High-resolution phonocardiogram parameters

The article describes the results of studying and analyzing phonocardiograms (PCGs) obtained during a physiological experiment with Blu-ray standard equipment. It provides the findings of a spectral and spectral-time analysis for signals with a sampling frequency of 10, 44.1 and 192 kHz. It shows that the differences in the PCG spectra of identical signals are unreliable. The article specifies the onset and disappearance moments of the harmonic components of heart sounds. It also provides recommendations on the sampling frequency and bit resolution of digitized PCG signals for telemetric systems

Design and Analysis of Rhesus Cytomegalovirus IL-10 Mutants as a Model for Novel Vaccines against Human Cytomegalovirus

Human cytomegalovirus (HCMV) expresses a viral ortholog (CMVIL-10) of human cellular interleukin-10 (cIL-10). Despite only ∼26% amino acid sequence identity, CMVIL-10 exhibits comparable immunosuppressive activity with cIL-10, attenuates HCMV antiviral immune responses, and contributes to lifelong persistence within infected hosts. The low sequence identity between CMVIL-10 and cIL-10 suggests vaccination with CMVIL-10 may generate antibodies that specifically neutralize CMVIL-10 biological activity, but not the cellular cytokine, cIL-10. However, immunization with functional CMVIL-10 might be detrimental to the host because of its immunosuppressive properties.Structural biology was used to engineer biologically inactive mutants of CMVIL-10 that would, upon vaccination, elicit a potent immune response to the wild-type viral cytokine. To test the designed proteins, the mutations were incorporated into the rhesus cytomegalovirus (RhCMV) ortholog of CMVIL-10 (RhCMVIL-10) and used to vaccinate RhCMV-infected rhesus macaques. Immunization with the inactive RhCMVIL-10 mutants stimulated antibodies against wild-type RhCMVIL-10 that neutralized its biological activity, but did not cross-react with rhesus cellular IL-10.This study demonstrates an immunization strategy to neutralize RhCMVIL-10 biological activity using non-functional RhCMVIL-10 antigens. The results provide the methodology for targeting CMVIL-10 in vaccine, and therapeutic strategies, to nullify HCMV's ability to (1) skew innate and adaptive immunity, (2) disseminate from the site of primary mucosal infection, and (3) establish a lifelong persistent infection

Near-Native Protein Loop Sampling Using Nonparametric Density Estimation Accommodating Sparcity

Unlike the core structural elements of a protein like regular secondary structure, template based modeling (TBM) has difficulty with loop regions due to their variability in sequence and structure as well as the sparse sampling from a limited number of homologous templates. We present a novel, knowledge-based method for loop sampling that leverages homologous torsion angle information to estimate a continuous joint backbone dihedral angle density at each loop position. The φ,ψ distributions are estimated via a Dirichlet process mixture of hidden Markov models (DPM-HMM). Models are quickly generated based on samples from these distributions and were enriched using an end-to-end distance filter. The performance of the DPM-HMM method was evaluated against a diverse test set in a leave-one-out approach. Candidates as low as 0.45 Å RMSD and with a worst case of 3.66 Å were produced. For the canonical loops like the immunoglobulin complementarity-determining regions (mean RMSD <2.0 Å), the DPM-HMM method performs as well or better than the best templates, demonstrating that our automated method recaptures these canonical loops without inclusion of any IgG specific terms or manual intervention. In cases with poor or few good templates (mean RMSD >7.0 Å), this sampling method produces a population of loop structures to around 3.66 Å for loops up to 17 residues. In a direct test of sampling to the Loopy algorithm, our method demonstrates the ability to sample nearer native structures for both the canonical CDRH1 and non-canonical CDRH3 loops. Lastly, in the realistic test conditions of the CASP9 experiment, successful application of DPM-HMM for 90 loops from 45 TBM targets shows the general applicability of our sampling method in loop modeling problem. These results demonstrate that our DPM-HMM produces an advantage by consistently sampling near native loop structure. The software used in this analysis is available for download at http://www.stat.tamu.edu/~dahl/software/cortorgles/

Temperaturverbreiterung und -verschiebung der phononenlosen Linien in den optischen Spektren dotierter Kristalle

Die Unmöglichkeit, mit den vorhandenen theoretischen Formeln die Hochtemperaturverschiebung der schmalen phononenlosen Linien (PLL) zu beschreiben, was vor allem mit dem Beitrag des Phononenflügels (PF) zu der zu messenden Halbwertbreite zusammenhängt. Eine nicht schlechte Übereinstimmung von allen untersuchten Niedertemperaturangaben zu der PLL-Verbreiterung mit den theoretischen Kurven, die in dieser Arbeit aufgestellt werden. Die Möglichkeit, im Versuch die Nichtspiegelbildlichkeit im PF, die durch die Veränderung der elastischen Kräfte bedingt ist, zu beobachten. Tatsächlich erweist sich zwei von vier Fällen die Veränderung der Kraftmatrix des Kristalls als ausreichend groß, damit die Nichtspiegelbildlichkeit erkennbar wird