Chemical synthesis, antibacterial activity and conformation of diptericin, an 82-mer peptide originally isolated from insects

The small amounts of antibacterial peptides that can be isolated from insects do not allow detailed studies of their range of activity, side-chain sugar requirements, or their conformation, factors that frequently play roles in the mode of action. In this paper, we report the solid-phase step-by-step synthesis of diptericin, an 82-mer peptide, originally isolated from Phormia terranovae. The unglycosylated peptide was purified to homogeneity by conventional reversed-phase high performance liquid chromatography, and its activity spectrum was compared to that Of synthetic unglycosylated drosocin, which shares strong sequence homology with diptericin's N-terminal domain. Diptericin appeared to have antibacterial activity:for only a limited number of Gram-negative bacteria. Diptericin's submicromolar potency against Escherichia coli strains indicated that, in a manner similar to drosocin, the presence of the carbohydrate side chain is not,necessary to kill bacteria. Neither the N-terminal, drosocin-analog fragment, nor the C-terminal, glycine-rich attacin-analog region was active against any of the bacterial strains studied, regardless of whether the Gal-GalNAc disaccharide units were attached. This suggested that the active site of diptericin fell outside the drosocin or attacin homology domains. In addition, the conformation of diptericin did not seem to play a role in the antibacterial activity, as was demonstrated by the complete lack of ordered structure by two-dimensional nuclear magnetic resonance spectroscopy and circular dichroism. Diptericin completely killed bacteria within I h, considerably faster than drosocin and the attacins; unlike some other, fast-acting antibacterial peptides, diptericin did not lyse normal mammalian cells. Taken together, these data suggest diptericin does not belong to any known class of antibacterial peptides.

Approach to designing rotating drum bioreactors for solid-state fermentation on the basis of dimensionless design factors

The development of large-scale solid-stale fermentation (SSF) processes is hampered by the lack of simple tools for the design of SSF bioreactors. The use of semifundamental mathematical models to design and operate SSF bioreactors can be complex. In this work, dimensionless design factors are used to predict the effects of scale and of operational variables on the performance of rotating drum bioreactors. The dimensionless design factor (DDF) is a ratio of the rate of heat generation to the rate of heat removal at the time of peak heat production. It can be used to predict maximum temperatures reached within the substrate bed for given operational variables. Alternatively, given the maximum temperature that can be tolerated during the fermentation, it can be used to explore the combinations of operating variables that prevent that temperature from being exceeded. Comparison of the predictions of the DDF approach with literature data for operation of rotating drums suggests that the DDF is a useful tool. The DDF approach was used to explore the consequences of three scale-up strategies on the required air flow rates and maximum temperatures achieved in the substrate bed as the bioreactor size was increased on the basis of geometric similarity. The first of these strategies was to maintain the superficial flow rate of the process air through the drum constant. The second was to maintain the ratio of volumes of air per volume of bioreactor constant. The third strategy was to adjust the air flow rate with increase in scale in such a manner as to maintain constant the maximum temperature attained in the substrate bed during the fermentation. (C) 2000 John Wiley & Sons, Inc.

Incorporating phase retardation effects into radiofrequency resonator models: application to magnetic resonance microscopy

A method is presented for including path propagation effects into models of radiofrequency resonators for use in magnetic resonance imaging. The method is based on the use of Helmholtz retarded potentials and extends our previous work on current density models of resonators based on novel inverse finite Hilbert transform solutions to the requisite integral equations. Radiofrequency phase retardation effects are most pronounced at high field strengths (frequencies) as are static field perturbations due to the magnetic materials in the resonators themselves. Both of these effects are investigated and a novel resonator structure presented for use in magnetic resonance microscopy.

Mesoionic pyridopyrimidinylium and pyridooxazinylium olates and non-mesoionic pyridopyrimidinones. Structures in the solid state, solution, and matrices

X-Ray crystal structures, C-13 NMR spectra and theoretical calculations (B3LYP/6-31G*) are reported for the mesoionic (zwitterionic) pyridopyrimidinylium- and pyridooxazinyliumolates 2a, 3a and 5a,b as well as the enol ether 11b and the enamine 11c. The 1-NH compounds like 1a, 2a and 3a exist in the mesoionic form in the crystal and in solution, but the OH tautomers such as 1b and 2b dominate in the gas phase as revealed by the Ar matrix IR spectra in conjunction with DFT calculations. All data indicate that the mesoionic compounds can be regarded as intramolecular pyridine-ketene zwitterions (cf. 16 --> 17) with a high degree of positive charge on the pyridinium nitrogen, a long pyridinium N-CO bond (ca. 1.44-1.49 Angstrom), and normal C=O double bonds (ca. 1.22 Angstrom). All mesoionic compounds exhibit a pronounced tilting of the olate C=O groups (the C=O groups formally derived from a ketene) towards the pyridinium nitrogen, giving NCO angles of 110-118 degrees. Calculations reveal a hydrogen bond with 6-CH, analogous to what is found in ketene-pyridine zwitterions and the C3O2-pyridine complex. The 2-OH tautomers of type 1b, 2b, and 11 also show a high degree of zwitterionic character as indicated by the canonical structures 11 12.

Magnetic resonance imaging and diseases of the liver and biliary tract. Part 2. Magnetic resonance cholangiography and angiography and conclusions

Magnetic resonance cholangiography (MRC) relies on the strong T-2 signal from stationary liquids, in this case bile, to generate images. No contrast agents are required, and the failure rate and risk of serious complications is lower than with endoscopic retrograde cholangiopancreatography (ERCP). Data from MRC can be summated to produce an image much like the cholangiogram obtained by using ERCP. In addition, MRC and conventional MRI can provide information about the biliary and other anatomy above and below a biliary obstruction. This provides information for therapeutic intervention that is probably most useful for hilar and intrahepatic biliary obstruction. Magnetic resonance cholangiography appears to be similar to ERCP with respect to sensitivity and specificity in detecting lesions causing biliary obstruction, and in the diagnosis of choledocholithiasis. It is also suited to the assessment of biliary anatomy (including the assessment of surgical bile-duct injuries) and intrahepatic biliary pathology. However, ERCP can be therapeutic as well as diagnostic, and MRC should be limited to situations where intervention is unlikely, where intrahepatic or hilar pathology is suspected, to delineate the biliary anatomy prior to other interventions, or after failed or inadequate ERCP. Magnetic resonance angiography (MRA) relies on the properties of flowing liquids to generate images. It is particularly suited to assessment of the hepatic vasculature and appears as good as conventional angiography. It has been shown to be useful in delineating vascular anatomy prior to liver transplantation or insertion of a transjugular intrahepatic portasystemic shunt. Magnetic resonance angiography may also be useful in predicting subsequent variceal haemorrhage in patients with oesophageal varices. (C) 2000 Blackwell Science Asia Pty Ltd.

Processing of urinary pheromones in Antechinus stuartii (Marsupialia: Dasyuridae): Functional magnetic resonance imaging of the brain

Little is known of the neural mechanisms of marsupial olfaction. However, functional magnetic resonance imaging (fMRI) has made it possible to visualize dynamic brain function in mammals without invasion. In this study, central processing of urinary pheromones was investigated in the brown antechinus, Antechinus stuartii, using fMRI. Images were obtained from 18 subjects (11 males, 7 females) in response to conspecific urinary olfactory stimuli. Significant indiscriminate activation occurred in the accessory olfactory bulb, entorhinal, frontal, and parietal cortices in response to both male and female urine. The paraventricular nucleus of hypothalamus, ventrolateral thalamic nucleus, and medial preoptic area were only activated in response to male urine. Results of this MRI study indicate that projections of accessory olfactory system are activated by chemo-sensory cues. Furthermore, it appears that, based on these experiments, urinary pheromones may act on the hypothalamo-pituitary-adrenocortical axis via the paraventricular nucleus of the hypothalamus and may play an important role in the unique life history pattern of A. stuartii. Finally, this study has demonstrated that fMRI may be a powerful tool for investigations of olfactory processes in mammals.

Cost effectiveness of adding magnetic resonance imaging to the usual management of suspected scaphoid fractures

Objective: To determine the cost effectiveness of a magnetic resonance imaging scan (MRI) within 5 days of injury compared with the usual management of occult scaphoid fracture. Methods: All patients with suspected scaphoid fractures in five hospitals were invited to participate in a randomised controlled trial of usual treatment with or without an MRI scan. Healthcare costs were compared, and a cost effectiveness analysis of the use of MRI in this scenario was performed. Results: Twenty eight of the 37 patients identified were randomised: 17 in the control group, 11 in the MRI group. The groups were similar at baseline and follow up in terms of number of scaphoid fractures, other injuries, pain, and function. Of the patients without fracture, the MRI group had significantly fewer days immobilised: a median of 3.0 (interquartile range 3.0-3.0) v 10.0 (7-12) in the control group (p = 0.006). The MRI group used fewer healthcare units (median 3.0, interquartile range 2.0-4.25) than the control group (5.0, 3.0-6.5) (p = 0.03 for the difference). However, the median cost of health care in the MRI group ($594.35 AUD, $551.35-667.23) was slightly higher than in the control group ($428.15, $124.40-702.65) (p = 0.19 for the difference). The mean incremental cost effectiveness ratio derived from this simulation was that MRI costs $44.37 per day saved from unnecessary immobilisation (95% confidence interval $4.29 to $101.02). An illustrative willingness to pay was calculated using a combination of the trials measure of the subjects' individual productivity losses and the average daily earnings. Conclusions: Use of MRI in the management of occult scaphoid fracture reduces the number of days of unnecessary immobilisation and use of healthcare units. Healthcare costs increased non-significantly in relation to the use of MRI in this setting. However, when productivity losses are considered, MRI may be considered cost effective, depending on the individual case.

Fronto-parietal activation in attention-deficit hyperactivity disorder, combined type: functional magnetic resonance imaging study

A functional magnetic resonance imaging mental rotation paradigm was used to investigate the patterns of activation of fronto-parietal brain areas in male adolescents with attention-deficit hyperactivity disorder, combined type (ADHD-CT) compared with age-, gender-, handedness- and performance IQ-matched healthy controls. The ADHD-CT group had (a) decreased activation of the 'action-attentional' system (including Brodmann's areas (BA) 46, 39,40) and the superior parietal (BA7) and middle frontal (BA10) areas and (b) increased activation of the posterior midline attentional system. These different neuroactivation patterns indicate widespread frontal, striatal and parietal dysfunction in adolescents with ADHD-CT. Declaration of interest None.

Molecular orbital calculations of two-electron states for P-donor solid-state spin qubits

We theoretically study the Hilbert space structure of two neighboring P-donor electrons in silicon-based quantum computer architectures. To use electron spins as qubits, a crucial condition is the isolation of the electron spins from their environment, including the electronic orbital degrees of freedom. We provide detailed electronic structure calculations of both the single donor electron wave function and the two-electron pair wave function. We adopted a molecular orbital method for the two-electron problem, forming a basis with the calculated single donor electron orbitals. Our two-electron basis contains many singlet and triplet orbital excited states, in addition to the two simple ground state singlet and triplet orbitals usually used in the Heitler-London approximation to describe the two-electron donor pair wave function. We determined the excitation spectrum of the two-donor system, and study its dependence on strain, lattice position, and interdonor separation. This allows us to determine how isolated the ground state singlet and triplet orbitals are from the rest of the excited state Hilbert space. In addition to calculating the energy spectrum, we are also able to evaluate the exchange coupling between the two donor electrons, and the double occupancy probability that both electrons will reside on the same P donor. These two quantities are very important for logical operations in solid-state quantum computing devices, as a large exchange coupling achieves faster gating times, while the magnitude of the double occupancy probability can affect the error rate.

Calculating current densities and fields produced by shielded magnetic resonance imaging probes

A method is presented for computing the fields produced by radio frequency probes of the type used in magnetic resonance imaging. The effects of surrounding the probe with a shielding coil, intended to eliminate stray fields produced outside the probe, are included. An essential feature of these devices is the fact that the conducting rungs of the probe are of finite width relative to the coil radius, and it is therefore necessary to find the distribution of current within the conductors as part of the solution process. This is done here using a numerical method based on the inverse finite Hilbert transform, applied iteratively to the entire structure including its shielding coils. It is observed that the fields are influenced substantially by the width of the conducting rungs of the probe, since induced eddy currents within the rungs become more pronounced as their width is increased. The shield is also shown to have a significant effect on both the primary current density and the resultant fields. Quality factors are computed for these probes and compared with values measured experimentally.

A nanometre-scale non-periodic structural variation in high temperature superconducting ceramics and the implications for properties

Non-periodic structural variation has been found in the high T-c cuprates, YBa2Cu3O7-x and Hg0.67Pb0.33Ba2Ca2Cu3O8+delta, by image analysis of high resolution transmission electron microscope (HRTEM) images. We use two methods for analysis of the HRTEM images. The first method is a means for measuring the bending of lattice fringes at twin planes. The second method is a low-pass filter technique which enhances information contained by diffuse-scattered electrons and reveals what appears to be an interference effect between domains of differing lattice parameter in the top and bottom of the thin foil. We believe that these methods of image analysis could be usefully applied to the many thousands of HRTEM images that have been collected by other workers in the high temperature superconductor field. This work provides direct structural evidence for phase separation in high T-c cuprates, and gives support to recent stripes models that have been proposed to explain various angle resolved photoelectron spectroscopy and nuclear magnetic resonance data. We believe that the structural variation is a response to an opening of an electronic solubility gap where holes are not uniformly distributed in the material but are confined to metallic stripes. Optimum doping may occur as a consequence of the diffuse boundaries between stripes which arise from spinodal decomposition. Theoretical ideas about the high T-c cuprates which treat the cuprates as homogeneous may need to be modified in order to take account of this type of structural variation.

Calculation of product state distributions from resonance decay via Lanczos subspace filter diagonalization: Application to HO2

Resonance phenomena associated with the unimolecular dissociation of HO2 have been investigated quantum-mechanically by the Lanczos homogeneous filter diagonalization (LHFD) method. The calculated resonance energies, rates (widths), and product state distributions are compared to results from an autocorrelation function-based filter diagonalization (ACFFD) method. For calculating resonance wave functions via ACFFD, an analytical expression for the expansion coefficients of the modified Chebyshev polynomials is introduced. Both dissociation rates and product state distributions of O-2 show strong fluctuations, indicating the dissociation of HO2 is essentially irregular. (C) 2001 American Institute of Physics.

A novel target-field method for finite-length magnetic resonance shim coils: I. Zonal shims

This paper presents a new approach for the design of genuinely finite-length shim and gradient coils, intended for use in magnetic resonance imaging equipment. A cylindrical target region is located asymmetrically, at an arbitrary position within a coil of finite length. A desired target field is specified on the surface of that region, and a method is given that enables winding patterns on the surface of the coil to be designed, to produce the desired field at the inner target region. The method uses a minimization technique combined with regularization, to find the current density on the surface of the coil. The method is illustrated for linear, quadratic and cubic magnetic target fields located asymmetrically within a finite-length coil.

The stochastic design of force-minimized compact magnets for high-field magnetic resonance imaging applications

New designs for force-minimized compact high-field clinical MRI magnets are described. The design method is a modified simulated annealing (SA) procedure which includes Maxwell forces in the error function to be minimized. This permits an automated force reduction in the magnet designs while controlling the overall dimensions of the system. As SA optimization requires many iterations to achieve a final design, it is important that each iteration in the procedure is rapid. We have therefore developed a rapid force calculation algorithm. Novel designs for short 3- and 4-T clinical MRI systems are presented in which force reduction has been invoked. The final designs provide large homogeneous regions and reduced stray fields in remarkable short magnets. A shielded 4-T design that is approximately 30% shorter than current designs is presented. This novel magnet generates a full 50-cm diameter homogeneous region.