Abstract. Though skyline queries already have claimed their place in retrieval over central databases, their application in Web information systems up to now was impossible due to the distributed aspect of retrieval over Web sources. But due to the amount, variety and volatile nature of information accessible over the Internet extended query capabilities are crucial. We show how to efficiently perform distributed skyline queries and thus essentially extend the expressiveness of querying today's Web information systems. Together with our innovative retrieval algorithm we also present useful heuristics to further speed up the retrieval in most practical cases paving the road towards meeting even the realtime challenges of on-line information services. We discuss performance evaluations and point to open problems in the concept and application of skylining in modern information systems. For the curse of dimensionality, an intrinsic problem in skyline queries, we propose a novel sampling scheme that allows to get an early impression of the skyline for subsequent query refinement.

Bayesian tomographic reconstruction algorithms generally require the efficient optimization of a functional of many variables. In this setting, as well as in many other optimization tasks, functional substitution (FS) has been widely applied to simplify each step of the iterative process. The function to be minimized is replaced locally by an approximation having a more easily manipulated form, e.g., quadratic, but which maintains sufficient similarity to descend the true functional while computing only the substitute. We provide two new applications of FS methods in iterative coordinate descent for Bayesian tomography. The first is a modification of our coordinate descent algorithm with one-dimensional (1-D) Newton-Raphson approximations to an alternative quadratic which allows convergence to be proven easily. In simulations, we find essentially no difference in convergence speed between the two techniques. We also present a new algorithm which exploits the FS method to allow parallel updates of arbitrary sets of pixels using computations similar to iterative coordinate descent. The theoretical potential speed up of parallel implementations is nearly linear with the number of processors if communication costs are neglected.

A specific group of transmembrane receptors, including the β1-adrenergic receptor (β1-AR), is internalized through a non-clathrin pathway known as Fast Endophilin Mediated Endocytosis (FEME). A key question is: how does the endocytic machinery assemble and how is it modulated by activated receptors during FEME. Here we show that endophilin, a major regulator of FEME, undergoes a phase transition into liquid-like condensates, which facilitates the formation of multi-protein assemblies by enabling the phase partitioning of endophilin binding proteins. The phase transition can be triggered by specific multivalent binding partners of endophilin in the FEME pathway such as the third intracellular loop (TIL) of the β1-AR, and the C-terminal domain of lamellipodin (LPD). Other endocytic accessory proteins can either partition into, or target interfacial regions of, these condensate droplets, and LPD also phase separates with the actin polymerase VASP. On the membrane, TIL promotes protein clustering in the presence of endophilin and LPD C-terminal domain. Our results demonstrate how the multivalent interactions between endophilin, LPD, and TIL regulate protein assembly formation on the membrane, providing mechanistic insights into the priming and initiation steps of FEME.

Background: We investigate whether deep learning (DL) neural networks can reduce erroneous human "judgment calls" on bedside echocardiograms and help distinguish Takotsubo syndrome (TTS) from anterior wall ST segment elevation myocardial infarction (STEMI). Methods: We developed a single-channel (DCNN[2D SCI]), a multi-channel (DCNN[2D MCI]), and a 3-dimensional (DCNN[2D+t]) deep convolution neural network, and a recurrent neural network (RNN) based on 17,280 still-frame images and 540 videos from 2-dimensional echocardiograms in 10 years (1 January 2008 to 1 January 2018) retrospective cohort in University of Iowa (UI) and eight other medical centers. Echocardiograms from 450 UI patients were randomly divided into training and testing sets for internal training, testing, and model construction. Echocardiograms of 90 patients from the other medical centers were used for external validation to evaluate the model generalizability. A total of 49 board-certified human readers performed human-side classification on the same echocardiography dataset to compare the diagnostic performance and help data visualization. Findings: The DCNN (2D SCI), DCNN (2D MCI), DCNN(2D+t), and RNN models established based on UI dataset for TTS versus STEMI prediction showed mean diagnostic accuracy 73%, 75%, 80%, and 75% respectively, and mean diagnostic accuracy of 74%, 74%, 77%, and 73%, respectively, on the external validation. DCNN(2D+t) (area under the curve [AUC] 0¢787 vs. 0¢699, P = 0¢015) and RNN models (AUC 0¢774 vs. 0¢699, P = 0¢033) outperformed human readers in differentiating TTS and STEMI by reducing human erroneous judgement calls on TTS. Interpretation: Spatio-temporal hybrid DL neural networks reduce erroneous human "judgement calls" in distinguishing TTS from anterior wall STEMI based on bedside echocardiographic videos.

ATP transiently increases the intracellular Ca2+ concentration in cardiac myocyte suspensions. Pretreatment with norepinephrine (NE) greatly potentiates the ATP response. We performed experiments on adult rat myocyte suspensions loaded with fura-2 to investigate the mechanism of NE potentiation. We found that forskolin (an activator of adenylate cyclase), 3-isobutyl-1-methylxanthine (an inhibitor of phosphodiesterase), and permeative adenosine 3',5'-cyclic monophosphate (cAMP) analogues potentiate the increase in cytosolic Ca2+ concentration induced by ATP. NE, forskolin, and 8-(4-chlorophenylthio)-cAMP all increase Vmax of the Ca2+ response curve of ATP. Measurement of cAMP by radioimmunoassay confirmed that the changes in the ATP response were accompanied by an increase in cAMP. These results suggest that the noradrenergic potentiation of the ATP-induced Ca2+ mobilization involves cAMP as a second messenger. Patch-clamp studies of isolated myocytes showed that neither NE nor forskolin alters the inward current elicited by ATP, but rather they increase the duration of secondary slow action potentials elicited by ATP. NE also increases the Ca2+ current through L-type Ca2+ channels in the myocytes. We conclude that NE potentiates the ATP-induced Ca2+ transient by increasing cAMP levels and that one of the early events is the increase of the inward Ca2+ current during the action potential.