Harvard College

Biomechanics Inc.

Hood Laboratories

Other

The United States of America, As Represented by the Secretary, Department of Health and Human Services

Children's Medical Center Corporation

The University of Chicago

Beth Israel Deaconess Medical Center, Inc.

Iit Research Institute

University of Paris

Cambridge Collaborative, Inc.

Jeffrey J Fredberg

James P Butler

Ramaswamy Krishnan

Bruno Louis

Chan Young Park

Gary Glass

John Lehr

Ning Wang

Donald Elliot Ingber

David A Weitz

Julian Solway

Daniel Tschumperlin

Fei Liu

Justin Mih

Allen Ehrlicher

Nickolai Dulin

Diane Luci

David Maloney

Dhananjay T Tambe

David McCormick

Xavier Trepat

Georgia Barlovatz-Meimon

Disclosed herein is a class of molecules termed remodilins that are effective in treating asthma, pulmonary fibrosis, and associated disorders. The molecules ameliorate asthma and pulmonary fibrosis symptoms by various mechanisms, including inhibiting airway smooth muscle contractile protein accumulation, reducing airway constrictor hyperresponsiveness, inhibiting bronchial fibroblast transformation into myofibroblasts, and/or treating or preventing airway or pulmonary fibrosis.

Remodilins for airway remodeling and organ fibrosis

Disclosed are systems, apparatus, devices and methods, including a method that includes determining traction forces exerted by a cellular monolayer on a substrate on which the monolayer is placed, and determining internal forces within and between cells of the monolayer based on the determined traction forces. In some embodiments, determining the internal forces of the cellular monolayer may include determining internal stresses within the cellular monolayer that act to balance the determined traction forces over at least part of the cellular monolayer. In some embodiments, determining of the internal stresses may also include setting boundary conditions at a boundary determined based on an optical field of view of an observed section of the monolayer.

Monolayer stress microscopy

A platform for biological assays includes a base substrate providing structural support to the platform, at least one surface of the base substrate coated with position markers, a first deformable layer positioned on top of the base substrate, and a second deformable layer positioned on top of the first deformable layer, the second deformable layer embedded with deformation markers.

Deformable platforms for biological assays

Embodiments provide techniques for measuring and characterizing the dynamics of cell traction forces. Tunable elastic gel substrates can be disposed in multi-well plates. The gels can be of a uniform predetermined thickness. A multi-well plate can be loaded with gels of different shear moduli. An array of punch indenters can be attached to a loading platen such that the each indenter is aligned to a gel substrate. The indenters can apply tensile or compressive strains to the gel substrates. The magnitude, duration, and frequency of the strain can be controlled by a motor assembly coupled to a control system. The apparatus can be disposed in an incubator for long term cell culture experiments. The cell culture can be observed while a strain is applied. A ring-shaped indenter can be mounted on a microscope, coaxial to the objective lens, and lowered by a calibrated amount onto the underlying gel.

Bio-matrix stretcher

Apparatus provides an output signal characteristic of the geometry of a confined volume. There is a conduit with an open first end for exchanging acoustical energy with the confined volume. An electroacoustical transducer is coupled to the conduit for launching acoustical energy into the conduit towards the opening in the confined volume producing an incident wave and a reflected wave to form a wave field representative of the geometry of the confined volume. In one embodiment, the acoustical energy is launched into a sidewall of the tube. At least first and second pressure-wave-sensing transducers are mounted along the length of the conduit in spaced relationship for providing first and second transduced signals representative of the wave field at spaced locations in the conduit. A processor processes the first and second transduced signals to provide an output signal characteristic of the geometry of the confined volume. In one embodiment, the processor provides high-pass filtering of the impulse response.

Airway geometry imaging

Apparatus provides an output signal characteristic of the geometry of a confined volume. There is a conduit with an open first end for exchanging acoustical energy with the confined volume. An electroacoustical transducer is coupled to the conduit for launching acoustical energy into the conduit towards the opening in the confined volume producing an incident wave and a reflected wave to form a transient wave field representative of the geometry of the confined volume. At least first and second pressure-wave-sensing transducers are mounted along the length of the conduit in spaced relationship for providing first and second transduced signals representative of the transient wave field at spaced locations in the conduit. A processor processes the first and second transduced signals to provide an output signal characteristic of the geometry of the confined volume.

Single hand supportable and operable apparatus for providing an output signal characteristic of the morphology of a respiratory tract includes an acoustic pipe for exchanging acoustical energy with the tract. The pipe has an open first end in communication with an opening in the respiratory tract. A transducer, such as a loudspeaker, is coupled to the pipe for launching acoustical energy into the pipe, producing an incident wave towards the opening in the tract and a reflected wave to form a transient wave field in the pipe representative of the morphology of the tract. Preferably, first and second pressure wave sensing transducers, such as microphones, mounted along the length of the pipe in spaced relationship provide first and second transduced signals representative of the transient wave field. A processor processes the first and second transduced signals to provide an output signal characteristic of the morphology of the tract, such as the cross-sectional area as a function of the distance from the opening in the tract.

Acoustic imaging

The present invention is directed to a method for regulating formation of a complex of a plasminogen activator, its receptor and one of its inhibitors. More specifically, this method involves contacting a target cell having a plasminogen activator receptor with a compound which interacts with a component of the complex such that a change in target cell cytoskeletal stiffness results.

Method for regulating formation of a complex of plasminogen activator,

Mechanical stresses and deformations are applied directly to cell surface receptors or molecules and measured using a system including a magnetic twisting device in combination with ferromagnetic microbeads coated with ligands for integrins or any other surface receptors. The system can be used diagnostically to characterize cells and molecules and to determine the effect of transformation and compounds, including drugs, on the cells and molecules. The system can also be used to induce cells to grow or alter production of molecules by the cells.

Method and system for measurement of mechanical properties of molecules

A sound source located inside a tube having one end inside the mouth or nose of a subject provides an acoustic transient signal that propagates into the respiratory system of the subject to provide reflections sensed by a single mircophone inside the tube between the sound source and the mouth of the subject for recording on a transient recorder or computer and display on an oscilloscope after passing through a low pass filter to provide an output signal representative of the acoustical properties of the airways of the subject. This output signal may be processed in accordance with the deconvolution integral and other algorithms to determine essentially the acoustic impulse response, impedance or effective cross-sectional area of the airways, typically as a function of the distance from a reference point, such as the end of the tube.

Acoustic pulse response measuring

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Sharon, MA, United States of America

Jeffrey J Fredberg