A queueing network model for semiconductor manufacturing

We develop an open queueing network model for rapid performance analysis of semiconductor manufacturing facilities. While the use of queueing models for performance evaluation of manufacturing systems is not new, our approach differs from others in the detailed ways in which we model the different tool groups found in semiconductor wafer fabrication, as well as the way in which we characterize the effect of rework and scrap on wafer lot sizes. As an application of the model, we describe a method for performing tool planning for semiconductor lines. The method is based on a marginal allocation procedure which uses performance estimates from the queueing network model to determine the number of tools needed to achieve a target cycle time, with the objective being to minimize overall equipment cost     

Development of a chipscale integrated microelectrode/microelectronic device for brain implantable neuroengineering applications

An ultralow power analog CMOS chip and a silicon based microelectrode array have been fully integrated to a microminiaturized "neuroport" for brain implantable neuroengineering applications. The CMOS integrated circuit (IC) includes preamplifier and multiplexing circuitry, and a hybrid flip-chip bonding technique was developed to fabricate a functional, encapsulated microminiaturized neuroprobe device. Our neuroport has been evaluated using various methods, including pseudospike detection and local excitation measurement, and showed suitable characteristics for recording neural activities. As a proof-of-concept demonstration, we have measured local field potentials from thalamocortical brain slices of rats, suggesting that the new neuroport can form a prime platform for the development of a microminiaturized neural interface to the brain in a single implantable unit. An alternative power delivery scheme using photovoltaic power converter, and an encapsulation strategy for chronic implantation are also discussed.     

A microelectrode/microelectronic hybrid device for brain implantable neuroprosthesis applications

We have designed, fabricated, and characterized a microminiaturized "neuroport" for brain implantable neuroprosthesis applications, using an analog CMOS integrated circuit and a silicon based microelectrode array. An ultra-low power, low-noise CMOS preamplifier array with integral multiplexing was designed to accommodate stringent thermal and electrophysiological requirements for implantation in the brain, and a hybrid integration approach was developed to fabricate a functional microminiaturized neuroprobe device. Measurements showed that our fully scalable 16-channel CMOS amplifier chip had an average gain of 44 dB, bandwidth from 10 Hz to 7.3 kHz, and an equivalent input noise of approximately 9 microVrms with an average power consumption per preamplifier of 52 microW, which is consistent with simulation results. As a proof-of-concept demonstration, we have measured local field potentials from thalamocortical brain slices of rats, showing oscillatory behavior with an amplitude about 0.5 mV and a period ranging 80-120 ms. The results suggest that the hybrid integrated neuroport can form a prime platform for the development of a next level microminiaturized neural interface to the brain in a single implantable unit.     

Detailed structural analysis of amyloidogenic wild-type transthyretin using a novel purification strategy and mass spectrometry

Wild-type transthyretin (TTR), normally a soluble plasma-circulating protein, can be amyloidogenic, i.e., form tissue-deposited fibrillar material in the extracellular matrix of various organs throughout the body. Senile systemic amyloidosis (SSA) is one such pathology and features TTR-containing amyloid deposits that are found primarily in the heart. The cause for this transition from soluble to insoluble protein in SSA is yet to be determined as specific structural features that might favor TTR fibrillogenesis have not yet been identified. The precise characterization of ex vivo fibril deposits might provide insight, but structural analyses of TTR from amyloid deposits have been hindered thus far by the lack of purification strategies that overcome the insolubility of the tissue-derived protein without degrading it. Consequently, the true biochemical nature of deposited TTR remains in question. In this study, we provide detailed analyses of both the soluble (serum) and deposited (tissue) forms of TTR from cases of SSA. In the serum, a distribution of mixed disulfides, specifically S-sulfonated and S-cysteinylated forms of TTR, as well as the unmodified protein were identified. The relative levels of the three TTR species in the SSA group were comparable to amounts present in sera from age-matched control groups. For characterization of the amyloid deposited TTR, we investigated cardiac tissue samples obtained from three separate cases of SSA. We report a novel chromatographic purification strategy performed under nonreducing conditions (to maintain cysteine disulfide status) and the use of this procedure in conjunction with detailed mass spectrometric analysis of TTR from the amyloid deposits. A series of C-terminal TTR fragments with N-termini ranging from amino acids 46 to 55 were identified. We also determined that the deposits in all samples contained Cys10 disulfide-linkedhomodimers composed of full-length TTR monomers. This last finding suggests an important role for Cys10 conjugation in the transition from soluble TTR to the pathological amyloid fibril.     

Further insights into the discoloration of TATB under ionizing radiation

ABSTRACT

To determine degradation products formed by exposure of TATB to ionizing radiation, a computational and experimental study is presented. Thermochemical and spectral data have been calculated using DFT at the MH06-HF/aug-cc-pVTZ level which suggest the formation of the cation radical derivative of TATB. Irradiated TATB samples showed the widely reported yellow-to-green discoloration, with measured CIE L*, a*, b* and RGB values correlating with total dose. Trace quantities of a mono-furazan derivative were detected by HPLC-MS; the discoloration is not attributed to this, but rather to the presence of a paramagnetic species (i.e., the cation), as detected by ESR measurements. Recrystallized irradiated TATB samples reverted to their original color, further suggesting it is the cation radical that is responsible for color change.     

Synthetic wind speed scenarios including diurnal effects: Implications for wind power dimensioning

This paper presents the application of a new approach for taking into consideration the variability of the wind resource at different temporal scales (hourly, daily, seasonal, annual) in generating scenarios for energy systems modelling. It is argued that Markov models and auto-regressive models, generally used for synthetic wind speed data generation, do not contain sufficient low-frequency information related to seasonal and diurnal patterns. Under high wind penetration scenarios, the daily pattern of the wind becomes increasingly important to energy system modelling and design. Statistical analysis of various wind locations in the Azores, Portugal, indicates that there are strong seasonal differences in magnitude and shape within a given day that will affect energy system design and performance. The proposed methodology evaluates the frequency of different wind day types, such as afternoon winds or morning winds, along with the magnitude of wind for locations with different quality wind resources. Application of the new methodology indicates that the inclusion of diurnal wind characteristics for the analysis of future energy systems provides better design information, especially as it pertains to generation investment requirements to meet island specific renewable penetration targets, and intra-day surpluses or shortages of wind generation in small energy networks.     

Prognostic significance of Bcl-2 protein expression and Bcl-2 gene rearrangement in diffuse aggressive non-Hodgkin's lymphoma

The prognostic significance of Bcl-2 protein expression and bcl-2 gene rearrangement in diffuse large cell lymphomas (DLCL) is controversial. Bcl-2 protein expression prevents apoptosis and may have an important role in clinical drug resistance. The presence of a bcl-2 gene rearrangement in de novo DLCL suggests a possible follicle center cell origin and perhaps a distinct clinical behavior more akin to low-grade non-Hodgkin's lymphoma (NHL). The purpose of this study was to determine the impact of Bcl-2 protein expression and bcl-2 gene rearrangement (mbr and mcr) on survival of a cohort of patients with DLCL who were uniformly evaluated and treated with effective chemotherapy. Patients included the original MACOP-B cohort (n = 121) and the initial 18 patients treated with the VACOP-B regimen (total = 139). All patients had advanced-stage disease, were 16 to 70 years old, and corresponded to Working Formulation categories F, G, or H. No patients had prior treatment, discordant lymphoma, or human immunodeficiency virus seropositivity. Paraffin sections from diagnostic biopsies were analyzed for bcl-2 gene rearrangement including mbr and mcr breakpoints by polymerase chain reaction and Bcl-2 protein expression by immunohistochemistry. With a median follow-up of 81 months, overall (OS), disease-free (DFS), and relapse-free survival (RFS) were measured to determine the prognostic significance of these parameters. Analyzable DNA was present in 118 of 139 (85%) cases, with 14 demonstrating a bcl-2 rearrangement (11 mbr, 3 mcr). All 14 of these bcl-2 gene rearrangement-positive cases were found in the 102 patients with a B-cell immunophenotype, but the presence of this rearrangement had no significant influence on survival. Bcl-2 protein expression was interpretable in 116 of 139 (83%) cases, with immunopositivity detected in 54 of 116 (47%). Using a cut-off of greater than 10% Bcl-2 immunopositive tumor cells for analysis, positive Bcl-2 protein expression was seen in 28 of 116 (24%) patients and the presence of this expression correlated with decreased 8-year OS (34% v 60%, P < .01), DFS (32% v 66%, P < .001), and RFS (25% v 59%, P < .001). Bcl-2 protein expression remained significant in multivariate analysis that included the clinical international prognostic index factors and immunophenotype (P < .02). In conclusion, although bcl-2 gene rearrangement status could not be shown to have an impact on outcome, Bcl-2 protein expression is a strong significant predictor of OS, DFS, and RFS in DLCLs.