Cis-regulatory basis of sister cell type divergence in the vertebrate retina

Multicellular organisms evolved via repeated functional divergence of transcriptionally related sister cell types, but the mechanisms underlying sister cell type divergence are not well understood. Here, we study a canonical pair of sister cell types, retinal photoreceptors and bipolar cells, to identify the ke

Do Electrostatic Interactions with Positively Charged Active Site Groups Tighten the Transition State for Enzymatic Phosphoryl Transfer?

The effect of electrostatic interactions on the transition-state character for enzymatic phosphoryl transfer has been a subject of much debate. In this work, we investigate the transition state for alkaline phosphatase (AP) using linear free-energy relationships (LFERs). We determined kcat/KM for a series of aryl sulfate ester monoanions to obtain the Brønsted coefficient, βlg, and compared the value to that obtained previously for a series of aryl phosphorothioate ester dianion substrates. Despite the difference in substrate charge, the observed Brønsted coefficients for AP-catalyzed aryl sulfate and aryl phosphorothioate hydrolysis (−0.76 ± 0.14 and −0.77 ± 0.10, respectively) are strikingly similar, with steric effects being responsible for the uncertainties in these values. Aryl sulfates and aryl phosphates react via similar loose transition states in solution. These observations suggest an apparent equivalency of the transition states for phosphorothioate and sulfate hydrolysis reactions at the AP active site and, thus, negligible effects of active site electrostatic interactions on charge distribution in the transition state

Delivery of Family-Based Treatment for Adolescent Anorexia Nervosa in a Public Health Care Setting: Research Versus Non-Research Specialty Care.

Comparing evidence-based psychotherapy (EBP) to usual care typically demonstrates the superiority of EBPs, although this has not been studied for eating disorders EBPs such as family-based treatment (FBT). The current study set out to examine weight outcomes for adolescents with anorexia nervosa who received FBT through a randomized clinical research trial (RCT, n = 54) or non-research specialty care (n = 56) at the same specialist pediatric eating disorder service. Weight was recorded throughout outpatient treatment (up to 18 sessions over 6 months), as well as at 6- and 12-month follow-up. Survival curves were used to examine time to weight restoration [greater than 95% median body mass index (mBMI)] as predicted by type of care (RCT vs. non-research specialty care), baseline clinical and demographic characteristics, and their potential interaction. Results did not indicate a significant main effect for type of care, but there was a significant effect for baseline weight (p = .03), such that weight restoration was achieved faster across both treatment types for those with a higher initial %mBMI. These data suggest that weight restoration achieved in non-research specialty care FBT was largely similar to that achieved in a controlled research trial. Clinical Trial Registration:http://www.anzctr.org.au/, identifier ACTRN12610000216011

Explaining anomalous responses to treatment in the Intensive Care Unit

The Intensive Care Unit (ICU) provides treatment to critically ill patients. When a patient does not respond as expected to such treatment it can be challenging for clinicians, especially junior clinicians, as they may not have the relevant experience to understand the patient’s anomalous response. Datasets for 10 patients from Glasgow Royal Infirmary’s ICU have been made available to us. We asked several ICU clinicians to review these datasets and to suggest sequences which include anomalous or unusual reactions to treatment. Further, we then asked two ICU clinicians if they agreed with their colleagues’ assessments, and if they did to provide possible explanations for these anomalous sequences. Subsequently we have developed a system which is able to replicate the clinicians’ explanations based on the knowledge contained in its several ontologies; further the system can suggest additional explanations which will be evaluated by the senior consultant

Approximating the inspiral of test bodies into Kerr black holes

We present a new approximate method for constructing gravitational radiation driven inspirals of test-bodies orbiting Kerr black holes. Such orbits can be fully described by a semi-latus rectum $p$, an eccentricity $e$, and an inclination angle $\iota$; or, by an energy $E$, an angular momentum component $L_z$, and a third constant $Q$. Our scheme uses expressions that are exact (within an adiabatic approximation) for the rates of change ($\dot{p}$, $\dot{e}$, $\dot{\iota}$) as linear combinations of the fluxes ($\dot{E}$, $\dot{L_z}$, $\dot{Q}$), but uses quadrupole-order formulae for these fluxes. This scheme thus encodes the exact orbital dynamics, augmenting it with approximate radiation reaction. Comparing inspiral trajectories, we find that this approximation agrees well with numerical results for the special cases of eccentric equatorial and circular inclined orbits, far more accurate than corresponding weak-field formulae for ($\dot{p}$, $\dot{e}$, $\dot{\iota}$). We use this technique to study the inspiral of a test-body in inclined, eccentric Kerr orbits. Our results should be useful tools for constructing approximate waveforms that can be used to study data analysis problems for the future LISA gravitational-wave observatory, in lieu of waveforms from more rigorous techniques that are currently under development.Comment: 15 pages, 5 figures, submitted to PR

How black holes get their kicks: Gravitational radiation recoil revisited

Gravitational waves from the coalescence of binary black holes carry away linear momentum, causing center of mass recoil. This "radiation rocket" effect has important implications for systems with escape speeds of order the recoil velocity. We revisit this problem using black hole perturbation theory, treating the binary as a test mass spiraling into a spinning hole. For extreme mass ratios (q = m1/m2 << 1) we compute the recoil for the slow inspiral epoch of binary coalescence very accurately; these results can be extrapolated to q ~ 0.4 with modest accuracy. Although the recoil from the final plunge contributes significantly to the final recoil, we are only able to make crude estimates of its magnitude. We find that the recoil can easily reach ~ 100-200 km/s, but most likely does not exceed ~ 500 km/s. Though much lower than previous estimates, this recoil is large enough to have important astrophysical consequences. These include the ejection of black holes from globular clusters, dwarf galaxies, and high-redshift dark matter halos.Comment: 4 pages, 2 figures, emulateapj style; minor changes made; accepted to ApJ Letter

Quantitative Patterns of Stylistic Influence in the Evolution of Literature

Literature is a form of expression whose temporal structure, both in content and style, provides a historical record of the evolution of culture. In this work we take on a quantitative analysis of literary style and conduct the first large-scale temporal stylometric study of literature by using the vast holdings in the Project Gutenberg Digital Library corpus. We find temporal stylistic localization among authors through the analysis of the similarity structure in feature vectors derived from content-free word usage, nonhomogeneous decay rates of stylistic influence, and an accelerating rate of decay of influence among modern authors. Within a given time period we also find evidence for stylistic coherence with a given literary topic, such that writers in different fields adopt different literary styles. This study gives quantitative support to the notion of a literary “style of a time” with a strong trend toward increasingly contemporaneous stylistic influence