Quantum trajectory phase transitions in the micromaser

We study the dynamics of the single atom maser, or micromaser, by means of the recently introduced method of thermodynamics of quantum jump trajectories. We find that the dynamics of the micromaser displays multiple space-time phase transitions, i.e., phase transitions in ensembles of quantum jump trajectories. This rich dynamical phase structure becomes apparent when trajectories are classified by dynamical observables that quantify dynamical activity, such as the number of atoms that have changed state while traversing the cavity. The space-time transitions can be either first-order or continuous, and are controlled not just by standard parameters of the micromaser but also by non-equilibrium "counting" fields. We discuss how the dynamical phase behavior relates to the better known stationary state properties of the micromaser.Comment: 7 pages, 5 figure

Toll-like receptor 3 activation is required for normal skin barrier repair following UV damage.

UV damage to the skin leads to the release of noncoding RNA (ncRNA) from necrotic keratinocytes that activates Toll-like receptor 3 (TLR3). This release of ncRNA triggers inflammation in the skin following UV damage. Recently, TLR3 activation was also shown to aid wound repair and increase the expression of genes associated with permeability barrier repair. Here, we sought to test whether skin barrier repair after UVB damage is dependent on the activation of TLR3. We observed that multiple ncRNAs induced expression of skin barrier repair genes, that the TLR3 ligand Poly (I:C) also induced expression and function of tight junctions, and that the ncRNA U1 acts in a TLR3-dependent manner to induce expression of skin barrier repair genes. These observations were shown to have functional relevance as Tlr3-/- mice displayed a delay in skin barrier repair following UVB damage. Combined, these data further validate the conclusion that recognition of endogenous RNA by TLR3 is an important step in the program of skin barrier repair

Importance of collection in gene set enrichment analysis of drug response in cancer cell lines

Gene set enrichment analysis (GSEA) associates gene sets and phenotypes, its use is predicated on the choice of a pre-defined collection of sets. The defacto standard implementation of GSEA provides seven collections yet there are no guidelines for the choice of collections and the impact of such choice, if any, is unknown. Here we compare each of the standard gene set collections in the context of a large dataset of drug response in human cancer cell lines. We define and test a new collection based on gene co-expression in cancer cell lines to compare the performance of the standard collections to an externally derived cell line based collection. The results show that GSEA findings vary significantly depending on the collection chosen for analysis. Henceforth, collections should be carefully selected and reported in studies that leverage GSEA

Resolving Gas Dynamics in the Circumnuclear Region of a Disk Galaxy in a Cosmological Simulation

Using a hydrodynamic adaptive mesh refinement code, we simulate the growth and evolution of a galaxy, which could potentially host a supermassive black hole, within a cosmological volume. Reaching a dynamical range in excess of 10 million, the simulation follows the evolution of the gas structure from super-galactic scales all the way down to the outer edge of the accretion disk. Here, we focus on global instabilities in the self-gravitating, cold, turbulence-supported, molecular gas disk at the center of the model galaxy, which provide a natural mechanism for angular momentum transport down to sub-pc scales. The gas density profile follows a power-law scaling as r^-8/3, consistent with an analytic description of turbulence in a quasi-stationary circumnuclear disk. We analyze the properties of the disk which contribute to the instabilities, and investigate the significance of instability for the galaxy's evolution and the growth of a supermassive black hole at the center.Comment: 16 pages (includes appendix), submitted to ApJ. Figures here are at low resolution; for higher resolution version, download http://casa.colorado.edu/~levinerd/ms.pd

On multi-path longitudinal spin relaxation in brain tissue

The purpose of this paper is to confirm previous reports that identified magnetization transfer (MT) as an inherent driver of longitudinal relaxation in brain tissue by asserting a substantial difference between the $T_1$ relaxation times of the free and the semi-solid spin pools. Further, we aim to identify an avenue towards the quantification of these relaxation processes on a voxel-by-voxel basis in a clinical imaging setting, i.e. with a nominal resolution of 1mm isotropic and full brain coverage in 12min. To this end, we optimized a hybrid-state pulse sequence for mapping the parameters of an unconstrained MT model. We scanned 4 people with relapsing-remitting multiple sclerosis (MS) and 4 healthy controls with this pulse sequence and estimated $T_1^f \approx 1.90$s and $T_1^s \approx 0.327$s for the free and semi-solid spin pool of healthy WM, respectively, confirming previous reports and questioning the commonly used assumptions $T_1^s = T_1^f$ or $T_1^s = 1$s. Further, we estimated a fractional size of the semi-solid spin pool of $m_0^s \approx 0.202$, which is larger than previously assumed. An analysis of $T_1^f$ in normal appearing white matter revealed statistically significant differences between individuals with MS and controls. In conclusion, we confirm that longitudinal spin relaxation in brain tissue is dominated by MT and that the hybrid state facilitates a voxel-wise fit of the unconstrained MT model, which enables the analysis of subtle neurodegeneration

Estrogen receptor negative/progesterone receptor positive breast cancer is not a reproducible subtype

Introduction: Estrogen receptor (ER) and progesterone receptor (PR) testing are performed in the evaluation of breast cancer. While the clinical utility of ER as a predictive biomarker to identify patients likely to benefit from hormonal therapy is well-established, the added value of PR is less well-defined. The primary goals of our study were to assess the distribution, inter-assay reproducibility, and prognostic significance of breast cancer subtypes defined by patterns of ER and PR expression. Methods: We integrated gene expression microarray (GEM) and clinico-pathologic data from 20 published studies to determine the frequency (n = 4,111) and inter-assay reproducibility (n = 1,752) of ER/PR subtypes (ER+/PR+, ER+/PR-, ER-/PR-, ER-/PR+). To extend our findings, we utilized a cohort of patients from the Nurses’ Health Study (NHS) with ER/PR data recorded in the medical record and assessed on tissue microarrays (n = 2,011). In both datasets, we assessed the association of ER and PR expression with survival. Results: In a genome-wide analysis, progesterone receptor was among the least variable genes in ER- breast cancer. The ER-/PR+ subtype was rare (approximately 1 to 4%) and showed no significant reproducibility (Kappa = 0.02 and 0.06, in the GEM and NHS datasets, respectively). The vast majority of patients classified as ER-/PR+ in the medical record (97% and 94%, in the GEM and NHS datasets) were re-classified by a second method. In the GEM dataset (n = 2,731), progesterone receptor mRNA expression was associated with prognosis in ER+ breast cancer (adjusted P <0.001), but not in ER- breast cancer (adjusted P = 0.21). PR protein expression did not contribute significant prognostic information to multivariate models considering ER and other standard clinico-pathologic features in the GEM or NHS datasets. Conclusion: ER-/PR+ breast cancer is not a reproducible subtype. PR expression is not associated with prognosis in ER- breast cancer, and PR does not contribute significant independent prognostic information to multivariate models considering ER and other standard clinico-pathologic factors. Given that PR provides no clinically actionable information in ER+ breast cancer, these findings question the utility of routine PR testing in breast cancer

Cost-Effectiveness of Highly Active Antiretroviral Therapy in South Africa

BACKGROUND: Little information exists on the impact of highly active antiretroviral therapy (HAART) on health-care provision in South Africa despite increasing scale-up of access to HAART and gradual reduction in HAART prices. METHODS AND FINDINGS: Use and cost of services for 265 HIV-infected adults without AIDS (World Health Organization [WHO] stage 1, 2, or 3) and 27 with AIDS (WHO stage 4) receiving HAART between 1995 and 2000 in Cape Town were compared with HIV-infected controls matched for baseline WHO stage, CD4 count, age, and socioeconomic status, who did not receive antiretroviral therapy (ART; No-ART group). Costs of service provision (January 2004 prices, US$1 = 7.6 Rand) included local unit costs, and two scenarios for HAART prices for WHO recommended first-line regimens: scenario 1 used current South African public-sector ART drug prices of$730 per patient-year (PPY), whereas scenario 2 was based on the anticipated public-sector price for locally manufactured drug of $181 PPY. All analyses are presented in terms of patients without AIDS and patients with AIDS. For patients without AIDS, the mean number of inpatient days PPY was 1.08 (95$950 for the No-ART group versus $1,342 and$793 PPY for the HAART group for scenario 1 and 2, respectively, whereas the incremental cost per life-year gained (LYG) was $1,622 for scenario 1 and$675 for scenario 2. For patients with AIDS, mean inpatients days PPY was 2.04 (95% CI: 1.63–2.52) for the HAART versus 15.36 (95% CI: 13.97–16.85) for the No-ART group. Mean outpatient visits PPY was 7.62 (95% CI: 6.81–8.49) compared with 6.60 (95% CI: 5.69–7.62) respectively. Average service provision PPY was $3,520 for the No-ART group versus$1,513 and $964 for the HAART group for scenario 1 and 2, respectively, whereas the incremental cost per LYG was cost saving for both scenarios. In a sensitivity analysis based on the lower (25$1,557 to $1,772 for the group without AIDS and from cost saving to$111 for patients with AIDS. CONCLUSION: HAART is a cost-effective intervention in South Africa, and cost saving when HAART prices are further reduced. Our estimates, however, were based on direct costs, and as such the actual cost saving might have been underestimated if indirect costs were also included

Magnetic Field Tomography in Nearby Galaxies with the Square Kilometre Array

Magnetic fields play an important role in shaping the structure and evolution of the interstellar medium (ISM) of galaxies, but the details of this relationship remain unclear. With SKA1, the 3D structure of galactic magnetic fields and its connection to star formation will be revealed. A highly sensitive probe of the internal structure of the magnetoionized ISM is the partial depolarization of synchrotron radiation from inside the volume. Different configurations of magnetic field and ionized gas within the resolution element of the telescope lead to frequency-dependent changes in the observed degree of polarization. The results of spectro-polarimetric observations are tied to physical structure in the ISM through comparison with detailed modeling, supplemented with the use of new analysis techniques that are being actively developed and studied within the community such as Rotation Measure Synthesis. The SKA will enable this field to come into its own and begin the study of the detailed structure of the magnetized ISM in a sample of nearby galaxies, thanks to its extraordinary wideband capabilities coupled with the combination of excellent surface brightness sensitivity and angular resolution.Comment: 11 pages, 1 figure; to appear as part of 'Cosmic Magnetism' in Proceedings 'Advancing Astrophysics with the SKA (AASKA14)', PoS(AASKA14)10