Autotuning Algorithmic Choice for Input Sensitivity

Empirical autotuning is increasingly being used in many domains to achieve optimized performance in a variety of different execution environments. A daunting challenge faced by such autotuners is input sensitivity, where the best autotuned configuration may vary with different input sets. In this paper, we propose a two level solution that: first, clusters to find input sets that are similar in input feature space; then, uses an evolutionary autotuner to build an optimized program for each of these clusters; and, finally, builds an adaptive overhead aware classifier which assigns each input to a specific input optimized program. Our approach addresses the complex trade-off between using expensive features, to accurately characterize an input, and cheaper features, which can be computed with less overhead. Experimental results show that by adapting to different inputs one can obtain up to a 3x speedup over using a single configuration for all inputs

Behavioural micro-dynamics of car ownership and travel in the Seattle metropolitan region from 1989 to 2002

In this paper data from 230 households observed in ten different occasions (waves) from 1989 to 2002 in the Puget Sound region are used to explore relationships among number of cars owned, number of trips driving alone, and number of trips sharing cars with household members. Using a mixture latent class Markov model we identify four distinct groups that are a High Mobility group with more cars and car trips, an Average Mobility group with lower car ownership and trips driving alone, a third group with relatively high car ownership but few car sharing trips, and a fourth group of Low Mobility characterized by the low car ownership and trips. Households change behaviour adapting to internal and external changes to their environment but they also anticipate changes and go through a "preparation" stage (e.g., adding another car in their fleet in expectation of adding another employed person). Land use plays a somewhat secondary role. The analysis also reveals three classes (hidden Markov chains) of households underlying behavioural dynamics with increases in the low car ownership categories (zero and one car per household), decreases in the high car ownership (three cars and four or more cars per household) and stable behaviour in the two cars per household group. Household membership in these classes is significantly influenced by householder ratings to parking availability, schedule flexibility, bus transfers, and day-to-day costs of driving. The findings here show attitudes and land use enhance understanding of longitudinal heterogeneity

Runx3 and T-box proteins cooperate to establish the transcriptional program of effector CTLs

Activation of naive CD8+ T cells with antigen induces their differentiation into effector cytolytic T lymphocytes (CTLs). CTLs lyse infected or aberrant target cells by exocytosis of lytic granules containing the pore-forming protein perforin and a family of proteases termed granzymes. We show that effector CTL differentiation occurs in two sequential phases in vitro, characterized by early induction of T-bet and late induction of Eomesodermin (Eomes), T-box transcription factors that regulate the early and late phases of interferon (IFN) γ expression, respectively. In addition, we demonstrate a critical role for the transcription factor Runx3 in CTL differentiation. Runx3 regulates Eomes expression as well as expression of three cardinal markers of the effector CTL program: IFN-γ, perforin, and granzyme B. Our data point to the existence of an elaborate transcriptional network in which Runx3 initially induces and then cooperates with T-box transcription factors to regulate gene transcription in differentiating CTLs

Visualizing B cell capture of cognate antigen from follicular dendritic cells

The prominent display of opsonized antigen by follicular dendritic cells (FDCs) has long favored the view that they serve as antigen-presenting cells for B cells. Surprisingly, however, although B cell capture of antigen from macrophages and dendritic cells has been visualized, acquisition from FDCs has not been directly observed. Using two-photon microscopy, we visualized B cell capture of cognate antigen from FDCs. B cell CXCR5 expression was required, and encounter with FDC-associated antigen could be detected for >1 wk after immunization. B cell–FDC contact times were often brief but occasionally persisted for >30 min, and B cells sometimes acquired antigen together with FDC surface proteins. These observations establish that FDCs can serve as sites of B cell antigen capture, with their prolonged display time ensuring that even rare B cells have the chance of antigen encounter, and they suggest possible information transfer from antigen-presenting cell to B cell

Endovascular baroreflex amplification for resistant hypertension: a safety and proof-of-principle clinical study

Summary Background Carotid baroreflex activation lowers blood pressure and might have potential application for the treatment of resistant hypertension. We did a proof-of-principle trial with a novel endovascular baroreceptor amplification device, MobiusHD (Vascular Dynamics, Mountain View, CA, USA), in patients with resistant hypertension. Methods CALM-FIM_EUR was a prospective, first-in-human, open-label study done at six European centres. Eligible patients were adults with resistant hypertension (office systolic blood pressure ≥160 mm Hg despite taking at least three antihypertensive agents, including a diuretic). MobiusHD devices were implanted unilaterally in the internal carotid artery. The primary endpoint was the incidence of serious adverse events at 6 months. Secondary endpoints included changes in office and 24 h ambulatory blood pressure. This trial is registered with ClinicalTrials.gov, number NCT01911897. Findings Between December, 2013, and February, 2016, 30 patients were enrolled and underwent successful implantation. Mean age was 52 years (SD 12), 15 patients (50%) were men, and mean antihypertensive use was 4·4 drugs (1·4). Mean office blood pressure was 184/109 mm Hg (18/14) at baseline and was reduced by 24/12 mm Hg (13–34/6–18) at 6 months (p=0·0003 for systolic and p=0·0001 diastolic blood pressure). Mean baseline 24 h ambulatory blood pressure was 166/100 mm Hg (17/14) at baseline and was reduced by 21/12 mm Hg (14–29/7–16) at 6 months (p<0·0001 for systolic and diastolic blood pressure). Five serious adverse events had occurred in four patients (13%) at 6 months: hypotension (n=2), worsening hypertension (n=1), intermittent claudication (n=1) and wound infection (n=1). Interpretation In patients with resistant hypertension, endovascular baroreceptor amplification with the MobiusHD device substantially lowered blood pressure with an acceptable safety profile. Randomised, double-blind, sham-controlled trials are warranted to investigate the use of this treatment further. Funding Vascular Dynamics

Razvoj i vrednovanje dvoslojnih tableta propranolol hidroklorida

The objective of the present research was to develop a bilayer tablet of propranolol hydrochloride using superdisintegrant sodium starch glycolate for the fast release layer and water immiscible polymers such as ethyl cellulose, Eudragit RLPO and Eudragit RSPO for the sustaining layer. In vitro dissolution studies were carried out in a USP 24 apparatus I. The formulations gave an initial burst effect to provide the loading dose of the drug followed by sustained release for 12 hrs from the sustaining layer of matrix embedded tablets. In vitro dissolution kinetics followed the Higuchi model via a non-Fickian diffusion controlled release mechanism after the initial burst release. FT-IR studies revealed that there was no interaction between the drug and polymers used in the study. Statistical analysis (ANOVA) showed no significant difference in the cumulative amount of drug release after 15 min, but significant difference (p 0.005) in the amount of drug released after 12 h from optimized formulations was observed.U radu je opisan razvoj dvoslojnih tableta propranolol hidroklorida, koristeći superdezintegrator škrob glikolat natrij u sloju za brzo oslobađanje i polimere koji se ne miješaju s vodom (etil celuloza, Eudragit RLPO i Eudragit RSPO) u sloju za usporeno oslobađanje. In vitro oslobađanje praćeno je u USP aparatu I te je uočeno početno naglo oslobađanje ljekovite tvari iza kojeg slijedi polagano oslobađanje tijekom 12 sati. In vitro kinetika oslobađanja prati Higouchijev model, dok mehanizam kontroliranog oslobađanja ne slijedi Fickov zakon poslije početnog naglog oslobađanja. FT-IR studije ukazuju da nema interakcije između ljekovite tvari i polimera upotrebljenih u oblikovanju. Statistička analiza (ANOVA) nije pokazala značajne razlike u kumulativnoj količini oslobođenog lijeka iz optimiranih formulacija poslije 15 minuta i polije 12 h

Convex duality and Orlicz spaces in expected utility maximization

In this paper we report further progress towards a complete theory of state-independent expected utility maximization with semimartingale price processes for arbitrary utility function. Without any technical assumptions we establish a surprising Fenchel duality result on conjugate Orlicz spaces, offering a new economic insight into the nature of primal optima and providing fresh perspective on the classical papers of Kramkov and Schachermayer (1999, 2003). The analysis points to an intriguing interplay between no-arbitrage conditions and standard convex optimization and motivates study of the Fundamental Theorem of Asset Pricing (FTAP) for Orlicz tame strategies

On the spontaneous stochastic dynamics of a single gene: complexity of the molecular interplay at the promoter

International audienceBACKGROUND: Gene promoters can be in various epigenetic states and undergo interactions with many molecules in a highly transient, probabilistic and combinatorial way, resulting in a complex global dynamics as observed experimentally. However, models of stochastic gene expression commonly consider promoter activity as a two-state on/off system. We consider here a model of single-gene stochastic expression that can represent arbitrary prokaryotic or eukaryotic promoters, based on the combinatorial interplay between molecules and epigenetic factors, including energy-dependent remodeling and enzymatic activities. RESULTS: We show that, considering the mere molecular interplay at the promoter, a single-gene can demonstrate an elaborate spontaneous stochastic activity (eg. multi-periodic multi-relaxation dynamics), similar to what is known to occur at the gene-network level. Characterizing this generic model with indicators of dynamic and steady-state properties (including power spectra and distributions), we reveal the potential activity of any promoter and its influence on gene expression. In particular, we can reproduce, based on biologically relevant mechanisms, the strongly periodic patterns of promoter occupancy by transcription factors (TF) and chromatin remodeling as observed experimentally on eukaryotic promoters. Moreover, we link several of its characteristics to properties of the underlying biochemical system. The model can also be used to identify behaviors of interest (eg. stochasticity induced by high TF concentration) on minimal systems and to test their relevance in larger and more realistic systems. We finally show that TF concentrations can regulate many aspects of the stochastic activity with a considerable flexibility and complexity. CONCLUSIONS: This tight promoter-mediated control of stochasticity may constitute a powerful asset for the cell. Remarkably, a strongly periodic activity that demonstrates a complex TF concentration-dependent control is obtained when molecular interactions have typical characteristics observed on eukaryotic promoters (high mobility, functional redundancy, many alternate states/pathways). We also show that this regime results in a direct and indirect energetic cost. Finally, this model can constitute a framework for unifying various experimental approaches. Collectively, our results show that a gene - the basic building block of complex regulatory networks - can itself demonstrate a significantly complex behavior