Objective. To determine the efficacy of local therapy with human angiostatin gene in murine collageninduced arthritis (CIA).Methods. DBA/1 mice were immunized with bovine type II collagen. Before the onset of arthritis, NIH3T3 fibroblasts, transduced with angiostatinexpressing retroviral vectors or control vectors, were transplanted into the knee cavity. The incidence of arthritis in the knee joints was evaluated histologically based on pannus formation and cartilage destruction. Paws were evaluated macroscopically for redness, swelling, and deformities and immunologically for levels of interleukin-1. Angiogenesis in paws and knee joints was studied by immunohistochemistry using anti-CD31 antibody and measurement of von Willebrand factor levels.Results. Pannus formation and cartilage erosion were dramatically reduced in knees transplanted with angiostatin-expressing cells. In addition, the onset of CIA in the ipsilateral paws below the knees injected with the angiostatin gene was significantly prevented. Furthermore, angiostatin gene transfer inhibited arthritisassociated angiogenesis.Conclusion. Local production of angiostatin in the knee was able to prevent the onset of CIA not only in the knee injected with genetically engineered cells, but also in the uninjected ipsilateral paw. This suggests that transfer of the angiostatin gene, and potentially also its protein, may provide a new, effective approach to the treatment of rheumatoid arthritis.
A simultaneous volumetric thickness-profile measurement method based on an acousto-optic tunable filter for transparent film deposited upon pattern structures is described. The nondestructive thickness profilometer prevents the destruction of samples such as one encounters in using a scanning-electron microscope and provides good accuracy. The information on the volumetric thickness profile is obtained through least-squares fitting with a phase model, ø(model)(k)=2kh+? (k, d)+(offset) , which has three unknowns: surface profile h, thickness d, and an indeterminate initial phase offset. Accurate phase information in the spectral domain can be obtained by introduction of the concept of spectral carrier frequency. Experimental results for a metal patterned sample show that the volumetric thickness profile can be determined within an error range of ~10 nm .
These results demonstrate that most HDI studies so far have examined PK interactions and have been limited to very few conventional drugs and herbal drugs. This suggests that more studies focusing on PD are necessary to understand interactions between commonly used herbal and conventional drugs.
In this study, a combined system of microneedles and a triboelectric nanogenerator (TENG) has been developed for drug delivery. A triboelectric device, which converts mechanical energy into alternating current (AC), was chosen to replace the electrophoresis (EP) effect. To directly generate triboelectricity from salmon deoxyribonucleic acid (SDNA)-based microneedles, a triboelectric series of SDNA film and chargeable polymers (polyimide and Teflon) was studied. The electrical output of the two charged polymers was compared to find a material that could be highly charged with SDNA. The electrical output was also compared as a function of the concentration of a drug embedded in the SDNA film, and the results confirmed that drug intercalation affected the carrier diffusion. The mechanical strength of the microneedles was assessed by histological analysis of their penetration into porcine cadaver skin. Furthermore, the output voltage of a system incorporating microneedles and TENG in cadaver skin, and in vitro drug release into gelatin were evaluated to examine potential application as an electrically active drug delivery system. The electrical output voltage of this system was ∼95 V. The mechanism of triboelectric perturbation to the skin has also been discussed. The system developed in this work is a new, facile approach toward effective drug delivery that replaces the existing EP method and expands the application of TENGs.
Microneedles, fabricated by nano-moulding technology show great promise in the field of drug delivery by enabling the painless self-administration of drugs in a patient-friendly manner. In this study, double-stranded salmon DNA (SDNA) was used as both a drug-delivery vehicle and structural material with a microneedle system. SDNA is non-toxic and demonstrates good mechanical robustness, mouldability, biocompatibility, bio-absorbability, and binding affinity with drug molecules for bio-functional applications. Benign fabrication conditions to protect temperature-sensitive biomolecules are used to produce SDNA structures of various sizes with a high aspect ratio (4: 1). Unlike existing dissolving microneedle structure materials, the special binding characteristics of doxorubicin hydrochloride, anti-cancer drug molecules, and SDNA demonstrate the stability of drug-molecule encapsulation via UV-absorption and photoluminescence analyses. Based on COMSOL simulation and in vitro analysis of the stratum corneum of porcine skin, the mechanical functionality of SDNA microneedles was evaluated in vitro by penetrating the stratum corneum of porcine skin. The SDNA microneedle dissolved and drug permeation was assessed using rhodamine, a drug surrogate. Owing to its many beneficial characteristics, we anticipate that the SDNA microneedle platform will serve as an effective alternative for drug delivery.
Freeform optics have emerged as promising components in diverse applications due to the potential for superior optical performance. There are many research fields in the area ranging from fabrication to measurement, with metrology being one of the most challenging tasks. In this paper, we describe a new variant of lateral shearing interferometer with a tunable laser source that enables 3D surface profile measurements of freeform optics with high speed, high vertical resolution, large departure, and large field-of-view. We have verified the proposed technique by comparing our measurement result with that of an existing technique and measuring a representative freeform optic.
The autofocusing is one of the important parts in the automated vision inspection or measurement using optical microscopes. Moreover, laser micromachining or laser lithography requires a high speed and precision autofocusing. In this paper, we propose and realize an autofocusing system using two cylindrical lenses, which is the enhanced version of the previous astigmatism method. It shows very good performances, especially very high speed and the largest range in comparison with the previous astigmatic methods. The performance of our autofocusing system was evaluated by tracing the linear stage whose position was monitored by a commercial laser interferometer. Then we applied the autofocusing to the direct laser lithographic system, and successfully fabricated circular symmetry patterns on a 300 mm diameter surface with the resolution of less than 1 microm within the defocusing range of +/-50 microm. The speed of the autofocusing was 150 Hz.
A new mirror mounting technique applicable to the primary mirror in a space telescope is presented. This mounting technique replaces conventional bipod flexures with flexures having mechanical shims so that adjustments can be made to counter the effects of gravitational distortion of the mirror surface while being tested in the horizontal position. Astigmatic aberration due to the gravitational changes is effectively reduced by adjusting the shim thickness, and the relation between the astigmatism and the shim thickness is investigated. We tested the mirror interferometrically at the center of curvature using a null lens. Then we repeated the test after rotating the mirror about its optical axis by 180° in the horizontal setup, and searched for the minimum system error. With the proposed flexure mount, the gravitational stress at the adhesive coupling between the mirror and the mount is reduced by half that of a conventional bipod flexure for better mechanical safety under launch loads. Analytical results using finite element methods are compared with experimental results from the optical interferometer. Vibration tests verified the mechanical safety and optical stability, and qualified their use in space applications.
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