Comments on the Canonical Measure in Cosmology

In the mini-superspace approximation to cosmology, the canonical measure can be used to compute probabilities when a cutoff is introduced in the phase space to regularize the divergent measure. However, the region initially constrained by a simple cutoff evolves non-trivially under the Hamiltonian flow. We determine the deformation of the regularized phase space along the orbits when a cutoff is introduced for the scale factor of the universe or for the Hubble parameter. In the former case, we find that the cutoff for the scale factor varies in the phase space and effectively decreases as one evolves backwards in time. In the later case, we calculate the probability of slow-roll inflation in a chaotic model with a massive scalar, which turns out to be cutoff dependent but not exponentially suppressed. We also investigate the measure problem for non-abelian gauge fields giving rise to inflation.Comment: 9 pages, 4 figures, revtex4-1, v2: minor typos correcte

Light Deflection, Lensing, and Time Delays from Gravitational Potentials and Fermat's Principle in the Presence of a Cosmological Constant

The contribution of the cosmological constant to the deflection angle and the time delays are derived from the integration of the gravitational potential as well as from Fermat's Principle. The findings are in agreement with recent results using exact solutions to Einstein's equations and reproduce precisely the new $\Lambda$-term in the bending angle and the lens equation. The consequences on time delay expressions are explored. While it is known that $\Lambda$ contributes to the gravitational time delay, it is shown here that a new $\Lambda$-term appears in the geometrical time delay as well. Although these newly derived terms are perhaps small for current observations, they do not cancel out as previously claimed. Moreover, as shown before, at galaxy cluster scale, the $\Lambda$ contribution can be larger than the second-order term in the Einstein deflection angle for several cluster lens systems.Comment: 6 pages, 1 figure, matches version published in PR

Expression of a pathogenic mutation of SOD1 sensitizes aprataxin-deficient cells and mice to oxidative stress and triggers hallmarks of premature ageing

Aprataxin (APTX) deficiency causes progressive cerebellar degeneration, ataxia and oculomotor apraxia in man. Cell free assays and crystal structure studies demonstrate a role for APTX in resolving 5'-adenylated nucleic acid breaks, however, APTX function in vertebrates remains unclear due to the lack of an appropriate model system. Here, we generated a murine model in which a pathogenic mutant of superoxide dismutase 1 (SOD1(G93A)) is expressed in an Aptx-/- mouse strain. We report a delayed population doubling and accelerated senescence in Aptx-/- primary mouse fibroblasts, which is not due to detectable telomere instability or cell cycle deregulation but is associated with a reduction in transcription recovery following oxidative stress. Expression of SOD1(G93A) uncovers a survival defect ex vivo in cultured cells and in vivo in tissues lacking Aptx. The surviving neurons feature numerous and deep nuclear envelope invaginations, a hallmark of cellular stress. Furthermore, they possess an elevated number of high-density nuclear regions and a concomitant increase in histone H3 K9 trimethylation, hallmarks of silenced chromatin. Finally, the accelerated cellular senescence was also observed at the organismal level as shown by down-regulation of insulin-like growth factor 1 (IGF-1), a hallmark of premature ageing. Together, this study demonstrates a protective role of Aptx in vivo and suggests that its loss results in progressive accumulation of DNA breaks in the nervous system, triggering hallmarks of premature ageing, systemically

Synorogenic evolution of large-scale drainage patterns: Isotope paleohydrology of sequential Laramide basins

In the past decade, we and others have compiled an extensive dataset of O, C and Sr isotope stratigraphies from sedimentary basins throughout the Paleogene North American Cordillera. In this study, we present new results from the Piceance Creek Basin of northwest Colorado, which record the evolving hydrology of the Eocene Green River Lake system. We then place the new data in the context of the broader Cordilleran dataset and summarize implications for understanding the synorogenic evolution of large-scale drainage patterns. The combined data reflect (1) a period of throughgoing foreland rivers heading in the Sevier fold-and-thrust belt and flowing east, (2) ponding of freshwater lakes in the foredeep as Laramide uplifts blocked drainage, (3) hydrologic closure that led to both intensive evaporation in the terminal sink of the Piceance Creek Basin and integration of catchments over length-scales \u3e1000 km, (4) infilling of basin accommodation by southward migrating magmatism in distal catchments, leading to the freshening and demise of intraforeland lakes that also stepped south over time

Physical States in Canonically Quantized Supergravity

We discuss the canonical quantization of $N=1$ supergravity in the functional Schrodinger representation. Although the form of the supersymmetry constraints suggests that there are solutions of definite order $n$ in the fermion fields, we show that there are no such states for any finite $n$. For $n=0$, a simple scaling argument definitively excludes the purely bosonic states discussed by D'Eath. For $n>0$, the argument is based on a mode expansion of the gravitino field on the quantization 3-surface. It is thus suggested that physical states in supergravity have infinite Grassmann number. This is confirmed for the free spin-3/2 field, for which we find that states satisfying the gauge constraints contain an infinite product of fermion mode operators.Comment: 36 pages (uses jnl.tex), CTP #227

A Subset of Secreted Proteins in Ascites Can Predict Platinum-Free Interval in Ovarian Cancer

The time between the last cycle of chemotherapy and recurrence, the platinum-free interval (PFI), predicts overall survival in high-grade serous ovarian cancer (HGSOC). To identify secreted proteins associated with a shorter PFI, we utilized machine learning to predict the PFI from ascites composition. Ascites from stage III/IV HGSOC patients treated with neoadjuvant chemotherapy (NACT) or primary debulking surgery (PDS) were screened for secreted proteins and Lasso regression models were built to predict the PFI. Through regularization techniques, the number of analytes used in each model was reduced; to minimize overfitting, we utilized an analysis of model robustness. This resulted in models with 26 analytes and a root-mean-square error (RMSE) of 19 days for the NACT cohort and 16 analytes and an RMSE of 7 days for the PDS cohort. High concentrations of MMP-2 and EMMPRIN correlated with a shorter PFI in the NACT patients, whereas high concentrations of uPA Urokinase and MMP-3 correlated with a shorter PFI in PDS patients. Our results suggest that the analysis of ascites may be useful for outcome prediction and identified factors in the tumor microenvironment that may lead to worse outcomes. Our approach to tuning for model stability, rather than only model accuracy, may be applicable to other biomarker discovery tasks

Out of equilibrium: understanding cosmological evolution to lower-entropy states

Despite the importance of the Second Law of Thermodynamics, it is not absolute. Statistical mechanics implies that, given sufficient time, systems near equilibrium will spontaneously fluctuate into lower-entropy states, locally reversing the thermodynamic arrow of time. We study the time development of such fluctuations, especially the very large fluctuations relevant to cosmology. Under fairly general assumptions, the most likely history of a fluctuation out of equilibrium is simply the CPT conjugate of the most likely way a system relaxes back to equilibrium. We use this idea to elucidate the spacetime structure of various fluctuations in (stable and metastable) de Sitter space and thermal anti-de Sitter space.Comment: 27 pages, 11 figure

A New Independent Limit on the Cosmological Constant/Dark Energy from the Relativistic Bending of Light by Galaxies and Clusters of Galaxies

We derive new limits on the value of the cosmological constant, $\Lambda$, based on the Einstein bending of light by systems where the lens is a distant galaxy or a cluster of galaxies. We use an amended lens equation in which the contribution of $\Lambda$ to the Einstein deflection angle is taken into account and use observations of Einstein radii around several lens systems. We use in our calculations a Schwarzschild-de Sitter vacuole exactly matched into a Friedmann-Robertson-Walker background and show that a $\Lambda$-contribution term appears in the deflection angle within the lens equation. We find that the contribution of the $\Lambda$-term to the bending angle is larger than the second-order term for many lens systems. Using these observations of bending angles, we derive new limits on the value of $\Lambda$. These limits constitute the best observational upper bound on $\Lambda$ after cosmological constraints and are only two orders of magnitude away from the value determined by those cosmological constraints.Comment: 5 pages, 1 figure, matches version published in MNRA

Where should patient safety be installed?

The structure of an organization is important, and structure has a profound influence on the way people work and what gets done. Where work units and individuals in an organization are placed, to whom they report, and with whom they are grouped signals power, prestige, and privilege. It also divides workers into groups with common interests and motivations. The question is, where should patient safety be placed in a health care organization? Such a question can be answered only within a framework of understanding that gives a clear definition to patient safety. We define safety, as do safety professionals from other industries, as the reduction of risk. This definition is also in concert with the risk management model that identifies claims management, risk financing, and loss control as its foundational triad.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141505/1/jhrm21285_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/141505/2/jhrm21285.pd