Principal-Agent Problem with Third Party: Information Design from Social Planner's Perspective

We study the principal-agent problem with a third party that we call social planner, whose responsibility is to reconcile the conflicts of interest between the two players and induce socially optimal outcome in terms of some given social utility function. The social planner owns no contractual power but manages to control the information flow between the principal and the agent. We design a simple workflow with two stages for the social planner. In the first stage, the problem is reformulated as an optimization problem whose solution is the optimal utility profile. In the second stage, we investigate information design and show that binary-signal information structure suffices to induce the socially optimal outcome determined in the first stage. The result shows that information plays a key role in social planning in the principal-agent model

Optical Manipulation and Sensing with Silicon Photonics

Optical trapping enables the non-contact manipulation of micro and nanoparticles with extremely high precision. Recent research on integrated optical trapping using the evanescent fields of photonic devices has opened up new opportunities for the manipulation of nano- and microparticles in lab-on-a-chip devices. Considerable interest has emerged for the use of optical microcavities as “sensors-on-a-chip”, due to the possibility for the label-free detection of nanoparticles and molecules with high sensitivity. This dissertation focuses on the demonstration of an on-chip optical manipulation system with multiple functionalities, including trapping, buffering, sorting, and sensing. We demonstrate the optically trapping of polystyrene particles with diameters from 110 nm to 5.6 $\mu m$ using silicon microrings and photonic crystal cavities. By integrating multiple microrings with different resonant wavelengths, we show that tuning the laser wavelength to the resonance wavelengths of different rings enables trapped particles to be transferred back and forth between the rings in a controllable manner. We term this functionality “buffering”. We furthermore demonstrate an integrated microparticle passive sorting system based on the near-field optical forces exerted by a 3-dB optical power splitter that consists of a slot waveguide and a conventional channel waveguide. In related work, we demonstrate an ultra-compact polarization splitter design leveraging the giant birefringence of silicon-on-insulator slot waveguides to achieve a high extinction ratio over the entire C band. We demonstrate trapping-assisted particle sensing, using the shift in the microcavity resonance induced by the trapped particle. We show that this permits the sensing of proteins via a binding assay approach, in which the presence of green fluorescent protein causes the particles to bind. By detecting the size distribution of particles clusters using the microcavity, we quantitatively detect the GFP concentration. In a complementary approach, we demonstrate a reusable and reconfigurable surface-enhanced Raman scattering (SERS) sensing platform. We use a photonic crystal cavity to trap silver nanoparticles in a controllable manner, and measure SERS from molecules on their surfaces. We anticipate that the on-chip sensing approaches we introduce could lead to various applications in nanotechnology and the environmental and life sciences.Engineering and Applied Science

14-3-3τ Regulates Beclin 1 and Is Required for Autophagy

Beclin 1 plays an essential role in autophagy; however, the regulation of Beclin 1 expression remains largely unexplored. An earlier ChIP-on-chip study suggested Beclin 1 could be an E2F target. Previously, we also reported that 14-3-3tau regulates E2F1 stability, and is required for the expression of several E2F1 target genes. 14-3-3 proteins mediate many cellular signaling processes, but its role in autophagy has not been investigated. We hypothesize that 14-3-3tau could regulate Beclin 1 expression through E2F1 and thus regulate autophagy.Using the RNAi technique we demonstrate a novel role for one of 14-3-3 isoforms, 14-3-3tau, in the regulation of Beclin 1 expression and autophagy. Depletion of 14-3-3tau inhibits the expression of Beclin 1 in many different cell lines; whereas, upregulation of 14-3-3tau induces Beclin 1. The regulation is physiologically relevant as an extracellular matrix protein tenascin-C, a known 14-3-3tau inducer, can induce Beclin 1 through 14-3-3tau. Moreover, rapamycin-induced, serum free-induced and amino acid starvation-induced autophagy depends on 14-3-3tau. We also show the expression of Beclin 1 depends on E2F, and E2F can transactivate the Beclin 1 promoter in a promoter reporter assay. Upregulation of Beclin 1 by 14-3-3tau requires E2F1. Depletion of E2F1, like 14-3-3tau, also inhibits autophagy.Taken together, this study uncovers a role for 14-3-3tau in Beclin 1 and autophagy regulation probably through regulation of E2F1

Association between ambient air pollution and hospital admissions, length of hospital stay and hospital cost for patients with cardiovascular diseases and comorbid diabetes mellitus: Base on 1,969,755 cases in Beijing, China, 2014–2019

Background: Evidence on the effects of the air pollutants on the hospital admissions, hospital cost and length of stay (LOS) among patients with comorbidities remains limited in China, particularly for patients with cardiovascular diseases and comorbid diabetes mellitus (CVD-DM). Methods: We collected daily data on CVD-DM patients from 242 hospitals in Beijing between 2014 and 2019. Generalized additive model was employed to quantify the associations between admissions, LOS, and hospital cost for CVD-DM patients and air pollutants. We further evaluated the attributable risk posed by air pollutants to CVD-DM patients, using both Chinese and WHO air quality guidelines as reference. Results: Per 10 ug/m3 increase of particles with an aerodynamic diameter \u3c 2.5 μm (PM2.5), particles with an aerodynamic diameter \u3c 10 μm (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), carbonic oxide (CO) and ozone (O3) corresponded to a 0.64% (95% CI: 0.57 to 0.71), 0.52% (95% CI: 0.46 to 0.57), 0.93% (95% CI: 0.67 to 1.20), 0.98% (95% CI: 0.81 to 1.16), 1.66% (95% CI: 1.18 to 2.14) and 0.53% (95% CI: 0.45 to 0.61) increment for CVD-DM patients’ admissions. Among the six pollutants, particulate pollutants (PM2.5 and PM10) in most lag days exhibited adverse effects on LOS and hospital cost. For every 10 ug/m3 increase in PM2.5 and PM10, the absolute increase with LOS will increase 62.08 days (95% CI: 28.93 to 95.23) and 51.77 days (95% CI:22.88 to 80.66), respectively. The absolute increase with hospital cost will increase 105.04 Chinese Yuan (CNY) (95% CI: 49.27 to 160.81) and 81.76 CNY (95% CI: 42.01 to 121.51) in PM2.5 and PM10, respectively. Given WHO 2021 air quality guideline as the reference, PM2.5 had the maximum attributable fraction of 3.34% (95% CI: 2.94% to 3.75%), corresponding to an avoidable of 65,845 (95% CI: 57,953 to 73,812) patients with CVD-DM. Conclusion: PM2.5 and PM10 are positively associated with hospital admissions, hospital cost and LOS for patients with CVD-DM. Policy changes to reduce air pollutants exposure may reduce CVD-DM admissions and substantial savings in health care spending and LOS

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment