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Gene variant databases are the backbone of DNA-based diagnostics. These databases, also called Locus-Specific DataBases (LSDBs), store information on variants in the human genome and the observed phenotypic consequences. The largest collection of public databases uses the free, open-source LOVD software platform. To cope with the current demand for online databases, we have entirely redesigned the LOVD software. LOVD3 is genome-centered and can be used to store summary variant data, as well as full case-level data with information on individuals, phenotypes, screenings, and variants. While built on a standard core, the software is highly flexible and allows personalization to cope with the largely different demands of gene/disease database curators. LOVD3 follows current standards and includes tools to check variant descriptions, generate HTML files of reference sequences, predict the consequences of exon deletions/duplications on the reading frame, and link to genomic views in the different genomes browsers. It includes APIs to collect and submit data. The software is used by about 100 databases, of which 56 public LOVD instances are registered on our website and together contain 1,000,000,000 variant observations in 1,500,000 individuals. 42 LOVD instances share data with the federated LOVD data network containing 3,000,000 unique variants in 23,000 genes. This network can be queried directly, quickly identifying LOVD instances containing relevant information on a searched variant.

Mobile elements are major drivers in changing genomic architecture and can cause disease. The detection of mobile elements is hindered due to the low mappability of their highly repetitive sequences. We have developed an algorithm, called Mobster, to detect non-reference mobile element insertions in next generation sequencing data from both whole genome and whole exome studies. Mobster uses discordant read pairs and clipped reads in combination with consensus sequences of known active mobile elements. Mobster has a low false discovery rate and high recall rate for both L1 and Alu elements. Mobster is available at http://sourceforge.net/projects/mobster. Background Mobile elements (MEs) or transposable elements are DNA sequences that can be autonomously copied or moved through the genome, yet their highly repetitive sequence structure makes them difficult to detect. In addition to being a major evolutionary driver in changing the genomic architecture, MEs have also directly resulted in pathogenic variation in a number of human diseases by inserting into functionally important regions and disrupting gene function [1,2]. MEs can be classified into two different classes depending on their mode of transposition. Class I retrotransposons travel through an RNA intermediate by copy and paste, while class II DNA transposons have a DNA intermediate and generally move by cut and paste. Together these elements make up the majority of the human genome, with estimates in the range of 45% to 69% of the human genome sequence belonging to one of these transposons classes [3,4].

We have performed static scattering experiments on the gel state of a suspension of disk-shaped charged colloidal particles. The combination of static light scattering and small-angle x-ray scattering experiments probes more than three orders of magnitude in the scattering vector q. We observe that, after application of shear, the form factor develops nematic-Iike order. This order decays to random orientation in the gel state. This suggests that local reorientation of the disks leads to the gel state, as opposed to aggregation.

We present results of an experimental study on the effect of the inclusion of ferroelectric thiourea particles in paraelectric amorphous KBr on the ferroelectric phase transition. The phase transition as a function of temperature has been observed with optical second‐harmonic generation (SHG) of infrared light. The Curie temperature Tc shows a minimum as a function of the volume fraction x of thiourea in the composites at x=0.4. We describe the experimentally observed density dependence of the Curie temperature in a phenomenological mean‐field model.

In this paper we present a new method for manufacturing steeply profiled grating structures composed of narrow lines and spaces embedded in transition metal layers. We focus on making EUV transmittive grating structures typically consisting of rectangular lines that are down to 40 nm wide, around 100 nm tall, up to 100 nm long, spaced at a 1-2 micrometers pitch, and embedded in 100 nm thick nickel-iron alloy absorber layers. The method comprises the use of a molybdenum plating base deposited on a silicon nitride coated silicon wafer, electron beam writing of down to 40 nm wide and 100 nm tall lines in negative tone hydrogen silsesquioxane (HSQ) resist, and electroplating of the desired metal absorber layer in between the resist lines, using the molybdenum layer as plating base. After processing both the HSQ resist and the thin plating base can remain respectively between and below the grating structure because these materials are relatively transparent to EUV radiation. The presence of HSQ in the plated metal spaces results in a flat top surface, preventing the adhesion of contaminants. Our measurements reveal the presence of rectangular HSQ lines, characterized by near vertical side walls, a high line-width uniformity and a low line-edge roughness. These structures are subsequently embedded in a homogeneously grown absorber, characterized by a low small-scale surface roughness and high-quality overall flatness. The process window, in terms of exposure dose and pre-exposure resist treatment, has been well established for various line width and line pitch settings.

In this paper we present the results of an elaborate study to investigate the properties of luminescent materials for EUV detection in EUV lithographic tools. The study presented here involves both bulk single crystalline samples and thin film samples. Bulk single crystalline samples with polished surfaces are industrially available, while thin film samples were home-made by performing physical vapor deposition of several luminescent materials on polished quartz substrates. Careful pre-selection of these phosphors was based on multiple strong criteria. The measured results presented here include time-resolved luminescence decay, luminescence spectra and luminescence linearity measurements under deep-UV (248 nm) and extreme-UV (13.5 nm) excitation. Our results indicate the possible use of two luminescent materials, being YAG:Ce (bulk) and CaS:Ce (thin film), for EUV detection in extreme-UV lithographic tools. Practical use of these luminescent materials, however, will require high extreme-UV powers in order to obtain a sufficient signal to noise ratio.© (2001) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

We have performed static scattering experiments on the gel state of a suspension of disk-shaped charged colloidal particles. The combination of static light scattering and small-angle x-ray scattering experiments probes more than three orders of magnitude in the scattering vector q. We observe that, after application of shear, the form factor develops nematic-Iike order. This order decays to random orientation in the gel state. This suggests that local reorientation of the disks leads to the gel state, as opposed to aggregation.

Structural relaxation in amorphous systems is an area of much current interest. Many studies have been devoted to the sol-gel transition in systems based on polymers @1‐3#, natural gelatine @4#, and gels based on spherical colloids @5‐7#. Here we report on the sol-gel transition in a system of charged disks with an aspect ratio of 25, suspended in water. In such systems the orientational degrees of freedom play a crucial role not only in the dynamics but also in the static structure of the gel. Molecular dynamics simulations on hard disk systems reveal a rich phase diagram with nematic and cubatic liquid crystalline phases @8#. However, before these liquid crystalline phases can be formed the system enters a glassy phase or gel. Current opinion favors the ‘‘house of cards’’ structure for the gel @9#, which implies a random structure with short range orientational order. On the average the disks are oriented with their positively charged rim towards the negatively charged base of their neighbor. Within this view the orientational degrees of freedom will play a crucial role in the formation of the gel. Structure and dynamics in the neighborhood of the transition can be studied best by using the noninvasive technique of light scattering, dynamic ~DLS! and static. DLS probes the density correlation function describing the time evolution of the density fluctuations. The striking feature, largely emerging from DLS measurements around the gel point @4‐6#, is the marked similarity of the behavior of the correlation function with the scenarios given by the mode cou

The analysis of non-stationary signals calls for speciflc tools which go beyond classical Fourier analysis. Here we present the discrete wavelet transform as a quantitative method to analyse the scaling properties of non-stationary and chaotic signals obtained by light scattering. The analysis is performed directly on the time-resolved scattered intensity. The result is the scaling exponent of the underlying power spectrum and the frequency window where the scaling can be observed. These properties are obtained with a higher accuracy and in a fraction of the time compared with the classical method of intensity correlation functions. As a test we applied the new method to the sol-gel transition of a suspension of disc-shaped colloidal particles in water.

In dynamic light scattering the intensity correlation function is calculated by means of a correlator from the measured scattered fluctuating intensity. Subsequently the intermediate scattering function, or its Fourier transform the dynamic structure factor, can be extracted from the correlation function. This by now classical method has, as any experimental technique, its own limitations. One of the limitations becomes apparent when the intensity correlation function possesses an algebraic tail. It is observed for example in colloidal or polymeric systems undergoing a glass transition1-3. Then it is possible, but difficult to extract the true intermediate scattering function of the system, even though the system is considered in equilibrium. Non-stationary systems or systems behaving chaotically in time pose a real problem. For a non-stationary system the zero frequency divergence in the power spectrum of the fluctuating intensity precludes any quantitative analysis by means of correlation functions, since an infinite time range should be covered. Examples are the formation of a glass or a gel, and turbulence.

In most transition metals, steeply profiled nanoscale structures can not easily be obtained by dry etching, due to the redeposition of the etch products. An alternative method is presented here, which comprises the deposition of a plating base, electron-beam writing of nanoscale structures in negative tone hydrogen silsesquioxane resist, and electroplating of the desired metal layer between the resist lines. This method is used for making transmittive and reflective masks, alignment marks, and other optical gratings, consisting of features down to 40 nm wide that are embedded in transition metal layers. These gratings can, e.g., be applied in extreme-UV lithographic sensors. More generally, other devices, e.g., magnetic recording heads, can also be manufactured using this technology.