Richard H. Bruce

Liveboard: a large interactive display supporting group meetings, presentations, and remote collaboration

This paper describes the Liveboard, a large interactive display system. With nearly one million pixels and an accurate, multi-state, cordless pen, the Liveboard provides a basis for research on user interfaces for group meetings, presentations and remote collaboration. We describe the underlying hardware and software of the Liveboard, along with several software applications that have been developed. In describing the system, we point out the design rationale that was used to make various choices. We present the results of an informal survey of Liveboard users, and describe some of the improvements that have been made in response to user feedback. We conclude with several general observations about the use of large public interactive displays.

Cytomorphology of circulating colorectal tumor cells:a small case series.

Several methodologies exist to enumerate circulating tumor cells (CTCs) from the blood of cancer patients; however, most methodologies lack high-resolution imaging, and thus, little is known about the cytomorphologic features of these cells. In this study of metastatic colorectal cancer patients, we used immunofluorescent staining with fiber-optic array scanning technology to identify CTCs, with subsequent Wright-Giemsa and Papanicolau staining. The CTCs were compared to the corresponding primary and metastatic tumors. The colorectal CTCs showed marked intrapatient pleomorphism. In comparison to the corresponding tissue biopsies, cells from all sites showed similar pleomorphism, demonstrating that colorectal CTCs retain the pleomorphism present in regions of solid growth. They also often retain particular cytomorphologic features present in the patients primary and/or metastatic tumor tissue. This study provides an initial analysis of the cytomorphologic features of circulating colon cancer cells, providing a foundation for further investigation into the significance and metastatic potential of CTCs.

Multiple Biomarker Expression on Circulating Tumor Cells in Comparison to Tumor Tissues from Primary and Metastatic Sites in Patients with Locally Advanced/Inflammatory, and Stage IV Breast Cancer, Using a Novel Detection Technology

Patients with locally advanced/inflammatory breast cancer (LABC/IBC) face a high likelyhood of recurrence and prognosis for relapsed, or de novo stage IV metastatic breast cancer (MBC) remains poor. Estrogen (ER) and HER2 receptor expression on primary or MBC allow targeted therapies, but an estimated 10–18% of tumors do not exhibit these biomarkers and survival in these cases is even poorer. Variations in discordance rates for the expression of ER and HER2 receptors have been observed between primary and metastatic tumors and such discordances may lead to suboptimal treatment. Circulating tumor cells (CTCs) are considered the seeds of residual disease and distant metastases and their characterization could help guide treatment selection. To explore this possibility, we used multiple biomarker assessment of CTCs in comparison to primary and metastatic tumor sites. Thirty-six patients with LABC/IBC, or stage IV MBC were evaluated. Blood samples were procured prior to initiating or changing therapy. CTCs were identified based on presence of cytokeratin and nucleus staining, and the absence of CD45. A multimarker assay was developed to simultaneously quantify expression of HER2, ER, and ERCC1, a DNA excision repair protein. Novel fiber-optic array scanning technology (FAST) was used for sensitive location of CTCs. CTCs were detected in 82% of MBC and 62% LABC/IBC cases. Multiplex marker expression was successfully carried out in samples from18 patients with MBC and in 8 patients with LABC/IBC that contained CTCs. In MBC, we detected actionable discordance rates of 40 and 23%, respectively for ER and HER2 where a biomarker was negative in the primary or metastatic tumor and positive in the CTCs. In LABC/IBC, actionable discordances were 60 and 20% for ER and HER2, respectively. Pilot trials evaluating the effectiveness of treatment selections based on actionable discordances between biomarker expression patterns on CTCs and primary or metastatic tumor sites may allow for a prospective assessment of CTC-based individualized targeted therapies.

Effects of frequency on optical emission, electrical, ion, and etching characteristics of a radio frequency chlorine plasma

The effects of excitation frequency (10 kHz–25 MHz) on plasma etching, voltage‐current characteristics, emission spectra, and ion densities and energies in the sheath of chlorine plasmas, have been studied at 0.3 Torr using several techniques. Emission spectra and mass spectral analysis of ions extracted from the sheath region show a dramatic increase in the Cl+ signal as frequency is lowered through the ion–transit frequency near ∼1 MHz. Concurrently, the voltage at constant power and energy of ions impinging on the electrodes increase dramatically, while the etch rate of poly‐Si increases due to ion‐enhanced reactions. The Cl+2 ion density and degree of Cl2 dissociation to Cl atoms were found to be roughly frequency independent.

Higher Throughput Calorimetry: Opportunities, Approaches and Challenges

Higher throughput thermodynamic measurements can provide value in structure-based drug discovery during fragment screening, hit validation, and lead optimization. Enthalpy can be used to detect and characterize ligand binding, and changes that affect the interaction of protein and ligand can sometimes be detected more readily from changes in the enthalpy of binding than from the corresponding free-energy changes or from protein-ligand structures. Newer, higher throughput calorimeters are being incorporated into the drug discovery process. Improvements in titration calorimeters come from extensions of a mature technology and face limitations in scaling. Conversely, array calorimetry, an emerging technology, shows promise for substantial improvements in throughput and material utilization, but improved sensitivity is needed.

Polysilicon TFT circuit design and performance

Both n- and p-channel polysilicon TFTs can be fabricated, allowing CMOS circuit techniques to be used. However, TFT characteristics are poor in comparison to conventional single-crystal MOSFETs, and relatively coarse design rules must be used to be compatible with processing on large-area glass plates. The authors examine these issues and describe the performance of a range of digital and analog circuit elements built using polysilicon TFTs. Digital circuit speeds in excess of 20 MHz are reported, along with operational amplifiers with over 80 dB of gain and more than 1-MHz unity-gain frequency. Several polysilicon TFT switched-capacitor circuits are also reported and shown to have adequate linearity, output swing, and settling time to form integrated data line drivers on an active-matrix liquid crystal display. >

Enthalpy array analysis of enzymatic and binding reactions

Enthalpy arrays enable label-free, solution-based calorimetric detection of molecular interactions in a 96-detector array format. The combination of the small size of the detectors and the ability to perform measurements in parallel results in a significant reduction of sample volume and measurement time compared with conventional calorimetry. We have made significant improvements in the technology by reducing the temperature noise of the detectors and improving the fabrication materials and methods. In combination with an automated measurement system, the advances in device performance and data analysis have allowed us to develop basic enzyme assays for substrate specificity and inhibitor activity. We have also performed a full titration of 18-crown-6 with barium chloride. These results point to future applications for enthalpy array technology, including fragment-based screening, secondary assays, and thermodynamic characterization of leads in drug discovery.

Circulating Tumor Cells From Well-Differentiated Lung Adenocarcinoma Retain Cytomorphologic Features of Primary Tumor Type

The detailed cytomorphologic appearance of circulating tumor cells (CTCs) in cancer patients is not well described, despite publication of multiple methods for enumerating these cells. In this case study, we present the cytomorphology of CTCs obtained from the blood of a woman with stage IIIB well-differentiated lung adenocarcinoma. Four years after she was diagnosed with her disease, 67 CTCs were identified in a blood sample using an immunofluorescent staining protocol and then subsequently stained with Wright-Giemsa. The cytomorphology of the CTCs was compared with the original tissue biopsy from 4 years prior. We found that CTCs and cells from the original biopsy had strikingly similar morphologic features, including large size in comparison to white blood cells and low nuclear to cytoplasmic ratios with voluminous cytoplasm. Careful cytomorphologic evaluation of CTCs will provide insights about the metastatic significance of these cells, which could yield widespread implications for the diagnosis, treatment, and management of cancer.

A simpler 100-V polysilicon TFT with improved turn-on characteristics

An improved polysilicon high-voltage thin-film transistor (HVTFT) structure for eliminating the current-pinching phenomenon often observed in the conventional offset-gate polysilicon HVTFTs is discussed. The device employs, in lieu of implantation, a metal field plate overlapping the entire offset region to control the conductivity of the offset region. By properly biasing the field plate to distribute the drain electric field at both ends, high-voltage operation of up to 100 V, suitable for many large-area applications, is achieved. Good turn-on characteristics without current pinching effects are consistently obtained. The structure also eliminates the lightly doped drain implant required in conventional offset-gate HVTFTs, resulting in a simpler and more reproducible process.<<ETX>>

ERCC1 expression in circulating tumor cells (CTCs) using a novel detection platform correlates with progression-free survival (PFS) in patients with metastatic non-small-cell lung cancer (NSCLC) receiving platinum chemotherapy.

PURPOSE To utilize a novel circulating tumor cell (CTC) technology to quantify ERCC1 expression on CTCs and determine whether ERCC1 expression levels predict efficacy of platinum-based chemotherapy in patients with metastatic non-small-cell lung cancer (NSCLC). EXPERIMENTAL DESIGN ERCC1 expression was measured in 17 metastatic NSCLC patients who received platinum-based therapy and had ≥2 intact CTCs with acceptable ERCC1 expression assay results. ERCC1 levels were determined from average expression on individual CTCs in each sample. Progression-free survival (PFS) was calculated from the date of therapy initiation. RESULTS PFS decreased with increasing ERCC1 expression (p<0.04, F-test, linear regression). Lack of ERCC1 expression was associated with longer PFS (266 days versus 172 days, log-rank, p<0.02) in a Kaplan-Meier analysis using ERCC expression level of 1 as a cutoff (range 0-30). The difference in survival was statistically significant with a hazard ratio of 4.20 (95% CI 1.25-14.1, p<0.02, log-rank). PFS was also observed to decrease with increased cytokeratin (CK) expression (p<0.01 long-rank (Cox regression) and F-test (linear regression)). The hazard ratio is 4.38 (95% CI 1.76-10.9) for each log-change in CK value until progression was noted on imaging. CONCLUSION Low expression of ERCC1 on CTCs correlates with PFS in patients with metastatic NSCLC receiving platinum-based therapy.