Miklós Erdélyi

An Integrated CAD Framework Linking VLSI Layout Editors and Process Simulators

As feature sizes in VLSI circuits extend into the far sub-micron range, new process techniques, such as using phase shifted masks for photolithography, will be needed. Under these conditions, the only means for the circuit designer to design compact and efficient circuits with good yield capabilities is to be able to see the effect of different design approaches on manufactured silicon, instead of solely relying on conservative general design rules. The integrated CAD framework accomplishes this by providing a link between a layout editor (Magic), advanced photolithographic techniques such as phase shifted masks, and a process simulator (Depict). This paper discusses some applications of this tool. A non- conventional process technique involving interferometric phase shifting and off-axis illumination has been evaluated using the tool. Also, a feature of the CAD framework which allows representation of a phase shifted mask, together with its layout analysis capability has been used to compact a piece of layout by inserting phase shifted elements into it.

Generation of diffraction-free beams for applications in optical microlithography

A new concept based on a Fabry–Perot interferometer for the generation of nondiffracting Bessel beams is described and proposed for potential applications in microlithography such as the fabrication of small isolated patterns. It was experimentally demonstrated that the depth of focus can be increased by a factor of about 2, and simultaneously the transverse resolution improved by a factor of 1.6, when using this technique to image contact holes. The properties of simultaneous imaging of two contact holes were also investigated. It was shown experimentally that, even in the most critical case (when the first diffraction rings overlap), undesirable interference effects between the adjacent contact holes can be eliminated by means of a phase shifting technique.

In situ measurements of the formation and morphology of intracellular β-amyloid fibrils by super-resolution fluorescence imaging.

Misfolding and aggregation of peptides and proteins is a characteristic of many neurodegenerative disorders, including Alzheimers disease (AD). In AD the β-amyloid peptide (Aβ) aggregates to form characteristic fibrillar structures, which are the deposits found as plaques in the brains of patients. We have used direct stochastic optical reconstruction microscopy, dSTORM, to probe the process of in situ Aβ aggregation and the morphology of the ensuing aggregates with a resolution better than 20 nm. We are able to distinguish different types of structures, including oligomeric assemblies and mature fibrils, and observe a number of morphological differences between the species formed in vitro and in vivo, which may be significant in the context of disease. Our data support the recent view that intracellular Aβ could be associated with Aβ pathogenicity in AD, although the major deposits are extracellular, and suggest that this approach will be widely applicable to studies of the molecular mechanisms of protein deposition diseases.

The Drosophila homolog of Aut1 is essential for autophagy and development.

The Drosophila homolog of yeast Aut1, CG6877/Draut1, is a ubiquitously expressed cytosolic protein. Draut1 loss of function was achieved by expression of an inverted repeat transgene inducing RNA interference. The effect is temperature‐dependent and resembles an allelic series as described by Fortier, E. and Belote, J.M. (Genesis 26 (2000) 240–244). Draut1 loss of function larvae are unable to induce autophagy and heterophagy in fat body cells before pupariation and die during metamorphosis. To our knowledge, this is the first report of a multicellular animal lacking the function of a gene participating in the protein conjugation systems of autophagy.

MOESIN Crosslinks Actin and Cell Membrane in Drosophila Oocytes and Is Required for OSKAR Anchoring

In Drosophila, development of the embryonic germ cells depends on posterior transport and site-specific translation of oskar (osk) mRNA and on interdependent anchoring of the osk mRNA and protein within the posterior subcortical region of the oocyte. Transport of the osk mRNA is mediated by microtubules, while anchoring of the osk gene products at the posterior pole of the oocyte is suggested to be microfilament dependent. To date, only a single actin binding protein (TropomyosinII) has been identified with a putative role in osk mRNA and protein anchoring. This communication demonstrates that mutations in the Drosophila moesin (Dmoe) gene that encodes another actin binding protein result in delocalization of osk mRNA and protein from the posterior subcortical region and, as a consequence, in failure of embryonic germ cell development. In Dmoe mutant oocytes, the subcortical actin network is detached from the cell membrane, while the polarized microtubule cytoskeleton is unaffected. In line with the earlier observations, colocalization of ectopic actin and OSK protein in Dmoe mutants suggests that the actin cytoskeleton anchors OSK protein to the subcortical cytoplasmic area of the Drosophila oocyte.

Web spam classification: a few features worth more

In this paper we investigate how much various classes of Web spam features, some requiring very high computational effort, add to the classification accuracy. We realize that advances in machine learning, an area that has received less attention in the adversarial IR community, yields more improvement than new features and result in low cost yet accurate spam filters. Our original contributions are as follows: • We collect and handle a large number of features based on recent advances in Web spam filtering. • We show that machine learning techniques including ensemble selection, LogitBoost and Random Forest significantly improve accuracy. • We conclude that, with appropriate learning techniques, a small and computationally inexpensive feature subset outperforms all previous results published so far on our data set and can only slightly be further improved by computationally expensive features. • We test our method on two major publicly available data sets, the Web Spam Challenge 2008 data set WEB-SPAM-UK2007 and the ECML/PKDD Discovery Challenge data set DC2010. Our classifier ensemble reaches an improvement of 5% in AUC over the Web Spam Challenge 2008 best result; more importantly our improvement is 3.5% based solely on less than 100 inexpensive content features and 5% if a small vocabulary bag of words representation is included. For DC2010 we improve over the best achieved NDCG for spam by 7.5% and over 5% by using inexpensive content features and a small bag of words representation.

Field measurements of volcanic gases using tunable diode laser based mid-infrared and Fourier transform infrared spectrometers

The first field measurements of volcanic gases using mid-IR difference frequency laser spectroscopy are reported. The results were obtained at the summit crater of Masaya volcano, Nicaragua, with the gases being drawn into a multi-pass cell and measured at reduced pressure. Automated sensitive and selective detection of CO2 ,S O 2 ,H 35,37 Cl, H2O, and CH4 was achieved. Simultaneous measurements obtained with open-path Fourier transform spectroscopy provide a useful comparison of the two optical techniques. We also consider the potential measurement of CO2 isotopic ratios in volcanic gases using laser-based spectroscopy. r 2002 Elsevier Science Ltd. All rights reserved.

Direct Observations of Amyloid β Self-Assembly in Live Cells Provide Insights into Differences in the Kinetics of Aβ(1–40) and Aβ(1–42) Aggregation

Summary Insight into how amyloid β (Aβ) aggregation occurs in vivo is vital for understanding the molecular pathways that underlie Alzheimer’s disease and requires new techniques that provide detailed kinetic and mechanistic information. Using noninvasive fluorescence lifetime recordings, we imaged the formation of Aβ(1–40) and Aβ(1–42) aggregates in live cells. For both peptides, the cellular uptake via endocytosis is rapid and spontaneous. They are then retained in lysosomes, where their accumulation leads to aggregation. The kinetics of Aβ(1–42) aggregation are considerably faster than those of Aβ(1–40) and, unlike those of the latter peptide, show no detectable lag phase. We used superresolution fluorescence imaging to examine the resulting aggregates and could observe compact amyloid structures, likely because of spatial confinement within cellular compartments. Taken together, these findings provide clues as to how Aβ aggregation may occur within neurons.

Near-infrared diode laser based spectroscopic detection of ammonia: a comparative study of photoacoustic and direct optical absorption methods

A photoacoustic spectroscopic (PAS) and a direct optical absorption spectroscopic (OAS) gas sensor, both using continuous-wave room-temperature diode lasers operating at 1531.8 nm, were compared on the basis of ammonia detection. Excellent linear correlation between the detector signals of the two systems was found. Although the physical properties and the mode of operation of both sensors were significantly different, their performances were found to be remarkably similar, with a sub-ppm level minimum detectable concentration of ammonia and a fast response time in the range of a few minutes.

Uracil-containing DNA in Drosophila: stability, stage-specific accumulation, and developmental involvement.

Base-excision repair and control of nucleotide pools safe-guard against permanent uracil accumulation in DNA relying on two key enzymes: uracil–DNA glycosylase and dUTPase. Lack of the major uracil–DNA glycosylase UNG gene from the fruit fly genome and dUTPase from fruit fly larvae prompted the hypotheses that i) uracil may accumulate in Drosophila genomic DNA where it may be well tolerated, and ii) this accumulation may affect development. Here we show that i) Drosophila melanogaster tolerates high levels of uracil in DNA; ii) such DNA is correctly interpreted in cell culture and embryo; and iii) under physiological spatio-temporal control, DNA from fruit fly larvae, pupae, and imago contain greatly elevated levels of uracil (200–2,000 uracil/million bases, quantified using a novel real-time PCR–based assay). Uracil is accumulated in genomic DNA of larval tissues during larval development, whereas DNA from imaginal tissues contains much less uracil. Upon pupation and metamorphosis, uracil content in DNA is significantly decreased. We propose that the observed developmental pattern of uracil–DNA is due to the lack of the key repair enzyme UNG from the Drosophila genome together with down-regulation of dUTPase in larval tissues. In agreement, we show that dUTPase silencing increases the uracil content in DNA of imaginal tissues and induces strong lethality at the early pupal stages, indicating that tolerance of highly uracil-substituted DNA is also stage-specific. Silencing of dUTPase perturbs the physiological pattern of uracil–DNA accumulation in Drosophila and leads to a strongly lethal phenotype in early pupal stages. These findings suggest a novel role of uracil-containing DNA in Drosophila development and metamorphosis and present a novel example for developmental effects of dUTPase silencing in multicellular eukaryotes. Importantly, we also show lack of the UNG gene in all available genomes of other Holometabola insects, indicating a potentially general tolerance and developmental role of uracil–DNA in this evolutionary clade.