A 65nm generation logic technology with 1.2nm physical gate oxide, 35nm gate length, enhanced cha... more A 65nm generation logic technology with 1.2nm physical gate oxide, 35nm gate length, enhanced channel strain, NiSi, 8 layers of Cu interconnect, and low-k ILD for dense high performance logic is presented. Transistor gate length is scaled down to 35nm while not scaling the gate oxide as a means to improve performance and reduce power. Increased NMOS and PMOS drive currents are achieved by enhanced channel strain and junction engineering. 193nm lithography along with APSM mask technology is used on critical layers to provide aggressive design rules and a 6-T SRAM cell size of 0.57μm2. Process yield, performance and reliability are demonstrated on a 70 Mbit SRAM test vehicle with >0.5 billion transistors.
Measurement of collagenolytic activity is of interest to a wide variety of investigators using ma... more Measurement of collagenolytic activity is of interest to a wide variety of investigators using mammalian tissue. In order to develop a method that would quantitative active collagenase from microquantities of human tissue, we employed zymography to the heart and uterus of neontal, adult, and postpartum rats. Collagenase rapidly cleaves native collagen into two fragments, which at 37°C form gelatin. Gelatin can also by hydrolyzed by collagenase, but at slower rate, and therefore we used gelatin to quantitate the amount of collagenase present in heart and uterine tissue and developed a method for the direct extraction of collagenase from small quantities of rat myocardium. Our method was found to be comparable with the chemical method reported by Masue et al. (Anal Biochem 1977; 17:215-21). The enzyme, which was not detected in normal adult rat cardiac tissue, was found to exist entirely in latent form and demonstrated typical properties of a mammalian collagenase/ gelatinase after activation by trypsin and plasma. We observed a 60–80% increase in collagenase activity after activation by these proteases and estimated that there is approximately 5 ± 2 pg of procollagenase per μg of normal adult rat left ventricle. Collagenolytic activity in the postpartum rat heart was found to be slightly (∼2–5%) reduced when compared to the adult heart but it was increased in the neonatal heart and postpartum uterus. This method allows for the rapid quantitative and qualitative measurement of collagenase activity in a variety of tissues containing collagenase/gelatinase activity. Our results indicate the most collagenase in the myocardium exists in latent form.
We demonstrate that single-nucleotide differences in a DNA sequence can be detected in homogeneou... more We demonstrate that single-nucleotide differences in a DNA sequence can be detected in homogeneous assays using molecular beacons. In this method, the region surrounding the site of a sequence variation is amplified in a polymerase chain reaction and the identity of the variant nucleotide is determined by observing which of four differently colored molecular beacons binds to the amplification product. Each of the molecular beacons is perfectly complementary to one variant of the target sequence and each is labeled with a different fluorophore. To demonstrate the specificity of these assays, we prepared four template DNAs that only differed from one another by the identity of the nucleotide at one position. Four amplification reactions were prepared, each containing all four molecular beacons, but each initiated with only one of the four template DNAs. The results show that in each reaction a fluorogenic response was elicited from the molecular beacon that was perfectly complementary to the amplified DNA, but not from the three molecular beacons whose probe sequence mismatched the target sequence. The color of the fluorescence that appeared in each tube during the course of the amplification indicated which nucleotide was present at the site of variation. These results demonstrate the extraordinary specificity of molecular beacons. Furthermore, the results illustrate how the ability to label molecular beacons with differently colored fluorophores enables simple multiplex assays to be carried out for genetic analysis.
A 65nm generation logic technology with 1.2nm physical gate oxide, 35nm gate length, enhanced cha... more A 65nm generation logic technology with 1.2nm physical gate oxide, 35nm gate length, enhanced channel strain, NiSi, 8 layers of Cu interconnect, and low-k ILD for dense high performance logic is presented. Transistor gate length is scaled down to 35nm while not scaling the gate oxide as a means to improve performance and reduce power. Increased NMOS and PMOS drive currents are achieved by enhanced channel strain and junction engineering. 193nm lithography along with APSM mask technology is used on critical layers to provide aggressive design rules and a 6-T SRAM cell size of 0.57μm2. Process yield, performance and reliability are demonstrated on a 70 Mbit SRAM test vehicle with >0.5 billion transistors.
Measurement of collagenolytic activity is of interest to a wide variety of investigators using ma... more Measurement of collagenolytic activity is of interest to a wide variety of investigators using mammalian tissue. In order to develop a method that would quantitative active collagenase from microquantities of human tissue, we employed zymography to the heart and uterus of neontal, adult, and postpartum rats. Collagenase rapidly cleaves native collagen into two fragments, which at 37°C form gelatin. Gelatin can also by hydrolyzed by collagenase, but at slower rate, and therefore we used gelatin to quantitate the amount of collagenase present in heart and uterine tissue and developed a method for the direct extraction of collagenase from small quantities of rat myocardium. Our method was found to be comparable with the chemical method reported by Masue et al. (Anal Biochem 1977; 17:215-21). The enzyme, which was not detected in normal adult rat cardiac tissue, was found to exist entirely in latent form and demonstrated typical properties of a mammalian collagenase/ gelatinase after activation by trypsin and plasma. We observed a 60–80% increase in collagenase activity after activation by these proteases and estimated that there is approximately 5 ± 2 pg of procollagenase per μg of normal adult rat left ventricle. Collagenolytic activity in the postpartum rat heart was found to be slightly (∼2–5%) reduced when compared to the adult heart but it was increased in the neonatal heart and postpartum uterus. This method allows for the rapid quantitative and qualitative measurement of collagenase activity in a variety of tissues containing collagenase/gelatinase activity. Our results indicate the most collagenase in the myocardium exists in latent form.
We demonstrate that single-nucleotide differences in a DNA sequence can be detected in homogeneou... more We demonstrate that single-nucleotide differences in a DNA sequence can be detected in homogeneous assays using molecular beacons. In this method, the region surrounding the site of a sequence variation is amplified in a polymerase chain reaction and the identity of the variant nucleotide is determined by observing which of four differently colored molecular beacons binds to the amplification product. Each of the molecular beacons is perfectly complementary to one variant of the target sequence and each is labeled with a different fluorophore. To demonstrate the specificity of these assays, we prepared four template DNAs that only differed from one another by the identity of the nucleotide at one position. Four amplification reactions were prepared, each containing all four molecular beacons, but each initiated with only one of the four template DNAs. The results show that in each reaction a fluorogenic response was elicited from the molecular beacon that was perfectly complementary to the amplified DNA, but not from the three molecular beacons whose probe sequence mismatched the target sequence. The color of the fluorescence that appeared in each tube during the course of the amplification indicated which nucleotide was present at the site of variation. These results demonstrate the extraordinary specificity of molecular beacons. Furthermore, the results illustrate how the ability to label molecular beacons with differently colored fluorophores enables simple multiplex assays to be carried out for genetic analysis.
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