Inferring TF activities and activity regulators from gene expression data with constraints from TF perturbation data

MOTIVATION: The activity of a transcription factor (TF) in a sample of cells is the extent to which it is exerting its regulatory potential. Many methods of inferring TF activity from gene expression data have been described, but due to the lack of appropriate large-scale datasets, systematic and objective validation has not been possible until now. RESULTS: We systematically evaluate and optimize the approach to TF activity inference in which a gene expression matrix is factored into a condition-independent matrix of control strengths and a condition-dependent matrix of TF activity levels. We find that expression data in which the activities of individual TFs have been perturbed are both necessary and sufficient for obtaining good performance. To a considerable extent, control strengths inferred using expression data from one growth condition carry over to other conditions, so the control strength matrices derived here can be used by others. Finally, we apply these methods to gain insight into the upstream factors that regulate the activities of yeast TFs Gcr2, Gln3, Gcn4 and Msn2. AVAILABILITY AND IMPLEMENTATION: Evaluation code and data are available at https://doi.org/10.5281/zenodo.4050573. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online

Active optics challenges of a thirty-meter segmented mirror telescopy

Ground-based telescopes operate in a turbulent atmosphere that affects the optical path across the aperture by changing both the mirror positions (wind seeing) and the air refraction index in the light path (atmospheric seeing). In wide field observations, when adaptive optics is not feasible, active optics are the only means of minimizing the effects of wind buffeting. An integrated, dynamic model of wind buffeting, telescope structure, and optical performance was devleoped to investigate wind energy propagation into primary mirror modes and secondary mirror rigid body motion.Although the rsults showed that the current level of wind modeling was not appropriate to decisively settle the need for optical feedback loops in active optics, the simulations strongly indicated the capability of a limited bandwidth edge sensor loop to maintain the continuity of the primary mirror inside the preliminary error budget. It was also found that the largest contributor to the wind seeing is image jitter, i.e. OPD tip/tilt

A new and efficient approach to time-dependent density-functional perturbation theory for optical spectroscopy

Using a super-operator formulation of linearized time-dependent density-functional theory, the dynamical polarizability of a system of interacting electrons is given a matrix continued-fraction representation whose coefficients can be obtained from the non-symmetric block-Lanczos method. The resulting algorithm allows for the calculation of the {\em full spectrum} of a system with a computational workload which is only a few times larger than that needed for {\em static} polarizabilities within time-independent density-functional perturbation theory. The method is demonstrated with the calculation of the spectrum of benzene, and prospects for its application to the large-scale calculation of optical spectra are discussed.Comment: 4 pages, 2 figure

Toward Controllable Hydraulic Coupling of Joints in a Wearable Robot

In this paper, we develop theoretical foundations for a new class of rehabilitation robot: body powered devices that route power between a user’s joints. By harvesting power from a healthy joint to assist an impaired joint, novel bimanual and self-assist therapies are enabled. This approach complements existing robotic therapies aimed at promoting recovery of motor function after neurological injury. We employ hydraulic transmissions for routing power, or equivalently for coupling the motions of a user’s joints. Fluid power routed through flexible tubing imposes constraints within a limb or between homologous joints across the body. Variable transmissions allow constraints to be steered on the fly, and simple valve switching realizes free space and locked motion. We examine two methods for realizing variable hydraulic transmissions: using valves to switch among redundant cylinders (digital hydraulics) or using an intervening electromechanical link. For both methods, we present a rigorous mathematical framework for describing and controlling the resulting constraints. Theoretical developments are supported by experiments using a prototype fluid-power exoskeleton

Understanding Potential Intraoperative Impediments for Learning Laparoscopic Nephrectomy

Purpose: We evaluated factors that impact the ability to learn hand-assisted laparoscopic donor nephrectomy (HALDN) to identify impediments to diffusion of this procedure. Methods: From February 2002 to June 2004, we collected data from our institutional database on 70 patients who underwent HALDN. Time for individual steps of the procedure (colon mobilization, kidney/ureter mobilization, renal vein tributary dissection, renal hilum dissection, removal of the kidney, and overall time) were recorded. The impact of patient factors on surgical times was assessed using a general linear model. The impact of individual operative steps on overall operative time was assessed using Pearson correlation. The influence of case experience and training level were evaluated graphically and in a multivariable model. Results: A total of 13 residents, 2 fellows, and 1 attending surgeon participated in procedures for 70 patients. Body mass index (P = 0.03) and male sex (P = 0.04) prolonged operative times. Colon mobilization and hilar dissection were most correlated with overall operative time. While experience improved operative times for several steps, level of training appeared more likely to influence the time for individual operative steps. Conclusions: Impediments to learning HALDN include patient factors, level of training, and particular surgical steps. Repeated exposure at increasing levels of training may improve diffusion of laparoscopic nephrectomy among urologists.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63194/1/end.2008.0439.pd

Substantial improvements not seen in health behaviors following corner store conversions in two Latino food swamps.

BackgroundThe effectiveness of food retail interventions is largely undetermined, yet substantial investments have been made to improve access to healthy foods in food deserts and swamps via grocery and corner store interventions. This study evaluated the effects of corner store conversions in East Los Angeles and Boyle Heights, California on perceived accessibility of healthy foods, perceptions of corner stores, store patronage, food purchasing, and eating behaviors.MethodsHousehold data (n = 1686) were collected at baseline and 12- to 24-months post-intervention among residents surrounding eight stores, three of which implemented a multi-faceted intervention and five of which were comparisons. Bivariate analyses and logistic and linear regressions were employed to assess differences in time, treatment, and the interaction between time and treatment to determine the effectiveness of this intervention.ResultsImprovements were found in perceived healthy food accessibility and perceptions of corner stores. No changes were found, however, in store patronage, purchasing, or consumption of fruits and vegetables.ConclusionsResults suggest limited effectiveness of food retail interventions on improving health behaviors. Future research should focus on other strategies to reduce community-level obesity