC) and developing thymocytes are essential for T cell development, but molecular insights on TEC and thymus homeostasis are still lacking. Here we identify distinct transcriptional programs of TEC that account for their age-specific properties, including proliferation rates, engraftability and function. Further analyses identify Myc as a regulator of fetal thymus development to support the rapid increase of thymus size during fetal life. Enforced Myc expression in TEC induces the prolonged maintenance of a fetal-specific transcriptional program, which in turn extends the growth phase of the thymus and enhances thymic output; meanwhile, inducible expression of Myc in adult TEC similarly promotes thymic growth. Mechanistically, this Myc function is associated with enhanced ribosomal biogenesis in TEC. Our study thus identifies age-specific transcriptional programs in TEC, and establishes that Myc controls thymus size

Corticotropin-Releasing Factor Receptor 1 in the Anterior Cingulate Cortex Mediates Maternal Absence-Induced Attenuation of Transport Response in Mouse Pups

A human infant initially shows non-selective sociality, and gradually develops selective attachment toward its caregiver, manifested as “separation anxiety.” It was unclear whether such sophistication of attachment system occurs in non-human mammals. To seek a mouse model of separation anxiety, we utilized a primitive attachment behavior, the Transport Response, in that both human and mouse newborns immediately stop crying and stay immobile to cooperate with maternal carrying. We examined the mouse Transport Response in three social contexts: 30-min isolation in a novel environment, 30-min maternal absence experienced with littermates in the home cage, and the control home-cage condition with the mother and littermates. The pups after postnatal day (PND) 13 attenuated their Transport Response not only in complete isolation but also by maternal absence, and activated several brain areas including the periventricular nucleus of the hypothalamus, suggesting that 30-min maternal absence was perceived as a social stress by mouse pups after PND13. This attenuation of Transport Response by maternal absence was independent with plasma corticosterone, but was diminished by prior administration of a corticotropin-releasing factor receptor 1 (CRFR1) antagonist. Among 18 brain areas examined, only neurons in the anterior cingulate cortex (ACC) co-express c-fos mRNA and CRFR1 after maternal absence. Consistently, excitotoxic ACC lesions inhibited the maternal absence-induced attenuation of Transport Response. These data indicate that the expression of mouse Transport Response is influenced not only by social isolation but also by maternal absence even in their home cage with littermates after PND13, at least partly via CRF-CRFR1 signaling in the ACC

STM observation of electronic wave interference effect in finite-sized graphite with dislocation-network structures

Superperiodic patterns near a step edge were observed by STM on several-layer-thick graphite sheets on a highly oriented pyrolitic graphite substrate, where a dislocation network is generated at the interface between the graphite overlayer and the substrate. Triangular- and rhombic-shaped periodic patterns whose periodicities are around 100 nm were observed on the upper terrace near the step edge. In contrast, only outlines of the patterns similar to those on the upper terrace were observed on the lower terrace. On the upper terrace, their geometrical patterns gradually disappeared and became similar to those on the lower terrace without any changes of their periodicity in increasing a bias voltage. By assuming a periodic scattering potential at the interface due to dislocations, the varying corrugation amplitudes of the patterns can be understood as changes in LDOS as a result of the beat of perturbed and unperturbed waves, i.e. the interference in an overlayer. The observed changes in the image depending on an overlayer height and a bias voltage can be explained by the electronic wave interference in the ultra-thin overlayer distorted under the influence of dislocation-network structures.Comment: 8 pages; 6 figures; Paper which a part of cond-mat/0311068 is disscussed in detai

Upper limits on the strength of periodic gravitational waves from PSR J1939+2134

The first science run of the LIGO and GEO gravitational wave detectors presented the opportunity to test methods of searching for gravitational waves from known pulsars. Here we present new direct upper limits on the strength of waves from the pulsar PSR J1939+2134 using two independent analysis methods, one in the frequency domain using frequentist statistics and one in the time domain using Bayesian inference. Both methods show that the strain amplitude at Earth from this pulsar is less than a few times $10^{-22}$.Comment: 7 pages, 1 figure, to appear in the Proceedings of the 5th Edoardo Amaldi Conference on Gravitational Waves, Tirrenia, Pisa, Italy, 6-11 July 200

Search for gravitational wave bursts in LIGO's third science run

We report on a search for gravitational wave bursts in data from the three LIGO interferometric detectors during their third science run. The search targets subsecond bursts in the frequency range 100-1100 Hz for which no waveform model is assumed, and has a sensitivity in terms of the root-sum-square (rss) strain amplitude of hrss ~ 10^{-20} / sqrt(Hz). No gravitational wave signals were detected in the 8 days of analyzed data.Comment: 12 pages, 6 figures. Amaldi-6 conference proceedings to be published in Classical and Quantum Gravit

Improving the sensitivity to gravitational-wave sources by modifying the input-output optics of advanced interferometers

We study frequency dependent (FD) input-output schemes for signal-recycling interferometers, the baseline design of Advanced LIGO and the current configuration of GEO 600. Complementary to a recent proposal by Harms et al. to use FD input squeezing and ordinary homodyne detection, we explore a scheme which uses ordinary squeezed vacuum, but FD readout. Both schemes, which are sub-optimal among all possible input-output schemes, provide a global noise suppression by the power squeeze factor, while being realizable by using detuned Fabry-Perot cavities as input/output filters. At high frequencies, the two schemes are shown to be equivalent, while at low frequencies our scheme gives better performance than that of Harms et al., and is nearly fully optimal. We then study the sensitivity improvement achievable by these schemes in Advanced LIGO era (with 30-m filter cavities and current estimates of filter-mirror losses and thermal noise), for neutron star binary inspirals, and for narrowband GW sources such as low-mass X-ray binaries and known radio pulsars. Optical losses are shown to be a major obstacle for the actual implementation of these techniques in Advanced LIGO. On time scales of third-generation interferometers, like EURO/LIGO-III (~2012), with kilometer-scale filter cavities, a signal-recycling interferometer with the FD readout scheme explored in this paper can have performances comparable to existing proposals. [abridged]Comment: Figs. 9 and 12 corrected; Appendix added for narrowband data analysi

Treatment of Late Stage Disease in a Model of Arenaviral Hemorrhagic Fever: T-705 Efficacy and Reduced Toxicity Suggests an Alternative to Ribavirin

A growing number of arenaviruses are known to cause viral hemorrhagic fever (HF), a severe and life-threatening syndrome characterized by fever, malaise, and increased vascular permeability. Ribavirin, the only licensed antiviral indicated for the treatment of certain arenaviral HFs, has had mixed success and significant toxicity. Since severe arenaviral infections initially do not present with distinguishing symptoms and are difficult to clinically diagnose at early stages, it is of utmost importance to identify antiviral therapies effective at later stages of infection. We have previously reported that T-705, a substituted pyrazine derivative currently under development as an anti-influenza drug, is highly active in hamsters infected with Pichinde virus when the drug is administered orally early during the course of infection. Here we demonstrate that T-705 offers significant protection against this lethal arenaviral infection in hamsters when treatment is begun after the animals are ill and the day before the animals begin to succumb to disease. Importantly, this coincides with the time when peak viral loads are present in most organs and considerable tissue damage is evident. We also show that T-705 is as effective as, and less toxic than, ribavirin, as infected T-705-treated hamsters on average maintain their weight better and recover more rapidly than animals treated with ribavirin. Further, there was no added benefit to combination therapy with T-705 and ribavirin. Finally, pharmacokinetic data indicate that plasma T-705 levels following oral administration are markedly reduced during the latter stages of disease, and may contribute to the reduced efficacy seen when treatment is withheld until day 7 of infection. Our findings support further pre-clinical development of T-705 for the treatment of severe arenaviral infections

Searching for a Stochastic Background of Gravitational Waves with LIGO

The Laser Interferometer Gravitational-wave Observatory (LIGO) has performed the fourth science run, S4, with significantly improved interferometer sensitivities with respect to previous runs. Using data acquired during this science run, we place a limit on the amplitude of a stochastic background of gravitational waves. For a frequency independent spectrum, the new limit is $\Omega_{\rm GW} < 6.5 \times 10^{-5}$. This is currently the most sensitive result in the frequency range 51-150 Hz, with a factor of 13 improvement over the previous LIGO result. We discuss complementarity of the new result with other constraints on a stochastic background of gravitational waves, and we investigate implications of the new result for different models of this background.Comment: 37 pages, 16 figure