The purpose of this study was to study changes in choroidal thickness (ChT) and choroidal blood perfusion (ChBP), and the correlation between them, in guinea pig myopia. METHODS. The reliability of optical coherence tomography angiography (OCTA) for measuring ChT and ChBP was verified in guinea pigs, after cervical dislocation (n ¼ 7) or temporal ciliary artery transection (n ¼ 6). Changes in refraction, axial length, ChT, and ChBP were measured during spontaneous myopia (n ¼ 9), monocular form-deprivation myopia (FDM, n ¼ 13), or lens-induced myopia (LIM, n ¼ 14), and after 4 days of recovery from FDM and LIM. RESULTS. The abolition (by cervical dislocation) or reduction (by temporal ciliary artery transection) of ChBP, and of the associated changes in ChT, were verified by OCTA, thus validating the method of measurement. In the spontaneous myopia group, ChT and ChBP were reduced by 25.2% and 31.9%, respectively. In FDM eyes, mean 6 SD ChT and ChBP decreased significantly compared with the untreated fellow eyes (ChT fellow: 76.13 6 9.34 lm versus 64.76 6 11.15 lm for FDM; ChBP fellow: 37.87 6 6.37 3 10 3 versus 30.27 6 6.06 3 10 3 for FDM) and increased after 4 days of recovery (ChT: 77.94 6 12.57 lm; ChBP: 37.41 6 6.11 3 10 3). Effects of LIM were similar to those of FDM. Interocular differences in ChT and ChBP were significantly correlated in each group (FDM: R ¼ 0.71, P < 0.001; LIM: R ¼ 0.53, P < 0.001). CONCLUSIONS. ChT and ChBP were significantly decreased in all three models of guinea pig myopia, and they both increased during recovery. Changes in ChT were positively correlated with changes in ChBP. Therefore, it is possible that the changes of ChT are responsible for the changes of ChBP or vice versa. Keywords: myopia, choroidal thickness, choroidal blood perfusion, guinea pig M yopia is commonly recognized as an ocular disorder that carries significant risks of visually blinding complications. 1,2 In recent decades, the prevalence and severity of myopia have been on the rise, and it is estimated that by 2050 there will be 4.76 billion people with myopia and 0.94 billion with high myopia. 3-6 Meanwhile, the total cost of myopia correction is also increasing, becoming a relatively large economic burden in urbanized countries. 7-9 With the drastic increase in the public health impact, as well as the socioeconomic burden of myopia, many researchers have focused on investigating the mechanisms underlying myopia development. Twenty years ago, in a seminal study, Wallman et al. found that choroidal thickness (ChT) in chicks significantly increased and decreased in response to positive and negative lens-induced defocus, causing hyperopic and myopic refractive shifts, respectively. 10 On removal of the imposed negative lens defocus, the choroid of the now myopic eye thickened, moving the retina forward toward the defocused image plane. Such bidirectional growth regulation has stimulated researchers to study the choroid as a target tissue for myopia control, and ChT has been investigated as a surrogate marker for...

Abstract. The surveillance and response system remains one of the biggest challenges to malaria elimination along the China-Myanmar border. In China, "1-3-7" approach was developed to guide elimination activities according to the National Malaria Elimination Program, which is a simplified set of targets that delineates responsibilities and actions. The time frame of the approach has been incorporated into the nationwide web-based disease reporting system: 1, case reporting within 1 day after diagnosis; 3, case investigation within 3 days; and 7, focus investigation and action within 7 days. Herein, the data on malaria cases in 2005-2014 and after the "1-3-7" implementation in 2013-2014 of the 18 counties at the China-Myanmar border are reviewed and analyzed. Results showed that the total cases decreased while the proportion of imported cases rose. The "1-3-7" was well executed, except for the "3" indicator, which was 96.3% accomplished on average in the 18 border counties, but needs to be further strengthened. More efforts are highlighted for timely and accurate case detection as well as proactive mapping of disease transmission hot spots to facilitate the elimination of border malaria.

Discs large (Dlg) is an essential polarity protein and a tumor suppressor originally characterized in Drosophila but is also well conserved in vertebrates. Like the majority of polarity proteins, plasma membrane (PM)/cortical localization of Dlg is required for its function in polarity and tumorigenesis, but the exact mechanisms targeting Dlg to PM remain to be fully elucidated. Here we show that, similar to the recently discovered polybasic polarity proteins such as Lgl and aPKC, Dlg also contains a positively charged polybasic domain that electrostatically binds the PM phosphoinositides PI4P and PI(4,5)P2. Electrostatic targeting by the polybasic domain contributes significantly to the PM localization of Dlg in follicular and early embryonic epithelial cells, and is crucial for Dlg to regulate both polarity and tumorigenesis. The electrostatic PM targeting of Dlg is controlled by a potential phosphorylation-dependent allosteric regulation of its polybasic domain, and is specifically enhanced by the interactions between Dlg and another basolateral polarity protein and tumor suppressor Scrib. Our studies highlight an increasingly significant role of electrostatic PM targeting of polarity proteins in regulating cell polarity.

Malicious insiders pose significant threats to information security, and yet the capability of detecting malicious insiders is very limited. Insider threat detection is known to be a difficult problem, presenting many research challenges. In this paper we report our effort on detecting malicious insiders from large amounts of work practice data. We propose novel approaches to detect two types of insider activities: (1) blendin anomalies, where malicious insiders try to behave similar to a group they do not belong to, and (2) unusual change anomalies, where malicious insiders exhibit changes in their behavior that are dissimilar to their peers' behavioral changes. Our first contribution focuses on detecting blend-in malicious insiders. We propose a novel approach by examining various activity domains, and detecting behavioral inconsistencies across these domains. Our second contribution is a method for detecting insiders with unusual changes in behavior. The key strength of this proposed approach is that it avoids flagging common changes that can be mistakenly detected by typical temporal anomaly detection mechanisms. Our third contribution is a method that combines anomaly indicators from multiple sources of information.

Mechanisms coupling the atypical PKC (aPKC) kinase activity to its subcellular localization are essential for cell polarization. Unlike other members of the PKC family, aPKC has no well-defined plasma membrane (PM) or calcium binding domains, leading to the assumption that its subcellular localization relies exclusively on protein–protein interactions. Here we show that in both Drosophila and mammalian cells, the pseudosubstrate region (PSr) of aPKC acts as a polybasic domain capable of targeting aPKC to the PM via electrostatic binding to PM PI4P and PI(4,5)P2. However, physical interaction between aPKC and Par-6 is required for the PM-targeting of aPKC, likely by allosterically exposing the PSr to bind PM. Binding of Par-6 also inhibits aPKC kinase activity, and such inhibition can be relieved through Par-6 interaction with apical polarity protein Crumbs. Our data suggest a potential mechanism in which allosteric regulation of polybasic PSr by Par-6 couples the control of both aPKC subcellular localization and spatial activation of its kinase activity.

Ocotillol-type saponins are one kind of tetracyclic triterpenoids, sharing a tetrahydrofuran ring. Natural ocotillol-type saponins have been discovered in Panax quinquefolius L., Panax japonicus, Hana mina, and Vietnamese ginseng. In recent years, the semisynthesis of 20(S/R)-ocotillol-type saponins has been reported. The biological activities of ocotillol-type saponins include neuroprotective effect, antimyocardial ischemia, antiinflammatory, antibacterial, and antitumor activities. Owing to their chemical structure, pharmacological actions, and the stereoselective activity on antimyocardial ischemia, ocotillol-type saponins are subjected to extensive consideration. In this review, we sum up the discovery, semisynthesis, biological activities, and metabolism of ocotillol-type saponins.

Mechanisms coupling the atypical PKC (aPKC) kinase activity to its subcellular localization are essential for regulating cell polarization but remain to be fully elucidated. Unlike other members of the PKC family, aPKC has no well-defined or calcium binding domains, leading to the assumption that its subcellular localization relies exclusively on protein-protein interactions. Here we show that in both Drosophila and mammalian cells the pseudosubstrate region (PSr) of aPKC acts as a polybasic domain sufficient to target aPKC to the plasma membrane (PM) via electrostatic binding to PM phosphoinositides. PM-targeting of aPKC requires the physical interaction between the N-terminal PB1 domains in both aPKC and Par-6, which not only allosterically exposes PSr to PM-binding, but also inhibits aPKC kinase activity.Such kinase inhibition requires the C-terminal domain of Par-6 and can be relieved through Par-6 interaction with apical polarity protein Crumbs. Our data suggest a mechanism in which allosteric regulation of polybasic PSr in aPKC by Par-6 couples the control of both aPKC subcellular localization and spatial activation of its kinase activity.3

Real-time recognition of walking-related activities is an important function that lower extremity assistive devices should possess. This article presents a real-time walking pattern recognition method for soft knee power assist wear. The recognition method employs the rotation angles of thighs and shanks as well as the knee joint angles collected by the inertial measurement units as input signals and adopts the rule-based classification algorithm to achieve the real-time recognition of three most common walking patterns, that is, level-ground walking, stair ascent, and stair descent. To evaluate the recognition performance, 18 subjects are recruited in the experiments. During the experiments, subjects wear the knee power assist wear and carry out a series of walking activities in an out-of-lab scenario. The results show that the average recognition accuracy of three walking patterns reaches 98.2%, and the average recognition delay of all transitions is slightly less than one step.