Structures and materials technology issues for reusable launch vehicles

Projected space missions for both civil and defense needs require significant improvements in structures and materials technology for reusable launch vehicles: reductions in structural weight compared to the Space Shuttle Orbiter of up to 25% or more, a possible factor of 5 or more increase in mission life, increases in maximum use temperature of the external surface, reusable containment of cryogenic hydrogen and oxygen, significant reductions in operational costs, and possibly less lead time between technology readiness and initial operational capability. In addition, there is increasing interest in hypersonic airbreathing propulsion for launch and transmospheric vehicles, and such systems require regeneratively cooled structure. The technology issues are addressed, giving brief assessments of the state-of-the-art and proposed activities to meet the technology requirements in a timely manner

Discovery of Five New Pulsars in Archival Data

Reprocessing of the Parkes Multibeam Pulsar Survey has resulted in the discovery of five previously unknown pulsars and several as-yet-unconfirmed candidates. PSR J0922-52 has a period of 9.68 ms and a DM of 122.4 pc cm^-3. PSR J1147-66 has a period of 3.72 ms and a DM of 133.8 pc cm^-3. PSR J1227-6208 has a period of 34.53 ms, a DM of 362.6 pc cm^-3, is in a 6.7 day binary orbit, and was independently detected in an ongoing high-resolution Parkes survey by Thornton et al. and also in independent processing by Einstein@Home volunteers. PSR J1546-59 has a period of 7.80 ms and a DM of 168.3 pc cm^-3. PSR J1725-3853 is an isolated 4.79-ms pulsar with a DM of 158.2 pc cm^-3. These pulsars were likely missed in earlier processing efforts due to their high DMs and short periods and the large number of candidates that needed to be looked through. These discoveries suggest that further pulsars are awaiting discovery in the multibeam survey data.Comment: 12 pages, 2 figures, 2 tables, accepted to Ap

Spelling in adolescents with dyslexia: errors and modes of assessment

In this study we focused on the spelling of high-functioning students with dyslexia. We made a detailed classification of the errors in a word and sentence dictation task made by 100 students with dyslexia and 100 matched control students. All participants were in the first year of their bachelor’s studies and had Dutch as mother tongue. Three main error categories were distinguished: phonological, orthographic, and grammatical errors (on the basis of morphology and language-specific spelling rules). The results indicated that higher-education students with dyslexia made on average twice as many spelling errors as the controls, with effect sizes of d ≥ 2. When the errors were classified as phonological, orthographic, or grammatical, we found a slight dominance of phonological errors in students with dyslexia. Sentence dictation did not provide more information than word dictation in the correct classification of students with and without dyslexia

Myxobacteria versus sponge-derived alkaloids: the bengamide family identified as potent immune modulating agents by scrutiny of LC-MS/ELSD libraries.

A nuclear factor-κB (NF-κB) luciferase assay has been employed to identify the bengamides, previously known for their anti-tumor activity, as a new class of immune modulators. A unique element of this study was that the bengamide analogs were isolated from two disparate sources, Myxococcus virescens (bacterium) and Jaspis coriacea (sponge). Comparative LC-MS/ELSD and NMR analysis facilitated the isolation of M. viriscens derived samples of bengamide E (8) and two congeners, bengamide E\u27 (13) and F\u27 (14) each isolated as an insperable mixture of diastereomers. Additional compounds drawn from the UC, Santa Cruz repository allowed expansion of the structure activity relationship (SAR) studies. The activity patterns observed for bengamide A (6), B (7), E (8), F (9), LAF 389 (12) and 13-14 gave rise to the following observations and conclusions. Compounds 6 and 7 display potent inhibition of NF-κB (at 80 and 90 nM, respectively) without cytotoxicity to RAW264.7 macrophage immune cells. Western blot and qPCR analysis indicated that 6 and 7 reduce the phosphorylation of IκBα and the LPS-induced expression of the pro-inflammatory cytokines/chemokines TNFα, IL-6 and MCP-1 but do not effect NO production or the expression of iNOS. These results suggest that the bengamides may serve as therapeutic leads for the treatment of diseases involving inflammation, that their anti-tumor activity can in part be attributed to their ability to serve as immune modulating agents, and that their therapeutic potential against cancer merits further consideration

Consonance perception beyond the traditional existence region of pitch

Some theories posit that the perception of consonance is based on neural periodicity detection, which is dependent on accurate phase locking of auditory nerve fibers to features of the stimulus waveform. In the current study, 15 listeners were asked to rate the pleasantness of complex tone dyads (2 note chords) forming various harmonic intervals and bandpass filtered in a high-frequency region (all components >5.8 kHz), where phase locking to the rapid stimulus fine structure is thought to be severely degraded or absent. The two notes were presented to opposite ears. Consonant intervals (minor third and perfect fifth) received higher ratings than dissonant intervals (minor second and tritone). The results could not be explained in terms of phase locking to the slower waveform envelope because the preference for consonant intervals was higher when the stimuli were harmonic, compared to a condition in which they were made inharmonic by shifting their component frequencies by a constant offset, so as to preserve their envelope periodicity. Overall the results indicate that, if phase locking is indeed absent at frequencies greater than ∼5 kHz, neural periodicity detection is not necessary for the perception of consonance

Stage-Specific Inhibition of MHC Class I Presentation by the Epstein-Barr Virus BNLF2a Protein during Virus Lytic Cycle

gamma-herpesvirus Epstein-Barr virus (EBV) persists for life in infected individuals despite the presence of a strong immune response. During the lytic cycle of EBV many viral proteins are expressed, potentially allowing virally infected cells to be recognized and eliminated by CD8+ T cells. We have recently identified an immune evasion protein encoded by EBV, BNLF2a, which is expressed in early phase lytic replication and inhibits peptide- and ATP-binding functions of the transporter associated with antigen processing. Ectopic expression of BNLF2a causes decreased surface MHC class I expression and inhibits the presentation of indicator antigens to CD8+ T cells. Here we sought to examine the influence of BNLF2a when expressed naturally during EBV lytic replication. We generated a BNLF2a-deleted recombinant EBV (ΔBNLF2a) and compared the ability of ΔBNLF2a and wild-type EBV-transformed B cell lines to be recognized by CD8+ T cell clones specific for EBV-encoded immediate early, early and late lytic antigens. Epitopes derived from immediate early and early expressed proteins were better recognized when presented by ΔBNLF2a transformed cells compared to wild-type virus transformants. However, recognition of late antigens by CD8+ T cells remained equally poor when presented by both wild-type and ΔBNLF2a cell targets. Analysis of BNLF2a and target protein expression kinetics showed that although BNLF2a is expressed during early phase replication, it is expressed at a time when there is an upregulation of immediate early proteins and initiation of early protein synthesis. Interestingly, BNLF2a protein expression was found to be lost by late lytic cycle yet ΔBNLF2a-transformed cells in late stage replication downregulated surface MHC class I to a similar extent as wild-type EBV-transformed cells. These data show that BNLF2a-mediated expression is stage-specific, affecting presentation of immediate early and early proteins, and that other evasion mechanisms operate later in the lytic cycle

Testing a Spectral Model of Tonal Affinity with Microtonal Melodies and Inharmonic Spectra

Tonal affinity is the perceived goodness of fit of successive tones. It is important because a preference for certain intervals over others would likely influence preferences for, and prevalences of, “higher-order” musical structures such as scales and chord progressions. We hypothesize that two psychoacoustic (spectral) factors—harmonicity and spectral pitch similarity—have an impact on affinity. The harmonicity of a single tone is the extent to which its partials (frequency components) correspond to those of a harmonic complex tone (whose partials are a multiple of a single fundamental frequency). The spectral pitch similarity of two tones is the extent to which they have partials with corresponding, or close, frequencies. To ascertain the unique effect sizes of harmonicity and spectral pitch similarity, we constructed a computational model to numerically quantify them. The model was tested against data obtained from 44 participants who ranked the overall affinity of tones in melodies played in a variety of tunings (some microtonal) with a variety of spectra (some inharmonic). The data indicate the two factors have similar, but independent, effect sizes: in combination, they explain a sizeable portion of the variance in the data (the model-data squared correlation is r2 = .64). Neither harmonicity nor spectral pitch similarity require prior knowledge of musical structure, so they provide a potentially universal bottom-up explanation for tonal affinity. We show how the model—as optimized to these data—can explain scale structures commonly found in music, both historical and contemporary, and we discuss its implications for experimental microtonal and spectral music

Unsuccessful therapy with adefovir and entecavir-tenofovir in a patient with chronic hepatitis B infection with previous resistance to lamivudine: a fourteen-year evolution of hepatitis B virus mutations

<p>Abstract</p> <p>Background</p> <p>Complex mutants can be selected under sequential selective pressure by HBV therapy. To determine hepatitis B virus genomic evolution during antiviral therapy we characterized the HBV quasi-species in a patient who did no respond to therapy following lamivudine breakthrough for a period of 14 years.</p> <p>Case Presentation</p> <p>The polymerase and precore/core genes were amplified and sequenced at determined intervals in a period of 14 years. HBV viral load and HBeAg/Anti-HBe serological profiles as well as amino transferase levels were also measured. A mixture of lamivudine-resistant genotype A2 HBV strains harboring the rtM204V mutation coexisted in the patient following viral breakthrough to lamivudine. The L180M+M204V dominant mutant displayed strong lamivudine-resistance. As therapy was changed to adefovir, then to entecavir, and finally to entecavir-tenofovir the viral load showed fluctuations but lamivudine-resistant strains continued to be selected, with minor contributions to the HBV quasi-species composition of additional resistance-associated mutations. At the end of the 14-year follow up period, high viral loads were predominant, with viral strains harboring the lamivudine-resistance signature rtL180M+M204V. The precore/core frame A1762T and G1764A double mutation was detected before treatment and remaining in this condition during the entire follow-up. Specific entecavir and tenofovir primary resistance-associated mutations were not detected at any time. Plasma concentrations of tenofovir indicated adequate metabolism of the drug.</p> <p>Conclusions</p> <p>We report the selection of HBV mutants carrying well-defined primary resistance mutations that escaped lamivudine in a fourteen-year follow-up period. With the exception of tenofovir resistance mutations, subsequent unselected primary resistance mutations were detected as minor populations into the HBV quasispecies composition during adefovir or entecavir monotherapies. Although tenofovir is considered an appropriate therapeutic alternative for the treatment of entecavir-unresponsive patients, its use was not effective in the case reported here.</p