Repression of glucocorticoid-stimulated angiopoietin-like 4 gene transcription by insulin.

Angiopoietin-like 4 (Angptl4) is a glucocorticoid receptor (GR) primary target gene in hepatocytes and adipocytes. It encodes a secreted protein that inhibits extracellular LPL and promotes adipocyte lipolysis. In Angptl4 null mice, glucocorticoid-induced adipocyte lipolysis and hepatic steatosis are compromised. Markedly, insulin suppressed glucocorticoid-induced Angptl4 transcription. To unravel the mechanism, we utilized small molecules to inhibit insulin signaling components and found that phosphatidylinositol 3-kinase and Akt were vital for the suppression in H4IIE cells. A forkhead box transcription factor response element (FRE) was found near the 15 bp Angptl4 glucocorticoid response element (GRE). Mutating the Angptl4 FRE significantly reduced glucocorticoid-induced reporter gene expression in cells. Moreover, chromatin immunoprecipitation revealed that GR and FoxO1 were recruited to Angptl4 GRE and FRE in a glucocorticoid-dependent manner, and cotreatment with insulin abolished both recruitments. Furthermore, in 24 h fasted mice, significant occupancy of GR and FoxO1 at the Angptl4 GRE and FRE was found in the liver. In contrast, both occupancies were diminished after 24 h refeeding. Finally, overexpression of dominant negative FoxO1 mutant abolished glucocorticoid-induced Angptl4 expression, mimicking the insulin suppression. Overall, we demonstrate that both GR and FoxO1 are required for Angptl4 transcription activation, and that FoxO1 negatively mediates the suppressive effect of insulin

STING-mediated disruption of calcium homeostasis chronically activates ER stress and primes T cell death

STING gain-of-function mutations cause lung disease and T cell cytopenia through unknown mechanisms. Here, we found that these mutants induce chronic activation of ER stress and unfolded protein response (UPR), leading to T cell death by apoptosis in th

Broadband energy-efficient optical modulation by hybrid integration of silicon nanophotonics and organic electro-optic polymer

Silicon-organic hybrid integrated devices have emerging applications ranging from high-speed optical interconnects to photonic electromagnetic-field sensors. Silicon slot photonic crystal waveguides (PCWs) filled with electro-optic (EO) polymers combine the slow-light effect in PCWs with the high polarizability of EO polymers, which promises the realization of high-performance optical modulators. In this paper, a broadband, power-efficient, low-dispersion, and compact optical modulator based on an EO polymer filled silicon slot PCW is presented. A small voltage-length product of V{\pi}*L=0.282Vmm is achieved, corresponding to an unprecedented record-high effective in-device EO coefficient (r33) of 1230pm/V. Assisted by a backside gate voltage, the modulation response up to 50GHz is observed, with a 3-dB bandwidth of 15GHz, and the estimated energy consumption is 94.4fJ/bit at 10Gbit/s. Furthermore, lattice-shifted PCWs are utilized to enhance the optical bandwidth by a factor of ~10X over other modulators based on non-band-engineered PCWs and ring-resonators.Comment: 12 pages, 4 figures, SPIE Photonics West Conference 201

The design and evaluation of multilingual social media portal: Working paper series--11-09

Web 2.0 has created a large amount of user-generated content from online social media such as forums, blogs, social-networking sites, etc. As a result, the volume of social media data has been growing exponentially. Such user-generated data contains valuable information about people's ideas and opinions toward products, services or social/political issues. However, certain issues related to social media data, including data integration and multilingual issues, are difficult to analyze with this type of data. This paper develops a general framework of social media portals. It can collect and incorporate data from heterogeneous social media sites, and provide unified data integration, search, and multilingual translation supports. To evaluate the performance of the proposed framework, a prototype system, the Dark Web Forums Portal, is built using social media from homeland security-related data sources. The user evaluation results show that, compared with alternative ways of searching and understanding multilingual social media content, the portal can help users locate information more quickly and effectively. Users also perceived significantly higher system quality, ease of use, usefulness, satisfaction, intention to use when using the portal. The results demonstrated the advancement of the proposed system framework

Long-term follow-up of patients with surgical intractable acromegaly after linear accelerator radiosurgery

Background/PurposeRadiotherapy is a crucial treatment for acromegalic patients with growth hormone (GH)-secreting pituitary tumors. However, its effect takes time. We retrospectively reviewed the long-term outcome of linear accelerator stereotactic radiosurgery (LINAC SRS) for patients with acromegaly from the perspective of biochemical remission and associated factors.MethodsTwenty-two patients presenting with residual or recurrent (GH)-secreting functional pituitary tumor between 1994 and 2004 who received LINAC SRS were enrolled and followed up for at least 3 years. Residual or recurrent tumor was defined as persistent elevated GH or insulin-like growth factor-1 (IGF-1) level and image-confirmed tumor after previous surgical treatment. Biochemical remission was defined as fasting GH less than 2.5 ng/mL with normal sex-and-age adjusted IGF-1.ResultsThe mean follow-up period was 94.7 months (range 36–161 months). Overall mean biochemical remission time was 53 months (median 30 months). Biochemical control was achieved in 15 patients (68.2%) over the follow up period. One patient experienced recurrence after SRS and underwent another operation. Initial GH at diagnosis and pre-SRS GH correlated with biochemical control (p = 0.005 and p < 0.0001, respectively). Further evaluation demonstrated that biochemical control stabilized after 7.5 years. Overall post-SRS hormone deficit persisted in five patients (22.7%).ConclusionIn comparison to other radiosurgery modalities, LINAC radiosurgery also provides a satisfactory outcome. SRS has maximum effect over the first 2 years and stabilizes after 7.5 years. Moreover, SRS elicits long-term biochemical effects and requires longer follow-up for better biochemical remission

De-wetting of evaporating drops on regular patterns of triangular posts

Directional wicking and spreading of liquids can be achieved by regular micro-patterns of specifically designed topographic features that break the reflection symmetry of the underlying pattern. The present study aims to understand the formation and stability of wetting films during the evaporation of volatile liquid drops on surfaces with a micro-pattern of triangular posts arranged in a rectangular lattice. Depending on the density and aspect ratio of the posts, we observe either spherical-cap shaped drops with a mobile three-phase contact line or the formation of circular or angular drops with a pinned three-phase contact line. Drops of the latter class eventually evolve into a liquid film extending to the initial footprint of the drop and a shrinking cap-shaped drop sitting on the film. The drop evolution is controlled by the density and aspect ratio of the posts, while no influence of the orientation of the triangular posts on the contact line mobility becomes evident. Our experiments corroborate previous results of systematic numerical energy minimization, predicting that conditions for a spontaneous retraction of a wicking liquid film depend weakly on the orientation of the film edge relative to the micro-pattern

Kinerja Sistem Komunikasi FSO (Free Space Optics) Menggunakan Cell-site Diversity Di Daerah Tropis

Kebutuhan masyarakat akan adanya layanan komunikasi multimedia seperti video conference, high speed internet, video streaming, dan lain sebagainya, saat ini terus meningkat. Untuk memenuhi kebutuhan tersebut, perlu adanya suatu sistem komunikasi nirkabel dengan kecepatan tinggi. Salah satunya yaitu dengan menggunakan FSO (Free Space Optics). FSO merupakan sistem komunikasi yang memungkinkan memiliki koneksi layaknya serat optik, namun media transmisi yang digunakan yaitu melalui atmosfer. Penggunaan FSO di daerah tropis memiliki kendala yang cukup serius yaitu tingginya intensitas curah hujan yang dapat mempengaruhi kinerja dari FSO. Semakin tinggi intensitas curah hujan, maka nilai redaman hujan juga semakin besar. Untuk mengatasi dampak redaman hujan tersebut, maka digunakan teknik cell-site diversity dengan selection combining. Penerapan teknik cell-site diversity pada sistem komunikasi FSO menggunakan variasi panjang lintasan 0,5 km, 1 km, 1,5 km, dan 2 km serta variasi sudut antar link sebesar 45°, 90°, 135°, dan 180°. Hasil dari penerapan teknik cell-site diversity menunjukkan bahwa adanya peningkatan kualitas sinyal FSO, dalam hal ini yaitu nilai SNR. Peningkatan nilai SNR terbesar didapatkan pada panjang lintasan 2 km dengan sudut antar link 180° serta pada link availability 99,9 %. Untuk konfigurasi cell-site diversity terbaik didapatkan pada sudut antar link sebesar 90° dan 180°

Dynamic Transcript Profiling of Candida Albicans Infection in Zebrafish: a Pathogen-Host Interaction Study

Candida albicans is responsible for a number of life-threatening infections and causes considerable morbidity and mortality in immunocompromised patients. Previous studies of C. albicans pathogenesis have suggested several steps must occur before virulent infection, including early adhesion, invasion, and late tissue damage. However, the mechanism that triggers C. albicans transformation from yeast to hyphae form during infection has yet to be fully elucidated. This study used a systems biology approach to investigate C. albicans infection in zebrafish. The surviving fish were sampled at different post-infection time points to obtain time-lapsed, genome-wide transcriptomic data from both organisms, which were accompanied with in sync histological analyses. Principal component analysis (PCA) was used to analyze the dynamic gene expression profiles of significant variations in both C. albicans and zebrafish. The results categorized C. albicans infection into three progressing phases: adhesion, invasion, and damage. Such findings were highly supported by the corresponding histological analysis. Furthermore, the dynamic interspecies transcript profiling revealed that C. albicans activated its filamentous formation during invasion and the iron scavenging functions during the damage phases, whereas zebrafish ceased its iron homeostasis function following massive hemorrhage during the later stages of infection. This was followed by massive hemorrhaging toward the end stage of infection. Most of the immune related genes were expressed as the infection progressed from invasion to the damage phase. Such global, inter-species evidence of virulence-immune and iron competition dynamics during C. albicans infection could be crucial in understanding control fungal pathogenesis