Extreme ultraviolet and X-ray spectroheliograph for OSO-H

A complex scientific instrument was designed, fabricated, tested, and calibrated for launch onboard OSO-H. This instrument consisted of four spectroheliographs and an X-ray polarimeter. The instrument is designed to study solar radiation at selected wavelengths in the X-ray and the extreme ultraviolet ranges, make observations at the H-alpha wavelength, and measure the degree of polarization of X-ray emissions

Two-stage phase II oncology designs using short-term endpoints for early stopping

Phase II oncology trials are conducted to evaluate whether the tumour activity of a new treatment is promising enough to warrant further investigation. The most commonly used approach in this context is a two-stage single-arm design with binary endpoint. As for all designs with interim analysis, its efficiency strongly depends on the relation between recruitment rate and follow-up time required to measure the patients’ outcomes. Usually, recruitment is postponed after the sample size of the first stage is achieved up until the outcomes of all patients are available. This may lead to a considerable increase of the trial length and with it to a delay in the drug development process. We propose a design where an intermediate endpoint is used in the interim analysis to decide whether or not the study is continued with a second stage. Optimal and minimax versions of this design are derived. The characteristics of the proposed design in terms of type I error rate, power, maximum and expected sample size as well as trial duration are investigated. Guidance is given on how to select the most appropriate design. Application is illustrated by a phase II oncology trial in patients with advanced angiosarcoma, which motivated this research

A novel compartment, the 'subqpical stem' of the aerial hyphae, is the location of a sigN-dependent, developmentally distinct transcription in Streptomyces coelicolor.

Streptomyces coelicolor has nine SigB-like RNA polymerase sigma factors, several of them implicated in morphological differentiation and/or responses to different stresses. One of the nine, SigN, is the focus of this article. A constructed sigN null mutant was delayed in development and exhibited a bald phenotype when grown on minimal medium containing glucose as carbon source. One of two distinct sigN promoters, sigNP1, was active only during growth on solid medium, when its activation coincided with aerial hyphae formation. Transcription from sigNP1 was readily detected in several whi mutants (interrupted in morphogenesis of aerial mycelium into spores), but was absent from all bld mutants tested, suggesting that sigNP1 activity was restricted to the aerial hyphae. It also depended on sigN, thus sigN was autoregulated. Mutational and transcription studies revealed no functional significance to the location of sigN next to sigF, encoding another SigB-like sigma factor. We identified another potential SigN target, nepA, encoding a putative small secreted protein. Transcription of nepA originated from a single, aerial hyphae-specific and sigN-dependent promoter. While in vitro run-off transcription using purified SigN on the Bacillus subtilis ctc promoter confirmed that SigN is an RNA polymerase sigma factor, SigN failed to initiate transcription from sigNP1 and from the nepA promoter in vitro. Additional in vivo data indicated that further nepA upstream sequences, which are likely to bind a potential activator, are required for successful transcription. Using a nepA–egfp transcriptional fusion we located nepA transcription to a novel compartment, the ‘subapical stem’ of the aerial hyphae. We suggest that this newly recognized compartment defines an interface between the aerial and vegetative parts of the Streptomyces colony and might also be involved in communication between these two compartments

Statistical shape modelling of the thoracic spine for the development of pedicle screw insertion guides

Spinal fixation and fusion are surgical procedures undertaken to restore stability in the spine and restrict painful or degenerative motion. Malpositioning of pedicle screws during these procedures can result in major neurological and vascular damage. Patient-specific surgical guides offer clear benefits, reducing malposition rates by up to 25%. However, they suffer from long lead times and the manufacturing process is dependent on third-party specialists. The development of a standard set of surgical guides may eliminate the issues with the manufacturing process. To evaluate the feasibility of this option, a statistical shape model (SSM) was created and used to analyse the morphological variations of the T4–T6 vertebrae in a population of 90 specimens from the Visible Korean Human dataset (50 females and 40 males). The first three principal components, representing 39.7% of the variance within the population, were analysed. The model showed high variability in the transverse process (~ 4 mm) and spinous process (~ 4 mm) and relatively low variation (< 1 mm) in the vertebral lamina. For a Korean population, a standardised set of surgical guides would likely need to align with the lamina where the variance in the population is lower. It is recommended that this standard set of surgical guides should accommodate pedicle screw diameters of 3.5–6 mm and transverse pedicle screw angles of 3.5°–12.4°

The actinobacterial transcription factor RbpA binds to the principal sigma subunit of RNA polymerase

RbpA is a small non-DNA-binding transcription factor that associates with RNA polymerase holoenzyme and stimulates transcription in actinobacteria, including Streptomyces coelicolor and Mycobacterium tuberculosis. RbpA seems to show specificity for the vegetative form of RNA polymerase as opposed to alternative forms of the enzyme. Here, we explain the basis of this specificity by showing that RbpA binds directly to the principal σ subunit in these organisms, but not to more diverged alternative σ factors. Nuclear magnetic resonance spectroscopy revealed that, although differing in their requirement for structural zinc, the RbpA orthologues from S. coelicolor and M. tuberculosis share a common structural core domain, with extensive, apparently disordered, N- and C-terminal regions. The RbpA-σ interaction is mediated by the C-terminal region of RbpA and σ domain 2, and S. coelicolor RbpA mutants that are defective in binding σ are unable to stimulate transcription in vitro and are inactive in vivo. Given that RbpA is essential in M. tuberculosis and critical for growth in S. coelicolor, these data support a model in which RbpA plays a key role in the σ cycle in actinobacteria

Variant -and individual dependent nature of persistent Anaplasma phagocytophilum infection

<p>Abstract</p> <p>Background</p> <p><it>Anaplasma phagocytophilum </it>is the causative agent of tick-borne fever in ruminants and human granulocytotropic anaplasmosis (HGA). The bacterium is able to survive for several months in immune-competent sheep by modifying important cellular and humoral defence mechanisms. Little is known about how different strains of <it>A. phagocytophilum </it>propagate in their natural hosts during persistent infection.</p> <p>Methods</p> <p>Two groups of five lambs were infected with each of two <it>16S </it>rRNA gene variants of <it>A. phagocytophilum</it>, i.e. <it>16S </it>variant 1 which is identical to GenBank no <ext-link ext-link-id="M73220" ext-link-type="gen">M73220</ext-link> and <it>16S </it>variant 2 which is identical to GenBank no <ext-link ext-link-id="AF336220" ext-link-type="gen">AF336220</ext-link>, respectively. The lambs were infected intravenously and followed by blood sampling for six months. <it>A. phagocytophilum </it>infection in the peripheral blood was detected by absolute quantitative real-time PCR.</p> <p>Results</p> <p>Both <it>16S </it>rRNA gene variants of <it>A. phagocytophilum </it>established persistent infection for at least six months and showed cyclic bacteraemias, but variant 1 introduced more frequent periods of bacteraemia and higher number of organisms than <it>16S </it>rRNA gene variant 2 in the peripheral blood.</p> <p>Conclusion</p> <p>Organisms were available from blood more or less constantly during the persistent infection and there were individual differences in cyclic activity of <it>A. phagocytophilum </it>in the infected animals. Two <it>16S </it>rRNA gene variants of <it>A. phagocytophilum </it>show differences in cyclic activity during persistent infection in lambs.</p

Isolation and characterization of potent antifungal strains of the Streptomyces violaceusniger clade active against Candida albicans

Streptomyces strains were isolated from a sagebrush rhizosphere soil sample on humic acid vitamin (HV) agar and water yeast extract (WYE) agar supplemented with 1.5% (w/w) phenol as a selective medium. Acidic, neutral and alkaline pH conditions were also used in the isolation procedures. The phenol treatment reduced the numbers of both actinomycetes and non-actinomycetes on plates under all three pH conditions. From phenol-amended HV and WYE agar, 16 strains were isolated in pure culture; 14 from the HV agar and two from the WYE agar. All the isolates were tested for their antifungal activities against Pythium ultimum P8 and five yeast strains, including two antifungal drug-resistant Candida albicans strains. HV isolates that showed broad-spectrum antifungal antibiotic activities were all found to be members of the Streptomyces violaceusniger clade, while those that did not were non-clade members. The phenol treatment was not selective for S. violaceusniger clade members. Therefore, we tested the spores of both S. violaceusniger clade and non-clade members using two biocides, phenol and hydrogen peroxide, as selection agents. Spores of non-clade members, such as S. coelicolor M145 and S. lividans TK 21, survived these two biocides just as well as S. violaceusniger clade members. Thus, in our hands, biocide resistance was not S. violaceusniger clade specific as previously reported. However, isolates showing broad-spectrum antifungal and antiyeast activity were all members of the clade. We conclude that screening of isolates for broad-spectrum antifungal/antiyeast activity is the preferred method of isolating S. violaceusniger clade strains rather than biocide-based selection. Phylogenetic analysis of the phenol-resistant isolates revealed that the HV isolates that exhibited broad-spectrum antifungal antibiotic activity were all clustered and closely related to the S. violaceusniger clade, while the isolates that did not exhibit antifungal antibiotic activity were all non-clade members

Tooth wear: the view of the anthropologist

Anthropologists have for many years considered human tooth wear a normal physiological phenomenon where teeth, although worn, remain functional throughout life. Wear was considered pathological only if pulpal exposure or premature tooth loss occurred. In addition, adaptive changes to the stomatognathic system in response to wear have been reported including continual eruption, the widening of the masticatory cycle, remodelling of the temporomandibular joint and the shortening of the dental arches from tooth migration. Comparative studies of many different species have also documented these physiological processes supporting the idea of perpetual change over time. In particular, differential wear between enamel and dentine was considered a physiological process relating to the evolution of the form and function of teeth. Although evidence of attrition and abrasion has been known to exist among hunter-gatherer populations for many thousands of years, the prevalence of erosion in such early populations seems insignificant. In particular, non-carious cervical lesions to date have not been observed within these populations and therefore should be viewed as ‘modern-day’ pathology. Extrapolating this anthropological perspective to the clinical setting has merits, particularly in the prevention of pre-mature unnecessary treatment