The role of the Niemann-Pick disease, type C1 protein in adipocyte insulin action.

The Niemann-Pick disease, type C1 (NPC1) gene encodes a transmembrane protein involved in cholesterol efflux from the lysosome. SNPs within NPC1 have been associated with obesity and type 2 diabetes, and mice heterozygous or null for NPC1 are insulin resistant. However, the molecular mechanism underpinning this association is currently undefined. This study aimed to investigate the effects of inhibiting NPC1 function on insulin action in adipocytes. Both pharmacological and genetic inhibition of NPC1 impaired insulin action. This impairment was evident at the level of insulin signalling and insulin-mediated glucose transport in the short term and decreased GLUT4 expression due to reduced liver X receptor (LXR) transcriptional activity in the long-term. These data show that cholesterol homeostasis through NPC1 plays a crucial role in maintaining insulin action at multiple levels in adipocytes

Cattle grazing mitigates the negative impacts of nitrogen addition on soil nematode communities

Livestock grazing and atmospheric nitrogen (N) deposition have been reported as important factors affecting soil communities. However, how different large herbivore grazing and N addition may interact to affect soil biota in grassland ecosystems is unclear. Nematodes are the most abundant metazoan in soil ecosystems, play critical roles in regulating carbon and nutrient dynamics, and are valuable bioindicators. We examined the independent and interactive effects of grazing regimes (no grazing; sheep grazing; cattle grazing; mixed grazing of sheep and cattle) and N addition (ambient N; N addition) on soil nematodes in a meadow steppe. We found that grazing and N addition interacted to influence total nematode abundance, trophic group abundance, generic richness, diversity and several nematode-based indices (maturity index, channel ratio, enrichment index). In cattle grazing treatment, N addition significantly increased total nematode abundance, and the abundance of bacterial feeders, plant feeders, and omnivore-predators, and generic richness. By contrast, in the sheep and mixed grazing treatments, N addition had a negative effect on the same variables. Moreover, N addition reduced nematode maturity, enrichment and structure indices, and enhanced nematode channel ratio, in most grazing treatments, except mixed grazing where N addition had no effect on these variables. Structural equation modeling (SEM) revealed that N addition indirectly reduced nematode abundance and richness through increased soil NO3−-N content, whereas the effects of grazing were associated with increased relative biomass of grasses. Our results suggested that the response of soil nematodes to N addition strongly depended on herbivore assemblages. Nitrogen addition enhanced soil nematode diversity and maintained a relatively complex and mature soil food web in the presence of cattle rather than sheep grazing. Furthermore, our study highlighted that under N deposition, cattle grazing could benefit the soil nematode community

Understanding and Controlling Angular Momentum Coupled Optical Waves in Chirally-Coupled-Core (CCC) Fibers.

In this dissertation a new type of fiber structure | so called Chirally-Coupled-Core (CCC) fiber | is extensively explored. Work presented here establishes theoretical, numerical and experimental foundations of describing optical phenomena in these novel structures, and provides with methods and tools required to design them. CCC fibers have been a very interesting topic of study due to their unusual symmetry (they are helically symmetric), novel nature of wave interactions within them, and the technological importance of their applications. We have discovered that operation of CCC fibers is based on optical wave interactions that involve both orbital and spin angular momentum of the propagating modes. This is the first and so far the only known example when optical angular momentum is involved in optical interactions. In this thesis we first show experimental evidence of multitude of optical resonances that cannot be explained within the framework of conventional phase-matched interactions. Then we show that these observations can be explained through optical-angular momentum assisted optical interactions of optical waves in these structures. Based on this approach we demonstrate a primary application of CCC structures: large core fibers that perform as effectively single mode fibers. Furthermore, we develop a rigorous theoretical model starting from Maxwell equations in curvilinear helical coordinates to describe CCC fiber properties. We show that theoretically predicted optical-resonance positions agree very well with experimental results. We also address the ultimate core-size scaling potential of effectively -single-mode CCC fibers. Due to the unusual nature of wave interactions in CCC structures all previously known numerical beam-propagation methods appear to be unsuitable for CCC structures. In order to provide with the numerical tools necessary to design and explore these fibers we have developed a new beam-propagation approach, which appears to provide with accurate predictions of CCC fiber performance.Ph.D.Electrical EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/86562/1/xqma_1.pd

Development and validation of a nomogram to predict the prognosis of patients with gastric cardia cancer

Abstract Our goal was to develop a prognostic nomogram to predict overall survival (OS) and cancer-specific survival (CSS) in patients with gastric cardia cancer (GCC). Patients diagnosed with GCC from 2004 to 2015 were screened from the surveillance, epidemiology, and end results (SEER) database. A nomogram was developed based on the variables associated with OS and CSS using multivariate Cox analysis regression models, which predicted 3- and 5-year OS and CSS. The predictive performance of the nomogram was evaluated using the consistency index (C-index), calibration curve and decision curve analysis (DCA), and the nomogram was calibrated for 3- and 5-year OS and CSS. A total of 7,332 GCC patients were identified and randomized into a training cohort (5,231, 70%) and a validation cohort (2,200, 30%). Multivariate Cox regression analysis showed that marital status, race, SEER stage, grade, T stage, N stage, M stage, tumor size, and surgery were independent risk factors for OS and CSS in GCC patients. Based on the multivariate Cox regression results, we constructed prognostic nomograms of OS and CSS. In the training cohort, the C-index for the OS nomogram was 0.714 (95% CI = 0.705–0.723), and the C-index for the CSS nomogram was 0.759 (95% CI = 0.746–0.772). In the validation cohort, the C-index for the OS nomogram was 0.734 (95% CI = 0.721–0.747), while the C-index for the CSS nomogram was 0.780 (95% CI = 0.759–0.801). Our nomogram has better prediction than the nomogram based on TNM stage. In addition, in the training and external validation cohorts, the calibration curves of the nomogram showed good consistency between the predicted and actual 3- and 5-year OS and CSS rates. The nomogram can effectively predict OS and CSS in GCC patients, which may help clinicians personalize prognostic assessments and clinical decisions

Large Mode Area Single Mode Fiber with a Twisted Polygon-Shaped Core

We present numerical studies on twisted polygon-shaped core fibers for achieving single mode operation with a large mode area propagation in this paper. These large mode area fibers can achieve single mode operation due to twisting-induced high losses to higher order modes and coupling higher order modes with leaky modes. A tail-like profile will appear in higher order modes when they couple with leaky modes, and the tail-like profile also indicates that these modes carry angular momentum. Numerical simulations show that twisted octagon-shaped core fiber with a core diameter of 80 μm can obtain first higher order mode losses larger than 19 dB/m while maintaining fundamental mode losses at about 0.15 dB/m. In the case of twisted heptagon-shaped core, an 80 μm diameter fiber design exists with more than 17 dB/m first higher order modes propagation losses and less than 0.14 dB/m fundamental mode losses