New targets for resolution of airway remodeling in obstructive lung diseases.

Airway remodeling (AR) is a progressive pathological feature of the obstructive lung diseases, including asthma and chronic obstructive pulmonary disease (COPD). The pathology manifests itself in the form of significant, progressive, and (to date) seemingly irreversible changes to distinct respiratory structural compartments. Consequently, AR correlates with disease severity and the gradual decline in pulmonary function associated with asthma and COPD. Although current asthma/COPD drugs manage airway contraction and inflammation, none of these effectively prevent or reverse features of AR. In this review, we provide a brief overview of the features and putative mechanisms affecting AR. We further discuss recently proposed strategies with promise for deterring or treating AR

Bitter Taste Receptors for Asthma Therapeutics.

Clinical management of asthma and chronic obstructive pulmonary disease (COPD) has primarily relied on the use of beta 2 adrenergic receptor agonists (bronchodilators) and corticosteroids, and more recently, monoclonal antibody therapies (biologics) targeting specific cytokines and their functions. Although these approaches provide relief from exacerbations, questions remain on their long-term efficacy and safety. Furthermore, current therapeutics do not address progressive airway remodeling (AR), a key pathological feature of severe obstructive lung disease. Strikingly, agonists of the bitter taste receptors (TAS2Rs) deliver robust bronchodilation, curtail allergen-induced inflammatory responses in the airways and regulate airway smooth muscle (ASM) cell proliferation and mitigate features of A

Coverage problems in mobile sensing

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering, 2008.Includes bibliographical references (p. 177-183).Sensor-networks can today measure physical phenomena at spatial and temporal scales that were not achievable earlier, and have shown promise in monitoring the environment, structures, agricultural fields and so on. A key challenge in sensor-networks is the coordination of four actions across the network: measurement (sensing), communication, motion and computation. The term coverage is applied to the central question of how well a sensor-network senses some phenomenon to make inferences. More formally, a coverage problem involves finding an arrangement of sensors that optimizes a coverage metric. In this thesis we examine coverage in the context of three sensing modalities. The literature on the topic has thus far focused largely on coverage problems with the first modality: static event-detection sensors, which detect purely binary events in their immediate vicinity based on thresholds. However, coverage problems for sensors which measure physical quantities like temperature, pressure, chemical concentrations, light intensity and so on in a network configuration have received limited attention in the literature. We refer to this second modality of sensors as estimation sensors; local estimates from such sensors can be used to reconstruct a field. Third, there has been recent interest in deploying sensors on mobile platforms. Mobility has the effect of increasing the effectiveness of sensing actions. We further classify sensor mobility into incidental and intentional motion. Incidentally mobile sensors move passively under the influence of the environment, for instance, a floating sensor drifting in the sea. We define intentional mobility as the ability to control the location and trajectory of the sensor, for example by mounting it on a mobile robot. We build our analysis on a series of cases. We first analyze coverage and connectivity of a network of floating sensors in rivers using simulations and experimental data, and give guidelines for sensor-network design. Second, we examine intentional mobility and detection sensors.(cont.) We examine the problem of covering indoor and outdoor pathways with reconfigurable camera sensor-networks. We propose and validate an empirical model for detection behavior of cameras. We propose a distributed algorithm for reconfiguring locations of cameras to maximize detection performance. Finally, we examine more general strategies for the placement of estimation sensors and ask when and where to take samples in order to estimate an unknown spatiotemporal field with tolerable estimation errors. We discuss various classes of error-tolerant sensor arrangements for trigonometric polynomial fields.by Ajay A. Deshpande.Ph.D

A pseudo-polynomial time O(log² n)-approximation algorithm for art gallery problems

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering; and, (S.M.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2006.Includes bibliographical references (p. 55-56).In this thesis, we give a pseudo-polynomial time O(log² n)-approximation algorithm for a variant of the art gallery problem the point-guard problem. The point-guard problem involves finding the minimum number of points and their positions so that guards located at these points cover the interior of the art gallery. Our algorithm is pseudo-polynomial in the sense that it is polynomial in the number of walls of the art gallery but is possibly exponential in the number of bits required to represent the positions of the vertices of the art gallery. Our approach involves reducing the point-guard problem to a new problem of choosing a minimum number of guard-locations from a finite set obtained by a special subdivision procedure. The new problem has the optimal solution at most three times the optional solution of the point-guard problem. We further reduce the new problem to the set cover problem and obtain an approximate solution to the set cover problem.by Ajay A. Deshpande.S.M

Effect of Palmitic Acid on B2 Receptor Expression In Airway Smooth Muscle Cells

Introduction: People with asthma and obesity struggle to control asthma flares. B2 agonists are often the acute treatment of choice during these flares, so the decreased asthma control in this population may be due to a decrease in B2 receptor activity. We tested the hypothesis that B2 receptor expression will decrease in airway smooth muscle cells exposed to Palmitic Acid, a saturated fatty acid, compared to Oleic Acid and untreated cells. Methods: Airway smooth muscle cells were plated and treated with Palmitic Acid and Oleic Acid at 100uM and 200uM concentrations while other untreated cells served as controls. Cells were lysed at 24 and 48 hours and their RNA was harvested for expansion using PCR with B2 and GAPDH primers. RT-PCR was used to quantify RNA expression. GAPDH was used as an expression control to normalize B2 values for each condition and the resulting dCq values for each condition were compared. Results: The Palmitic Acid group did not show significant decrease in B2 expression compared to the control or Oleic Acid groups. This was consistent across all concentrations and time points. There was no significant change in receptor expression for any condition. Discussion: These results did not support our hypothesis that B2 expression would decrease in cells treated with Palmitic Acid. The expression of this receptor and its activity is not regulated as we hypothesized illustrating need to explore other factors that may contribute to the difference of the B2 receptor agonist response in obese people with asthma

Bitter Taste Receptor Agonists Mitigate Features of Allergic Asthma in Mice.

Asthma is characterized by airway inflammation, mucus secretion, remodeling and hyperresponsiveness (AHR). Recent research has established the bronchodilatory effect of bitter taste receptor (TAS2R) agonists in various models. Comprehensive pre-clinical studies aimed at establishing effectiveness of TAS2R agonists in disease models are lacking. Here we aimed to determine the effect of TAS2R agonists on features of asthma. Further, we elucidated a mechanism by which TAS2R agonists mitigate features of asthma. Asthma was induced in mice using intranasal house dust mite or aerosol ova-albumin challenge, and chloroquine or quinine were tested in both prophylactic and treatment models. Allergen challenge resulted in airway inflammation as evidenced by increased immune cells infiltration and release of cytokines and chemokines in the lungs, which were significantly attenuated in TAS2R agonists treated mice. TAS2R agonists attenuated features of airway remodeling including smooth muscle mass, extracellular matrix deposition and pro-fibrotic signaling, and also prevented mucus accumulation and development of AHR in mice. Mechanistic studies using human neutrophils demonstrated that inhibition of immune cell chemotaxis is a key mechanism by which TAS2R agonists blocked allergic airway inflammation and exerted anti-asthma effects. Our comprehensive studies establish the effectiveness of TAS2R agonists in mitigating multiple features of allergic asthma

Obesity and Obstructive Airways Disease: Clinical Correlates and Therapeutic Considerations

Obese patients are more likely to suffer from severe asthma symptoms and less likely to be able to control them. In obese patients, there is evidence that shows decreased efficacy of inhaled corticosteroids and beta-2 adrenergic agonists, the core treatment options for achieving and maintaining asthma control. This may be due to mechanical reasons like decreased ventilation and medication delivery, but there are many more pathologies of obesity that interact with pathways of both asthma pathology and asthma control. This review explores the epidemiological significance of obesity, many physiological changes in patients with obesity, the physiological interactions of asthma and obesity in patients with both issues, and the therapeutic impacts of these interactions with asthma to find appropriate areas where new research is needed. More research to understand the mechanism of decreased inhaled corticosteroid and beta-2 adrenergic agonist efficacy is necessary to improve treatment efficacy and decrease morbidity and mortality in this population of patients with asthma

Proteomics-Based Approach for Detailing the Allergenic Profile of Cannabis Chemotypes

Allergic sensitization to cannabis is an emerging public health concern and is difficult to clinically establish owing to lack of standardized diagnostic approaches. Attempts to develop diagnostic tools were largely hampered by the Schedule I restrictions on cannabis, which limited accessibility for research. Recently, however, hemp was removed from the classified list, and increased accessibility to hemp allows for the evaluation of its practical clinical value for allergy diagnosis. We hypothesized that the proteomic profile is preserved across different cannabis chemotypes and that hemp would be an ideal source of plant material for clinical testing. Using a proteomics-based approach, we examined whether distinct varieties of cannabis plant contain relevant allergens of cannabis. Cannabis extracts were generated from high tetrahydrocannabinol variety (Mx), high cannabidiol variety (V1-19) and mixed profile variety (B5) using a Plant Total Protein Extraction Kit. Hemp extracts were generated using other standardized methods. Protein samples were subjected to nanoscale tandem mass spectrometry. Acquired peptides sequences were examined against the Cannabis sativa database to establish protein identity. Non-specific lipid transfer protein (Can s 3) level was measured using a recently developed ELISA 2.0 assay. Proteomic analysis identified 49 distinct potential allergens in protein extracts from all chemotypes. Most importantly, clinically relevant and validated allergens, such as profilin (Can s 2), Can s 3 and Bet v 1-domain-containing protein 10 (Can s 5), were identified in all chemotypes at label-free quantification (LFP) intensities \u3e 106. However, the oxygen evolving enhancer protein 2 (Can s 4) was not detected in any of the protein samples. Similarly, Can s 2, Can s 3 and Can s 5 peptides were also detected in hemp protein extracts. The validation of these findings using the ELISA 2.0 assay indicated that hemp extract contains 30-37 ng of Can s 3 allergen per µg of total protein. Our proteomic studies indicate that relevant cannabis allergens are consistently expressed across distinct cannabis chemotypes. Further, hemp may serve as an ideal practical substitute for clinical testing, since it expresses most allergens relevant to cannabis sensitization, including the validated major allergen Can s 3

Can follow-up examination of tuberculosis patients be simplified? A study in Chhattisgarh, India

Each follow-up during the course of tuberculosis treatment currently requires two sputum examinations. However, the incremental yield of the second sputum sample during follow-up of different types of tuberculosis patients has never been determined precisely