Driving magnetostructural transitions in layered intermetallic compounds.

We report the dramatic effect of applied pressure and magnetic field on the layered intermetallic compound Pr(0.5)Y(0.5)Mn(2)Ge(2). In the absence of pressure or magnetic field this compound displays interplanar ferromagnetism at room temperature and undergoes an isostructural first order magnetic transition (FOMT) to an antiferromagnetic state below 158 K, followed by another FOMT at 50 K due to the reemergence of ferromagnetism as praseodymium orders (T(C)(Pr)). The application of a magnetic field drives these two transitions towards each other, whereas the application of pressure drives them apart. Pressure also produces a giant magnetocaloric effect such that a threefold increase of the entropy change associated with the lower FOMT (at T(C)(Pr)) is seen under a pressure of 7.5 kbar. First principles calculations, using density functional theory, show that this remarkable magnetic behavior derives from the strong magnetoelastic coupling of the manganese layers in this compound.

International guidelines for the diagnosis and management of hereditary haemorrhagic telangiectasia.

BACKGROUND: HHT is an autosomal dominant disease with an estimated prevalence of at least 1/5000 which can frequently be complicated by the presence of clinically significant arteriovenous malformations in the brain, lung, gastrointestinal tract and liver. HHT is under-diagnosed and families may be unaware of the available screening and treatment, leading to unnecessary stroke and life-threatening hemorrhage in children and adults. OBJECTIVE: The goal of this international HHT guidelines process was to develop evidence-informed consensus guidelines regarding the diagnosis of HHT and the prevention of HHT-related complications and treatment of symptomatic disease. METHODS: The overall guidelines process was developed using the AGREE framework, using a systematic search strategy and literature retrieval with incorporation of expert evidence in a structured consensus process where published literature was lacking. The Guidelines Working Group included experts (clinical and genetic) from eleven countries, in all aspects of HHT, guidelines methodologists, health care workers, health care administrators, HHT clinic staff, medical trainees, patient advocacy representatives and patients with HHT. The Working Group determined clinically relevant questions during the pre-conference process. The literature search was conducted using the OVID MEDLINE database, from 1966 to October 2006. The Working Group subsequently convened at the Guidelines Conference to partake in a structured consensus process using the evidence tables generated from the systematic searches. RESULTS: The outcome of the conference was the generation of 33 recommendations for the diagnosis and management of HHT, with at least 80% agreement amongst the expert panel for 30 of the 33 recommendations.

Synthetic peptides form ion channels in artificial lipid bilayer membranes.

Ion permeability of cell membranes is considered to be mediated by ion channels. The synthesis and testing of four peptides having the sequence (Leu-Ser-Leu-Gly)n and expected to form beta126,6-helical ion channels in lipid bilayer membranes is reported. The two peptides capable of forming helices four turns in length have been demonstrated to form ion channels in an artificial lipid bilayer membrane system. The ion selectivity of the channels is consistent with the predicted beta12-helical model in which ions traversing the channel are coordinated by serine hydroxyl groups arrayed in the interior of the channel.

Tuneable Magnetic Phase Transitions in Layered CeMn2Ge(2-x)Six Compounds.

The structural and magnetic properties of seven CeMn2Ge(2-x)Six compounds with x = 0.0-2.0 have been investigated in detail. Substitution of Ge with Si leads to a monotonic decrease of both a and c along with concomitant contraction of the unit cell volume and significant modifications of the magnetic states - a crossover from ferromagnetism at room temperature for Ge-rich compounds to antiferromagnetism for Si-rich compounds. The magnetic phase diagram has been constructed over the full range of CeMn2Ge(2-x)Six compositions and co-existence of ferromagnetism and antiferromagnetism has been observed in CeMn2Ge1.2Si0.8, CeMn2Ge1.0Si1.0 and CeMn2Ge0.8Si1.2 with novel insight provided by high resolution neutron and X-ray synchrotron radiation studies. CeMn2Ge(2-x)Six compounds (x = 0, 0.4 and 0.8) exhibit moderate isothermal magnetic entropy accompanied with a second-order phase transition around room temperature. Analysis of critical behaviour in the vicinity of TC(inter) for CeMn2Ge2 compound indicates behaviour consistent with three-dimensional Heisenberg model predictions.

Interference fringe scale for absolute ocular fundus measurement.

Measurements of the human ocular fundus in the three spatial dimensions have not been absolute because measuring techniques have used the optical system of the eye as part of the total ophthalmoscopic system. The ophthalmoscopic magnification due to the total dioptric power of an individual eye can vary substantially from that of the average eye. A new method has been developed to form interference fringes on the fundus so that the fringe spacing can be calculated within a small error by using measured values. The photographed fringes then act as a scale at the fundus with the fringe spacings serving as the graduations, thus allowing accurate absolute measurements of the fundus through the interfering ocular media.

Vasoactive intestinal peptide and the stimulation of lactotroph growth by oestradiol in rats.

Treatment with a high dose of oestradiol for 6 months caused hyperprolactinaemia and pituitary hyperplasia in female Wistar-Furth rats. Changes in the vasoactive intestinal peptide (VIP) and dopamine content of the hypothalamus and pituitary were also found. The hypothalamic dopamine concentration was only slightly reduced and, although the concentration of dopamine in the pituitary was less in treated animals, the total pituitary content was increased. The concentration of VIP in the pituitary was increased by oestradiol treatment but decreased in the non-median eminence hypothalamus. In the median eminence the VIP content was increased by oestradiol treatment and the amount present correlated positively and significantly with pituitary wet weight in animals treated with both oestradiol and fluphenazine. In Fischer 344 rats, oestradiol produced greater incremental changes in pituitary wet weight and plasma concentrations of prolactin than in Wistar controls and the increase in the pituitary concentration of VIP was five times greater. Although peptide turnover has not been measured, these results suggest that oestradiol, as well as having a direct action, stimulates pituitary lactotrophs by increasing pituitary concentrations of VIP.

The challenge posed by endocrine-disrupting chemicals.

Rapid regulatory developments in the area of environmental endocrine disruption present a series of potential problems that are identified and illustrated with examples taken from the recent literature. A list of priorities is provided, including the need for additional epidemiological and wildlife studies, the derivation of a coordinated testing strategy, agreement on the toxicities expected of endocrine disrupting agents, and acceptance that whole animal assays will be uniquely critical in this area of toxicology. The intrinsic difficulty of attempting to simultaneously study all aspects of endocrine disruption indicates the need to reduce the scope of the problem, which can be achieved by first studying toxicities mediated by sex hormone receptors.

Characterization of a rearrangement in the c-MYB promoter in the acute lymphoblastic leukemia cell line CCRF-CEM.

Despite the frequent description of 6q- structural abnormalities in human leukemias and lymphomas, rearrangements of the c-MYB locus have not been detected. We have detected a rearrangement in the c-MYB proto-oncogene in the cell line CCRF-CEM, an immature T-cell leukemia cell line which is not 6q-. Due to this rearrangement, a large portion of the c-MYB promoter conserved between the human and murine c-MYB genes is lost. The rearranged locus, which we have designated MRR (MYB rearranged region), has been cloned and mapped to chromosome 6. Field inversion gel electrophoresis (FIGE) studies reveal that the MRR sequence is linked to the c-MYB locus, suggesting that the rearrangement is due to a submicroscopic deletion. The rearrangement appears to have no effect on c-MYB promoter activity as analyzed in CCRF-CEM cells. The normal locus of the MRR sequence has been cloned from a human placental genomic library. Partial sequence analysis of this clone reveals that a portion of the DNA lost in the rearrangement shows a high degree of homology to a member of the myc family of oncogenes. Thus the characterization of this rearrangement has yielded a new set of probes for the study of chromosome 6q abnormalities in human leukemias and lymphomas and provides the first evidence for potential involvement of the c-MYB locus itself in submicroscopic deletions within chromosome 6.

Mood-induced changes on the Implicit Association Test in recovered depressed patients.

A mood induction paradigm was used to examine dysphoria-related changes in two types of cognitive processing in individuals who had previously experienced depression. Formerly depressed patients (n = 23) and never-depressed controls (n = 27) completed the Dysfunctional Attitudes Scale, a self-report measure of effortful processing, and performed the Implicit Association Test, an automatic-reaction time task that measures evaluative bias, before and after a negative-mood induction. The formerly depressed group showed both an increase in endorsement of dysfunctional attitudes and a more negative evaluative bias for self-relevant information after the induction, relative to controls--however, there was no association between the mood-linked changes observed on these two measures. The shift in evaluative bias shown by the formerly depressed group was similar to that seen in a group of 32 currently depressed individuals. These findings suggest that even a mild negative mood in formerly depressed individuals can reinstate some of the cognitive features observed in depression itself.

Covariation bias for phylogenetic versus ontogenetic fear-relevant stimuli.

In the present study, two groups of 21 subjects with either high or low fear of both snakes (or spiders) and damaged electrical outlets/appliances participated in a two phase experiment. After reading a description of an illusory correlation experiment, subjects were asked to imagine themselves participating in it. They rated their expectations for the number of occasions on which slides of snakes, electrical outlets, and flowers would be followed by either a shock, tone, or nothing. As predicted, both high and low-fear subjects reported an expectancy bias for both phylogenetic and ontogenetic fear-relevant stimuli and shock. In the second phase subjects were actually exposed to the random slide/outcome presentation. Only high-fear subjects demonstrated a covariation bias which was specific to phylogenetic fear-relevant slides and shock, indicating all other biases were effectively attenuated.

Safety evaluation of phytosterol esters. Part 1. Assessment of oestrogenicity using a combination of in vivo and in vitro assays.

Phytosterols are natural constituents of the human diet, and as part of an extensive programme of safety evaluation studies investigating their use as a novel food ingredient, the possible oestrogenic effects of phytosterols have been investigated using a combination of in vitro and in vivo assays. Competitive binding with the immature rat uterine oestrogen receptor (ER) has been used to measure the ability of phytosterols to bind to ERs while the transcriptional activation of oestrogen-responsive genes has been examined in an oestrogen-inducible yeast screen. Phytosterols did not display any activity in these in vitro assays. Uterotrophic assays have been conducted to investigate the potential for phytosterols to elicit an oestrogenic response when administered orally to immature female rats (n = 10) at doses of 0, 5, 50 or 500 mg/kg/day for 3 consecutive days. Phytosterols (a well characterized mixture of beta-sitosterol, campesterol and stigmasterol) and phytosterol esters (the previous phytosterol mixture esterified with fatty acids from sunflower oil) did not exhibit oestrogenic activity in the immature female rat using uterine wet weight as the endpoint. Beta-oestradiol (0.4 mg/kg/day) consistently produced a significant increase in uterus weights. Coumestrol (a known phytoestrogen) was also tested as a weak positive control and produced a dose response at doses of 20, 40 and 80 mg/kg/day in the uterotrophic assay. In conclusion, we have shown that phytosterols do not bind to the ER and do not stimulate transcriptional activity of the human ER in a recombinant yeast strain. In addition, there was no indication of oestrogenicity from the uterotrophic assay when the material was administered by oral gavage to immature female rats.

Ultrastructure of normal monkey liver.

The normal ultrastructure of the liver of rhesus and cynomolgus monkeys is described. A classification of type A and B periportal hepatocytes is introduced together with a discussion of the high incidence of mitochondrial abnormalities. It is suggested that the rhesus monkey is more suitable as an experimental model than the cynomolgus since its liver ultrastructure is less variable.

The magnetocaloric effect and critical behaviour of the Mn(0.94)Ti(0.06)CoGe alloy.

Structural, magnetic and magnetocaloric properties of the Mn(0.94)Ti(0.06)CoGe alloy have been investigated using x-ray diffraction, DC magnetization and neutron diffraction measurements. Two phase transitions have been detected, at T(str) = 235 K and T(C) = 270 K. A giant magnetocaloric effect has been obtained at around T(str) associated with a structural phase transition from the low temperature orthorhombic TiNiSi-type structure to the high temperature hexagonal Ni(2)In-type structure, which is confirmed by neutron study. In the vicinity of the structural transition, at T(str), the magnetic entropy change, -ΔS(M) reached a maximum value of 14.8 J kg(-1) K(-1) under a magnetic field of 5 T, which is much higher than that previously reported for the parent compound MnCoGe. To investigate the nature of the magnetic phase transition around T(C) = 270 K from the ferromagnetic to the paramagnetic state, we performed a detailed critical exponent study. The critical components γ, ß and δ determined using the Kouvel-Fisher method, the modified Arrott plot and the critical isotherm analysis agree well. The values deduced for the critical exponents are close to the theoretical prediction from the mean-field model, indicating that the magnetic interactions are long range. On the basis of these critical exponents, the magnetization, field and temperature data around T(C) collapse onto two curves obeying the single scaling equation M(H,ε) = Îµ(ß)f ± (H/ε(ß+γ)).

Magnetism and magnetic structures of PrMn2Ge2-xSix.

The structural and magnetic properties of seven PrMn2Ge2-xSix compounds with Si concentrations in the range x = 0.0-2.0 have been investigated by x-ray diffraction, magnetic (5-350 K), differential scanning calorimetry (300-500 K) and neutron diffraction (3-480 K) measurements. Replacement of Ge by Si leads to a contraction of the unit cell and significant modifications to the magnetic states--a crossover from ferromagnetism at room temperature for Ge-rich compounds to antiferromagnetism for Si-rich compounds. The compositional dependence of the room temperature lattice parameters exhibits non-linear behaviour around x = 1.2, reflecting the presence of magnetovolume effects. Re-entrant ferromagnetism has been observed in both PrMn2Ge1.0Si1.0 and PrMn2Ge0.8Si1.2 compounds with co-existence of canted ferromagnetism and canted antiferromagnetism detected, with both compounds exhibiting a larger unit cell volume in the canted Fmc state than in the canted AFmc. Combined with earlier studies of this system, the magnetic phase diagram has been constructed over the full range of PrMn2Ge2-xSix compositions (x = 0.0-2.0) and over the temperature range of interest (T = 3-480 K). In common with other systems in the RMn2X2 series, the overall magnetic behaviour of PrMn2Ge2-xSix compounds is governed by the strong dependence of the magnetic couplings on the Mn-Mn spacing within the ab-plane. Both total manganese moment µ(Mn)(tot) and in-plane manganese moment µ(Mn)(ab) at 5 K are found to decrease with increasing Si content, which can be ascribed to the reduction of Mn-Mn separation distance and stronger Si-Mn hybridization compared with Ge-Mn hybridization. Pr site ferromagnetic ordering occurs for x < 1.6 below T(Pr)(C).

Critical magnetic transition in TbNi2Mn--magnetization and Mössbauer spectroscopy.

The structural and magnetic properties of the TbNi(2)Mn(x) series (0.9 ≤ x ≤ 1.10) have been investigated using x-ray diffraction, field- and temperature-dependent AC magnetic susceptibility, DC magnetization (5-340 K; 0-5 T) and (57)Fe Mössbauer spectroscopy (5-300 K). TbNi(2)Mn(x) crystallizes in the MgCu(2)-type structure (space group Fd3m). The additional contributions to the magnetic energy terms from transition-metal-transition-metal interactions (T-T) and rare-earth-transition-metal interactions (R-T) in RNi(2)Mn compounds contribute to their increased magnetic ordering temperatures compared with RNi(2) and RMn(2). Both the lattice constant a and the Curie temperature T(C) exhibit maximal values at the x = 1 composition indicating strong magnetostructural coupling. Analyses of the AC magnetic susceptibility and DC magnetization data of TbNi(2)Mn around the Curie temperature T(C) = 147 K confirm that the magnetic transition is second order with critical exponents ß = 0.77 ± 0.12, γ = 1.09 ± 0.07 and δ = 2.51 ± 0.06. These exponents establish that the magnetic interactions in TbNi(2)Mn are long range despite mixed occupancies of Tb and Mn atoms at the 8a site and vacancies. The magnetic entropy - ΔS(M) around T(C) is proportional to (µ(0)H/T(C))(2/3) in agreement with the critical magnetic analyses. The Mössbauer spectra above T(C) are fitted by two sub-spectra in agreement with refinement of the x-ray data while below T(C) three sub-spectra are required to represent the three inequivalent local magnetic environments.

Structures of membrane proteins.

The possible conformations of integral membrane proteins are restricted by the nature of their environment. In order to satisfy the requirement of maximum hydrogen bonding, those portions of the polypeptide chain which are in contact with lipid hydrocarbon must be organized into regions of regular secondary structure. As possible models of the intramembranous regions of integral membrane proteins, three types of regular structures are discussed. Two, the alpha helix and the beta-pleated sheet, are regularly occurring structural features of soluble proteins. The third is a newly proposed class of conformations called beta helices. These helices have unique features which make them particularly well-suited to the lipid bilayer environment. The central segment of the membrane-spanning protein glycophorin can be arranged into a beta helix with a hydrophobic exterior and a polar interior containing charged amino-acid side chains. Such structures could function as transmembrane ion channels. A model of the activation process based on a hypothetical equilibrium between alpha and beta helical forms of a transmembrane protein is presented. The model can accurately reproduce the kinetics and voltage dependence of the channels in nerve.

Doubly curved crystal point-focusing x-ray monochromators: geometrical and practical optics.

The geometrical optics of symmetrical point-focusing x-ray monochromators made with elastically bent ideal monocrystalline wafers in the geometry employed by Despujols and Berreman are reinvestigated. Sharpness of focus is limited mainly by accuracy of curvature of the crystal wafer and by thermal diffuse scattering. Monochromaticity is limited by these factors and by source and crystal dimensions in the plane of reflection and rarely by the inherent width of the reflection band of the curved crystal. Two existing monochromators reflect about 2-3% of the incident CuKalpha(1) radiation.