A Tightly Controlled Conditional Knockdown System Using the Tol2 Transposon-Mediated Technique

Background: Gene knockdown analyses using the in utero electroporation method have helped reveal functional aspects of genes of interest in cortical development. However, the application of this method to analyses in later stages of brain development or in the adult brain is still difficult because the amount of injected plasmids in a cell decreases along with development due to dilution by cell proliferation and the degradation of the plasmids. Furthermore, it is difficult to exclude the influence of earlier knockdown effects. Methodology/Principal Findings: We developed a tightly controlled conditional knockdown system using a newly constructed vector, pT2K-TBI-shRNAmir, based on a Tol2 transposon-mediated gene transfer methodology with the tetracycline-inducible gene expression technique, which allows us to maintain a transgene for a long period of time and induce the knockdown of the gene of interest. We showed that expression of the endogenous amyloid precursor protein (APP) was sharply decreased by our inducible, stably integrated knockdown system in PC12 cells. Moreover, we induced an acute insufficiency of Dab1 with our system and observed that radial migration was impaired in the developing cerebral cortex. Such inhibitory effects on radial migration were not observed without induction, indicating that our system tightly controlled the knockdown, without any expression leakage in vivo. Conclusions/Significance: Our system enables us to investigate the brain at any of the later stages of development or in th

Advancements in the Epsilon Launch Vehicle\u27s Rideshare Capability and Future Missions

Fifth Epsilon launch vehicle (Epsilon-5) with Innovative Satellite Technology Demonstration-2 was successfully launched from JAXA Uchinoura Space Center in Kagoshima, Japan on November 9, 2021. Successful injection of nine satellites with high accuracy demonstrated the capability of Epsilon launch vehicle for rideshare missions of various satellite sizes. The new Epsilon Satellite Mount Structure-II (ESMS-II) and an adapter was developed to launch more satellites. In the paper, we first introduce Epsilon launch vehicle and its multi-launch capability. Then, we describe the mission design of Epsilon-5 and rideshare specific configuration. Finally, we mention the rideshare opportunity provided by Epsilon launch vehicle in the future

Volcanic magma reservoir imaged as a low-density body beneath Aso volcano that terminated the 2016 Kumamoto earthquake rupture

Additional file 2: Figure S2. Calculated density contrast models beneath Aso volcano in horizontal slices at depths of 3.1, 4.9, and 8.2 km: (a), (b), (c), (d), (e), and (f) correspond to density contrasts of ±0.15, ±0.20 ±0.25, ±0.30, ±0.35, and ±0.40 g/cm3, respectively (Additional file 5: Table S1)

Analysis of the Optimum Tapering Angle in Microanastomosis Using Computational Fluid Dynamics

Background: In free flap transfer, size discrepancy between the vascular pedicle and recipient vessel can create a problem for microsurgeons and sometimes induces postoperative thrombus formation. When there is a major difference between the diameters of the vascular pedicle and the recipient vessel, the larger vessel is often tapered to perform the anastomosis properly. However, the decision on the tapering angle used depends mostly on the operator’s experience. In this study, computational fluid dynamics (CFD) was used to investigate the optimum tapering angle. Methods: Using ANSYS ICEM 16.0 (ANSYS Japan, Tokyo, Japan), simulated vessels of diameters 1.5 mm and 3.0 mm were designed and then used to produce four anastomosis models with the 3.0-mm vessel tapered at angles of 15º, 30º, 60º, and 90º (no tapering). Venous perfusion with a mean value of 13.0 mL/min was simulated, and this was passed through the four anastomosis models in both the forward direction (F), from the smaller to the larger vessel, and the retrograde direction (R), from the larger to the smaller vessel. The velocity, wall shear stress (WSS), and oscillatory shear index (OSI) were measured in these eight patterns and then analyzed using OpenFOAM version 5. Results: The decrease in velocity was limiting. The WSS was greater in the R direction than the F direction at every tapering angle. The OSI also tended to be almost the same in the F direction, and lower at smaller tapering angles in the R direction. And, it was greater in the F direction than in the R direction at every tapering angle. The OSI values for 15º and 30º were almost identical in the R direction. Conclusion: The risk of thrombus formation is thought to be lower when tapering is used for anastomosis if the direction of flow is from the larger to the smaller vessel, rather than vice versa. These results also suggest that the optimum tapering angle is approximately 30º in both directions

Free Flap Blood Flow Evaluated Using Two-Dimensional Laser Speckle Flowgraphy

Objective. We investigated the efficiency of laser speckle flowgraphy for evaluating blood flow in free flaps used for plastic surgery. Methods. We measured blood flow using a visual laser meter capable of providing two-dimensional color graphic representations of flow distribution for a given area using a dynamic laser speckle effect. Using laser speckle flowgraphy, we examined the blood flow of 20 free flaps applied following the excision of head and neck tumors. Results. After anastomosis of the feeding and draining blood vessels and sewing the flap, musculocutaneous (MC) flaps showed significantly lower blood flow than jejunal or omental flaps (P < .05). The ratio of blood flow decrease from the edge to the center was significantly greater in MC flaps than in jejunal or omental flaps (P < .001). Conclusion. Laser speckle flowgraphy is useful for the perioperative measurement of blood flow in free flaps used in plastic surgery. This method is a highly useful, practical, and reliable tool for assessing cutaneous blood flow and is expected to be applicable to several clinical fields

Evaluation of tritium production rate in a blanket mock-up using a compact fusion neutron source

We report a neutronics study of a blanket mock-up using a discharge-type compact fusion neutron source. Deuterium–deuterium fusion neutrons were irradiated to the mock-ups composed of tritium breeder and neutron reflector/moderator. The tritium production rate (TPR) per source neutron was measured by a single-crystal diamond detector with a 6Li-enriched lithium fluoride film convertor after the calibration process. Despite the low neutron yield, energetic alpha and triton particles via 6Li(n, t)α neutron capture as well as 12C via elastic scattering were successfully detected by the SDD with high signal to noise ratios. The TPRs were experimentally evaluated with errors of 8.4%–8.5% at the 1σ level at the positions with high thermal neutron fluxes where the errors were dominantly introduced by uncertainties in the monitoring of the neutron production rate. The calculated to experimental (C/E) values of TPR were evaluated to be 0.91–1.27 (FENDL-2.1) and 0.94–1.28 (FENDL-3.1). As the neutron source can generate 14 MeV neutrons using a mixed gas of deuterium and tritium, this approach provides more opportunities for blanket neutronics experiments

Full-endoscopic disc cleaning surgery

It has been reported that Modic change of the lumbar spine endplate includes three types: i.e. . edema or inflammation for type 1, fatty marrow change for type 2 and sclerotic change for type 3. Basically, type 1 Modic change may be related to the chronic low back pain. There are two kinds of the treatment for the type 1 Modic change to heal the pain : the anti-inflammatory drugs, and intra-discal injection of steroid. When the inflammatory change would be intractable, surgical intervention is needed. The gold standard for the surgical intervention is the segmental fusion of the affected level. The fusion surgery may cause the adjacent degeneration ; thus, motion preservation surgery is better, if possible. Our department started the motion preservation full-endoscopic intradiscal debridement surgery for this pathology, since some of the type 1 Modic change may be chronic discitis by P. Acnes. In this paper, we describe the first patient of type 1 Modic change who was successfully treated by the full-endoscopic intra-discal debridement and drainage under the local anesthesia. We named this procedure as transforaminal full-endoscopic disc cleaning surgery (FEDC). Finally, pathology, conservative and surgical intervention of Modic change was discussed

The Usefulness of Diffusion-weighted Imaging in Observing Localized Extension of Endometrial Cancer

Endometrial cancer is the seventh most common human malignancy and the most common form of cancer treated in women by obstetrics and gynecology departments. Until now, magnetic resonance imaging (MRI) has been used for pre-surgical evaluation of endometrial cancer and evaluating the depth of myometrial invasion, in addition to being a valuable diagnostic tool. Diffusion-weighted imaging (DWI) has been reported as useful in distinguishing between benign and malignant tumors when observing lesions in the endometrium. Subsequent reports suggest that DWI is also effective in identifying malignancy and diagnosing local extension in a range of tissues. Based on this, we implemented a study of the effectiveness of DWI in identifying local extension of endometrial cancer. This study enrolled patients undergoing surgery at this hospital for cancer of the uterine body during the six years from January 2008 to February 2014. Cases in which images were unclear or the lesions were too small to be described by MRI examination were excluded, leaving 61 patients in the study. Using the results from pre-surgical MRI, a sequence comprising a T2-weighted axial view alone and a T2-weighted axial view to which a diffusion-weighted axial view had been added was created for each patient. Two radiologists then independently examined the image sequence to determine localized extension. Following surgery, the pre-surgical assessment was compared to the localized extension determined by histopathology of post-surgical samples to evaluate the effectiveness of adding diffusion-weighted imaging to the process. The first radiographic interpreter\u27s rate of correct diagnosis using the T2-weighted axial view alone was 45 out of 55 cases (81.8%), while using the T2-weighted axial view to which a diffusion-weighted axial view had been added gave a correct diagnosis rate of 51 out of 55 cases (92.7%). The second radiographic interpreter\u27s rate of correct diagnosis using the T2-weighted axial view alone was 41 out of 55 cases (74.5%), while using the T2-weighted axial view with diffusion-weighted axial view added gave a correct diagnosis rate of 51 out of 55 cases (92.7%). These differences were statistically significant based on the McNemar testing. This study confirmed that DWI is an effective means of diagnosing localized extension from images. It is anticipated that DWI will be used in the future clinical workplace to provide more accurate pre-surgical diagnoses

Comparison of 1.5 T(Tesla) and 3.0 T(Tesla) Magnetic Resonance Imaging for Evaluating Local Extension of Endometrial Cancer

Magnetic resonance imaging (MRI) is an important means of evaluating local extension of endometrial cancer. The 3.0 Tesla (T) MRI system introduced in 2005 improved the diagnostic capabilities of this modality due to an increased signal to noise ratio; however, it was also susceptible to artifacts and debate remains regarding the clinical applicability of 3.0 T MRI in the pelvic region. A few reports have compared 1.5 T and 3.0 T MRI for determining the degree of progression of endometrial cancer. Therefore, we conducted a comparative study of the diagnostic capability of 1.5 T and 3.0 T MRI for the local extension of endometrial cancer. Over the 6 years and 8 months from 1 January 2008 to 30 August 2014, preoperative MRI has been conducted at our hospital including T2-weighted imaging, diffusion-weighted imaging, and dynamic contrast-enhanced MRI for cases of endometrioid adenocarcinoma requiring surgery. We investigated 60 subjects after excluding cases for which the tumor could not be imaged and cases that underwent surgery 2 months or more after undergoing MRI. Two radiologists used magnetic resonance images taken preoperatively to determine local extension using T2-weighted, diffusion-weighted, and dynamic-study images. Results for local extension were compared with those of postoperative histopathology. Results indicated no significant difference in accurate diagnosis rates between 1.5 T and 3.0 T MRI for any of the imaging modalities examined by both radiologists