North Brunswick, NJ, United States
North Brunswick, NJ, United States

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Patz S.,Harvard University | Muradyan I.,Harvard University | Hrovat M.I.,Mirtech, Inc. | Dabaghyan M.,Harvard University | And 3 more authors.
New Journal of Physics | Year: 2011

We used hyperpolarized 129Xe NMR to measure pulmonary alveolar surface area per unit gas volume SA/Vgas, alveolar septal thickness h and capillary transit time τ, three critical determinants of the lung's primary role as a gas exchange organ. An analytical solution for a simplified diffusion model is described, together with a modification of the xenon transfer contrast imaging technique utilizing 90° radio-frequency pulses applied to the dissolved phase, rather than traditional 180° pulses. With this approach, three-dimensional (3D) maps of SA/Vgas were obtained. We measured global SA/Vgas, h and τ in four normal subjects, two subjects with mild interstitial lung disease (ILD) and two subjects with mild chronic obstructive pulmonary disease (COPD). In normals, SA/Vgas decreased with increasing lung volume from ∼320 to 80 cm-1; bothh ∼13μm and τ ∼ 1.5 s were relatively constant. For the two ILD subjects, h was, respectively, 36 and 97% larger than normal, quantifying an increased gas/blood tissue barrier; SA/Vgas and τ were normal. The two COPD subjects. © IOP Publishing Ltd and Deutsche Physikalische Gesellschaft.


Makimura H.,Harvard University | Stanley T.L.,Harvard University | Sun N.,Harvard University | Hrovat M.I.,Massachusetts General Hospital | And 3 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2011

Context: Previous studies have suggested a relationship between GH and mitochondrial function. However, little is known about the relationship of specific GH indices and in vivo measures of mitochondrial function in humans. Objective: The objective of this study was to determine the association between GH, IGF-I, and phosphocreatine (PCr) recovery, a measure of mitochondrial function, in otherwise healthy adults. Design: Thirty-seven healthy men and women were studied at a single university medical center. Subjects underwent GH stimulation testing with GH releasing hormone-arginine and measurement of IGF-I. Mitochondrial function was determined by PCr recovery after submaximal exercise by 31Phosphorous magnetic resonance spectroscopy. Subjects underwent assessment of lean and fat mass with use of dual energy X-ray absorptiometry. Results: There were no differences in PCr recovery between men and women (men 20.7±1.5 vs. women 24.8±1.4 mM/min; P > 0.05). IGF-I (r = 0.33; P = 0.04) was associated with PCr recovery in all subjects. Among men, IGF-I (r = 0.69; P = 0.003), peak stimulated GH (r = 0.52; P = 0.04), and GH area under the curve (AUC) (r = 0.53; P = 0.04) were significantly associated with PCr recovery. However, neither IGF-I, peak stimulated GH, nor GH AUC (all P > 0.05) were associated with PCr recovery in women. After adjusting for age, race, and physical activity, IGF-I remained significantly associated with PCr recovery (β = 0.10; P = 0.02) among men. Conclusions: IGF-I, peak stimulated GH, and GH AUC are associated with skeletal muscle PCr recovery in men. Copyright © 2011 by The Endocrine Society.


McCormack S.E.,Harvard University | McCarthy M.A.,Harvard University | Farilla L.,Harvard University | Hrovat M.I.,Harvard University | And 4 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2011

Context: Periods of rapid growth require an increase in energy use and substrate formation. Mitochondrial function contributes to each of these and therefore may play a role in longitudinal growth. Methods: Twenty-nine children and adolescents of ages 8-15 yr were enrolled in a comprehensive longitudinal assessment of glucose homeostasis and mitochondrial function. Fasting laboratory studies and an estimate of mitochondrial function (as assessed by the time to recovery of phosphocreatine (PCr) concentration after submaximal quadriceps extension/flexion exercise using 31P magnetic resonance spectroscopy) were obtained at baseline and annually for 2 yr. Results: Data were complete for 23 subjects. Subjects were 11.3 ± 1.9 (SD) yr old at the beginning of the study; 61% were male. Average annualized growth velocity at 1 yr for boys was 7.1 ± 1.5 cm/yr and for girls 6.5 ± 1.7 cm/yr. More rapid recovery of PCr concentration, suggestive of greater skeletal muscle oxidative phosphorylation capacity at baseline, was associated with faster growth velocity in the subsequent year (r 2 = 0.29; P = 0.008). In multivariate modeling, baseline mitochondrial function remained significantly and independently associated with growth (R 2 for model = 0.51; P = 0.05 for effect of phosphocreatine recovery time constant), controlling for age, gender, Tanner stage, body mass index Z-score, and height Z-score. Conclusions: We report a novel association between time to recovery of PCr concentration after submaximal exercise and faster annual linear growth in healthy children. Future studies are needed to determine the physiological mechanisms and clinical consequences of this observation. Copyright © 2011 by The Endocrine Society.


Disclosed are adsorption complexes that include 1-methylcyclopropene (1-MCP) and a metal coordination polymer network (MCPN), wherein the MCPN is a porous material, and the 1-MCP is adsorbed into the MCPN. Also disclosed are kits for containing 1-MCP that include the adsorption complex in a 1-MCP-impermeable package. Also disclosed are methods of releasing 1-methylcyclopropene (1-MCP) from the kit that include the application of aqueous fluids, heat, and/or pressure.


Grant
Agency: Department of Agriculture | Branch: | Program: SBIR | Phase: Phase II | Award Amount: 499.95K | Year: 2015

NON-TECHNICAL SUMMARYFAO estimates annual global food loss and waste at roughly 30% of cereal crops, 40 to 50% of root crops, fruits and vegetables and 20percent of oilseed crops with an estimated value for total food loss at US$1-trillion. Many factors along the value chain from farm fields to the family table contribute to food loss and waste however one unseen factor goes unnoticed, the plant hormone ethylene. Ethylene triggers over ripening in bananas, tomatoes, apples and other fruits and vegetables leading to spoilage and food waste. In cereal and oilseed crops, heat and drought stress triggers over production of ethylene leading to reduced pollination, reduced seed weight, and yield loss. Controlling the effects of ethylene both in fruit and vegetable packages, storage, shipment and at the retailer and in the fields greatly contribute to reducing food loss and waste.Research underway by MirTech is leading to novel ways to deliver of an ethylene blocking agent, a bio-pesticide known as 1-MCP (1-methyl cyclopropene). This new delivery technology will enable farmers, food packers, shipping companies, retailers and wholesalers to reduce food loss and waste by maintaining fruit quality and freshness and preventing yield losses in the field to fruit, vegetable, cereal crops and oilseed crop. Already MirTech has been granted patents on this new area of technology. If ultimately successful, MirTech will deliver a critically important tool into the hands of US growers, food packers and shippers and ultimately benefit every consumer.


Grant
Agency: National Science Foundation | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 224.93K | Year: 2016

The broader impact/commercial potential of this Small Business Innovation Research Phase I project will be better preservation of perishable food produce. The proposed new functionalized packaging film for perishable foods, incorporates innovative technologies to eliminate harmful microbes, lock in just-harvested aroma and taste, extend shelf-life from field to the kitchen table, and reduce food waste. These benefits will accrue to farmers and field workers, to shippers and truckers, to retailers who realize less produce waste, and o consumers. The proposed technology incorporates a novel nano-adsorbent metal organic framework (MOF) a molecular 'sponge' into a multi-layer packaging film which can deliver microbial protection, slow down the ripening process during shipment and deliver just-harvested quality in our fruits and vegetables. MOFs are a novel material technology which potentially could transform packaging from ?just plastic bags? to true active packaging. The technical objectives in this Phase I research project are to determine the technical feasibility to extrude a multi-layer film with the nano-adsorbent metal organic framework (MOF) material incorporated in a layer within linear low density polyethylene (LLDPE) film. This functionalized film structure will be selectively permeable via the embedded MOF structures to allow the exchange of gases, including ethylene, O2, CO2, other biologically active gases and certain antimicrobial compounds such as chlorine dioxide. Control of fruit and vegetable respiration (O2/CO2 balance), control endogenous and exogenous ethylene, and the delivery antimicrobial gases via MOFs could be the single most important recent technology breakthrough that allows producers in distant markets to delivery fresh produce. This research project will seek to identify MOFs with the appropriate gas exchange properties, heat stability in the blown film extrusion process and proper orientation within the film structure. Collaborative research is needed to select likely MOF candidates, to incorporate these MOFs in films extruded on pilot scale equipment, and to characterize effectiveness at a university-based postharvest laboratory to enable rapid technology development, impartial assessments, and effective reduction to practice.


Grant
Agency: NSF | Branch: Standard Grant | Program: | Phase: SMALL BUSINESS PHASE I | Award Amount: 224.93K | Year: 2016

The broader impact/commercial potential of this Small Business Innovation Research Phase I project will be better preservation of perishable food produce. The proposed new functionalized packaging film for perishable foods, incorporates innovative technologies to eliminate harmful microbes, lock in just-harvested aroma and taste, extend shelf-life from field to the kitchen table, and reduce food waste. These benefits will accrue to farmers and field workers, to shippers and truckers, to retailers who realize less produce waste, and o consumers. The proposed technology incorporates a novel nano-adsorbent metal organic framework (MOF) a molecular sponge into a multi-layer packaging film which can deliver microbial protection, slow down the ripening process during shipment and deliver just-harvested quality in our fruits and vegetables. MOFs are a novel material technology which potentially could transform packaging from ?just plastic bags? to true active packaging.

The technical objectives in this Phase I research project are to determine the technical feasibility to extrude a multi-layer film with the nano-adsorbent metal organic framework (MOF) material incorporated in a layer within linear low density polyethylene (LLDPE) film. This functionalized film structure will be selectively permeable via the embedded MOF structures to allow the exchange of gases, including ethylene, O2, CO2, other biologically active gases and certain antimicrobial compounds such as chlorine dioxide. Control of fruit and vegetable respiration (O2/CO2 balance), control endogenous and exogenous ethylene, and the delivery antimicrobial gases via MOFs could be the single most important recent technology breakthrough that allows producers in distant markets to delivery fresh produce. This research project will seek to identify MOFs with the appropriate gas exchange properties, heat stability in the blown film extrusion process and proper orientation within the film structure. Collaborative research is needed to select likely MOF candidates, to incorporate these MOFs in films extruded on pilot scale equipment, and to characterize effectiveness at a university-based postharvest laboratory to enable rapid technology development, impartial assessments, and effective reduction to practice.


Grant
Agency: Department of Agriculture | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 100.00K | Year: 2016

The objective of this project is to develop an in-transit ripening technology for pears that would help fulfill the long sought need of the industry, which is to deliver and display ripened ready-to-eat pears year-round at retail. The motivation is to overcome the limitations of the current supply chain logistics wherein fruits may be delivered to retail in lower than desirable consumer preferred eating quality which would impact repeat sales and subsequent consumption of fresh pears. The proposed technology will help the industry improve distribution efficiency and tap into new market segments such as quick service restaurants, school meal programs, long distance domestic and international export markets for fresh pears and other climacteric fruits.The technology is typically used in long distance transits (for example, from a producer in Oregon to a distribution center in Michigan) which allow sufficient time for the technology to work properly. An optional component of this technology is to include 1-methylcyclopropene gas (1-MCP) for quality management of the ripened fruits at the distribution centers. This would help delay further ripening and provide a sufficient marketing/consumer consumption window of 7 to 8 days that would fit well with the once a week shopping habit of majority of American consumers.In Phase I, we will develop an ethylene encapsulation system, in the form of a powder or gel, to be placed inside a water vapor permeable sachet. The release of ethylene can be activated by water vapor generated from the respiration of fresh pears during transit.The technical objective is to optimize the ethylene adsorption structures to provide the desirable release profiles of ethylene for ripening pears and other fruits. Our team has many years of experience working with fresh fruits including pears, encapsulation technology, and shelf life extension technologies. This experience will help ensure the success of this project. We also have strong support from the produce industry, which will provide us with guidance and technical assistance for the development and commercialization of our technology. Besides fresh market pear, the application of our technology will be extended to other fruits in Phase II of this project.


Grant
Agency: Department of Agriculture | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 99.40K | Year: 2014

The objective of this project is to develop a sprayable water-based 1-methylcycopropene (1-MCP) liquid formulation for apple, to manage the undesirable effects of ethylene when the fruits are still attached to the tree and during post-harvest storage. The motivation is to overcome the limitations of current delivery formulations to improve quality and extend the shelf life of fruits, a major impediment in quick service restaurant and school meal program fruit product offerings for kids. The successful development of our new liquid formulation can additionally help improve global food security by reducing fruit loss, and increasing fruit availability in markets that are far to reach with the current technologies. It can also help in increasing the export of apple from the United States which is currently at risk due to European new regulations.The current delivery formulation involves using a-cyclodextrin to encapsulate 1-MCP and triggering the release of 1-MCP by hydration. Although this formulation is effective, its use is largely limited to enclosed environments. The current sprayable formulations are promising, but its limitations include the use of extremely high concentrations of the active ingredient and the rapid loss of 1-MCP to the atmosphere, leading to poor response efficiency and variable or poor efficacy. To overcome these limitations, we propose to develop a new water-based 1-MCP liquid formulation that is sprayable, stable, storable, has minimum or no loss during application, and can be used alone or in combination with other antioxidants/fungicides to the target tissues of apple to inhibit scald formation and ethylene mediated undesirable effects.We propose three concepts to develop the new 1-MCP liquid formulation. The first concept involves structural and functional modifications of the 1-MCP encapsulating materials, the second concept involves controlled release of the encapsulated 1-MCP, and the third concepts involved combination of the first and second concepts to develop a commercially viable product. We are highly encouraged by our preliminary data that support the technical soundness of these concepts.The new sprayable 1-MCP liquid formulation will be prepared by encapsulating 1-MCP in & beta;-cyclodextrin cross-linked nanosponges suspended in a blend of polyol/hydrocolloid, such as glycerol/ hydroxypropyl cellulose. The nanosponges are further modified to manipulate the polarity and hydrophobicity of the inclusion complex for achieving the maximum 1-MCP inclusion rate and better control in release on hydration, while the suspending colloidal solution would form a tortuous path for 1-MCP to diffuse thereby further controlling release on dilution and spraying. The formulation will be designed to retain 1-MCP in the encapsulating material during application and allow its controlled release slowly to the target tissue on application, thereby providing all the above mentioned benefits of the technology.Our team has many years of experience working with 1-MCP, encapsulation technology, and shelf life extension of fresh produce. This experience will help ensure the success of this project. We also have strong support from the produce industry, which will provide us with guidance and technical assistance for the development and commercialization of our technology. Besides apple, the application of our technology will be extended to other climacteric fruits in Phase II of this project.


Grant
Agency: Department of Health and Human Services | Branch: | Program: STTR | Phase: Phase I | Award Amount: 499.13K | Year: 2012

DESCRIPTION (provided by applicant): Ventilator Induced Lung Injury (VILI) is a common cause of morbidity and sometimes mortality in critically ill patients with respiratory failure. The types of VILI include barotraumas, volutrauma, atelectrauma, and biotrauma. Thus ventilator setting is a delicate balance between achieving sufficient ventilation but avoiding excessive pressure and overdistension or too little pressure and excessive shear stress when ventilatory units cycle between open and closed. In addition, critically ill patients most often cannot be moved to a CT scanner, which is the traditional method for evaluating adequate ventilation. Thus in order to optimally adjust ventilator settings in an ICU, there is a need for a noninvasive, relativelyportable device that can measure regional ventilation. To address this need, in this application, we propose building a portable ventilation stethoscope (VS). The Ventilation Stethoscope is a portable device designed to measure quantitative regional ventilation using the same principles as in Magnetic Resonance Imaging (MRI). Unlike the traditional MRI system, the device is portable, smaller, and performs a measurement of regional ventilation with a single probe (similar to a stethoscope). Thus the VS is alow field (~0.01T) magnetic resonance spectrometer. To enhance sensitivity hyperpolarized 129Xe gas will be injected into the ventilator output. A key aspect of this proposal is the development of a portable continuous flow xenon laser polarizer to producea steady source of hyperpolarized 129Xe gas. The VS probe will consist of permanent magnets integrated with the rf coil into a single planar structure such that it has a region of magnetic field homogeneity external to the structure itself that is projectd into the lung at a known depth. With this device, we propose to demonstrate the measurement of regional ventilation in healthy adult human volunteers. PUBLIC HEALTH RELEVANCE: Ventilator Induced Lung Injury is a common cause of complications andsometimes death in critically ill patients with respiratory failure. This is especially true in the NICU. We propose to build a portable magnetic resonance device that will allow measurement of regional ventilation in the intensive care unit in patients who are being mechanically ventilated. The utility of this device will be to allow clinicians to optimally adjust ventilator settings to allow ventilation but to avoid lung injury.

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