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

Lack of association between dietary fructose and hyperuricemia risk in adults

<p>Abstract</p> <p>Background</p> <p>High serum uric acid concentration (hyperuricemia) has been studied for its relationship with multiple adverse health outcomes, such as metabolic syndrome. Intervention studies have produced inconsistent outcomes for the relationship between fructose intake and serum uric acid concentration.</p> <p>Methods</p> <p>The association of dietary fructose intake with hyperuricemia risk in adults was examined using logistic regression and U.S. NHANES 1999-2004 databases. A total of 9,384 subjects, between the ages 20 and 80 years, without diabetes, cancer, or heart disease, were included.</p> <p>Results</p> <p>The highest added or total fructose intake (quartiles by grams or % energy) was not associated with an increase of hyperuricemia risk compared to the lowest intake with or without adjustment (odds ratios = 0.515-0.992). The associations of alcohol and fiber intakes with the risk were also determined. Compared to the lowest intake, the highest alcohol intake was associated with increased mean serum uric acid concentration (up to 16%, <it>P </it>< 0.001) and hyperuricemia risk (odds ratios = 1.658-1.829, <it>P </it>= 0.057- < 0.001); the highest fiber intake was correlated with decreases of uric acid concentration (up to 7.5%, <it>P </it>< 0.002) and lower risk (odds ratios = 0.448-0.478, <it>P </it>= 0.001- < 0.001). Adults who were over 50 y old, male, or obese had significantly greater risk.</p> <p>Conclusions</p> <p>The data show that increased dietary fructose intake was not associated with increased hyperuricemia risk; while increased dietary alcohol intake was significantly associated with increased hyperuricemia risk; and increased fiber intake was significantly associated with decreased hyperuricemia risk. These data further suggest a potential effect of fructose consumption in an ordinary diet on serum uric acid differs from results found in some short-term studies using atypical exposure and/or levels of fructose administration.</p