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We studied the p53 mutational spectra of 34 lip and 60 intra-oral squamous-cell carcinomas and examined possible etiological and prognostic correlations for these tumor sites. For the p53 analysis of exons 5–8, we used PCR/TGGE screening followed by DNA sequencing. Mutations were found in 18/34 (53%) lip and 22/60 (38%) intra-oral carcinomas. The p53 mutational spectrum of the intra-oral carcinomas comprised transitions and transversions in nearly equal frequency (11 to 10). In comparison, transitions were 3.5 times more frequent than transversions (14 to 4) in carcinomas of the lip. The predominant types of base change found in intra-oral tumors were G:C-to-T:A transversions and G:C-to-A:T transitions (32% each), while in lip tumors G:C-to-A:T transitions (70%) were the most frequent. The rate of lip tumors with mutations was higher in non-smokers (8/13) than in smokers (9/20). In contrast, p53 mutations in intra-oral tumors clustered in smokers (18/47 vs. 2/10). G:C-to-T:A transversions, regarded as tobacco smoke–associated in lung cancer, were found in 2 moderate and 4 heavy smokers with intra-oral cancer. This base substitution was found in none of our lip cancers. In lip tumors, a high rate of mutations occurred at dipyridine sites (13/18); among these were 8 C-to-T transitions and 1 CC-to-TT tandem base transition. These changes are characteristic of DNA damage caused by UV light. The presence of mutational events at the DNA-binding surface of the p53 protein may correlate with poor clinical outcome. However, we could not find any statistically significant correlations between p53 status and survival. Only the recurrence-free interval was significantly shortened in cases with mutations affecting residues of the DNA-binding surface of the p53 protein. Int. J. Cancer 88:82–86, 2000. © 2000 Wiley-Liss, Inc.

A 16.6 cm/sup 2/ monolithic large-area integrated multiprocessor system comprising nine identical programmable video signal processing elements was reconfigured by excimer laser-formed connections and discontinuities of conductor lines in a redundant bus system. The total yield enhancement of processors using laser reconfiguration amounts to 13.3%. On the prototypes, up to six processors per chip were functional at 66 MHz, providing a peak arithmetic performance of 6 GOPS per multiprocessor system. The power supply to defective processors with a high stand-by power consumption was terminated by laser, leading to a halving of power consumption. Furthermore, for the improvement of the laser process, vertical links between two metallization levels were formed on two chips with different standard CMOS layer sequences on special test structures. For the yield statistics of the formed vertical links, a contact resistance R/sub K/ larger than 3 /spl Omega/ was treated as a failure. With the laser processing of vertical links with an area of 14/spl times/14 /spl mu/m/sup 2/, a yield of 100% has been achieved. Beyond those, conventional accelerated life time tests were performed to examine the reliability of laser-formed vertical links. In microelectronic systems, a failure rate of 10 FIT/layer in 11.4 years corresponding to 0.1% failures is accepted. An extrapolation of Black's equation to operating conditions (100/spl deg/C, 2.5 mA) resulted in a failure rate of 0.1% in a time of 39 years.

This paper presents a method that enables an estimation of the per-unit-length capacitance of transmission lines on VLSI CMOS chips with the help of ring oscillators. For the determination of the line capacitance four different ring oscillators possessing transmission lines of various lengths are implemented upon test chips for process characterization. A simple analytical model of the ring oscillator is developed and a formula derived that estimates the per-unit-length capacitance of the transmission lines out of the periods of oscillation of the ring oscillators. SPICE simulation results (E-SPICE as well as H-SPICE) using process parameters for a 1.5-/spl mu/m CMOS process are included. An experimental verification was also performed by implementing the ring oscillators on a test chip for a 0.8-/spl mu/m CMOS technology. The determined line parameters are valid for a frequency range up to about 500 MHz. >

The ”Internet of Things” has led to a number of standardization efforts that can make proprietary protocols for home automation obsolete. One of the latest developments is the Constrained Application Protocol (CoAP) that is intended to be used as the HTTP-replacement for smart objects that are connected to the Internet. Early adaptors in industry and academia already have developed a plethora of applications that build on this new standard and have contributed valuable insights and implementation experience. While most of the new applications interoperate in a reasonable manner, the integration of legacy is one of the biggest challenges. Many existing protocols for home automation have been designed with a narrow focus on very limited devices that communicate with each other in a local network. CoAP, in contrast, mimics the architectural style that represents the fundamental basis of the Web, and therefore follows a very different design approach. In this paper, we present a basic design concept to interconnect CoAP and the proprietary FS20 protocol for home automation. The key aspects of our approach are the mapping of FS20 device addresses to path segments of CoAP URIs and to map FS20 commands to the four basic CoAP operations for creation, retrieval, update and deletion of resources, and the dynamic discovery of new nodes to register their capabilities with the CoAP service. To prove the feasibility of this approach, we have developed a multi-protocol gateway for a popular low-budget integrated access device.

SUMMARY Low-temperature electron microscopy combined with electron diffraction allows determination of the state of structural preservation as well as that of the solidified cellular water in frozen-hydrated sections. Apple leaves frozen at high pressure and cryosectioned with glass knives covered with a very thin layer of frozen water exhibit a minimum of artefacts and are thin enough for structural analysis. The Zeiss 902 EM energy-filtering microscope helps to improve the poor contrast of frozen-hydrated sections by imaging in the zero-loss mode. All sections analysed showed the electron diffraction pattern of vitreous water. This is ideal: the character of the liquid phase is preserved. A very high yield of good cryosections is achieved because the samples are vitrified and the friction on the glass knife surface is reduced by a thin ice layer.

Configurable interconnection arrays for wafer scale integration (WSI) constitute an application for thin-film multichip modules (MCMs) based on silicon. Laser-formed vertical links allow short cycle times and introduce redundancy into the MCSi (multichip on silicon) technique. As personalization is performed after complete wafer processing, large-volume manufacturing without individual process steps is possible. Laser process parameters developed for a standard CMOS double-level metallization are adapted to a double-level sandwich metallization. Burn-in measurements are carried out with currents up to 150 mA. Laser contacts are found to be suitable for different standard double-level metallizations and for configuration of interconnection arrays. >

A 16.6 cm/sup 2/ monolithic large area integrated multiprocessor system comprising 9 identical programmable video signal processing elements was reconfigured by excimer laser formed connections and discontinuities of conductor lines in a redundant bus system. The yield enhancement of functional processors amounts to 13.3%. On two prototypes, the laser reconfiguration of the bus system led to 4 functional processors per chip at 66 MHz, providing a peak arithmetic performance of 4 GOPS per multiprocessor system. The power supply to defective processors with a high stand-by power consumption was terminated by laser, leading to a halving of power consumption. Furthermore, for the improvement of the laser process, vertical links between two metallization levels were formed on two chips with different standard CMOS layer sequences on special test structures. For the yield statistics of the formed vertical links, a contact resistance R/sub K/>3 /spl Omega/ was treated as a failure. With the laser processing of vertical links with an area of 14/spl times/14 /spl mu/m/sup 2/, a yield of 100% has been achieved. Beyond those, conventional accelerated life time tests were performed to examine the reliability of laser formed vertical links. An extrapolation of Black's equation to operating conditions (100/spl deg/C, 2.5 mA) resulted in a failure rate of 0.1% in 39 years.

Laser processing of vertical links has been studied on three different layer sequences with main emphasis on statistics. Experiments were carried out with a Nd:YAG and an excimer laser using a fixed number of pulses adapted to the layer sequence. Laser antifuses of different design and sizes were fabricated. Simple expanded interconnections of dimensions 10*10 mu m/sup 2/ (10/sup 2/), 14/sup 2/ and 20/sup 2/ (sequence 1 and 2) and 9.6/sup 2/, 12.6/sup 2/ and 19.5/sup 2/ (sequence 3) turned out to be best suitable. Applying two Nd:YAG pulses, maximum yield of 100% was obtained from 14/sup 2/ and 20/sup 2/-structures with low mean resistances R/sub m/ of 0.18 and 0.104 Omega , and a standard deviation sigma /sub R/ of 0.145 and 0.06 Omega respectively. Yield obtained from 19.5/sup 2/ was 100% with R/sub m/=0.219, and sigma /sub R/=0.199 Omega using 3 pulses and two contacts per structure. By application of two excimer pulses, maximum yield of sequence 2 was 100% obtained from 14/sup 2/- and 20/sup 2/-structures with R/sub m/=0.125 Omega and 0.163 Omega and a sigma /sub R/ of 0.095 and 0.12 Omega respectively. Application of three excimer pulses on 12.6/sup 2/-structures lead to a yield of 99.6% with R/sub m/=0.552 and sigma /sub R/=0.357 Omega . In all yield evaluations, resistances >or=3 Omega were treated as a failure. >

Excimer-laser-formed vertical links between two metallization levels are demonstrated on special test chips, fabricated by ES2 in a standard CMOS process. Yield is 100% using link structures of 20 mu m*20 mu m and 14 mu m*14 mu m linear dimension and two identical laser pulses. Mean contact resistance is less than 200 Omega . A new test chip is built using sandwich layers for metallization and spin-on glass planarization. Temperature and humidity cycling of processed antifuses was carried out. >

Contact chains containing 30 to 37 links, alternated by probe pads, were investigated. Test structures were fabricated with two different layer sequences. Laser antifuses are simple expanded interconnections. Current densities, scaled by first level interconnections (3 mu m/sup 2/, resp. 3.6 mu m/sup 2/), were varied from 0.66*10/sup 6/ A/cm/sup 2/ to 1*10/sup 6/ A/cm/sup 2/, and substrate temperatures from 180 degrees C to 270 degrees C. The test procedure results in multiple censored data, which can be treated by application of hazard plots. Best results were obtained from 14*14 mu m/sup 2/ expansions of sequence 1, connected by two Nd:YAG pulses. A conservative extrapolation of Black's equation to 80 degrees C/1 mA with E/sub A/=0.4 eV, T=T/sub SUB/, and n=-2 showed, that only for two sets of test parameters, a 10 FIT/layer was slightly below 10 years. >

Nd:YAG laser processing of vertical links and cutting of interconnections in both metallization levels have been investigated. Main emphasis was on examination of the statistics of laser processing and the reliability of the processed antifuses. For this purpose, a special test chip has been designed and fabricated in a standard double level CMOS process. Laser cutting of interconnections is possible with one pulse in both metallization levels without passivation opening. For laser linking with the pulsed Nd:YAG, simply expanded interconnections turned out to be best suitable. Structures which are passivated prior to laser processing showed a significantly higher yield than depassivated combined with improved reproducibility of laser processing. Best yield of 99.4% with contact resistances >

We studied the p53 mutational spectra of 34 lip and 60 intra-oral squamous-cell carcinomas and examined possible etiological and prognostic correlations for these tumor sites. For the p53 analysis of exons 5-8, we used PCR/TGGE screening followed by DNA sequencing. Mutations were found in 18/34 (53%) lip and 22/60 (38%) intra-oral carcinomas. The p53 mutational spectrum of the intra-oral carcinomas comprised transitions and transversions in nearly equal frequency (11 to 10). In comparison, transitions were 3.5 times more frequent than transversions (14 to 4) in carcinomas of the lip. The predominant types of base change found in intra-oral tumors were G:C-to-T:A transversions and G:C-to-A:T transitions (32% each), while in lip tumors G:C-to-A:T transitions (70%) were the most frequent. The rate of lip tumors with mutations was higher in non-smokers (8/13) than in smokers (9/20). In contrast, p53 mutations in intra-oral tumors clustered in smokers (18/47 vs. 2/10). G:C-to-T:A transversions, regarded as tobacco smoke-associated in lung cancer, were found in 2 moderate and 4 heavy smokers with intra-oral cancer. This base substitution was found in none of our lip cancers. In lip tumors, a high rate of mutations occurred at dipyridine sites (13/18); among these were 8 C-to-T transitions and 1 CC-to-TT tandem base transition. These changes are characteristic of DNA damage caused by UV light. The presence of mutational events at the DNA-binding surface of the p53 protein may correlate with poor clinical outcome. However, we could not find any statistically significant correlations between p53 status and survival. Only the recurrence-free interval was significantly shortened in cases with mutations affecting residues of the DNA-binding surface of the p53 protein.

Survival rates were not significantly different 5 days after 20-min unilateral ischemia followed by contralateral nephrectomy: 58% in 20-day-old vs. 77% in 55-day-old rats. This experimental approach was used to characterize age dependent differences in the susceptibility of the glutathione system to ischemia and protective effects of treatment with vitamin E (10 mg/100 g b.wt. once daily s.c.) on the outcome after renal ischemia. The degree of postischemic changes (GSH, gamma-GT, TBARS) was the highest on days 1 and 2 after ischemia; at this time, survival rates were similar in young and adult rats. In adult animals, both glutathione content and the activity of gamma-GT were significantly reduced after ischemia whereas in immature rats only the glutathione content was distinctly diminished. At the 5th day after ischemia the parameters were almost normalized in the two age groups. Repeated administration of vitamin E improved the survival rate in adult rats up to 100%; in young animals, lethality was not influenced by vitamin E treatment. This reflects the beneficial effects of vitamin E on the glutathione system in adults whereas the vitamin was without effect on the immature rats' glutathione system.

After 45-min bilateral warm renal ischemia lethality amounted to 45% and 82% in 55- and 20-day-old rats, respectively (n = 176). Lethality rates were not significantly different after 20-min unilateral ischemia followed by contralateral nephrectomy after 24 hours (34 vs. 48% in young vs. adult rats; n = 168). The latter experimental approach was used to characterize age dependent differences in the susceptibility to ischemia. The degree of postischemic renal damage was the highest at the 1st and 2nd days after ischemia; at this time, lethality rates were similar in young and adult rats. However, urea concentration in serum was significantly more enhanced in young animals whereas that of creatinine was increased to the same extent in both age groups. The increase in protein excretion into urine was similar in young and adult rats, too. Furthermore, urine flow rates and GFR were significantly diminished after ischemia, independent of age. However, excretion of Na+ and K+ was distinctly more depressed in immature individuals. Finally, the glutathione content in kidney tissue of both age groups was reduced and lipid peroxidation was significantly higher after ligation of the renal arteries. The relative changes were similar in both age groups although the glutathione content was significantly lower in 20-day-old control rats. 4-5 days after ischemia, most parameters returned to baseline values. In 55-day-old rats, 45-min ischemia has more severe consequences on renal function compared to 20-min ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Solute influx into the thylakoid lumen during freezing in vitro causes a volume increase. After freezing at -20°C for 3 h in sucrose solutions at initial concentrations above 0.1 osmolal thylakoids showed a threefold increase in volume after thawing compared to unfrozen controls. Electron microscopy showed that thylakoids frozen in situ swell during thawing. Depending on the freezing conditions, extensive osmotic stress may lead to mechanical membrane rupture with the concomitant release of the lumenal protein plastocyanin. Membrane rupture can also be shown in vitro under non-freezing conditions, although to a lesser degree, it is proportional to the permeability of the solutes used to suspend the membranes. Thylakoids frozen and thawed in vitro are less extensible than unfrozen controls, leading to rupture under less severe osmotic stress and thereby increasing damage.