An Inexact Primal-Dual Smoothing Framework for Large-Scale Non-Bilinear Saddle Point Problems

We develop an inexact primal-dual first-order smoothing framework to solve a class of non-bilinear saddle point problems with primal strong convexity. Compared with existing methods, our framework yields a significant improvement over the primal oracle complexity, while it has competitive dual oracle complexity. In addition, we consider the situation where the primal-dual coupling term has a large number of component functions. To efficiently handle this situation, we develop a randomized version of our smoothing framework, which allows the primal and dual sub-problems in each iteration to be solved by randomized algorithms inexactly in expectation. The convergence of this framework is analyzed both in expectation and with high probability. In terms of the primal and dual oracle complexities, this framework significantly improves over its deterministic counterpart. As an important application, we adapt both frameworks for solving convex optimization problems with many functional constraints. To obtain an $\varepsilon$-optimal and $\varepsilon$-feasible solution, both frameworks achieve the best-known oracle complexities (in terms of their dependence on $\varepsilon$)

Second-order Nonlinear Optical Microscopy of Spider Silk

Asymmetric $\rm \beta$-sheet protein structures in spider silk should induce nonlinear optical interaction such as second harmonic generation (SHG) which is experimentally observed for a radial line and dragline spider silk by using an imaging femtosecond laser SHG microscope. By comparing different spider silks, we found that the SHG signal correlates with the existence of the protein $\rm \beta$-sheets. Measurements of the polarization dependence of SHG from the dragline indicated that the $\rm \beta$-sheet has a nonlinear response depending on the direction of the incident electric field. We propose a model of what orientation the $\rm \beta$-sheet takes in spider silk.Comment: 8 pages, 8 figures, 1 tabl

Sum frequency generation spectroscopy of the attachment disc of a spider

The pyriform silk of the attachment disc of a spider was studied using infrared-visible vibrational sum frequency generation (SFG) spectroscopy. The spider can attach dragline and radial lines to many kinds of substrates in nature (concrete, alloy, metal, glass, plant branches, leaves, etc.) with the attachment disc. The adhesion can bear the spider's own weight, and resist the wind on its orb web. From our SFG spectroscopy study, the NH group of arginine side chain and/or NH$_{2}$ group of arginine and glutamine side chain in the amino acid sequence of the attachment silk proteins are suggested to be oriented in the disc. It was inferred from the observed doublet SFG peaks at around 3300 cm$^{-1}$ that the oriented peptide contains two kinds of structures.Comment: 21 pages, 8 figure

A trust and reputation model based on bayesian network for web services

Trust and reputation for web services emerges as an important research issue in web service selection. Current web service trust models either do not integrate different important sources of trust (subjective and objective for example), or do not focus on satisfying different user’s requirements about different quality of service (QoS) attributes such as performance, availability etc. In this paper, we propose a Bayesian network trust and reputation model for web services that can overcome such limitations by considering several factors when assessing web services’ trust: direct opinion from the truster, user rating (subjective view) and QoS monitoring information (objective view). Our comprehensive approach also addresses the problems of users’ preferences and multiple QoSbased trust by specifying different conditions for the Bayesian network and targets at building a reasonable credibility model for the raters of web services

Prion protein lowering is a disease-modifying therapy across prion disease stages, strains and endpoints

Lowering of prion protein (PrP) expression in the brain is a genetically validated therapeutic hypothesis in prion disease. We recently showed that antisense oligonucleotide (ASO)-mediated PrP suppression extends survival and delays disease onset in intracerebrally prion-infected mice in both prophylactic and delayed dosing paradigms. Here, we examine the efficacy of this therapeutic approach across diverse paradigms, varying the dose and dosing regimen, prion strain, treatment timepoint, and examining symptomatic, survival, and biomarker readouts. We recapitulate our previous findings with additional PrP-targeting ASOs, and demonstrate therapeutic benefit against four additional prion strains. We demonstrate that \u3c25% PrP suppression is sufficient to extend survival and delay symptoms in a prophylactic paradigm. Rise in both neuroinflammation and neuronal injury markers can be reversed by a single dose of PrP-lowering ASO administered after the detection of pathological change. Chronic ASO-mediated suppression of PrP beginning at any time up to early signs of neuropathology confers benefit similar to constitutive heterozygous PrP knockout. Remarkably, even after emergence of frank symptoms including weight loss, a single treatment prolongs survival by months in a subset of animals. These results support ASO-mediated PrP lowering, and PrP-lowering therapeutics in general, as a promising path forward against prion disease

Field synergy analysis of pollutant dispersion in street canyons and its optimization by adding wind catchers

The microenvironment, which involves pollutant dispersion of the urban street canyon, is critical to the health of pedestrians and residents. The objectives of this work are twofold: (i) to effectively assess the pollutant dispersion process based on a theory and (ii) to adopt an appropriate stratigy, i.e., wind catcher, to alleviate the pollution in the street canyons. Pollutant dispersion in street canyons is essentially a convective mass transfer process. Because the convective heat transfer process and the mass transfer process are physically similar and the applicability of field synergy theory to turbulence has been verified in the literature, we apply the field synergy theory to the study of pollutant dispersion in street canyons. In this paper, a computational fluid dynamics (CFD) simulation is conducted to investigate the effects of wind catcher, wind speed and the geometry of the street canyons on pollutant dispersion. According to the field synergy theory, Sherwood number and field synergy number are used to quantitatively evaluate the wind catcher and wind speed on the diffusion of pollutants in asymmetric street canyons. The results show that adding wind catchers can significantly improve the air quality of the step-down street canyon and reduce the average pollutant concentrations in the street canyon by 75%. Higher wind speed enhances diffusion of pollutants differently in different geometric street canyons

Characterization of the structure and control of the blood-nerve barrier identifies avenues for therapeutic delivery

The blood barriers of the nervous system protect neural environments but can hinder therapeutic accessibility. The blood-brain barrier (BBB) is well characterized, consisting of endothelial cells with specialized tight junctions and low levels of transcytosis, properties conferred by contacting pericytes and astrocytes. In contrast, the blood-nerve barrier (BNB) of the peripheral nervous system is poorly defined. Here, we characterize the structure of the mammalian BNB, identify the processes that confer barrier function, and demonstrate how the barrier can be opened in response to injury. The homeostatic BNB is leakier than the BBB, which we show is due to higher levels of transcytosis. However, the barrier is reinforced by macrophages that specifically engulf leaked materials, identifying a role for resident macrophages as an important component of the BNB. Finally, we demonstrate the exploitation of these processes to effectively deliver RNA-targeting therapeutics to peripheral nerves, indicating new treatment approaches for nervous system pathologies