Statistical tests of the IBM PC pseudorandom number generator

The widespread use of IBM personal computers in biomedical research and medical practice is evidenced by a variety of journal articles. Many of the application programs are written in the BASIC language, they model a stochastic process, and they depend on the Microsoft random number generator. Unfortunately, the Microsoft generator has exhibited a number of flaws including, for some seeds, a lack of uniformity of generated sequences of numbers, and serial correlation within such sequences. This paper provides evidence of these problems for several seeds, and provides suggestions for acceptable seeds which ensure that the generated sequences of numbers pass two fundamental statistical tests for randomness.     

A novel metal-insulator-metal structure for field-programmabledevices

A metal-insulator-metal (MIM) capacitor structure has been developed for use in field-programmable gate arrays (FPGAs) as a voltage-programmable link (VPL). The structure relies on a combination of a refractory metal and aluminum as the lower electrode, and either a similar combination or aluminum alone as the top electrode. The insulator is prepared by means of plasma-enhanced chemical vapor deposition (PECVD). It comprises a sandwich of nearly stoichiometric silicon dioxide interposed between two like layers of silicon-rich silicon nitride. The structure has displayed characteristics desirable for use in emerging FPGA technology, including high density, low on-resistance, reduced capacitance, and low programming voltage     

Evaluation of diamond films by nuclear magnetic resonance and Raman spectroscopy

The quality of chemically vapor deposited diamond films was assessed in terms of sp²/sp³ content as determined by solid-state nuclear magnetic resonance (NMR) and Raman spectroscopy. While the results of the two techniques are in qualitative agreement, only the NMR spectra yield quantitative values for the sp²/sp³ ratio. Only sp³ carbon was observed in the NMR spectra of very high quality hot-filament, microwave plasma, and d.c. arc-jet chemically vapor deposited films. As expected, Raman spectroscopy is extremely sensitive to sp² bonded carbon, identifying small amounts below the detection limit of the NMR spectrometer. Comparison of the two techniques, however, indicates that Raman spectroscopy may be so sensitive to sp² bonded carbon that sp³ bonded carbon in films containing as much as 90% sp³ bonded material may remain undetected. NMR linewidths indicate that the sp³ carbon in such material shows more disorder than that found in high-quality polycrystalline films.     

Kozak Similarity Score Algorithm Identifies Alternative Translation Initiation Codons Implicated in Cancers

Ribosome profiling and mass spectroscopy have identified canonical and noncanonical translation initiation codons (TICs) that are upstream of the main translation initiation site and used to translate oncogenic proteins. There have previously been conflicting reports about the patterns of nucleotides that surround noncanonical TICs. Here, we use a Kozak Similarity Score algorithm to find that nearly all of these TICs have flanking nucleotides closely matching the Kozak sequence. Remarkably, the nucleotides flanking alternative noncanonical TICs are frequently closer to the Kozak sequence than the nucleotides flanking TICs used to translate the gene’s main protein. Of note, the 5′ untranslated region (5‘UTR) of cancer-associated genes with an upstream TIC tend to be significantly longer than the same region in genes not associated with cancer. The presence of a longer-than-typical 5′UTR increases the likelihood of ribosome binding to upstream noncanonical TICs, and may be a distinguishing feature of a number of genes overexpressed in cancer. Noncanonical TICs that are located in the 5′UTR, although thought by some to be disadvantageous and suppressed by evolution, may translate oncogenic proteins because of their flanking nucleotides.     

Inductively coupled plasma etching for large format HgCdTe focal plane array fabrication

Inductively coupled plasma (ICP) using hydrogen-based gas chemistry has been developed to meet requirements for deep HgCdTe mesa etching and shallow CdTe passivation etching in large format HgCdTe infrared focal plane array (FPA) fabrication. Large format 2048×2048, 20-μm unit-cell short wavelength infrared (SWIR) and 2560×512, 25-μm unit-cell midwavelength infrared (MWIR) double-layer heterojunction (DLHJ) p-on-n HgCdTe FPAs fabricated using ICP processing exhibit >99% pixel operability. The HgCdTe FPAs are grown by molecular beam epitaxy (MBE) on Si substrates with suitable buffer layers. Midwavelength infrared detectors fabricated from 4-in. MBE-grown HgCdTe/Si substrates using ICP for mesa delineation and CdTe passivation etching demonstrate measured spectral characteristics, RoA product, and quantum efficiency comparable to detectors fabricated using wet chemical processes. Mechanical samples prepared to examine physical characteristics of ICP reveal plasma with high energy and low ion angle distribution, which is necessary for fine definition, high-aspect ratio mesa etching with accurate replication of photolithographic mask dimensions.     

1,4-Cyclohexanecarboxylates: potent and selective inhibitors of phosophodiesterase 4 for the treatment of asthma

Evaluation of a variety of PDE4 inhibitors in a series of cellular and in vivo assays suggested a strategy to improve the therapeutic index of PDE4 inhibitors by increasing their selectivity for the ability to inhibit PDE4 catalytic activity versus the ability to compete for high affinity [3H]rolipram-binding sites in the central nervous system. Use of this strategy led ultimately to the identification of cis-4-cyano-4-[3-(cyclopentyloxy)-4-methoxyphenyl]cyclohexane-1-carboxyl ic acid (1, SB 207499, Ariflo), a potent second-generation inhibitor of PDE4 with a decreased potential for side effects versus the archetypic first generation inhibitor, (R)-rolipram.     

Codistribution of procathepsin B and mature cathepsin B forms in human prostate tumors detected by confocal and immunofluorescence microscopy

Ascorbic acid can recycle alpha-tocopherol from the tocopheroxyl free radical in lipid bilayers and in micelles, but such recycling has not been demonstrated to occur across cell membranes. In this work the ability of intracellular ascorbate to protect and to recycle alpha-tocopherol in intact human erythrocytes and erythrocyte ghosts was investigated. In erythrocytes that were 80% depleted of intracellular ascorbate by treatment with the nitroxide Tempol, both 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH) and ferricyanide oxidized alpha-tocopherol to a greater extent than in cells not depleted of ascorbate. In contrast, in erythrocytes in which the intracellular ascorbate concentration had been increased by loading with dehydroascorbate, loss of alpha-tocopherol was less with both oxidants than in control cells. Protection against AAPH-induced oxidation of alpha-tocopherol was not prevented by extracellular ascorbate oxidase, indicating that the protection was due to intracellular and not to extracellular ascorbate. Incubation of erythrocytes with lecithin liposomes also generated an oxidant stress, which caused lipid peroxidation in the liposomes and depleted erythrocyte alpha-tocopherol, leading to hemolysis. Ascorbate loading of the erythrocytes delayed liposome oxidation and decreased loss of alpha-tocopherol from both cells and from alpha-tocopherol-loaded liposomes. When erythrocyte ghosts were resealed to contain ascorbate and challenged with free radicals generated by AAPH outside the ghosts, intravesicular ascorbate was totally depleted over 1 h of incubation, whereas alpha-tocopherol decreased only after ascorbate was substantially oxidized. These results suggest that ascorbate within the erythrocyte protects alpha-tocopherol in the cell membrane by a direct recycling mechanism.     

Speaker Verification Using Support Vector Machines and High-Level Features

High-level characteristics such as word usage, pronunciation, phonotactics, prosody, etc., have seen a resurgence for automatic speaker recognition over the last several years. With the availability of many conversation sides per speaker in current corpora, high-level systems now have the amount of data needed to sufficiently characterize a speaker. Although a significant amount of work has been done in finding novel high-level features, less work has been done on modeling these features. We describe a method of speaker modeling based upon support vector machines. Current high-level feature extraction produces sequences or lattices of tokens for a given conversation side. These sequences can be converted to counts and then frequencies of n-gram for a given conversation side. We use support vector machine modeling of these n-gram frequencies for speaker verification. We derive a new kernel based upon linearizing a log likelihood ratio scoring system. Generalizations of this method are shown to produce excellent results on a variety of high-level features. We demonstrate that our methods produce results significantly better than standard log-likelihood ratio modeling. We also demonstrate that our system can perform well in conjunction with standard cesptral speaker recognition systems.