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Persistent infection with high-risk human papillomaviruses (hrHPV) can result in the formation of anogenital cancers. As hrHPV proteins E6 and E7 are required for cancer initiation and maintenance, they are ideal targets for immunotherapeutic interventions. Previously, we have described the development of DNA vaccines for the induction of HPV16 E6 and E7 specific T cell immunity. These vaccines consist of ‘gene-shuffled’ (SH) versions of HPV16 E6 and E7 that were fused to Tetanus Toxin Fragment C domain 1 (TTFC) and were named TTFC-E6SH and TTFC-E7SH. Gene-shuffling was performed to avoid the risk of inducing malignant transformation at the vaccination site. Here, we describe the preclinical safety evaluation of these candidate vaccines by analysis of their transforming capacity in vitro using established murine fibroblasts (NIH 3T3 cells) and primary human foreskin keratinocytes (HFKs). We demonstrate that neither ectopic expression of TTFC-E6SH and TTFC-E7SH alone or in combination enabled NIH 3T3 cells to form colonies in soft agar. In contrast, expression of HPV16 E6WT and E7WT alone or in combination resulted in effective transformation. Similarly, retroviral transduction of HFKs from three independent donors with both TTFC-E6SH and TTFC-E7SH alone or in combination did not show any signs of immortalization. In contrast, the combined expression of E6WT and E7WT induced immortalization in HFKs from all donors. Based on these results we consider it justified to proceed to clinical evaluation of DNA vaccines encoding TTFC-E6SH and TTFC-E7SH in patients with HPV16 associated (pre)malignancies.
Partikelmesstechnik
(2012)
Der Schutz von Produkten vor der Kontamination durch Partikel gilt als eine zentrale Aufgabe der Reinraumtechnik. Da es dabei um Kontaminationseffekte weit unterhalb der visuellen Wahrnehmbarkeit geht, braucht es leistungsfähige Verfahren, um die Messgröße „Partikelkontamination“ über den gesamten Bereich, den Anwender fordern, präzise zu bestimmen. Neben der Partikelhäufigkeit ist dabei die Größe der Partikel, die sowohl das Transportverhalten wie auch die mögliche Wirkung auf das Produkt beeinflusst, von entscheidender Bedeutung. Ferner kann es für die Ermittlung von Kontaminationsquellen von Interesse sein, die Form und die chemische Natur der Partikel zu bestimmen (z. B. textile Fasern, Metallabrieb, flüssige Tröpfchen). Die Partikelhäufigkeit wird üblicherweise als Konzentration, d. h. bezogen auf das analysierte Gasvolumen angegeben. Bei den in reinen Technologien üblichen niedrigen Konzentrationen dient als Häufigkeitsmaß die Partikelanzahlkonzentration, also die Partikelanzahl pro Volumeneinheit des Trägermediums.
Determination of the frictional coefficient of the implant-antler interface : experimental approach
(2012)
The similar bone structure of reindeer antler to human bone permits studying the osseointegration of dental implants in the jawbone. As the friction is one of the major factors that have a significant influence on the initial stability of immediately loaded dental implants, it is essential to define the frictional coefficient of the implant-antler interface. In this study, the kinetic frictional forces at the implant-antler interface were measured experimentally using an optomechanical setup and a stepping motor controller under different axial loads and sliding velocities. The corresponding mean values of the static and kinetic frictional coefficients were within the range of 0.5–0.7 and 0.3–0.5, respectively. An increase in the frictional forces with increasing applied axial loads was registered. The measurements showed an evidence of a decrease in the magnitude of the frictional coefficient with increasing sliding velocity. The results of this study provide a considerable assessment to clarify the suitable frictional coefficient to be used in the finite element contact analysis of antler specimens.
Many applications in computational science and engineering require the computation of eigenvalues and vectors of dense symmetric or Hermitian matrices. For example, in DFT (density functional theory) calculations on modern supercomputers 10% to 30% of the eigenvalues and eigenvectors of huge dense matrices have to be calculated. Therefore, performance and parallel scaling of the used eigensolvers is of upmost interest. In this article different routines of the linear algebra packages ScaLAPACK and Elemental for parallel solution of the symmetric eigenvalue problem are compared concerning their performance on the BlueGene/P supercomputer. Parameters for performance optimization are adjusted for the different data distribution methods used in the two libraries. It is found that for all test cases the new library Elemental which uses a two-dimensional element by element distribution of the matrices to the processors shows better performance than the old ScaLAPACK library which uses a block-cyclic distribution.
Cardiac MR (CMR) at ultrahigh (≥7.0 T) fields is regarded as one of the most challenging MRI applications. At 7.0 T image quality is not always exclusively defined by signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR). Detrimental effects bear the potential to spoil the signal-to-noise (SNR) and contrast-to-noise (CNR) benefits of cardiac MR (CMR) at 7.0 T. B₁⁺-inhomogeneities and signal voids represent the main challenges. Various pioneering coil concepts have been proposed to tackle these issues, enabling cardiac MRI at 7.0 T. This includes a trend towards an ever larger number of transmit and receive channels. This approach affords multi-dimensional B₁⁺ modulations to improve B₁⁺ shimming performance and to enhance RF efficiency. Also, parallel imaging benefits from a high number of receive channels enabling two-dimensional acceleration. Realizing the limitations of existing coil designs tailored for UHF CMR and recognizing the opportunities of a many element TX/RX channel architecture this work proposes a modular, two dimensional 32-channel transmit and receive array using loop elements and examines its efficacy for enhanced B¹+ homogeneity and improved parallel imaging performance.