Characterization of diffraction gratings in a rigorous domain with optical scatterometry: hierarchical neural-network model

Characterization of microstructures with features from submicrometers to hundreds of micrometers requires versatile methods. Profilometry and optical microscopy cannot cope with submicrometer features, and atomic-force microscopy, scanning-electron microscopy, and near-field microscopy are inherently slow, off-line methods. In optical scatterometry, the laser light scattered from a sample is measured and the sample profile is subsequently characterized. We propose the use of a two-stage model based on neural networks: rough categorization followed by refinement, thus reducing the need for prior information on the sample. We simulate the method for a submicrometer diffraction grating characterized by five parameters. It is shown that intensity measurements of few diffraction orders by use only of one wavelength are enough to yield rms errors of less than 2 nm for the parameters (approximately 2-3% of the optimal values of the parameters).     

Genetic changes in intraductal breast cancer detected by comparative genomic hybridization

Ductal carcinoma in situ (DCIS) is considered a direct precursor of invasive ductal breast cancer (IDC). We combined tissue microdissection and comparative genomic hybridization to identify genetic changes in five DCIS lesions with no invasion and in two that were adjacent to IDC. Extensive genetic changes characterized pure DCIS cases with gains of 1q, 6q, 8q, and Xq as well as losses of 17p and chromosome 22 being most often involved. Except for the Xq gain, these changes are also common to IDC. Separate analysis of DCIS and IDC components in the same tumor revealed an almost identical pattern of genetic changes in one case, whereas substantial differences were found in another. We conclude that many of the common genetic changes in IDC may take place before development of invasive growth. However, a simple linear progression model may not always account for the DCIS-IDC transition.     

Tissue microarrays for high-throughput molecular profiling of tumor specimens

The impact of oral treatment with insulin on disease development was studied in diabetes prone BB rats. Because of the positive outcome of a prior study in non obese diabetic (NOD) mice, BB rats received insulin in combination with a bacterial adjuvant. Porcine insulin was given orally twice weekly from 35-100 days of age, the E. coli preparation OM-89 was fed on alternate days. Other groups received vehicle, the bacterial adjuvant, or insulin alone. Both insulin containing oral dosing regimens induced a transient non significant delay in diabetes onset. Insulin alone, however did not decrease the final diabetes incidence. Oral dosing with insulin plus adjuvant caused exacerbation of disease development as judged from the decreased survival rate in comparison with the insulin treated group (p < 0.05). Intra-islet infiltration also increased (p < 0.005) compared with the insulin or vehicle treated groups. The effect correlated with enhanced interferon gamma (IFNgamma) and decreased interleukin 10 (IL-10) gene expression in the gut suggesting a shift towards proinflammatory T helper 1 (Th1) reactivity (p < 0.01). Although treatment with adjuvant alone also increased the degree of insulitis, an enhanced incidence of diabetes and a shift in cytokine expression was only seen in the group receiving insulin plus adjuvant. Taken together, the data suggest that treatment with a bacterial adjuvant and oral insulin may alter the gut immunoregulatory state such that disease promoting rather than protective immune responses are induced.     

Polygon approximation of the fringes of diffractive elements

In the electron-beam fabrication of interferogram-type diffractive elements, such as diffractive lenses, continuous fringes are often approximated by polygons to reduce the data volume. Local wave-front errors are then generated that scatter light and give rise to background noise. A roughness parameter beta is introduced to quantify local phase errors in polygon-encoded diffractive structures. An efficient numerical method is developed to compute the Fresnel diffraction pattern of a polygon aperture. Polygon-approximated diffractive axicons and lenses are then investigated to determine the dependence of the signal fidelity on beta. It is found, e.g., that the maximum local phase error must be as large as pi/6 rad before the Strehl ratio S of a paraxial diffractive lens reduces below S = 0.9. However, much smaller errors can noticeably break the circular symmetry of the diffraction pattern.     

Food control officers perception of the challenges in implementing new food control requirements in Finland

In addition to the food control officers’ former tasks, new EU and Finnish legislations have established new obligations for them, such as building up a quality system, amending a control plan and expanding the collection of fees to cover all the control targets. In order to study the implementation of these new tasks, an electronic survey was sent to the local food control officials in Finland. Our study shows that there will be significant differences in implementing the new food control requirements in Finland by our local units when we take into consideration the time of implementation, the approach and content of control plans, and the quality systems or fees. Especially the risk-based estimation of the control objects seems to have created a challenge in both the quality systems and in the control plans; in only 16% of the municipalities, the risk estimations had been calculated for each control object and in most cases, this estimation was made and the control frequency was decided on solely by their own inspector of the object alone. Furthermore, the amount of the planned fees per hour varied from 21 Euros to 45 Euros. Several respondents also expressed that they had no knowledge of the grounds for the charges of future inspections or the amount of fees. What is apparent is that the new approach will be implemented relatively slowly in Finland and there is a risk of the different treatment of business operators depending on their geographical location.     

Independent amplification and frequent co-amplification of three nonsyntenic regions on the long arm of chromosome 20 in human breast cancer

DNA amplification at 20q13.2 is common in breast cancer, correlates with poor prognosis, and may reflect location of an important oncogene. Recently, other regions along 20q were also found to undergo amplification. Here, amplification levels and patterns of co-amplification were analyzed by interphase fluorescence in situ hybridization at 14 loci along 20q in 146 uncultured breast carcinomas and 14 cell lines. Three regions were independently amplified in uncultured tumors: RMC20C001 region at 20q13.2 (highly amplified in 9.6% of the cases), PTPN1 region 3 Mb proximal (6.2%), and AIB3 region at 20q11 (6.2%). Co-amplifications involving two or three of these regions were seen in 11 of the 19 highly amplified tumors. The results suggest that three distinct nonsyntenic regions along 20q may be important and that complex chromosomal rearrangements underlie their frequent co-amplification in breast cancer.     

Increased copy number at 17q22-q24 by CGH in breast cancer is due to high-level amplification of two separate regions

Our understanding of sodium transport defects has exploded in the past 18 months, and has provided unique insights into epithelial transport processes and unusual clinical syndromes resulting from mutations of specific transporters. These genetic disorders disturb sodium balance, with both sodium retaining and sodium wasting disorders as the consequence.     

c-myc copy number gains in bladder cancer detected by fluorescence in situ hybridization

Amplification and overexpression of c-myc have been suggested as prognostic markers in human cancer. To assess the role of c-myc gene copy number alterations in bladder cancer, 87 bladder tumors were examined for c-myc aberrations by fluorescence in situ hybridization. Dual labeling hybridization with a repetitive pericentromeric probe specific for chromosome 8 and a probe for the c-myc locus (at 8q24) was performed to analyze c-myc copy number in relation to chromosome 8 copy number on a cell by cell basis. A clear-cut c-myc amplification (up to 40 to 150 copies per cell) was found in 3 tumors. There was a low level c-myc copy number increase in 32 of the remaining 84 tumors. There was no association of low level c-myc copy number increase with c-myc protein overexpression. This suggests that a c-myc gene copy number gain as detected by fluorescence in situ hybridization does not necessarily reflect a disturbed c-myc gene function but may indicate a structural chromosome 8 abnormality including gain of distal 8q. The strong association of low level c-myc (8q) gains with tumor grade (P < 0.0001), stage (P < 0.0001), chromosome polysomy (P < 0.0001), p53 protein expression (P = 0.0019), p53 deletion (P = 0.0403), and tumor cell proliferation (Ki67 labeling index; P = 0.0021) is consistent with a role of chromosome 8 alterations in bladder cancer progression.