An electronic module having a high density of silicon IC chips is provided by mounting the chips in tapered through-holes in a silicon substrate, filling the edge gaps between the chips and the substrate with a glass so that the chips, the filler glass, and the substrate have a smooth upper surface adapted to receive monolithic interconnections formed by planar metallization methods. The resulting assembly is enclosed in a housing also formed substantially from silicon, which contains electrically isolated pins for contacting the input-output electrodes of the assembly. Preferential etching is used to form the through-holes in the substrate as well as various alignment means on the substrate and other parts of the housing so that they are self-aligning during assembly. Improved performance, reliability, and low cost is obtained.

1. Field of the Invention
This invention relates in general to electronic circuit modules, and, more particularly, to improved means and methods for providing high density circuit assemblies and modules having a multiplicity of interconnected integrated circuit chips or other components.
2. Background Art
Modern fabrication techniques make it possible to pack very large numbers of high speed semiconductor devices into individual integrated circuit (IC) chips or die. However, in order to build functioning systems, the individual ICs must be electrically interconnected in some way. Historically this has been done by mounting the individual IC die in sealed packages. These sealed packages protect the die from the environment and provide rugged external leads or pads which can be used for interconnecting the ICs in the system. The packaged die are generally mounted by their leads on a circuit board which contains the interconnect wiring. The circuit board often has multiple layers of interconnect wiring and may be fabricated of metallized plastics, ceramics, or impregnated paper or fabric. A significant disadvantage of this method is that the wiring length from die to die, through the individual packages and along the conductors of the circuit board, is many times the size of the IC die. With very high speed devices, these comparatively long wiring lengths cause significant propagation delays, reducing the overall system performance.
More recently, it has been possible to produce IC die which are themselves hermetically sealed so that they may be mounted directly on the circuit board or substrate rather than being housed in individual packages. The circuit board or assembly is then encapsulated as a whole to form a module. Omitting the individual packages permits the die to be closer together, thus reducing the propagation delay in the circuit board. While this provides some improvement, it does not completely solve the problem of excess propagation delay. Further, severe problems having to do with reliability and with removing heat still remain.
The IC die or chips have bonding pads which are connected to the wiring pattern on the circuit board by a variety of off-chip connection means, generally involving soldering or welding. Examples are wire bonds, flexible tapes, beam leads, and solder bumps. A significant difficulty with these prior art approaches is that in most cases the metallurgy needed to make such off-chip connections is different than the metallurgy used for the on-chip interconnections within the IC chip. It is well known that the reliability of off-chip interconnections is substantially poorer than the reliability of on-chip interconnections. Further, these prior art off-chip connections utilize much more area on the circuit board or substrate than is desired. This contributes to the comparatively low packing density of prior art circuit modules, even when the individual die packages are omitted, and the continued significant propagation delays associated therewith.
Prior art modules have utilized materials having markedly different coefficients of thermal expansions. As a consequence thermal stresses are induced during temperature cycling. This further degrades reliability of the finished modules. Additionally, prior art modules have not provided simple and effective means for removal of heat from the many IC chips or other components within the module. Thus, a need continues to exist for improved modules for integrated circuits and other components, particularly high density modules, having improved packing density, propagation delay, heat dissipation, ease of manufacture, and cost.
Accordingly, it is an object of the present invention to provide an improved means and method for electronic modules for integrated circuits having a high packing density.
It is a further object of the present invention to provide an improved means and method for electronic modules wherein the number of welded or soldered joints required to interconnect the IC chips or other components within the module is reduced.
It is an additional object of the present invention to provide an improved means and method for electronic modules wherein the generation of mechanical stress from temperature changes is reduced.
It is a further object of the present invention to provide an improved means and method for electronic modules wherein the materials used for the module comprise the same material as used for the integrated circuit chip.
It is an additional object of the present invention to provide an improved means and method for electronic modules wherein the principle elements of the module are self aligning for easy assembly.
It is a further object of the present invention to provide an improved means and method for electronic modules wherein the individual IC chips are mounted in a supporting member so as to have accessible rear faces adapted for contacting a planar heat sink, and exposed front faces which are smoothly joined to, and optimally, part of the interconnect wiring surface.
It is an additional object of the present invention to provide an arrangement for including semiconductor die prepared using different processing technologies (e.g. TTL, NMOS, linear, ECL, etc.) within the same monolithic substrate.
It is a further object of the present invention to provide a means and method for incorporating pretested die in a monolithic substrate which can be interconnected using planar metallization technology.


For direct and on-line study of the physiological states of cell cultures, a robust flow injection system has been designed and interfaced with flow cytometry (FI-FCM). The core of the flow injection system includes a microchamber designed for sample processing. The design of the microchamber allows not only an accurate on-line dilution but also on-line cell fixation, staining, and washing. The flow injection part of the system was tested by monitoring the optical density of a growing E.coli culture on-line using a spectrophotometer. The entire growth curve, from lag phase to stationary phase, was obtained with frequent sampling. The system is thus particularly useful since it operates automatically without direct operator supervision for extended time periods.

There is ample evidence that growing cells are heterogeneous entities that differ from one another in their physiological states. Microbial heterogeneity may arise due to phenotypic changes associated with the cell cycle (Dien and Srienc, 1991, 1992), due to changes in the microenvironments of individual cells (Fowler and Dunlop, 1989, Dunlop and Ye, 1990), or due to mutations resulting in genotypic variations in the population (Hall, 1995). Thus, rates of growth associated parameters such as protein synthesis or substrate uptake are distributed in the population. From a biochemical engineering perspective, these population dynamics have profound implications since the overall productivity of the microbial process depends upon the contribution of each individual cell. One method to estimate such dynamics is by the use of flow cytometry.
In a process environment, rapid, repeated, and long term on line manual analysis is usually impractical, if not impossible. Therefore, a certain degree of automation is desirable, particularly for more complex analysis procedures such as flow cytometry. To date, a number of flow injection systems have been designed and widely used in microbial process control and automatic analysis (Ruzicka and Hansen, 1975, 1988; Reed, 1990; Munch et al., 1992), but most of them monitor population averaged properties. The concept of automatic flow cytometric analysis was introduced by Omann et al. (1985), who constructed a sample instruction devise fitted to a Becton Dickinson FACS cytometer. Kelley (1989) also developed a similar device. Pennings et al. (1987) developed a system based on continuous pumping cells and reagents with a peristaltic pump. Although the capabilities of these designs are rather limited, they are pioneering designs in automatic flow cytometry. Successful on line flow cytometry was demonstrated using a flow injection technique (Ruzicka, 1992).
The present invention provides for a flow injection system interfaced with a flow cytometer and a bioreactor to perform on line assessment of single cell property distributions. The versatility and performance of this system are demonstrated in several preliminary examples that show the utility of the system since it provides detailed quantitative information on growing cell populations that cannot be obtained with any other existing method.
Materials and Methods
Cell Strains, Growth Medium, Growth Conditions, and Staining Conditions
E. coli strain K12 was used in the growth experiment involving on line monitoring of optical density. Cells were grown in 300 mL 2XGYT complex medium (Sambrook, et al., s1989) in a 1 L flask placed in a 30xc2x0 C. water bath and shaken at 225 rmp. The culture was aerated at 1 vvm by a peristaltic pump through an airstone (Cole Parmer, Vernon Hills, Ill.) immersed in the medium E.coli BL21 cells transformed with the plasmid pRSET/S65T (a kind gift from Dr. R. Y. Tsien, Howard Hughes Medical Center, San Diego) were used in the experiment to study the Gfp fluorophore formation kinetics and batch growth dynamics. The plasmid contains an ampicillin resistance marker gene, and the Gfp gene under the control of a T7RNA polymerase promoter. Cells were grown in LB complex medium containing ampicillin (100 xcexcg/mL). Production of T7 RNA polymerase was regulated using an IPTG inducible lacZ promoter present in the host chromosome. IPTG (200 xcexcg/mL) was used to induce Gfp expression, and chloramphenicol (30 xcexcg/mL) was used to inhibit the protein synthesis when needed (Sambrook et al., 1989)
Saccharomyces cerevisiae strain YPH399a (MATa, ade2-101, leu2xcex941, lys2-80, his3xcex94200, trplxcex9463, ura3-52) cells were grown overnight on 3 mL YPD medium (Bacto yeast extract, 1% w/v, bacto peptone, 2% w/v, dextrose, 2% w/v) at 30xc2x0 C. and 225 rpm in a 15 mL polystyrene test tube (Falxon). Cells were diluted to a concentration of ca. 1xc3x97106 cells in fresh medium, and the tube was placed on ice. Samples were automatically withdrawn into the microchamber of the flow injection system. Inside the microchamber, samples were washed with ice cold PBS, treated with chromatin denaturation solution (0,1 N HCl, 0.5% w/v Triton X-100, 1.75% w/v NaCl), washed with ice cold PBS, and strained with mithramycin A (Sigma, 30 xcexcg/mL in PBS, 2mM MgCl2). Fixation and denaturation steps were 2 minutes long, washes were 1 minute lone, and cells were tainted with mithramycin for 10 minutes. Fixation, denaturation, and washing were performed by continuously pumping the appropriate reagent through the microchamber while mixing the suspended cells using a magnetic stir-bar. A source of reagent is connected to a port of the microchamber such that reagent flows through this port and through the membrane and contact the sample on the sample handling side of the membrane.
FI-FCM System
The equipment used to construct the flow injection system is listed in Table 1. The components were interfaced to a personal computer using DT 2805 and DAS 1601 data acquisition and system control boards through DI/O and D/A subsystems. Labtech Notebook software (Laboratories Technology Corporation, Wilmington, Mass.) was used to control both boards. FIG. 1 shows a schematic overview of this FI-FCM system which consists of three subsystems: (i) sample delivery, (ii) sample handling, and (iii) sample injection and analysis.
A sample delivery loop transferred the cell culture from a bioreactor to the flow injection system. A static degassing unit was designed to release air bubbles trapped in the sample (FIG. 2a), and sample was continuously re circulated in this loop. During sampling periods, the cell culture with air bubbles was allowed to accumulate in the glass tube, and a weak vacuum was applied using a peristaltic pump. Due to a combination of static hydraulic buoyancy force and vacuum air bubbles were rapidly eliminated from the medium through a 0.45 xcexcm inline filter. The degassed sample was then fed into the microchamber of the sample handling subsystem for further processing. The sample residence time in the delivery loop was minimized since the environmental conditions (in particular, the aeration) in the tubing are not the same as those in the bioreactor,. However, care was taken to avoid shear induced damage of the sample that might result from the use of very high flow rates in the tubing. Hence, Cole Parmer Masterflex silicon tubing (size #13, I.D. 0.75 mm) and a flow rate of 5 mL/min (0.19 m/sec) were used, resulting in a residence time of 10.5 sec.
The sample handling consists of a 10 position switching valve (#1, Table 1) connected with a precise peristaltic pump (#4 Table 1) to select up to 10 different streams, and a two way injection valve (#2 Table 1) incorporated with a microchamber to load and infect samples (FIG. 2b,c). The key component in sample handling is the microchamber which has been designed to allow on line sample dilution and staining (FIG. 2d). The unit essentially represents a stirred tank reactor with three ports that serve as inlets and outlets. Since dilution, staining processes, and other enzymatic reactions are basically mixing process, they can be easily carried out in the microchamber in a predictable manner.
Port A and B are directly connected to the microchamber, while Port C is connected to the microchamber through an inline filter. With this inline filter, fluids can flow through the microchamber freely but cells are retained inside. To load sample into the microchamber outlet C is blocked (FIG. 2d), sample is pumped through microchamber from port A to Port B. To perform on line dilution of cell samples, water is pumped through the microchamber from Port A to Port B at a predetermined flow rate F for a certain time t, such that the sample is diluted by a factor D given by
D(t)=C(t)/C0=e(F/V)txe2x80x83xe2x80x83(1)
where V is the volume of the microchamber and C0 is the initial cell concentration. In practice, the volume term is modified to account for the dead volume of the connection tubing. To perform on line staining port C is opened while port B is blocked. Solutions such as PBS, or ethanol are pumped through the microchamber from port A to port C, so that cells inside the microchamber can be washed, fixed and stained. After samples are so processed, they are injected into the flow cytometer for analysis.
The flow cytometer used was an Ortho Cytofluorograf IIs (Ortho Diagnostics Systems, Westwood, Mass.) equipped with an argon ion laser (Innova 90-5, Coherent Inc., Palo Alto, Calif.) and a Cicero data acquisition system (Cytomation, Fort Collins, Colo.). The laser was operated at 488 nm (Gfp) or 457 nm (mithramycin), and 100 mW beam power. A bandpass filter (525xc2x115 nm) and an OG530 longpass filter were used to collect Gfp and mithramycin fluorescences respectively. Data were acquired in listmode, pulse area, linear, and logarithmic configurations.
Results and Discussion
System Performance
To test the sample handling system a growth study of E.coli cells was carried out using a spectrophotometer as the detection device instead of a flow cytometer. The purpose of the experiment was to test the reliability of the sampling, degassing, and the dilution subsystems. A satisfactory performance of the system would yield the growth curve of a cell culture with frequent sampling points over the entire growth period by automatically carrying out dilutions to keep absorbance readings in the linear range when higher cell densities were reached.
The output transmittance signals of the spectrophotometer were acquired using the A/D subsystem of DT2805 board. A typical output signal is shown in FIG. 3a. The signal resembles a gamma distribution due to the dispersion of the sample in the carrier stream. the sample concentration was determined by integrating over the entire duration of the signal pulse. Since the dispersion of the cell culture within the carrier stream is not linearly related with the sample concentration, the recorded transmittance signals are not directly proportional to the sample concentration. This relationship can be described by the Taylor dispersion (Taylor, 1953) as follows:                               C                                (            t            )                          =                                                            M                /                π                                                          xe2x80x83                                                          R                2                                                                    4                                                  xe2x80x83                                                π                                                  xe2x80x83                                                Et                                                                    xe2x80x83                                                                        e                                                  (                                      z                    -                    vt                                    )                                            2                        /            4                                          xe2x80x83                              Et                                    (        2        )
where C(t) is the concentration of the sample a the position of the detector at time t, M is the total amount of the sample injected into the carrier stream, E is the dispersion coefficient, R is the diameter of the tube, v is the velocity of the stream, and Z is the distance between the detector and the point of the injection. Transmittance is related to cell concentration according to Beer Lambert""s law (Zubay, 1993),
V(t)=10(1xe2x88x92KC(t))xe2x80x83xe2x80x83(3)
where V(t) is the transmittance output and K is extinction coefficient. Combing equations 2 and 3, the following expression can be derived to relate the amount of sample to the measured transmittance signal:                                       (                      1            -                          log                                            xe2x80x83                                          V                                )                        dt                          xe2x80x83                        ∞                          xe2x80x83                        M                            (        4        )            xe2x80x83(1xe2x88x92logV)dt∞Mxe2x80x83xe2x80x83(4)
Equation 4 is valid over the same linear range described by Beer Lambert""s law. This was determined to be the case for sample absorbances less than 2.0 (FIG. 3b). Therefore, on line dilutions were necessary for dense samples. A zero order algorithm was used to calculate the dilution factor for the next sample (Dj+k) based on the current concentration measurement (Ci) and the initial sample concentration (C0). The algorithm
Di+1=Ci/C0xe2x80x83xe2x80x83(5)
is valid when the frequency of sampling is greater than the frequency of cell division.
The lag phase, exponential growth phase, and the stationary phase can be clearly recognized in the growth curve thus obtained (FIG. 3c). On line measurements showed very few variations associated with measurement errors, and measurements were thus stable and consistent. The on line dilution started automatically 11 hours after the start of the growth experiment, and dilution factors increased from 1 to 27 over the span of the experiment (FIG. 3d). The degassing unit was able to efficiently remove air bubbles from the cell culture samples even during the late stages of the experiment when the cell culture was very dense (OD-40). The two abnormal points shown in FIG. 3a are probably due to air bubbles that likely have originated from open ports on the 10-Position Switching Valve. This potential problem can be avoided by sealing unused ports. One can note that the dilution factors calculated after the overshoots in the measurements did not diverge away, indicating that the zero order algorithm is stable for this application.
Reproducibility of the On-line Flow Cytometry Measurements
A stable sample stream is very important to obtain accurate measurements on a flow cytometer. Hence, pressurized air was used to drive sample from the microchamber to the flow cytometer (FIG. 2e). Most FI systems usually use a mechanical syringe pump. Using the syringe pump, it was found that the coefficient of variation of light scatter distributions of calibration beads obtained was higher than 10% with strong concomitant background noise. In contrast, the use of pressurized air to drive samples gave reproducible, noise free light scatter distributions of calibration beads.
To test whether the on-line measurements indeed yield the correct distributions, fly replicates of light scattering intensity distributions of S.cerevisiae cells measured on-line and off-line were compared (FIG. 4a). It can be seen that the distributions obtained from on-line measurements can be superimposed over those from off-line measurements. The Kolmogorov-Smirnov (K-S) statistic test (Neter, 1988) was performed to verify that the distributions can be considered statistically identical with a confidence level greater than 0.99. Thus, on-line measurements give the same information as off-line measurements.
Reproducibility of on-line measurements as a function of time was tested by comparing light scattering intensity distributions of uniform calibration beads (2.013xc2x10.0251xcexcm, Duke Scientific) measured every ten minutes over a span of 4 hours. Variance in light scattering distributions of these beads is a useful indicator of the optical alignment of the flow cytometer. Hence this measurement was used to estimate the stability of the on-line measurements. It was observed that the coefficient of variation (CV) of the distributions fluctuated very little over four hours of periodic sampling (FIG. 4b). A statistical analysis confirmed that the CVs were identical with 95% confidence (t test, Neter, 1988), confirming that the measurements and the instrument settings were not subject to a drift over time.
The flow rate of samples that can be applied in a flow cytometer depends upon the sample concentration. The arrival of cells of a given concentration at the analysis point in the flow cytometer is governed by Poisson statistics. Hence, sample concentrations have to be adjusted to ensure that the probability of 2 or more cells being analyzed simultaneously is minimized. Here, a threshold of 1% was set for coincident events, i.e., samples whose probability of coincidence of two or more cells exceeded 1% of the probability of single event occurrence were diluted prior to analysis. The lower end of sample concentrations was determined by the minimum number of events desired for acquisition and the time available for sample collection. In our system, the working range of sample concentrations resulted in event flow rates between 100 and 1000 events per second. To examine whether samples whose concentrations varied in this working range were processed similarly, their time profiles (i.e., number of events as a function of time) were analyzed after sample injected for a range of concentrations. Under ideal circumstances with no sample dispersion, these profiles would be described by exponentially decaying functions with the specific rate of decrease equal to the dilution rate of samples out of the mircochamber. The time profiles obtained experimentally were normalized to unit area to yield event frequency profiles for ease of comparison, and they were found to be identical (FIG. 4c). This observation has several important implications. First, the window between the time of injection of sample and the time of analysis of sample was independent of the actual sample concentration. Second, the relative cell number density of the same can be determined as the product of the number of events counted within a fixed time window (for e.g., the xe2x80x9csampling periodxe2x80x9d, FIG. 4c) and the factor dilution. Third, the actual profiles obtained were compared to ideal profiles described above, and they were found to be very similar. After reaching a maximum less than 10 seconds after the sample front reaches the analysis point in the flow cytometer, event frequencies decreased as described by the ideal profile. This implies that the microchamber can indeed be approximated as an ideal stirred tank reactor. Finally, any residual sample is completely flushed away during the flushing period, and hence there is no cross contamination between successive samples. Thus, the system was robust in handling a range in cell concentrations, and yielded very reliable data.
Monitoring Cell Population Dynamics
To simplify the process, we initially measured native properties of cells. These are usually restricted to light scatter intensity measurements. While these parameters are very useful in discriminating cell populations and, in some cases, in estimating cell viability, they usually cannot be directly related to intrinsic quantitative biological properties of cells. Hence, we have expressed the green fluorescent protein (Gfp) to obtain naturally fluorescent protein that has been expressed in many heterologous hosts (Cubitt et al., 1995), and is very useful reporter for quantitative, non invasive detection of single cell gene expression (Subramanian and Srienc, 1996, Natarajan et al., 1998). Gfp expression was induced by the addition of IPTG to exponentially growing E.coli cells. The objective of the experiment was to examine the heterogeneity in levels of protein expression in single cells in an exponentially growing population. Hence, protein synthesis was inhibited five minutes after induction by addition of chloramphenicol. Thus, expression of Gfp in all cells was restricted to a xe2x80x9cpulsexe2x80x9d of finite time. The time of induction is designated as time xe2x80x9c0xe2x80x9d in the graph shown (FIG. 5). The culture was sampled and analyzed every 10 minutes using on-line flow cytometry after induction and inhibition of protein synthesis. On-line dilution was not performed because inhibition of protein synthesis resulted in growth arrest and the cell concentration remained constant.
Shown in FIG. 5a is the time evolution of the cellular fluorescence distribution. The population was initially non fluorescent. After induction, the cells gradually increased in their fluorescence. The increase in the mean fluorescence value of the population (comparable to a population averaged assay) is shown in FIG. 5c (xe2x80x9c100%xe2x80x9d). The kinetics of increase in mean fluorescence are sigmoidal, possibly because nascent Gfp molecules have to fold, cyclize, and oxidize the fluorophore sequentially prior to turning fluorescent. The increase in fluorescence saturates approximately 3 hours post induction. however, a significant fraction of the population remains non fluorescent (20%, FIG. 5d). This subpopulation can be better visualized in the cytogram of FALS versus fluorescence (FIG. 5b). In addition, there is significant heterogeneity in expression among fluorescent cells, indicating variability in the capacity to produce heterologous protein in the population. From a biotechnological process perspective uniform maximal expression of protein is desirable among all cells in the population. One should note that this maximum expression level cannot be inferred from the mean of the entire heterogeneous population due to the presence of non producers and low-level producers. Rather, a single cell assay of the kind described here is necessary. In the above experiment, a choice of the top 10% or 5% of fluorescent cells indicated that this maximum capacity is 3- or 4-fold greater than the population average value (FIG. 5c).
Monitoring Batch Growth Dynamics of E.coli
In order to test the system over longer time periods, the FI-FCM system was used to monitor the growth dynamics of E.coli cells from lag phase to stationary phase. On-line dilution up to 700 fold was performed over the course of growth. E. coli BL21 cells transformed with plasmid pRSET/S65T were grown at 37xc2x0 C. in complex medium containing ampicillin as a selection marker. Even though the culture was grown under non-inducing conditions, leaky expression of Gfp was observed in the population. The cell culture was sampled and analyzed every 10 minutes, and forward angle light scattering (FALS), right angle light scattering (RALS), and fluorescence intensity signals were collected.
After a short lag phase of ca. 20 minutes, cells grew exponentially for four hours, then entered stationary phase (FIG. 6a). The time evolution of the size (approximated by FALS intensity) distribution of growing E.coli culture from lag phase to stationary phase is shown (FIG. 6b). If growth of cells were balanced, then frequency distributions of various properties such as cell size or protein content would be expected to be time invariant. In the early exponential growth phase, the peak of the FALS distribution shifted to the right (including an increase in mean cell size), reached a maximum value, shifted back to lower mean intensity during late exponential growth. A similar trend is observed in the mean FALS signal intensity (FIG. 6d). Thus, growth was exponential, but not balanced. FALS intensity distribution of the growing culture was also monitored. Although Gfp synthesis was not induced, there was sufficient leaky expression of the protein for the fluorescence to be detectable. Interestingly, heterogeneity of expression was observed even among uninduced cells (FIG. 6c). Levels of leaky expression were seen to be inversely correlated to the growth phase as lag- and stationary-phase cells were more fluorescent than exponentially growing cells (FIG. 6d). Additionally, protein content distributions in the population also change with time during the exponential growth period, further indicating that growth was unbalanced as a time invariant physiological state is never reached.
Monitoring Cell Cycle Distribution of S.cerevisiae
To demonstrate the staining capability of FI-FCM system, DNA content of S.cerevisiae cells were measured on-line as described in Methods. Even the application of a simple, single stain requires multiple preparatory steps during which cell samples might potentially be lost. To eliminate this possibility, a 0.2 xcexcm inline filter was used to retain cells while they were treated with various chemicals. The flow through port C was analyzed for presence of cells after each step to ensure the integrity of the membrane. Membrane clogging, frequently a problem in many membrane systems, was virtually eliminated in our design because of co-existing tangential flow between ports A and B, continuous vigorous stirring in the mircochamber, and dilution of cells to a concentration of ca. 105 per mL prior to initiation of staining. Vigorous stirring also ensured that cells did not clump together during the fixation step.
In order to demonstrate staining capability, replicates of a sample of S.cerevisiae cells in late exponential phase were washed, fixed, treated with chromatin denaturation solution, stained with mithramycin (MI), and analyzed on the FCM. An asynchronous population would be expected to have a bimodal DNA distribution, where the two modes correspond to cells in the G1 phase (FIG. 7c). DNA distributions obtained were compared with autofluorescence measurements on fixed and denatured cells that had not been stained. Autofluorescence distribution is clearly unimodal, and well separated from the stained distributions (FIG. 7c). IN comparison, staining does not affect light scatter intensity measurements, hence FALS distributions of unstained and stained cells are identical (FIG. 7a). DNA distributions for three replicate samples were also found to be statistically identical, ensuring reproducibility of the staining process (K-S test, Neter, 1988). Since the entire process is automated, it is easy to envision the use of more complicated staining protocols to tag and quantitate other cellular components also.
Discussion
To determine the state of a growing cell culture, conventional monitoring systems typically evaluate measurable quantities of the abiotic phase from which the state of the culture is inferred. Direct measurement of the physiological state is usually not possible because quantitative methods to rapidly assay the composition of the biomass are limited. Furthermore, the properties of individual cells are different and distributed over a range of physiological states. Therefore, population average data provide only limited information, and accurate information must be sought at the single cell level.
Fredrickson and co workers (1967, 1968) proposed a general mathematical framework, known as population balance theory, to describe cell growth and its interaction with the environment (see also Ramkrishna, 1979, 1985). In this theory, the state of individual cells is specified by the physiological state vector, a collection of state properties such as cell size, protein content, or DNA content. The resulting population balance equations essentially are number balances on individual cells of a population, which keep track of, not only the generation and disappearance of cells, but also of the continuous change in the identity of cells due to physiological growth processes. This modeling framework (known as corpuscular and structured) most realistically represents the evolution of a heterogeneous microbial population. Versions of this model have been used to extract growth parameters from single cell property distributions obtained using flow cytometry (Dien and Srienc, 1991, Kromenaker and Srienc, 1991, 1994 a,b,c). These analyses were however performed off-line for special cases. In general, it has been difficult to apply the population balance model to real microbial processes due to lack of experimental data that would permit identification of model parameters. Such data could possibly be generated by flow cytometry interfaced with appropriate instrumentation for on-line sample processing and analysis.
Hence, we designed and constructed a versatile and modular flow injection flow cytometry (FI-FCM) system. To display the detail of information that can be obtained, the system was used to monitor the heterogeneity of protein expression in an E.coli cell population. The results clearly reveal the need for single cell analysis, since cellular content of even a single component such as Gfp content was distributed in the population. Frequent, automated sampling permitted observation of smooth trends of cellular phenomena. This data could be used to generate accurate estimates of the kinetics of transient events. Furthermore, it has been shown that the system can be used to monitor long term fermentation processes during the course of which cell concentrations would change significantly. Since the system does not require any operator intervention, it is particularly suitable for process monitoring and control applications. The data obtained can be used to determine the detailed physiological state of distribution of the cell population. Additionally, single cell growth parameters can be evaluated. In order to better define the composition of single cells, the range of cellular components that can be monitored can be explained by taking advantage of the design of our microchamber, which permits on-line cell fixation, and staining, as demonstrated in this work.
The presented examples demonstrate that the developed system represents a powerful tool to study cell physiology in a detail that was previously not possible. Moreover, the FI-FCM system will be advantageous for monitoring bioreactors in studies involving transient growth phenomena, estimation of cellular kinetics, or study of synchronous or cyclic trends that might not be observed with infrequent sampling. The system thus has significant potential in biotechnology for the monitoring of microbial populations without the need for excessive manual intervention.

Flow injection flow cytometry system for on-line monitoring of biroreactors and method for monitoring


A polymer composition is disclosed composed of morpholino subunit structures linked together by uncharged, chiral linkages, one-three atoms in length. These chiral linkages join the morpholino nitrogen of one subunit to the 5' exocyclic carbon of an adjacent subunit. Each subunit contains a purine or pyrimidine base-pairing moiety effective to bind by hydrogen bonding to a specific base or base-pair in a target polynucleotide.

Polymers which are designed for base-specific binding to polynucleotides have significant potential both for in vitro detection of specific genetic sequences characteristic of pathogens and for in vivo inactivation of genetic sequences causing many diseases--particularly viral diseases.
Standard ribo- and deoxyribonucleotide polymers have been widely used both for detection of complementary genetic sequences, and more recently, for inactivating targeted genetic sequences. However, standard polynucleotides suffer from a number of limitations when used for base-specific binding to target oligonucleotides. These limitations include (i) restricted passage across biological membranes, (ii) nuclease sensitivity, (ii) target binding which is sensitive to ionic concentration, and (iv) susceptibility to cellular strand-separating mechanisms.
In principle, the above limitations can be overcome or minimized by designing polynucleic acid analogs in which the bases are linked along an uncharged backbone. Examples of uncharged nucleic acid analogs have been reported. Pitha et al (1970a, b) have disclosed a variety of homopolymeric polynucleotide analogs in which the normal sugar-phosphate backbone of nucleic acids is replaced by a polyvinyl backbone. These nucleic acid analogs were reported to have the expected Watson/Crick pairing specificities with complementary polynucleotides, but with substantially reduced Tm values (Pitha, 1970a). One serious limitation of this approach is the inability to construct polymers by sequential subunit addition, for producing polymers with a desired base sequence. Thus the polymers cannot be used for base-specific binding to selected target sequences.
Polynucleotide analogs containing uncharged, but stereoisomeric, methylphosphonate linkages between the deoxyribonucleoside subunits have also been reported (Miller, 1979, 1980; Jayaraman; Murakami; Blake, 1985a, 1985b; Smith). More recently a variety of analogous uncharged phosphoramidate-linked oligonucleotide analogs have also been reported (Froehler, 1988). These polymers comprise deoxynucleosides linked by the 3'OH group of one subunit and the 5'OH group of another subunit via an uncharged chiral phosphorous-containing group. These compounds have been shown to bind to and selectively block single-strand polynucleotide target sequences. However, uncharged phosphorous-linked polynucleotide analogs using deoxyribonucleoside subunits are particularly costly and difficult to prepare; the subunit starting material is quite costly and of limited availability.
More recently, deoxyribonucleotide analogs having uncharged and achiral subunit linkages have been constructed (Stirchak 1987). These uncharged, achiral deoxyribonucleoside-derived analogs are, as mentioned above, limited by relatively high cost of starting materials.

Uncharged morpolino-based polymers having phosphorous containing chiral intersubunit linkages


A LED circuit is provided. The LED circuit comprises: an inductor, a group of LEDs, a power MOS and a switching circuit. The switching circuit comprises: an error amplifier generating an error output, a PWM, a RC circuit and a control means. The PWM generates a switching signal according to the error output to control the power MOS to charge or discharge the group of LEDs; the RC circuit comprises at least one first capacitor each comprising a switch, at least one second capacitors; and a resistive means connected in series between the first and the second capacitors and the error output. The control means generates a control signal according to the dimming signal to turn on the switches to activate the first capacitors during the active period of the dimming signal and turn off the switches to deactivate the first capacitors during the inactive period of the dimming signal.

1. Field of Invention
The present invention relates to a LED circuit. More particularly, the present invention relates to a LED circuit having fast compensation mechanism.
2. Description of Related Art
LEDs are estimated to be four times as efficient as conventional incandescent lights. They are also claimed to be more economically sound than compact fluorescent bulbs that contain harmful mercury and are supposed to last a lot longer than the conventional lighting. Thus, LEDs may become the mainstream of the lighting technology.
The switching circuit in the LED circuit is to perform charge and discharge on the LEDs. The PWM in the switching circuit requires a RC circuit with large RC constant to perform compensation. However, the conventional design of the RC circuit with large RC constant can provide large amount of charging current but result in low discharging activity. Thus the switching activity of the LED circuit losses the linearity due to the RC circuit.
Accordingly, what is needed is a LED circuit with a new design of the switching circuit to provide the compensation mechanism without losing of the linearity.


An intelligent jack provides a physical port identifier (PPID) to an upstream device, such as a network switch. The network switch receives the PPID on a particular physical port. The network switch accesses port configuration data to configure the particular physical port, such as to a particular virtual local area network (VLAN). Port connection data associating the physical port with the PPID may be generated. Changes to the port connection data may generate an alarm.

Computer networks may use structured cabling to exchange signals. The structured cabling may include wires, optical fibers, waveguides, and so forth that are deployed within a facility to provide connectivity to connected devices. The structured cabling may terminate at an endpoint, such as a jack, at a particular location in the facility. It is possible for a jack to be incorrectly connected to a device such as a switch, such that the jack provides connectivity to a network other than that desired. As a result, a potential security vulnerability may be exposed.
While implementations are described herein by way of example, those skilled in the art will recognize that the implementations are not limited to the examples or figures described. It should be understood that the figures and detailed description thereto are not intended to limit implementations to the particular form disclosed but, on the contrary, the intention is to cover all modifications, equivalents, and alternatives falling within the spirit and scope as defined by the appended claims. The headings used herein are for organizational purposes only and are not meant to be used to limit the scope of the description or the claims. As used throughout this application, the word "may" is used in a permissive sense (i.e., meaning having the potential to), rather than the mandatory sense (i.e., meaning must). Similarly, the words "include," "including," and "includes" mean including, but not limited to.


A method of adding alloying elements, including highly reactive metals such s lithium, to molten aluminum so that the normally occurring oxidation reaction of such elements with the atmosphere is minimized. After adding all alloying elements, except the highly reactive metals, to the molten aluminum, and after the alloyed melt has been subjected to a degassing and filtering process, the reactive metals are introduced in a mixing crucible as the final step prior to the casting operation. The desired concentration of reactive metal in the melt is achieved by controlling the relative amounts of reactive metal and alloyed melt. Uniformity of the mixture is controlled by mechanical stirring. The alloyed metal is then cast into ingots.

The present invention relates to methods of making aluminum alloys, and more particularly to a method of alloying aluminum with highly reactive metallic elements which tend to increase the oxidation rate of the melt, as for example, lithium.
Prior methods for melting aluminum alloys in preparation for ingot casting practices generally employ the addition of alloying elements to the aluminum melt in large melting furnaces. While minor alloying elements such as titanium-boron may be added at some point after the molten metal has left the melting furnace, this method is not employed for major alloying elements where concentrations of such elements must be carefully controlled. One of the major problems encountered with prior art alloying methods is that hydrogen is absorbed by the molten metal as a result of the reaction between the melt and the moisture in the air in the open furnaces. To minimize oxidation reactions, molten salt flux has been used on top of the molten metal. Yet even where the flux has been employed, large concentrations of hydrogen are found in the melt, and, unless removed, cause an unacceptable degree of porosity in the ingots. This "degassing", as the practice is commonly known in the art, is accomplished by bubbling a gas, usually containing chlorine, through the melt. A final degassing may be performed in a smaller holding furnace located closer to the casting station.
When lithium is used as an alloying element, it can only be added after all degassing has been completed. Lithium is added in either a solid or liquid state to the melting furnace or to the smaller holding furnace. In either case, it must be held under the surface of the melt until it dissolves.
Many difficulties have been encountered with lithium additions. Principally lithium has been found to significantly increase the oxidation rate of the melt. Lithium also contaminates the refractories in the furnace lining, making the furnace unsuitable for melting lithium-free alloys without a costly relining of the furnace. Special refractories and materials which are resistant to attack by lithium must be used throughout the melting and metal transfer stages. Moreover, the aluminum melt cannot be effectively degassed after the lithium is added without a resulting loss of much of the lithium. Thus because of the increased rate of oxidation after the addition of lithium, as well as the long holding time before all the metal finally solidifies in the ingot, significant loss of the costly lithium is very probable, and control of the desired concentration of lithium becomes critical. Another problem encountered concerns the considerable quantities of hydrogen which are absorbed by the melt after the lithium is introduced. Stirring the melt, after addition of the lithium, is performed to encourage uniformity of the composition, but in fact disrupts the protective cover of flux and results in further oxidation and hydrogen absorption. One proposed method for controlling this undesired oxidation involves covering the entire system (melting furnace, metal transfer troughs, holding furnace, and ingot casting station) and maintaining a dry, inert atmosphere over the molten metal. Unfortunately, implementation of this method would require redesign and reconstruction of the furnaces. Use of the method would also complicate control and monitoring of the casting procedures and equipment, and would be financially prohibitive.

Method of adding alloy additions in melting aluminum base alloys for ingot casting

The United States of America as represented by the Secretary of the Navy


A contactless power transmission device includes: a plurality of power transmission coil units; a plurality of detection units configured to detect a foreign substance on and around each power transmission coil unit; a communication unit configured to communicate with a vehicle; and a control unit configured to select one of the plurality of power transmission coil units based on information about a mounting position of a power reception device from the vehicle obtained by the communication unit, and to guide, when a detection unit detects a foreign substance at the selected power transmission coil unit, the vehicle toward a power transmission coil unit different from the selected power transmission coil unit, before the vehicle stops. This can prevent a reduction in power transfer efficiency due to a foreign substance or the like in a power transmission device including a plurality of power transmission coils.

In recent years, various contactless charging systems have been proposed, and some of them have been proposed to be used to charge a vehicle.
A vehicle may be charged, for example, by contactlessly transferring electric power from a power transmission coil of a power transmission device to a power reception device (for example, a power reception coil) of the vehicle (for example, Japanese Patent Laying-Open No. 2013-126326).


The method provides technical nitrogen instead of pure nitrogen in liquid form which has to be heated to be brought in gaseous form for laser cutting. Atmospheric air is compressed and driven through a cascade of high density bundles of hollow membrane fibers to permeate oxygen and air""s component gases and yield technical nitrogen, and the pressure of the technical nitrogen is boosted to feed the laser cutting equipment. The method thus improves the laser cutting so as to avoid the drawbacks resulting from use of nitrogen in liquid form obtained by the cryogenic process by using technical nitrogen obtained via the aforesaid hollow fiber membrane technology in an efficient and cost effective manner.

This invention relates to a method for laser cutting wherein nitrogen is used to avoid oxidation of the metal during passage of the laser beam.
Laser cutting is state of the art for cutting of thick or thin metal parts according to most diverse geometries. As sublimation of the metal occurs at various temperatures over and under the part being cut, the laser beam is confined by means of pure nitrogen which acts as a cutting gas to prevent fusion of the metal which would allow alloy of air molecules to the metal.
Pure nitrogen is obtained by a cryogenic process and supplied in liquid form. The liquid nitrogen is therefore heated to be brought in gaseous form to feed the laser cutting equipment at a pressure about 25 bar and at a rate of 50 m3/hour or a multiple thereof depending on the number of laser beams of the cutting machine.
The use of pure nitrogen in liquid form is very expensive due to the cryogenic process. Handling thereof is also expensive because it requires heavy containers to withstand a pressure of approximately 30 bar during storage and transit. Furthermore, heater equipment is needed to heat the liquid nitrogen to bring it in gaseous form to feed the cutting machine. All these operations require precautions and safety measures in terms of personnel and equipment and they are energy consuming, which further raises the cost of laser cutting.
In the mid-1980""s, based on the varying rates of permeation of air""s component gases, a hollow fiber membrane technology was developed to generate technical nitrogen, i.e., gaseous nitrogen up to about 99,9% pure. According to this technology, compressed air passes through a high density bundle of hollow membrane fibers whereby the relatively fast gases present in the airxe2x80x94oxygen, carbon dioxide and water vaporxe2x80x94diffuse through the semi-permeable membrane surface, leaving behind a stream of high purity gaseous nitrogen. The operational performance of the system is determined by a number of factors. For example, the flow rate of nitrogen produced by the membrane fibers varies inversely with the nitrogen purity required. The nitrogen flow rate is directly related to the air supply pressure. Further, the nitrogen flow increases as the temperature of the feed air increases. The membrane fibers are engineered into modules available in an array of sizes and capacities, and the system is an advantageous source of nitrogen when liquid nitrogen supplies are impractical, unreliable and cost-prohibitive.
U.S. Pat. No. 5,763,855, the content of which is incorporated herein by reference thereto, discloses a method for laser cutting wherein nitrogen is used to avoid oxidation of the metal during passage of the laser beam, comprising the steps of providing an atmospheric air supply; compressing said atmospheric air; driving said compressed atmospheric air through a first density bundle of hollow membrane fibers to permeate oxygen and air""s component gases through said hollow membrane fibers and yield technical nitrogen at a first purity at the end of said first high density bundle of hollow membrane fibers; and collecting said technical nitrogen at the end of said first high density bundle of hollow membrane fibers.
U.S. Pat. No. 5,383,957, the content of which is incorporated herein by reference thereto, discloses a multistage membrane system for the production of high purity gases.
What is needed therefore is a means to improve the laser cutting by a method which avoids the drawbacks resulting from use of nitrogen in liquid form obtained by the cryogenic process by using technical nitrogen obtained via the aforesaid hollow fiber membrane technology in an efficient and cost effective manner.
The method provides technical nitrogen instead of pure nitrogen in liquid form which has to be heated to be brought in gaseous form for laser cutting. Atmospheric air is compressed and driven through a cascade of high density bundles of hollow membrane fibers to permeate oxygen and air""s component gases and yield technical nitrogen, and the pressure of said technical nitrogen is boosted to feed the laser cutting equipment. The method thus improves the laser cutting so as to avoid the drawbacks resulting from use of nitrogen in liquid form obtained by the cryogenic process by using technical nitrogen obtained via the aforesaid hollow fiber membrane technology in an efficient and cost effective manner.


An improved process for production of phenylalkylsulfonate compounds whereby the proportion of the 2-alkylphenylsulfonate isomer is reduced relative to the higher numbered isomers thereof (3-alkyl; 4-alkyl; etc.). After alkylation of aromatic compounds to produce a mixture of alkylbenzenes, the 2-alkylbenzene isomer is selectively cracked to lower boiling products, leaving the higher numbered isomers substantially unreacted. Subsequent sulfonation results in alkylphenylsulfonate derivatives having improved detergency properties.

1. Field of the Invention
The present invention relates to improved alkylphenylsulfonate detergent compounds. In particular, it is concerned with a method of producing alkylphenylsulfonates having reduced 2-alkylphenylsulfonate isomer content.
2. Description of the Prior Art
Linear alkylbenzene sulfonates containing alkyl side chains of approximately 8 to 16 carbon atoms in length are used as surface active agents in commercial detergent compositions. The scientific literature on the subject has indicated that the average location on the alkyl chain of the phenyl group can have significant and important effects on the detergency properties of the sulfonate. It has been found that by minimizing attachment of the aromatic ring to the alkyl chain at the #2 and #3 carboon atom positions and maximizing the content of isomers having a more centrally located phenyl group is of particular benefit with respect to important detergency considerations. For instance, it has been demonstrated in studies of various dodecylphenylsulfonate isomers and mixtures that one may achieve significant increases in solubility, wetting power and foaming power merely by shifting the average phenyl group location to more internal positions on the alkyl chain. [Tjepkena et al., 5th World Petroleum Congress, Sect. 4, No. 21 (1959).]
Alkylphenylsulfonates are commonly prepared from alkylbenzene compounds, the position of the phenyl group in the intermediate being fixed during the initial reaction of benzene with the linear olefin. The production of the alkylbenzene is conventionally carried out in the presence of a Friedel-Crafts catalyst (e.g. AlCl.sub.3) to yield a mixture of all of the possible positional isomers. Attempts to reduce the external alkylbenzene isomer concentration (i.e. the 2-alkylbenzene), and thereby increase the relative concentration of the more desirable internal isomers (3-alkylbenzene; 4-alkylbenzene; etc.), have been reported, but only small reductions of the 2-alkylbenzene isomer content have been achieved.

Preparation of improved alkylphenylsulfonates


A communication system, method, and components are described. Specifically, a communication system having the ability to carry a transitive context and communicate the transitive context to new participant user agents for continuity through all related call dialogs is disclosed. The transitive context communication is possible through the use of a newly created SIP dialog using a REFER message and/or an INVITE message for all call flows and topology change operations.

Using Session Initiation Protocol (SIP), calls can be moved around using what is known as call redirection. Using SIP, applications may also send requests to initiate new calls. Call redirection may include but is not limited to common movements of a call like transferring a call to another person, conferencing participants into calls, joining two calls into a conference, and extending a call where a call moves from one device to another and the users remain the same. Call initiation may include manual call out from a person or automatic call out from a communication system. When a call topology changes or a particular type of call is initiated, a calling and/or called party may have no idea why the call is coming to him or her or why a call should go out. Lack of context can be particularly problematic for calls received by, initiated by, and subsequently moved around inside a contact center.
One example of a redirected call with no context delivery is the transfer of a call to a contact center supervisor. When the transferred call comes in to the supervisor, the supervisor may have no idea what to expect since the transferred call provides no context. The lack of context is typically handled today in contact centers with a feature known as attended transfer, where an agent verbally relays the context of the call to the supervisor to whom the call is being transferred. Once the context is verbally relayed, the call is transferred to the supervisor and the agent drops off of the call. Other strategies that attempt to relay some call information include Hypertext Transfer Protocol (HTTP)/web information, case identification (ID) number, ticket/work item number, customer number, customer information tagging, information appending, etc. A standard approach to provide context for variety of call topologies, including behavior for called, calling, requested, moved, and transferred calls is needed.


A process for production of self-assembled quantum dots is described which does not entail any processing steps before or after growth of the quantum dots. The process uses in situ formation of three dimensional islands which occurs during epitaxy of material with a different lattice parameter than the substrate. Further deposition of the substrate material then produces single or multiple buried two dimensional layers of randomly distributed or selectively positioned and substantially uniform sized quantum dots. These layers are free of defects and interface states. The lateral dot diameters vary between 140 to 300 Angstroms by appropriate choice of deposition parameters.

1. Field of the Invention
The invention relates to the field of fabrication processes and structures for quantum dots, and in particular, for semiconductor quantum dots and the process for making the same using strains created in the epitaxial growth layer as a result of differences in crystalline lattice spacing.
2. Description of the Prior Art
The fabrication of very small semiconductor structures to exploit the quantum mechanical behavior of carriers within semiconductor material is well established. However, the fabrication of practical structures for quantum confinement in two dimensions (quantum wire) and in three dimensions (quantum dots) has generally been unsatisfactory. In an attempt to attain the highest levels of confinement, as in a quantum dot, several methods have been used, including growth on vicihal surfaces. See O. Brantit et al., Phys. Rev. B 44, 8043 (1991) for the use of cluster formation from solution precursors; see M. L. Steigerwald et al., Ann. Rev. Mater. Sci. 19, 471 (1989), and M. A. Olshavsky et al., J. Amer. Chem. Soc. 112, 9438 (1990), for gas-phase nucleation; see A. Saunders et al., Appl. Phys. Lett. 60, 950 (1992), see G. D. Stucky et al., Science 247, 669 (1990), for loading of semiconductors and mesoporous cages; and for several other ex-situ processing techniques, see Optics of Excitons in Confined Systems, A. Quatropani Editor Institute of Physics, London, (1991). Most of these prior techniques suffer from poor interface quality and size nonuniformity giving rise to large surface recombination velocities.
Highly strained heteroepitaxial growth generally proceeds by the formation of islands after initial layer-by-layer growth which is referred to as StranskiKrastanow growth. Recent studies of indium gallium arsenide, (InGaAs) on gallium arsenide (GaAs) by scanning tunneling microscopy and transmission electron microscopy and of germanium/silicon (Ge/Si) by transmission electron microscopy have demonstrated that at the initial stages of formation, these islands are dislocation-free and coherently strained to the substrate, See S. Guha et al., Appl. Phys. Lett. 57, 2110 (1990); for transmission electron microscopy see D. J. Eaglesham et al., Phys. Rev. Lett. 64, 1943 (1990); and for transmission electron microscopy in Ge/Sisee M. Krishnamurthy et al., J. Appl. Phys. 69, 6461 (1991) and B. G. Orr et al., Euro Phys. Lett. 19, 33 (1992).
Though a clear mechanism for this strain relief has yet to emerge, it is thought to occur by elastic relaxation of the nearest substrate layer or by kinetics of strain induced surface roughening, C. W. Syder et al., Phys. Rev. Lett. 66,3032 (1991). It is clear that at the initial stages of growth, introduction of dislocations arising out of misfit relief can be avoided. At the later stages of growth, dislocations may form when the islands coalesce, leading to the degradation of the layer. Consequently, most of the studies have concentrated on suppressing island formation, such as shown by M. Kopel et al., Phys. Rev. Lett. 63, 632 (1989), or on using growth kinetics to extend the onset of islanding. Studies of the microstructure evolution of coherent islands have been reported for germanium on silicon by M. Krishnamurthy et al. supra and M. Tabuchi et al., Science and Technology Mesoscopic Structures, S. Namba et al. editor (Springer, Tokyo 1992) at page 379. It was shown that under certain growth conditions, sharp island-size distributions could be obtained, M. Krishnamurthy et al. supra. A study of the InAs three dimensional islands on GaAs surfaces was performed and the optical properties were reported, although island-size distributions or defects associated with them were not considered.
What is needed then is a methodology for fabricating quantum dot structures without any of the additional processing steps which the prior art studies would dictate is required, and for fabricating quantum dot structures with a uniformity of defect-free dots with sharply peaked, size distributions.

Quantum dot fabrication process using strained epitaxial growth

The Regents of the University of California


A portable pouch opener for countertop positioning for opening and filling a bag includes a portable housing positionable upon a desktop bench workspace. The housing has a magazine containing a supply of bags to be opened and filled. A first suction device is mounted for being moved into engagement with a bag in the magazine. The first suction device has a source of vacuum to activate the first suction device when placed into contact with one wall of the bag. Vacuum from the first suction device is withdrawn from the bag, attaching the bag to the first suction device, to remove the bag from the magazine and bring it to an opening position. An opposite facing wall of the bag is in contact with a second suction device having a source of vacuum, so that said opposite facing wall is engaged by said second suction device. Then the first suction device is retracted to separate the walls of the bag to produce an opening into the bag, allowing the bag to be filled and optionally sealed.

Pouch and bag openers are known for insertion of products. However, these stationary bag openers are often complicated and bulky, and not portable.
These complicated and bulky pouch and bag opening machines can be useful for packaging of pre-measured liquid or solid food products from automated dispensers which control the exact amount of food introduced into the package.
However, in manufacture of small medical devices, the product to be inserted is often a single discrete, specially manufactured device such as a syringe, a patient monitoring device or a precision single use surgical or dental tool. There are occasions when more than one device will need to be inserted, or one or more devices will need to be inserted with other components, desiccants, instructions, etc. They are often transported manually during manufacture and sterilization, and are not conducive to insertion by complicated bulky packaging machines at a single location in a manufacturing facility.
In the absence of complicated, costly bulky stationary packaging devices, especially in small medical device manufacturing facilities, the pouches for holding single items are manually opened and sealed, often increasing the risk of repetitive stress injuries, such as carpal tunnel syndrome, to the employees conducting the pouch opening and insertion of products therein.
In addition, the use of complicated and bulky stationary pouch and bag openers prevents their portability, which restricts their use in different locations of a manufacturing facility. These stationary machines can't be readily moved between operator. stations.
Moreover, the permanently installed, bulky pouch opening machines cannot be moved to other locations, such as at facilities of remote contractors manufacturing parts for insertion into the pouches.
Among related patents include U.S. Pat. No. 2,601,480 of Williams for a frame mounted bag opening and spreading mechanism which uses puffs of air to open the bags, U.S. Pat. No. 2,732,988 of Feinstein for a base-mounted multi-mechanism packing and sealing apparatus, U.S. Pat. No. 2,969,629 of Blais for a multi-slotted packaging apparatus for bales of smaller boxes, U.S. Pat. No. 2,973,612 of McGowan for a multi-gear, multi-pulley bag opener mechanism with a mechanical funnel skirt made of two pivotable skirt halves and U.S. Pat. No. 3,225,515 of Inglett for an automated bag hanger.
Other related patents include U.S. Pat. Nos. 3,243,937 of Ragan and U.S. Pat. No. 3,495,378 of Kipers, both for bag openers having a plurality of bag opening elements on a continuous belt, U.S. Pat. No. 3,896,605 of Chevalier for a bag opener with moving jaws, U.S. Pat. No. 3,990,216 of Martin for a post mounted bag feeder and closer using fluid pressurized clamps, U.S. Pat. No. 4,057,951 of Schneider for a cam and gear controlled packaging machine for filling food packages and U.S. Pat. No. 4,078,358 of Henderson for a floor mounted bag transporter and filler.
U.S. Pat. No. 4,172,349 of Lipes discloses a bagging machine having a mechanical retractor for opening a bag and U.S. Pat. No. 4,509,313 of Koppe describes a pouch forming and filling apparatus which synchronizes the filling of pouches from a plurality of product dispensing funnels and the sealing of the filled bags.
Other patents include U.S. Pat. No. 4,554,776 of Chikatani for a floor mounted filling and binding packaging machine, U.S. Pat. No. 5,351,465 of Fortnam for a bag opener with arcuate strip springs which spread apart, U.S. Pat. No. 5,442,898 of Gabree and U.S. Pat. No. 6,263,645 of Burford for openers and fillers for bags which use the pressurized force of air jets to open the bags, U.S. Pat. No. 5,802,817 of Hood for an opener and filler for a wicketed bag which uses a pressurized fluid to open the bags and U.S. Pat. No. 6,318,051 of Preiss for an inserter mechanism for inserting individual pills into plastic blister packs for single dosages.
However, these generally bulky, complicated stationary prior art devices do not describe portable devices which can be easily set up for insertion of single discrete, specially manufactured devices which can be moved between operator stations to fit the rapidly changing needs of manufacturers, especially in the specialty medical manufacturing field at variable locations, both on and off site.

Adaptive Manufacturing Technologies, Inc.


There is provided an anti-bacterial mildewproofing laminate, comprising at least two films or sheets each having organic substance permeability different from one another; and at least one adhesive layer which comprises an anti-bacterial mildewproofing agent containing parachlorometaxylenol as an active ingredient, and which intervenes between the adjacent films or sheets so that they are clad to one another. The above laminate exhibits durable anti-bacterial and mildewproofing actions without any special processing, is inexpensive, and shows anti-bacterial and mildewproofing actions even on surfaces out of contact with the laminate

1. Field of the Invention
The present invention relates to a laminate having anti-bacterial and mildewproofing actions, and more particularly to a laminate having anti-bacterial and mildewproofing actions such as a laminated film and a laminated sheet having anti-bacterial and mildewproofing actions, and a bag made of the same.
2. Description of the Related Arts
Recently, greater importance of an anti-bacterial and mildewproofing properties of various articles is emphasized not only in facilities wherein hygienic control is required, such as hospitals, but also in homes in general, and along therewith, impartment of anti-bacterial and mildewproofing actions to films, sheets, bags, and the like for packaging is demanded.
Conventionally, as films having an anti-bacterial effect, films are known that are made by mixing an inorganic type anti-bacterial agent containing a metal or metal ions in a synthetic resin. However, although the anti-bacterial effect of this type of films lasts long, this type of films has the defect that the effect is exhibited only on the surfaces brought into contact with the film.
On the other hand, a bag is suggested that contains an anti-bacterial agent of an organic substance (natural substance) type that exhibits an anti-bacterial effect also on surfaces not in contact therewith, but generally the effect of the anti-bacterial is poor in durability, and to make it durable, a special treatment such as microcapsulization is needed, leading to the defect that the cost is increased remarkably.

Laminate having anti-bacterial and mildewproofing actions


A vibration control device of an active type for a structure comprising a first additional mass body movable relative to the structure; spring means for giving a period to the additional mass body which synchronizes with the natural period of the structure; a second additional mass body supported by and movable relative to the first additional mass body; and drive means for applying a control force between the first and second additional mass bodies in response to a sensed vibrations of an earthquake or the like. Laminated rubber support provides main spring means for synchronizing with the assumed natural period of the structure. Auxiliary spring means, such as laminated rubber or coil springs, is separately provided for fine tuning the period of the device. The responses from the structure are reduced by adjusting the difference between the assumed and actual natural periods of the structure by use of the auxiliary spring means and by providing the control force from the drive means.

1. Field of the Invention
The field of invention is vibration control devices and the means to control these devices, which are employed to protect structures from the destructive forces of earthquake, high winds, and the like.
2. Description of Related Art
Examples of vibration control devices of the dynamic damper type (DD) in the subject field of invention are illustrated in Japanese Patent Laid-open No. 63-76932 and Japanese Patent Publication No. 3-38386.
Prior art FIG. 10 of the subject application shows a vibration model of a DD applied to a structure, wherein m.sub.1 is a mass of a main body of the structure, constituting a main vibration system, and m.sub.d is a mass of an additional mass body constituting a damping system. The spring constant of the main body of the structure is identified as k.sub.1. The main body of the structure and the additional mass body are connected by means of a spring having a spring constant k.sub.d and a damper having a damping coefficient c.sub.d. Displacement of the mass m.sub.1 is indicated by the arrow x.sub.1, and counter displacement of mass m.sub.d is indicated by the arrow x.sub.d.
A natural angular frequency of the main vibration system is given by: EQU .omega..sub.1 =(k.sub.1 /m.sub.1 ).sup.1/2
The mass m.sub.d of the damping system is normally designed so that the ratio of the mass m.sub.d to the mass m.sub.1 of the main vibration system may be set to approximately become: EQU .mu.=m.sub.d /m.sub.1 .gtoreq.0.01
At this time, the natural angular frequency of the damping system is given by: EQU .omega..sub.d =(1/1+.mu.).omega..sub.1
A damping coefficient c.sub.d and a damping factor h.sub.d are represented by the following equations, respectively:
c.sub.d =2 m.sub.d .omega..sub.d h.sub.d PA1 h.sub.d =[3.mu./8(1+.mu.)].sup.1/2
There are also active mass drivers (AMD) which function as vibration control devices, e.g. , U.S. Pat. No. 5,022,201 (Japanese Patent Laid-open Nos. 1-275866, 1-275867, 1-275868, and 1-275869.
Prior art FIG. 11 shows a vibration model of an AMD which applies a control force u(t) by means of hydraulic power or electromagnetic force of an actuator positioned between the main body of the structure having a mass m and the additional mass body having a mass m.sub.d, to actively control the vibration of the structure.
In the prior art control device of FIG. 11, assuming that a spring between the main body of the structure and the additional mass body constituting a vibration control device is set pursuant to the equation EQU .omega..sub.d .ltoreq.(1/2).omega..sub.1,
the control force u(t) is given by the following equation: EQU u(t)=G.sub.1 (dx.sub.1 /dx)+G.sub.2 (dx.sub.d /dt)
wherein G.sub.1 is a gain in a circuit including an automatic gain control circuit (AGC) or the like against the response speed of the structure and attains the correspondences of large inputs through small inputs, wherein G.sub.2 becomes a negative value. The second term in the above equation gives a damping property to the additional mass body and attains a stability thereof by adding the product of a gain G.sub.2 and vibration speed to the control force of the additional mass body.
As shown in prior art FIG. 12, a spring having a spring constant k.sub.d is added to the AMD described above, in parallel with the control force u(t) to obtain a vibration control effect by means of less control force in comparison with that of an active tuned mass damper (designated as ATMD hereafter. )
In an ATMD, a spring constant k.sub.d is set so that the vibration of an additional mass body may synchronize with that of a structure, that is, EQU .omega..sub.d =.omega..sub.1
and the control force u(t) is, for example, given by the following equation, EQU u(t)=G.sub.1 (dx.sub.1 /dt)+G.sub.2 (dx.sub.d /dt)+G.sub.3 (x.sub.1 -x.sub.d)
wherein G.sub.3 is a gain having a negative sign and cancels a part of the inertial force applied to the additional mass body at a vibration time due to the third term in the above equation, so that the additional mass body may be vibrated by less control force.
Japanese Patent Publication No. 3-70075 discloses a vibration control device of an active type for controlling structural vibration due to an earthquake or the like. A second additional mass body having a mass less than the first additional mass body of the DD is connected to the first additional mass body of the DD through a spring and an actuator, wherein a control force is applied to the second additional mass body by the actuator.
In the above-mentioned vibration control device, the DD has an advantage in that no energy supply to the device is necessary. The vibration control effect is determined by the mass ratio of the first additional mass body to the mass of the structure. Therefore, it is necessary to have a large first additional mass body with which it is difficult to obtain a sufficient vibration control.
In the case of the AMD, more control can be expected by the use of an additional mass body having a small mass in comparison with that in the case of the DD. However, an energy supply is necessary, and it is necessary to arrange additional facilities and equipment for the energy supply. These additional facilities include a specially designed control circuit for applying a predetermined control force in accordance with the vibration responses of the structure and the additional mass body; means to secure stability of the device; and means to prevent malfunction of the device.
As described above, the ATMD has an advantage in that the control force can be lessened in comparison with that in the case of the AMD, but it takes time to synchronize the vibration of the additional mass body with the vibration of the structure EQU (.omega..sub.d =.omega..sub.1)
Furthermore, in the ATMD a portion of the inertial force can be canceled by providing a term corresponding to the spring force in order to obtain a large control effect by less control force. However, there is a problem in that a synchronizing period is newly generated for a period longer than the natural period of the structure in the periodic components of the earthquake, wherein the amplitude of the additional mass body increases so that control becomes difficult.


The invention relates to a process for recovering alkali and heat from a black liquor (5) containing silicate from a soda cook of e.g. grass, reed, straw and bagasse. In the process the black liquor (5) is treated with a gas (6) containing carbon dioxide to precipitate silica and lignin, the precipitate (9) is separated (2) from the black liquor, which is evaporated (3) and burnt (4) to generate heat and to recover a sodium carbonate melt. In the invention the black liquor (5) containing silicate is neutralised with a surplus of the gas (6) containing carbon dioxide, which preferably contains over 60% by volume of carbon dioxide. The evaporation (3) of black liquor mainly takes place after the precipitate (9) rich in silica has been separated (2). The combustion is performed with pure oxygen gas or oxygen-enriched air (14), after the black liquor has been brought to a temperature near its boiling point by direct contact with the hot exhaust gases from combustion, all these operations under a substantial over-pressure of at least 100 kPa. With this procedure, a sodium carbonate melt is recovered and a gas (17) containing over 60% by volume of carbon dioxide is formed, which is used to neutralise the black liquor (5) containing silicate.

The production of chemical pulp for paper production chiefly uses wood as a raw material. However, about 10% of the chemical pulp produced the world over is produced from other plants and plant residues such as grass, reed, straw and bagasse. The characteristic of these raw materials is that they contain, among other substances, considerably more silicon than wood does.
Chemical paper pulp is produced by cooking the raw material with chemicals, non-fibrous material being then chemically dissolved. The cellulose fibres constituting the paper pulp will remain. A large part of the dissolved material consists of lignin, but also of other organic and inorganic substances. The production of chemical pulp from wood mainly implements the sulphate process, in which sodium hydroxide and sodium sulphide are active components of the cooking liquor. For the cooking of non-wood raw material sodium hydroxide alone is required as an active chemical, and for this reason the major part of chemical pulp production from these raw materials is performed with the process called the soda process.
In the soda process the raw material is heated together with an alkaline cooking liquor containing sodium hydroxide to a temperature in the range from 140 to 170.degree. C. under pressure. The cooking liquor should have a high alkaline concentration. Under these conditions, the main portion of lignin will be dissolved from the raw material, however, also the main portion of the silicon in the raw material will react with the sodium hydroxide, forming water-soluble sodium silicate. Thus the black liquor produced in cooking will contain silicate ions in addition to lignin and other organic compounds.
On principle, sodium hydroxide can be recovered from the black liquor and the organic substance in the black liquor can be utilised as a fuel for energy generation. Contrary to the sulphate process, in which the cooking liquor contains sulphide ions and the combustion of black liquor requires a chemically reducing environment in the bottom section of the combustion equipment, the black liquor obtained by using the soda process can be burnt even under highly oxidising conditions. Chemical recovery is performed by evaporating the black liquor to a suitable dry matter content and by burning the evaporated liquor by means of excess oxygen. The inorganic combustion residue, consisting mainly of sodium carbonate, is dissolved in water and causticised with burnt lime to form sodium hydroxide, which in turn is used in pulp cooking. This is the practice in the case of black liquors poor in silicate. However, the presence of silicate in the black liquor entails serious problems regarding recovery. The main problems consist in scaling of the heat exchange surfaces of the evaporator in which the black liquor is concentrated, high viscosity of the concentrated black liquor, which impedes liquor combustion, and forming of calcium silicate in the lime used for converting the sodium carbonate to sodium hydroxide. The calcium silicate makes recycling of the lime difficult or quite impossible. Due to the problems caused by silicate, pulp mills using e.g. straw as a raw material are unable to reclaim the black liquor and to recover sodium hydroxide from this, but instead discharge the black liquor. This is evidently a heavy financial burden for the mill and very detrimental to the environment around the mill.
There have been attempts to solve the problems caused by silicate in the black liquor over the past 20 years. It is a well-known chemical fact that, when the acidity, i.e. the pH of the solution is reduced, the silicate ions will form a partly gelly and partly crystalline silica (cf. e.g. Chemical Abstracts, Vol. 89, No 61292, 1978). Methods for removing silicate from black liquor have been developed on the basis of this crystallisation. A process following the procedure described here was installed at the RAKTA company's mill in Egypt. The pH reduction is performed by introducing flue gas containing carbon dioxide into the black liquor. In accordance with the described procedure, the substance containing silicon is separated from the black liquor by sedimentation and/or centrifugation, after which the silicon is precipitated as a mixture of silica and calcium silicate by adding burnt or slaked lime. The process has been patented by J. Mulder and P. Gutmann (Germany, 3003090 8/1981).
All the same, the RAKTA installation never worked satisfactorily in the practice. The reason for this is that, in order to convert a sufficient portion of the silicate into a crystalline and hence separable form, the pH must be so much decreased that also a portion of the lignin in the black liquor will be converted into a gelatinous phase and that makes the separation of the silica and the gelatinous lignin from the liquor very difficult. Removal of lignin from the liquor will decrease its calorific value, so it will not be high enough to allow it to be burnt in steam boilers developed for liquor combustion. Another attempt to enhance the techniques developed in the late 70's is being made at a mill in Tamil Nadu, India. This process still follows the same principle as the RAKTA process. The operation aims at recycling crystal nuclei of silica at a pH high enough to selectively precipitate silica without coprecipitation of lignin.
Another means of removing silicon from the chemical recovery cycle at a mill which produces paper pulp from straw following the soda process is described in the Indian patent 17 1289 from 1989. In this process, the silicate-containing black liquor is evaporated to an approx. 40% dry matter content, after which it is mixed with dry organic material, e.g. rice husks, the ensuing dry matter content being approx. 60 per cent. The mixture is burnt on a chain grate in the furnace of a steam boiler. The inorganic combustion residue, containing mainly sodium carbonate and sodium silicate, is dissolved in water, and flue gases containing carbon dioxide are introduced in the aqueous solution. The carbon dioxide reduces the pH, and then the silicate forms poorly soluble silica, which is filtrated out of the solution. In this manner, the silicon can be removed without the lignin interfering with the separation of the precipitate or it losing its energy content. The process of the patent involves the problem of requiring the combustion temperature to be maintained within the range from 750 to 820.degree. C. to prevent the ashes from melting and to simultaneously completely burn the organic substance completely. These aims are considered to be very difficult to achieve at a full-scale plant, and the process has not been industrially implemented so far.
U.S. Pat. No. 4,504,356 also discloses a process for removing silicate from black liquor, in which the black liquor is first evaporated and is subsequently treated with flue gases, which are supplied in an amount of 30 to 40 m.sup.3 per m.sup.3 of black liquor. The precipitated silica is separated, diluted and washed with water. However, the evaporation of the silicate-containing black liquor causes problems due to scaling etc., and the problems with co-precipitation of lignin are not overcome.
A further inconvenience of these known processes is that flue gases are used as the carbon dioxide source. Flue gases are obtained in the combustion of an organic substance by means of air and they contain 10 to 20% by volume of carbon dioxide, whereas the major portion of the gas consists of the nitrogen in the combustion air. This inert portion of the flue gas will not be absorbed by the alkaline solution containing silicate, but will instead pass through this and cause foaming.
The purpose of the present invention is to eliminate the drawbacks of these known processes and to provide a process for economical and trouble-free recovery of alkali and heat from black liquor containing silicate in an environment-friendly manner.
The main characteristics of the present invention are set forth in the accompanying claims.

Process for recovering alkali and black liquor containing silicatae


A random sample is obtained from an inverted tree data structure by maintaining a cardinality estimate for each intermediate node in the tree, and selecting a leaf node at random by descending from the root node and performing an acceptance/rejection selection at each intermediate node weighted proportional to the cardinality estimates of the children and weighted inversely proportional to the cardinality estimate of the intermediate node. Even though the selection of an intermediate node is based upon only an estimate of the true cardinality of the intermediate node, the error in the estimate does not cause bias in the overall sampling method because any bias in the selection of the intermediate node is cancelled by an opposite bias in the selection of the child of the intermediate node. The cardinality estimates are maintained when a leaf is inserted or deleted from the data structure by checking whether the insertion or deletion causes the cardinality estimate of a parent of the leaf node to differ from the actual cardinality by a predetermined error bound, and if so, the cardinality estimate of the parent is updated, and the checking and updating process is escalated up the tree. The error bound is adjustable for balancing rejection rate during sampling against I/O overhead of cardinality maintenance during database updates.

1. Technical Field
The present invention relates to data processing, and more particularly to random sampling of data items in a hierarchical data structure such as a "tree."
2. Description of the Related Art
Data items in a database are regularly sampled for statistical applications such as financial auditing, inventory control, and quality control. Although various sampling methods are used, the objective is to select a representative sample of the data items, so that conclusions about a large population of data items in the database can be estimated from a relatively small number of data items in the sample. See, for example, D. Montgomery, Introduction to Statistical Quality control, Wiley, 1985, pp. 23-55 and 351-429.
A widely used method of sampling is known as "random" sampling. Random sampling on a set of data items numbered 1 to K is defined as a selection of a subset of data items having numbers that are randomly scattered on the [1:K] interval. Preferably, the numbers are also uniformly distributed over the [1:K] interval. This special case is known as simple or unbiased random sampling, and it prevents any correlation of the sampled subset with any meaningful data characteristic.
In most database systems, data items are indexed by keys to permit retrieval of specified data items, but the data items are not assigned consecutive numbers. If consecutive numbers were initially assigned as keys, for example, then the deletion of a single data item, except the one assigned the highest key, would require re-assignment of some of the keys to preserve consecutive numbering. For complex data structures, re-assignment of consecutive numbers to the data items also interferes with activities such as compression, clustering, and multi-table intermix.
One kind of complex data structure in widespread use is a hierarchical data structure that looks like an inverted tree. For this reason it is known simply as a tree. The MS-DOS (Trademark) operating system for personal computers written by Microsoft Corporation, for example, uses a tree for indexing files stored in disk memory. The tree is known as a directory for a disk drive. The tree includes a main directory corresponding to the "root" of the tree, a subdirectory for each "branch" or intermediate node of the tree, and a file for each "leaf" of the tree. The root directory, each subdirectory, and each file is assigned a name. Although the file name is a "key" for a specified file, it does not uniquely specify the file, because the same file name can be assigned to different files in different directories. A file is accessed by searching a specified path in the tree, beginning with the root directory. Therefore a file is specified by a "path name" including the root name followed by any subdirectory names along the path, followed by the file name. A backslash ( ) symbol is used as a delimiter between the various names. See, for example, MS-DOS Version 3.3 Reference Guide, Compaq Computer Corporation (February 1988), pp. 2-1 to 2-16.
Trees are also widely used in relational database systems for sorted indexed retrieval of records. Each record is a row in a table, and a key is assigned to each record. Each record is also a leaf in a hierarchical index in the form of an inverted tree, but in this case each leaf in the tree has the same depth. In other words, each leaf is connected to the root by the same number of branches.
Sorted indexed retrieval is an efficient method of retrieving exact matches in response to the complete value of the key (corresponding to the "path name" described above combined with the key assigned to the row in table). Sorted indexed retrieval is also useful for finding out whether a row with a certain key value exists in a table. The search for a record having a specified complete key value is facilitated by maintaining the "branch names" in a sorted list in the root directory and each sub-directory of the tree.
To define a tree index for a database, a database administrator may issue a "CREATE INDEX" statement to the database system. In this "CREATE INDEX" statement, the administrator specifies a string of identifiers of attribute fields in each table, and in response the database system creates a tree having a level of branches corresponding to each attribute field, and at each level, the database system creates a branch corresponding to each distinct value in the attribute field appearing in the tables. The "CREATE INDEX" command may also indicate that the indexes of keys are to be maintained in a sorted condition.
Further details about sorted tree indexing are found in Hobbs & England, Rdb/VMS--A Comprehensive Guide, Digital Press, Digital Equipment Corporation, Maynard, Mass. (1991). Design considerations for database management systems using tree indexing are also described in Carey et al., "Object and File Management in the EXODUS Extensible Database System," Proceedings of the Twelfth International Conference on Very Large Data Bases, Koyoto, (August, 1986) pp. 91-100.
Current methods for random sampling of data items from trees are either highly biased or expensive. Some of these methods are compared and contrasted in Olken & Rotem, "Random Sampling from B.sup.+ trees," Proceedings of the Fifteenth International conference on Very Large Data Bases, Amsterdam, 1989, pp. 269-277.
An easy method of random sampling from a tree is to perform a random walk from the root to a leaf. In other words, while descending from the root, a branch is selected randomly at each level. This method, however, may deliver an extremely biased sampling, because the nodes at each level may have different numbers of branches, leading to preferred selection of paths having fewer branches. Experiments with indexes in the Rdb/VMS (Trademark) database system, for example, have shown that a small region of an index can contain a majority of the samples, making this easy method highly biased.
For a tree having all of its leaves at the same bottom level, it is known to eliminate bias by performing an acceptance/rejection test at each level during descent from the root so that each branch at each level has an equal chance of being selected, and therefore each leaf will have an equal chance of being selected. In other words, the sampling of a leaf will be simple and unbiased. Acceptance/rejection sampling in such a fashion, however, requires a probability of selecting any one branch at each node to be less than or equal to the probability of selecting the branch at the node having the maximum number of branches. The maximum number of branches in a tree is referred to as the "maximum fanout." In most systems the maximum fanout is either very large or limited only by the memory capacity of a single index page of the particular data processing system, but many nodes will have only a few branches. These conditions dictate that acceptance-rejection sampling in the above fashion requires a high average rate of rejection. In some typical Rdb/VMS (Trademark) database systems, rejection rates have varied from 99% for a large 913K index to 99.999,993% for a small 8K index, based on the maximum fanout actually found in these databases. Acceptance/rejection sampling in the above fashion therefore requires an inordinate amount of processing time and is impractical.
Another method of random sampling on trees provides simple or unbiased sampling, but at the expense of high overhead in both processing time and data structure maintenance. It is based on the conceptually simple method of identifying the number (K) of leaves, numbering the leaves 1 to K, and then randomly picking a number i within the range [1:K] to select the leaf associated with the number n. The simplicity of this method depends upon storing, for each node in the tree (except the leaves), the number r of leaves that are descendants of the node. Such a tree is known as a "ranked" tree.
In such a ranked tree, it is possible to select an ith leaf during a straight descent from the root by computing a running sum of the numbers of leaves that are descendants at each node along the descent, and selecting branches dependent upon a comparison of the number i to the running sum. To select a leaf at random, the number i is selected at random from the range [1:K], where K is the number of leaves. Although this method provides simple and unbiased sampling, it is impractical, because when a leaf is inserted or deleted, the cardinalities r along the entire path from the root to the leaf have to be updated.

Simple random sampling on pseudo-ranked hierarchical data structures in a data processing system