Sample preparation for high-throughput sequencing (HTS) includes treatment with various laboratory components, potentially carrying viral nucleic acids, the extent of which has not been thoroughly ...investigated. Our aim was to systematically examine a diverse repertoire of laboratory components used to prepare samples for HTS in order to identify contaminating viral sequences.
A total of 322 samples of mainly human origin were analysed using eight protocols, applying a wide variety of laboratory components. Several samples (60% of human specimens) were processed using different protocols. In total, 712 sequencing libraries were investigated for viral sequence contamination.
Among sequences showing similarity to viruses, 493 were significantly associated with the use of laboratory components. Each of these viral sequences had sporadic appearance, only being identified in a subset of the samples treated with the linked laboratory component, and some were not identified in the non-template control samples. Remarkably, more than 65% of all viral sequences identified were within viral clusters linked to the use of laboratory components.
We show that high prevalence of contaminating viral sequences can be expected in HTS-based virome data and provide an extensive list of novel contaminating viral sequences that can be used for evaluation of viral findings in future virome and metagenome studies. Moreover, we show that detection can be problematic due to stochastic appearance and limited non-template controls. Although the exact origin of these viral sequences requires further research, our results support laboratory-component-linked viral sequence contamination of both biological and synthetic origin.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Plasmodium knowlesi is an intracellular malaria parasite whose natural vertebrate host is Macaca fascicularis (the 'kra' monkey); however, it is now increasingly recognized as a significant cause of ...human malaria, particularly in southeast Asia. Plasmodium knowlesi was the first malaria parasite species in which antigenic variation was demonstrated, and it has a close phylogenetic relationship to Plasmodium vivax, the second most important species of human malaria parasite (reviewed in ref. 4). Despite their relatedness, there are important phenotypic differences between them, such as host blood cell preference, absence of a dormant liver stage or 'hypnozoite' in P. knowlesi, and length of the asexual cycle (reviewed in ref. 4). Here we present an analysis of the P. knowlesi (H strain, Pk1(A+) clone) nuclear genome sequence. This is the first monkey malaria parasite genome to be described, and it provides an opportunity for comparison with the recently completed P. vivax genome and other sequenced Plasmodium genomes. In contrast to other Plasmodium genomes, putative variant antigen families are dispersed throughout the genome and are associated with intrachromosomal telomere repeats. One of these families, the KIRs, contains sequences that collectively match over one-half of the host CD99 extracellular domain, which may represent an unusual form of molecular mimicry.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
•Copper pillars are imaged using 6 different 3D imaging techniques.•3rd generation synchrotron beamlines and lab equipments are assessed.•A new sample preparation for synchrotron tomography is ...successfully tested.•The final volumes are compared, based on image quality and analysis time.
In microelectronics, recently developed 3D integration offers the possibility to stack the dice or wafers vertically instead of putting their different parts next to one another, in order to save space. As this method becomes of greater interest, the need for 3D imaging techniques becomes higher. We here report a study about different 3D characterization techniques applied to copper pillars, which are used to stack different dice together. Destructive techniques such as FIB/SEM, FIB/FIB, and PFIB/PFIB slice and view protocols have been assessed, as well as non-destructive ones, such as laboratory-based and synchrotron-based computed tomographies. A comparison of those techniques in the specific case of copper pillars is given, taking into account the constraints linked to the microelectronics industry, mainly concerning resolution and sample throughput. Laboratory-based imaging techniques are shown to be relevant in the case of punctual analyses, while synchrotron based tomographies offer highly resolved volumes for larger batches of samples.
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Recent applications require vertical chip stacking to increase the performance of many devices without the need of advanced node components. Image sensors and vision systems will embed more and more ...smart functions, for instance, image processing, object recognition, and movement detection. In this perspective, the combination of Cu-to-Cu direct hybrid bonding technology with Through-Silicon-Via (TSV) will allow 3D interconnection between pixels and the associated computing and memory structures, each function fabricated on a separate wafer. Wafer-to-wafer hybrid bonding was achieved with multi-pitch design—1–4 μm—of single levels of Cu damascene patterned on 300 mm silicon substrates. Defect-free bonding, as far as the extreme edge of the wafer, was demonstrated on a stack with three wafers. Middle wafers thinning was done with grinding only and with a thickness uniformity (TTV) <2 μm to an ultimate thinning as low as 3 μm. Alignment performance was characterized by post-bonding for two superposed hybrid bonding interfaces. In our set of wafers, modeling the alignment with translation, rotation, and scaling components enables us to optimize the residuals down to 3σ < 100 nm. A process flow of thin TSV with a fine pitch of 2 μm for high-density vertical interconnect through a three-wafer stack was developed. Via-last TSV architecture was adopted with 1 μm TSV diameter and 10 μm thickness. Lithography, etching solutions, Ti/TiN barrier deposition, and void-free Cu filling solutions were demonstrated. TSV cross sections after CMP and connections with top and bottom Cu damascene lines show good profile control. Process developments are matured and can be reliably used in the fabrication of an electrical test vehicle including vertical interconnects associating multi-wafers stacking with a hybrid bonding process and high-density thin TSV applicable to low pitches (<5 μm).
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
As reverse transcription is predominantly performed by retrotransposable elements, the process is often entirely associated with the propagation of these elements. However, as a unique tool for ...transmitting information from the dynamic RNA to the more inert DNA, reverse transcription has been instrumental in shaping extant genomes. This review aims at presenting the diversity by which reverse transcription has influenced modern genomic structures.
Future generations of integrated circuits will require interconnects with metallic lines at dimensions below 50
nm. When Cu is used, the electron mean free path becomes similar to the characteristic ...dimensions of the structure of the metallic line (grain size, interface and wall spacing). This induces a large metal resistivity increase which has a negative impact on the circuit performance. Cu resistivity models have been proposed using the classical Fuchs and Sondheimer approach for surface effect, and the Mayadas and Shatzkes approach for the grain boundary effect (FS–MS approach). In these models, three adjustable parameters must be used. Good agreement between experimental resistivity vs linewidth curves and models can easily be obtained. However, numerous fitting parameter sets can be obtained with equivalent fitting quality and opposite physical meaning. In this work, experiments dedicated to model parameter extraction are proposed and released. They are based on the used of Cu lines with various line widths and heights. Special care is taken in the accuracy of resistivity and dimensions measurements. Classical resistivity increase with line width and line height decrease is observed. Using the FS–MS approach, the observed resistivity behaviour is modelled. In this case, limited fitting parameter options are obtained. For Cu narrow lines confined with Ta, these parameters suggest high surface effect, medium grain boundary effect and low impurity content inside the lines.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
An alternative, and quicker way of assessing the electromigration (EM) reliability of Cu interconnects is investigated. It is based on observations of de-wetting and contact angle measurement of Cu ...thin films. Contact angle results are compared to EM tests, and the correlation between Cu de-wetting and electromigration performance is demonstrated. PVD TaN
x
/Ta or ALD TaN barrier layers are tested, while the seed layer is either pure copper or a CuAl
1 at%. In addition, three types of barrier treatments are investigated: different exposure times to plasma of ALD TaN; tantalum flash between ALD TaN and pure copper seed deposition; ALD TaN exposure to atmospheric oxygen.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
8.
The biology of intron gain and loss Jeffares, Daniel C.; Mourier, Tobias; Penny, David
Trends in genetics,
2006, 2006-Jan, 2006-1-00, 20060101, Volume:
22, Issue:
1
Journal Article
Peer reviewed
Intron density in eukaryote genomes varies by more than three orders of magnitude, so there must have been extensive intron gain and/or intron loss during evolution. A favored and partial explanation ...for this range of intron densities has been that introns have accumulated stochastically in large eukaryote genomes during their evolution from an intron-poor ancestor. However, recent studies have shown that some eukaryotes lost many introns, whereas others accumulated and/or gained many introns. In this article, we discuss the growing evidence that these differences are subject to selection acting on introns depending on the biology of the organism and the gene involved.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
9.
Evaluation of (hfac)Cu(MHY) for Cu CVD Joulaud, M; Angekort, C; Doppelt, P ...
Microelectronic engineering,
10/2002, Volume:
64, Issue:
1
Journal Article, Conference Proceeding
Peer reviewed
Copper deposition using (hfac)Cu(MHY) (Gigacopper
®) for interconnections metallization by Cu CVD is presented. We compared it to (hfac)Cu(VTMS) (Cupraselect
®) in terms of deposition rate, specific ...resistivity and uniformity. Gigacopper
® appears to give a higher deposition rate than Cupraselect
® and about the same specific resistivity. Water addition is a critical point. It permits improved uniformity and specific resistivity provided it is added during the nucleation step in a very precise volume. We also studied the influence of other parameters, such as precursor flow rate and reactor pressure, on the film deposition. The use of Cu CVD as seed layer for Cu ECD depositions was also explored on full sheet wafers. Adhesion can be greatly enhanced by a specific anneal procedure with a slow cool down to limit stresses in the film.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
10.
Eukaryotic Intron Loss Mourier, Tobias; Jeffares, Daniel C.
Science (American Association for the Advancement of Science),
05/2003, Volume:
300, Issue:
5624
Journal Article
Peer reviewed
Recently attention has been drawn to eukaryotic genomes with very few introns and to the biased position of introns within genes. Jeffares and Mourier show that intron-poor eukaryptes for which ...genome data is available have a five inch bias in the position of their introns within genes.
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