De-novo design of complementary (antisense) peptide mini-receptor inhibitor of interleukin 18 (IL-18).

Complementary (antisense) peptide mini-receptor inhibitors are complementary peptides designed to be receptor-surrogates that act by binding to selected surface features of biologically important proteins thereby inhibiting protein-cognate receptor interactions and subsequent biological effects. Previously, we described a complementary peptide mini-receptor inhibitor of interleukin-1beta (IL-1beta) that was designed to bind to an external surface loop (beta-bulge) of IL-1beta (Boraschi loop) clearly identified in the X-ray crystal structure of this cytokine. Here, we report the de-novo design and rational development of a complementary peptide mini-receptor inhibitor of cytokine interleukin-18 (IL-18), a protein for which there is no known X-ray crystal structure. Using sequence homology comparisons with IL-1beta, putative IL-18 surface loops are identified and used as a starting point for design, including a loop region 1 thought to be equivalent with the Boraschi loop of IL-1beta. Only loop region 1 complementary peptides are found to be promising leads as mini-receptor inhibitors of IL-18 but these are prevented from being properly successful owing to solubility problems. The application of "M-I pair mutagenesis" and inclusion of a C-terminal arginine residue are then sufficient to solve this problem and convert one lead peptide into a functional complementary peptide mini-receptor inhibitor of IL-18. This suggests that the biophysical and biological properties of complementary peptides can be improved in a rational and logical manner where appropriate, further strengthening the potential importance of complementary peptides as inhibitors of protein-protein interactions, even when X-ray crystal structural information is not readily available

Influence of positional correlations on the propagation of waves in a complex medium with polydisperse resonant scatterers

We present experimental results on a model system for studying wave propagation in a complex medium exhibiting low frequency resonances. These experiments enable us to investigate a fundamental question that is relevant for many materials, such as metamaterials, where low-frequency scattering resonances strongly influence the effective medium properties. This question concerns the effect of correlations in the positions of the scatterers on the coupling between their resonances, and hence on wave transport through the medium. To examine this question experimentally, we measure the effective medium wave number of acoustic waves in a sample made of bubbles embedded in an elastic matrix over a frequency range that includes the resonance frequency of the bubbles. The effective medium is highly dispersive, showing peaks in the attenuation and the phase velocity as functions of the frequency, which cannot be accurately described using the Independent Scattering Approximation (ISA). This discrepancy may be explained by the effects of the positional correlations of the scatterers, which we show to be dependent on the size of the scatterers. We propose a self-consistent approach for taking this "polydisperse correlation" into account and show that our model better describes the experimental results than the ISA

No relationship between intelligence and facial attractiveness in a large, genetically informative sample

Theories in both evolutionary and social psychology suggest that a positive correlation should exist between facial attractiveness and general intelligence, and several empirical observations appear to corroborate this expectation. Using highly reliable measures of facial attractiveness and IQ in a large sample of identical and fraternal twins and their siblings, we found no evidence for a phenotypic correlation between these traits. Likewise, neither the genetic nor the environmental latent factor correlations were statistically significant. We supplemented our analyses of new data with a simple meta-analysis that found evidence of publication bias among past studies of the relationship between facial attractiveness and intelligence. In view of these results, we suggest that previously published reports may have overestimated the strength of the relationship and that the theoretical bases for the predicted attractiveness–intelligence correlation may need to be reconsidered

Macrocerebellum: Neuroimaging and Clinical Features of a Newly Recognized Condition

Other than hamartomatous enlargement of the cerebellum as in Lhermitte-Duclos syndrome, diffuse enlargement of the cerebellum is not clearly described. We report four patients (ages 9 months to 2 years) with diffusely enlarged cerebelli as identified by measurement of the cerebellum and comparison to age appropriate normal values. The cerebellar measurements were determined in absolute numbers and expressed as ratios of cerebellum to whole brain and supratentorial brain. The clinical features of these four children (3 boys, 1 girl) consistently include global developmental delay, tone abnormalities, preserved reflexes, delayed or abnormal maturation of the visual system (oculomotor apraxia), and deficient or delayed myelination of cerebral white matter. The etiology of the macrocerebellum is unknown but we propose that the cerebellum is responding to the elaboration of growth factors intended to augment the slow development of cerebral structures. Regardless of the etiology, the finding of a macrocerebellum appears to allow the clinician to predict the clinical features of the patient and probably represents a marker for disturbed cerebral development. (J Child Neurol 1997;12:365-368).Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline

Evaluation of a web-based asthma self-management system: a randomised controlled pilot trial

Background Asthma is the most common chronic condition of childhood and disproportionately affects inner-city minority children. Low rates of asthma preventer medication adherence is a major contributor to poor asthma control in these patients. Web-based methods have potential to improve patient knowledge and medication adherence by providing interactive patient education, monitoring of symptoms and medication use, and by facilitation of communication and teamwork among patients and health care providers. Few studies have evaluated web-based asthma support environments using all of these potentially beneficial interventions. The multidimensional website created for this study, BostonBreathes, was designed to intervene on multiple levels, and was evaluated in a pilot trial. Methods An interactive, engaging website for children with asthma was developed to promote adherence to asthma medications, provide a platform for teamwork between caregivers and patients, and to provide primary care providers with up-to-date symptom information and data on medication use. Fifty-eight (58) children primarily from inner city Boston with persistent-level asthma were randomised to either usual care or use of BostonBreathes. Subjects completed asthma education activities, and reported their symptoms and medication use. Primary care providers used a separate interface to monitor their patients’ website use, their reported symptoms and medication use, and were able to communicate online via a discussion board with their patients and with an asthma specialist. Results After 6-months, reported wheezing improved significantly in both intervention and control groups, and there were significant improvements in the intervention group only in night-time awakening and parental loss of sleep, but there were no significant differences between intervention and control groups in these measures. Emergency room or acute visits to a physician for asthma did not significantly change in either group. Among the subgroup of subjects with low controller medication adherence at baseline, adherence improved significantly only in the intervention group. Knowledge of the purpose of controller medicine increased significantly in the intervention group, a statistically significant improvement over the control group. Conclusions This pilot study suggests that a multidimensional web-based educational, monitoring, and communication platform may have positive influences on pediatric patients’ asthma-related knowledge and use of asthma preventer medications

A convenient and efficient synthesis of (S)-lysine and (S)-arginine homologues via olefin cross-metathesis

A convenient five step synthesis of (S)-homolysine, incorporating a key olefin cross-metathesis step in the chain extension methodology, has been developed, together with a six step related synthesis of a new homologue of arginine, (S)-bishomoarginine

Evaluation of phase-diversity techniques for solar-image restoration

Phase-diversity techniques provide a novel observational method for overcomming the effects of turbulence and instrument-induced aberrations in ground-based astronomy. Two implementations of phase-diversity techniques that differ with regard to noise model, estimator, optimization algorithm, method of regularization, and treatment of edge effects are described. Reconstructions of solar granulation derived by applying these two implementations to common data sets are shown to yield nearly identical images. For both implementations, reconstructions from phase-diverse speckle data (involving multiple realizations of turbulence) are shown to be superior to those derived from conventional phase-diversity data (involving a single realization). Phase-diverse speckle reconstructions are shown to achieve near diffraction-limited resolution and are validated by internal and external consistency tests, including a comparison with a reconstruction using a well-accepted speckle-imaging method

Characteristics of Mantle Fabrics beneath the South-Central United States: Constraints from Shear-Wave Splitting Measurements

New shear-wave splitting measurements at permanent broadband seismic stations in the south-central United States reveal the orientation and degree of polarization of mantle fabrics, and provide constraints on models for the formation of these fabrics. For stations on the stable North American craton, correspondence between observed polarization direction of the fast wave and the trend of Proterozoic and Paleozoic structures associated with rifts and orogenic belts implies a lithospheric origin for the observed anisotropy. The largest splitting times (up to 1.6 s) are observed at stations located in the ocean-continent transition zone, in which the fast directions are parallel to the Gulf of Mexico continental margin. The parallelism and the geometry of the keel of the craton beneath the study area suggest that asthenospheric flow around the keel of the North American craton, lithospheric fabrics developed during Mesozoic rifting, or a combination of these factors are responsible for the observed anisotropy on stations above the transitional crust