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At least 667 records · Page 37
All sourcesNASA NTRSDOE OSTI
DOE OSTI2016

First Delayed Resection Findings After Irreversible Electroporation (IRE) of Human Localised Renal Cell Carcinoma (RCC) in the IRENE Pilot Phase 2a Trial

IntroductionIt is postulated that focal IRE affords complete ablation of soft-tissue tumours while protecting the healthy peritumoral tissue. Therefore, IRE may be an interesting option for minimally invasive, kidney-tissue-sparing, non-thermal ablation of renal tumours.AimWith this current pilot study (“IRENE trial”), we present the first detailed histopathological data of IRE of human RCC followed by delayed tumour resection. The aim of this interim analysis of the first three patients was to investigate the ablation efficiency of percutaneous image-guided focal IRE in RCC, to assess whether a complete ablation of T1a RCC and tissue preservation with the NanoKnife system is possible and to decide whether the ablation parameters need to be altered.MethodsFollowing resection 4 weeks after percutaneous IRE, the success of ablation and detailed histopathological description were used to check the ablation parameters.ResultsThe IRE led to a high degree of damage to the renal tumours (1 central, 2 peripheral; size range 15–17 mm). The postulated homogeneous, isomorphic damage was only partly confirmed. We found a zonal structuring of the ablation zone, negative margins and, enclosed within the ablation zone, very small tumour residues of unclear malignancy.ConclusionAccording to these initial, preliminary study results of the first three renal cases, a new zonal distribution of IRE damage was described and the curative intended, renal saving focal ablation of localised RCC below <3 cm by percutaneous IRE by the NanoKnife system appears to be possible, but needs further, systematic evaluation for this treatment method and treatment protocol.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

HYBRID simulations of diffraction-limited focusing with Kirkpatrick-Baez mirrors for a next-generation In Situ hard X-ray nanoprobe

Next-generation hard X-ray nanoprobe beamlines such as the In Situ Nanoprobe (ISN) beamline being planned at the Advanced Photon Source aim at providing very high spatial resolution while also enabling very high focused flux, to study complex materials and devices using fast, multidimensional imaging across many length scales. The ISN will use diffractive optics to focus X-rays with a bandpass of ΔE/E = 10 –4 into a focal spot of 20 nm or below. Reflective optics in Kirkpatrick-Baez geometry will be used to focus X-rays with a bandpass as large as ΔE/E = 10 –2 into a focal spot of 50 nm. Diffraction-limited focusing with reflective optics is achieved by spatial filtering and use of a very long, vertically focusing mirror. Furthermore, to quantify the performance of the ISN beamline, we have simulated the propagation of both partially and fully coherent wavefronts from the undulator source, through the ISN beamline and into the mirror-based focal spot. Simulations were carried out using the recently developed software “HYBRID.”

43 PARTICLE ACCELERATORS↗
DOE OSTI2012

XIAP reverses various functional activities of FRNK in endothelial cells

Highlights: Black-Right-Pointing-Pointer FRNK domain is recruited into focal adhesion (FA), controlling endothelial cell adhesion. Black-Right-Pointing-Pointer XIAP binds the FRNK domain of FAK. Black-Right-Pointing-Pointer XIAP inhibits recruitment of FRNK into Fas and FRNK-promoted cell adhesion. Black-Right-Pointing-Pointer XIAP plays a key role in vascular functions of FRNK or FRNK domain-mediated vascular functions of FAK. -- Abstract: In endothelial cells, focal adhesion kinase (FAK) regulates cell proliferation, migration, adhesion, and shear-stimulated activation of MAPK. We recently found that FAK is recruited into focal adhesion (FA) sites through interactions with XIAP (X-chromosome linked inhibitor of apoptosis protein) and activated by Src kinase in response to shear stress. In this study, we examined which domain(s) of FAK is(are) important for various vascular functions such as FA recruiting, XIAP-binding and shear stress-stimulated ERK activation. Through a series of experiments, we determined that the FRNK domain is recruited into FA sites and promotes endothelial cell adhesion. Interestingly, XIAP knockdown was shown to reduce FA recruitment of FRNK and the cell adhesive effect of FRNK. In addition, we found that XIAP interacts with FRNK, suggesting cross-talk between XIAP and FRNK. We also demonstrated that FRNK inhibits endothelial cell migration and shear-stimulated ERK activation. These inhibitory effects of FRNK were reversed by XIAP knockdown. Taken together, we can conclude that XIAP plays a key role in vascular functions of FRNK or FRNK domain-mediated vascular functions of FAK.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

TRPM7 is required for ovarian cancer cell growth, migration and invasion

Highlights: • Silence of TRPM7 in ovarian cancer cells inhibits cell proliferation, migration and invasion. • Silence of TRPM7 decreases phosphorylation levels of Akt, Src and p38 in ovarian cancer cells. • Silence of TRPM7 increases expression of filamentous actin and number of focal adhesions in ovarian cancer cells. - Abstract: Our previous study demonstrated that the melastatin-related transient receptor potential channel 7 (TRPM7) was highly expressed in ovarian carcinomas and its overexpression was significantly associated with poor prognosis in ovarian cancer patients. However, the function of TRPM7 in ovarian cancer is mostly unknown. In this study, we examined the roles of TRPM7 in ovarian cancer cell proliferation, migration and invasion. We found that short hairpin RNA interference-mediated silence of TRPM7 significantly inhibited cell proliferation, colony formation, migration and invasion in multiple ovarian cancer cell lines. Mechanistic investigation revealed that silence of TRPM7 decreased phosphorylation levels of Akt, Src and p38 and increased filamentous actin and focal adhesion number in ovarian cancer cells. Thus, our results suggest that TRPM7 is required for proliferation, migration and invasion of ovarian cancer cells through regulating multiple signaling transduction pathways and the formation of focal adhesions.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Micropillar displacements by cell traction forces are mechanically correlated with nuclear dynamics

Cells sense physical cues at the level of focal adhesions and transduce them to the nucleus by biochemical and mechanical pathways. While the molecular intermediates in the mechanical links have been well studied, their dynamic coupling is poorly understood. In this study, fibroblast cells were adhered to micropillar arrays to probe correlations in the physical coupling between focal adhesions and nucleus. For this, we used novel imaging setup to simultaneously visualize micropillar deflections and EGFP labeled chromatin structure at high spatial and temporal resolution. We observed that micropillar deflections, depending on their relative positions, were positively or negatively correlated to nuclear and heterochromatin movements. Our results measuring the time scales between micropillar deflections and nucleus centroid displacement are suggestive of a strong elastic coupling that mediates differential force transmission to the nucleus. - Highlights: • Correlation between focal adhesions and nucleus studied using novel imaging setup. • Micropillar and nuclear displacements were measured at high resolution. • Correlation timescales show strong elastic coupling between cell edge and nucleus.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2019

Kindlin Is Mechanosensitive: Force-Induced Conformational Switch Mediates Cross-Talk among Integrins

Mechanical stresses directly regulate the function of several proteins of the integrin-mediated focal adhesion complex as they experience intra- and extracellular forces. Kindlin is a largely overlooked member of the focal adhesion complex whose roles in cellular mechanotransduction are only recently being identified. Recent crystallographic experiments have revealed that kindlins can form dimers that bind simultaneously to two integrins, providing a mechanistic explanation of how kindlins may promote integrin activation and clustering. In this study, using the newly identified molecular structure, we modeled the response of the kindlin2 dimer in complex with integrin β1 to mechanical cytoskeletal forces on integrins. Using molecular dynamics simulations, we show that forces on integrins are directly transmitted to the kindlin2 dimerization site, resulting in a shift in an R577-S550/E553 interaction network at this site. Under force, R577 on one protomer switches from interacting with S550 to forming new hydrogen bonds with E553 on the neighboring protomer, resulting in the strengthening of the kindlin2 dimer in complex with integrin β1. This force-induced strengthening is similar to the catch-bond mechanisms that have previously been observed in other adhesion molecules. So, based on our results, we propose that the kindlin2 dimer is mechanosensitive and can strengthen integrin-mediated focal adhesions under force by shifting the interactions at its dimerization sites.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Land-use history, fire regime, and large-mammal herbivory affect deer-preferred plant diversity in longleaf pine woodlands

Since ecological systems often experience multiple disturbances, understanding changes in important ecological interactions, such as plant-herbivore interactions, may require studies capable of disentangling the unique and interactive effects of multiple forms of disturbance. For example, understanding how mammalian herbivores affect plant communities may require understanding how widespread past disturbances, such as agricultural land use, interact with contemporary disturbances, such as prescribed fire. Here, we tested if past agricultural land use and contemporary fire regime modified the effects of mammalian herbivory on focal plant communities by measuring the richness of plant species preferred by deer at 26 longleaf pine woodlands containing paired open and large-mammal exclusion plots. Land-use history significantly affected the community composition of deer-preferred species, and focal species were 8.19 times more likely to be present in post-agricultural sites than non-agricultural sites. Large-mammal herbivory only affected plant species richness in woodlands with low fire frequencies wherein focal species were on average 2.23 times more likely to be present in exclusion plots than open plots. These results suggest that past and present disturbances can mediate contemporary plant-animal interactions and may explain spatial patterns in the intensity of large-mammal herbivory. Our findings also suggest that common management practices, such as use of prescribed burns, may indirectly promote plant species richness by reducing deer herbivory.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2012

A Multimodal Approach Including Craniospinal Irradiation Improves the Treatment Outcome of High-risk Intracranial Nongerminomatous Germ Cell Tumors

Purpose: To evaluate whether a multimodal approach including craniospinal irradiation (CSI) improves treatment outcome in nongerminomatous germ cell tumor (NGGCT) patients. Methods and Materials: We reviewed the records of 32 patients with NGGCTs. Fourteen patients belonged to the intermediate prognosis group (immature teratoma, teratoma with malignant transformation, and mixed tumors mainly composed of germinoma or teratoma), and 18 patients belonged to the poor prognosis group (other highly malignant tumors). Patients with pure germinoma or mature teratoma were excluded from this study. Nineteen patients were treated with a combination of surgery, chemotherapy, and radiotherapy (RT); 9 patients received chemotherapy plus RT; 3 patients received surgery plus RT; and 1 patient received RT alone. Twenty-seven patients received CSI with a median of 36 Gy (range, 20-41 Gy) plus focal boost of 18-30.6 Gy, and 5 patients received whole-brain RT (WBRT) (20-36 Gy) or focal RT (50.4-54 Gy). The rate of total and subtotal resection was 71.9%. The median follow-up for surviving patients was 121 months. Results: Treatment failed in 7 patients. Three of the 5 patients who received focal RT or WBRT had local failure. Four cerebrospinal fluid (CSF) failures occurred after CSI. No failure occurred in the intermediate prognosis group. Ten-year recurrence-free survival (RFS) and overall survival (OS) for all patients were 77.6% and 74.6%, respectively. Ten-year RFS for the intermediate and poor prognosis groups were 100% and 61.1%, respectively (p = 0.012). OS for the two groups were 85.1% and 66.7%, respectively (p = 0.215). Tumor histology and CSI were significant prognostic factors for RFS, and CSI was significantly associated with OS. Conclusions: A multimodal approach was effective for treating NGGCTs. CSI should be considered for patients with poor prognostic histology.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2015

Comparison of [{sup 11}C]choline Positron Emission Tomography With T2- and Diffusion-Weighted Magnetic Resonance Imaging for Delineating Malignant Intraprostatic Lesions

Purpose: The purpose of this study was to compare the accuracy of [{sup 11}C]choline positron emission tomography (CHOL-PET) with that of the combination of T2-weighted and diffusion-weighted (T2W/DW) magnetic resonance imaging (MRI) for delineating malignant intraprostatic lesions (IPLs) for guiding focal therapies and to investigate factors predicting the accuracy of CHOL-PET. Methods and Materials: This study included 21 patients who underwent CHOL-PET and T2W/DW MRI prior to radical prostatectomy. Two observers manually delineated IPL contours for each scan, and automatic IPL contours were generated on CHOL-PET based on varying proportions of the maximum standardized uptake value (SUV). IPLs identified on prostatectomy specimens defined reference standard contours. The imaging-based contours were compared with the reference standard contours using Dice similarity coefficient (DSC), and sensitivity and specificity values. Factors that could potentially predict the DSC of the best contouring method were analyzed using linear models. Results: The best automatic contouring method, 60% of the maximum SUV (SUV{sub 60}) , had similar correlations (DSC: 0.59) with the manual PET contours (DSC: 0.52, P=.127) and significantly better correlations than the manual MRI contours (DSC: 0.37, P<.001). The sensitivity and specificity values were 72% and 71% for SUV{sub 60}; 53% and 86% for PET manual contouring; and 28% and 92% for MRI manual contouring. The tumor volume and transition zone pattern could independently predict the accuracy of CHOL-PET. Conclusions: CHOL-PET is superior to the combination of T2W/DW MRI for delineating IPLs. The accuracy of CHOL-PET is insufficient for gland-sparing focal therapies but may be accurate enough for focal boost therapies. The transition zone pattern is a new classification that may predict how well CHOL-PET delineates IPLs.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

Limited Margin Radiation Therapy for Children and Young Adults With Ewing Sarcoma Achieves High Rates of Local Tumor Control

Purpose: To determine the rate of local failure using focal conformal, limited margin radiation therapy (RT) and dose escalation for tumors ≥8 cm (greatest dimension at diagnosis) in children and young adults with Ewing sarcoma (EWS). Methods and Materials: Eligible patients with EWS were treated on a phase 2 institutional trial of focal conformal, limited margin RT using conformal or intensity modulated techniques. The treatment volume incorporated a 1-cm constrained margin around the gross tumor. Unresected tumors, <8 cm at diagnosis, received a standard dose of 55.8 Gy and tumors ≥8 cm, an escalated dose to 64.8 Gy. Patients with microscopic residual disease after resection received adjuvant RT to 50.4 Gy. Adjuvant brachytherapy was permitted in selected patients. Results: Forty-five patients were enrolled: 26 with localized and 19 with metastatic disease. Median (range) age, tumor size, and follow-up were 13.0 years (2.9-24.7 years), 9.0 cm (2.4-17.0 cm), and 54.5 months (1.9-122.2 months), respectively. All patients received systemic chemotherapy. The median (range) RT dose for all patients was 56.1 Gy (45-65.5 Gy). Seventeen patients received adjuvant, 16 standard-dose, and 12 escalated-dose RT. Failures included 1 local, 10 distant, and 1 local/distant. The estimated 10-year cumulative incidence of local failure was 4.4% ± 3.1%, with no statistical difference seen between RT treatment groups and no local failures in the escalated-dose RT treatment group. Conclusions: Treatment with focal conformal, limited margin RT, including dose escalation for larger tumors, provides favorable local tumor control in EWS.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2015

Morphology and orientation of β-BaB{sub 2}O{sub 4} crystals patterned by laser in the inside of samarium barium borate glass

Nonlinear optical β-BaB{sub 2}O{sub 4} crystal lines (β-BBO) were patterned in the inside of 8Sm{sub 2}O{sub 3}–42BaO–50B{sub 2}O{sub 3} glass by irradiations of continuous-wave Yb:YVO{sub 4} lasers with a wavelength of 1080 nm (power: P=0.8–1.0 W, scanning speed: S=0.2–2.5 μm/s), in which the laser focal position was moved gradually from the surface to the inside. The morphology, size, and orientation of β-BBO crystals were examined from polarization optical microscope and birefringence imaging observations. It was demonstrated that c-axis oriented β-BBO crystals with long lengths (e.g., 20 mm) were patterned in the inside of the glass. The morphology of β-BBO in the cross-section of lines was a rectangular shape with rounded corners, and the volume of β-BBO formed increased with increasing laser power and with decreasing laser scanning speed. The maximum depth in the inside from the surface for β-BBO patterning increased with increasing laser power, e.g., D{sub max}∼100 μm at P=0.8 W, D{sub max}∼170 μm at P=0.9 W, and D{sub max}∼200 μm at P=1 W. The present study proposes that the laser-induced crystallization opens a new door for applied engineering in glassy solids. - Graphical abstract: This figure shows the POM photographs for β-BaB{sub 2}O{sub 4} crystal lines patterned by cw Yb:YVO{sub 4} fiber laser irradiations with a laser power of P=0.8 W and a laser scanning speed S=2 μm/s in the glass. The laser focal point was moved gradually from the surface into the inside. The results shown in Fig. 1 demonstrate that it is possible to pattern highly oriented β-BaB{sub 2}O{sub 4} crystals even in the inside of glasses. - Highlights: • β-BaB{sub 2}O{sub 4} crystal lines were patterned in the inside of a glass by lasers. • Laser focal position was moved gradually from the surface to the inside. • Birefringence imaging was observed. • Morphology, size, and orientation of crystals were clarified. • Crystal lines with long lengths (e.g., 20 mm) were patterned at the depth of 200 μm.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2012

Non-destructive characterisation of polymers and Al-alloys by polychromatic cone-beam phase contrast tomography

X-ray computed tomography (XCT) has become a very important tool for the non-destructive characterisation of materials. Continuous improvements in the quality and performance of X-ray tubes and detectors have led to cone-beam XCT systems that can now achieve spatial resolutions down to 1 {mu}m and even below. Since not only the amplitude but also the phase of an X-ray beam is altered while passing through an object, phase contrast effects can occur even for polychromatic sources when the spatial coherence due to a small focal spot size is high enough. This can lead to significant improvements over conventional attenuation-based X-ray computed tomography. Phase contrast can increase by edge enhancement the visibility of small structures and of features which are only slightly different in attenuation. We report on the possibilities of polychromatic cone-beam phase contrast tomography for non-destructive characterisation of materials. A carbon fibre-reinforced polymer and the Al-alloys AlMg5Si7 and AlSi18 were investigated with high resolution cone-beam X-ray computed tomography with a polychromatic tube source. Under certain conditions strong phase contrast resulting in an upward and downward overshooting of the grey values across edges was observed. The phase effects are much stronger for the polymer than for the Al-alloys. The influence on the phase contrast of the parameters, including source-detector distance, focal spot size and tube acceleration voltage is presented. Maximum phase contrast was observed for a maximum distance between the source and the detector, for a low voltage and a minimum focal spot size at the X-ray source. The detectability of the different phases is improved by the edge enhancement and the resulting improvement of sharpness. Thus, a better segmentation of the carbon fibres in the fibre-reinforced polymer and of the Mg{sub 2}Si-phase in the AlMg5Si7-alloy is achieved. Primary and eutectic Si cannot be detected by attenuation-based X-ray computed tomography due to the small difference in X-ray attenuation between the Si and the Al-matrix in AlSi18. However, phase contrast effects lead to a significant detectability and the large primary Si particles become clearly visible in the tomograms of AlSi18. - Highlights: Black-Right-Pointing-Pointer Phase contrast increases with increasing distance object-detector and with decreasing U, X-ray spot. Black-Right-Pointing-Pointer The detectability of details is improved by the phase contrast. Black-Right-Pointing-Pointer For the carbon fibre-reinforced polymer the visibility of the carbon fibres is improved. Black-Right-Pointing-Pointer For AlMg5Si7 the detectability of the phases Fe-aluminides and Mg{sub 2}Si particles is improved. Black-Right-Pointing-Pointer For AlSi18 primary Si particles with a size > 50 {mu}m become detectable because of the phase contrast.

36 MATERIALS SCIENCE↗
DOE OSTI2013

Volumetric-modulated arc therapy (RapidArc) vs. conventional fixed-field intensity-modulated radiotherapy for {sup 18}F-FDG-PET-guided dose escalation in oropharyngeal cancer: A planning study

Fluorine-18-fluorodeoxyglucose-positron emission tomography ({sup 18}F-FDG-PET)–guided focal dose escalation in oropharyngeal cancer may potentially improve local control. We evaluated the feasibility of this approach using volumetric-modulated arc therapy (RapidArc) and compared these plans with fixed-field intensity-modulated radiotherapy (IMRT) focal dose escalation plans. Materials and methods: An initial study of 20 patients compared RapidArc with fixed-field IMRT using standard dose prescriptions. From this cohort, 10 were included in a dose escalation planning study. Dose escalation was applied to {sup 18}F-FDG-PET–positive regions in the primary tumor at dose levels of 5% (DL1), 10% (DL2), and 15% (DL3) above standard radical dose (65 Gy in 30 fractions). Fixed-field IMRT and double-arc RapidArc plans were generated for each dataset. Dose-volume histograms were used for plan evaluation and comparison. The Paddick conformity index (CI{sub Paddick}) and monitor units (MU) for each plan were recorded and compared. Both IMRT and RapidArc produced clinically acceptable plans and achieved planning objectives for target volumes. Dose conformity was significantly better in the RapidArc plans, with lower CI{sub Paddick} scores in both primary (PTV1) and elective (PTV2) planning target volumes (largest difference in PTV1 at DL3; 0.81 ± 0.03 [RapidArc] vs. 0.77 ± 0.07 [IMRT], p = 0.04). Maximum dose constraints for spinal cord and brainstem were not exceeded in both RapidArc and IMRT plans, but mean doses were higher with RapidArc (by 2.7 ± 1 Gy for spinal cord and 1.9 ± 1 Gy for brainstem). Contralateral parotid mean dose was lower with RapidArc, which was statistically significant at DL1 (29.0 vs. 29.9 Gy, p = 0.01) and DL2 (29.3 vs. 30.3 Gy, p = 0.03). MU were reduced by 39.8–49.2% with RapidArc (largest difference at DL3, 641 ± 94 vs. 1261 ± 118, p < 0.01). {sup 18}F-FDG-PET–guided focal dose escalation in oropharyngeal cancer is feasible with RapidArc. Compared with conventional fixed-field IMRT, RapidArc can achieve better dose conformity, improve contralateral parotid sparing, and uses fewer MU.

61 RADIATION PROTECTION AND DOSIMETRY↗
DOE OSTI2016

The GCT camera for the Cherenkov Telescope Array

The Gamma Cherenkov Telescope (GCT) is one of the designs presented for the Small Sized Telescope (SST) section of the Cherenkov Telescope Array (CTA). The GCT uses dual-mirror optics, resulting in a compact telescope with good image quality and a large field of view with a smaller, more economical, camera than is achievable with conventional single mirror solutions. The photon counting GCT camera is designed to record the flashes of atmospheric Cherenkov light from gamma and cosmic ray initiated cascades, which last only a few tens of nanoseconds. The GCT optics require that the camera detectors follow a convex surface with a radius of curvature of 1 m and a diameter of ~35 cm, which is approximated by tiling the focal plane with 32 modules. The initial camera prototype is equipped with multi-anode photomultipliers, each comprising an 8×8 array of 6×6 mm 2 pixels to provide the required angular scale, adding up to 2048 pixels in total. Detector signals are shaped, amplified and digitised by electronics based on custom ASICs that provide digitisation at 1 GSample/s. The camera is self-triggering, retaining images where the focal plane light distribution matches predefined spatial and temporal criteria. The electronics are housed in the liquid-cooled, sealed camera enclosure. LED flashers at the corners of the focal plane provide a calibration source via reflection from the secondary mirror. The first GCT camera prototype underwent preliminary laboratory tests last year. In November 2015, the camera was installed on a prototype GCT telescope (SST-GATE) in Paris and was further used to successfully record the first Cherenkov light of any CTA prototype, and the first Cherenkov light seen with such a dual-mirror optical system. A second full-camera prototype based on Silicon Photomultipliers is under construction. Up to 35 GCTs are envisaged for CTA.

47 OTHER INSTRUMENTATION↗
DOE OSTI2021

Vinculin is required for neuronal mechanosensing but not for axon outgrowth

Integrin receptors are transmembrane proteins that bind to the extracellular matrix (ECM). In most animal cell types integrins cluster together with adaptor proteins at focal adhesions that sense and respond to external mechanical signals. In the central nervous system (CNS), ECM proteins are sparsely distributed, the tissue is comparatively soft and neurons do not form focal adhesions. Thus, how neurons sense tissue stiffness is currently poorly understood. Here, we found that integrins and the integrin-associated proteins talin and focal adhesion kinase (FAK) are required for the outgrowth of neuronal processes. Vinculin, however, whilst not required for neurite outgrowth was a key regulator of integrin-mediated mechanosensing of neurons. During growth, growth cones of axons of CNS derived cells exerted dynamic stresses of around 10–12 Pa on their environment, and axons grew significantly longer on soft (0.4 kPa) compared to stiff (8 kPa) substrates. Depletion of vinculin blocked this ability of growth cones to distinguish between soft and stiff substrates. These data suggest that vinculin in neurons acts as a key mechanosensor, involved in the regulation of growth cone motility.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2020

Dynamic Focusing with High-Quality-Factor Metalenses

Metasurface lenses provide an ultrathin platform in which to focus light, but weak light–matter interactions limit their dynamic tunability. Here we design submicron-thick, ultrahigh quality factor (high-Q) metalenses that enable dynamic modulation of the focal length and intensity. Using full-field simulations, we show that quality factors exceeding 5000 can be generated by including subtle, periodic perturbations within the constituent Si nanoantennas. Such high-Q resonances enable lens modulation based on the nonlinear Kerr effect, with focal lengths varying from 4 to 6.5 μm and focal intensities decreasing by half as input intensity increases from 0.1 to 1 mW/μm 2 . We also show how multiple high-Q resonances can be embedded in the lens response through judicious placement of the perturbations. Our high-Q lens design, with quality factors 2 orders of magnitude higher than existing lens designs, provides a foundation for reconfigurable, multiplexed, and hyperspectral metasurface imaging platforms.

36 MATERIALS SCIENCE↗
DOE OSTI2018

ZIKA virus infection causes persistent chorioretinal lesions

Zika-infected patients can have eye involvement ranging from mild conjunctivitis to severe chorioretinal lesions, however the possible long-term sequelae of infection and timeline to recovery remain unknown. Here we describe the partial recovery of chorioretinal lesions in an immunocompetent patient diagnosed with bilateral posterior uveitis associated with Zika infection and show that some lesions resolved with focal atrophy evident as pigmentary changes on funduscopy. To better understand the progression of the lesions and correlate the changes in fundus imaging with local viral load, immune responses, and retinal damage, we developed a symptomatic mouse model of ocular Zika virus infection. Imaging of the fundus revealed multiple hypopigmentary patches indicative of chorioretinal degeneration as well as thinning of the retina that mirror the lesions in patients. Microscopically, the virus primarily infected the optic nerve, retinal ganglion cells, and inner nuclear layer cells, showing thinning of the outer plexiform layer. During acute infection, the eyes showed retinal layer disorganization, retinitis, vitritis, and focal choroiditis, with mild cellular infiltration and increased expression of tumor necrosis factor, interferon-γ, granzyme B, and perforin. Focal areas of gliosis and retinal degeneration persisted 60 dpi. The model recapitulates features of ZIKA infections in patients and should help elucidate the mechanisms underlying the damage to the eyes and aid in the development of effective therapeutics.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2018

Spatiotemporal control of laser intensity

The controlled coupling of a laser to a plasma has the potential to address grand scientific challenges including reaching the Schwinger limit, developing compact free electron lasers, extending linear colliders to TeV energies, and generating novel light sources for probing electron dynamics within molecules. Currently, many such applications have limited flexibility and poor control over the laser focal volume. Here we present an advanced focusing scheme called a “flying focus” where a chromatic focusing system combined with chirped laser pulses enables a small–diameter laser focus to propagate nearly 100 times its Rayleigh length, while decoupling the speed at which the peak intensity moves from its group velocity. This unprecedented spatiotemporal control over the laser focal volume allows the laser focus to co- or counter–propagate along its axis at any velocity. Experiments validating the concept measured subluminal (-0.09c) to superluminal (39c) focal spot velocities generating a nearly constant peak intensity over 4.5 mm.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗