CERN-based experiments and Monte-Carlo studies on focused dose delivery with very high energy electron (VHEE) beams for radiotherapy applications.

Very High Energy Electron (VHEE) beams are a promising alternative to conventional radiotherapy due to their highly penetrating nature and their applicability as a modality for FLASH (ultra-high dose-rate) radiotherapy. The dose distributions due to VHEE need to be optimised; one option is through the use of quadrupole magnets to focus the beam, reducing the dose to healthy tissue and allowing for targeted dose delivery at conventional or FLASH dose-rates. This paper presents an in depth exploration of the focusing achievable at the current CLEAR (CERN Linear Electron Accelerator for Research) facility, for beam energies >200 MeV. A shorter, more optimal quadrupole setup was also investigated using the TOPAS code in Monte Carlo simulations, with dimensions and beam parameters more appropriate to a clinical situation. This work provides insight into how a focused VHEE radiotherapy beam delivery system might be achieved.

Focused VHEE (very high energy electron) beams and dose delivery for radiotherapy applications.

This paper presents the first demonstration of deeply penetrating dose delivery using focused very high energy electron (VHEE) beams using quadrupole magnets in Monte Carlo simulations. We show that the focal point is readily modified by linearly changing the quadrupole magnet strength only. We also present a weighted sum of focused electron beams to form a spread-out electron peak (SOEP) over a target region. This has a significantly reduced entrance dose compared to a proton-based spread-out Bragg peak (SOBP). Very high energy electron (VHEE) beams are an exciting prospect in external beam radiotherapy. VHEEs are less sensitive to inhomogeneities than proton and photon beams, have a deep dose reach and could potentially be used to deliver FLASH radiotherapy. The dose distributions of unfocused VHEE produce high entrance and exit doses compared to other radiotherapy modalities unless focusing is employed, and in this case the entrance dose is considerably improved over existing radiations. We have investigated both symmetric and asymmetric focusing as well as focusing with a range of beam energies.

Circular dichroism spectral data and metadata in the Protein Circular Dichroism Data Bank (PCDDB): a tutorial guide to accession and deposition.

The Protein Circular Dichroism Data Bank (PCDDB) is a web-based resource containing circular dichroism (CD) and synchrotron radiation circular dichroism spectral and associated metadata located at http://pcddb.cryst.bbk.ac.uk. This resource provides a freely available, user-friendly means of accessing validated CD spectra and their associated experimental details and metadata, thereby enabling broad usage of this material and new developments across the structural biology, chemistry, and bioinformatics communities. The resource also enables researchers utilizing CD as an experimental technique to have a means of storing their data at a secure site from which it is easily retrievable, thereby making their results publicly accessible, a current requirement of many grant-funding agencies world-wide, as well as meeting the data-sharing requirements for journal publications. This tutorial provides extensive information on searching, accessing, and downloading procedures for those who wish to utilize the data available in the data bank, and detailed information on deposition procedures for creating and validating entries, including comprehensive explanations of their contents and formats, for those who wish to include their data in the data bank.

Fabrication and magnetic properties of Ni nanowire arrays with ultrahigh axial squareness.

Poly- and single-crystalline Ni nanowire arrays showing ultrahigh axial squareness are fabricated by direct-current electrodeposition in pores of anodic aluminum oxide templates. High voltage is shown to be the key in order for Ni nanowires to have a (220) preferred orientation. 2-Dimensional nucleation theory is used to understand the growth of the nanowires. Based on the structure and growth analyses, the magnetic properties of different kinds of nanowires are explained.

Analysis of peptaibol sequence composition: implications for in vivo synthesis and channel formation.

The sequence entries in the Peptaibol Database were analysed to provide information on compositional features of this unusual family of peptides. The non-standard amino acid alpha-aminoisobutyric acid represents almost 40% of the residues in all the known sequences. Glutamine is the only significant polar residue in peptaibols, and the position and number of these residues appear to be related to their functional properties as ion channels. Aromatic residues are clustered at the termini, which may contribute to stabilization of the peptide vertically within the bilayer. The peptide chain length is strongly weighted towards the longer members of the family (16-20 residues) and likely to be an important feature in their mode of action as transmembrane permeabilizers. The significant skewing towards even numbers of residues and the bias in pairwise distributions of amino acids have implications for the nature of the in vivo synthesis of these peptides via large non-ribosomal protein complexes.

The peptaibol database: a sequence and structure resource.

The peptaibols are a large family of membrane-active peptides with considerable sequence homology, but with different biological properties and three-dimensional structures. They constitute a rich resource of naturally occurring 'mutants' which are potentially valuable for structure/function studies of ion channels. A searchable on-line database of sequences and structures of the peptaibols has been created at http://www.cryst.bbk.ac.uk/peptaibol, as a resource for the biological and structural community. In this paper, the contents and organization of the website are discussed as well as procedures for submission of new entries to the database. At present, more than 300 peptaibol sequences are stored in the database. Each sequence entry contains its full literature reference and information about its biological source. Tools are provided for searching for specific peptaibol sequences or groupings of sequences, and for locating peptaibols containing specified sequence motifs. In addition the website acts as a database for structural information. The coordinates of all currently available peptaibol x-ray and NMR structures are included and complemented, where appropriate. with molecular graphics illustrations. These include figures of model channel structures and comparisons between different peptaibol structures. The peptaibol database thus provides a tool for ready access to information and a means of investigating the sequences and structures of this class of polypeptides.

DICHROWEB: an interactive website for the analysis of protein secondary structure from circular dichroism spectra.

A user-friendly website for the analysis of protein secondary structures from Circular Dichroism (CD) and Synchrotron Radiation Circular Dichroism (SRCD) spectra has been created.

Enhanced efficiency of electrostatically charged insecticide aerosols.

The bioefficacy of a standard domestic aerosol insecticide has been compared with that of a similar spray in which the droplets were electrostatically charged. The aerosol was charged without the need for an external power supply, by enhancing natural charge separation processes that occur during atomisation. The charge-to-mass ratio achieved was 1.1 x 10(-4) C kg-1, compared with 2.2 x 10(-5) C kg-1 for the standard aerosol. Efficiency was assessed for insects in free flight. A direct space-spray application method was used to study the bioefficacy of these aerosols on houseflies, Musca domestica, and an indirect space-spray method on houseflies and mosquitoes, Culex quinquefasciatus. Two levels of concentration of active ingredients were compared. At low concentrations of 1.57 g kg-1 of bioallethrin and 0.29 g kg-1 of bioresmethrin, the charged aerosol achieved a significant reduction in KDT50 (time at which 50% of the flies were knocked down), compared with the standard aerosol. In the direct spray application to houseflies, the KDT50 was reduced by 50%, while in the indirect spray the KDT50 was reduced by 40%. In the indirect spray of mosquitoes, the KDT50 was reduced by 22%. With higher active ingredient concentrations of 2.09 g kg-1 for bioallethrin and 0.39 g kg-1 for bioresmethrin, the charged aerosol also demonstrated faster knockdown than the standard, but the improvement was less marked. In the direct spray application to houseflies, the KDT50 was reduced by 21% compared with the standard aerosol, while in the indirect spray the KDT50 was reduced by 16%. In the indirect spray of mosquitoes, the KDT50 was reduced by 24%. The percentage mortality after 24 h was also increased with the charged aerosol. Charge carried by the droplets results in increased interception of the insecticide, as the droplets are attracted to the insects in flight and space charge effects within the aerosol could cause improved dispersion in the test chamber.

Modification of left-right pairing during the development of individual crest synapses in the rat interpeduncular nucleus.

The synaptic organization of the rat interpeduncular nucleus is highly ordered in the normal adult. By 90 days of age, 90% of crest synapses in its intermediate subnuclei are formed by two cholinergic endings, one from each medial habenula. Stereological calculation of the number of crest synapses per intermediate subnucleus, based on total samples of crest synapses in 3-4 sections through the subnucleus, allows comparisons of afferent pairing among ages without interference by other developmental changes. Between 21 and 90 days of age, the total number of crest synapses per intermediate subnucleus increases tenfold (p less than 10(-8], from 90,000 at 21 days of age, through 130,000 at 28 days, 440,000 at 45 days, to 1,000,000 at 90 days. The volume of the intermediate subnucleus increases fivefold during the same interval. Electron microscopic degeneration was used to estimate the pairing of left and right habenula afferents at crest synapses at the same ages. Through 21 days of age, only one-third of crest synapses are formed with pairing of one left and one right medial habenula afferent, whereas two-third have both afferent endings arising from the same medial habenula. At 28 days of age left-right pairing has increased to 43%, and at 45 days of age 53%, or 240,000, are so paired. The number of same-side paired crest synapses at 45 days, 210,000, is 3.5 times the number so paired at 21 days (p = .003). This indicates continued formation of considerable numbers of crest synapses with this transient mode of airing as late as 45 days of age.(ABSTRACT TRUNCATED AT 250 WORDS)

Serum cholesterol, triglyceride, and high-density-lipoprotein concentrations in men with different dietary and exercise regimens in Puriscal, Costa Rica.

Mean serum cholesterol and triglyceride concentrations were higher for two groups of sedentary middle-aged and elderly men than for a group of physically-active, middle-aged farmers, all from rural Puriscal, Costa Rica. The mean serum cholesterol, triglyceride, and high-density lipoprotein (HDL)-risk factor levels of the three groups were all higher than the comparable US means. Dietary fat and cholesterol intake were also greater for the Puriscal men than for the comparable US counterpart. No correlations were found between dietary fat or cholesterol and the corresponding serum levels. Age was correlated with serum cholesterol and HDL-risk factor values. Weight was also correlated with these variables as well as with serum triglyceride concentrations. A high prevalence of obesity was found among the middle-aged sedentary men.

Gestational changes in the germinal matrix of the normal rhesus monkey fetus.

To explain the reported predisposition to germinal matrix hemorrhage in premature infants, pathogenetically important morphological features of the germinal matrix should be present in the 3rd trimester and rapidly change near term. Such features were sought in this study of the germinal matrix and its vasculature in normal rhesus monkey fetuses. The matrix cells, glia, ependyma, and capillaries showed no important structural changes during the 3rd trimester. The terminal vein tributaries were greatly enlarged by 148 days, but cellular and collagen support in their walls was minimal at this time. The latter features developed by the final days of gestation. These findings do not support a structural immaturity or specialization of the germinal matrix predisposing to germinal matrix hemorrhage. Our results, therefore, support the recent emphasis on physiological parameters in the pathogenesis and prevention of germinal matrix hemorrhage.