BackgroundAlthough behavioral risk factors are strongly associated with urinary tract infection (UTI) risk, the role of genetics in acquiring this disease is poorly understood.Methodology/Principal FindingsTo test the hypothesis that polymorphisms in Toll-like receptor (TLR) pathway genes are associated with susceptibility to UTIs, we conducted a population-based case-control study of women ages 18–49 years. We examined DNA variants in 9 TLR pathway genes in 431 recurrent cystitis (rUTI) cases, 400 pyelonephritis cases, and 430 controls with no history of UTIs. In the Caucasian subgroup of 987 women, polymorphism TLR4_A896G was associated with protection from rUTI, but not pyelonephritis, with an odds ratio (OR) of 0.54 and a 95% confidence interval (CI) of 0.31 to 0.96. Polymorphism TLR5_C1174T, which encodes a variant that abrogates flagellin-induced signaling, was associated with an increased risk of rUTI (OR(95%CI): 1.81 (1.00–3.08)), but not pyelonephritis. Polymorphism TLR1_G1805T was associated with protection from pyelonephritis (OR(95%CI): 0.53 (0.29–0.96)).ConclusionsThese results provide the first evidence of associations of TLR5 and TLR1 variants with altered risks of acquiring rUTI and pyelonephritis, respectively. Although these data suggest that TLR polymorphisms are associated with adult susceptibility to UTIs, the statistical significance was modest and will require further study including validation with independent cohorts.

In light of anatomical evidence suggesting differential connection patterns in central vs. peripheral representations of cortical areas, we investigated the extent to which the response properties of cells in the primary visual area (V1) of the marmoset change as a function of eccentricity. Responses to combinations of the spatial and temporal frequencies of visual stimuli were quantified for neurons with receptive fields ranging from 3 degrees to 70 degrees eccentricity. Optimal spatial frequencies and stimulus speeds reflected the expectation that the responses of cells throughout V1 are essentially uniform, once scaled according to the cortical magnification factor. In addition, temporal frequency tuning was similar throughout V1. However, spatial frequency tuning curves depended both on the cell's optimal spatial frequency and on the receptive field eccentricity: cells with peripheral receptive fields showed narrower bandwidths than cells with central receptive fields that were sensitive to the same optimal spatial frequency. Although most V1 cells had separable spatial and temporal frequency tuning, the proportion of neurons displaying significant spatiotemporal interactions increased in the representation of far peripheral vision (> 50 degrees). In addition, of the fewer than 5% of V1 cells that showed robust (spatial frequency independent) selectivity to stimulus speed, most were concentrated in the representation of the far periphery. Spatiotemporal interactions in the responses of many cells in the peripheral representation of V1 reduced the ambiguity of responses to high-speed (> 30 degrees/s) signals. These results support the notion of a relative specialization for motion processing in the far peripheral representations of cortical areas, including V1.

We show that many existing elastic body simulation approaches can be interpreted as descent methods, under a nonlinear optimization framework derived from implicit time integration. The key question is how to find an effective descent direction with a low computational cost. Based on this concept, we propose a new gradient descent method using Jacobi preconditioning and Chebyshev acceleration. The convergence rate of this method is comparable to that of L-BFGS or nonlinear conjugate gradient. But unlike other methods, it requires no dot product operation, making it suitable for GPU implementation. To further improve its convergence and performance, we develop a series of step length adjustment, initialization, and invertible model conversion techniques, all of which are compatible with GPU acceleration. Our experiment shows that the resulting simulator is simple, fast, scalable, memory-efficient, and robust against very large time steps and deformations. It can correctly simulate the deformation behaviors of many elastic materials, as long as their energy functions are second-order differentiable and their Hessian matrices can be quickly evaluated. For additional speedups, the method can also serve as a complement to other techniques, such as multi-grid.

The constitution of traditional Chinese medicine was established in 1970s by Chinese scholars, in which the constitutions of Chinese people were classified into nine types for study. The phlegm-dampness constitution is one of the nine constitutions and is the most common type in constitution study. Genomics studies found four upregulated genes: COPS8, GNPDA1, CD52 and ARPC3; and six downregulated genes: GSPT2, CACNB2, FLJ20584, UXS1, IL21R and TNPO in the phlegm-dampness constitution. Gene functional analyses on genes affecting the differences between the phlegm-dampness constitution and the balanced constitution indicated that people with phlegm-dampness constitution were susceptible to hyperlipemia and diabetes. Results of epidemiological surveys also revealed that people with phlegm-dampness constitution have a much higher risk of obesity, metabolic syndrome, hypertension and diabetes than people with a balanced constitution. Therefore, differentiation of phlegm-dampness constitution could be performed in the normal population with the Constitution of Chinese Medicine Scale to estimate the risks of those diseases for prediction. For people with phlegm-dampness constitution, Chinese medicine could be used to reduce risk of related diseases. Constitution-based strategies in disease prevention and treatment are consistent with the current proposed 4P medical mode (personalized, predictive, preventive and participatory). With the rising burden of global disease and increasing medical expenditure, the objectives of medicine are transforming from treatment to prevention. Thus, studies on the phlegm-dampness constitution of traditional Chinese medicine are significantly important for the prediction and prevention of related diseases and maintenance of human health.

We solve a challenging yet practically useful variant of 3D Bin Packing Problem (3D-BPP). In our problem, the agent has limited information about the items to be packed into a single bin, and an item must be packed immediately after its arrival without buffering or readjusting. The item's placement also subjects to the constraints of order dependence and physical stability. We formulate this online 3D-BPP as a constrained Markov decision process (CMDP). To solve the problem, we propose an effective and easy-to-implement constrained deep reinforcement learning (DRL) method under the actor-critic framework. In particular, we introduce a prediction-and-projection scheme: The agent first predicts a feasibility mask for the placement actions as an auxiliary task and then uses the mask to modulate the action probabilities output by the actor during training. Such supervision and projection facilitate the agent to learn feasible policies very efficiently. Our method can be easily extended to handle lookahead items, multi-bin packing, and item re-orienting. We have conducted extensive evaluation showing that the learned policy significantly outperforms the state-of-the-art methods. A preliminary user study even suggests that our method might attain a human-level performance.