A Stochastic Compartmental Model for Fast Axonal Transport

In this paper we develop a probabilistic micro-scale compartmental model and use it to study macro-scale properties of axonal transport, the process by which intracellular cargo is moved in the axons of neurons. By directly modeling the smallest scale interactions, we can use recent microscopic experimental observations to infer all the parameters of the model. Then, using techniques from probability theory, we compute asymptotic limits of the stochastic behavior of individual motor-cargo complexes, while also characterizing both equilibrium and non-equilibrium ensemble behavior. We use these results in order to investigate three important biological questions: (1) How homogeneous are axons at stochastic equilibrium? (2) How quickly can axons return to stochastic equilibrium after large local perturbations? (3) How is our understanding of delivery time to a depleted target region changed by taking the whole cell point-of-view

Pay for Performance from Future Fund Flows: The Case of Private Equity

Lifetime incomes of private equity general partners are affected by their current funds’ performance through both carried interest profit sharing provisions, and also by the effect of the current fund’s performance on general partners’ abilities to raise capital for future funds. We present a learning-based framework for estimating the market-based pay for performance arising from future fundraising. For the typical first-time private equity fund, we estimate that implicit pay for performance from expected future fundraising is approximately the same order of magnitude as the explicit pay for performance general partners receive from carried interest in their current fund, implying that the performance-sensitive component of general partner revenue is about twice as large as commonly discussed. Consistent with the learning framework, we find that implicit pay for performance is stronger when managerial abilities are more scalable and weaker when current performance contains less new information about ability. Specifically, implicit pay for performance is stronger for buyout funds compared to venture capital funds, and declines in the sequence of a partnership’s funds. Our framework can be adapted to estimate implicit pay for performance in other asset management settings in which future fund flows and compensation depend on current performance.Private equity; Venture capital; Fundraising; Compensation; Incentives

UVOT Measurements of Dust and Star Formation in the SMC and M33

When measuring star formation rates using ultraviolet light, correcting for dust extinction is a critical step. However, with the variety of dust extinction curves to choose from, the extinction correction is quite uncertain. Here, we use Swift/UVOT to measure the extinction curve for star-forming regions in the SMC and M33. We find that both the slope of the curve and the strength of the 2175 Angstrom bump vary across both galaxies. In addition, as part of our modeling, we derive a detailed recent star formation history for each galaxy.Comment: 6 pages, 5 figures, conference proceedings from Swift: 10 years of Discovery, held in Rome (2-5 Dec. 2014

The Evolution of the Far-UV Luminosity Function and Star Formation Rate Density of the Chandra Deep Field South from z=0.2-1.2 with Swift/UVOT

We use deep Swift UV/Optical Telescope (UVOT) near-ultraviolet (1600A to 4000A) imaging of the Chandra Deep Field South to measure the rest-frame far-UV (FUV; 1500A) luminosity function (LF) in four redshift bins between z=0.2 and 1.2. Our sample includes 730 galaxies with u < 24.1 mag. We use two methods to construct and fit the LFs: the traditional V_max method with bootstrap errors and a maximum likelihood estimator. We observe luminosity evolution such that M* fades by ~2 magnitudes from z~1 to z~0.3 implying that star formation activity was substantially higher at z~1 than today. We integrate our LFs to determine the FUV luminosity densities and star formation rate densities from z=0.2 to 1.2. We find evolution consistent with an increase proportional to (1+z)^1.9 out to z~1. Our luminosity densities and star formation rates are consistent with those found in the literature, but are, on average, a factor of ~2 higher than previous FUV measurements. In addition, we combine our UVOT data with the MUSYC survey to model the galaxies' ultraviolet-to-infrared spectral energy distributions and estimate the rest-frame FUV attenuation. We find that accounting for the attenuation increases the star formation rate densities by ~1 dex across all four redshift bins.Comment: 20 pages, 8 figures, 6 tables; accepted for publication in Ap

Perceptions of fecal microbiota transplantation for Clostridium difficile infection: factors that predict acceptance.

BackgroundDespite the effectiveness of fecal microbiota transplantation (FMT) for treating recurrent Clostridium difficile (C. difficile) infection, some patients are reluctant to accept this therapy. Our study examined attitudes towards FMT and factors that contribute to patients' acceptance of this treatment.MethodsWe distributed patient surveys at a Veterans Affairs hospital, a public hospital, and an academic faculty practice. Multivariable logistic regression was performed, adjusting for factors associated with FMT acceptance on univariate analysis and prior experience with C. difficile infection.ResultsOf 267 patients, only 12% knew of FMT prior to the survey, but 77% would undergo the procedure if medically indicated. On multivariable analysis, those with children and with college degrees or higher were more likely to agree to FMT (odds ratio [OR] 2.11, 95% confidence interval [CI] 1.02-4.35; OR 2.27, 95% CI 1.11-4.60 respectively). Sixty-five respondents (71%) chose colonoscopy as the preferred vehicle for FMT, while nasogastric tube was least preferred. Disease transmission was the most common concern (30%, n=242), and FMT success rate was the least selected concern (9.1%).ConclusionsMost patients in a diverse sample of gastroenterology clinics had no prior knowledge of FMT, but were receptive to the procedure. Having children and higher education levels were predictors for FMT acceptance. Our findings suggest that barriers to FMT utilization may be overcome with counseling about safety concerns. More data on the risk of transmitting diseases or clinical characteristics, such as obesity, through FMT are needed and will be important for the acceptance of this procedure

Association of sperm protein 17 with A-kinase anchoring protein 3 in flagella

BACKGROUND: Sperm protein 17 (Sp17) is a three-domain protein that contains: 1) a highly conserved N-terminal domain that is 45% identical to the human type II alpha regulatory subunit (RII alpha) of protein kinase A (PKA); 2) a central sulphated carbohydrate-binding domain; and 3) a C-terminal Ca++/calmodulin (CaM) binding domain. Although Sp17 was originally discovered and characterized in spermatozoa, its mRNA has now been found in a variety of normal mouse and human tissues. However, Sp17 protein is found predominantly in spermatozoa, cilia and human neoplastic cell lines. This study demonstrates that Sp17 from spermatozoa binds A-kinase anchoring protein 3 (AKAP3), confirming the functionality of the N-terminal domain. METHODS: In this study in vitro precipitation and immunolocalization demonstrate that Sp17 binds to AKAP3 (AKAP110) in spermatozoa. RESULTS: Sp17 is present in the head and tail of spermatozoa, in the tail it is in the fibrous sheath, which contains AKAP3 and AKAP4. Recombinant AKAP3 and AKAP4 RII binding domains were synthesized as glutathione S-transferase (GST) fusion proteins immobilized on glutathione-agarose resin and added to CHAPS extracts of human spermatozoa. Western blots of bound and eluted proteins probed with anti-Sp17 revealed that AKAP3 bound and precipitated a significant level of Sp17 while AKAP4 did not. AKAP4 binds AKAP3 and expression of AKAP3 is reduced in AKAP4 knockout sperm, therefore we tested AKAP4 knockout spermatozoa for Sp17 and found that there was a reduction in the amount of Sp17 expressed when compared to wild type spermatozoa. Co-localization of AKAP3 and Sp17 by immunofluorescence was demonstrated along the length of the principal piece of the flagella. CONCLUSIONS: As predicted by its N-terminal domain that is 45% identical to the human RIIα of PKA, Sp17 from spermatozoa binds the RII binding domain of AKAP3 along the length of the flagella

Das Narrative Policy Framework: Ein Reiseführer für Policy-Narrative

The last decade has seen the rise of the Narrative Policy Framework (NPF) as a valuable theoretical framework for advancing knowledge of the policy process. In this article, we investigate the NPF’s “travel” capacities across geographies, political systems, policy fields, levels of analysis, methodological approaches, and other theories of the policy process. We assess these capabilities by reviewing extant research and mapping newly explored territories. While we find that the NPF embodies all necessary conditions to travel to different settings, the empirical applications remain largely confined to the U.S. and European contexts, environmental policy, the meso level of analysis, the use of content analysis of documents as a methodological approach, and only a few combinations with other theories of the policy process. Our findings indicate that the NPF can travel well. However, we call for further research to conceptualize the NPF’s macro level, to replicate NPF scholarship beyond liberal democratic institutional contexts, and to affirm the framework’s capacity to be generalizable in varied settings.In den letzten zehn Jahren hat sich das Narrative Policy Framework (NPF) zum wegweisenden theoretischen Rahmen bei der Erklärung der Rolle von Narrativen in Politikgestaltungsprozessen entwickelt. Dieser Artikel untersucht die Kapazitäten des NPF, in anderen Regionen und politischen Systemen, neuen Politikfeldern, Analyseebenen und methodologischen Ansätzen sowie in Kombination mit weiteren Theorien des Politikprozesses angewandt zu werden. Diese „Reisefähigkeit“ des NPF wird anhand eines systematischen Reviews der bestehenden NPF-Literatur bewertet. Dabei werden neue, kürzlich erkundete Territorien speziell hervorgehoben. Das systematische Review zeigt, dass das NPF zwar alle notwendigen Bedingungen erfüllt, um in verschiedene Umgebungen zu reisen. Trotzdem beschränken sich bisherige empirische Anwendungen des NPF weitgehend auf die amerikanischen und europäischen Kontexte, die Umweltpolitik, die Meso-Ebene der Analyse, die Inhaltsanalyse von Dokumenten und auf nur wenige Kombinationen mit anderen Theorien des Politikprozesses. Diese Ergebnisse weisen darauf hin, dass das NPF grundsätzlich gut reisen kann. Wir fordern jedoch weitere Forschung, um die Makro-Ebene des NPF zu konzeptualisieren, NPF-Forschung außerhalb von liberal-demokratischen Systemen zu replizieren und die Generalisierbarkeit des NPF in verschiedenen Kontexten zu bestätigen

The p80 homology region of TEP1 is sufficient for its association with the telomerase and vault RNAs, and the vault particle

TEP1 is a protein component of two ribonucleoprotein complexes: vaults and telomerase. The vault-associated small RNA, termed vault RNA (VR), is dependent upon TEP1 for its stable association with vaults, while the association of telomerase RNA with the telomerase complex is independent of TEP1. Both of these small RNAs have been shown to interact with amino acids 1–871 of TEP1 in an indirect yeast three-hybrid assay. To understand the determinants of TEP1–RNA binding, we generated a series of TEP1 deletions and show by yeast three-hybrid assay that the entire Tetrahymena p80 homology region of TEP1 is required for its interaction with both telomerase and VRs. This region is also sufficient to target the protein to the vault particle. Electrophoretic mobility shift assays using the recombinant TEP1 RNA-binding domain (TEP1–RBD) demonstrate that it binds RNA directly, and that telomerase and VRs compete for binding. VR binds weakly to TEP1–RBD in vitro, but mutation of VR sequences predicted to disrupt helices near its central loop enhances binding. Antisense oligonucleotide-directed RNase H digestion of endogenous VR indicates that this region is largely single stranded, suggesting that TEP1 may require access to the VR central loop for efficient binding