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Inhalation exposure and risk from mobile source air toxics in future years.

Modeling of inhalation exposure and risks resulting from exposure to mobile source air toxics can be used to evaluate impacts of reductions from control programs on overall risk, as well as changes in relative contributions of different source sectors to risk, changes in contributions of different pollutants to overall risk, and changes in geographic distributions of risk. Such analysis is useful in setting regulatory priorities, and informing the decision-making process. In this paper, we have conducted national-scale air quality, exposure, and risk modeling for the US in the years 2015, 2020, and 2030, using similar tools and methods as the 1999 National-Scale Air Toxics Assessment. Our results suggest that US Environmental Protection Agency emission control programs will substantially reduce average inhalation cancer risks and potential noncancer health risks from exposure to mobile source air toxics. However, cancer risk and noncancer hazard due to inhalation of air toxics will continue to be a public health concern.

Air Pollutants↗

Screening potential blood donors at risk for human immunodeficiency virus.

Even though all blood donated for transfusion is tested for the presence of human immunodeficiency virus (HIV) antibodies, there exists a period of time after infection by the virus before these antibodies can be detected. Blood donated during this window period is capable of transmitting the virus. Therefore, the blood of persons who are at risk for acquired immune deficiency syndrome (AIDS) should not enter the blood supply. Over a period of 4 months, 6573 potential blood donors who entered fixed and mobile blood collection sites in two cities were exposed to alternative interventions the aim of which was to exclude persons at risk for AIDS. We compared the interventions to one another and to existing materials in terms of the numbers of at-risk persons who did or did not donate for transfusion, the amount of attention paid to the materials, the scores on a comprehension test, and the self-reports by the subjects of attitudes towards the various interventions. At-risk donors who were asked direct AIDS risk behavior questions in addition to the current health history questions were more likely to be screened out than those who underwent alternative health history interviews (p less than 0.01). Potential donors paid more attention to the experimental brochures than to the experimental video or current materials (p less than 0.05). Comprehension scores were better for the new brochure and the video than for the current brochure (p less than 0.05). Donors were not offended by the experimental interventions.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗

Evaluation of heavy metal availability prior to an in situ soil phytoremediation program.

Metal mobility and the fractionation of elements and thus the biological uptake of Zn, Pb and Cd by plants were investigated using a simplified analytical procedure for soluble and bioavailable metals using a four-step sequential extraction procedure. Results showed that there was a low proportion of immediately soluble metals, as well as a high proportion of metals that could be released and would so be available for plant uptake. In the sequential extraction procedure, considering the total partition, there was a large proportion of Pb, Cd and Zn extracted in a readily mobile form. In acidic soils the content of metals in ready mobile form (exchangeable-bound to carbonates as well as to Fe and Mn oxides) and bound to organic matter constitutes an important source of potentially available elements. The same pattern was observed in alkaline soils, where almost 80% of the metals could be remobilized and be potentially available to plants. Knowing the metal partitioning and mobility of heavy metals it is very important for evaluating the phytoremediation efficiency.

Biodegradation, Environmental↗

Electromyographic study on end-to-end anastomosis of the recurrent laryngeal nerve in dogs.

The effectiveness of anastomosis of a divided recurrent laryngeal nerve was studied with electromyography as well as visual observation. Results obtained through this investigation permitted the following conclusions: 1. Regenerated potentials were recorded from both the involved thyroarytenoid and posterior cricoarytenoid muscles for an average of 5 to 6 weeks postoperatively. 2. Average onset of recovery of spontaneous adduction was 10 weeks following surgery, and four dogs regained complete recovery of adduction in 13 to 14 weeks. Average onset of recovery of spontaneous abduction was 11.8 weeks postoperatively, and none of the four dogs displayed complete recovery. 3. The time delay between the onset of regenerated potentials and onset of recovery of cord mobility averaged 4.2 weeks for adduction and 6.4 weeks for abduction. 4. Incomplete recovery of movements of the reinnervated vocal cord might be due to an inadequate number of effective motor units. 5. End-to-end anastomosis of the recurrent laryngeal nerve can be performed as one method of reinnervating the denervated intrinsic laryngeal muscles, and further histological studies should be carried out to determine if the regenerated nerve fibers actually have decreased.

Action Potentials↗

Regulation of elastinolytic cysteine proteinase activity in normal and cathepsin K-deficient human macrophages.

Human macrophages mediate the dissolution of elastic lamina by mobilizing tissue-destructive cysteine proteinases. While macrophage-mediated elastin degradation has been linked to the expression of cathepsins L and S, these cells also express cathepsin K, a new member of the cysteine proteinase family whose elastinolytic potential exceeds that of all known elastases. To determine the relative role of cathepsin K in elastinolysis, monocytes were differentiated under conditions in which they recapitulated a gene expression profile similar to that observed at sites of tissue damage in vivo. After a 12-d culture period, monocyte-derived macrophages (MDMs) expressed cathepsin K in tandem with cathepsins L and S. Though cysteine proteinases are acidophilic and normally confined to the lysosomal network, MDMs secreted cathepsin K extracellularly in concert with cathepsins L and S. Simultaneously, MDMs increased the expression of vacuolar-type H(+)-ATPase components, acidified the pericellular milieu, and maintained extracellular cathepsin K in an active form. MDMs from a cathepsin K-deficient individual, however, retained the ability to express, process, and secrete cathepsins L and S, and displayed normal elastin-degrading activity. Thus, matrix-destructive MDMs exteriorize a complex mix of proteolytic cysteine proteinases, but maintain full elastinolytic potential in the absence of cathepsin K by mobilizing cathepsins L and S.

Cathepsin B↗

General rules for the optimal external porosity of LC supports.

We present a series of numerically calculated plate height and flow resistance data obtained for an idealized chromatographic support mimic with variable bed porosity (0.3 </= epsilon </= 0.9), yielding a unique insight into how the main chromatographic performance parameters can be expected to vary with the external bed porosity, unbiased by any differences in molecular diffusivity or retention factor. The influence of pore heterogeneity effects is considered as well. It is found that the product h(min)nu(opt) depends only very weakly on epsilon and on the degree of pore heterogeneity. It is also found that the minimal separation impedance E(min) decreases monotonically with epsilon. This shows that the minimal plate height increase that can be expected for large porosity systems is always more than compensated by their reduced flow resistance, in agreement with the current observations in real silica monolith columns. Using the computed plate height data in an optimization analysis, it is found that large porosity supports can always potentially yield shorter analysis times or larger plate numbers than small porosity supports but need submicrometer feature sizes to actually achieve this. Assuming a lower limit on the producible or useable structural feature sizes, it is found that small N separations can best be performed with a small porosity packing, whereas large N separations require a large porosity packing if the column length (L) is left free. A plot yielding epsilon(opt) as a function of the required plate number has been established, showing that roughly epsilon(opt) approximately log(N) in both the ordered and the disordered support cases. It is also shown that the maximal increase in peak capacity ever to be expected from the use of high porosity supports is a factor of 2 (if the mobile-phase viscosity can be kept constant), potentially to be increased by a factor of 1.5 by increasing the homogeneity of the packing.

Journal Article↗

Discrete gap breathers in a diatomic Klein-Gordon chain: stability and mobility.

A one-dimensional diatomic chain with harmonic intersite potential and nonlinear external potential is considered (the Klein-Gordon model). Localized solutions of the corresponding nonlinear differential equations with frequencies inside the gap of the linear wave spectrum--"gap breathers"--are studied numerically. The linear stability analysis for these solutions is performed while changing the system parameters from the anticontinuous to the continuous limit. Two different types of solutions are considered: symmetric centered at a heavy atom and antisymmetric centered at a light atom, respectively. Different mechanisms of instability, oscillatory as well as nonoscillatory, of the gap breathers are studied, and the influence of the instabilities on the breather solutions is investigated in the dynamics simulations. In particular, the presence of an "inversion of stability" regime, with simultaneous nonoscillatory instabilities of symmetric and antisymmetric solutions with respect to antisymmetric perturbations, is found, yielding practically radiationless mobility.

Journal Article↗

Modified Henry function for the electrophoretic mobility of a charged spherical colloidal particle covered with an ion-penetrable uncharged polymer layer.

An approximate expression is derived for the electrophoretic mobility of a spherical charged colloidal particle carrying low zeta potential covered with an ion-penetrable uncharged polymer layer in an electrolyte solution. This expression, which becomes Henry's mobility formula in the absence of the polymer layer, is a modification of Henry's mobility formula by taking into account the presence of the uncharged polymer layer.

Algorithms↗

Mobilization of hematopoietic stem cells.

Hematopoietic stem cell transplantation has been extensively exploited as a therapeutic and research modality and has revolutionized current patient care. At present, more and more medical centers use peripheral blood progenitor cells for transplantation by mobilizing hematopoietic stem cells from bone marrow to peripheral blood because of potential advantages of peripheral blood stem cell transplantation over bone-marrow transplantation. Different effective mobilization regimens have been developed recently with chemotherapeutic agents, hematopoietic growth factors or their combination. This article reviews current developments related to hematopoietic stem cell mobilization including the biology of hematopoietic stem cells, strategies for mobilization, management for mobilization failure, mechanisms of mobilization, and side effects during mobilization. Finally, the Initiation-Amplification-Emigration-Adaptation Model is proposed to help aid understanding of the mechanisms of hematopoietic stem cell mobilization and to stimulate development of novel and optimal mobilization strategies for patient care.

Hematopoietic Stem Cell Mobilization↗

Extending the hand of knowledge: promoting mobile technologies.

The widespread use of handheld computers and other mobile devices in the healthcare environment and their potential for providing access to information has prompted health sciences librarians everywhere to learn more about this technology. Early in 2001, the Health Sciences Library (HSL) at the University of North Carolina at Chapel Hill began exploring ways to support mobile computing. This paper describes the four basic approaches taken by the librarians that helped establish the HSL as a leader in the area of mobile technologies.

Academic Medical Centers↗

Gap solitons in quasiperiodic optical lattices.

Families of solitons in one- and two-dimensional (1D and 2D) Gross-Pitaevskii equations with the repulsive nonlinearity and a potential of the quasicrystallic type are constructed (in the 2D case, the potential corresponds to a fivefold optical lattice). Stable 1D solitons in the weak potential are explicitly found in three band gaps. These solitons are mobile, and they collide elastically. Many species of tightly bound 1D solitons are found in the strong potential, both stable and unstable (unstable ones transform themselves into asymmetric breathers). In the 2D model, families of both fundamental and vortical solitons are found and are shown to be stable.

Journal Article↗

Soil management practices shape the abundance, diversity, and spread of antimicrobial resistance.

Agricultural soils are critical hotspots of antimicrobial resistance genes (ARGs). Yet, the environmental factors shaping these reservoirs and the hazards they pose to humans and livestock remain poorly understood. Because management practices introduce antibiotics, heavy metals, and nonantibiotic biocides, they can rapidly select for resistance. Most studies have examined components of management practices in isolation, overlooking the multiple stressors of modern industrial agriculture. Here, we used a large-scale field experiment to examine how multiple stressors from soil and crop management interact to shape antimicrobial resistance. We combined shotgun metagenomics, phylogenomics, and risk-score analyses to quantify the diversity of ARGs, mobile genetic elements (MGEs), and the transmission potential of drug-resistant pathogens. Relative to other management systems, intensive, chemically reliant monoculture systems, typical of the US Corn Belt, create strong selective pressures promoting more abundant and diverse ARGs and MGEs. These systems therefore carry greater potential to transmit ARGs, including those with relevance to both livestock and public health such as tetA and blaPAM, likely mediated by integration and excision. In contrast, less-intensive, lower-input systems with diverse crop rotations maintained resistomes with lower abundance, diversity, and transmission potential. Our results suggest that these patterns could arise due to the divergent effects of management practices on overall soil microbial diversity, an ecological barrier that can suppress ARGs. This study highlights the need to understand the combined stressors of agricultural practices, beyond antimicrobial use, to design effective strategies to mitigate antimicrobial resistance.

Soil Microbiology↗

FcRH1: an activation coreceptor on human B cells.

B-cell activation and differentiation is regulated through the coordinated function of a dynamic array of cell surface receptors. At different stages in their differentiation, human B cells may express one or more members of a large family of immunoglobulin Fc receptor homologs (FcRH) with regulatory potential. Among these newly identified transmembrane molecules, FcRH1 is unique in having 2 immunoreceptor tyrosine-based activation motif (ITAM)-like motifs in its intracellular domain. Here we used the Fab fragments of new monoclonal anti-FcRH1 antibodies and mRNA analysis to evaluate FcRH1 expression and function during B-cell differentiation. FcRH1 expression begins in pre-B cells, reaches peak levels on naive B cells, and is down-regulated after B cells are activated to begin to form germinal centers. This FcRH1 down-regulation coincides with dramatic enlargement of the pre-germinal center cells, cell cycle entry, and other overt signs of activation that include CD80 and CD86 up-regulation and immunoglobulin D (IgD) down-regulation. In vitro analysis indicates that ligation of FcRH1 leads to its tyrosine phosphorylation and to modest B-cell activation and proliferation. Concomitant FcRH1 ligation enhances B-cell antigen receptor (BCR)-induced Ca(2+) mobilization and proliferation. FcRH1 thus has the potential to serve as an activating coreceptor on B cells.

Animals↗

Microbial studies in the Canadian nuclear fuel waste management program.

Atomic Energy of Canada Limited (AECL) has developed a concept for permanent geological disposal of used nuclear fuel in Canada. This concept, based on a multibarrier system, would involve disposal of nuclear fuel waste in titanium or copper containers, surrounded by compacted clay-based buffer and backfill materials, in a vault 500-1000 m deep in granitic rock of the Canadian Shield. Subsurface environments will not be sterile and an experimental program was initiated in 1991 by AECL to address and quantify the potential effects of microbial action on the integrity of the disposal vault. This microbial program focuses on answering specific questions in areas such as the survival of bacteria in compacted clay-based buffer materials under relevant radiation, temperature and desiccation conditions; mobility of microbes in compacted buffer materials; the potential for microbially influenced corrosion of containers; microbial gas production in backfill material; introduction of nutrients as a result of vault excavation and operation; the presence and activity of microbes in deep granitic groundwaters; and the effects of biofilms on radionuclide migration in the geosphere. This paper summarizes the results to date from the research activities at AECL.

Bacterial Physiological Phenomena↗

hATpin, a family of MITE-like hAT mobile elements conserved in diverse plant species that forms highly stable secondary structures.

We identified a 178 bp mobile DNA element in lettuce with characteristic CGAGC/GCTCG repeats in the subterminal regions. This element has terminal inverted repeats and 8-bp target site duplications typical of the hAT superfamily of class II mobile elements, but its small size and potential to form a single-stranded stable hairpin-like secondary structure suggest that it is related to MITE elements. In silico searches for related elements identified 252 plant sequences with 8-bp target site duplications and sequence similarity in their terminal and subterminal regions. Some of these sequences were predicted to encode transposases and may be autonomous elements; these constituted a separate clade within the phylogram of hAT transposases. We demonstrate that the CGAGC/GCTCG pentamer maximizes the hairpin stability compared to any other pentamer with the same C + G content, and the secondary structures of these elements are more stable than for most MITEs. We named these elements collectively as hATpin elements because of the hAT similarity and their hairpin structures. The nearly complete rice genome sequence and the highly advanced genome annotation allowed us to localize most rice elements and to deduce insertion preferences. hATpin elements are distributed on all chromosomes, but with significant bias for chromosomes 1 and 10 and in regions of moderate gene density. This family of class II mobile elements is found primarily in monocot species, but is also present in dicot species.

Base Sequence↗

Genes controlled by the essential YycG/YycF two-component system of Bacillus subtilis revealed through a novel hybrid regulator approach.

The YycG/YycF two-component system, originally identified in Bacillus subtilis, is very highly conserved and appears to be specific to low G + C Gram-positive bacteria. This system is required for cell viability, although the basis for this and the nature of the YycF regulon remained elusive. Using a combined hybrid regulator/transcriptome approach involving the inducible expression of a PhoP'-'YycF chimerical protein in B. subtilis, we have shown that expression of yocH, which encodes a potential autolysin, is specifically activated by YycF. Gel mobility shift and DNase I footprinting assays were used to show direct binding in vitro of purified YycF to the regulatory regions of yocH as well as ftsAZ, previously reported to be controlled by YycF. Nucleotide sequence analysis and site-directed mutagenesis allowed us to define a potential consensus recognition sequence for the YycF response regulator, composed of two direct repeats: 5'-TGT A/T A A/T/C-N5-TGT A/T A A/T/C-3'. A DNA-motif analysis indicates that there are potentially up to 10 genes within the B. subtilis YycG/YycF regulon, mainly involved in cell wall metabolism and membrane protein synthesis. Among these, YycF was shown to bind directly to the region upstream from the ykvT gene, encoding a potential cell wall hydrolase, and the intergenic region of the tagAB/tagDEF divergon, encoding essential components of teichoic acid biosynthesis. Definition of a potential YycF recognition sequence allowed us to identify likely members of the YycF regulon in other low G + C Gram-positive bacteria, including several pathogens such as Listeria monocytogenes, Staphylococcus aureus and Streptococcus pneumoniae.

Bacillus subtilis↗

Maximum survival in pediatric trauma: the ideal system.

One hundred consecutive pediatric trauma deaths (0.01-18 yrs) were analyzed for their survival potential in an optimally functioning EMS/Trauma system in Mobile, Alabama (1980-1982). Thorough evaluation of all phases of care by paramedic run sheets, ER records, hospital records, and autopsy reports, revealed that 47/100 victims could have never survived due to the extreme nature of their injuries, and 53/100 victims had the potential of surviving if the EMS/Trauma system functioned optimally. Errors in care were identified in those cases deemed potentially salvageable. Identification phase errors were found in 79% of potentially salvageable victims. Field treatment errors occurred in 36%, transport errors in 23%, and definitive care errors in 17% of those considered to be potentially salvageable. By evaluating where in an EMS/Trauma system errors occur and then by correcting those errors, it should be possible to minimize the mortality rate in pediatric trauma.

Adolescent↗

Functional analysis of a metal response element in the regulatory region of flounder cytochrome P450 1A and implications for environmental monitoring of pollutants.

Cytochrome P450 1A (CYP 1A) is a member of a multigene family of xenobiotic metabolizing enzymes. CYP 1A is highly inducible by numerous environmental contaminants including polycyclic aromatic hydrocarbons (PAHs) and is widely used in biomonitoring studies. Therefore, understanding the regulation of this gene is important for accurate interpretation of biomarker data. We describe here the functional role of a metal response element (MRE) in the European flounder CYP 1A promoter region. To help elucidate the potential role of this MRE, reporter gene constructs, with or without site-directed mutagenesis, were used in conjunction with a dual-luciferase assay. The electrophoretic mobility shift assay (EMSA) was also used to investigate potential protein binding at this MRE site. Treatment with the prototypical PAH 3-methylcholanthrene (3MC) (1.0 microM) produced a dose-dependent response at the CYP 1A promoter, whereas treatment with cadmium (0-1.0 microM) produced little transcriptional activity at either the wild-type or mutated promoter. Cotreatment with cadmium (1.0 microM) and 3MC (1.0 microM) reduced induction at this promoter to 1.83-fold compared to 3MC treatment alone (4.0-fold induction). Mutation of the MRE site resulted in abolishment of this cadmium-related loss of 3MC-dependent activity. Furthermore, a retarded band was observed in the EMSA when the MRE was used as a probe and incubated with liver nuclear protein from flounder treated with cadmium. The results not only add to knowledge of the diversity in vertebrate CYP 1A regulation but also raise the complexity of interpretation of CYP 1A induction in monitoring studies that involve mixtures of PAHs and metals.

Animals↗