Gated multi-cycle integration (GMCI) for focal plane array (FPA) applications

In this thesis, the model and the theory of gated multi-cycle integration (GMCI) were first developed specifically for focal plane array dealing with repetitive or modulated image. The operational modes of GMCI include gated integration (GI), phase sensitive integration (PSI), multi-point summation, multi-point subtraction, multi-sample averaging and some of their combinations. Thus, the analytic theory of GMCI somehow unifies the theories of gated integration, phase sensitive detection, multiple summation and average. PSI works with background and/or dark current subtraction. As a result, the storage well of a pixel is mainly used for signal integration even if there exists a strong background. Thus, the signal-to-noise ratio, the dynamic range, the sensitivity of the detection and the noise equivalent temperature are greatly improved. For a storage well of 106 electrons, the sensitivity of the FPA operated at PSI mode could be improved by 3 orders. In addition, the transmission windows of PSI peak at odd harmonics of the modulation frequency, and therefore, the detector\u27s IN and other low frequency noise can be attenuated. A switched capacitor integrator was designed and fabricated with HP-0.5gm CMOS processing to demonstrate the feasibility of GMCI. The primary experimental results showed that the minimum detectable signal could be 5 orders less than the background, which is impossible for the conventional readout methods employed by current staring FPAs. The fixed patterns associated with switching charge injection, feedthrough, offset voltage of operational amplifier were addressed and suppressed by taking the differentia of two sampled voltages that correspond to signal integrations with 180° phase difference while keeping the same fixed pattern. GMCI, operated at PSI with multiple averages, is expected to become a powerful method in dealing with repetitive weak image swamped by strong background

Forest plot of the hazard ratio (HR) for the association of YAP1 expression with disease-free survival. (Random-effects model).

<p>The HRs of individual studies are shown as squares, with the size proportional to the weight of each study in the overall estimate; 95% CIs are shown as horizontal lines. The pooled HRs and their 95% CIs are shown as a dashed vertical line and a diamond, respectively.</p

Prognostic Value of Yes-Associated Protein 1 (YAP1) in Various Cancers: A Meta-Analysis

<div><p>Background</p><p>Yes-associated protein 1 (YAP1) is an effector of Hippo pathway, which is critical for regulating organ size, cell proliferation and tumor growth in mammals. Many previous studies have explored the relationship between YAP1 and various types of cancer. However, these studies were limited by the small samples size and the findings were inconsistent among them. Therefore, a meta-analysis was conducted to assess the association between YAP1 and malignancies.</p><p>Methods</p><p>A systematic literature search was conducted for eligible studies in the PubMed, Corchane Library, Web of Knowledge, EMBASE and CBM disc databases from inception to August 1^st 2014. After heterogeneity analysis, pooled harzad ratio (<i>HR</i>) with 95% confidence interval (95%<i>CI</i>) using both fixed and random effect models were estimated in STATA 10.0. Meta regression analysis, subgroup analysis and sensitivity analysis were performed to explore the potential sources of heterogeneity and to evaluate the robustness of the result. Publication bias was assessed by Egger’s test and funnel plot.</p><p>Results</p><p>A total of 21 unique articles from 2009 to 2014, comprising 2983 patients, were analyzed in the meta-analysis. The association of YAP1 expression and overall survival time (OS) was evaluated in 20 studies including 2067 patients. Positive YAP1 showed poorer OS (HR = 1.826; 95% CI = 1.465–2.275; <i>p</i> <0.002). For evaluating disease-free survival time (DFS), 10 studies with 1139 patients were analyzed. Positive YAP1 indicated worse DFS (HR = 2.114; 95%CI = 1.406–3.179; <i>p</i> <0.001). Subgroup analysis showed that both positive nuclear YAP1 (HR = 1.390, 95% CI: 0.810–2.400, <i>p</i> = 0.729) and up-regulation overall YAP1 (HR = 2.237, 95% CI: 1.548–3.232, <i>p</i> <0.001) had poorer OS for patients with malignancies. Similarly, both positive nuclear YAP1 (HR = 3.733, 95% CI: 1.469–9.483, <i>p</i> = 0.001) and up-regulation overall YAP1 (HR = 1.481, 95% CI: 1.163–1.886, <i>p</i> = 0.554) showed worse DFS. The patients with urogenital system cancer had the poorest OS (HR = 2.133, 95% CI: 1.549–2.937, <i>p</i> = 0.020). The patients with alimentary system cancer had the most significant impact on DFS (HR = 1.879, 95% CI: 1.537–2.297, <i>p</i> <0.001).</p><p>Conclusion</p><p>Both overall and nuclear YAP1 overexpression are intimately associated with adverse OS and DFS in numerous cancers, suggesting that YAP1 may act as a potential therapeutic targets of these malignancies in the future.</p></div

Sensitivity analysis based on stepwise omitting one study at a time for Disease-free survival

<p>Sensitivity analysis based on stepwise omitting one study at a time for Disease-free survival</p

Results of overall and subgroup analyses for effects of YAP1 expression on overall and disease-free survival in cancer.

<p>Note: <i>P</i>^a for Z test, <i>P</i>^b for <i>x</i>²-based Q test, N: number of studies include, Heterogeneity test: Q, df, Pb, I2 and 95%CI for I2.</p

Characteristics of studies included in the meta-analysis for DFS.

<p>*: read from survial curves</p><p>Note: No.: Number of patients for survial analysis; T: Depth of invasion; N: lymph node metastasis; M: distant metastasis, G:Histological differentiation, well differentiated (G1), moderately differentiated (G2), poorly differentiated (G3), undifferentiated (G4);</p

Forest plot of the hazard ratio (HR) for the association of YAP1 expression with disease-free survival. (Random-effects model).

<p>The HRs of individual studies are shown as squares, with the size proportional to the weight of each study in the overall estimate; 95% CIs are shown as horizontal lines. The pooled HRs and their 95% CIs are shown as a dashed vertical line and a diamond, respectively.</p

Sensitivity analysis based on stepwise omitting one study at a time for overall survival.

<p>Sensitivity analysis based on stepwise omitting one study at a time for overall survival.</p

Begg’s funnel plot for the evaluation of potential publication bias on overall estimate of overall survival.

<p>The vertical line in the funnel plot indicates the random-effects summary estimate, while the sloping lines indicate the expected 95% confidence intervals for a given standard error, assuming no heterogeneity between studies. Each study is represented by a circle.</p

Forest plot of the hazard ratio (HR) for the association of YAP1 expression with overall survival. (Random-effects model).

<p>The HRs of individual studies are shown as squares, with the size proportional to the weight of each study in the overall estimate; 95% CIs are shown as horizontal lines. The pooled HRs and their 95% CIs are shown as a dashed vertical line and a diamond, respectively.</p