Characterization of Nucleotide Misincorporation Patterns in the Iceman's Mitochondrial DNA

BACKGROUND: The degradation of DNA represents one of the main issues in the genetic analysis of archeological specimens. In the recent years, a particular kind of post-mortem DNA modification giving rise to nucleotide misincorporation ("miscoding lesions") has been the object of extensive investigations. METHODOLOGY/PRINCIPAL FINDINGS: To improve our knowledge regarding the nature and incidence of ancient DNA nucleotide misincorporations, we have utilized 6,859 (629,975 bp) mitochondrial (mt) DNA sequences obtained from the 5,350-5,100-years-old, freeze-desiccated human mummy popularly known as the Tyrolean Iceman or Otzi. To generate the sequences, we have applied a mixed PCR/pyrosequencing procedure allowing one to obtain a particularly high sequence coverage. As a control, we have produced further 8,982 (805,155 bp) mtDNA sequences from a contemporary specimen using the same system and starting from the same template copy number of the ancient sample. From the analysis of the nucleotide misincorporation rate in ancient, modern, and putative contaminant sequences, we observed that the rate of misincorporation is significantly lower in modern and putative contaminant sequence datasets than in ancient sequences. In contrast, type 2 transitions represent the vast majority (85%) of the observed nucleotide misincorporations in ancient sequences. CONCLUSIONS/SIGNIFICANCE: This study provides a further contribution to the knowledge of nucleotide misincorporation patterns in DNA sequences obtained from freeze-preserved archeological specimens. In the Iceman system, ancient sequences can be clearly distinguished from contaminants on the basis of nucleotide misincorporation rates. This observation confirms a previous identification of the ancient mummy sequences made on a purely phylogenetical basis. The present investigation provides further indication that the majority of ancient DNA damage is reflected by type 2 (cytosine-->thymine/guanine-->adenine) transitions and that type 1 transitions are essentially PCR artifacts

Virtual reality interfaces for feature-based computer-aided design systems

A computer-aided design (CAD) system with a virtual reality (VR) interface simplifies the design of complex mechanical parts. To add a design feature (e.g., a hole,slot, or protrusion), the designer can navigate in the part to the appropriate face of the part where he/she wishes to attach the feature, and sketch directly on that face.Besides convenience, this method of feature specification implicitly enforces feature accessibility constraints, and also provides hints to the process-planner regarding the order in which the features may be manufactured. We detail the design of a VR-based prototype CAD system. The system maintains the knowledge of part cavities and their adjacencies, and a triangulated boundary-representation of an approximating polyhedron. We present incremental provably correct algorithms for updatingthis representation as the user edits the part. We also show how this representation supports real-time displays, navigation, and collision detection. The user-interface of the CAD system relies on these capabilities to provide the above-mentioned advantages

Morphology and substructure of lath martensites in dilute Zr---Nb alloys

The morphology and substructure of lath martensites formed in ß quenched dilute Zr---Nb alloys are described. The laths are arranged in a nearly parallel manner within any given colony or packet. Packets of alternately twin related laths and clusters of three mutually twin related lath martensite variants have been observed and the twinning plane is of {1I̅01}<SUB>H</SUB> type. With increasing niobium content a continuous transition from large colonies of lath martensites, through smaller lath colonies, to individual plates of the acicular martensites occurs. The lath-lath interface consists of regularly spaced parallel arrays of dislocations of &lt;2I̅I̅3&gt;type. The habit plane traces of lath martensite lie close to {334} type poles and the operating lattice invariant shear mode is {I̅101}<SUB>H</SUB>&lt;2 I̅I̅3&gt;<SUB>H</SUB> shear system. This result is consistent with results predicted by the phenomenological theory. The preferred two and three habit plane variant grouping clustering is explained on the basis of self-accommodation effects

Metrics and evidence for healthy ageing

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Efficacy of low-dose alpha interferon therapy in HBV-related chronic liver disease in Asian Indians: a randomized controlled trial

Background/Aims: Interferon therapy has been shown to be effective in Western patients with chronic hepatitis due to hepatitis B viral infection, but not in Asian Chinese. Its efficacy in Asian Indian subjects with chronic HBV infection is not known. Methods: Forty-one patients with HBV-related chronic liver disease received randomly either: (a) recombinant alpha 2b interferon (n=20) 3 MIU, subcutaneously, three times a week for 4 months, or (b) no treatment (n = 21). Patients were followed up for 12 months after completion of therapy. Results: In the interferon-treated group, complete response (loss of HBV-DNA and HBeAg) was significantly higher than spontaneous clearance in the control group (50% vs. 4.8% p&lt;0.05). Seroconversion to anti-HBe was seen in 35% of the treated and 4.8% of the control group (p&lt;0.05) at 4 months; it was noticeably higher in patients with chronic hepatitis than in those with cirrhosis. In the responders, alanine aminotransferase levels nearly normalized. One year after interferon therapy, HBeAg and HBV-DNA clearance was observed in 65% of patients, with HBsAg clearance in 15%. Reactivation was not seen in any patient. Side-effects were transient and minimal. Conclusion: Low-dose recombinant alpha interferon therapy is quite effective and safe in Asian Indians with chronic liver disease due to hepatitis B infection