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Meloty-Kapella L.,University of California at Los Angeles | Shergill B.,University of California at Irvine | Kuon J.,University of California at Los Angeles | Botvinick E.,University of California at Irvine | And 2 more authors.
Developmental Cell | Year: 2012

Notch signaling induced by cell surface ligands is critical to development and maintenance of many eukaryotic organisms. Notch and its ligands are integral membrane proteins that facilitate direct cell-cell interactions to activate Notch proteolysis and release the intracellular domain that directs Notch-specific cellular responses. Genetic studies suggest that Notch ligands require endocytosis, ubiquitylation, and epsin endocytic adaptors to activate signaling, but the exact role of ligand endocytosis remains unresolved. Here we characterize a molecularly distinct mode of clathrin-mediated endocytosis requiring ligand ubiquitylation, epsins, and actin for ligand cells to activate signaling in Notch cells. Using a cell-bead optical tweezers system, we obtained evidence for cell-mediated mechanical force dependent on this distinct mode of ligand endocytosis. We propose that the mechanical pulling force produced by endocytosis of Notch-bound ligand drives conformational changes in Notch that permit activating proteolysis.

Madsen S.J.,University of Nevada, Las Vegas | Hirschberg H.,Beckman Laser Institute
Journal of Biophotonics | Year: 2010

The blood-brain barrier (BBB) poses a significant impediment for the delivery of therapeutic drugs into the brain. This is particularly problematic for the treatment of malignant gliomas which are characterized by diffuse infiltration of tumor cells into normal brain where they are protected by a patent BBB. Selective disruption of the BBB, followed by administration of anti-cancer agents, represents a promising approach for the elimination of infiltrating glioma cells. A summary of the techniques (focused ultrasound, photodynamic therapy and photochemical internalization) for site-specific opening of the BBB will be discussed in this review. Each approach is capable of causing localized and transient opening of the BBB with minimal damage to surrounding normal brain as evidenced from magnetic resonance images and histology. © 2010 by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

News Article | January 5, 2016

These are images from endotracheal tubes: a) 5000× SEM image of 120-h postintubation endotracheal tube showing the presence of extracellular polymeric substrate; (b) 5000× SEM image of same endotracheal tube in a different location; (c) 15,000× SEM of same endotracheal tube focusing in on a cluster of cells; and (d) corresponding OCT image. doi:10.1117/1.JBO.20.12.126010 The ability to better detect and assess bacteria linked to a form of pneumonia prevalent in hospital intensive care units (ICUs) could soon become possible, according to research reported in the latest issue of the Journal of Biomedical Optics. The journal is published by SPIE, the international society for optics and photonics. Andrew Heidari and other researchers at the University of California Irvine, the Beckman Laser Institute, and N8 Medical demonstrated that optical coherence tomography (OCT) can be used to determine the presence of biofilm—bacterial growth that results from the attachment and subsequent multiplication of microorganisms to a synthetic surface. Biofilm has been linked to ventilator-associated pneumonia (VAP), which is a prevalent infection in hospital intensive care units (ICUs). Using OCT, the team was able to visualize and assess the extent of airway obstruction from biofilm deposited on intubated endotracheal tubes in vivo. "This is a newsworthy application for those working in the ICU," said David Sampson of the University of Western Australia. "Infection is an ever-present risk, and an easier way to check for biofilm could see such checks done more often and infection rates lowered, which would be a great outcome." The current method for biofilm characterization utilizes scanning electron microscopy (SEM), a lengthy process that requires extracting a sample, drying it, and coating it with a thin gold layer, none of which can be performed in vivo. OCT, on the other hand, is a noninvasive imaging technology that can provide high-resolution cross-sectional images of various biological samples, and can be adapted to provide three-dimensional volumetric information. In this study, extubated patients' endotracheal tubes were imaged using both OCT and SEM. Biofilm was present in both images, and the researchers were able to use the OCT image to measure a reduction in endotracheal inner lumen area between a 1-day intubation sample tube and a 5-day sample tube. The study showed that OCT can be used to both detect the presence of biofilm and gather further information about the extent of biofilm formation from the thickness of biofilm observed. In the future, the research group plans to use OCT images to analyze the thickness and structure of the biofilm at which intubated patients in the ICU contract VAP. Explore further: Nowhere to hide: New device sees bacteria behind the eardrum More information: Andrew E. Heidari et al. Visualizing biofilm formation in endotracheal tubes using endoscopic three-dimensional optical coherence tomography, Journal of Biomedical Optics (2015). DOI: 10.1117/1.JBO.20.12.126010

Ortiz A.E.,Harvard University | Nelson J.S.,Beckman Laser Institute
Facial Plastic Surgery | Year: 2012

Background and ObjectivesPort-wine stains (PWSs) are capillary vascular malformations that are commonly resistant to treatment. Currently, the pulsed dye laser (PDL) is the treatment of choice. Multiple treatments are required and complete blanching after laser irradiation is rarely achieved. We review current therapeutic modalities for PWSs and recent developments for enhanced clearance. Study Design/Materials and MethodsRelevant literature was reviewed including PDL modifications for improved efficacy, alternative laser devices for treatment-resistant PWSs, and the addition of agents to modulate the wound-healing response after laser irradiation. ResultsAlthough PDL is the treatment of choice for PWSs, increased understanding of interactions between PWSs and PDL has led to improvements in therapeutic outcome in terms of lesion blanching. ConclusionsPreliminary evidence of combination therapy using antiangiogenic agents after laser irradiation appears promising and could lead to the development of a new standard of care for PWSs. Copyright © 2012 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

Warren R.V.,Beckman Laser Institute
International Journal of Obesity | Year: 2016

Background:Changes in subcutaneous adipose tissue (AT) structure and metabolism have been shown to correlate with the development of obesity and related metabolic disorders. Measurements of AT physiology could provide new insight into metabolic disease progression and response to therapy. An emerging functional imaging technology, diffuse optical spectroscopic imaging (DOSI), was used to obtain quantitative measures of near infrared (NIR) AT optical and physiological properties.Methods:Ten overweight or obese adults were assessed during 3 months on calorie-restricted diets. DOSI-derived tissue concentrations of hemoglobin, water and lipid and the wavelength-dependent scattering amplitude (A) and slope (b) obtained from 30 abdominal locations and three time points (T0, T6, T12) were calculated and analyzed using linear mixed-effects models and were also used to form 3D surface images.Results:Subjects lost a mean of 11.7±3.4% of starting weight, while significant changes in A (+0.23±0.04 mm-1, adj. P<0.001),b (−0.17±0.04, adj. P<0.001), tissue water fraction (+7.2±1.1%, adj. P<0.001) and deoxyhemoglobin (1.1±0.3 μM, adj. P<0.001) were observed using mixed-effect model analysis.Discussion:Optical scattering signals reveal alterations in tissue structure that possibly correlate with reductions in adipose cell volume, while water and hemoglobin dynamics suggest improved AT perfusion and oxygen extraction. These results suggest that DOSI measurements of NIR optical and physiological properties could be used to enhance understanding of the role of AT in metabolic disorders and provide new strategies for diagnostic monitoring of obesity and weight loss.International Journal of Obesity advance online publication, 19 April 2016; doi:10.1038/ijo.2016.43. © 2016 Macmillan Publishers Limited

Yudovsky D.,Beckman Laser Institute | Durkin A.J.,Beckman Laser Institute
Journal of Biomedical Optics | Year: 2011

Monitoring of tissue blood volume and oxygen saturation using biomedical optics techniques has the potential to inform the assessment of tissue health, healing, and dysfunction. These quantities are typically estimated from the contribution of oxyhemoglobin and deoxyhemoglobin to the absorption spectrum of the dermis. However, estimation of blood related absorption in superficial tissue such as the skin can be confounded by the strong absorption of melanin in the epidermis. Furthermore, epidermal thickness and pigmentation varies with anatomic location, race, gender, and degree of disease progression. This study describes a technique for decoupling the effect of melanin absorption in the epidermis from blood absorption in the dermis for a large range of skin types and thicknesses. An artificial neural network was used to map input optical properties to spatial frequency domain diffuse reflectance of two layer media. Then, iterative fitting was used to determine the optical properties from simulated spatial frequency domain diffuse reflectance. Additionally, an artificial neural network was trained to directly map spatial frequency domain reflectance to sets of optical properties of a two layer medium, thus bypassing the need for iteration. In both cases, the optical thickness of the epidermis and absorption and reduced scattering coefficients of the dermis were determined independently. The accuracy and efficiency of the iterative fitting approach was compared with the direct neural network inversion. © 2011 Society of Photo-Optical Instrumentation Engineers (SPIE).

Yu L.,Beckman Laser Institute | Chen Z.,Beckman Laser Institute
Journal of Biomedical Optics | Year: 2010

We demonstrate the use of Doppler variance (standard deviation) imaging for 3-D in vivo angiography in the human eye. In addition to the regular optical Doppler tomography velocity and structural images, we use the variance of blood flow velocity to map the retina and choroid vessels. Variance imaging is subject to bulk motion artifacts as in phase-resolved Doppler imaging, and a histogram-based method is proposed for bulk-motion correction in variance imaging. Experiments were performed to demonstrate the effectiveness of the proposed method for 3-D vasculature imaging of human retina and choroid. © 2010 Society of Photo-Optical Instrumentation Engineers.

Tromberg B.J.,Beckman Laser Institute | Cerussi A.E.,Beckman Laser Institute
Clinical Cancer Research | Year: 2010

Diffuse optical spectroscopy (DOS), which is used to image tumor metabolic response to neoadjuvant chemotherapy (NAC), shows large changes in tumor functional parameters with significant reductions in oxy- and deoxyhemoglobin for responders versus nonresponders. Although investigational, DOS may provide a cost-effective, risk-free method for optimizing NAC drug and dosing strategies for individual patients. ©2010 AACR.

Wang Y.,Beckman Laser Institute | Lin C.-Y.,Beckman Laser Institute | Nikolaenko A.,Beckman Laser Institute | Raghunathan V.,Beckman Laser Institute | Potma E.O.,Beckman Laser Institute
Advances in Optics and Photonics | Year: 2011

The basics of four-wave mixing (FWM) and recent advances in FWM microscopy are reviewed with a particular emphasis on applications in the field of nanomaterials. The vast progress in nanostructure synthesis has triggered a need for advanced analytical tools suitable to interrogate nanostructures one at a time. The single-nanostructure sensitivity of optical microscopy has solidified the optical approach as a reliable technique for examining the electronic structure of materials at the nanoscale. By zooming in on the individual, optical microscopy has permitted detailed investigations of the linear optical response of nanomaterials such as semiconducting quantum dots and plasmon active nanometals. Besides studying the linear optical properties of nanostructures, optical microscopy has also been used to probe the nonlinear optical properties of nanoscale materials. FWM microscopy, a coherent third-order optical imaging technique, has shown great potential as a tool for investigating the nonlinear optical response of nanostructures. FWM microscopy not only permits the characterization of the nonlinear susceptibility of individual nanostructures, it also offers a route to explore the time-resolved dynamics of electronic and vibrational excitations on single structures. In addition, FWM produces strong signals from nanomaterials that are compatible with fast imaging applications, which holds promise for biological imaging studies based on nanoparticle labels that are not prone to photobleaching. © 2010 Optical Society of America.

Gardner A.R.,Beckman Laser Institute | Venugopalan V.,Beckman Laser Institute
Optics Letters | Year: 2011

We present an approach to solving the radiative transport equation (RTE) for layered media in the spatial frequency domain (SFD) using Monte Carlo (MC) simulations. This is done by obtaining a complex photon weight from analysis of the Fourier transform of the RTE. We also develop a modified shortcut method that enables a single MC simulation to efficiently provide RTE solutions in the SFD for any number of spatial frequencies. We provide comparisons between the modified shortcut method and conventional discrete transform methods for SFD reflectance. Further results for oblique illumination illustrate the potential diagnostic utility of the SFD phase-shifts for analysis of layered media. © 2011 Optical Society of America.

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