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Objectives The objective of the study was to validate PCr/ATP ratios as an in vivo marker for cardiac mitochondrial function.Background Cardiac energy status, measured as PCr/ATP ratio with 31P-MRS in vivo, was shown to be a prognostic factor in heart failure and is lowered in cardiometabolic disease. As mitochondrial function is also hampered in these diseases and oxidative phosphorylation is the major contributor to ATP synthesis, the PCr/ATP ratio might be a reflection of cardiac mitochondrial function.Methods Thirty-eight patients scheduled for open heart surgery were enrolled in this study. Before surgery, cardiac 31P-MRS was performed. During surgery, tissue specimens from the right atrial appendage were obtained for the ex vivo assessment of mitochondrial function using high-resolution respirometry.Results The patient population included was heterogenous resulting in wide ranges of PCr/ATP ratios and ADP-stimulated respiration rates (PCr/ATP ranging from 0.533 to 1.717; ADP-stimulated respiration rates ranging from 28.5 to 94.6 pmol/mg/s). Correlation analysis however showed no relationship between PCr/ATP and ADP-stimulated respiration rates fueled by various substrates (octanoylcarnitine R2 2 2 = 0.005, p = 0.71; pyruvate R2 = 0.040, p = 0.26).Conclusions Our results do not support the use of cardiac energy status (PCr/ATP) as a surrogate marker of mitochondrial function in the heart. The dissociation of the two parameters in the present study suggests that mitochondrial function is not the only determinant of cardiac energy status.Condensed abstractThis study does not support the use of in vivo cardiac energy status (PCr/ATP ratio) as a surrogate marker of ex vivo mitochondrial function (maximal oxidative respiration). Although both PCr/ATP and mitochondrial function are reduced in cardiovascular disease, the dissociation of the two parameters in the present study shows that PCr/ATP is determined by more factors than only mitochondrial function. Hence, PCr/ATP is not a good marker for mitochondrial function, but it can be a valuable marker for cardiometabolic health in cardiometabolic studies.Trial registration: https://clinicaltrials.gov (NCT03049228).

Falls among older adults are often attributed to declining muscle strength with ageing. Associations between muscle strength and balance control have been reported, but the evidence for, and key mechanisms of resistance exercise in fall prevention are unclear. No studies have directly examined the relationship between muscle fibre characteristics and reactive balance control. Here, we address whether or not Type II muscle fibre characteristics associate with reactive balance during walking in young and older adults with varying muscle fibre type composition. We analyse muscle biopsy-derived fibre characteristics and stability during a treadmill-based walking perturbation (trip-like) task of healthy young adults, healthy, normally active older adults, trained older adults and physically impaired older adults. We find no significant associations between Type II muscle fibre properties and reactive balance during walking, indicating that practitioners and researchers should consider more than just the muscle tissue properties when assessing and intervening on fall risk.

Mild cold acclimation for 10 days has been previously shown to markedly improve insulin sensitivity in patients with type 2 diabetes. Here we show in a single-arm intervention study (Trialregister.nl ID: NL4469/NTR5711) in nine patients with type 2 diabetes that ten days of mild cold acclimation (16–17 °C) in which observable, overt shivering was prevented, does not result in improved insulin sensitivity, postprandial glucose and lipid metabolism or intrahepatic lipid content and only results in mild effects on overnight fasted fat oxidation, postprandial energy expenditure and aortic augmentation index. The lack of marked metabolic effects in this study is associated with a lack of self-reported shivering and a lack of upregulation of gene expression of muscle activation or muscle contraction pathways in skeletal muscle and suggests that some form of muscle contraction is needed for beneficial effects of mild cold acclimation., Cold acclimation has been shown to have beneficial metabolic effects, including improved insulin sensitivity in patients with type 2 diabetes. Here the authors show that a mild cold acclimation regiment during which overt shivering was prevented did not result in improved insulin sensitivity in a small group of patients with type 2 diabetes.

Exercise training reduces intrahepatic lipid (IHL) content in people with elevated liver fat content. It is unclear, however, whether exercise training reduces IHL content in people with normal liver fat content. Here, we measured the effect of exercise training on IHL content in people with and people without nonalcohol fatty liver. We further measured changes in insulin sensitivity and hepatic energy metabolism. Eleven males with nonalcoholic fatty liver (NAFL) and 11 body mass index-matched individuals without nonalcoholic fatty liver (CON) completed a 12-wk supervised exercise training program. IHL content (proton magnetic resonance spectroscopy), maximal oxidative capacity (V̇o2max, spiroergometry), total muscle strength, body composition, insulin sensitivity (hyperinsulinemic-euglycemic clamp), hepatic ATP-to-total phosphorus ratio, and the hepatic phosphomonoester-to-phosphodiester (PME/PDE) ratio (phosphorus magnetic resonance spectroscopy) were determined. IHL content reduced with exercise training ( P = 0.014) in the whole study population. The relative reduction in IHL content was comparable in NAFL (−34.5 ± 54.0%) and CON (−28.3 ± 60.1%) individuals ( P = 0.800). V̇o2max ( P < 0.001), total muscle strength ( P < 0.001), and skeletal muscle insulin sensitivity ( P = 0.004) increased, whereas adipose tissue ( P = 0.246) and hepatic ( P = 0.086) insulin sensitivity did not increase significantly. Hepatic ATP-to-total phosphorus ratio ( P = 0.987) and PME/PDE ratio ( P = 0.792) did not change. Changes in IHL content correlated with changes in body weight ( r = 0.451, P = 0.035) and changes in hepatic PME/PDE ratio ( r = 0.569, P = 0.019). In conclusion, exercise training reduced intrahepatic lipid content in people with nonalcoholic fatty liver and in people with normal intrahepatic lipid content, and the percent reduction in intrahepatic lipid content was similar in both groups.

Intramyocellular lipids (IMCL) hamper insulin sensitivity albeit not in endurance-trained athletes (Trained). Compared to type 2 diabetes patients (T2DM), Trained subjects have high levels of Perilipin 5 (PLIN5). Here, we tested if the fraction of PLIN5 coated LDs is a determinant of skeletal muscle insulin sensitivity and contributes to the athlete's paradox. Muscle biopsies were taken from 8 Trained, Lean sedentary, Obese and T2DM subjects. Trained, Obese and T2DM subjects were matched for total IMCL content. Confocal images were analysed for lipid area fraction, LD size and number and PLIN5+ and PLIN5- LDs were measured. A stepwise linear regression was performed to identify factors explaining observed variance in GIR. Trained and T2DM subjects stored IMCL differently; Trained had a higher number of LDs compared to T2DM (0.037 ± 0.004 μm−2 vs. 0.023 ± 0.003 μm−2, P = 0.024), that were non-significantly smaller (0.27 ± 0.01 μm2 vs. 0.32 ± 0.02 μm2, P = 0.197, Trained vs. T2DM). Even though total PLIN5 protein content was almost double in Trained vs. T2DM (1.65 ± 0.21 AU vs. 0.89 ± 0.09 AU, P = 0.004), PLIN5 coating did not affect LD number or size significantly. Of the observed variance in GIR, the largest fraction by far (70.2%) was explained by maximal oxygen uptake, adding PLIN5 protein content or PLIN5+ LDs increased the explained variance in GIR (74.7% and 80.7% for PLIN5 protein content and PLIN5+ LDs, respectively). Thus, the putative relation between PLIN5 and insulin sensitivity is at best indirect and is apparent only in conjunction with maximal oxygen uptake. Hence, PLIN5 abundance cannot be causally linked to the athlete's paradox. This article is protected by copyright. All rights reserved

Objective Intramyocellular lipid (IMCL) storage negatively associates with insulin resistance, albeit not in endurance-trained athletes. We investigated the putative contribution of lipid droplet (LD) morphology and subcellular localization to the so-called athlete's paradox. Methods We performed quantitative immunofluorescent confocal imaging of muscle biopsy sections from endurance Trained, Lean sedentary, Obese, and Type 2 diabetes (T2DM) participants (n = 8/group). T2DM patients and Trained individuals were matched for IMCL content. Furthermore we performed this analysis in biopsies of T2DM patients before and after a 12-week exercise program (n = 8). Results We found marked differences in lipid storage morphology between trained subjects and T2DM: the latter group mainly store lipid in larger LDs in the subsarcolemmal (SS) region of type II fibers, whereas Trained store lipid in a higher number of LDs in the intramyofibrillar (IMF) region of type I fibers. In addition, a twelve-week combined endurance and strength exercise program resulted in a LD phenotype shift in T2DM patients partly towards an ‘athlete-like’ phenotype, accompanied by improved insulin sensitivity. Proteins involved in LD turnover were also more abundant in Trained than in T2DM and partly changed in an ‘athlete-like’ fashion in T2DM patients upon exercise training. Conclusions Our findings provide a physiological explanation for the athlete's paradox and reveal LD morphology and distribution as a major determinant of skeletal muscle insulin sensitivity., Highlights • Distinct lipid droplet morphology and distribution underlies the athletes' paradox. • Muscle lipid storage occurs in a fiber type specific manner. • Exercise training shifts LD morphology towards an athletes' phenotype.

Today’s CD-SEM metrology is challenged when it comes to measuring complex features found in patterning hotspots (like tip to tip, tip to side, necking and bridging). Metrology analysis tools allow us to extract SEM contours of a feature and convert them into a GDS format from which dimensional data can be extracted. While the CD-SEM is being used to take images, the actual measurement and the choice of what needs to be measured is done offline. Most of the time this method is used for OPC model creation but barely for process variability analysis at nominal process conditions. We showed in a previous paper [1] that it is possible to study lithography to etch transfer behavior of a hotspot using SEM contours. The goal of the current paper is to go extend this methodology to quantify process variability of 2D features using a new tooling to measure contour data.

A 5-day High-Fat High-Calorie diet (HFHC-diet) reduces insulin-stimulated glucose disposal (Rd) in South Asian, but not Caucasian healthy lean males. We aimed to investigate if differences in myocellular lipid handling are underlying this differential response. A two-step hyperinsulinemic-euglycemic clamp and muscle biopsies were performed in 12 healthy lean Caucasian and South Asian males (BMI 2, 19–25 years) before and after a 5-day HFHC-diet (regular diet + 375 mL cream/day; 1275 kcal/day; 94% fat). Triglyceride extractions and Western Blots for lipid droplet and mitochondrial proteins were performed. Intramyocellular lipid content and HFHC-diet response were similar between ethnicities (group effect: P = 0.094; diet effect: +~30%, P = 0.044). PLIN5 protein content increased upon the HFHC-diet (P = 0.031) and tended to be higher in South Asians (0.87 ± 0.42 AU vs. 1.35 ± 0.58 AU, P = 0.07). 4-HNE tended to increase in South Asians upon the HFHC-diet (interaction effect: P = 0.057). In Caucasians ΔPLIN5 content correlated with ΔRd (Caucasians: r = 0.756, P = 0.011; South Asians: r = −0.085, P = 0.816), while in South Asians Δ4-HNE associated with ΔPLIN5 content (Caucasians: r = 0.312, P = 0.380; South Asians: r = 0.771, P = 0.003). These data indicate that in Caucasians, PLIN5 may be protective against HFHC-diet induced insulin resistance, which for reasons not yet understood is not observed in South Asians, who possess increased lipid peroxidation levels.

The concept of the multi-source focus correlation method was presented in 2015 [1, 2]. A more accurate understanding of real on-product focus can be obtained by gathering information from different sectors: design, scanner short loop monitoring, scanner leveling, on-product focus and topography. This work will show that chip topography can be predicted from reticle density and perimeter density data, including experimental proof. Different pixel sizes are used to perform the correlation in-line with the minimum resolution, correlation length of CMP effects and the spot size of the scanner level sensor. Potential applications of the topography determination will be evaluated, including optimizing scanner leveling by ignoring non-critical parts of the field, and without the need for time-consuming offline topography measurements.

For the last 25 years, maskless lithography (ML2) has always been perceived as a promising technology because of its superior resolution and flexibility. However, the very low throughput of ML2 compared to that of optical lithography has prevented it from being used in high volume manufacturing. Consequently, this technology has always been used for niche applications. With ever decreasing critical dimensions (CD), increasing cycle time and escalating mask-set cost, ML2 may become a reliable solution to the following applications:*device engineering driven by resolution requirements, *fast and economical product prototyping driven by the cycle time, *low volume manufacturing driven by the high cost of mask sets. Currently, only single beam tools are used, but worldwide efforts are being carried out in order to develop new tools based on the concept of multi beams (10,000-100,000 beamlets). These tools use photons, high energy electrons (100kev) or low energy electrons (10kev). Cost of ownership modelling (COO) was carried to determine the conditions when ML2 approach is more economical than all mask based lithography for prototyping or low volume production. It is assumed that ML2 is applicable for patterning the critical layers only. There exists a business operating case at which a decrease in the mask set expense outweighs an increase in the depreciation cost, which would render utilization of ML2 economically beneficial. The conditions of economically justifiable use of ML2 will be examined.

Contains fulltext : 57907.pdf (Publisher’s version ) (Closed access) OBJECTIVE: To investigate whether the detection of proliferation-associated Ki-67 antigen may be of value in differentiating between reserve cell hyperplasia (RCH) and small cell lung cancer (SCLC). STUDY DESIGN: Retrospectively, 20 Papanicolaou-stained bronchial brushes or washings from 20 patients were selected. Ten were diagnosed as RCH (and had no SCLC in follow-up) and the other 10 as SCLC (histologically confirmed). All 20 Papanicolaou-stained slides were restained with the monoclonal antibody MIB1, directed against Ki-67 antigen; that simple and reliable procedure was described recently. In each specimen 5 coherent cell groups were identified, corresponding to RCH or SCLC, respectively; photographed; and studied for Ki-67 antigen expression after MIB1 staining of the slides. At least 3 cell groups remained in each specimen. The Ki-67 labeling index (LI) of the specimens was determined as the number of MIB1-positive cells divided by the total number of cells in the remaining cell groups. RESULTS: All cases of SCLC showed a mean Ki-67 LI of at least .415 (mean .684, SD .151), whereas in the cases with RCH the mean Ki-67 LI never was more than .158 (mean .048, SD .049). The difference was highly significant (P

Formalin-fixed and paraffin-embedded tissue specimens of normal and dysplastic cervical epithelia (five CIN1, seven CIN2, five CIN3, and five normal) were assessed by an immunoperoxidase technique, using the monoclonal antibody MIB1, regonizing a formalin-fixation-resistant epitope on the cell proliferation-associated Ki-67 antigen. An image analysis system was used to measure four parameters associated with proliferative activity: the Ki-67 labelling index (LI), the number of Ki-67-positive nuclei per unit length of basement membrane, and the maximum value and 90th percentile of the relative distances of Ki-67-positive nuclei from the basement membrane. All these four proliferation-related parameters were highly correlated with the grade of dysplastic change in the epithelium (0.90 < r < 0.97, p < 0.0001). The best correlation was found for the 90th percentile of the relative distance and with this parameter all CIN lesions could be correctly classified. The means and standard deviations of the Ki-67 LIs in normal epithelium, CIN1, CIN2, and CIN3 lesions were 0.07 +/- 0.03, 0.16 +/- 0.03, 0.25 +/- 0.06, and 0.39 +/- 0.06, respectively. These findings support the theory that CIN involves a progressive dysfunction of the proliferative activity of cervical epithelial cells. Image analysis of MIB1 is a promising alternative method for the objective, reproducible, and reliable classification of dysplastic changes in cervical epithelium.

We hypothesized that imagery training would improve the fast onset of neuromuscular activation and thereby fast knee extensor isometric torque development. Forty young healthy participants, not involved in strength training, were assigned to one of four groups: physical training, imagery training, placebo training or control. The three training groups had three 15 min sessions per week for 4 weeks, with a 90° knee angle but were tested also at 120°. At 90° knee angle, maximal torque increased (∼8%) similarly in all three training groups. The torque–time integral (contractile impulse) over the first 40 ms after torque onset (TTI40) increased (P < 0.05) after physical training (by ∼100%), but only at 90°. This increase was significantly different from the delta values (change pre to post) in the control and placebo groups, whereas delta values in the imagery group were similar to those in the placebo group. The increases in TTI40 following physical training were related (r 2 = 0.81, P < 0.05) to significant increases of knee extensor rectified surface EMG at torque onset (EMG40). In conclusion, only physical training led to a knee angle specific increase of contractile impulse that was significantly different from placebo and controls and that was related to improved onset of neuromuscular activation.

The desire to reduce cost in volume manufacturing has driven up the throughput in the lithographic exposure machines. As a result the power transmitted in the projection optics increases. Although small, the absorption levels in the lens materials are not zero, which leads to localized heating of the lens and hence lens aberrations. To squeeze out the maximum process windows, the pupil shapes have transformed from simple annular shapes to shapes with very concentrated poles. As a result, the exposure energy transported through the lens is no longer equally distributed over the lenses of the projection options. Instead only a fraction of the lens gets to transport the total power. This concentration of power further aggravates the lens heating induced aberrations and enhances the importance of advanced lens heating control schemes which are available on ASML scanners. To analyze the effects of lens heating on the final imaging, a model was developed by the lens manufacturer Carl Zeiss SMT GmbH, and incorporated into a litho simulation environment by ASML BRION. This tool can be used to analyze the impact of dose/throughput, illumination shapes and reticle layout on aberrations. It provides a means to assess potential lens heating issues even before production masks are manufactured. Moreover, this computational tool opens the possibility to calculate parameters for lens heating correction, rather than measuring them, saving valuable machine time. In this paper, the performance of the novel computational lens heating control is demonstrated on wafer and compared with the traditional way of measuring the relevant parameters. In addition, a modeling study is performed to assess possible lens heating effects for freeform or non-traditional source shapes, thereby demonstrating the advanced correction potential of ASML latest aberration manipulator, called FlexWaveTM.

Once a process is set-up in an integrated circuit (IC) manufacturer's fabrication environment, any drift in the proximity fingerprint of the cluster will negatively impact the yield. In complement to the dose, focus and overlay control of the cluster, it is therefore also of ever growing importance to monitor and maintain the proximity stability (or CD through pitch behavior) of each cluster. In this paper, we report on an experimental proximity stability study of an ASML XT:1900i cluster for a 32 nm poly process from four different angles. First, we demonstrate the proximity stability over time by weekly wafer exposure and CD through pitch measurements. Second, we investigate proximity stability from tool-to-tool. In a third approach, the stability over the exposure field (intra-field through-pitch CD uniformity) is investigated. Finally, we verify that proximity is maintained through the lot when applying lens heating correction. Monitoring and maintaining the scanner's optical proximity through time, through the lot, over the field, and from toolto- tool, involves extensive CD metrology through pitch. In this work, we demonstrate that fast and precise CD through pitch data acquisition can be obtained by scatterometry (ASML YieldStar TM S-100), which significantly reduces the metrology load. The results of this study not only demonstrate the excellent optical proximity stability on a XT:1900i exposure cluster for a 32 nm poly process, but also show how scatterometry enables thorough optical proximity control in a fabrication environment.

C045 node (65nm half pitch) technology processes are driving the development of immersion lithography techniques and infrastructures and C032 node (45nm half pitch) is following in its tracks. As semiconductor development enters the arena of low leakage, high-performance devices using immersion lithography, the 45nm hp technology adds more pressure of decreasing pitches and feature sizes using the most cost effective method available. The Crolles2 Alliance is in the first phases of the push for very low k1 193nm lithography for our technology development. Many resolution enhancement techniques are being explored to fill the low k1 realm; including implementation of these techniques and more aggressive integrations to support the device parameters. However, the early development of 45nm hp node along with the need for better focus and dose control algorithms, imaging of pitches to allow for the packing density will present significant challenges to photolithography even when considering super hyper-NA immersion lithography. Reflectivity variations, thin film interference through the complex film stacks, and increased sensitivity to feature size is posing a challenge for maintaining good and consistent features. This paper discusses an analysis and early results covering the beginning development of 45nm hp with >1NA immersion lithography. Specifically, parameters such as illumination and enhancement techniques, processing capability, application of OPC at a very low k1, process integration, mask effects, and defectivity as discussed.

The lithography prognosticator of the early 1980's declared the end of optics for sub-0.5mm imaging. However, significant improvements in optics, photoresist and mask technology continued through the mercury lamp lines (436, 405 & 365nm) and into laser bands of 248nm and to 193nm. As each wavelength matured, innovative optical solutions and further improvements in photoresist technology have demonstrated that extending imaging resolution is possible thus further reducing k 1 . Several author have recently discussed manufacturing imaging solutions for sub-0.3k 1 and the integration challenges. Our industry will continue to focus on the most cost effective solution. What continues to motivate lithographers to discover new and innovative lithography solutions? The answer is cost. Recent publications have demonstrated sub 0.30 k 1 imaging. The development of new tooling, masks and even photoresist platforms impacts cost. The switch from KrF to ArF imaging materials has a significant impact on process integration. This paper will focus on the usefulness of beyond water immersion for 22nm logic node. Data will be presented demonstrating the impact of higher refractive index photoresist systems have on the further extension of ArF Immersion.

Contains fulltext : 51698.pdf (Publisher’s version ) (Closed access) Global glomerulosclerosis can be divided in the vascular (obsolescent) type and the glomerulopathic (solidified) type. In biopsies from children with recurrent nephrotic syndrome owing to minimal change nephropathy (MCN), we noticed small, globally sclerosed glomeruli that appeared to be distinct from global glomerulosclerosis. These small sclerosed glomeruli are best described as involuted glomeruli. We have characterized these involuted glomeruli in detail. We studied biopsies of 18 children (11 male, 7 female) with frequently relapsing MCN and evaluated possible explanatory variables. The involuted glomeruli can be differentiated from the other types of global glomerulosclerosis. Most notable is the presence of vital podocytes and parietal epithelial cells, which have retained their staining characteristics, in between the matrix, and the absence of periglomerular and tubulo-interstitial fibrosis. We observed involuted glomeruli in 12 out of 18 biopsies; the median percentage of involuted glomeruli was 6% (range 0-33%). The percentage of involuted glomeruli correlated with age at renal biopsy and the interval between onset of disease and time of renal biopsy, but not with gender, age at onset of disease, or prednisone dose. Multivariate analysis revealed that the interval between onset of disease and time of renal biopsy was the only independent predictor. In conclusion, glomerular involution is a special form of global glomerulosclerosis. The absence of periglomerular and tubulo-interstitial fibrosis suggests a different pathogenesis. Glomerular involution is a slow process. The clinical data suggest that involution is related to the duration of the disease process.

Semiconductor manufacturers are in the midst of the next technology node C045 (65nm half-pitch) development. The difference this time is that the heavy lifting is being done while swimming. Generally, for the C065 node (hp90), critical layers will be processed using 193-nm scanners with numerical apertures up to 0.85. It is also clear that the capabilities and potential benefits of immersion lithography (at this wavelength and NA) should to be examined, in addition to the development of immersion lithography for the C045 and C032 technology generations. The potential benefits of immersion lithography; increased DOF in the near term and hyper-NA imaging in the next phase, have been widely reported. A strategy of replacing conventional "dry" lithographic process steps with immersion lithographic process steps would allow the benefits of immersion to be realized much earlier. To fully realize this advantage a direct comparison of immersion lithography's benefits and therefore speed learning is needed. However, such an insertion should be "transparent": i.e. the "immersion process" should run with the same reticles (OPC) and resists, as the conventional process. In an effort to gain this knowledge about the immersion processes, we have chosen a path of optimizing and ramping-up the lithographic process for the C065 technology node. In this paper, we report on the compatibility of inserting immersion lithography processes into an established C065 process running in a pilot manufacturing line. We will present an initial assessment of some critical parameters for the implementation of immersion lithography. This assessment includes: OPC compatibility, imaging, process integration, and defectivity all compared to the dry process of record. Finally, conclusions will be made as to the overall readiness of immersion to support C065 node processing in direct transfer from dry and its extendibility to C045. In this work, the C045 technology node (hp65) is the main target vehicle. However, a successful introduction of immersion technology may allow a strategy change complementary with the previous (C065) technology node (i.e. run C065 immersion in production and benefit from larger process windows).

On-going complex integration schemes and developments in processes present significant challenges to lithography in manufacturing advanced semiconductor integrated circuits. Although APC solutions are in place to assist in achieving robust CD control and overlay, there is a great need to increase the 'knowledge' of the system with respect to other contributors impacting the process. The problem becomes more complex in case of an ASIC Prototyping Fab where there is no big runner concept. This leads to the need of a product effect management requirement (Product layout and reticles impact). For this reason, we developed the multivariate R2R controller. This paper discusses the multi-variant methodology and results of a new R2R regulation algorithm in a 65nm node process. Specifically, parameters such as linear combinations of terms, alignment variation for overlay modeled parameters (inter-field / intra-field), CD impacts (reticles, process, tool, STI stack etc) are studied. New solutions for future technology nodes are presented in this paper. It includes for each contributor a multivariate method to assess vector responses and noise contribution. This is being applied on CD and Overlay measurement feedback. For each source of variation (or "Contributor"), the multivariate controller provides the estimated level of compensation requested to meet the target and the level of noise induced on lot processing. At the moment the multivariate R2R controller runs in production. A real evaluation of the existing sources of variations and noise is possible and demonstrated. The result is a significant regulation performance improvement.

Achieving a proper focus setting in sub-micron optical lithography is extremely important. A technique has been developed for the determination of optimal focus setting on production lots. Using aerial image simulation the dimensions of the test structure studied have been optimized. With a simple optical microscope a judgement can be made about the focus setting. As the depth of focus becomes comparable to the resist thickness, it was observed that different methods of focus determination do not give the same results.

A brief review of the laser-liquid interaction is presented. A 1 nanosecond duration nitrogen laser has been used as the light source for Mach Zehnder interferometry of the first few microseconds following the impact of a carbon dioxide laser pulse on water and partially transmitting cyclohexane. Quantitative analysis of the interferograms using an Abel inversion procedure has been carried out. Ultra violet laser induced cavitation has been observed.© (1983) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.