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1
Hopko, Sandra N., I. Charles Ume, and Dathan S. Erdahl. "Development of a Flexible Laser Ultrasonic Probe." Journal of Manufacturing Science and Engineering 124, no. 2 (April 29, 2002): 351–57. http://dx.doi.org/10.1115/1.1379369.
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Ultrasonics is a widely used nondestructive testing technique, which is often applied off-line for weld quality inspection. Laser ultrasonic (LU) inspection systems have the potential for on-line application, providing the means to identify unacceptable welds as they are formed. Because LU systems are non-contacting, they can be used for testing moving specimens or for operation in hazardous and/or high temperature environments. A highly versatile system can be created when an optical fiber delivery system is incorporated into the design. Introduction of a focusing objective increases the allowable working distance and permits stronger generation using material ablation as the generating mechanism. This paper describes the development of a laser ultrasonic probe using an optical fiber delivery system with a distal end, focusing objective. The optical fiber delivery system can be configured as a single fiber source, a linear array (fiber bundle) or a phased array. Results include experimentally obtained directivity patterns demonstrating ultrasonic generation using ablation sources. Thermoelastic source results are also included. This paper demonstrates the potential of the fiber tool and presents an overview of the weld control scheme.
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Weierstall, Uwe. "Liquid sample delivery techniques for serial femtosecond crystallography." Philosophical Transactions of the Royal Society B: Biological Sciences 369, no. 1647 (July 17, 2014): 20130337. http://dx.doi.org/10.1098/rstb.2013.0337.
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X-ray free-electron lasers overcome the problem of radiation damage in protein crystallography and allow structure determination from micro- and nanocrystals at room temperature. To ensure that consecutive X-ray pulses do not probe previously exposed crystals, the sample needs to be replaced with the X-ray repetition rate, which ranges from 120 Hz at warm linac-based free-electron lasers to 1 MHz at superconducting linacs. Liquid injectors are therefore an essential part of a serial femtosecond crystallography experiment at an X-ray free-electron laser. Here, we compare different techniques of injecting microcrystals in solution into the pulsed X-ray beam in vacuum. Sample waste due to mismatch of the liquid flow rate to the X-ray repetition rate can be addressed through various techniques.
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Ashley, S., S. G. Brooks, A. A. Gehani, R. C. Kester, and M. R. Rees. "Thermal characteristics of sapphire contact probe delivery systems for laser angioplasty." Lasers in Surgery and Medicine 10, no. 3 (1990): 234–44. http://dx.doi.org/10.1002/lsm.1900100304.
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Lesinski, S. George, and Kylie Giesken. "Optical Fiber for CO2 Laser Otosclerosis Surgery." Otolaryngology–Head and Neck Surgery 139, no. 2_suppl (August 2008): P57. http://dx.doi.org/10.1016/j.otohns.2008.05.184.
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Objective To determine the safety and efficacy of new handheld optical fibers for CO2 laser stapedotomy and stapedectomy revision. Advantages of the new CO2 optic fibers are: convenience, reliability and precision. Disadvantages are: special adaptor required for laser console, limited spot size and cost. Omniguides’ handheld optic fibers introduce a safe, effective, and precise delivery system for CO2 laser otosclerosis surgery. Methods Prospective study of 25 consecutive otosclerosis patients. Researchers at Massachusetts Institute of Technology have developed a flexible optical fiber (photonic bandgap reflector) which can deliver CO2 laser energy through a handheld probe with minimal loss of laser energy. Omniguide introduced a 0.9 mm (O.D.) fiber in 2007 specifically for otologic surgery. This clinical study analyzes the safety and effectiveness of this new technology for CO2 laser otosclerosis surgery. To determine appropriate energy parameters, stapedotomy was performed in the laboratory on human temporal bones. Subsequently, 25 consecutive otosclerosis patients underwent CO2 laser stapedotomy (21) or stapedectomy revision (4) employing these handheld fibers. 6-month post op audiograms were analyzed for air/bone gaps and nerve loss according to AAO-HNS guidelines. Results 21/21 primary and 3/4 revision patients closed the air/bone gap to within 15 decibels (mean 0.5, 1, 2, 3 KHz). There was no nerve loss at these frequencies. Three patients demonstrated a slight loss at 4 KHz (2–15 db, 1–20 db) compared with their preop audiograMS These results compare favorably with previous otosclerosis surgery performed by the author with microscope mounted CO2 lasers. Conclusions Advantages of the new CO2 optic fibers are: convenience, reliability and precision. Disadvantages are: special adaptor required for laser console, limited spot size and cost. Omniguides’ handheld optic fibers introduce a safe, effective and precise delivery system for CO2 laser otosclerosis surgery.
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Dadey, David Y. A., Ashwin A. Kamath, Matthew D. Smyth, Michael R. Chicoine, Eric C. Leuthardt, and Albert H. Kim. "Utilizing personalized stereotactic frames for laser interstitial thermal ablation of posterior fossa and mesiotemporal brain lesions: a single-institution series." Neurosurgical Focus 41, no. 4 (October 2016): E4. http://dx.doi.org/10.3171/2016.7.focus16207.
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OBJECTIVE The precision of laser probe insertion for interstitial thermal therapy of deep-seated lesions is limited by the method of stereotactic guidance. The objective of this study was to evaluate the feasibility of customized STarFix 3D-printed stereotactic platforms to guide laser probe insertion into mesiotemporal and posterior fossa targets. METHODS The authors conducted a retrospective review of 5 patients (12–55 years of age) treated with laser interstitial thermal therapy (LITT) in which STarFix platforms were used for probe insertion. Bone fiducials were implanted in each patient's skull, and subsequent CT scans were used to guide the design of each platform and incorporate desired treatment trajectories. Once generated, the platforms were mounted on the patients' craniums and used to position the laser probe during surgery. Placement of the laser probe and the LITT procedure were monitored with intraoperative MRI. Perioperative and follow-up MRI were performed to identify and monitor changes in target lesions. RESULTS Accurate placement of the laser probe was observed in all cases. For all patients, thermal ablation was accomplished without intraoperative complications. Of the 4 patients with symptomatic lesions, 2 experienced complete resolution of symptoms, and 1 reported improved symptoms compared with baseline. CONCLUSIONS Customized stereotactic platforms were seamlessly incorporated into the authors' previously established LITT workflow and allowed for accurate treatment delivery.
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Li, Yuchao, Hongbao Xin, Chang Cheng, Yao Zhang, and Baojun Li. "Optical separation and controllable delivery of cells from particle and cell mixture." Nanophotonics 4, no. 3 (November 6, 2015): 353–60. http://dx.doi.org/10.1515/nanoph-2015-0008.
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Abstract Cell separation and delivery have recently gained significant attention in biological and biochemical studies. In thiswork, an optical method for separation and controllable delivery of cells by using an abruptly tapered fiber probe is reported. By launching a laser beam at the wavelength of 980 nm into the fiber, a mixture of cells with sizes of ~5 and ~3 μm and poly(methyl methacrylate) particles with size of 5 μm are separated into three chains along the direction of propagation of light. The cell and particle chains are delivered in three dimensions over 600 μm distance. Experimental results are interpreted by numerical simulations. Optical forces and forward migration velocities of different particles and cells are calculated and discussed.
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Calzavacca, Paolo, Roger G. Evans, Michael Bailey, Rinaldo Bellomo, and Clive N. May. "Variable responses of regional renal oxygenation and perfusion to vasoactive agents in awake sheep." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 309, no. 10 (November 15, 2015): R1226—R1233. http://dx.doi.org/10.1152/ajpregu.00228.2015.
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Vasoactive agents are used in critical care to optimize circulatory function, but their effects on renal tissue oxygenation in the absence of anesthesia remain largely unknown. Therefore, we assessed the effects of multiple vasoactive agents on regional kidney oxygenation in awake sheep. Sheep were surgically instrumented with pulmonary and renal artery flow probes, and combination fiber-optic probes, in the renal cortex and medulla, comprising a fluorescence optode to measure tissue Po2 and a laser-Doppler probe to assess tissue perfusion. Carotid arterial and renal venous cannulas enabled measurement of arterial pressure and total renal oxygen delivery and consumption. Norepinephrine (0.1 or 0.8 μg·kg−1·min−1) dose-dependently reduced cortical and medullary laser Doppler flux (LDF) and Po2 without significantly altering renal blood flow (RBF), or renal oxygen delivery or consumption. Angiotensin II (9.8 ± 2.1 μg/h) reduced RBF by 21%, renal oxygen delivery by 28%, oxygen consumption by 18%, and medullary Po2 by 38%, but did not significantly alter cortical Po2 or cortical or medullary LDF. Arginine vasopressin (3.3 ± 0.5 μg/h) caused similar decreases in RBF and renal oxygen delivery, but did not significantly alter renal oxygen consumption or cortical or medullary LDF or Po2. Captopril had no observable effects on cortical or medullary LDF or Po2, at a dose that increased renal oxygen delivery by 24%, but did not significantly alter renal oxygen consumption. We conclude that vasoactive agents have diverse effects on regional kidney oxygenation in awake sheep that are not predictable from their effects on LDF, RBF, or total renal oxygen delivery and consumption.
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Ashley, S., S. G. Brooks, A. A. Gehani, R. C. Kester, and M. R. Rees. "Percutaneous laser recanalisation of femoropopliteal occlusions using continuous wave Nd-YAG laser and sapphire contact probe delivery system." European Journal of Vascular Surgery 8, no. 4 (June 1994): 494–501. http://dx.doi.org/10.1016/s0950-821x(05)80971-5.
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Liu, Xiaole, Jie Yuan, Dong Wu, Xiaobin Zou, Qing Zheng, Weina Zhang, and Hongxiang Lei. "All-optical targeted drug delivery and real-time detection of a single cancer cell." Nanophotonics 9, no. 3 (December 5, 2019): 611–22. http://dx.doi.org/10.1515/nanoph-2019-0318.
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AbstractTargeted drug delivery and real-time detection both play an important role for studying the specificity of a single cancer cell and the development of anticancer drugs. However, a method that simultaneously enables safe and efficient targeted drug delivery and noninvasive, free-label cell detection is highly desirable but challenging. Here, we report an all-optical method that combines fiber optical tweezers with laser Raman microspectroscopy, which can achieve targeted drug delivery to a single cancer cell using optical manipulation in vitro quickly and accurately by a tapered fiber probe, and simultaneously record the corresponding active characteristics of the targeted cancer cell under the contact of delivered drug through a Raman spectrometer. Using the method, drug delivery and release can be flexibly controlled by turning on/off the trapping laser beam propagating in the fiber, which can avoid the complex systems and is highly autonomous and controllable. Moreover, the detection of cell activity does not require any dye calibration and processing, and it is noninvasive. In addition, for a single suspension cell, optical trapping of the cell using another fiber tip can overcome the low efficiency of targeted drug delivery and the poor stability of the Raman spectrum caused by Brownian motion of the cell. This all-optical method provides a promising approach to conduct pharmacologic studies with the reaction of cancer cell and drugs at the level of a single cell.
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Brennan, James F., George I. Zonios, Thomas D. Wang, Richard P. Rava, Gary B. Hayes, Ramachandra R. Dasari, and Michael S. Feld. "Portable Laser Spectrofluorimeter System for in Vivo Human Tissue Fluorescence Studies." Applied Spectroscopy 47, no. 12 (December 1993): 2081–86. http://dx.doi.org/10.1366/0003702934066505.
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A compact, portable spectrofluorimeter which measures broad-band fluorophores with high sensitivity is described. This instrument is specifically designed for acquisition of human tissue autofluorescence spectra in vivo. Pulsed excitation laser light at 337 nm and in the 370–700 nm wavelength range is provided, and the resulting fluorescence can be measured with 10-nm resolution. The system produces single-pulse spectra in human artery wall tissues with a signal-to-noise ratio of 100:1. An optically shielded fiber-optic probe for light delivery and collection permits calibrated intensity information to be obtained.
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Muroya, T., K. Kawasaki, Y. Suehiro, T. Kunugi, K. Umayahara, T. Akiya, H. Iwabuchi, et al. "Application of PDT for Uterine Cervical Cancer." Diagnostic and Therapeutic Endoscopy 5, no. 3 (January 1, 1999): 183–90. http://dx.doi.org/10.1155/dte.5.183.
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We have been performing PDT using Excimer Dye Laser (EDL) or YAG-OPO laser, a type of low power laser, both of which have a considerably higher degree of tissue penetration even when compared to PDT using Argon Dye Laser (ADL).PDT is a relatively simple procedure without any bleeding and does not require anesthesia since it causes no pain. PDT is performed 48 h after intravenous injection of 1.5–2.0 mg/kg of PHE (Photofrin®). Precise spot irradiation is possible using a colposcope with an optical laser path. We also use a cervical probe which enables photoirradiation of the entire cervical canal.We have performed PDT on 131 cases (95 CIS, 31 dysplasia, 1 vulval dysplasia (VIN), 3 squamous cell carcinoma, microinvasion, and 1 CIS + endocervical adenocarcinoma, microinvasion). Of these cases, 127 became CR (96.9%). The first CR case was 10 years ago and no recurrence has been observed yet.PDT is extremely effective to preserve fertility. Except for sensitive reactions to sunlight, there are no noticeable side effects or difficulties related to pregnancy or delivery. We expect that in the near future PDT will be performed using diode lasers and without hospitalization due to new photosensitizers which have shorter retention times.
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Ross, Calum A., David G. MacLachlan, Brian J. E. Smith, Rainer J. Beck, Jonathan D. Shephard, Nick Weston, and Robert R. Thomson. "A Miniature Fibre-Optic Raman Probe Fabricated by Ultrafast Laser-Assisted Etching." Micromachines 11, no. 2 (February 11, 2020): 185. http://dx.doi.org/10.3390/mi11020185.
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Optical biopsy describes a range of medical procedures in which light is used to investigate disease in the body, often in hard-to-reach regions via optical fibres. Optical biopsies can reveal a multitude of diagnostic information to aid therapeutic diagnosis and treatment with higher specificity and shorter delay than traditional surgical techniques. One specific type of optical biopsy relies on Raman spectroscopy to differentiate tissue types at the molecular level and has been used successfully to stage cancer. However, complex micro-optical systems are usually needed at the distal end to optimise the signal-to-noise properties of the Raman signal collected. Manufacturing these devices, particularly in a way suitable for large scale adoption, remains a critical challenge. In this paper, we describe a novel fibre-fed micro-optic system designed for efficient signal delivery and collection during a Raman spectroscopy-based optical biopsy. Crucially, we fabricate the device using a direct-laser-writing technique known as ultrafast laser-assisted etching which is scalable and allows components to be aligned passively. The Raman probe has a sub-millimetre diameter and offers confocal signal collection with 71.3% ± 1.5% collection efficiency over a 0.8 numerical aperture. Proof of concept spectral measurements were performed on mouse intestinal tissue and compared with results obtained using a commercial Raman microscope.
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Missios, Symeon, Kimon Bekelis, and Gene H. Barnett. "Renaissance of laser interstitial thermal ablation." Neurosurgical Focus 38, no. 3 (March 2015): E13. http://dx.doi.org/10.3171/2014.12.focus14762.
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Laser interstitial thermal therapy (LITT) is a minimally invasive technique for treating intracranial tumors, originally introduced in 1983. Its use in neurosurgical procedures was historically limited by early technical difficulties related to the monitoring and control of the extent of thermal damage. The development of magnetic resonance thermography and its application to LITT have allowed for real-time thermal imaging and feedback control during laser energy delivery, allowing for precise and accurate provision of tissue hyperthermia. Improvements in laser probe design, surgical stereotactic targeting hardware, and computer monitoring software have accelerated acceptance and clinical utilization of LITT as a neurosurgical treatment alternative. Current commercially available LITT systems have been used for the treatment of neurosurgical soft-tissue lesions, including difficult to access brain tumors, malignant gliomas, and radiosurgery-resistant metastases, as well as for the ablation of such lesions as epileptogenic foci and radiation necrosis. In this review, the authors aim to critically analyze the literature to describe the advent of LITT as a neurosurgical, laser excision tool, including its development, use, indications, and efficacy as it relates to neurosurgical applications.
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Young, Matthew A., Douglas A. Stuart, Olga Lyandres, Matthew R. Glucksberg, and Richard P. Van Duyne. "Surface-enhanced Raman spectroscopy with a laser pointer light source and miniature spectrometer." Canadian Journal of Chemistry 82, no. 10 (October 1, 2004): 1435–41. http://dx.doi.org/10.1139/v04-098.
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The initial steps toward a miniature, field portable sensor based on surface-enhanced Raman spectroscopy (SERS) are presented. It is demonstrated that a low-cost miniaturized Raman system can be used in place of a larger, higher-cost conventional Raman system. This system was developed by sequentially replacing components of a laboratory scale Raman spectroscopy system with smaller, lower-cost, commercially available components. For example, a green laser pointer was used as the excitation source, a reflectance probe fiber-optic cable was used for laser delivery and collection, and a compact card-based spectrometer was used for dispersion and detection. Spectra, collected with the laser pointer Raman system, are presented of a resonant (Rhodamine 6G) and a non-resonant (trans-1,2-bis(4-pyridyl)ethylene) molecule as well as a self-assembled monolayer (1-decanethiol). Small, low-cost sensors are in demand for a variety of applications, and SERS is positioned to contribute significantly with its remarkable sensitivity and molecular specificity.Key words: Raman, SERS, fiber-optics, sensor.
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Hagemann, Johannes, Malte Vassholz, Hannes Hoeppe, Markus Osterhoff, Juan M. Rosselló, Robert Mettin, Frank Seiboth, et al. "Single-pulse phase-contrast imaging at free-electron lasers in the hard X-ray regime." Journal of Synchrotron Radiation 28, no. 1 (January 1, 2021): 52–63. http://dx.doi.org/10.1107/s160057752001557x.
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X-ray free-electron lasers (XFELs) have opened up unprecedented opportunities for time-resolved nano-scale imaging with X-rays. Near-field propagation-based imaging, and in particular near-field holography (NFH) in its high-resolution implementation in cone-beam geometry, can offer full-field views of a specimen's dynamics captured by single XFEL pulses. To exploit this capability, for example in optical-pump/X-ray-probe imaging schemes, the stochastic nature of the self-amplified spontaneous emission pulses, i.e. the dynamics of the beam itself, presents a major challenge. In this work, a concept is presented to address the fluctuating illumination wavefronts by sampling the configuration space of SASE pulses before an actual recording, followed by a principal component analysis. This scheme is implemented at the MID (Materials Imaging and Dynamics) instrument of the European XFEL and time-resolved NFH is performed using aberration-corrected nano-focusing compound refractive lenses. Specifically, the dynamics of a micro-fluidic water-jet, which is commonly used as sample delivery system at XFELs, is imaged. The jet exhibits rich dynamics of droplet formation in the break-up regime. Moreover, pump–probe imaging is demonstrated using an infrared pulsed laser to induce cavitation and explosion of the jet.
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Nam, Ki Hyun. "Polysaccharide-Based Injection Matrix for Serial Crystallography." International Journal of Molecular Sciences 21, no. 9 (May 8, 2020): 3332. http://dx.doi.org/10.3390/ijms21093332.
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Serial crystallography (SX) provides an opportunity to observe the molecular dynamics of macromolecular structures at room temperature via pump-probe studies. The delivery of crystals embedded in a viscous medium via an injector or syringe is widely performed in synchrotrons or X-ray free-electron laser facilities with low repetition rates. Various viscous media have been developed; however, there are cases in which the delivery material undesirably interacts chemically or biologically with specific protein samples, or changes the stability of the injection stream, depending on the crystallization solution. Therefore, continued discovery and characterization of new delivery media is necessary for expanding future SX applications. Here, the preparation and characterization of new polysaccharide (wheat starch (WS) and alginate)-based sample delivery media are introduced for SX. Crystals embedded in a WS or alginate injection medium showed a stable injection stream at a flow rate of < 200 nL/min and low-level X-ray background scattering similar to other hydrogels. Using these media, serial millisecond crystallography (SMX) was performed, and the room temperature crystal structures of glucose isomerase and lysozyme were determined at 1.9–2.0 Å resolutions. WS and alginate will allow an expanded application of sample delivery media in SX experiments.
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Raskolupova, Valeria I., Tatyana V. Popova, Olga D. Zakharova, Anastasia E. Nikotina, Tatyana V. Abramova, and Vladimir N. Silnikov. "Human Serum Albumin Labelling with a New BODIPY Dye Having a Large Stokes Shift." Molecules 26, no. 9 (May 3, 2021): 2679. http://dx.doi.org/10.3390/molecules26092679.
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BODIPY dyes are photostable neutral derivatives of 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene. These are widely used as chemosensors, laser materials, and molecular probes. At the same time, BODIPY dyes have small or moderate Stokes shifts like most other fluorophores. Large Stokes shifts are preferred for fluorophores because of higher sensitivity of such probes and sensors. The new boron containing BODIPY dye was designed and synthesized. We succeeded to perform an annulation of pyrrole ring with coumarin heterocyclic system and achieved a remarkable difference in absorption and emission maximum of obtained fluorophore up to 100 nm. This BODIPY dye was equipped with linker arm and was functionalized with a maleimide residue specifically reactive towards thiol groups of proteins. BODIPY residue equipped with a suitable targeting protein core can be used as a suitable imaging probe and agent for Boron Neutron Capture Therapy (BNCT). As the most abundant protein with a variety of physiological functions, human serum albumin (HSA) has been used extensively for the delivery and improvement of therapeutic molecules. Thiolactone chemistry provides a powerful tool to prepare albumin-based multimodal constructions. The released sulfhydryl groups of the homocysteine functional handle in thiolactone modified HSA were labeled with BODIPY dye to prepare a labeled albumin-BODIPY dye conjugate confirmed by MALDI-TOF-MS, UV-vis, and fluorescent emission spectra. Cytotoxicity of the resulting conjugate was investigated. This study is the basis for a novel BODIPY dye-albumin theranostic for BNCT. The results provide further impetus to develop derivatives of HSA for delivery of boron to cancer cells.
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Zhao, J. L., P. E. Pergola, L. J. Roman, and D. L. Kellogg. "Bioactive nitric oxide concentration does not increase during reactive hyperemia in human skin." Journal of Applied Physiology 96, no. 2 (February 2004): 628–32. http://dx.doi.org/10.1152/japplphysiol.00639.2003.
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This study examined whether nitric oxide (NO) is involved in the cutaneous response to reactive hyperemia (RH) in the human forearm. We enrolled seven healthy volunteers. NO concentrations were monitored using a NO selective amperometric electrode (ISO-NOP200, World Precision Instruments) inserted into the skin of the forearm. Laser-Doppler flowmetry (Moor Instruments) was used for monitoring skin blood flow (SkBF) at the same site. SkBF and NO levels were monitored and recorded continuously throughout the experiment. An intradermal microdialysis probe was inserted adjacent to the NO electrode for drug delivery. Data collection began 140 min after the NO electrodes and microdialysis probes were inserted. RH was achieved by the inflation of a blood pressure cuff to 25 mmHg above systolic pressure for 7 min after which the pressure in the cuff was abruptly released. Acetylcholine (ACh) was given by microdialysis probe at the end of RH study to verify the ability of the electrode system to detect changes in the NO concentration. SkBF and NO data before RH and immediately, 2, 5, 7, and 10 min after cuff deflation were used for analysis. SkBF increased immediately after release of the occlusion ( P < 0.0001) and remained elevated for 2 min. No significant NO changes occurred with the increases in LDF. ACh induced increases in both SkBF and NO ( P < 0.000 and P < 0.037, respectively). We conclude that RH increases SkBF by mechanisms that do not require a measurable increase in NO concentrations.
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Paturu, Mounica, Afshin Salehi, Matthew Caine, Tatenda Mahlokozera, Hiroko Yano, Eric Leuthardt, Robyn Klein, Robert Schmidt, and Albert Kim. "EXTH-35. LASER INTERSTITIAL THERMAL THERAPY INCREASES BLOOD-BRAIN BARRIER AND BLOOD-TUMOR BARRIER PERMEABILITY IN A MOUSE MODEL OF GLIOBLASTOMA." Neuro-Oncology 21, Supplement_6 (November 2019): vi89. http://dx.doi.org/10.1093/neuonc/noz175.367.
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Abstract INTRODUCTION A central challenge in glioblastoma treatment is the presence of the blood-brain barrier (BBB) and blood-tumor barrier (BTB), which prevent access of drugs to the brain and tumor respectively. Recent evidence in patients suggests laser interstitial thermal therapy (LITT), used clinically for tumor ablation, locally disrupts BBB integrity, potentially creating a therapeutic window to deliver otherwise brain-impermeant agents. METHODS A mouse model for LITT, established using a Nd-YAG laser coupled to a 600 mm fiber optic and thermocouple probe, was inserted via burrhole to target the somatosensory cortex. Syngeneic GL261 tumor cells were stereotactically implanted prior to LITT. BBB and BTB permeability were assessed through measurement of fluorescein and doxorubicin after IV injection. Permeability of IV dextran (10 and 70 kDa) and human IgG was monitored by immunohistochemistry (IHC) analysis. Mechanisms of BBB breakdown in vivo were explored utilizing electron microscopy and IHC. RESULTS By fluorescein assay, LITT-induced BBB and BTB permeability began one day post-treatment and was sustained for at least 2 weeks. Additionally, both normal brain and brain tumors demonstrated an increase in Dextran 10 kDa, Dextran 70 kDa, and human IgG extravasation after IV injection in vivo. Mechanistically, we provide evidence that LITT triggers both a decrease in tight junction integrity and an increase in brain endothelial cell transcytosis. As proof-of-concept that LITT can enhance tumor delivery of systemic drugs, LITT increased IV doxorubicin permeability in brain in vivo. Moreover, LITT plus doxorubicin significantly increased survival in brain tumor-bearing mice compared to doxorubicin or LITT alone. CONCLUSIONS Our data suggest that LITT increases BBB and BTB permeability over a defined time window to large molecular weight agents, including antibodies, through multiple cellular mechanisms. Our preclinical results with LITT plus doxorubicin, which mirror a current clinical trial, indicate LITT can enhance the efficacy of systemically delivered drugs.
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Kaminski, Radoslaw, Jason Benedict, Elzbieta Trzop, Katarzyna Jarzembska, Bertrand Fournier, and Philip Coppens. "First steps towards time-resolved 'in-house' X-ray diffraction experiments." Acta Crystallographica Section A Foundations and Advances 70, a1 (August 5, 2014): C775. http://dx.doi.org/10.1107/s2053273314092249.
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High-intensity X-ray sources, such as synchrotrons or X-ray free electron lasers, providing up to 100 ps time-resolution allow for studying very short-lived excited electronic states in molecular crystals. Some recent examples constitute investigations of Rh...Rh bond shortening,[1] or metal-to-ligand charge transfer processes in CuI complexes.[2] Nevertheless, in cases in which the lifetime of excited state species exceeds 10 μs it is now possible, due to the dramatic increase in the brightness of X-ray sources and the sensitivity of detectors, to use laboratory equipment to explore structural changes upon excitation. Consequently, in this contribution we present detailed technical description of the 'in-house' X-ray diffraction setup allowing for the laser-pump X-ray-probe experiments within the time-resolution at the order of 10 μs or larger. The experimental setup consists of a modified Bruker Mo-rotating-anode diffractometer, coupled with the high-frequency Nd:YAG laser (λ = 355 nm). The required synchronization of the laser pulses and the X-ray beam is realized via the optical chopper mounted across the beam-path. Chopper and laser capabilities enable high-repetition-rate experiments reaching up to 100 kHz. In addition, the laser shutter is being directly controlled though the original diffractometer software, allowing for collection of the data in a similar manner as done at the synchrotron (alternating light-ON & light-OFF frames). The laser beam itself is split into two allowing for improved uniform light delivery onto the crystal specimen. The designed setup was tested on the chosen set of crystals exhibiting rather long-lived excited state, such as, the Cu2Br2L2 (L = C5H4N-NMe2) complex, for which the determined lifetime is about 100 μs at 90 K. The results shall be presented. Research is funded by the National Science Foundation (CHE1213223). KNJ is supported by the Polish Ministry of Science and Higher Education through the "Mobility Plus" program.
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Harding, S. E. "Mucoadhesive interactions." Biochemical Society Transactions 31, no. 5 (October 1, 2003): 1036–41. http://dx.doi.org/10.1042/bst0311036.
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The adhesive properties of certain types of biopolymer can be used to increase the residence time of orally or nasally administered drugs. A fuller understanding of the molecular processes underpinning such ‘mucoadhesive’ phenomena will help in the optimal design of delivery systems. The interactions involved are, however, less well defined compared with those often encountered in protein-recognition phenomena: mucoadhesive interaction products can be very large and polydisperse, so to probe them we need to adopt a different strategy to those used by protein biochemists. Reviewed herein is some of the recent work at physiological or near-physiological solution conditions involving molecular hydrodynamics – with analytical ultracentrifugation and SEC-MALLs (size-exclusion chromatography coupled to multi-angle laser light scattering) as the cornerstones – reinforced by viscometry and the imaging probes of electron microscopy and atomic force microscopy. These clearly demonstrate the mucoadhesive properties of both an unusual cationic protein [Deacon, Davis, Waite and Harding (1998) Biochemistry 37, 14108–14112] and more significantly chitosan polysaccharides of varying degrees of charge/acetylation as a function of solution conditions, and are providing the platform for the construction of stable formulations.
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Spence, John C. H. "Approaches to time-resolved diffraction using an XFEL." Faraday Discuss. 171 (2014): 429–38. http://dx.doi.org/10.1039/c4fd00025k.
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We describe several schemes for time-resolved imaging of molecular motion using a free-electron laser (XFEL), in response to the many challenges and opportunities which XFEL radiation has created for accurate time-resolved measurement of structure. For pump–probe experiments using crystals, the problem of recording full Bragg reflections (not partials) in each shot arises. Two solutions, the use of the large bandwith which necesarily results from using attosecond pulses, and the use the coherent convergent beam mode are suggested. We also show that with attosecond recording times shorter than the temporal coherence time, Bragg reflections excited by different wavelengths from different reflections can interfere, providing structure factor phase information. For slower processes, a mixing jet sample-delivery device is described to allow snapshot solution scattering during molecular reactions on the microsecond scale. For optically excited membrane proteins, we suggest the use of the lipid cubic phase sample delivery device operating at atmospheric pressure. The use of two-color and split-and-delay schemes is suggested for improved accuracy in the Monte-Carlo method of serial femtosecond crystallography (SFX).
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Comber, David B., E. Bryn Pitt, Hunter B. Gilbert, Matthew W. Powelson, Emily Matijevich, Joseph S. Neimat, Robert J. Webster, and Eric J. Barth. "Optimization of Curvilinear Needle Trajectories for Transforamenal Hippocampotomy." Operative Neurosurgery 13, no. 1 (July 25, 2016): 15–22. http://dx.doi.org/10.1227/neu.0000000000001361.
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Abstract BACKGROUND: The recently developed magnetic resonance imaging–guided laser-induced thermal therapy offers a minimally invasive alternative to craniotomies performed for tumor resection or for amygdalohippocampectomy to control seizure disorders. Current laser-induced thermal therapies rely on linear stereotactic trajectories that mandate twist-drill entry into the skull and potentially long approaches traversing healthy brain. The use of robotically driven, telescoping, curved needles has the potential to reduce procedure invasiveness by tailoring trajectories to the curved shape of the ablated structure and by enabling access through natural orifices. OBJECTIVE: To investigate the feasibility of using a concentric tube robot to access the hippocampus through the foramen ovale to deliver thermal therapy and thereby provide a percutaneous treatment for epilepsy without drilling the skull. METHODS: The skull and both hippocampi were segmented from dual computed tomography/magnetic resonance image volumes for 10 patients. For each of the 20 hippocampi, a concentric tube robot was designed and optimized to traverse a trajectory from the foramen ovale to and through the hippocampus from head to tail. RESULTS: Across all 20 cases, the mean distances (errors) between the hippocampus medial axis and backbone of the needle were 0.55, 1.11, and 1.66 mm for the best, mean, and worst case, respectively. CONCLUSION: These curvilinear trajectories would provide accurate transforamenal delivery of an ablation probe to typical hippocampus volumes. This strategy has the potential both to decrease the invasiveness of the procedure and to increase the completeness of hippocampal ablation.
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Sung, Daeho, Daewoong Nam, Myong-jin Kim, Seonghan Kim, Kyung Sook Kim, Sang-Youn Park, Sun Min Hwang, et al. "Single-Shot Coherent X-ray Imaging Instrument at PAL-XFEL." Applied Sciences 11, no. 11 (May 30, 2021): 5082. http://dx.doi.org/10.3390/app11115082.
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We developed a single-shot coherent X-ray imaging instrument at the hard X-ray beamline of the Pohang Accelerator Laboratory X-ray Free Electron Laser (PAL-XFEL). This experimental platform was established to conduct a variety of XFEL experiments, including coherent diffraction imaging (CDI), X-ray photon correlation spectroscopy (XPCS), and coherent X-ray scattering (CXS). Based on the forward-scattering geometry, this instrument utilizes a fixed-target method for sample delivery. It is well optimized for single-shot-based experiments in which one expects to observe the ultrafast phenomena of nanoparticles at picosecond temporal and nanometer spatial resolutions. In this paper, we introduce a single-shot coherent X-ray imaging instrument and report pump–probe coherent diffraction imaging (PPCDI) of Ag nanoparticles as an example of its applications.
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Nam, Ki Hyun. "Lard Injection Matrix for Serial Crystallography." International Journal of Molecular Sciences 21, no. 17 (August 19, 2020): 5977. http://dx.doi.org/10.3390/ijms21175977.
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Serial crystallography (SX) using X-ray free electron laser or synchrotron X-ray allows for the determination of structures, at room temperature, with reduced radiation damage. Moreover, it allows for the study of structural dynamics of macromolecules using a time-resolved pump-probe, as well as mix-and-inject experiments. Delivering a crystal sample using a viscous medium decreases sample consumption by lowering the flow rate while being extruded from the injector or syringe as compared to a liquid jet injector. Since the environment of crystal samples varies, continuous development of the delivery medium is important for extended SX applications. Herein, I report the preparation and characterization of a lard-based sample delivery medium for SX. This material was obtained using heat treatment, and then the soluble impurities were removed through phase separation. The lard injection medium was highly stable and could be injected via a syringe needle extruded at room temperature with a flow rate < 200 nL/min. Serial millisecond crystallography experiments were performed using lard, and the room temperature structures of lysozyme and glucose isomerase embedded in lard at 1.75 and 1.80 Å, respectively, were determined. The lard medium showed X-ray background scattering similar or relatively lower than shortenings and lipidic cubic phase; therefore, it can be used as sample delivery medium in SX experiments.
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Wang, Yuhling, De-Fu Jhang, Tsung-Sheng Chu, Chia-Hui Tsao, Chia-Hua Tsai, Chiung-Cheng Chuang, Tzong-Rong Ger, Li-Tzong Chen, Wun-Shaing Wayne Chang, and Lun-De Liao. "An Adjustable Dark-Field Acoustic-Resolution Photoacoustic Imaging System with Fiber Bundle-Based Illumination." Biosensors 11, no. 8 (August 3, 2021): 262. http://dx.doi.org/10.3390/bios11080262.
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Photoacoustic (PA) imaging has become one of the major imaging methods because of its ability to record structural information and its high spatial resolution in biological tissues. Current commercialized PA imaging instruments are limited to varying degrees by their bulky size (i.e., the laser or scanning stage) or their use of complex optical components for light delivery. Here, we present a robust acoustic-resolution PA imaging system that consists of four adjustable optical fibers placed 90° apart around a 50 MHz high-frequency ultrasound (US) transducer. In the compact design concept of the PA probe, the relative illumination parameters (i.e., angles and fiber size) can be adjusted to fit different imaging applications in a single setting. Moreover, this design concept involves a user interface built in MATLAB. We first assessed the performance of our imaging system using in vitro phantom experiments. We further demonstrated the in vivo performance of the developed system in imaging (1) rat ear vasculature, (2) real-time cortical hemodynamic changes in the superior sagittal sinus (SSS) during left-forepaw electrical stimulation, and (3) real-time cerebral indocyanine green (ICG) dynamics in rats. Collectively, this alignment-free design concept of a compact PA probe without bulky optical lens systems is intended to satisfy the diverse needs in preclinical PA imaging studies.
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Nie, Kun, Qi An, Jeffrey Zink, Xiang Yu, and Yihe Zhang. "Layer by Layer Mesoporous Silica-Hyaluronic Acid-Cyclodextrin Bifunctional “Lamination”: Study of the Application of Fluorescent Probe and Host–Guest Interactions in the Drug Delivery Field." Materials 11, no. 9 (September 17, 2018): 1745. http://dx.doi.org/10.3390/ma11091745.
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The layer-by-layer technique was exploited to adjust the magnitude of the host–guest interactions between adamantane and cyclodextrin. The effect depends on numerous complex and changeable growth profiles of the films and the number of bilayers. These composite films of mesoporous silica nanoparticles and hyaluronic acid–cyclodextrin(HA-CD) were constructed to load the fluorescent dyes and peptides. The release rates of these molecules would decrease with an increase in the number of layers. A laser scanning confocal microscope was utilized to obtain the diffusion coefficient of fluorescein isothiocyanate. Hybrid films could be applied to increase the loading of different kinds of molecules and could also be integrated into the lamination to delay the rate of release.
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Spence, J. C. H. "XFELs for structure and dynamics in biology." IUCrJ 4, no. 4 (May 10, 2017): 322–39. http://dx.doi.org/10.1107/s2052252517005760.
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The development and application of the free-electron X-ray laser (XFEL) to structure and dynamics in biology since its inception in 2009 are reviewed. The research opportunities which result from the ability to outrun most radiation-damage effects are outlined, and some grand challenges are suggested. By avoiding the need to cool samples to minimize damage, the XFEL has permitted atomic resolution imaging of molecular processes on the 100 fs timescale under near-physiological conditions and in the correct thermal bath in which molecular machines operate. Radiation damage, comparisons of XFEL and synchrotron work, single-particle diffraction, fast solution scattering, pump–probe studies on photosensitive proteins, mix-and-inject experiments, caged molecules, pH jump and other reaction-initiation methods, and the study of molecular machines are all discussed. Sample-delivery methods and data-analysis algorithms for the various modes, from serial femtosecond crystallography to fast solution scattering, fluctuation X-ray scattering, mixing jet experiments and single-particle diffraction, are also reviewed.
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Kuriakose, Maju, Christopher D. Nguyen, Mithun Kuniyil Ajith Singh, and Srivalleesha Mallidi. "Optimizing Irradiation Geometry in LED-Based Photoacoustic Imaging with 3D Printed Flexible and Modular Light Delivery System." Sensors 20, no. 13 (July 6, 2020): 3789. http://dx.doi.org/10.3390/s20133789.
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Photoacoustic (PA) imaging–a technique combining the ability of optical imaging to probe functional properties of the tissue and deep structural imaging ability of ultrasound–has gained significant popularity in the past two decades for its utility in several biomedical applications. More recently, light-emitting diodes (LED) are being explored as an alternative to bulky and expensive laser systems used in PA imaging for their portability and low-cost. Due to the large beam divergence of LEDs compared to traditional laser beams, it is imperative to quantify the angular dependence of LED-based illumination and optimize its performance for imaging superficial or deep-seated lesions. A custom-built modular 3-D printed hinge system and tissue-mimicking phantoms with various absorption and scattering properties were used in this study to quantify the angular dependence of LED-based illumination. We also experimentally calculated the source divergence of the pulsed-LED arrays to be 58° ± 8°. Our results from point sources (pencil lead phantom) in non-scattering medium obey the cotangential relationship between the angle of irradiation and maximum PA intensity obtained at various imaging depths, as expected. Strong dependence on the angle of illumination at superficial depths (−5°/mm at 10 mm) was observed that becomes weaker at intermediate depths (−2.5°/mm at 20 mm) and negligible at deeper locations (−1.1°/mm at 30 mm). The results from the tissue-mimicking phantom in scattering media indicate that angles between 30–75° could be used for imaging lesions at various depths (12 mm–28 mm) where lower LED illumination angles (closer to being parallel to the imaging plane) are preferable for deep tissue imaging and superficial lesion imaging is possible with higher LED illumination angles (closer to being perpendicular to the imaging plane). Our results can serve as a priori knowledge for the future LED-based PA system designs employed for both preclinical and clinical applications.
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Morelli, Andrea, Luigi Tritapepe, Monica Rocco, Giorgio Conti, Alessandra Orecchioni, Andrea De Gaetano, Umberto Picchini, Paolo Pelaia, Carlo Reale, and Paolo Pietropaoli. "Terlipressin versus Norepinephrine to Counteract Anesthesia-induced Hypotension in Patients Treated with Renin-Angiotensin System Inhibitors: Effects on Systemic and Regional Hemodynamics." Anesthesiology 102, no. 1 (January 1, 2005): 12–19. http://dx.doi.org/10.1097/00000542-200501000-00006.
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Background Terlipressin has been suggested as the ideal drug to treat anesthesia-induced hypotension in patients under long-term renin-angiotensin system inhibitor treatment for arterial hypertension. The authors compared the effects of terlipressin and norepinephrine on systemic hemodynamic parameters and gastric mucosal perfusion using a laser Doppler flowmetry technique in patients treated with renin-angiotensin system inhibitors who experienced hypotension at induction of anesthesia. Methods Thirty-two patients scheduled for carotid endarterectomy under general anesthesia and treated with renin-angiotensin system inhibitors had hypotension after induction of general anesthesia. They were randomized to receive 1 mg of terlipressin (n = 16) or norepinephrine infusion (n = 16) to counteract anesthesia-induced hypotension. A laser Doppler probe was introduced into the gastric lumen. All measurements were performed just before surgery, during hypotension, at 30 min, and at 4 h. Results Terlipressin produced an increase in mean arterial pressure and a decrease in gastric mucosal perfusion detected by laser Doppler flowmetry (P < 0.05) over 30 min that were sustained for 4 h. During the infusion, norepinephrine produced an increase in mean arterial pressure and in gastric mucosal perfusion detected by laser Doppler flowmetry (P < 0.05). If compared to norepinephrine, terlipressin reduced oxygen delivery and oxygen consumption (P < 0.05) and increased arterial lactate concentrations (P < 0.05). Conclusion This study showed the efficacy of terlipressin in the treatment of hypotension episodes in anesthetized patients chronically treated with renin-angiotensin system inhibitors, angiotensin converting-enzyme inhibitors, and angiotensin II receptor antagonists. However, the negative effects on gastric mucosal perfusion and the risk of iatrogenic oxygen supply dependency of terlipressin need to be taken into account.
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Kellogg, D. L., Y. Liu, I. F. Kosiba, and D. O’Donnell. "Role of nitric oxide in the vascular effects of local warming of the skin in humans." Journal of Applied Physiology 86, no. 4 (April 1, 1999): 1185–90. http://dx.doi.org/10.1152/jappl.1999.86.4.1185.
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Local warming of skin induces vasodilation by unknown mechanisms. To test whether nitric oxide (NO) is involved, we examined effects of NO synthase (NOS) inhibition with N G-nitro-l-arginine methyl ester (l-NAME) on vasodilation induced by local warming of skin in six subjects. Two adjacent sites on the forearm were instrumented with intradermal microdialysis probes for delivery ofl-NAME and sodium nitroprusside. Skin blood flow was monitored by laser-Doppler flowmetry (LDF) at microdialysis sites. Local temperature (Tloc) of the skin at both sites was controlled with special LDF probe holders. Mean arterial pressure (MAP; Finapres) was measured and cutaneous vascular conductance calculated (CVC = LDF/MAP = mV/mmHg). Data collection began with a control period (Tloc at both sites = 34°C). One site was then warmed to 41°C while the second was maintained at 34°C. Local warming increased CVC from 1.44 ± 0.41 to 4.28 ± 0.60 mV/mmHg ( P < 0.05). Subsequent l-NAME administration reduced CVC to 2.28 ± 0.47 mV/mmHg ( P < 0.05 vs. heating), despite the continued elevation of Tloc. At a Tloc of 34°C,l-NAME reduced CVC from 1.17 ± 0.23 to 0.75 ± 0.11 mV/mmHg ( P < 0.05). Administration of sodium nitroprusside increased CVC to levels no different from those induced by local warming. Thus NOS inhibition attenuated, and sodium nitroprusside restored, the cutaneous vasodilation induced by elevation of Tloc; therefore, the mechanism of cutaneous vasodilation by local warming requires NOS generation of NO.
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Estevadeordal, J., S. Gogineni, L. Goss, W. Copenhaver, and S. Gorrell. "Study of Wake-Blade Interactions in a Transonic Compressor Using Flow Visualization and DPIV." Journal of Fluids Engineering 124, no. 1 (August 24, 2001): 166–75. http://dx.doi.org/10.1115/1.1429638.
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Flow-field interactions are studied in a high-through-flow, axial-flow transonic compressor using Digital Particle Image Velocimetry (DPIV). Measurement of instantaneous velocities in two-dimensional (2D) planes in the main flow direction allows characterization of the unsteadiness of spatial structures from an upstream blade row and their interaction with the downstream rotor. The measurement system is specially designed for a large transonic environment, which introduces conditions that differ from those generally encountered by traditional DPIV systems. Viewing windows on the compressor housing are used to allow optical access, and the design of a special optical probe permits laser-sheet delivery through one of the wake generators (WG). The system is synchronized with the blade passage and is remotely monitored and controlled. Through flow visualization and instantaneous and ensemble-averaged quantities, it clearly captures the interactions of the wake with the potential field of the rotor leading edge (LE) and its bow shock, vortex shedding, vortex-blade synchronization, wake chopping, and boundary-layer flow at the housing for several configurations.
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Leithner, Christoph, Georg Royl, Nikolas Offenhauser, Martina Füchtemeier, Matthias Kohl-Bareis, Arno Villringer, Ulrich Dirnagl, and Ute Lindauer. "Pharmacological Uncoupling of Activation Induced Increases in CBF and CMRO2." Journal of Cerebral Blood Flow & Metabolism 30, no. 2 (September 30, 2009): 311–22. http://dx.doi.org/10.1038/jcbfm.2009.211.
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Neurovascular coupling provides the basis for many functional neuroimaging techniques. Nitric oxide (NO), adenosine, cyclooxygenase, CYP450 epoxygenase, and potassium are involved in dilating arterioles during neuronal activation. We combined inhibition of NO synthase, cyclooxygenase, adenosine receptors, CYP450 epoxygenase, and inward rectifier potassium (Kir) channels to test whether these pathways could explain the blood flow response to neuronal activation. Cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) of the somatosensory cortex were measured during forepaw stimulation in 24 rats using a laser Doppler/spectroscopy probe through a cranial window. Combined inhibition reduced CBF responses by two-thirds, somatosensory evoked potentials and activation-induced CMRO2 increases remained unchanged, and deoxy-hemoglobin (deoxy-Hb) response was abrogated. This shows that in the rat somatosensory cortex, one-third of the physiological blood flow increase is sufficient to prevent microcirculatory increase of deoxy-Hb concentration during neuronal activity. The large physiological CBF response is not necessary to support small changes in CMRO2. We speculate that the CBF response safeguards substrate delivery during functional activation with a considerable ‘safety factor’. Reduction of the CBF response in pathological states may abolish the BOLD–fMRI signal, without affecting underlying neuronal activity.
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Slivka, Adam, Yang K. Chen, Douglas K. Pleskow, Peter D. Stevens, Raj J. Shah, Ram Chuttani, and Alexander Meining. "721 Real-Time Microscopic Evaluation of Indeterminate Strictures: Comparison of Cholangioscopy vs Catheter Delivery for Probe-Based Confocal Laser Endomicroscopy (pCLE) - A Multi-Center Experience Using Cellvizio." Gastrointestinal Endoscopy 73, no. 4 (April 2011): AB146—AB147. http://dx.doi.org/10.1016/j.gie.2011.03.108.
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Cronshaw, Mark, Steven Parker, Eugenia Anagnostaki, Valina Mylona, Edward Lynch, and Martin Grootveld. "Photobiomodulation Dose Parameters in Dentistry: A Systematic Review and Meta-Analysis." Dentistry Journal 8, no. 4 (October 6, 2020): 114. http://dx.doi.org/10.3390/dj8040114.
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Objective: This systematic review and meta-analysis of published randomized controlled trials examines a possible relationship between optical spot size at surface tissue, irradiance, radiant exposure, total energy delivered, operator technique and reported clinical outcomes. Background: Clinical photobiomodulation (PBM) therapy has achieved a high level of evidence-based acceptance in the mitigation of oral mucositis associated with cancer radiotherapy and chemotherapy, and supportive clinical research in relation to orthodontic tooth movement, oral medical conditions, including burning mouth syndrome, xerostomia and lichen planus. Inconsistent outcomes have been reported not withstanding a substantial body of primary supportive research from clinical, in vitro and animal studies. Materials and Methods: PubMed, Cochrane Database of Reviews and Google Scholar search engines were applied to identify human clinical trials of PBM therapy in clinical dentistry. A total of 766 articles between February 2009 and June 2020 were identified and following a full text evaluation, 38 papers with sufficient data to permit analyses are included in this investigation. Results: Following a detailed assessment of potential factors that may have an influence in clinical outcome, a clear trend is apparent associating optical spot size to a positive or negative effect. Furthermore, there is a clear difference in the reported results in relation to total energy applied, delivery techniques and optical parameters, which merits further investigation. Factorial statistical analyses identified an association between smaller optical surface applications and an overall lower level of reported clinical success in treating superficial and deeper targets, and correspondingly sub-surface larger target tissues were found to be more responsive to therapy by use of a larger optical surface spot size. Moreover, use of multiple small diameter probe applications was found to provide inconsistent results. Conclusions: Many factors can confound clinical success including variations in anatomy, site location, clinical condition and subject individuality. To achieve higher levels of predictable outcome, a mature appreciation of these factors, plus an expanded understanding of laser parametry, tissue volume and target depth to deliver an adequate dose within current recommended guidelines, is essential.
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Pei, Qin Yu, Rui Wang, Xue Qin Jin, and Guo Jing Gou. "Recombination of CdHgTe Quantum Dot and “Dextran - Magnetic Layered Double Hydroxide - Fluorouracil” System for Cell Imaging." Materials Science Forum 914 (February 2018): 11–18. http://dx.doi.org/10.4028/www.scientific.net/msf.914.11.
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In this paper, we synthesized a CdHgTe type water-soluble quantum dots, combined in the next time with the drug delivery system "dextran - magnetic layered double hydroxide - fluorouracil" (DMF), built a new nanostructures platform QD@DMF for blending the fluorescent probe function of quantum dot together with the magnetic targeting curative effect of the DMF system. The Fluorescence spectrophotometer, Ultraviolet spectrophotometer, TEM and XRD were used to characterize the luminescent properties, particle morphology and phase characteristics of the QD@DMF samples. The experiments on cell imaging were carried out by laser con-focal scan microscopy technique. Results showed that the CdHgTe QDs could be successfully grafted onto the surface of the DMF system through electrostatic coupling, forming a special structure based on magnetic layered double hydroxide with a near-infrared emission wavelength in 575~780 nm. Compared with QDs, the QD@DMF composite could significantly improve the cell imaging effect, the label intensity increased with the magnetic field intensity and obeyed the linear relationship Dmean = 1.760+0.013B. The fluorescent magnetic nanoparticles maintained not only the super-paramagnetic of DMF but also the photoluminescence properties of the QDs, implicating that the QD@DMF composite may be an effective multifunction tool for optical bio-imaging and magnetic targeted therapy.
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Pollock, D. M., and W. J. Arendshorst. "Tubuloglomerular feedback and blood flow autoregulation during DA1-induced renal vasodilation." American Journal of Physiology-Renal Physiology 258, no. 3 (March 1, 1990): F627—F635. http://dx.doi.org/10.1152/ajprenal.1990.258.3.f627.
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The effect of renal vasodilation produced by the dopamine DA1-receptor agonist, fenoldopam (SKF-82526), on tubuloglomerular feedback (TGF) activity and the autoregulation of renal blood flow (RBF) was determined in euvolemic rats. Fenoldopam (2.5 micrograms.kg-1.min-1 iv) increased RBF by 17% (electromagnetic flow probe) while glomerular filtration rate (GFR) was unchanged; mean arterial pressure was decreased by 6%. Superficial cortical blood flow was increased by 12% (laser-Doppler flowmetry) while single-nephron GFR (SNGFR) and estimated glomerular capillary pressure (stop-flow pressure, Psf) were stable. SNGFR measured at proximal and distal sites along the same nephron was not affected by fenoldopam. Partial inhibition of TGF was indicated by the constancy of distal SNGFR and the proximal-distal SNGFR difference in the presence of increased distal delivery of native fluid. However, fenoldopam did not affect feedback control of Psf evaluated by perfusing artificial fluid through Henle's loop at 0-62 nl/min. Despite the decrease in renal vascular resistance over an arterial pressure range of 130 to 70 mmHg, RBF was autoregulated efficiently during fenoldopam infusion. These results indicate that DA1-receptor activation dilates the preglomerular and efferent arterioles without affecting GFR or glomerular pressure. However, this vasodilatory mechanism operates independent of autoregulation and TGF-induced changes in glomerular pressure such that preglomerular vessels remain responsive to the appropriate signals from these intrinsic control systems. The ability of fenoldopam to blunt feedback control of SNGFR may depend on changes in the filtration coefficient independent of glomerular pressure and/or a constituent of natural tubular fluid.
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Glownia, James M., Karl Gumerlock, Henrik T. Lemke, Takahiro Sato, Diling Zhu, and Matthieu Chollet. "Pump–probe experimental methodology at the Linac Coherent Light Source." Journal of Synchrotron Radiation 26, no. 3 (April 26, 2019): 685–91. http://dx.doi.org/10.1107/s160057751900225x.
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Experimental methods that use free-electron laser (FEL) sources that can deliver short X-ray pulses below a 10 fs pulse duration and traditional optical lasers are ideal tools for pump–probe experiments. However, these new methods also come with a unique set of challenges, such as how to accurately determine temporal overlap between two sources at the femtosecond scale and how to correct for the pulse-to-pulse beam property fluctuations of the FEL light derived from the self-amplified spontaneous emission process. Over the past several years of performing pump–probe experiments at the Linac Coherent Light Source (LCLS), new methods and tools have been developed to improve the ways experimental timing is measured, monitored and scanned. The aim of this article is to present an overview of the most commonly used techniques at LCLS to perform pump–probe-type experiments.
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Gesuele, Felice. "Ultrafast Hyperspectral Transient Absorption Spectroscopy: Application to Single Layer Graphene." Photonics 6, no. 3 (August 29, 2019): 95. http://dx.doi.org/10.3390/photonics6030095.
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We describe the basic principles and the experimental implementation of the hyperspectral transient absorption technique, based on femtosecond laser sources. In this technique the samples were optically “pumped” using the femtosecond tunable pulse delivered by an Optical Parametric Amplifier, and “probed” for changes in transmission in a broad spectral range with a “white light” laser-generated supercontinuum. The spectra were collected by a pair of multichannel detectors which allowed retrieval of the absorbance change in a wide spectral range in one time. The use of the supercontinuum probe introduced artifacts in the measured 2D data set which could be corrected with a proper calibration of the chirp. The configuration with crossed polarization for pump and probe pulse extended the spectral measured range above and below the pump energy within the same experiment. We showed the versatility of the technique by applying it to the investigation of the charge carrier dynamics in two-dimensional single layer graphene.
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Britz, Alexander, Tadesse A. Assefa, Andreas Galler, Wojciech Gawelda, Michael Diez, Peter Zalden, Dmitry Khakhulin, et al. "A multi-MHz single-shot data acquisition scheme with high dynamic range: pump–probe X-ray experiments at synchrotrons." Journal of Synchrotron Radiation 23, no. 6 (October 10, 2016): 1409–23. http://dx.doi.org/10.1107/s1600577516012625.
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The technical implementation of a multi-MHz data acquisition scheme for laser–X-ray pump–probe experiments with pulse limited temporal resolution (100 ps) is presented. Such techniques are very attractive to benefit from the high-repetition rates of X-ray pulses delivered from advanced synchrotron radiation sources. Exploiting a synchronized 3.9 MHz laser excitation source, experiments in 60-bunch mode (7.8 MHz) at beamline P01 of the PETRA III storage ring are performed. Hereby molecular systems in liquid solutions are excited by the pulsed laser source and the total X-ray fluorescence yield (TFY) from the sample is recorded using silicon avalanche photodiode detectors (APDs). The subsequent digitizer card samples the APD signal traces in 0.5 ns steps with 12-bit resolution. These traces are then processed to deliver an integrated value for each recorded single X-ray pulse intensity and sorted into bins according to whether the laser excited the sample or not. For each subgroup the recorded single-shot values are averaged over ∼107 pulses to deliver a mean TFY value with its standard error for each data point,e.g.at a given X-ray probe energy. The sensitivity reaches down to the shot-noise limit, and signal-to-noise ratios approaching 1000 are achievable in only a few seconds collection time per data point. The dynamic range covers 100 photons pulse−1and is only technically limited by the utilized APD.
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Wild, Jan, Peter Pira, Tomas Burian, Ludek Vysin, Libor Juha, Zdenek Zelinger, Stanislav Danis, et al. "Ablation of single-crystalline cesium iodide by extreme ultraviolet capillary-discharge laser." Nukleonika 65, no. 4 (December 1, 2020): 205–10. http://dx.doi.org/10.2478/nuka-2020-0031.
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AbstractExtreme ultraviolet (XUV) capillary-discharge lasers (CDLs) are a suitable source for the efficient, clean ablation of ionic crystals, which are obviously difficult to ablate with conventional, long-wavelength lasers. In the present study, a single crystal of cesium iodide (CsI) was irradiated by multiple, focused 1.5-ns pulses of 46.9-nm radiation delivered from a compact XUV-CDL device operated at either 2-Hz or 3-Hz repetition rates. The ablation rates were determined from the depth of the craters produced by the accumulation of laser pulses. Langmuir probes were used to diagnose the plasma plume produced by the focused XUV-CDL beam. Both the electron density and electron temperature were sufficiently high to confirm that ablation was the key process in the observed CsI removal. Moreover, a CsI thin film on MgO substrate was prepared by XUV pulsed laser deposition; a fraction of the film was detected by X-ray photoelectron spectroscopy.
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Yan, Yan, Maryam Basij, Alpana Garg, Aneesha Varrey, Ali Alhousseini, Richard Hsu, Edgar Hernandez-Andrade, Roberto Romero, Sonia S. Hassan, and Mohammad Mehrmohammadi. "Spectroscopic photoacoustic imaging of cervical tissue composition in excised human samples." PLOS ONE 16, no. 3 (March 3, 2021): e0247385. http://dx.doi.org/10.1371/journal.pone.0247385.
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Objective Cervical remodeling is an important component in determining the pathway of parturition; therefore, assessing changes in cervical tissue composition may provide information about the cervix’s status beyond the measurement of cervical length. Photoacoustic imaging is a non-invasive ultrasound-based technology that captures acoustic signals emitted by tissue components in response to laser pulses. This optical information allows for the determination of the collagen-to-water ratio (CWR). The purpose of this study was to compare the CWR evaluated by using spectroscopic photoacoustic (sPA) imaging in cervical samples obtained from pregnant and non-pregnant women. Methods This cross-sectional study comprised cervical biopsies obtained at the time of hysterectomy (n = 8) and at the scheduled cesarean delivery in pregnant women at term who were not in labor (n = 8). The cervical CWR was analyzed using a fiber-optic light-delivery system integrated to an ultrasound probe. The photoacoustic signals were acquired within the range of wavelengths that cover the peak absorption of collagen and water. Differences in the CWR between cervical samples from pregnant and non-pregnant women were analyzed. Hematoxylin and eosin and Sirius Red stains were used to compare the collagen content of cervical samples in these two groups. Results Eight cervix samples were obtained after hysterectomy, four from women ≤41 years of age and four from women ≥43 years of age; all cervical samples (n = 8) from pregnant women were obtained after 37 weeks of gestation at the time of cesarean section. The average CWR in cervical tissue samples from pregnant women was 18.7% (SD 7.5%), while in samples from non-pregnant women, it was 55.0% (SD 20.3%). There was a significantly higher CWR in the non-pregnant group compared to the pregnant group with a p-value <0.001. A subgroup analysis that compared the CWR in cervical samples from pregnant women and non-pregnant women ≤41 years of age (mean 46.3%, SD 23.1%) also showed a significantly higher CWR (p <0.01). Lower collagen content in the pregnancy group was confirmed by histological analysis, which revealed the loss of tissue composition, increased water content, and collagen degradation. Conclusion The proposed bimodal ultrasound and sPA imaging system can provide information on the biochemical composition of cervical tissue in pregnant and non-pregnant women. Photoacoustic imaging showed a higher collagen content in cervical samples from non-pregnant women as compared to those from pregnant women, which matched with the histological analysis. This novel imaging method envisions a new potential for a sensitive diagnostic tool in the evaluation of cervical tissue composition.
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Keller, Gregory S. "Use of the KTP Laser in Cosmetic Surgery." American Journal of Cosmetic Surgery 9, no. 2 (June 1992): 177–80. http://dx.doi.org/10.1177/074880689200900210.
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The KTP is a versatile laser system when used for cosmetic surgery. When combined with a hexascanner or small spot size handpiece, it is equivalent to a continuous-wave yellow dye laser or copper vapor laser in the treatment of vascular lesions. The KTP laser wavelength (532 nm) is near the peak of a hemoglobin absorption curve as is the wavelength of the continuous-wave yellow dye or copper vapor laser. The KTP laser is also excellent for use in the treatment of Lentigines. The solar lentigines of the hand, arm, and leg are particularly treatable. The hexascanner delivery system makes the KTP laser particularly time-efficient when used to treat the multiple lesions that usually occur with this condition. The KTP laser can also be combined with special quartz contact probes and used for incisional cosmetic surgery such as blepharoplasty, rhytidectomy, forehead lifting, and new “endolaser” small-incision cosmetic surgery. The contact probes focus and defocus the laser quickly allowing the precision use of the laser deep under a flap with a spot size of 0.1 mm. The coagulative abilities of the laser allow an almost bloodless dissection. The Laserlift™ produces less swelling and bruising for the patient and allows the surgeon to complete complicated surgery with excellent visualization in a bloodless field.
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Galler, Andreas, Wojciech Gawelda, Mykola Biednov, Christina Bomer, Alexander Britz, Sandor Brockhauser, Tae-Kyu Choi, et al. "Scientific instrument Femtosecond X-ray Experiments (FXE): instrumentation and baseline experimental capabilities." Journal of Synchrotron Radiation 26, no. 5 (August 9, 2019): 1432–47. http://dx.doi.org/10.1107/s1600577519006647.
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The European X-ray Free-Electron Laser (EuXFEL) delivers extremely intense (>1012 photons pulse−1 and up to 27000 pulses s−1), ultrashort (<100 fs) and transversely coherent X-ray radiation, at a repetition rate of up to 4.5 MHz. Its unique X-ray beam parameters enable novel and groundbreaking experiments in ultrafast photochemistry and material sciences at the Femtosecond X-ray Experiments (FXE) scientific instrument. This paper provides an overview of the currently implemented experimental baseline instrumentation and its performance during the commissioning phase, and a preview of planned improvements. FXE's versatile instrumentation combines the simultaneous application of forward X-ray scattering and X-ray spectroscopy techniques with femtosecond time resolution. These methods will eventually permit exploitation of wide-angle X-ray scattering studies and X-ray emission spectroscopy, along with X-ray absorption spectroscopy, including resonant inelastic X-ray scattering and X-ray Raman scattering. A suite of ultrafast optical lasers throughout the UV–visible and near-IR ranges (extending up to mid-IR in the near future) with pulse length down to 15 fs, synchronized to the X-ray source, serve to initiate dynamic changes in the sample. Time-delayed hard X-ray pulses in the 5–20 keV range are used to probe the ensuing dynamic processes using the suite of X-ray probe tools. FXE is equipped with a primary monochromator, a primary and secondary single-shot spectrometer, and a timing tool to correct the residual timing jitter between laser and X-ray pulses.
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Nango, Eriko, Minoru Kubo, Kensuke Tono, and So Iwata. "Pump-Probe Time-Resolved Serial Femtosecond Crystallography at SACLA: Current Status and Data Collection Strategies." Applied Sciences 9, no. 24 (December 14, 2019): 5505. http://dx.doi.org/10.3390/app9245505.
Full textAbstract:
Structural information on protein dynamics is a critical factor in fully understanding the protein functions. Pump-probe time-resolved serial femtosecond crystallography (TR-SFX) is a recently established technique for visualizing the structural changes or reactions in proteins that are at work with high spatial and temporal resolution. In the pump-probe method, protein microcrystals are continuously delivered from an injector and exposed to an X-ray free-electron laser (XFEL) pulse after a trigger to initiate a reaction, such as light, chemicals, temperature, and electric field, which affords the structural snapshots of intermediates that occur in the protein. We are in the process of developing the device and techniques for pump-probe TR-SFX while using XFEL produced at SPring-8 Angstrom Compact Free-Electron Laser (SACLA). In this paper, we described our current development details and data collection strategies for the optical pump X-ray probe TR-SFX experiment at SACLA and then reported the techniques of in crystallo TR spectroscopy, which is useful in clarifying the nature of reaction that takes place in crystals in advance.
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Chen, Zhemin, Pengbing Hu, Qingqiang Meng, and Xinyong Dong. "Novel Optical Fiber Dynamic Light Scattering Measurement System for Nanometer Particle Size." Advances in Materials Science and Engineering 2013 (2013): 1–4. http://dx.doi.org/10.1155/2013/250121.
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We present a novel optical fiber dynamic light scattering measurement system for nanometer particle size. A multimode fiber probe is used to highly efficiently couple and deliver laser light, while a single-mode fiber probe is used to only receive single scattering light. This design not only improves the measuring ability of the system but also provides flexibility in choosing scattering angle for measurement. By using this system, four kinds of polystyrene nanoparticles are evaluated. Experimentation shows the measured sizes of the nanoparticles are well consistent with the nominal ones, verifying the feasibility of the system.
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Grigoropoulos, Costas P., David J. Hwang, and Anant Chimmalgi. "Nanometer-Scale Laser Direct-Write Using Near-Field Optics." MRS Bulletin 32, no. 1 (January 2007): 16–22. http://dx.doi.org/10.1557/mrs2007.10.
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AbstractThis article summarizes research on laser-based processing and structuring of materials at the nanoscale using optical near-field schemes. Both apertureless and tapered fiber near-field scanning optical microscope probes can deliver highly confined irradiation at sufficiently high intensities to cause morphological and structural changes in materials at the nanometer level. The energy emitted by the probes and the absorption within the target material are predicted by carrying out calculations of the near-field electromagnetic distribution. The effects of shrinking laser beam dimensions compete with the energy diffusion into the target material. Experimental results have shown well-controlled subtractive material modification with minimum feature size in the neighborhood of 10 nm. Precise patterning can be achieved via laser-assisted chemical etching. Control of the nucleation of nanostructures via rapid melting and crystallization is demonstrated. The article concludes with an outlook to applications.
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Xu, Peipei, Baoan Chen, Jingyuan Li, and Xuemei Wang. "Gambogic Acid Combined With CdTe QDs For Leukemia Cancer Cells Inhibition and Their Bio-Safety For Rat Brain." Blood 122, no. 21 (November 15, 2013): 5028. http://dx.doi.org/10.1182/blood.v122.21.5028.5028.
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Abstract The development of new anticancer agents typically involves long research cycles, high cost and low efficiency and so on. There has been a growing public interest in the use of complementary and alternative medicine for cancer treatment and drug discovery. The emergence of nanotechnology and nanomaterials has greatly stimulated research in drug delivery and optimization. As a good fluorescence probe and simultaneously as potential drug carrier, Cadmium-Tellurium quantum dots (CdTe QDs) can optimize the use and a new potential therapy method of some drug-active compounds. Based on these considerations, we have explored the possibility to connect cysteamine (Cys) modified CdTe QDs (Cys-CdTe) to gambogic acid (GA). These functional QDs were studied for multi-functional drug delivery to investigate the synergetic effect of these composites between GA and QDs for human leukemia caner cells K562 and their drug-resistant cell line K562/A02 in vitro. Also the neurotoxicity of different drug systems for Sprague Dawley (SD) rat brain was analyzed by in vivo real-time microdialysis. The nanocomposites of GA loaded CdTe QDs were prepared and the drug releasing of GA-CdTe nanocomposites was performed at the medium of pH 6.0 and 7.4 in vitro. The cytotoxicity of GA and the nanocomposites for K562 and K562/A02 cells was studied by MTT, cell morphology, and flow cytometry. The labeling and imaging of CdTe QDs and the nanocomposites for cancer cells was performed by laser confocal fluorescence microscopy. Different drug systems were respectively injected into SD rat by vena caudalis and cerebrospinal fluid was collected by microdialysis in vivo. The neurotoxicity of different drug systems for rat brain was investigated by the changes of amino acid content in the cerebrospinal fluid. The Cys modified CdTe QDs showed the good fluorescence characteristics, with the wide excitation spectrum and narrow emission spectrum. The CdTe QDs could label in human leukemia cancer cells not only for K562 but also K562/A02 , which had the potential application in the cell imaging. Following the electrostatic attraction, surface adsorption et al, these CdTe QDs had the good capability of drug delivery with the high drug-loading and envelopment capacity. Also these GA-CdTe nanocomposites showed the pH sensitivity for the drug release and improved the drug's un-dissolvability. The GA-CdTe nanocomposites also had the fluorescence characteristics for labeling the different kinds of leukemia cancer cells. Gambogic acid play an important role in cancer therapy and also showed the sensitivity for the multidrug resistance (MDR) of K562/A02 cells in this study. The results indicated that GA-CdTe nanocomposites could significantly enhance the drug accumulation to improve the cytotoxicity and considerably overcome the multidrug resistance. GA-CdTe nanocomposites induced the arrest of G0/G1 phase to promote the cells apoptosis. The combination between GA and CdTe QDs can optimize the new potential therapeutic method for GA with the real time labeling and tracing during the disease therapy. The neurotoxicity of GA and GA-CdTe nanocomposites for rat brain was firstly explored by using the microdialysis in vivo. The results indicated that GA had the serious neurotoxicity through the concentration changes of amino acids for the rat brain. The concentration of some excitatory amino acids was remarkably increased. For the GA-CdTe nanocomposites based on CdTe QDs, the side effect of GA was visibly cut down, and the time to cause the neurotoxicity was apparently shortened. These nanocomposites own the better biocompatibility and bio-safety for the relevant cancer treatment in vitro and in vivo. This raises the promising possibility of the application of these fluorescent nanocomposites based on CdTe QDs for the target cancer therapy. The combination of GA with Cys-CdTe QDs can optimize the use and new potential multi-mode therapy of cancers. This may shed new light to exploit the potential application of the active compounds from Traditional Chinese Medicine (TCM). Disclosures: No relevant conflicts of interest to declare.
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Gentile, Richard D. "Ultrasound-Assisted Rhytidectomy Including Sub-SMAS and Subplatysmal Dissection." Facial Plastic Surgery 36, no. 04 (August 2020): 430–46. http://dx.doi.org/10.1055/s-0040-1714119.
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AbstractEnergy-based facelifting techniques are a relatively new genre of surgery. In this approach, the energy-based device—whether laser, radiofrequency plasma, or ultrasound—can be used in the superficial plane to elevate skin flaps before performing more traditional facelift techniques involving the superficial musculoaponeurotic system (SMAS) or platysma. The initial reports of utilizing fiber lasers as surgical tools date back to approximately 2007 and initial lipolasers were used to elevate facial skin flaps. The other energy-based devices were also tested. The author has probably the largest series of energy-based facial rejuvenation procedures, having performed over 3,000 of these procedures. The advantages of laser-assisted rhytidectomy include hemostasis, facilitated dissection in areas hard to elevate conventionally such as nasolabial folds or distal neck and the remodeling and tightening of tissue that results from the activation of the wound healing cascade of neocollagenesis and wound contraction. The author currently has a preference for energy device used during rhytidectomy and it is a high frequency ultrasound energy delivered by a five-ring 2.9- and 3.7-mm probe. The use of the ultrasound dissector in both superficial and deep procedures is highlighted in this article with emphasis on its use for deep cervicoplasty and subplatysmal procedures as well as sub-SMAS elevations of the facial deep plane.
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Amrania, H., L. Drummond, R. C. Coombes, S. Shousha, L. Woodley-Barker, K. Weir, W. Hart, I. Carter, and C. C. Phillips. "New IR imaging modalities for cancer detection and for intra-cell chemical mapping with a sub-diffraction mid-IR s-SNOM." Faraday Discussions 187 (2016): 539–53. http://dx.doi.org/10.1039/c5fd00150a.
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We present two new modalities for generating chemical maps. Both are mid-IR based and aimed at the biomedical community, but they differ substantially in their technological readiness. The first, so-called “Digistain”, is a technologically mature “locked down” way of acquiring diffraction-limited chemical images of human cancer biopsy tissue. Although it is less flexible than conventional methods of acquiring IR images, this is an intentional, and key, design feature. It allows it to be used, on a routine basis, by clinical personnel themselves. It is in the process of a full clinical evaluation and the philosophy behind the approach is discussed. The second modality is a very new, probe-based “s-SNOM”, which we are developing in conjunction with a new family of tunable “Quantum Cascade Laser” (QCL) diode lasers. Although in its infancy, this instrument can already deliver ultra-detailed chemical images whose spatial resolutions beat the normal diffraction limit by a factor of ∼1000. This is easily enough to generate chemical maps of the insides of single cells for the first time, and a range of new possible scientific applications are explored.