A Continuum Poisson-Boltzmann Model for Membrane Channel Proteins

Membrane proteins constitute a large portion of the human proteome and perform a variety of important functions as membrane receptors, transport proteins, enzymes, signaling proteins, and more. The computational studies of membrane proteins are usually much more complicated than those of globular proteins. Here we propose a new continuum model for Poisson-Boltzmann calculations of membrane channel proteins. Major improvements over the existing continuum slab model are as follows: 1) The location and thickness of the slab model are fine-tuned based on explicit-solvent MD simulations. 2) The highly different accessibility in the membrane and water regions are addressed with a two-step, two-probe grid labeling procedure, and 3) The water pores/channels are automatically identified. The new continuum membrane model is optimized (by adjusting the membrane probe, as well as the slab thickness and center) to best reproduce the distributions of buried water molecules in the membrane region as sampled in explicit water simulations. Our optimization also shows that the widely adopted water probe of 1.4 {\AA} for globular proteins is a very reasonable default value for membrane protein simulations. It gives an overall minimum number of inconsistencies between the continuum and explicit representations of water distributions in membrane channel proteins, at least in the water accessible pore/channel regions that we focus on. Finally, we validate the new membrane model by carrying out binding affinity calculations for a potassium channel, and we observe a good agreement with experiment results.Comment: 40 pages, 6 figures, 5 table

Establishment of the prediction equations of 1RM skeletal muscle strength in 60- to 75-year-old Chinese men and women

The purpose of this study was to establish the one-repetition maximum (1RM) prediction equations of biceps curl, bench press, and squat from the submaximal skeletal muscle strength of 4-10RM or 11-15RM in older adults. The first group of 109 participants aged 60-75 years was recruited to measure their 1RM, 4-10RM, and 11-15RM of the three exercises. The 1RM prediction equations were developed by multiple regression analyses. A second group of participants with the similar physical characteristics to the first group was used to evaluate the equations. The actual measured 1RM of the second group correlated significantly to the predicted 1RM obtained from the equations (r values were from 0.633 to 0.985), and standard error of estimate ranged from 1.08 to 5.88. Therefore, the equations can be utilized to predict 1RM from submaximal skeletal muscle strength accurately for older adults

Stochastic Downsampling for Cost-Adjustable Inference and Improved Regularization in Convolutional Networks

It is desirable to train convolutional networks (CNNs) to run more efficiently during inference. In many cases however, the computational budget that the system has for inference cannot be known beforehand during training, or the inference budget is dependent on the changing real-time resource availability. Thus, it is inadequate to train just inference-efficient CNNs, whose inference costs are not adjustable and cannot adapt to varied inference budgets. We propose a novel approach for cost-adjustable inference in CNNs - Stochastic Downsampling Point (SDPoint). During training, SDPoint applies feature map downsampling to a random point in the layer hierarchy, with a random downsampling ratio. The different stochastic downsampling configurations known as SDPoint instances (of the same model) have computational costs different from each other, while being trained to minimize the same prediction loss. Sharing network parameters across different instances provides significant regularization boost. During inference, one may handpick a SDPoint instance that best fits the inference budget. The effectiveness of SDPoint, as both a cost-adjustable inference approach and a regularizer, is validated through extensive experiments on image classification

Soccer training: an effective exercise mode to prevent and treat childhood obesity?

Exercise training has been recognized as an effective treatment for childhood obesity. Clinical experience has shown that great efforts are needed to train children around 10 years old when using traditional aerobic exercise modes, such as walking and running. To seek more attractive training methods for children, in this paper, we review the current literature to evaluate the effectiveness of soccer training on childhood obesity prevention and treatment. Future research direction and sport injury prevention are also discussed

Quasi-compactons in inverted nonlinear photonic crystals

We study large-amplitude one-dimensional solitary waves in photonic crystals featuring competition between linear and nonlinear lattices, with minima of the linear potential coinciding with maxima of the nonlinear pseudopotential, and vice versa (inverted nonlinear photonic crystals, INPhCs), in the case of the saturable self-focusing nonlinearity. Such crystals were recently fabricated using a mixture of SU-8 and Rhodamine-B optical materials. By means of numerical methods and analytical approximations, we find that large-amplitude solitons are broad sharply localized stable pulses (quasi-compactons, QCs). With the increase of the totalpower, P, the QC's centroid performs multiple switchings between minima and maxima of the linear potential. Unlike cubic INPhCs, the large-amplitude solitons are mobile in the medium with the saturable nonlinearity. The threshold value of the kick necessary to set the soliton in motion is found as a function of P. Collisions between moving QCs are considered too.Comment: 11 pages, 8 figures, Physical Review A, in pres

Aerobic exercise training at maximal fat oxidation intensity improves body composition, glycemic control, and physical capacity in older people with type 2 diabetes

Background: Aerobic training has been used as one of the common treatments for type 2 diabetes; however, further research on the individualized exercise program with the optimal intensity is still necessary. The purpose of this study was to investigate the effects of supervised exercise training at the maximal fat oxidation (FATmax) intensity on body composition, glycemic control, lipid profile, and physical capacity in older people with type 2 diabetes. Methods: Twenty-four women and 25 men with type 2 diabetes, aged 60–69 years. The exercise groups trained at the individualized FATmax intensity for 1 h/day for 3 days/week over 16 weeks. No dietary intervention was introduced during the experimental period. Whole body fat, abdominal fat, oral glucose tolerance test, lipid profile, and physical capacity were measured before and after the interventions. Results: FATmax intensity was at 41.3 ± 3.2% VO2max for women and 46.1 ± 10.3% VO2max for men. Exercise groups obtained significant improvements in body composition, with a special decrease in abdominal obesity; decreased resting blood glucose concentration and HbA1c; and increased VO2max, walking ability, and lower body strength, compared to the non-exercising controls. Daily energy intake and medication remained unchanged for all participants during the experimental period. Conclusion: Beside the improvements in the laboratory variables, the individualized FATmax training can also benefit daily physical capacity of older people with type 2 diabetes

Predominance of Th2 polarization by Vitamin D through a STAT6-dependent mechanism

<p>Abstract</p> <p>Background</p> <p>Vitamin D has several reported immunomodulatory properties including the reduced generation of pro-inflammatory CD4+ T helper 1 (Th1) cells and the increase in levels of the anti-inflammatory Th2 subset. Less clear has been the impact of vitamin D on the pro-inflammatory Th17 subset, and whether and how vitamin D may preferentially drive the polarization of one of the T helper subsets.</p> <p>Methods</p> <p>Using human peripheral blood-derived mononuclear cells and mouse splenocytes and lymph node cells in culture, we examined whether and how vitamin D preferentially skews T cells towards the Th1, Th2 or Th17 subsets. Mice afflicted with the multiple sclerosis-like condition, experimental autoimmune encephalomyelitis (EAE), were examined in vivo for the relevance of the tissue culture-derived results.</p> <p>Results</p> <p>We report that the biologically active form of vitamin D, 1,25-dihydroxyvitamin D3 {1,25(OH)2D3}, consistently generates human and murine Th2 cells in culture, frequently leaving unchanged the levels of Th1/Th17 cytokines. As a result, the ratio of Th2 to Th1 and Th17 is increased by 1,25(OH)2D3. The upregulation of Th2 to Th1 or Th17 subsets by 1,25(OH)2D3 is enabled by an increase of the GATA-3 transcription factor, which itself is promoted upstream by an elevation of the STAT6 transcription factor. In mice, the alleviation of EAE severity by 1,25(OH)2D3 is accompanied by elevation of levels of GATA-3 and STAT6. Significantly, the efficacy of 1,25(OH)2D3 in ameliorating EAE is completely lost in mice genetically deficient for STAT6, which was accompanied by the inability of 1,25(OH)2D3 to raise GATA-3 in STAT6 null lymphocytes.</p> <p>Conclusions</p> <p>These results of vitamin D promoting a Th2 shift through upstream GATA-3 and STAT6 transcription factors shed mechanistic understanding on the utility of vitamin D in MS.</p