Fault tolerant attitude control for small unmanned aircraft systems equipped with an airflow sensor array.

Inspired by sensing strategies observed in birds and bats, a new attitude control concept of directly using real-time pressure and shear stresses has recently been studied. It was shown that with an array of onboard airflow sensors, small unmanned aircraft systems can promptly respond to airflow changes and improve flight performances. In this paper, a mapping function is proposed to compute aerodynamic moments from the real-time pressure and shear data in a practical and computationally tractable formulation. Since many microscale airflow sensors are embedded on the small unmanned aircraft system surface, it is highly possible that certain sensors may fail. Here, an adaptive control system is developed that is robust to sensor failure as well as other numerical mismatches in calculating real-time aerodynamic moments. The advantages of the proposed method are shown in the following simulation cases: (i) feedback pressure and wall shear data from a distributed array of 45 airflow sensors; (ii) 50% failure of the symmetrically distributed airflow sensor array; and (iii) failure of all the airflow sensors on one wing. It is shown that even if 50% of the airflow sensors have failures, the aircraft is still stable and able to track the attitude commands.

Redox control of indoleamine 2,3-dioxygenase expression and activity in human monocyte-derived dendritic cells is independent of changes in oxygen tension.

Dendritic cells (DCs) initiate adaptive immune responses to pathogens and tumours and maintain tolerance to self and innocuous antigens. These functions occur in organs and tissues exhibiting wide variations in nutrients, growth factors, redox and oxygen tension. Understanding how these microenvironmental factors influence DCs to affect immunological outcomes is of increasing relevance with the emerging success of DC-based cellular vaccines. In a previous study, we examined whether redox, an important environmental cue, could influence DC expression of the immunosuppressive enzyme indoleamine 2,3-dioxygenase (IDO). IDO-competent DCs promote long-term immune homoeostasis by limiting exaggerated inflammatory responses and directing regulatory T-cell effector function. To alter redox, we manipulated the activity of the cystine/glutamate antiporter, which functions to maintain intracellular and extracellular redox. The results of that study showed that redox perturbation strongly induced IDO expression and activity in DCs. While this study was performed using standard cell culture techniques with DCs cultured under 5% CO2 and 20% O2, it is clear that DCs capture and present antigens in inflamed tissues and secondary lymphoid organs which exhibit low oxygen tension (1-5% O2). Therefore, here we investigated whether oxygen tension influences DC expression of IDO in the context of homoeostatic and altered redox.

Interaction of oral bacteria with gingival epithelial cell multilayers.

Primary gingival epithelial cells were cultured in multilayers as a model for the study of interactions with oral bacteria associated with health and periodontal disease. Multilayers maintained at an air-liquid interface in low-calcium medium displayed differentiation and cytokeratin properties characteristic of junctional epithelium. Multilayers were infected with fluorescently labeled Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum or Streptococcus gordonii, and bacterial association was determined by confocal microscopy and quantitative image analysis. Porphyromonas gingivalis invaded intracellularly and spread from cell to cell; A. actinomycetemcomitans and F. nucleatum remained extracellular and showed intercellular movement through the multilayer; whereas S. gordonii remained extracellular and predominantly associated with the superficial cell layer. None of the bacterial species disrupted barrier function as measured by transepithelial electrical resistance. P. gingivalis did not elicit secretion of proinflammatory cytokines. However, A. actinomycetemcomitans and S. gordonii induced interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), IL-6 and IL-8 secretion; and F. nucleatum stimulated production of IL-1ß and TNF-α. Aggregatibacter actinomycetemcomitans, F. nucleatum and S. gordonii, but not P. gingivalis, increased levels of apoptosis after 24 h infection. The results indicate that the organisms with pathogenic potential were able to traverse the epithelium, whereas the commensal bacteria did not. In addition, distinct host responses characterized the interaction between the junctional epithelium and oral bacteria.

Hair receptor sensitivity to changes in laminar boundary layer shape.

Biologists have shown that bat wings contain distributed arrays of flow-sensitive hair receptors. The hair receptors are hypothesized to feedback information on airflows over the bat wing for enhanced stability or maneuverability during flight. Here, we study the geometric specialization of hair-like structures for the detection of changes in boundary layer velocity profiles (shapes). A quasi-steady model that relates the flow velocity profile incident on the longitudinal axis of a hair to the resultant moment and shear force at the hair base is developed. The hair length relative to the boundary layer momentum thickness that maximizes the resultant moment and shear-force sensitivity to changes in boundary layer shape is determined. The sensitivity of the resultant moment and shear force is shown to be highly dependent on hair length. Hairs that linearly taper to a point are shown to provide greater output sensitivity than hairs of uniform cross-section. On an order of magnitude basis, the computed optimal hair lengths are in agreement with the range of hair receptor lengths measured on individual bat species. These results support the hypothesis that bats use hair receptors for detecting changes in boundary layer shape and provide geometric guidelines for artificial hair sensor design and application.

Cholera toxin, E. coli heat-labile toxin, and non-toxic derivatives induce dendritic cell migration into the follicle-associated epithelium of Peyer's patches.

The follicle-associated epithelium (FAE) of Peyer's patches (PPs) transports antigens and microorganisms into mucosal lymphoid tissues where they are captured by subepithelial dendritic cells (DCs). Feeding of cholera toxin (CT) induced migration of subepithelial DCs to interfollicular T-cell areas within 24 h. This study investigated short-term effects of CT, Escherichia coli heat-labile toxin, and non-toxic derivatives on DC migration. CT or CTB injected into ligated intestinal loops induced significant increase in CD11c+ DCs within the FAE within 90 min. In mice fed CT intragastrically, DC numbers in the FAE increased by 1 h, were maximal by 2 h, declined between 8 and 12 h, and were reversed by 24 h. Feeding of native LT, recombinant CTB, dibutyryl cyclic AMP, and to a lesser extent mutated CT(E29H) or mutated LT(R192G) had the same effect. Thus, both A and B subunits of enterotoxins, presumably acting through distinct signaling pathways, may promote capture of incoming antigens and pathogens by PP DCs.

A short working distance multiple crystal x-ray spectrometer.

For x-ray spot sizes of a few tens of microns or smaller, a millimeter-sized flat analyzer crystal placed approximately 1 cm from the sample will exhibit high energy resolution while subtending a collection solid angle comparable to that of a typical spherically bent crystal analyzer (SBCA) at much larger working distances. Based on this observation and a nonfocusing geometry for the analyzer optic, we have constructed and tested a short working distance (SWD) multicrystal x-ray spectrometer. This prototype instrument has a maximum effective collection solid angle of 0.14 sr, comparable to that of 17 SBCA at 1 m working distance. We find good agreement with prior work for measurements of the Mn Kbeta x-ray emission and resonant inelastic x-ray scattering for MnO, and also for measurements of the x-ray absorption near-edge structure for Dy metal using Lalpha(2) partial-fluorescence yield detection. We discuss future applications at third- and fourth-generation light sources. For concentrated samples, the extremely large collection angle of SWD spectrometers will permit collection of high-resolution x-ray emission spectra with a single pulse of the Linac Coherent Light Source. The range of applications of SWD spectrometers and traditional multi-SBCA instruments has some overlap, but also is significantly complementary.

Drug interactions between oral contraceptives and antibiotics.

OBJECTIVE: To evaluate the evidence on possible drug interactions between antibiotics and oral contraceptives (OCs) that may lead to OC failure. DATA SOURCES: MEDLINE and Lexis/Nexis Medical Library searches for 1966-1999 using the key word "oral contraceptives," cross-indexed with the terms "antibiotics," "adverse effects," and "pregnancy," and MEDLINE search using the additional MeSH term "drug interactions." No language restrictions were used. METHODS OF STUDY SELECTION: A total of 167 articles were retrieved for analysis. Another 32 articles were identified by review of the references cited in these publications. Articles were selected based on their ability to provide information on the relationship between antibiotic therapy and OC efficacy in otherwise compliant users (defined as women with unplanned pregnancies who reported compliance with their OC regimen). Additionally, studies that either directly measured the effects of antibiotics on the pharmacokinetics of OC components, or that analyzed the effects of antibiotics on measures of ovulation in OC users were accepted. TABULATION, INTEGRATION, AND RESULTS: At least 30 cases have been reported of pregnancies occurring in women taking OCs and antibiotics, particularly rifampin. Approximately 20% of pregnant women reporting to family planning or abortion clinics reported concomitant OC and antibiotic use. Information from adverse event reporting databases generally mirrors the types of information gleaned from these case reports and clinical surveys and accounts for approximately one-third of reported cases. Retrospective surveys, primarily from dermatology-based practices, also have reported 24 pregnancies in OC users who concomitantly received therapy with antibiotics, most commonly tetracyclines and penicillins. Apparent OC failure rates in clinical surveys were within the usual range expected for patterns of typical use. In pooled results obtained from relatively small populations, oral antibiotics, with the exception of rifampin, have not significantly affected the pharmacokinetics of ethinyl estradiol, levonorgestrel, and norethindrone or reduced the serum concentrations of gonadotropins. However, individual patients have been identified who experienced significant decreases in the plasma concentration of these components of OCs and who appeared to ovulate. CONCLUSION: Rifampin impairs the effectiveness of OCs. Pharmacokinetic studies of other antibiotics have not shown any systematic interaction between antibiotics and OC steroids. However, individual patients do show large decreases in the plasma concentrations of ethinyl estradiol when they take certain other antibiotics, notably tetracycline and penicillin derivatives. Because it is not possible to identify these women in advance, a cautious approach is advised.

The multiple roles of major histocompatibility complex class-I-like molecules in mucosal immune function.

The human major histocompatibility complex (MHC) on chromosome 6 encodes three classical class-I genes: human leukocyte antigens (HLA) A, B, and C. These polymorphic genes encode a 43- to 45-kDa cell surface glycoprotein that, in association with the 12-kDa beta2-microglobulin molecule, functions in the presentation of nine amino acid peptides to the T-cell receptor of CD8-bearing T lymphocytes and killer inhibitory receptors on natural killer cells. In addition to these ubiquitously expressed, polymorphic proteins, the human genome also encodes several nonclassical MHC class-I-like, or class Ib, genes that, in general, encode nonpolymorphic molecules involved in various specific immunological functions. Many of these genes, including CD1, the neonatal Fc receptor for IgG, HLA-G, HLA-E, the MHC class-I chain-related gene A, and Hfe, are prominently displayed on epithelial cells, suggesting an important role in epithelial cell biology.

MHC class I-related neonatal Fc receptor for IgG is functionally expressed in monocytes, intestinal macrophages, and dendritic cells.

The neonatal Fc receptor (FcRn) for IgG, an MHC class I-related molecule, functions to transport IgG across polarized epithelial cells and protect IgG from degradation. However, little is known about whether FcRn is functionally expressed in immune cells. We show here that FcRn mRNA was identifiable in human monocytes, macrophages, and dendritic cells. FcRn heavy chain was detectable as a 45-kDa protein in monocytic U937 and THP-1 cells and in purified human intestinal macrophages, peripheral blood monocytes, and dendritic cells by Western blot analysis. FcRn colocalized in vivo with macrosialin (CD68) and Ncl-Macro, two macrophage markers, in the lamina propria of human small intestine. The heavy chain of FcRn was associated with the beta(2)-microglobulin (beta(2)m) light chain in U937 and THP-1 cells. FcRn bound human IgG at pH 6.0, but not at pH 7.5. This binding could be inhibited by human IgG Fc, but not Fab. FcRn could be detected on the cell surface of activated, but not resting, THP-1 cells. Furthermore, FcRn was uniformly present intracellularly in all blood monocytes and intestinal macrophages. FcRn was detectable on the cell surface of a significant fraction of monocytes at lower levels and on a small subset of tissue macrophages that expressed high levels of FcRn on the cell surface. These data show that FcRn is functionally expressed and its cellular distribution is regulated in monocytes, macrophages, and dendritic cells, suggesting that it may confer novel IgG binding functions upon these cell types relative to typical Fc gamma Rs: Fc gamma RI, Fc gamma RII, and Fc gamma RIII.

Safety of over-the-counter inhalers for asthma: report of the council on scientific affairs.

The occasional use of over-the-counter (OTC) epinephrine inhalers appears to be safe and effective when used according to labeled instruction by individuals with mild, intermittent asthma. However, gross misuse of these products can cause severe adverse reactions, including death. Limited survey data suggest that approximately 20% of individuals using OTC epinephrine inhalers have mild-to-moderate persistent asthma. According to recent consensus guidelines, these individuals should be under a physician's care and receiving corticosteroid therapy. If these products continue to be marketed, labeling should be strengthened to better educate users about appropriate and inappropriate use of OTC epinephrine inhalers intended for patients with mild, intermittent asthma.

Heterogeneity of detergent-insoluble membranes from human intestine containing caveolin-1 and ganglioside G(M1).

In intestinal epithelia, cholera and related toxins elicit a cAMP-dependent chloride secretory response fundamental to the pathogenesis of toxigenic diarrhea. We recently proposed that specificity of cholera toxin (CT) action in model intestinal epithelia may depend on the toxin's cell surface receptor ganglioside G(M1). Binding G(M1) enabled the toxin to elicit a response, but forcing the toxin to enter the cell by binding the closely related ganglioside G(D1a) rendered the toxin inactive. The specificity of ganglioside function correlated with the ability of G(M1) to partition CT into detergent-insoluble glycosphingolipid-rich membranes (DIGs). To test the biological plausibility of these hypotheses, we examined native human intestinal epithelia. We show that human small intestinal epithelia contain DIGs that distinguish between toxin bound to G(M1) and G(D1a), thus providing a possible mechanism for enterotoxicity associated with CT. We find direct evidence for the presence of caveolin-1 in DIGs from human intestinal epithelia but find that these membranes are heterogeneous and that caveolin-1 is not a structural component of apical membrane DIGs that contain CT.

Weight loss is correlated with an improved lipoprotein profile in obese postmenopausal women.

BACKGROUND: Changes in plasma lipid and lipoprotein distributions that occur after menopause increase the risk of cardiovascular disease in women, especially in those who are overweight. OBJECTIVE: The purpose of this study was to evaluate the impact of a nine-month weight reduction program on plasma lipids, dietary intake and abdominal fat obesity. DESIGN: A partial crossover design was used to study a weight loss treatment consisting of Phentermine hydrochloride (Fastin, SmithKline Beecham Pharmaceuticals, Philadelphia, PA) therapy plus a low energy diet (5040 kJ/d). Forty-seven obese, postmenopausal Caucasian women (BMI of 30-38 kg/m2) were randomized into two groups, both of which received drug and diet treatment over six months. However, Group I started the intervention program three months later than Group II. Plasma total, HDL and LDL cholesterol and triacylglycerol were measured, body composition was assessed by anthropometry and dual energy x-ray absorptiometry, and food frequency records were collected at four timepoints. RESULTS: Over nine months, women in Group II reduced body weight (14.4%), lowered plasma concentrations of LDL cholesterol (14% to 26%) and triacylglycerol (15%) and raised plasma HDL cholesterol concentration (15%). These plasma lipid changes decreased the total cholesterol/HDL cholesterol ratio from 4.3 to 3.2. All subjects decreased abdominal fat measurements and energy and cholesterol intakes, as well as percentage of energy derived from total and saturated fat during the study. Most subjects also increased dietary fiber consumption. CONCLUSION: Both weight loss and diet modifications are associated with an improved plasma lipid profile in obese postmenopausal women.

Expression of CD80 promoter in transgenic mice.

CD80 is a very potent co-stimulatory factor which is required for complete T-cell activation. Here, we use transgenic mice as a tool to map the promoter of the CD80 gene. We engineered three different CD80 promoter driven luciferase transgenes: -3084, -1073 and -215. With these transgenes, we have generated three groups of transgenic mice. Our results showed that the -3084 CD80 promoter/luciferase transgene was sufficient to confer tissue-specific expression of the CD80 gene. When the promoter sequence was deleted to -1073, the normal tissue-specific expression was lost. A brain-specific element was mapped between -1073 nt and -215 nt. This element caused up to ninefold higher expression of the CD80 promoter/luciferase in brain tissue of -1073 CD80 promoter/luciferase transgenic animals as compared to -3084 CD80 promoter/luciferase transgenic animals. In contrast to results with a cell culture system, little luciferase activity was detected in -215 CD80 promoter/luciferase transgenic animals.

The infectious complications of anabolic-androgenic steroid injection.

One million individuals in the United States alone are estimated to be current or past users of anabolic-androgenic steroids. In the United States fifty-percent of anabolic-androgenic steroid users administer their compounds intramuscularly, and twenty-five percent of adolescent anabolic-androgenic steroid users share needles, placing these young adults at risk for infections related to injection. To examine the medical literature for reports of infections attributable to anabolic-androgenic steroids, we conducted a MEDLINE (1966-1998) and AIDSLINE (1980-1998) world literature review to examine all references that attributed infections to anabolic-androgenic steroid injection. Infections associated with anabolic-androgenic steroid injection include three cases of HIV, one case of hepatitis B, one case of hepatitis C, eight abscesses, and a case of fungal endophthalmitis. No cross-sectional or prospective studies exist that document the risk of infections related to anabolic-androgenic steroid injection. These serious infectious complications of anabolic-androgenic steroid injection may be avoided with education and prevention techniques. Infections occurring in anabolic-androgenic steroid users are not as common as in intravenous drug users.

Bidirectional FcRn-dependent IgG transport in a polarized human intestinal epithelial cell line.

The MHC class I-related Fc receptor, FcRn, mediates the intestinal absorption of maternal IgG in neonatal rodents and the transplacental transport of maternal IgG in humans by receptor-mediated transcytosis. In mice and rats, expression of FcRn in intestinal epithelial cells is limited to the suckling period. We have recently observed, however, clear expression of FcRn in the adult human intestine, suggesting a function for FcRn in intestinal IgG transport beyond neonatal life in humans. We tested this hypothesis using the polarized human intestinal T84 cell line as a model epithelium. Immunocytochemical data show that FcRn is present in T84 cells in a punctate apical pattern similar to that found in human small intestinal enterocytes. Solute flux studies show that FcRn transports IgG across T84 monolayers by receptor-mediated transcytosis. Transport is bidirectional, specific for FcRn, and dependent upon endosomal acidification. These data define a novel bidirectional mechanism of IgG transport across epithelial barriers that predicts an important effect of FcRn on IgG function in immune surveillance and host defense at mucosal surfaces.

Needle exchange program participation by anabolic steroid injectors, United States 1998.

A significant number of people are currently misusing and abusing anabolic steroids. Hepatitis B, C, and HIV have all been documented to occur among anabolic steroid injectors (ASIs), most likely from the sharing of injection equipment. A survey was administered to 42 needle exchange programs (NEPs) from 17 states in the US to determine ASI participation. Sixty percent of the NEPs surveyed reported having at least some ASIs as participants, however, only 512 ASIs were identified among the 36,000 total monthly participants (1.4%). With the expanding number of NEPs in the US, it is possible to reach a higher proportion of ASIs with clean syringes and education, thus offering the means to prevent the spread of infection in this population.