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The NCCN Guidelines for Bladder Cancer provide recommendations for the diagnosis, evaluation, treatment, and follow-up of patients with bladder cancer and other urinary tract cancers (upper tract tumors, urothelial carcinoma of the prostate, primary carcinoma of the urethra). These NCCN Guidelines Insights summarize the panel discussion behind recent important updates to the guidelines regarding the treatment of non–muscle-invasive bladder cancer, including how to treat in the event of a bacillus Calmette-Guérin (BCG) shortage; new roles for immune checkpoint inhibitors in non–muscle invasive, muscle-invasive, and metastatic bladder cancer; and the addition of antibody–drug conjugates for metastatic bladder cancer.

Background: Natural language processing models such as ChatGPT can generate text-based content and are poised to become a major information source in medicine and beyond. The accuracy and completeness of ChatGPT for medical queries is not known. Methods: Thirty-three physicians across 17 specialties generated 284 medical questions that they subjectively classified as easy, medium, or hard with either binary (yes/no) or descriptive answers. The physicians then graded ChatGPT-generated answers to these questions for accuracy (6-point Likert scale; range 1 – completely incorrect to 6 – completely correct) and completeness (3-point Likert scale; range 1 – incomplete to 3 - complete plus additional context). Scores were summarized with descriptive statistics and compared using Mann-Whitney U or Kruskal-Wallis testing. Results: Across all questions (n=284), median accuracy score was 5.5 (between almost completely and completely correct) with mean score of 4.8 (between mostly and almost completely correct). Median completeness score was 3 (complete and comprehensive) with mean score of 2.5. For questions rated easy, medium, and hard, median accuracy scores were 6, 5.5, and 5 (mean 5.0, 4.7, and 4.6; p=0.05). Accuracy scores for binary and descriptive questions were similar (median 6 vs. 5; mean 4.9 vs. 4.7; p=0.07). Of 36 questions with scores of 1-2, 34 were re-queried/re-graded 8-17 days later with substantial improvement (median 2 vs. 4; pConclusions: ChatGPT generated largely accurate information to diverse medical queries as judged by academic physician specialists although with important limitations. Further research and model development are needed to correct inaccuracies and for validation.

Objective The purpose of this study was to test the hypothesis that a significant temporal relationship exists between asthma and attention deficit hyperactivity disorder (ADHD).Methods The population dataset consisted of 95,846,511 physician diagnoses for 768,460 (46% male) individuals spanning 1993–2010. Four groups were labeled as having neither Asthma nor ADHD, Asthma only, ADHD only, or both Asthma and ADHD and formed the basis of calculating the odds ratios for each sex describing the association of Asthma and ADHD by age, and, in addition, a prospective sample age (

This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Bladder Cancer focuses on the clinical presentation and workup of suspected bladder cancer, treatment of non–muscle-invasive urothelial bladder cancer, and treatment of metastatic urothelial bladder cancer because important updates have recently been made to these sections. Some important updates include recommendations for optimal treatment of non–muscle-invasive bladder cancer in the event of a bacillus Calmette-Guérin (BCG) shortage and details about biomarker testing for advanced or metastatic disease. The systemic therapy recommendations for second-line or subsequent therapies have also been revised. Treatment and management of muscle-invasive, nonmetastatic disease is covered in the complete version of the NCCN Guidelines for Bladder Cancer available at NCCN.org. Additional topics covered in the complete version include treatment of nonurothelial histologies and recommendations for nonbladder urinary tract cancers such as upper tract urothelial carcinoma, urothelial carcinoma of the prostate, and primary carcinoma of the urethra.

Rice is an important human staple food vulnerable to heavy metal contamination due to its unique physiology and growth environment. High yield with low heavy metal contamination is a common but highly challenging goal for rice breeders worldwide due to lack of genetic knowledge. In this report, a comprehensive GWAS analyses for ionomic and agronomic traits based on 3,259,478 SNPs were performed using two univariate methods and two multivariate methods. Under the criterium p-value

Salmonella biofilms act as a continuous source for cross-contamination in the food processing environments. In this study, a stable rugose morphotype of Salmonella was first induced by sequential exposure to subinhibitory concentrations (SICs) of sodium hypochlorite (NaOCl) (ranging from 50 to 300 ppm over 18-day period) in tryptic soy broth. Then, rugose and smooth morphotypes of Salmonella Typhimurium ATCC 14028 and Salmonella Heidelberg ATCC 8326 were characterized for biofilm forming abilities on polystyrene and stainless steel surfaces. Rugose morphotype of both ATCC 14028 and ATCC 8326 exhibited higher Exopolysaccharide (EPS) formation than smooth morphotype (p ≤ 0.05). Also, the SICs of NaOCl (200 or 300 ppm in broth model) increased the biofilm formation ability of rugose morphotype of ATCC 8326 (p ≤ 0.05) but decreased that of ATCC 14028. The 2-day-old Salmonella biofilms were treated with biocidal concentrations of 50, 100, or 200 ppm NaOCl (pH 6.15) in water for 5, 10, or 20 min at room temperature. The biofilm reduction in CFU/cm2 for the rugose was lower than the smooth morphotype on both surfaces (p ≤ 0.05) by lethal NaOCl in water. Scanning electron micrographs on both polystyrene and stainless steel surfaces demonstrated that the rugose morphotype produced a denser biofilm than the smooth morphotype. Transmission electron micrographs revealed the cell wall roughness in rugose morphotype, which may help in tolerance to NaOCl. The gene expression data indicate that the expression of biofilm regulator (csgD), curli (csgA, csgB, and csgC), and cellulose (bcsE) was significantly increased in rugose morphotype when induced by sequential exposure of NaOCl SICs. These findings reveal that the rugose morphotype of S. Typhimurium and S. Heidelberg produced significantly denser biofilm on food contact surfaces, which also increased with sequential exposure to SICs of NaOCl in the case of S. Heidelberg, and these biofilms were more tolerant to biocidal NaOCl concentrations commonly used in the food processing plants.

Accurate analysis of link performance including deterministic and random effects as well as advanced signal conditioning schemes is crucial in modern high-speed I/O design. In recent years, statistical link performance tools such as LinkLab and StatEye are introduced to efficiently analyze the overall link performance with both deterministic and random noise. The statistical-domain analysis has limitations in terms of its capability of accurately simulating system nonlinearity, jitter, as well as coding. In this paper, we present a new hybrid approach that combines statistical and time-domain techniques to efficiently overcome these limitations. The proposed method has several key contributions: 1) capture system nonlinearity; 2) separately simulate short-term deterministic jitter in the time domain and long-term deterministic and random jitter in the statistical domain; 3) co-simulate clock and data channels to capture jitter tracking; and 4) co-simulate signal and power integrity to include simultaneous switching output noise. We demonstrate this hybrid approach by studying the jitter tracking capability of a clock forwarding scheme and the effectiveness of coding in terms of system bit error rate.

Accurate analysis of system timing and voltage margin including deterministic and random jitter is crucial in high-speed I/O system designs. Traditional SPICE-based simulation techniques can precisely simulate various deterministic jitter sources, such as intersymbol interference (ISI) and crosstalk from passive channels. The inclusion of random jitter in SPICE simulations, however, results in long simulation time. Innovative simulation techniques based on a statistical simulation framework have been recently introduced to cosimulate deterministic and random jitter effects efficiently. This paper presents new improvements on this statistical simulation framework. In particular, we introduce an accurate jitter modeling technique which accounts for bounded jitter with arbitrary spectrum in addition to Gaussian jitter. We also present a rigorous approach to model duty cycle distortion (DCD). A number of I/O systems are considered as examples to validate the proposed modeling methodology.

Boundary layer wind data observed by a Doppler lidar and sonic anemometers during the mornings of three intensive observational periods (IOP2, IOP3, and IOP7) of the Joint Urban 2003 (JU2003) field experiment are analyzed to extract the mean and turbulent characteristics of airflow over Oklahoma City, Oklahoma. A strong nocturnal low-level jet (LLJ) dominated the flow in the boundary layer over the measurement domain from midnight to the morning hours. Lidar scans through the LLJ taken after sunrise indicate that the LLJ elevation shows a gradual increase of 25–100 m over the urban area relative to that over the upstream suburban area. The mean wind speed beneath the jet over the urban area is about 10%–15% slower than that over the suburban area. Sonic anemometer observations combined with Doppler lidar observations in the urban and suburban areas are also analyzed to investigate the boundary layer turbulence production in the LLJ-dominated atmospheric boundary layer. The turbulence kinetic energy was higher over the urban domain mainly because of the shear production of building surfaces and building wakes. Direct transport of turbulent momentum flux from the LLJ to the urban street level was very small because of the relatively high elevation of the jet. However, since the LLJ dominated the mean wind in the boundary layer, the turbulence kinetic energy in the urban domain is correlated directly with the LLJ maximum speed and inversely with its height. The results indicate that the jet Richardson number is a reasonably good indicator for turbulent kinetic energy over the urban domain in the LLJ-dominated atmospheric boundary layer.

A simple analytical form is used to model turbulent velocity spectra. This form has 2 free constants that can be calculated by turbulence measurements with a non-linear curve fitting method. The Joint Urban 2003 (JU2003) field experiments were undertaken in Oklahoma City during the summer of 2003. Sonic anemometer data taken using Lawrence Livermore National Laboratory s 83 m pseudo tower from JU2003 are analyzed. We present the results of characteristics of the urban turbulence velocity spectra. In particular, we focus on the features of spectral peak frequency and wavelength. Their variations with wind direction and atmospheric stability, within and above the urban canopy, are discussed in detail.

A multigrid numerical method has been applied to a three-dimensional, high-resolution diagnostic model for flow over complex terrain using a mass-consistent approach. The theoretical background for the model is based on a variational analysis using mass conservation as a constraint. The model was designed for diagnostic wind simulation at the microscale in complex terrain and in urban areas. The numerical implementation takes advantage of a multigrid method that greatly improves the computation speed. Three preliminary test cases for the model’s numerical efficiency and its accuracy are given. The model results are compared with an analytical solution for flow over a hemisphere. Flow over a bell-shaped hill is computed to demonstrate that the numerical method is applicable in the case of parameterized lee vortices. A simulation of the mean wind field in an urban domain has also been carried out and compared with observational data. The comparison indicated that the multigrid method takes only 3%–5% of the time that is required by the traditional Gauss–Seidel method.

Sixteen land-surface schemes participating in the Project for the Intercomparison of Land-surface Schemes (PILPS) Phase 2(c) were run using 10 years (1979–1988) of forcing data for the Red–Arkansas River basins in the Southern Great Plains region of the United States. Forcing data (precipitation, incoming radiation and surface meteorology) and land-surface characteristics (soil and vegetation parameters) were provided to each of the participating schemes. Two groups of runs are presented. (1) Calibration–validation runs, using data from six small catchments distributed across the modeling domain. These runs were designed to test the ability of the schemes to transfer information about model parameters to other catchments and to the computational grid boxes. (2) Base-runs, using data for 1979–1988, designed to evaluate the ability of the schemes to reproduce measured energy and water fluxes over multiple seasonal cycles across a climatically diverse, continental-scale basin. All schemes completed the base-runs but five schemes chose not to calibrate. Observational data (from 1980–1986) including daily river flows and monthly basin total evaporation estimated through an atmospheric budget analysis, were used to evaluate model performance. In general, the results are consistent with earlier PILPS experiments in terms of differences among models in predicted water and energy fluxes. The mean annual net radiation varied between 80 and 105 W m −2 (excluding one model). The mean annual Bowen ratio varied from 0.52 to 1.73 (also excluding one model) as compared to the data-estimated value of 0.92. The run-off ratios varied from a low of 0.02 to a high of 0.41, as compared to an observed value of 0.15. In general, those schemes that did not calibrate performed worse, not only on the validation catchments, but also at the scale of the entire modeling domain. This suggests that further PILPS experiments on the value of calibration need to be carried out.

The energy components of sixteen Soil-Vegetation Atmospheric Transfer (SVAT) schemes were analyzed and intercompared using 10 years of surface meteorological and radiative forcing data from the Red-Arkansas River basin in the Southern Great Plains of the United States. Comparisons of simulated surface energy fluxes among models showed that the net radiation and surface temperature generally had the best agreement among the schemes. On an average (annual and monthly) basis, the estimated latent heat fluxes agreed (to within approximate estimation errors) with the latent heat fluxes derived from a radiosonde-based atmospheric budget method for slightly more than half of the schemes. The sensible heat fluxes had larger differences among the schemes than did the latent heat fluxes, and the model-simulated ground heat fluxes had large variations among the schemes. The spatial patterns of the model-computed net radiation and surface temperature were generally similar among the schemes, and appear reasonable and consistent with observations of related variables, such as surface air temperature. The spatial mean patterns of latent and sensible heat fluxes were less similar than for net radiation, and the spatial patterns of the ground heat flux vary greatly among the 16 schemes. Generally, there is less similarity among the models in the temporal (interannual) variability of surface fluxes and temperature than there is in the mean fields, even for schemes with similar mean fields.

A memory system that meets the bandwidth, power efficiency, and capacity needs of future computing systems is presented in this paper. A 6.4 Gbps single-ended DDR memory interface for the controller and the DRAM was designed in a 28-nm CMOS process for a main memory system with dual-rank DIMMs. The architecture features a novel clocking scheme, per-pin timing adjustment, dynamic point-to-point signaling topology, and near ground signaling. The system V-T budget simulations and the characterization results of the fabricated memory interface are presented.

The objective of this study is to examine the effects of extracts from raw and cooked lentil on angiotensin II (Ang II)-induced cardiac hypertrophy, fibrosis, and hypertension in normotensive rats. Subcutaneous infusion of Ang II (200 ng/kg/min) using osmotic minipump significantly resulted in the elevation of blood pressure measured using telemetry in conscious rats. Histological examination revealed that Ang II infusion for 4 weeks induced significant cardiac hypertrophy, perivascular fibrosis in the heart and kidney. Rats received lentil extracts (oral administration for 4 weeks) significantly attenuated Ang II-induced elevation in blood pressure, cardiac hypertrophy, perivascular fibrosis. To examine whether the protective effect of lentil extracts on cardiac hypertrophy is mediated by attenuation of blood pressure or directly act on the cardiomyocytes, we examined the effect of lentil extracts on Ang II-induced hypertrophy in cultured cardiomyocytes. The result demonstrated that pretreatment of cardiomyocytes with cooked or raw lentil extract significantly attenuated the Ang II-induced increases in the size of cells. In addition, these lentil extracts also attenuated Ang II-induced increases in the ROS levels in cardiomyocytes. In summary, the results demonstrate that extracts from cooked or raw lentil prevent Ang II-induced elevation in blood pressure, perivascular fibrosis, and cardiac hypertrophy. The cardiac protective effect on Ang II-induced cardiac hypertrophy may be mediated by a direct action in cardiac tissue via reduction of oxidative stress.

High-speed link design in a 3D package system poses unique challenges due to the fact that it provides limited visibility to signal quality and that supply noise induced jitter is large due to a poor power distribution network in a small form factor. This paper outlines a statistical link simulation flow to accurately capture the impact of timing jitter due to power supply noise in 3D systems. The analysis includes on-chip jitter accumulation and link-level jitter tracking by considering both passive channel and on-chip signal path. On-chip measurement techniques which allow in-situ testing of the overall link margin are also described.

Historically, the block layers are considered "non critical ", as ones requiring less challenging ground rules. However, continuous technology-driven scaling has brought these layers to a point, where resolution, tolerance and aspect ratio issue of block masks now present significant process and material challenges. Some of these challenges will be discussed in this paper. In recent bulk technology nodes, the deep well implants require an aspect ratio of up to 5:1 in conventional resist leading to small process margin for line collapse and/or residue. New integration schemes need to be devised to alleviate these issues, i.e. scaling down the energy of the implant and the STI deep trench to reduce resist thickness, or new hard mask solutions with high stopping power to be dry etched. Underlying topography creates severe substrate reflectivity issues that affect CD, tolerance, profiles and defectivity. In addition to the CD offset due to the substrate, the implant process induces CD shrinkage and resists profile degradation that affects the devices. Minimizing these effects is paramount for controlling implant level processes and meeting overall technology requirements. These "non-critical" layers will require the development of more complex processes and integration schemes to be able to support the future technology nodes. We will characterize these process constraints, and propose some process / integration solutions for scaling down from 28nm to 20 nm technology node.

The paper describes a process/design co-optimization effort based on an SRAM design to enable a single exposure contact process for the 28nm technology half node. As a start, a change to the wiring concept of the standard SRAM design was implemented. The resulting individual contact layer elements may seem even more resolution critical to the casual observer. But in reality, the flexibility for source-mask optimization had been significantly improved. In a second step, wafer targets and mask dimension options (using various kinds of OPC methods and SRAF strategies) were run through several optimization iterations. This included interlevel considerations due to stringent overlap requirements. Several promising SRAM design as well as mask options were identified and experimentally verified to finally converge to an optimum mask and wafer target layout. Said optimum solution still supports an automated OPC approach using standard EDA tools and off the shelf OPC strategies. In a last step, a 1Mbit electrically testable SRAM was designed and manufactured together with alternative SRAM designs and process options. After explaining the changes to the wiring of the SRAM design, the paper discusses in great detail various mask optimization solutions and their consequences on wafer target and printability. Simulation and experimental results are compared and the concluding optimized solution is explained. Furthermore, some key lithography and etch process elements that became the single exposure process enabler are explained in more detail. Finally, the paper will take a look at electrical results of the 1Mbit electrically testable SRAM as the ultimate proof of concept.

As data rate pushes to 10Gbps and beyond, timing jitter has become one of the major factors that limit the link performance. Thorough understanding of the link jitter characteristics and accurate modeling of their impact on link performance is a must even at early design stage. This paper discusses the characteristics of timing jitter in typical I/O interfaces and overviews various jitter modeling methods proposed in the literature during the past few years. Recommendations are given based on the characteristics of timing jitter and their locations.

Implant level photolithography processes are becoming more challenging each node due to everdecreasing CD and resist edge placement requirements, and the technical challenge is exacerbated by the business need to develop and maintain low-cost processes. Optical Proximity Correction (OPC) using models created based on data from plain silicon substrate is not able to accommodate the various real device/design scenarios due to substrate pattern effects. In this paper, we show our systematic study on substrate effect (RX/STI) on implant level lithography CD printing. We also explain the CD variation mechanism and validate by simulation using well calibrated physical resist model. Based on the results, we propose an approach to generate substrate-aware OPC rules to correct for such substrate effects.

Characterization of I/O channels in 3D package systems is quite challenging as it is difficult to observe signal quality. A traditional way of measuring each device in a component level does not capture complex interaction in 3D integration. Although a sense line can be designed to externally measure noise on power lines, it is not feasible for signal lines as it significantly alters the signal quality. Hence, on-chip measurement features are highly desirable for 3D package systems including emerging Through-Silicon Vias (TSV) technology. In this paper, four key on-chip measurement concepts and circuitries are reviewed: eScope for measuring overall link margins, eWave for capturing a signal waveform, nScope for generating and monitoring on-chip power noise, and zScope for measuring power distribution network (PDN). These circuitries are implemented in a low power differential memory interface. The test vehicle is built based on Package-on-Package (PoP) environment. Measurements from the test vehicle are compared with the predicted data based on simulation.

An apothecial discomycete from diseased branches of Japanese red pine in Georgia was found to be conspecific with Cenangium atropurpureum. After comparison of the Georgia material with Ce. ferruginosum, the type species, it was concluded that on the basis of ectal excipular characteristics, Ce. atropurpureum is better accommodated in Crumenulopsis. This species differs from European species of Crumenulopsis in the oval shape of the ascospore, presence of a gelatinous ascospore sheath, and possession of a diffusible purplish pigment in KOH. It differs from the Florida species, Cr. lacrimiformia, in the shape of the ascospore and ascospore sheath, larger size of the ascoma, presence of the purple pigment, and host species.

Statistical link analysis has gained significant importance as high-speed interconnect designs require accurate bit error rate prediction with device jitter and noise. Currently available statistical analysis techniques focus on modeling of data channels and the impact of a clock channel is often ignored or primitively approximated using a simple receiver sampling distribution. Thus, it ignores any jitter tracking between data and clock signals. In this paper, a general formulation is presented to model the common jitter source between data and clock signals in order to capture any jitter tracking between them. To demonstrate the usage of the proposed formulation, we have derived various models for commonly used clocking architectures, such as the forwarded clocking scheme in XDR™, DDR, and GDDR systems and the common source RefClk architecture used in PCIe channels. The formulation is verified numerically by using an internally developed CAD tool.

This paper describes the design and characterization of a low power differential memory interface targeted for mobile applications. The initial design of the memory interface achieves 2.7 to 4.3GB/s data bandwidth and consumes 3.3mW/Gb/s at 4.3GB/s operation. The design allows two x16 stacked dies to be fit into a 12mm PoP package, achieving a 12.8GB/s aggregated data bandwidth based on 3.2Gb/s per pin. A low swing signaling based on a voltage-mode differential driver is reviewed and its performance is analyzed. We demonstrate that, compared to LPDDR2 memory interface based on single-ended signaling, the differential memory interface overcomes most of channel related issues such as crosstalk and SSO noise and provides a very clean channel response. Thus, the resulting extra system margin can be used to compensate for extra timing jitter and system noise, enabling lower power and lower system cost. To evaluate the impact of timing jitter and system noise to system performance, a statistical link modeling and simulation methodology is employed. Two test systems are built based on wirebond-based Package-on-Package (PoP) and BGA-based Chip-to-Chip (C2C) module to characterize the memory system performance and to validate the memory statistical link model. The correlation result showed a good agreement in the system bit error rates (BER) between measurement and simulation.

A complete and comprehensive description of the high resolution wind (HRW) model is presented. The HRW model has been in development at the U.S. Army Research Laboratory, formerly U.S. Army Atmospheric Sciences Laboratory, since 1978. This model is a two-dimensional, diagnostic atmospheric surface-layer wind model with a horizontal grid spacing of the order of 100 m over a domain of about 5 by 5 km. It uses Gauss? principle of least constraint and a direct variational relaxation method to adjust an initially uniform wind field to conform with topography, mass conservation, and buoyancy forces. A distinctive feature of the model is the use of a non-orthogonal, terrain following, warped coordinate system. A valuable observational dataset of surface wind has been provided from the field study of Meteorology and Diffusion Over Non-Uniform Areas (MADONA) at Porton Down, Salisbury, England during September and October 1992. Using the MADONA data, a critical evaluation for the HRW model for 39 cases has been carried out. The results of this study are presented, indicating both the range of validity and the limitations of the HRW model.

Single-ended signaling systems, popular in memory I/O interfaces, are limited by signal and power integrity issues such as crosstalk and simultaneous switching output noise (SSO). At high data rates, the single-ended systems also suffers from random noise and timing jitter. In this paper, we present an integrated signal and power integrity simulation flow that combines statistical and transient simulation methods to enable the characterization of single-ended systems to account for random timing jitter in addition to the traditional SI issues focused on the deterministic noise such as intersymbol interference (ISI), crosstalk, and SSO noise. To include SSO noise, we co-simulate power distribution network (PDN) and channel models and treat SSO noise as another form of crosstalk. To capture any system nonlinearity, we employ time-domain based multi-edge response (MER) method to characterize the deterministic and passive portion of channels. Then, random noise and timing jitter impact are included via statistical approach. We use GDDR system to demonstrate our simulation flow.

Conventional ways of summing component specifications to balance voltage and timing budgets are increasingly problematic as data rates continue to scale higher for high speed links. For instance, performance degradation caused by transmitter jitter is more severe than that caused by receiver jitter due to jitter coloring by the passive channel. Furthermore, certain jitter components could interact in the system so it is inaccurate to treat them as independent variables. A system voltage and timing budgeting process hence requires a sophisticated method to accurately predict the overall system performance based on the component specifications. With the recent introduction of a statistical CAD tool, the impact of each individual component, including both deterministic and random jitter, can be co-simulated [l]-[3]. This paper demonstrates the usage of this statistical CAD tool for modeling component budgets. We verify the accuracy of our modeling approach by correlating with a FlexIOreg parallel link interface. Then, we apply the proposed methodology to a PCI Expressreg bus system to estimate the system performance based on published component jitter specification.

Jitter Amplification is a real concern in the design of PCB clock channels if the frequency of the clock is high and the PCB trace is relatively long. In this paper, we confirm the earlier finding of clock channel jitter amplification [1], using a multiple edge response (MER) simulation method instead of jitter impulse response for the channel. However, we show that both white Random Jitter (wRJ) and Sinusoidal Jitter (SJ) amplification are a function of the signal loss in the channel, and as such, are reduced significantly with equalization. Furthermore, simulated CMOS Tx RJ, which is dominated by its low frequency components, is amplified less than is wRJ, even for channels with >20dB signal loss. Measurement results are correlated with simulations for 2-6 GHz clocks on a channel containing 24-inches of PCB trace.

Accurate analysis of system timing and voltage margin at a target bit error rate across process, voltage, and temperature variations is required for high volume production of high speed systems. This in turn requires a statistical simulation framework to model the effectiveness of advanced signaling techniques such as transmitter equalization and receiver decision feedback. Furthermore, for data and telecommunication networking serial links, one must also carefully model the clock-data recovery circuits (CDR) and understand their impact on system voltage and timing margin. In this paper, we first present a stochastic simulation framework and describe a modeling methodology for CDR circuits. We then compare the simulation results based on CDR modeling to a simple method, which uses a quadrature sampling based timing recovery model. Finally, we correlate the simulation results to lab measurements to validate the proposed approach.

Arecoline, an areca quid (AQ) component, has been shown to inhibit the secretion and activity of matrix metalloproteinase-2 (MMP-2) in fibroblast cultures. This study assessed whether MMP-2 expression was inhibited in the saliva samples and tumor specimens of oral tumor patients with a long-term history of AQ consumption. The net effect of crude AQ extract (AQE) on MMP-2 expression by oral cells was also investigated.Western blot analysis, zymography, and reverse transcriptase-polymerase chain reaction were used to detect MMP-2 protein and mRNA in saliva and tumor samples, as well as in the conditioned media (CM) of oral cell cultures.The level of MMP-2 protein was significantly higher in the saliva samples of 12 oral tumor patients who had a minimum 10-year AQ-consuming history than in those of 12 non-AQ-using healthy controls (p0.05). MMP-2 mRNA was expressed in 26 of 28 oral squamous cell carcinoma (OSCC) specimens. MMP-2 protein was also detectable in the tested OSCC homogenates. Short-term stimulation with 10% AQE increased the secretion of MMP-2 protein in the CM of oral epidermoid carcinoma cell Meng-1 (an OSCC cell line) and oral fibroblasts.MMP-2 expression is elevated rather than inhibited in most oral tumor patients with long-term AQ usage. Short-term AQE stimulation also increases the secretion of MMP-2 by oral epithelial cells and fibroblasts. Our results suggest that AQ consumption may promote oral tumor progression through the induction of MMP-2 secretion.