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1.
Sensors (Basel) ; 16(3): 313, 2016 Mar 02.
Article in English | MEDLINE | ID: mdl-26950126

ABSTRACT

Radiometric calibration of the Dual-Wavelength Echidna(®) Lidar (DWEL), a full-waveform terrestrial laser scanner with two simultaneously-pulsing infrared lasers at 1064 nm and 1548 nm, provides accurate dual-wavelength apparent reflectance (ρ(app)), a physically-defined value that is related to the radiative and structural characteristics of scanned targets and independent of range and instrument optics and electronics. The errors of ρ(app) are 8.1% for 1064 nm and 6.4% for 1548 nm. A sensitivity analysis shows that ρ(app) error is dominated by range errors at near ranges, but by lidar intensity errors at far ranges. Our semi-empirical model for radiometric calibration combines a generalized logistic function to explicitly model telescopic effects due to defocusing of return signals at near range with a negative exponential function to model the fall-off of return intensity with range. Accurate values of ρ(app) from the radiometric calibration improve the quantification of vegetation structure, facilitate the comparison and coupling of lidar datasets from different instruments, campaigns or wavelengths and advance the utilization of bi- and multi-spectral information added to 3D scans by novel spectral lidars.

2.
Immunology ; 143(3): 416-27, 2014 Nov.
Article in English | MEDLINE | ID: mdl-24831554

ABSTRACT

Interleukin-4 (IL-4) and IL-13 are critical drivers of immune activation and inflammation in ulcerative colitis, asthma and other diseases. Because these cytokines may have redundant function, dual targeting holds promise for achieving greater efficacy. We have recently described a bifunctional therapeutic targeting IL-4 and IL-13 developed on a novel protein scaffold, generated by combining specific binding domains in an optimal configuration using appropriate linker regions. In the current study, the bifunctional IL-4/IL-13 antagonist was evaluated in the murine oxazolone-induced colitis model, which produces disease with features of ulcerative colitis. The bifunctional IL-4/IL-13 antagonist reduced body weight loss throughout the 7-day course of the model, and ameliorated the increased colon weight and decreased colon length that accompany disease. Colon tissue gene expression was modulated in accordance with the treatment effect. Concentrations of serum amyloid P were elevated in proportion to disease severity, making it an effective biomarker. Serum concentrations of the bifunctional IL-4/IL-13 antagonist were inversely proportional to disease severity, colon tissue expression of pro-inflammatory genes, and serum amyloid P concentration. Taken together, these results define a panel of biomarkers signifying engagement of the IL-4/IL-13 pathway, confirm the T helper type 2 nature of disease in this model, and demonstrate the effectiveness of dual cytokine blockade.


Subject(s)
Antibodies, Monoclonal/pharmacology , Colitis, Ulcerative/metabolism , Interleukin-13/antagonists & inhibitors , Interleukin-4/antagonists & inhibitors , Recombinant Fusion Proteins/pharmacology , Animals , Antibodies, Monoclonal/administration & dosage , Antibodies, Neutralizing/administration & dosage , Antibodies, Neutralizing/pharmacology , Colitis, Ulcerative/chemically induced , Colitis, Ulcerative/drug therapy , Colitis, Ulcerative/genetics , Disease Models, Animal , Gene Expression Regulation/drug effects , Interleukin-13 Receptor alpha2 Subunit/antagonists & inhibitors , Mice , Oxazolone/adverse effects , Recombinant Fusion Proteins/administration & dosage , Serum Amyloid A Protein/metabolism , Serum Amyloid P-Component/metabolism , Severity of Illness Index
3.
Appl Opt ; 52(21): 5194-200, 2013 Jul 20.
Article in English | MEDLINE | ID: mdl-23872766

ABSTRACT

We describe a high etendue (0.12 cm(2) sr) camera that, without moving parts, simultaneously images four ultraviolet bands centered at 140, 175, 215, and 255 nm on a single detector into a minimum of ~7500 resolution elements. In addition to being an efficient way to make color photometric measurements of a static scene, the camera described here enables detection of spatial and temporal information that can be used to reveal energy dependent physical phenomena to complement the capability of other instruments ranging in complexity from filter wheels to integral field spectrographs.


Subject(s)
Diagnostic Imaging/instrumentation , Color , Colorimetry/instrumentation , Colorimetry/methods , Equipment Design , Image Processing, Computer-Assisted/methods , Light , Optics and Photonics , Time Factors , Ultraviolet Rays
4.
Am J Respir Cell Mol Biol ; 49(1): 37-46, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23449738

ABSTRACT

IL-4 and IL-13 comprise promising targets for therapeutic interventions in asthma and other Th2-associated diseases, but agents targeting either IL-4 or IL-13 alone have shown limited efficacy in human clinical studies. Because these cytokines may involve redundant function, dual targeting holds promise for achieving greater efficacy. We describe a bifunctional therapeutic targeting IL-4 and IL-13, developed by a combination of specific binding domains. IL-4-targeted and IL-13-targeted single chain variable fragments were joined in an optimal configuration, using appropriate linker regions on a novel protein scaffold. The bifunctional IL-4/IL-13 antagonist displayed high affinity for both cytokines. It was a potent and efficient neutralizer of both murine IL-4 and murine IL-13 bioactivity in cytokine-responsive Ba/F3 cells, and exhibited a half-life of approximately 4.7 days in mice. In a murine model of ovalbumin-induced ear swelling, the bifunctional molecule blocked both the IL-4/IL-13-dependent early-phase response and the IL-4-dependent late-phase response. In the ovalbumin-induced lung inflammation model, the bifunctional IL-4/IL-13 antagonist reduced the IL-4-dependent rise in serum IgE titers, and reduced IL-13-dependent airway hyperresponsiveness, lung inflammation, mucin gene expression, and serum chitinase responses. Taken together, these findings demonstrate the effective dual blockade of IL-4 and IL-13 with a single agent, which resulted in the modulation of a more extensive range of endpoints than could be achieved by targeting either cytokine alone.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Immunoglobulin E/immunology , Interleukin-13/antagonists & inhibitors , Interleukin-4/antagonists & inhibitors , Pneumonia/drug therapy , Animals , Anti-Inflammatory Agents, Non-Steroidal/immunology , Binding Sites , Bronchial Hyperreactivity/drug therapy , Bronchial Hyperreactivity/immunology , CHO Cells , Cricetinae , Cross-Linking Reagents/chemistry , Ear/physiopathology , Female , Half-Life , Interleukin-13 Receptor alpha2 Subunit/immunology , Interleukin-13 Receptor alpha2 Subunit/metabolism , Mice , Mice, Inbred C57BL , Molecular Conformation , Neutralization Tests , Ovalbumin/adverse effects , Ovalbumin/immunology , Pneumonia/immunology , Protein Binding , Protein Interaction Domains and Motifs , Single-Chain Antibodies/metabolism
5.
Appl Opt ; 51(29): 7069-79, 2012 Oct 10.
Article in English | MEDLINE | ID: mdl-23052087

ABSTRACT

We present flight results from the optical pointing control system onboard the Planetary Imaging Concept Testbed Using a Rocket Experiment (PICTURE) sounding rocket. PICTURE (NASA mission number: 36.225 UG) was launched on 8 October 2011, from White Sands Missile Range. It attempted to directly image the exozodiacal dust disk of ϵ Eridani (K2V, 3.22 pc) down to an inner radius of 1.5 AU using a visible nulling coronagraph. The rocket attitude control system (ACS) provided 627 milliarcsecond (mas) RMS body pointing (~2'' peak-to-valley). The PICTURE fine pointing system (FPS) successfully stabilized the telescope beam to 5.1 mas (0.02λ/D) RMS using an angle tracker camera and fast steering mirror. This level of pointing stability is comparable to that of the Hubble Space Telescope. We present the hardware design of the FPS, a description of the limiting noise sources and a power spectral density analysis of the FPS and rocket ACS in-flight performance.

6.
Surg Endosc ; 26(12): 3616-21, 2012 Dec.
Article in English | MEDLINE | ID: mdl-22733191

ABSTRACT

BACKGROUND: Magnetic endoscopic imagers (MEIs) are being introduced during colonoscopy, principally for training. They aid recognition and resolution of loops. This has potential to improve technique resulting in increased completion rates and better patients' experience. OBJECTIVE: To determine whether the use of a MEI improves colonoscopists' performance. DESIGN: Cohort study. SETTINGS: Endoscopy unit in a district general hospital. PATIENTS: Consecutive patients undergoing colonoscopy during a 33 month period were studied. INTERVENTION: Patients underwent colonoscopy with or without the use of a magnetic endoscopic imager. MAIN OUTCOME MEASURES: Patient comfort and colonoscopy completion rates with and without the use of a magnetic endoscopic imager. Other data recorded included sedation and analgesia doses, patient age and gender, bowel preparation quality, antispasmodic dose, time of day, and consciousness level. RESULTS: A total of 5,879 colonoscopies were performed. A magnetic endoscopic imager was used for 4,873. A greater proportion of patients in the imager group had the lowest discomfort score (56.2 vs. 39.8%, logistic regression; p = 0.005). Doses of midazolam were similar in both groups (1.93 vs. 2.14 mg for imager and nonimager groups respectively). Completion rates were 94.5% with an imager and 91% without (logistic regression; p = 0.088). Logistic regression analysis showed that buscopan improved completion rate but detrimental factors included increasing patient age, discomfort, poor bowel preparation, and an afternoon procedure. Factors not influencing completion included gender, sedation and analgesia doses, and consciousness level. There was no correlation between documented reason for failure and use of the imager. LIMITATIONS: This was a nonrandomized trial although improved with logistic regression analysis. CONCLUSIONS: Magnetic endoscopic imager use improves patient comfort during colonoscopy but has not been shown to improve completion.


Subject(s)
Colonoscopy/standards , Diagnostic Imaging/instrumentation , Intraoperative Care/instrumentation , Cohort Studies , Female , Humans , Magnetic Phenomena , Male , Middle Aged , Prospective Studies
7.
J Immunol ; 187(1): 561-9, 2011 Jul 01.
Article in English | MEDLINE | ID: mdl-21622864

ABSTRACT

Human studies using Abs to two different, nonoverlapping epitopes of IL-13 suggested that epitope specificity can have a clinically significant impact on clearance of IL-13. We propose that Ab modulation of IL-13 interaction with IL-13Rα2 underlies this effect. Two Abs were administered to healthy subjects and mild asthmatics in separate dose-ranging studies and allergen-challenge studies. IMA-638 allows IL-13 interaction with IL-13Rα1 or IL-13Rα2 but blocks recruitment of IL-4Rα to the IL-13/IL-13Rα1 complex, whereas IMA-026 competes with IL-13 interaction with IL-13Rα1 and IL-13Rα2. We found ∼10-fold higher circulating titer of captured IL-13 in subjects treated with IMA-026 compared with those administered IMA-638. To understand how this difference could be related to epitope, we asked whether either Ab affects IL-13 internalization through cell surface IL-13Rα2. Humans inducibly express cell surface IL-13Rα2 but lack the soluble form that regulates IL-13 responses in mice. Cells with high IL-13Rα2 expression rapidly and efficiently depleted extracellular IL-13, and this activity persisted in the presence of IMA-638 but not IMA-026. The potency and efficiency of this clearance pathway suggest that cell surface IL-13Rα2 acts as a scavenger for IL-13. These findings could have important implications for the design and characterization of IL-13 antagonists.


Subject(s)
Interleukin-13 Receptor alpha2 Subunit/metabolism , Interleukin-13/immunology , Interleukin-13/metabolism , Isoantibodies/physiology , Receptors, Scavenger/metabolism , Animals , Antibody-Dependent Cell Cytotoxicity/immunology , Dose-Response Relationship, Immunologic , Drug Delivery Systems , Extracellular Space/immunology , Extracellular Space/metabolism , HT29 Cells , Humans , Interleukin-13/antagonists & inhibitors , Interleukin-13 Receptor alpha2 Subunit/antagonists & inhibitors , Interleukin-13 Receptor alpha2 Subunit/biosynthesis , Macaca fascicularis , Mice , Mice, Inbred BALB C , Receptors, Scavenger/antagonists & inhibitors , Receptors, Scavenger/physiology
8.
J Phys Chem A ; 113(22): 6213-6, 2009 Jun 04.
Article in English | MEDLINE | ID: mdl-19438220

ABSTRACT

Fluorescent imaging of single helicene molecules is applied to study the optical activity of chiral fluorophores. In contrast to the previous report by Hassey et al. (Science 2006, 314, 1437), the dissymmetry factors of single chiral fluorophores are found not to differ significantly from the bulk value of |g| < 10(-4) at 457 nm. Linear dichroism and birefringence of the dichroic mirror inside the fluorescence microscope change the polarization state of the incoming laser beam significantly; i.e., circular polarized light sent into the microscope becomes highly elliptically polarized after reflection from the dichroic mirror. Compensation for this effect should be made to avoid artifacts brought by linear dichroism in single immobilized molecules.


Subject(s)
Fluorescence , Luminescent Measurements , Polycyclic Compounds/chemistry , Artifacts , Circular Dichroism , Stereoisomerism , Uncertainty
9.
Appl Opt ; 48(10): 1936-42, 2009 Apr 01.
Article in English | MEDLINE | ID: mdl-19340149

ABSTRACT

We describe an all-reflective system for narrowband imaging suitable for imaging emission lines in the far ultraviolet. The system, which we call a monochromatic imager, combines a pupil plane grating monochromator with a telescope and camera to image a scene in one or more very narrow bands. The monochromator uses physical stops at its input and output apertures, and, as a result, the system has excellent rejection of out-of-band and off-axis light.

10.
J Pharmacol Exp Ther ; 325(3): 882-92, 2008 Jun.
Article in English | MEDLINE | ID: mdl-18337474

ABSTRACT

Interleukin (IL)-13 is a key cytokine driving allergic and asthmatic responses and contributes to airway inflammation in cynomolgus monkeys after segmental challenge with Ascaris suum antigen. IL-13 bioactivity is mediated by a heterodimeric receptor (IL-13Ralpha1/IL-4Ralpha) and can be inhibited in vitro by targeting IL-13 interaction with either chain. However, in cytokine systems, in vitro neutralization activity may not always predict inhibitory function in vivo. To address the efficacy of two different IL-13 neutralization mechanisms in a primate model of atopic disease, two humanized monoclonal antibodies to IL-13 were generated, with highly homologous properties, differing in epitope recognition. Ab01 blocks IL-13 interaction with IL-4Ralpha, and Ab02 blocks IL-13 interaction with IL-13Ralpha1. In a cynomolgus monkey model of IgE responses to A. suum antigen, both Ab01 and Ab02 effectively reduced serum titers of Ascaris-specific IgE and diminished ex vivo Ascaris-triggered basophil histamine release, assayed 8 weeks after a single administration of antibody. The two antibodies also produced comparable reductions in pulmonary inflammation after lung segmental challenge with Ascaris antigen. Increased serum levels of IL-13, lacking demonstrable biological activity, were seen postchallenge in animals given either anti-IL-13 antibody but not in control animals given human IgG of irrelevant specificity. These findings demonstrate a potent effect of IL-13 neutralization on IgE-mediated atopic responses in a primate system and show that IL-13 can be efficiently neutralized by targeting either the IL-4Ralpha-binding epitope or the IL-13Ralpha1-binding epitope.


Subject(s)
Antigens, Helminth/immunology , Ascaris/immunology , Immunoglobulin E/blood , Immunoglobulin G/immunology , Inflammation/immunology , Interleukin-13/immunology , Lung/immunology , Receptors, Interleukin-13/immunology , Animals , Antibodies, Helminth/immunology , Basophils/immunology , Bronchoalveolar Lavage Fluid/immunology , Epitopes/immunology , Histamine Release/immunology , Humans , Macaca fascicularis , Male
11.
J Allergy Clin Immunol ; 119(5): 1251-7, 2007 May.
Article in English | MEDLINE | ID: mdl-17379289

ABSTRACT

BACKGROUND: Airway inflammation is a hallmark feature of asthma and a driver of airway hyperresponsiveness. IL-13 is a key inducer of airway inflammation in rodent models of respiratory disease, but a role for IL-13 has not been demonstrated in primates. OBJECTIVE: We sought to test the efficacy of a neutralizing antibody to human IL-13 in a cynomolgus monkey model of lung inflammation. METHODS: Using cynomolgus monkeys (Macaca fascicularis) that are sensitized to Ascaris suum through natural exposure, we developed a reproducible model of acute airway inflammation after segmental A suum antigen challenge. This model was used to test the in vivo efficacy of mAb13.2, a mouse mAb directed against human IL-13, and IMA-638, the humanized counterpart of mAb13.2. Bronchoalveolar lavage (BAL) cells and BAL fluid were collected before and after antigen challenge and assayed for cellular content by means of differential count. RESULTS: Total BAL cell count, eosinophil number, and neutrophil number were all reduced in animals treated with mAb13.2 or IMA-638 compared with values in control animals that were untreated, given saline, or treated with human IgG of irrelevant specificity. In addition, levels of eotaxin and RANTES in BAL fluid were reduced in anti-IL-13-treated animals compared with levels seen in control animals. CONCLUSION: These findings support a role for IL-13 in maintaining lung inflammation in response to allergen challenge in nonhuman primates. CLINICAL IMPLICATIONS: IL-13 neutralization with a specific antibody could be a useful therapeutic strategy for asthma.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Ascariasis/immunology , Interleukin-13/antagonists & inhibitors , Pneumonia/immunology , Pneumonia/prevention & control , Amino Acid Sequence , Animals , Antibodies, Blocking/therapeutic use , Antigens, Helminth/immunology , Ascaris suum , Bronchoalveolar Lavage Fluid/chemistry , Bronchoalveolar Lavage Fluid/cytology , Cytokines/biosynthesis , Enzyme-Linked Immunosorbent Assay , Female , Humans , Interleukin-13/genetics , Interleukin-13/immunology , Macaca fascicularis , Male , Molecular Sequence Data , Pneumonia/metabolism , Sequence Homology, Amino Acid
12.
Am J Respir Cell Mol Biol ; 36(3): 368-76, 2007 Mar.
Article in English | MEDLINE | ID: mdl-17023688

ABSTRACT

IL-13 contributes to airway hyperresponsiveness, mucus secretion, inflammation, and fibrosis, suggesting that it plays a central role in asthma pathogenesis. Neutralization of IL-13 with sIL-13Ralpha2-Fc (sIL-13R) reduces allergen-induced airway responses in rodent models of respiratory disease, but its efficacy in a large animal model has not been previously reported. In this study, we determined whether two different strategies for IL-13 neutralization modified experimental asthma in sheep. Sheep with natural airway hypersensitivity to Ascaris suum antigen were treated intravenously either with sIL-13R, a strong antagonist of sheep IL-13 bioactivity in vitro, or with IMA-638 (IgG1, kappa), a humanized antibody to human IL-13. Higher doses of IMA-638 were used because, although it is a potent antagonist of human IL-13, this antibody has 20 to 30 times lower binding and neutralization activity against sheep IL-13. Control animals received human IgG of irrelevant specificity. Sheep were treated 24 h before inhalation challenge with nebulized A. suum. The effects on antigen-induced early and late bronchial responses, and antigen-induced hyperresponsiveness, were assessed. Both sIL-13R and IMA-638 provided dose-dependent inhibition of the antigen-induced late responses and airway hyperresponsiveness. The highest dose of IMA-638 also reduced the early phase response. These findings suggest that IL-13 contributes to allergen-induced airway responses in this sheep model of asthma, and that neutralization of IL-13 is an effective strategy for blocking these A. suum-induced effects.


Subject(s)
Asthma/drug therapy , Asthma/immunology , Disease Models, Animal , Interleukin-13/antagonists & inhibitors , Interleukin-13/immunology , Sheep, Domestic/immunology , Amino Acid Sequence , Animals , Antibodies/pharmacology , Ascaris suum/physiology , Asthma/chemically induced , Asthma/physiopathology , Base Sequence , Bronchial Hyperreactivity/parasitology , Bronchial Hyperreactivity/pathology , Bronchoconstriction/drug effects , Bronchoconstriction/immunology , Carbachol/pharmacology , Female , HT29 Cells , Humans , Interleukin-13/chemistry , Interleukin-13/genetics , Kinetics , Molecular Sequence Data , Neutralization Tests , Receptors, Interleukin-13/metabolism , Sheep, Domestic/parasitology , Solubility/drug effects , Surface Plasmon Resonance , Time Factors
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