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Electrical Design-for-Manufacturability (DFM) checks are developed to quantify layout enhancements and their impact on circuit performance for analog designs. A database containing circuit topologies of analog matched devices is built. Then, connectivity checks scan the schematics for topologies from the database. If a matching topology were detected, the matched devices are mapped to layout for layout matching checks. If layout mismatches are detected, electrical DFM checks are used to quantify the imbalance in terms of parasitic resistance and capacitance. The electrical DFM checks are applied to quantify the impact due to routing, fill, and DFM fixing on three, 22nm analog design blocks. Fill insertion’s contribution to RC change is the greatest followed by routing and DFM fixing, with a maximum change of 7%, 5%, and less than 1%, respectively. Symmetry-aware layout insertions preserve the matching of electrical parameters, showing zero mismatch. All designs pass electrical DFM checks as results are within the expected design tolerances.

A symmetry-aware DFM layout insertion flow for matched circuits is developed for enhancing analog and mixed-signal designs. Pattern capture is used to categorize the matched circuits to unique groups of layout patterns and store them in a pattern database, in which each pattern has an associated group identification, a match location, a region of extent, and a symmetry constraint. Using the stored information in the pattern database, DFM layout insertions are applied to the base pattern and replicated for the symmetric patterns to generate an optimized layout, thus preserving the original symmetry. The impact of the DFM insertions on analog circuit performance was quantified using electronic simulators. The application of symmetry-aware DFM enhancements to analog designs achieves nearly 100% DFM compliance with negligible 0.1-0.2% impact to analog electrical parameters.

A suite of DFM enablement is enhanced to address the unique needs of analog, RF, and mmWave designs in the custom design flow. The DFM rules and patterns are made stricter beyond baseline requirements, and new DFM rules and patterns are added to further reduce layout-dependent device variability. Auto-fixing in the custom design flow is enhanced to meet these new requirements. New DFM enablement is developed for device matching for differential circuits and sensitive devices. Lastly, novel DFM fill strategies are implemented to reduce the variability of passive devices operating at high frequencies. Using DFM-aware fill, a 2% quality-factor loss for a mmWave inductor operating at 30 GHz is shown to be sufficient for meeting manufacturing planarity requirements.

A pattern matching and rule-based polygon clustering methodology with DFM scoring is proposed to detect decomposition-induced manufacturability detractors and fix the layout designs prior to manufacturing. A pattern matcher scans the layout for pre-characterized patterns from a library. If a pattern were detected, rule-based clustering identifies the neighboring polygons that interact with those captured by the pattern. Then, DFM scores are computed for the possible layout fixes: the fix with the best score is applied. The proposed methodology was applied to two 20nm products with a chip area of 11 mm2 on the metal 2 layer. All the hotspots were resolved. The number of DFM spacing violations decreased by 7-15%.

A pattern-based methodology for optimizing SADP-compliant layout designs is developed based on identifying cut mask patterns and replacing them with pre-characterized fixing solutions. A pattern-based library of difficult-tomanufacture cut patterns with pre-characterized fixing solutions is built. A pattern-based engine searches for matching patterns in the decomposed layouts. When a match is found, the engine opportunistically replaces the detected pattern with a pre-characterized fixing solution. The methodology was demonstrated on a 7nm routed metal2 block. A small library of 30 cut patterns increased the number of more manufacturable cuts by 38% and metal-via enclosure by 13% with a small parasitic capacitance impact of 0.3%.

High-sensitivity C-reactive protein (hs-CRP) concentrations and obesity are proposed to have a significant relationship with impairment of lung function, but little has been reported to date on the association between CRP gene and lung function. We studied the association of three tagSNPs (tag single nucleotide polymorphisms) of CRP gene and their interactions with central obesity on lung function. A total of 384 asthmatic adults and 384 controls who were 1:1 matched by sex and age were recruited for this study. Three tagSNPs polymorphisms for CRP rs1417938, rs1800947 and rs1205 were selected from HapMap data and genotyping by using TaqMan allelic discrimination assay. A questionnaire interview, body composition and pulmonary function tests were performed. CRP single nucleotide polymorphisms (SNPs) did not increase the risk of asthma, but CRP rs1205 CC genotype significantly decreased the predictive value of forced vital capacity (FVC) in the asthma group (adjusted mean change = −7.54%, 95% CI = −13.82 to −1.25%). Waist-to-hip ratio, not body mass index, also decreased the predictive value of FVC in asthmatics. The subjects with central obesity who carried CRP SNPs have a significant reduction effect in lung function. The current results suggest that central obesity may play a major role in lung function, and these effects were modified significantly by the polymorphisms for CRP gene.

Uniaxial stress is widely used in advanced CMOS technologies to boost transistor performance. Conventional compact transistor models rely on empirical fitting of the average channel stress value to predict mobility and, hence, transistor performance. This approach can lead to significant errors for deeply scaled technologies. In this paper, stress profiles are modeled in analytical form, using a physically based approach. The stress model is validated by 3-D TCAD simulations. A nanometer-scale transistor intrinsic delay formula based on injection velocity theory is then applied. The predicted variation in transistor performance compares well with the measured silicon data for a 45-nm strained CMOS technology.

Background: Adult asthma is caused by interaction effects of multiple genetic and environmental factors. Some studies have suggested that antioxidant enzyme activity and gene polymorphisms may play important roles in the context of asthma. Therefore, our study objectives were to investigate the association between asthma, antioxidant activities and the polymorphisms of manganese superoxide dismutase (Mn-SOD) or catalase (CAT). Materials and Methods: A case-control study, for which we recruited 250 asthmatic adults and 250 age- and sex-matched controls. All subjects completed a questionnaire. Waist and hip circumference measurements, a lung function test and DNA genotyping were performed. In total, 50 incident cases and 50 matched controls who were non-smokers or had quit smoking for at least 1 year were selected in order to investigate SOD and CAT activity levels. Results: In our study, we did not find a significant association between Mn-SOD Ala16Val, CAT C–262T and asthma. The level of SOD activity in new-onset asthma patients was significantly lower than in control subjects (p < 0.0005). The level of CAT activity in new-onset asthma patients was significantly higher than in control subjects (p < 0.0005). Conclusions: The levels of SOD and CAT activity were significantly related to adult asthma. SOD and CAT activity may be good tools to differentiate potential asthma sufferers. This would enable us to further investigate the mechanism of defective antioxidant enzymes in the context of asthma pathogenesis.

Summary Background Several studies have suggested that the association between obesity and asthma may be stronger in females than in males, but the reason is still unclear. Objective The aim of this study was to investigate whether differences in high-sensitivity C-reactive protein (hs-CRP) levels explain why obesity is associated with asthma in females but not in males. Methods This study prospectively enrolled 754 subjects 18 years old from hospital-based asthma patients and population-based controls. We measured adiposity factors [body mass index (BMI), waist circumference and waist-hip ratio], hs-CRP and total IgE levels. Results After adjusting for potential confounding factors, we found a significant association between BMI and asthma in females with a significant interaction of gender and BMI on asthma (χ2=10.2, P=0.004). If hs-CRP was added to the logistic model, the interaction was attenuated but still significant (χ2=7.02, P=0.03). After adjusting for BMI, we did not find that circulating hs-CRP concentrations were significantly associated with asthma in males and females. Conclusion We found that BMI was associated with asthma in females, but our results do not support the suggestion that hs-CRP levels contribute significantly to the link between obesity and asthma with respect to gender disparity. Cite this as: T.-N. Wang, M.-C. Lin, C.-C. Wu, M.-S. Huang, S. Y. Leung, C.-C. Huang, P.-S. Ho and Y.-C. Ko, Clinical & Experimental Allergy, 2011 (41) 72–77.

Background: Asthma is a complex disorder, which is known to be affected by interactions between genetic and environmental factors. The human Eotaxin 1 and CCR3 attract eosinophils and Th2-lymphocytes to migrate to the inflammatory foci that could represent a key mechanism in allergy and asthma. Objective: We hypothesized that Eotaxin1 gene Ala23Thr and A-384 G, and CCR3 gene T51C polymorphisms are associated with plasma Eotaxin levels and predispose individuals to asthma pathogenesis. Methods: One hundred seventy-eight hospital-based asthmatic children and 277 community-based controls aged from 5 to 12 years were recruited in southern Taiwan. Whole blood samples and questionnaires were collected. In this study, we addressed genetic effects of Eotaxin 1 and CCR3 genes on asthma, plasma IgE and Eotaxin 1 levels. Results: In comparison with subjects with Ala23Ala genotype, Ala23Thr polymorphism of the Eotaxin 1 gene showed a significant protective effect on asthma (AOR = 0.58, 95% CI = 0.37–0.92). We demonstrated that the mean Eotaxin 1 concentration was significantly higher in subjects with Ala23Ala than in subjects with Thr23Thr (P = 0.005) or Ala23Thr (P = 0.07), which showed a gene-dose dependent relationship. But, we observed that the A-384G polymorphism of Eotaxin 1 gene and T51C polymorphism of CCR3 gene are not associated with asthma. Conclusion: This study finding provide a strong evidence that Eotaxin 1 Thr23Thr homozygote has a protective effect on asthma and significantly decreases plasma Eotaxin 1 concentrations in asthmatics in Taiwan.

A pattern-based methodology for optimizing stitches is developed based on identifying stitch topologies and replacing them with pre-characterized fixing solutions in decomposed layouts. A topology-based library of stitches with predetermined fixing solutions is built. A pattern-based engine searches for matching topologies in the decomposed layouts. When a match is found, the engine opportunistically replaces the predetermined fixing solution: only a design rule check error-free replacement is preserved. The methodology is demonstrated on a 20nm layout design that contains over 67 million, first metal layer stitches. Results show that a small library containing 3 stitch topologies improves the stitch area regularity by 4x.

Although family studies have established that asthma has a hereditary basis, little evidence has been presented about the family risk of simple asthma (AS or nonatopic asthma) and asthma with other atopic diseases (AWAD or atopic asthma) after adjusting for potential risk factors. In this study, data were collected on demographic variables and a wide range of known risk factors for asthma. Study participants were asthmatic adolescents and controls, and their relatives. The role of a familial history of asthma and atopic diseases in predicting asthma risk among asthmatic adolescents and their relatives was evaluated in a population-based family study conducted in southern Taiwan. Asthma risk factor data were collected through telephone interviews with students' parents for 207 asthmatic adolescents 11-16 years of age, their 1600 relatives, and 207 nonasthmatic adolescents in the control group and their 1638 relatives. The results show (after adjusting potential confounders) that a family history of asthma is highly associated with asthma in adolescents. Having two or more family members with asthma was associated with a 3.4-fold (95% confidence interval [CI] = 1.0-12.0) increased risk of asthma among adolescents. Logistic regression was used to assess the effects of having an asthmatic relative and the effect of atopic diseases among relatives of cases. Having a family history of asthma and other atopic conditions, such as rhinitis and atopic dermatitis (adjusted odds ratio [AOR] = 3.64, 95% CI = 2.29-5.74 and AOR = 1.94, 95% CI = 1.53-2.46, respectively), was found to be a significant predictor of asthma in children. Along with a history of allergic rhinitis or atopic dermatitis, familial risks of asthma occurring in adolescents with and without other atopic diseases will be analyzed separately. A critical finding was the significant difference in a risk of asthma and atopic diseases among the relatives of asthma cases with atopic diseases and controls. However, for relatives of asthma cases without atopic diseases compared to control probands, AORs were highly significant for family history of asthma, but not for the family history of atopic diseases. These findings suggest that both forms of asthma may be hereditary, but there are differences in their modes of inheritance. Atopic status itself did not predispose a child to AS. A concomitant inheritance of a predisposition to asthma and atopic condition for AWAD cases was suggested.

Although asthma has a significant heritable component, the mode of inheritance remains controversial because of the complexity of the disease and the influence of environmental factors. Segregation analysis for asthma are performed with and without a history of atopic diseases (dermatitis and rhinitis) after adjusting for environmental factors. To investigate whether asthma may be inherited through a major gene with two alleles, the REGD program of the Statistical Analysis for Genetic Epidemiology (SAGE) package was conducted in 1,990 individuals from 227 families with at least one asthmatic child in a cross-sectional study of respiratory diseases in Southern Taiwan. Other covariates adjusted for included age, sex, current smoking, and environmental tobacco smoking. The hypothesis of Mendelian model and no parent-offspring transmission was rejected. However, when the variables of atopic disease and environmental factors were included in the model as covariates, the models for a two-allele gene with a recessive or codominant inheritance could not be rejected, and Akaike's Information Criterion was smaller (1,377.13) for the recessive model than all of the other models tested, assuming a major gene with a population frequency of 0.56 ± 0.04. However, Mendelian model without family effect was rejected. In conclusion, a history of asthma in parents is a strong risk factor for asthma in offspring. Under the assumptions of the applied segregation, at least one major gene exists that could be a gene involved also in allergy. However, the data suggest that a single locus gene explains a portion of asthma that is related to the history of atopic diseases. In addition, a polygenic/multifactorial (genetic and environmental factors) influence with a recessive component inheritance may be involved in the pathogenesis of asthma. Am. J. Med. Genet. 93:373–380, 2000. © 2000 Wiley-Liss, Inc.

Decomposition-aware layout design improvements for 8, 9, 11, and 13-track 20/14nm standard cells are presented. Using a decomposition-aware scoring methodology that quantifies the manufacturability of layouts, the Double Patterning Technology (DPT)-compliant layouts are optimized for DPT-specific metrics that include: the density difference between the two decomposition mask layers, the enclosure of stitching areas, the density of stitches, and the design regularity of stitching areas. For a 9-track standard cell, eliminating the stitches from the layout design improved the composite score from 0.53 to 0.70.

A pattern matching methodology that identifies non-decomposition-friendly designs and provides localized guidance for layout-fixing is presented for double patterning lithography. This methodolog y uses a library of patterns in which each pattern has been pre-characterized as impossible-to-decompose and annotated with a design rule for guiding the layout fixes. A pattern matching engine identifies these problematic patterns in design, which allows the layout designers to anticipate and prevent d ecomposition errors, prior to layout decomposition. The methodology has been demonstrated on a 180 um 2 layout migrated from the previous 28nm technology node for the metal 1 layer. Using a small library of just 18 patterns, the pattern matching engine identified 119 out of 400 decomposition errors, which constituted coverage of 29.8%. Keywords: Pattern matching, odd-cycles, coloring conflicts, double patterning, decomposition, design flow, design rule, DRC Plus, automated decomposition algorithm, DPT

A Double Patterning Technology (DPT)-aware scoring methodology that systematically quantifies the quality of DPTcompliant layout designs is described. The methodology evaluates layouts based on a set of DPT-specific metrics that characterizes layout-induced process variation. Specific metrics include: the spacing variability between two adjacent oppositely-colored features, the density differences between the two exposure masks, and the stitching area's sensitivity to mask misalignment. These metrics are abstracted to a scoring scale from 0 to 1 such that 1 is the optimum. This methodology provides guidance for opportunistic layout modifications so that DPT manufacturability-related issues are mitigated earlier in design. Results show that by using this methodology, a DPT-compliant layout improved from a composite score of 0.66 and 0.78 by merely changing the decomposition solution so that the density distribution between the two exposure masks is relatively equal.© (2012) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only.

This paper addresses the framework for building critical recommended rules and a methodology for devising scoring models using simulation or silicon data. Recommended rules need to be applied to critical layout configurations (edge or polygon based geometric relations), which can cause yield issues depending on layout context and process variability. Determining of critical recommended rules is the first step for this framework. Based on process specifications and design rule calculations, recommended rules are characterized by evaluating the manufacturability response to improvements in a layout-dependent parameter. This study is applied to critical 20nm recommended rules. In order to enable the scoring of layouts, this paper also discusses a CAD framework involved in supporting use-models for improving the DFM-compliance of a physical design.© (2012) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only.

A pattern-based methodology for guiding the generation of DPT-compliant layouts using a foundry-characterized library of “difficult to decompose” patterns with known corresponding solutions is presented. A pattern matching engine scans the drawn layout for patterns from the pattern library. If a match were found, one or more DPT-compliant solutions would be provided for guiding the layout modifications. This methodology is demonstrated on a sample 1.8 mm 2 layout migrated from a previous technology. A small library of 12 patterns is captur ed, which accounts fo r 59 out of the 194 DPT-compliance check violations examined. In addition, the methodology can be used to recommend specific changes to the original drawn design to improve manufacturability. This methodology is compatible with any physical design flows that use automated decomposition algorithms. Keywords: Pattern matching, double patterning, decomposition, design flow, design rule check, DRC Plus, automated decomposition algorithm, DPT

Background: Asthma is a common chronic inflammatory respiratory disease. Previous studies have suggested that the pathogenesis of asthma may be affected by epigenetic regulation. The purpose of this study is to characterize the effect of the methylation of each CpG site in the ADAM33 (a disintegrin and metalloproteinase 33) gene in adult asthma. Methods: A human CpG island microarray was used to examine 4 asthmatic cases and 4 healthy controls, and the results suggested that there might be differences in methylation within exon 9 of the ADAM33 gene. Therefore, we designed a case-control study with 50 asthmatic patients and 50 age- and sex-matched healthy controls to examine the relationship between the CpG methylation of the ADAM33 gene and asthma using bisulfite deoxyribonucleic acid modification and sequencing. Results: Bisulfite sequencing experiments showed that the 14 CpG sites in exon 9 of the ADAM33 gene were highly methylated (100%) in all individuals. The proportions of methylation of the 14 CpG sites in ADAM33 in the case group were not different from those of the control group. The methylation of exon 9 of this locus was not associated with age, sex, IgE levels, or lung function. This study found no association between the methylation of CpG sites in exon 9 of the ADAM33 gene and adult asthma. Conclusions: The 14 CpG sites were highly methylated in the case and control groups. Further investigation of exon 9 in ADAM33 in a larger population is needed to evaluate its role in asthma.

Techniques for identifying and mitigating effects of process variation on the electrical performance of integrated circuits are described. These results are from multi-discipline, collaborative university-industry research and emphasize anticipating sources of variation up-stream early in the circuit design phase. The lithography physics research includes design and testing electronic monitors in silicon at 45 nm and fast-CAD tools to identify systematic variations for entire chip layouts. The device research includes the use of a spacer (sidewall transfer) gate fabrication process to suppress random variability components. The Design-for-Manufacturing research includes double pattern decomposition in the presence of bimodal CD behavior, process-aware reticle inspection, tool-aware dose trade-off between leakage and speed, the extension of timing analysis methodology to capture across process-window effects and electrical processwindow characterization.

Several studies have suggested that the association between obesity and asthma may be stronger in females than in males, but the reason is still unclear.The aim of this study was to investigate whether differences in high-sensitivity C-reactive protein (hs-CRP) levels explain why obesity is associated with asthma in females but not in males.This study prospectively enrolled 754 subjects ≥ 18 years old from hospital-based asthma patients and population-based controls. We measured adiposity factors [body mass index (BMI), waist circumference and waist-hip ratio], hs-CRP and total IgE levels.After adjusting for potential confounding factors, we found a significant association between BMI and asthma in females with a significant interaction of gender and BMI on asthma (χ(2) =10.2, P=0.004). If hs-CRP was added to the logistic model, the interaction was attenuated but still significant (χ(2) =7.02, P=0.03). After adjusting for BMI, we did not find that circulating hs-CRP concentrations were significantly associated with asthma in males and females.We found that BMI was associated with asthma in females, but our results do not support the suggestion that hs-CRP levels contribute significantly to the link between obesity and asthma with respect to gender disparity.

Experimental results are reported for ring oscillators (ROs) fabricated using 45nm generation CMOS technology and inverter layouts that are designed to identify and quantify sources of circuit performance variation due to gate etch/lithography, gate-to-active misalignment, and CESL-induced stress. The measured RO frequency data show that within-chip variation is negligible in comparison with chip-to-chip variation. Standard-deviation over mean (σ/μ) values among 36 RO instances show a slight channel area dependence of 0.2% versus sqrt(area) -1 . For a typical wafer, 3% RO frequency change due to gate etch/focus variations, 2-3nm overlay error, and a 5% increase by doubling the length of diffusion (LOD) can be measured.

As the gate length (Lg) of a MOSFET is scaled down and carrier transport is enhanced increasingly via process-induced strain, the transistor drive current becomes limited by the carrier injection velocity from the source into the channel [1]. Hence, the quasi-ballistic transport model proposed by Lundstrom et al. [2] is more suitable for predicting nanoscale MOSFET behavior. By self-consistently solving for the charge density at the top of the potential barrier and the surface Fermi level, it is straightforward to calculate the transistor current

Visualization at the mask plane of the effects of illumination, proximity, and defocus is used to give physical insight into restricted design rules, layout choices, and residual edge placement errors. To facilitate this work, a pattern matching code has been tuned, tested, and enhanced. The richness of the original code with complex match factors, mask Boolean operations, and mask weights and phases has been adapted to operate on clear-field attenuated-phase-shifting masks with asymmetrical illumination. To account for illumination effects, the aberration spillover is multiplied by the Fourier transform of the angular distribution of the intensity spectrum incident on the mask. In a study of binary mask layouts, the R-squared correlation of the prediction of image intensity with Pattern Match Factor increased from 0.57 to 0.89 when annular illumination was included in the spillover function. In addition, features to visualize the mutual coherence, shifts of the illumination, and source maps have been added.

Parameter-specific and simulation-calibrated ring oscillator (RO) inverter layouts are described for identifying and quantitatively modeling sources of circuit performance variation from source/drain stress, shallow trench isolation (STI) stress, lithography, etch, and misalignment. This paper extends the RO approach by adding physical modeling/simulation of the sources of variability to tune the layouts of monitors for enhanced sensitivity and selectivity. Poly and diffusion layout choices have been guided by fast-CAD pattern matching. The accuracy of the fast-CAD estimate from the Pattern Matcher for these lithography issues is corroborated by simulations in Mentor Graphics Calibre. Generic conceptual results are given based on the experience from preparing of proprietary layouts that pass DRC check for a 45 nm test chip with ST Micro. Typical improvements in sensitivity of 2 fold are possible with layouts for lithography focus. A layout monitor for poly to diffusion misalignment based on programmable off-sets shows a 0.8% change in RO frequency per 1nm poly to diffusion off-set. Layouts are also described for characterizing stress effects associated with diffusion area size, asymmetry, vertical spacing, and multiple gate lengths.

This paper applies process and circuit simulation to examine plausible explanations for measured differences in ring oscillator frequencies and to develop layout and electronic circuit concepts that have increased sensitivity to lithographic parameters. Existing 90nm ring oscillator test chip measurements are leveraged, and the performance of ring oscillator circuit is simulated across the process parameter variation space using HSPICE and the Parametric Yield Simulator in the Collaborative Platform for DfM. These simulation results are then correlated with measured ring oscillator frequencies to directly extract the variation in the underlying parameter. Hypersensitive gate layouts are created by combining the physical principles in which the effects of illumination, focus, and pattern geometry interact. Using these principles and parametric yield simulations, structures that magnify the focus effects have been found. For example, by using 90 O phase shift probe, parameter-specific layout monitors are shown to be five times more sensitive to focus than that of an isolated line. On the design side, NMOS or PMOS-specific electrical circuits are designed, implemented, and simulated in HSPICE.

Aerial image simulation of interdigitated sidewall capacitor layouts and extraction of feature changes are used to estimate the parametric performance spread of DC Metal-Oxide-Metal (MOM) mixed signal capacitors as a function of the normalized lithographic resolution k1. Since minimum feature sizes are utilized, the variation of MOM capacitors is attributed to lithography spacing. In this paper, k1 of 0.8, 0.56, 0.40, and 0.28 are studied. The DC capacitance shows a worst-case variability of 42%. While line-end-shortening is a small fractional change in finger length and proves to be not a critical factor in variability, spacing width proves to be the main source of the variability in DC capacitance. Different annular illumination settings are explored for mitigating the variability in spacing width. Co-design of the pitch and illumination shows that for each k1, there is an optimal annular illumination radius. The optimal set of sigmas (i.e. sigma_in and sigma_out) can control the variability between linewidths and spacing widths to 20%.

This paper proposes a novel method of identifying interactions between neighboring standard cells via fast-CAD pattern matching. Studies of cell-to-cell interactions for both metal 1 and poly layouts are made for selected samples from libraries for 130 and 90 nm generations provided under an NDA agreement by ST Microelectronics. Both simulation and pattern matching are utilized to identify and quantify hot-spots. The physical basis for pattern matching is described. In validating pattern matching compared to full simulation, changes in linewidth for a fixed defocus setting varied quadratically with pattern match factor and can be modeled by a parabolic equation with an r-squared value of 0.77. Results demonstrate that there is a considerable best-to-worst variation of 4-7% in the linewidth among neighbors, which is produced through a focus swing of 0.58 Rayleigh Units (RU). The focus swing is oscillatory with cell separation distance, and a slight shift in spacing on the order of 0.5 λ /NA can mitigate lateral interaction effects.

Embedded systems are often assembled from black box components. System-level analyses, including verification and timing analysis, typically assume the system description, such as RTL or source code, as an input. There is therefore a need to automatically generate formal models of black box components to facilitate analysis. We propose a new method to generate models of real-time embedded systems based on machine learning from execution traces, under a given hypothesis about the system's model of computation. Our technique is based on a novel formulation of the model generation problem as learning a dependency graph that indicates partial ordering between tasks. Tests based on an industry case study demonstrate that the learning algorithm can scale up and that the deduced system model accurately reflects dependencies between tasks in the original design. These dependencies help us formally prove properties of the system and also extract data dependencies that are not explicitly stated in the specifications of black box components

Exploratory prototype DfM tools, methodologies and emerging physical process models are described. The examples include new platforms for collaboration on process/device/circuits, visualization and quantification of manufacturing effects at the mask layout level, and advances toward fast-CAD models for lithography, CMP, etch and photomasks. The examples have evolved from research supported over the last several years by DARPA, SRC, Industry and the Sate of California U.C. Discovery Program. DfM tools must enable complexity management with very fast first-cut accurate models across process, device and circuit performance with new modes of collaboration. Collaborations can be promoted by supporting simultaneous views in naturally intuitive parameters for each contributor. An important theme is to shift the view point of the statistical variation in timing and power upstream from gate level CD distributions to a more deterministic set of sources of variations in characterized processes. Many of these nonidealities of manufacturing can be expressed at the mask plane in terms of lateral impact functions to capture effects not included in design rules. Pattern Matching and Perturbation Formulations are shown to be well suited for quantifying these sources of variation.

Summary Background Asthma is a multi-factorial disorder caused by complex interactions between genetic and environmental factors. IFN-γ and IFN regulatory factor 1 (IRF-1) affect Th1/Th2 cytokine balance, and influence the differentiation of Th2 cells, which influence the development of asthma. Objective This study investigated CA repeats polymorphism of the IFN-γ gene and GT repeats polymorphism of the IRF-1 gene, which may predispose individuals to asthma pathogenesis. Methods In the present study, we used the transmission/disequilibrium test (TDT) to investigate the relationship between asthma and the IFN-γ and IRF-1 polymorphisms by studying 348 subjects composed of 232 parents and 116 asthmatic children. Results For global TDT test, IFN-γ CA repeats and IRF-1 GT repeat polymorphisms showed a significant association with asthma in children (P=0.009 and 0.017, respectively). We demonstrated that 13 CA repeats (138 bp) of IFN-γ gene and 11 GT repeats (306 bp) of IRF-1 gene are significantly preferentially transmitted to asthmatic children (T/NT=89/61, χ2=8.43, P

Recent data have shown that Dome C, on the Antarctic plateau, is an exceptional site for astronomy, with atmospheric conditions superior to those at any existing mid-latitude site. Dome C, however, may not be the best site on the Antarctic plateau for every kind of astronomy. The highest point of the plateau is Dome A, some 800 m higher than Dome C. It should experience colder atmospheric temperatures, lower wind speeds, and a turbulent boundary layer that is confined closer to the ground. The Dome A site was first visited in January 2005 via an overland traverse, conducted by the Polar Research Institute of China. The PRIC plans to return to the site to establish a permanently manned station within the next decade. The University of New South Wales, in collaboration with a number of international institutions, is currently developing a remote automated site testing observatory for deployment to Dome A in the 2007/8 austral summer as part of the International Polar Year. This self-powered observatory will be equipped with a suite of site testing instruments measuring turbulence, optical and infrared sky background, and sub-millimetre transparency. We present here a discussion of the objectives of the site testing campaign and the planned configuration of the observatory.

Summary Background Asthma is now known to be an inflammatory response caused by the release of inflammatory mediators and cytokines. Tumour necrosis factor (TNF) is a potent cytokine in the inflammation response of the airway, and the polymorphisms of TNF genes have been associated with asthma. Objective This study investigated two variants, TNF-α-308*2 and lymphotoxin (LT)-α-NcoI*1, which may predispose individuals to asthma and atopy pathogenesis. Methods PCR-based assays were performed to determine LT-α-NcoI*1 and TNF-α-308*2 genotypes among our subjects, with 128 atopic asthmatics and 51 non-atopic asthmatics, 55 atopic controls, and 78 non-atopic controls in this genetic case–control study. Results The TNF-α-308*2 polymorphism increased in subjects with atopic asthma vs. non-atopic controls after adjusting for age distribution (adjusted odds ratios, AOR=2.73, 95% confidence interval, CI=1.16–6.64), but was not associated with non-atopic asthma (AOR=2.40, 95% CI=0.81–7.09). LT-α-NcoI*1 did not show an independent association with either atopic asthma or any one phenotype of specific IgE. The synergistic effect between these two genes was conducted, and the interaction between TNF-α-308*2 and LT-α-NcoI*1 polymorphisms was seen for atopic asthma (OR=2.59, 95% CI=1.10–6.10) when compared with all controls. Conclusion We have concluded that TNF-α-308 may be a risk factor for atopic asthma, whereas the LT-α-NcoI polymorphism may modify risk to atopic asthma with TNF-α-308.

The Protocol Machine Expert System (PMES) for implementing communication protocols is described. The objective is to develop and implement a general model for communication protocols based on the principles of finite-state machines. The authors have designed an inference method and knowledge representation method, based on semantic networks, for implementing this model. A semantic net consists of points called nodes connected by links called arcs that describe the relations between the nodes. The authors have added interactive capability and automatic error detection to check for invalid external events and other types of errors in their model. They have illustrated the use of PMES by applying it to the TCP (transmission control protocol) of the US Department of Defense Model for Communication. >

To estimate the prevalence of gout and to examine its risk factors among Taiwan's Aborigines compared with non-Aborigines.Data were collected from persons older than 40 years living in 3 aboriginal and 2 non-aboriginal districts in Taiwan by a community survey. Cases of gout were identified from self-reporting of a doctor's diagnosis based on clinical criteria. Baseline variables and biochemical data were examined as risk factors for the development of gout.The prevalence of gout history was found to be 15.2% (25/165) and 4.8% (11/231) among aboriginal men and women, respectively, compared with a prevalence rate of 0.3% among non-Aborigines. A logistic regression model showed that aboriginal men older than 60 years with hyperuricemia were more severely affected by gout than any other group (p0.05).A high prevalence of gout among Taiwanese Aborigines was observed in this study and race was the most significant risk factor associated with the disease.

The relationship between death from cerebrovascular disease and the levels of magnesium and calcium in drinking water was examined using an ecological design. The study area consisted of 227 municipalities in Taiwan. Data on the levels of magnesium and calcium in drinking water have been collected from the Taiwan Water Supply Corporation (TWSC). These levels of magnesium and calcium were compared using the standardized mortality ratios (SMRs) for cerebrovascular disease (1981-1990). A statistically significant inverse relationship was present between cerebrovascular mortality and levels of both magnesium and calcium after adjusting for urbanization index. After adjustment for calcium levels in drinking water and urbanization index, the weighted multivariate-adjusted regression coefficient indicated a decrease of 0.248 in the standardized mortality ratios (SMRs) for every 100 mg/L increase in magnesium levels in drinking water. The results from this study strengthen the hypothesis that magnesium in drinking water helps to prevent death from cerebrovascular disease.

To explore the relationship between the body mass index (BMI) and uric acid in different races before growing up into adulthood, we selected a total of 1236 five to 14 year-old children in the period from March to December 1994. The children originated from three Aboriginal tribes (the Bunun, and the Paiwan tribes--classified as South-Aborigines and Atayal tribe as North-Aborigines) and two non-Aboriginal tribes (Fukein-Taiwanese and Hakka), all of whom are from the following four countries: Chien-Shih, Sandimen, Gaushuh and Sanmin. The results showed that the percentage of hyperuricemia (or = 7.5 mg/dl) was 28.5% (352/1236) and of obesity (BMIor = 22 kg/m2) was 9.5% (118/1236). Increased uric acid concentration was found to be related to age, sex, BMI, race, triglyceride (TG) and cholesterol levels in both the primary analysis and after the adjusted logistic regression model. Obesity did not vary with sex (OR = 1.0; 95% CI = 0.7-1.5), or with Aborigines in north Taiwan as compared with non-Aborigines (OR = 1.0, 95% CI = 0.6-1.6), but the logistic regression model adjusted for age indicated large BMI values for children with high serum uric acid concentration, triglyceride levels and the Aborigines who originated from south Taiwan. It was concluded from this study that both of the North-Aborigines and South-Aborigines made an important influence on serum uric acid concentration in children, especially the South-Aborigines made difference to BMI as compared with non-Aborigines and North-Aborigines.

Standardized incidence ratios (SIR) of malignant neoplasms in Taiwanese Aborigines were analyzed. In all, 995 cases of cancers had been reported in 30 Taiwanese Aboriginal communities between 1981 and 1987. In the same time period, 137, 159 cases were registered in Taiwan and carefully categorized according to race, gender, site and frequency of occurrence. Sex and tribe-specific standardized incidence ratios with 95% confidence interval were calculated. We found that the standardized incidence ratios of all cancers in Aborigines was lower than that in the general population of Taiwan for both Aboriginal men (0.72, 95% CI:0.67-0.78) and women (0.66, 95% CI:0.59-0.72). Of selected malignant neoplasms, SIR for nasopharyngeal carcinoma was slightly elevated in men, especially in the Bunun and Rukai tribes and significantly elevated in Paiwan women (2.95, 95% CI:1.65-4.87). The SIR for gastric cancer was significantly elevated for both men (SIR = 1.22, 95% CI:1.03-1.44) and women (1.48, 95% CI:1.14-1.92), especially in Atayal and Bunun men and Atayal women. There was a higher than expected level of incidence of penis cancer and other male genital cancers, especially in Paiwan people, with the SIR as large as 6.24 (95% CI:2.02-14.53). The SIR of lymph node cancer was significantly increased in Bunun (4.21, 95% CI:1.36-9.81) and Yamei women (CI:1.50-44.89), but not for all Aboriginal men. Colon, rectum, lung, bladder and oral cancers in aboriginal men and colon, rectum, lung, breast and cervical cancer in women occurred significantly less frequently than in the general population. The SIR of colon and rectum carcinoma was significant lower for both men (0.45, 95% CI:0.32-0.61) and women (0.25, 95% CI:0.13-0.42), particularly in the Atayal and Paiwan tribes. The SIR of lung cancer was 0.52 (95% CI:0.41-0.66) in Atayal, Bunun, Paiwan men and 0.58 (95% CI:0.38-0.86) in Paiwan women. There were significantly lower than expected levels of incidence of bladder (0.18, 95% CI:0.02-0.65) and oral cancer (0.29, 95% CI:0.08-0.74) for Atayal men. Aboriginal women had significantly lower SIR of cervical cancer (0.46) especially in Atayal, Bunun, Paiwan women and of breast cancer (0.38) especially in the Atayal and Paiwan women. But cancer of esophagus, liver, gallbladder, pancreas, and prostate occurred among Aboriginal people at the same rate as in the general Taiwan.

Mortality among Aborigines tribes in Taiwan from malignant neoplasms in the 1971-80 and 1981-90 decades were analyzed. Sex and tribe specific standardized mortality ratios were calculated from death certificate data and compared with the number of expected deaths derived from the cancer mortality of the entire population of Taiwan. Mortality due to oral cancer was statistically significantly higher than expected among Paiwan men in the 1971-80 decade and among Paiwan women from 1971-80 and 1981-90; as was mortality from nasopharyngeal cancer among Bunun, Paiwan and Rukai men from 1981-90 and among Bunun and Paiwan women from 1971-80 and 1981-90; mortality due to stomach cancer among the Atayal, Bunun and Paiwan people from 1971-80 and 1981-90, among Rukai men from 1971-80 and among the Tsou and mixed group women from 1981-90; mortality from liver cancer among Atayal and Bunun men in 1971-80, among Bunun women from 1971-80 and 1981-90 and among Paiwan women in 1981-90; mortality due to nasal cavity, middle ear and paranasal sinuses cancer among Rukai men from 1981-90; and mortality due to bone cancer among Tsou men and Atayal women from 1981-90. Mortality due to colorectal cancer was statistically significantly lower than expected among mixed group men from 1971-80 and in Atayal women from 1981-90; as was mortality from lung cancer among Atayal men and Paiwan women from 1971-80 and among Paiwan and mixed group men in the 1981-90 decade. Overall, the standardized mortality ratio of all cancers in aborigines was a little higher than in the general population of Taiwan. However, differences for ratio or site existed in different tribes.

Key physical phenomena associated with resists, illumination, lenses and masks are used to show the progress in models and algorithms for modeling optical projection printing as well as current simulation challenges in managing process complexity for manufacturing. The amazing current capability and challenges for projection printing are discussed using the 22 nm device generation. A fundamental foundation for modeling resist exposure, partial coherent imaging and defect printability is given. The technology innovations of resolution enhancement and chemically amplified resist systems and their modeling challenges are overviewed. Automated chip-level applications in pattern pre-compensation and design-anticipation of residual process variations require new simulation approaches.

Erythrophagocytosis was induced in Kupffer cells of rats by intraperitoneal injection of Pyrogallol. The fate of the sequestered erythrocytes was studied light-microscopically and electron-microscopically over a period from 30 min to 8 weeks.