CARMIL family proteins as multidomain regulators of actin-based motility

CARMILs are large multidomain proteins that regulate the actin-binding activity of capping protein (CP), a major capper of actin filament barbed ends in cells. CARMILs bind directly to CP and induce a conformational change that allosterically decreases but does not abolish its actin-capping activity. The CP-binding domain of CARMIL consists of the CP-interaction (CPI) and CARMIL-specific interaction (CSI) motifs, which are arranged in tandem. Many cellular functions of CARMILs require the interaction with CP; however, a more surprising result is that the cellular function of CP in cells appears to require binding to a CARMIL or another protein with a CPI motif, suggesting that CPI-motif proteins target CP and modulate its actin-capping activity. Vertebrates have three highly conserved genes and expressed isoforms of CARMIL with distinct and overlapping localizations and functions in cells. Various domains of these CARMIL isoforms interact with plasma membranes, vimentin intermediate filaments, SH3-containing class I myosins, the dual-GEF Trio, and other adaptors and signaling molecules. These biochemical properties suggest that CARMILs play a variety of membrane-associated functions related to actin assembly and signaling. CARMIL mutations and variants have been implicated in several human diseases. We focus on roles for CARMILs in signaling in addition to their function as regulators of CP and actin. </jats:p

More than Dollars for Scholars: The Impact of the Dell Scholars Program on College Access, Persistence and Degree Attainment

Although college enrollment rates have increased substantially over the last several decades, socioeconomic inequalities in college completion have actually widened over time. A critical question, therefore, is how to support low-income and first-generation students to succeed in college after they matriculate. We investigate the impact of the Dell Scholars Program which provides a combination of generous financial support and individualized advising to scholarship recipients before and throughout their postsecondary enrollment. The program's design is motivated by a theory of action that, in order to meaningfully increase the share of lower-income students who earn a college degree, it is necessary both to address financial constraints students face and to provide ongoing support for the academic, cultural and other challenges that students experience during their college careers. We isolate the unique impact of the program on college completion by capitalizing on an arbitrary cutoff in the program's algorithmic selection process. Using a regression discontinuity design, we find that although being named a Dell Scholar has no impact on initial college enrollment or early college persistence, scholars at the margin of eligibility are significantly more likely to earn a bachelor's degree on-time or six years after high school graduation. These impacts are sizeable and represent a nearly 25 percent or greater increase in both four- and six-year bachelor's attainment. The program is resource intensive. Yet, back-of-theenvelope calculations indicate that the Dell Scholars Program has a positive rate of return

Cardiac Memory-induced T-wave Inversions

Introduction: Cardiac memory refers to T-wave inversions that result when normal ventricular activation resumes following a period of abnormal ventricular activation.Case Report: We present a case of a 29-year-old man with a pacemaker who presented with new, deep symmetric T-wave inversions caused by cardiac memory.Discussion: Abnormal ventricular activation is most commonly induced by ventricular pacing but can also occur in the setting of transient left bundle branch blocks, ventricular tachycardia, and intermittent ventricular pre-excitation.Conclusion: Recognition of this phenomenon may help to reduce unnecessary admissions, cardiac testing, and cardiac catheterizations

Efficient growth of complex graph states via imperfect path erasure

Given a suitably large and well connected (complex) graph state, any quantum algorithm can be implemented purely through local measurements on the individual qubits. Measurements can also be used to create the graph state: Path erasure techniques allow one to entangle multiple qubits by determining only global properties of the qubits. Here, this powerful approach is extended by demonstrating that even imperfect path erasure can produce the required graph states with high efficiency. By characterizing the degree of error in each path erasure attempt, one can subsume the resulting imperfect entanglement into an extended graph state formalism. The subsequent growth of the improper graph state can be guided, through a series of strategic decisions, in such a way as to bound the growth of the error and eventually yield a high-fidelity graph state. As an implementation of these techniques, we develop an analytic model for atom (or atom-like) qubits in mismatched cavities, under the double-heralding entanglement procedure of Barrett and Kok [Phys. Rev. A 71, 060310 (2005)]. Compared to straightforward postselection techniques our protocol offers a dramatic improvement in growing complex high-fidelity graph states.Comment: 15 pages, 10 figures (which print to better quality than when viewed as an on screen pdf

Is the cosmic microwave background really non-Gaussian?

Two recent papers have claimed detection of non-Gaussian features in the COBE DMR sky maps of the cosmic microwave background. We confirm these results, but argue that Gaussianity is still not convincingly ruled out. Since a score of non-Gaussianity tests have now been published, one might expect some mildly significant results even by chance. Moreover, in the case of one measure which yields a detection, a bispectrum statistic, we find that if the non-Gaussian feature is real, it may well be due to detector noise rather than a non-Gaussian sky signal, since a signal-to-noise analysis localizes it to angular scales smaller than the beam. We study its spatial origin in case it is nonetheless due to a sky signal (eg, a cosmic string wake or flat-spectrum foreground contaminant). It appears highly localized in the direction b=39.5, l=257, since removing a mere 5 pixels inside a single COBE beam area centered there makes the effect statistically insignificant. We also test Guassianity with an eigenmode analysis which allows a sky map to be treated as a random number generator. A battery of tests of this generator all yield results consistent with Gaussianity.Comment: Revised to match accepted ApJL version. 4 pages with 2 figs included. Links and color fig at http://www.sns.ias.edu/~max/gaussianity_frames.html or from [email protected]

Detecting clinically meaningful biomarkers with repeated measurements in an Electronic Health Record

Electronic health record (EHR) data are becoming an increasingly common data source for understanding clinical risk of acute events. While their longitudinal nature presents opportunities to observe changing risk over time, these analyses are complicated by the sparse and irregular measurements of many of the clinical metrics making typical statistical methods unsuitable for these data. In this paper, we present an analytic procedure to both sample from an EHR and analyze the data to detect clinically meaningful markers of acute myocardial infarction (MI). Using an EHR from a large national dialysis organization we abstracted the records of 64,318 individuals and identified 5,314 people that had an MI during the study period. We describe a nested case-control design to sample appropriate controls and an analytic approach using regression splines. Fitting a mixed-model with truncated power splines we perform a series of goodness-of-fit tests to determine whether any of 11 regularly collected laboratory markers are useful clinical predictors. We test the clinical utility of each marker using an independent test set. The results suggest that EHR data can be easily used to detect markers of clinically acute events. Special software or analytic tools are not needed, even with irregular EHR data.Comment: 23 pages, 3 figure

Quantum computation via translation-invariant operations on a chain of qubits

A scheme of universal quantum computation on a chain of qubits is described that does not require local control. All the required operations, an Ising-type interaction and spatially uniform simultaneous one-qubit gates, are translation-invariant.Comment: Comment after Eq. (2) inserted, journal versio

Terrestrial Planet Formation I. The Transition from Oligarchic Growth to Chaotic Growth

We use a hybrid, multiannulus, n-body-coagulation code to investigate the growth of km-sized planetesimals at 0.4-2 AU around a solar-type star. After a short runaway growth phase, protoplanets with masses of roughly 10^26 g and larger form throughout the grid. When (i) the mass in these `oligarchs' is roughly comparable to the mass in planetesimals and (ii) the surface density in oligarchs exceeds 2-3 g/sq cm at 1 AU, strong dynamical interactions among oligarchs produce a high merger rate which leads to the formation of several terrestrial planets. In disks with lower surface density, milder interactions produce several lower mass planets. In all disks, the planet formation timescale is roughly 10-100 Myr, similar to estimates derived from the cratering record and radiometric data.Comment: Astronomical Journal, accepted; 22 pages + 15 figures in ps format; eps figures at http://cfa-www.harvard.edu/~kenyon/dl/ revised version clarifies evolution and justifies choice of promotion masse