Sick building syndrome--know your ventilation rates.

To summarise, although the occurrence of sick building syndrome could be due to a range of causal factors, research shows that it is probable that low outside air intake volume and pollution generated by the ventilation system and the building contents play a role in producing its effects. This being so, it is important that the flow of outside air into the building and the distribution of fresh or mixed air around the interior are known and controlled. However it is difficult to control the flow rate by conventional means and the use of fixed minimum position dampers is not likely to maintain a minimum fresh air flow rate under most wind velocities. What is needed is a control system which relies on direct measurement of air flow rate connected to a modulated minimum outside air intake damper to provide a constant and verifiable volume of fresh air flow. Flow sensors also open up the possibility of direct measurement and control of return and mixed air volumes and of course the flow of air anywhere else in the system.     

Design and synthesis of a series of potent and orally bioavailable noncovalent thrombin inhibitors that utilize nonbasic groups in the P1 position

As part of an ongoing effort to prepare therapeutically useful orally active thrombin inhibitors, we have synthesized a series of compounds that utilize nonbasic groups in the P1 position. The work is based on our previously reported lead structure, compound 1, which was discovered via a resin-based approach to varying P1. By minimizing the size and lipophilicity of the P3 group and by incorporating hydrogen-bonding groups on the N-terminus or on the 2-position of the P1 aromatic ring, we have prepared a number of derivatives in this series that exhibit subnanomolar enzyme potency combined with good in vivo antithrombotic and bioavailability profiles. The oxyacetic amide compound 14b exhibited the best overall profile of in vitro and in vivo activity, and crystallographic studies indicate a unique mode of binding in the thrombin active site.     

Detection of polyomaviral DNA in clinical samples from immunocompromised patients: correlation with clinical disease

Characterization of the region between HLA-B and the TNF loci in the human MHC revealed the presence of duplicated loci, named CL1 and CL2, that included repeat sequences. Development and use of a PCR typing methodology that amplified both CL microsatellites simultaneously indicated that PCR product patterns analysed on native agarose gels were allelic (Abraham et al., 1992). The purpose of the current study was to determine the molecular explanation for the unique patterns achieved. Sequence analysis of the CL1 locus from 32 chromosomes representing 10 ancestral haplotypes indicated that six alleles were present. The CL microsatellites also provided an opportunity to study the evolutionary relationships between MHC haplotypes from different racial groups. Sequence comparison of closely related ancestral haplotypes from different racial groups suggested that the CL1 microsatellite has not changed in the period since divergence.     

Novel oxide-dispersion-strengthened copper alloys from rapidly solidified precursors: Part 1. Microstructural development

ZrO₂, Y₂O₃, and rare earth oxides with related structures are attractive candidates for dispersion strengthening of copper alloys but pose significant processing challenges owing to the low solubility of the oxide-forming elements in Cu. It is shown that the problems may be circumvented by a synthesis approach coupling rapid solidification and internal oxidation, followed by standard powder metallurgy consolidation. Cu-Zr and Cu-Y alloys were melt spun into ribbons ∼-50-to 150-Μm thick and internally oxidized at 1023 to 1223 K to yield ∼1 vol pct of ZrO₂ or Y₂O₃ particles ranging in size from 5 nm up to ∼3150 nm. The coarser oxides result from direct oxidation of the intermetallic segregate, whereas the finer ones are generated by a dissolution-reprecipitation process. The relative proportions of fine and coarse oxides and the homogeneity of the distribution are related to segregation scale in the melt-spun ribbon and the relative permeabilities of oxygen and the oxidizable element in the alloy, which depend on the internal oxidation temperature. The oxide dispersoids were mostly cubic zirconia or cubic yttria and exhibited predominantly cube-on-cube orientation relationships with the matrix. Analysis of particle shapes revealed that the dominant interfaces are of the type {001}_OX ∥ {001}_Cu and {1ˉ11}_OX ∥ {1ˉ11}_Cu and could be explained by image charge interaction concepts. Extrusion produced an elongated grain structure but no significant changes in the oxide distribution. MICHAEL S. NAGORKA, formerly Graduate Research Assistant, High Performance Composites Center, Materials Department, College of Engineering, University of California at Santa Barbara     

MRI of the foot and ankle

The foot and ankle are among the hardest of all areas to image because of the complex three-dimensional anatomy. Magnetic resonance imaging (MRI), with its multiplanar capabilities, excellent soft-tissue contrast, ability to image bone marrow, noninvasiveness, and lack of ionizing radiation, has become a valuable tool in evaluating patients with foot and ankle problems. MRI is more specific than bone scintigraphy and provides more information than ultrasound and computed tomography. Arthroscopy of the ankle is limited to the articular surface and joint space. MRI allows a global evaluation of the bones, tendons, ligaments, and other structures with a single examination that exceeds the capabilities of all other available techniques. This monograph was written to provide a useful guide to basic technique, indications, positioning, anatomy, and interpretation of foot and ankle MRI. The first part describes the performance of the MRI examination with reference to the positioning of the foot, types of coils, and advantages and disadvantages of the different sequences and imaging planes. The next section was written by an experienced foot and ankle orthopedic surgeon and outlines the indications for MRI for the common foot and ankle symptom complexes and the information that the surgeon hopes to obtain from the study. This is followed by a review of pertinent anatomy, as it applies to imaging, with emphasis on osseous structures, ligaments, tendons, and muscles. The final section is a comprehensive review of the common pathologic conditions encountered in the foot and ankle. We hope that radiologists and radiologists-in-training find this article a useful reference tool and gain a better understanding of this complex area of musculoskeletal imaging.     

Crucial role of tumor necrosis factor (TNF) receptor 2 and membrane-bound TNF in experimental cerebral malaria

Tumor necrosis factor (TNF) has been implicated in the pathogenesis of experimental cerebral malaria (CM), but the respective role of its two types of receptors has not been established. A significant increase in the expression of TNF-receptor 2 (TNFR2, p75), but not of TNFR1 (p55), was found on brain microvessels at the time of CM in susceptible animals. Moreover, mice genetically deficient for TNFR2 (Tnfr2null) were significantly protected from experimental CM, in contrast to TNFR1-deficient (Tnfr1null) mice, which were as susceptible as wild-type mice. To identify the factors involved in the protection from CM conferred by the lack of TNFR2, we assessed in both knockout and control mice the serum concentrations of mediators that are critical for the development of CM, as well as the up-regulation of intercellular adhesion molecule-1 (ICAM-1) in the brain microvessels. No significant difference in serum levels of TNF and interferon-gamma was found between infected wild-type and Tnfr1null or Tnfr2null mice. Interestingly, the pronounced ICAM-1 up-regulation and leukocyte sequestration, typically occurring in brain microvessels of CM-susceptible animals, was detected in infected control and Tnfr1null mice-both of which developed CM-whereas no such ICAM-1 up-regulation or leukocyte sequestration was observed in Tnfr2null mice, which were protected from CM. Making use of microvascular endothelium cells (MVEC) isolated from wild-type, Tnfr1null or Tnfr2null mice, we show that soluble TNF requires the presence of both TNF receptors, whereas membrane-bound TNF only needs TNFR2 for TNF-mediated ICAM-1 up-regulation in brain MVEC. Thus, only in MVEC lacking TNFR2, neither membrane-bound nor soluble TNF cause the up-regulation of ICAM-1 in vitro. In conclusion, these results indicate that the interaction between membrane TNF and TNFR2 is crucial in the development of this neurological syndrome.