Digital-to-analog conversion by pulse-count modulation methods

Three low-cost digital-to-analog converters (DACs) are described and compared. These designs can easily be implemented in an integrated circuit: the conventional pulse-width modulation (PWM) DAC, the new pulse-count modulation (PCM) DAC and the first-order noise shaping (FONS) DAC. All three methods control the ratio of the sum of all pulse durations to the constant total period. As the pulse durations are integral multiples of a unit pulse, all three can be classified as pulse-count modulation methods. Block diagrams of all three DACs consisting of a simple digital circuit and a low-pass filter are presented. For a constant digital input value the worst case ripple of the filter output is used to calculate the cutoff frequency of the low-pass filter. Approximations for the 3 dB cutoff frequency of first-order, second-order and fourth-order Butterworth low-pass filters are given. The dynamic properties are analyzed in the time domain (settling time) and in the frequency domain (unfiltered output spectrum of a full-scale sine wave input). The main influences on the static accuracy are analyzed. A case study demonstrates the abilities of PCM and FONS     

High-power deuterium Raman laser at 632 nm

We demonstrate a continuous-wave deuterium Raman laser that generates more than 160 mW of Stokes output power despite severe thermal effects. This output power represents nearly an order-of-magnitude increase over any previously reported continuous-wave Raman laser and is the first such system to our knowledge that uses deuterium gas as the Raman medium. The high output power is achieved through careful consideration of the electronic feedback design, frequency actuators, and pump-laser intensity noise.     

Effects of gabapentin on the different components of peripheral and central neuropathic pain syndromes: a pilot study

Anticonvulsants are widely used in the treatment of neuropathic pain, and are assumed to act preferentially on lancinating, shooting pain. In the present study, the effects of gabapentin, a novel anticonvulsant, were evaluated systematically on both spontaneous and evoked pain in 18 patients with peripheral nerve injuries or central lesions. Gabapentin was administered orally in gradually increasing doses up to a maximum of 2,400 mg/day. Evaluations of spontaneous ongoing and paroxysmal pain, allodynia and hyperalgesia were performed at the beginning of the study ('baseline') and 6 weeks after the steady-state dose had been reached. Quantitative sensory tests were used to measure detection and pain thresholds to mechanical and thermal stimuli and the responses to suprathreshold stimuli. Gabapentin induced a moderate and statistically significant relief of ongoing spontaneous pain and was particularly effective in reducing paroxysmal pain. A striking finding was the significant effect on brush-induced and cold allodynia. In contrast, no effects were observed on detection and pain thresholds to static mechanical and hot stimuli. Side effects were generally minor and did not interfere with everyday activities. The present study suggests that gabapentin has preferential antihyperalgesic and/or antiallodynic effects, and is equally effective in pain due to peripheral nerve injuries and central lesions.     

Apropos of a rare case of bilateral orbital metastasis of malignant melanoma of the choroid

We report a case of bilateral orbital metastasis from an ocular choroidal melanoma which had required enucleation eight years earlier. This uncommon case was fully documented with clinical, radiological and pathological studies. Magnetic resonance imaging was particularly contributive showing very characteristic sequences. The patient was given focal palliative cobalt radiotherapy. We compared this case with previous reports in the litterature.     

Prediction of signal peptide functional properties: a study of the orientation and angle of insertion of yeast invertase mutants and human apolipoprotein B signal peptide variants

A number of studies have introduced mutations into the yeastinvertase signal peptide, using it as a model system to elucidatefeatures for targeting, translocation and intracellular transportUsing molecular modelling of the invertase signal peptide wehave analysed the hydrophobicity potential and the change inthe dielectric constant of the energy transfer, when the moleculemoves from a hydrophobic to a hydrophilic phase at the simulatedhydrophobic-hydrophilic interface. This modelling has been carriedout on wild type and mutant invertase signal peptides of alteredfunction, previously reported in the literature. While the predictedangle of insertion correlates with the measured extent of invertasesecretion, with an optimum angle of 45, mutations that changethe angle of orientation reduce the extent of invertase secretion.We have applied these same molecular modelling principles tothe naturally occurring variants of the human apolipo-proteinB (apoB) signal peptide, that confer a secretion defective phenotypewhen fused to yeast invertase and expressed in yeast. Our modellingthus identifies a strong correlation between the predicted angleof insertion of the signal peptide into the membrane and itsability to direct secretion.     

Sexual and asexual development of Cryptosporidium parvum in five oocyst- or sporozoite-infected human enterocytic cell lines

The human enterocytic cell lines Caco-2, HT29, HCT8 and the Caco-2 clones TC7 and PF11 were studied for their ability to support Cryptosporidium parvum development. Following the addition in cultures of either oocysts or excysted sporozoites, immunofluorescent and transmission electron microscopy revealed the presence of all stages of the parasite life cycle by both procedures, and no difference in the ratio of infected cells was found among cell lines. More oocysts were seen in cell monolayers infected with oocysts than with sporozoites (p < 0.0001). The number of meronts observed was the same after either oocysts or sporozoites inoculation. Data suggest that the two methods yield a same cell infection rate.     

Prediction of the antigenic sites of the cystic fibrosis transmembrane conductance regulator protein by molecular modelling

Antibodies are powerful tools for studying the in situ localizationand physiology of proteins. The prediction of epitopes by molecularmodelling has been used successfully for the papilloma virus,and valuable antibodies have been raised [Muller et aL (1990)J. Gen. Virol, 71, 2709–2717]. We have improved the modellingapproach to allow us to predict epitopes from the primary sequencesof the cystic fibrosis transmembrane conductance regulator.The procedure involves searching for fragments of primary sequenceslikely to make amphipathic secondary structures, which are hydrophilicenough to be at the surface of the folded protein and thus accessibleto antibodies. Amphipathic helices were predicted using themethods of Berzofsky, Eisenberg and Jahnig. Their hydrophobichydrophilicinterface was calculated and drawn, and used to predict theorientation of the helices at the surface of the native protein.Amino acids involved in turns were selected using the algorithmof Eisenberg. Tertiary structures were calculated using ‘FOLDING’,a software developed by R.Brasseur for the prediction of smallprotein structures [Brasseur (1995) J. MoL Graphics, in press].We selected sequences that folded as turns with at least fiveprotruding polar residues. One important property of antibodiesis selectivity. To optimize the selectivity of the raised antibodies,each sequence was screened for similarity (FASTA) to the proteinsequences from several databanks. Ubiquitous sequences werediscarded. This approach led to the identification of 13 potentialepitopes in the cystic fibrosis transmembrane conductance regulator:seven helices and six loops.     

Congenital toxoplasmosis and seroconversion at the end of pregnancy: clinical observations

OBJECTIVE: To determine the knowledge of HIV-disease management and the adherence to contemporary guidelines among British Columbia physicians whose practices focused on HIV/AIDS. DESIGN: Self-administered mail survey. PARTICIPANTS: All 659 physicians registered in a province-wide HIV/AIDS drug treatment program. OUTCOME MEASURES: Data on demographic and personal characteristics of respondents, level of HIV-related experience, use of preventive vaccinations and tests, and preferred approaches to the prophylaxis and treatment of common opportunistic infections. Knowledge scores in 4 areas of patient care, as well as an overall score, were computed by comparing respondents' answers with the therapeutic strategies recommended at the time of the survey. Associations between physician characteristics and knowledge scores were identified by linear regression analysis. RESULTS: Of the 659 physicians surveyed, 65% returned responses: only 38% returned completed surveys while a further 27% returned a follow-up survey that asked nonrespondents about their demographic characteristics and HIV-related experience. Scores for specific areas of patient management ranged from 29% for the treatment of opportunistic infections to 62% for preventive measures, with a mean overall score of 47%. Physician knowledge in all areas of patient care was associated with the number of HIV-positive patients in the practice (p = 0.003 to p < 0.001). Physicians who were younger were more knowledgeable regarding preventive measures (p = 0.001); those whose practice location was in Vancouver had a greater knowledge of prophylaxis (p = 0.047); and those who had medical specialty training were more knowledgeable about the treatment of opportunistic infections (p = 0.009). CONCLUSIONS: There is substantial disparity in how physicians approach the management of HIV and related conditions. Deviations from therapeutic guidelines are common and may be associated with physician characteristics, particularly lack of experience in managing HIV.     

Prediction of epitopes and production of monoclonal antibodies against gastric H,K-ATPase

Monoclonal antibodies (mAbs) were produced against gastric H,K-ATPase using a theoretical and experimental strategy based on prediction of linear epitopes by molecular modelling followed by production of anti- peptide antibodies. By analysing the alpha subunit sequence, we predicted several epitopes corresponding to amino acids K519-L533, E543- Y553 and S786-L798 and produced monoclonal antibodies HK519, HK543 and HK786. All three react against gastric H,K-ATPase in RaLISA, immunohistochemistry and Western blots demonstrating that they recognize the native and the SDS-denatured ionic pump and that the epitopes are located at the surface of the native ATPase. Antibody Kd are in the range 6-10x10(-8) M. Monoclonal antibody HK519 is a competitive inhibitor of ATP, in agreement with ATP binding to K519. Neither mAb 543, nor mAb 786 inhibit the ATPase activity. Monoclonal antibody 95111, whose epitope is mapped between residues C529 and E561, competes with mAb HK543 but not with the other two. We suggest that the 95111 epitope is overlapping or very close to the HK543-553 sequence. Induction of E1 conformer by binding FITC to K519 increases the number of mAb 95111 and mAb HK543 epitopes but not that of mAb 786, supporting the fact that the fragment E543-Y553 changes accessibility, maybe during the E1-E2 transconformation.