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Renal cell carcinoma with Xp11.2 translocation involving the TFE3 gene (TFE3-RCC) is a recently identified subset of RCC with unique morphology and clinical presentation. The chimeric PRCC-TFE3 protein produced by Xp11.2 translocation has been shown to transcriptionally activate its downstream target genes that play important roles in carcinogenesis and tumor development of TFE3-RCC. However, the underlying molecular mechanisms remain poorly understood. Here we show that in TFE3-RCC cells, PRCC-TFE3 controls heme oxygenase 1 (HMOX1) expression to confer chemoresistance. Inhibition of HMOX1 sensitized the PRCC-TFE3 expressing cells to genotoxic reagents. We screened for a novel chlorambucil-polyamide conjugate (Chb) to target PRCC-TFE3-dependent transcription, and identified Chb16 as a PRCC-TFE3-dependent transcriptional inhibitor of HMOX1 expression. Treatment of the patient-derived cancer cells with Chb16 exhibited senescence and growth arrest, and increased sensitivity of the TFE3-RCC cells to the genotoxic reagent etoposide. Thus, our data showed that the TFE3-RCC cells acquired chemoresistance through HMOX1 expression and that inhibition of HMOX1 by Chb16 may be an effective therapeutic strategy for TFE3-RCC.

Purpose Totally implantable central venous access port implantation is typically performed in the supine position. However, some patients cannot adopt the supine position due to severe pain and/or dyspnea. The present study evaluated the technical feasibility of peripherally inserted central catheter port system (PICC-PORT) implantation in the sitting position in such cases. Materials and methods In the sitting position method, PICC-PORT implantation was performed with the patients seated on a videofluoroscopy chair positioned between the limbs of an angiographic C-arm and the operative upper arm positioned on an arm stand. From January 2019 to September 2021, eight patients underwent PICC-PORT implantations using this sitting method. We also evaluated 251 consecutive patients with conventional supine position PICC-PORT implantation as controls. Differences in technical success, procedure time and complications were retrospectively assessed between the two groups. Results Procedural success rates were 100% in both groups. Median procedure times in the sitting and conventional groups were 42 and 44 min, respectively. No complications were observed in the sitting group. There were no significant differences between the two groups in procedure time (p = 0.674) and complications (p = 1.000). Conclusion Implantation of PICC-PORT in the sitting position is technically feasible and useful.

Hemorrhage arising from the coronary sinus is very rare and can be lethal. It has historically been treated surgically. The present patient had coronary sinus rupture secondary to esophageal cancer and an abscess in the pericardium. Due to her poor general status, this patient was contraindicated for surgery and underwent endovascular therapy. The hemorrhage was treated by stent graft deployment and the patient was temporarily discharged. Two months later, CT showed that the stent graft was occluded by thrombosis. The patient died without hemorrhage 2.5 months thereafter.

Background: The KRAS inhibitor KR12, based on pyrrole-imidazole polyamide (PIP), has been developed and shown to exhibit efficacy in mouse experiments. Because some PIP species exhibit tumor accumulation capability, we decided to evaluate whether the PIP portion of KR12 exhibits tumor accumulation. We employed the CAM assay that provides a simple method for tumor accumulation evaluation. Methods: KR12 PIP was synthesized and conjugated to TAMRA to produce a fluorescently labeled reagent (KR12-TAMRA). This reagent was injected into a fertilized chicken egg that has been transplanted with human cancer cells. Distribution of the red fluorescence was examined by cutting out tumor as well as various organs from the embryo. Results: The red fluorescence of KR12-TAMRA was found to overlap with the green fluorescence of the tumor formed with GFP-expressing cancer cells. We also observed nuclear localization of KR12-TAMRA. Treatment of KR12 that contained the alkylating agent CBI in the tumor-bearing chicken egg resulted in tumor growth inhibition. Conclusions: KR12 contains a PIP that has two key features: tumor accumulation and nuclear localization. KR12 conjugated with CBI exhibits inhibition of tumor growth in the CAM model.

To evaluate the radiopacity of contrast-loaded superabsorbent polymer microspheres (SAP-MS) under X-ray imaging. SAP-MS were suspended in contrast material (iodixanol) and the diameter change was assessed. The diameter of contrast-loaded SAP-MS in saline was measured sequentially. Radiography of the contrast-loaded SAP-MS was evaluated as radiopacity by contrast-to-noise ratio and visibility by multiple reader scoring. Under digital subtraction angiography, contrast-loaded SAP-MS were injected into a flow model. The flow speed was 1–10 cm/s, and images were acquired at 1–7.5 frames per second using a pulse width of 10–85 ms. Images were assessed by multiple reader scoring. The diameter of SAP-MS increased to 4.0–5.0 times its original size for approximately 15 min. The diameter of contrast-loaded SAP-MS in saline further increased by 10–30% within several minutes and returned to the previous size. Radiopacity and visibility of contrast-loaded SAP-MS decreased in 30 min after mixing with saline. Visibility was better with slow flow speed and narrow pulse width. For effective observation, contrast-loaded SAP-MS should be kept in non-diluted contrast material until use. The conditions of slower flow and use of a narrow pulse width are recommended.

Steep retrograde doping devices were fabricated using undoped epitaxial Si channels with inserted oxygen layers. The effects of boron transient enhanced diffusion (TED) on threshold voltage (Vth) mismatch were investigated. Suppression of boron TED was effective for reducing V th mismatch of steep retrograde doping devices as well as flat doping profile devices.

Distribution of radiation by C-arm cone-beam computed tomography (CBCT) in the angiographic suite and effectiveness of protection devices were assessed. CBCT image of a human phantom was obtained by a rotation of 220 degrees during 8 seconds of exposure. One hundred and twelve dosimeters were placed at different positions around the beam entry site, and color maps of dose distributions were drawn for horizontal and vertical planes. The measurements showed the highest radiation dose over 600 μGy by a single CBCT image acquisition at a distance of 60 cm from the beam entry site and a height of 90 cm from the floor. The color maps demonstrated the dose distribution to be more intense at the bilateral directions of the phantom. With the use of a ceiling-mounted transparent lead-acryl screen and a table-suspended lead curtain, the doses were reduced by 45–92 % at a direction of 210 degrees and a distance of 120 cm.

We developed an epigenetically active, cooperative DNA binding transcription factor platform assisted by cucurbit[7]uril (CB7) host–guest modules. This new type of molecule termed ePIP–HoGu not only mimics the operation of transcription factors as a pair but also recruits the epigenetic modifier to a particular DNA locus.

Purpose To assess the safety and effectiveness of polidocanol sclerotherapy combined with transarterial embolization using a liquid adhesive agent (n-butyl cyanoacrylate, NBCA) for treatment of extracranial arteriovenous malformations (AVMs). Materials and Methods Twenty-three patients with symptomatic AVMs in the head and neck (6), upper (7) and lower extremity (10) with a mean age of 42 years (range 4–74) treated with polidocanol sclerotherapy were retrospectively assessed. AVMs were classified according to the angiographic morphology of the nidus. There were 2 type I, 6 type II, 6 type IIIa and 9 type IIIb. Arterial embolization using NBCA was performed to reduce arterial flow before sclerotherapy. Polidocanol mixed with contrast material or carbon dioxide was delivered by percutaneous direct puncture. Results Treatment was successfully performed in all patients. In the mean follow-up period of 38 months, symptoms resolved or improved in 20/23 patients (87.0%). AVMs were devascularized 100% in 2 patients, 76–99% in 13, 50–75% in 7 and

Resistivity increase in nano-level Cu wires is becoming a critical issue for high speed ULSIs. We have established a new manufacturing process utilizing very high purity 9N electrolyte and optimized additives to control nano-structures of Cu wires, and we realized Cu wires for practical use with 50% lower resistivity than those made with the conventional process. Using STEM analyses and phase field simulation, we also ascertained the reason for getting the very low resistivity Cu wires.

To determine the incidence and risk factors of renal dysfunction after abdominal endovascular aortic repair (EVAR) and thoracic endovascular aortic repair (TEVAR). The study consisted of 227 patients treated with EVAR and 90 with TEVAR for aortic aneurysms. Parameters, including patients’ background factors, preoperative renal function, contrast dose and aortic wall irregularity on CT images were assessed in relation to postoperative renal dysfunction. Deterioration of renal function was observed in 33 of 218 patients (15.1%) after EVAR and in 7 of 79 (8.9%) patients after TEVAR. Hemodialysis was required in one patient after EVAR. In EVAR, renal dysfunction correlated with age (p = 0.034) and occlusion of accessory renal artery (p = 0.0001). In TEVAR, renal dysfunction correlated with age (p = 0.021), contrast dose (p = 0.042) and irregularity of the descending aortic wall (p = 0.023). In a multiple regression analysis, postoperative renal dysfunction was correlated with occlusion of accessory renal artery (p = 0.0003) after EVAR, and age (p = 0.02), contrast dose (p = 0.026) and irregularity of the descending aortic wall (p = 0.042) after TEVAR. Occlusion of accessory renal artery in EVAR, and age, contrast dose and irregularity of the descending aortic wall in TEVAR were considered to be predictors of postoperative renal dysfunction.

Large DNA molecules have been utilized as a model system to investigate polymer physics. However, DNA visualization via intercalating dyes has generated equivocal results due to dye-induced structural deformation, particularly unwanted unwinding of the double helix. Thus, the contour length increases and the persistence length changes so unpredictably that there has been a controversy. In this paper, we used TAMRA-polypyrrole to stain single DNA molecules. Since this staining did not change the contour length of B-form DNA, we utilized TAMRA-polypyrrole stained DNA as a tool to measure the persistence length by changing the ionic strength. Then, we investigated DNA stretching in nanochannels by varying the ionic strength from 0.06 mM to 47 mM to evaluate several polymer physics theories proposed by Odijk, de Gennes and recent papers to deal with these regimes.

Resistivity increase in nano-level Cu wires is becoming a critical issue for high speed ULSIs. We have established the new manufacturing process utilizing very high-purity 9N electrolyte and optimized additives to control nano-structures of Cu wires, and we realized Cu wires with resistivity 50% lower than that of wires made by a conventional process. We also have ascertained the reason for getting very low resistivity Cu wires by STEM analyses and first-principle simulation.

This study was designed to assess the safety and effectiveness of ethanolamine oleate (EO) sclerotherapy combined with transarterial embolization using a liquid adhesive agent (n-butyl cyanoacrylate, NBCA) for treatment of extracranial arteriovenous malformations (AVMs).Twenty-four patients with symptomatic AVMs in the head and neck (n = 15), extremity (n = 5), and trunk (n = 4) with a mean age of 44 years (range, 18-78) treated with EO sclerotherapy were retrospectively assessed. AVMs were classified according to the angiographic morphology of the nidus. There were 7 type II (arteriolovenous fistulae), 6 type IIIa (arteriolovenulous fistulae with nondilated fistula), and 11 type IIIb (arteriolovenulous fistulae with dilated fistula). Transarterial embolization using NBCA was performed to reduce arterial flow before sclerotherapy. EO mixed with contrast material was delivered by percutaneous direct puncture or by catheterization into the draining vein under balloon occlusion.Three (13%) of 24 patients were cured, 17 (71%) had partial remission, and 4 (16%) no remission. Treatment was considered effective (cure and partial remission) in 20 patients (83%). Four patients (16%) experienced transient minor complications, including self-healing skin ulcer (n = 3) and localized deep venous thrombosis (n = 1). There were no major complications.EO sclerotherapy combined with transarterial embolization using NBCA is safe and effective for treating extracranial AVMs with an acceptable risk of minor complications.

Fluorescence in situ hybridization (FISH) is a powerful tool used in karyotyping, cytogenotyping, cancer diagnosis, species specification, and gene-expression analysis. Although widely used, conventional FISH protocols are cumbersome and time consuming. We have now developed a FISH method using exciton-controlled hybridization-sensitive fluorescent oligodeoxynucleotide (ECHO) probes. ECHO–FISH uses a 25-min protocol from fixation to mounting that includes no stringency washing steps. We use ECHO–FISH to detect both specific DNA and RNA sequences with multicolor probes. ECHO–FISH is highly reproducible, stringent, and compatible with other fluorescent cellular labeling techniques. The resolution allows detection of intranuclear speckles of poly(A) RNA in HeLa cells and dissociated hippocampal primary cultures, and mRNAs in the distal dendrites of hippocampal neurons. We also demonstrate detection of telomeric and centromeric DNA on metaphase mouse chromosomes. The simplicity of the ECHO–FISH method will likely accelerate cytogenetic and gene-expression analysis with high resolution.

Subnuclear poly(A)(+) RNA localization in living mammalian cells was visualized by ratiometric analysis using hybridization-sensitive fluorescent oligonucleotide probes. Probes were oligonucleotides, which contained a Cy5 fluorescent dye at the strand end and a thiazole orange double-labeled nucleotide inside strand. A ratiometric analysis using poly(A)-targeting probes revealed a distribution of the probe itself as red fluorescence and localization of the target RNA sequence in cell nuclei as green fluorescence. The fluorescence of the subnuclear poly(A)(+) RNA hybridized with the poly(A)-targeting probes was observed as puncta in interchromatin areas.

Hybridization-sensitive fluorescent probes have an inherent disadvantage: self-dimerization of the probe prevents the fluorescence quenching prior to hybridization with the target, resulting in a high background signal. To avoid self-dimerization of probes, we focused on a base pair formed by 2'-deoxyinosine (I) and N(4)-ethyl-2'-deoxycytidine (E). I and E bases form more stable base pairs with cytosine and guanine, respectively, compared with an I/E base pair. New hybridization-sensitive fluorescent probes, IE probes, were prepared containing three unnatural nucleotides, I, E and D(514) as a doubly thiazole orange-labeled nucleotide. The IE probes had low thermostability, sufficient to avoid self-dimerization. Absorption spectra of the IE probes exhibited a hybridization-dependent shift of the absorption maximum, suggesting that excitonic interaction was working between the thiazole orange dyes in the probe. Interdye excitonic interaction of IE probes was very effective; thus, replacement of guanine and cytosine with I and E improved the ratio of fluorescence intensities after and before hybridization (I(hybrid)/I(nonhybrid)). Although a significant weakness in fluorescence intensity was observed for several IE probes after hybridization with the target sequence when both or either of the bases adjacent to D(514) is E, a dramatic recovery of the fluorescence intensity of hybrids was observed when any E adjacent to D(514) was replaced with cytosine. Improvement of the I(hybrid)/I(nonhybrid) value by incorporation of I and E helped the design of a long probe sequence for mRNA imaging.

A 2′-deoxycytidine derivative modified by two thiazole orange dyes has been designed for functional expansion of hybridization-sensitive fluorescence probes. This nucleotide was synthesized by a procedure that included protection of the cytosine amino group by di( n -butyl)formamidine formation, followed by incorporation into DNA. The fluorescence of the synthesized DNA was controlled by excitonic interaction, showing strong fluorescence upon hybridization with the target nucleic acid and effective quenching in a single-stranded state of the probe.

A hybridization-sensitive, quencher-free fluorescent probe for RNA detection has been designed using the concept of fluorescence quenching caused by the intramolecular excitonic interaction of fluo...

We have designed a doubly thiazole orange labeled nucleoside showing high fluorescence intensity for a hybrid with the target DNA and effective quenching for a single-stranded state. Knowing how much the fluorescence emission and quenching of this probe depend on the probe sequence and why there is such a sequence dependence is important for effective probe design, we synthesized more than 30 probe sequences and measured their fluorescence intensities. When the probe hybridized with the target DNA strands, there was strong emission, whereas the emission intensity was much weaker before hybridization; however, self-dimerization of probes suppressed fluorescence quenching. In particular, the G/C base pairs neighboring the labeled nucleotide in a self-dimeric structure resulted in a low quenching ability for the probe before hybridization. On the other hand, mismatched base pair formation around the labeled site decreased the fluorescence intensity because the neighboring sequence is the binding site of the tethered thiazole orange dyes. The hybridization enhanced the fluorescence of the probe even when the labeled nucleotide was located at the end of the probe strand; however, the partial lack of duplex structure resulted in a decrease in the fluorescence intensity of the hybrid.

To evaluate the results of uterine artery embolization (UAE) for symptomatic uterine leiomyoma by use of porous gelatin particles (PGP) in comparison with conventional hand-cut gelatin sponge particles. One hundred and fifteen consecutive patients who had undergone UAE were retrospectively assessed. The first 64 patients were treated with hand-cut gelatin sponge and the last 51 with PGP. Extent of infarction, volume reduction of the dominant leiomyoma on magnetic resonance (MR) imaging, and change in symptoms were assessed. UAE was successfully performed for all patients. No major complications were observed. MR images one month after UAE showed that the mean extent of infarction of the dominant leiomyoma was 97 % for patients treated with PGP and 96 % for those treated with hand-cut gelatin sponge. Volume reductions of the dominant leiomyoma after 3, 6, 12, and 24 months were, respectively, 45, 56, 62, and 66 % for use of PGP and 45, 57, 63, and 68 % for use of hand-cut gelatin sponge. Symptoms including heavy menstrual bleeding, heavy menstrual pain, and abdominal heaviness had improved by 95–100 % at 12 months. There was no difference between the two groups. UAE with PGP is safe, and as effective as conventional gelatin sponge particles.

This is the first report of abnormal behavior in the soft error rate (SER) dependence on supply voltage (Vcc) for a bottom-gated polysilicon PMOS thin-film transistor (TFT) static random access memory (SRAM). We found that the TFT SER does not continuously improve (as is expected and desirable) with increasing Vcc when Vcc exceeds -Vth (threshold voltage) of the TFT within a range of about 0-2 V. This was confirmed with samples of TFT with Vth intentionally varied from 0 to -5 V (by adjusting channel doping). A possible explanation of this Vcc independence is proposed in the form of a SPICE simulation with as little as a 0.1-V TFT transient Vth shift due to the TFT's floating body. The accelerated SER was measured by using an Americium alpha particle source.

During fabrication of semiconductor devices, the stresses on a silicon substrate sometimes cause dislocations and worsen the electric characteristics of the device. Therefore, a dislocation-free fabrication process needs to be developed to improve reliability. In this paper, a process design method using stress singularity parameters (K and λ) is proposed. In order to prevent the dislocation generation, the process parameters, such as the device structure, materials and process temperatures, are set to keep the stress singularity parameters (K and λ) under the critical values of dislocation generation Kdc. These parameters are predicted using FEM method considering the internal stress of thin films. The process design was applied to a bipolar transistor and a MOS transistor and the experimental results agreed very well with the prediction. It was confirmed that this new process design method is effective in improving device reliabirity.

Bleomycin (BLM)-mediated degradation of parallel-stranded (ps) DNA duplex was investigated by HPLC product analysis of the oxidized DNA fragments. It was revealed that Co– and Fe–BLMs effectively degraded a ps DNA decamer at 5′-GC site in a similar manner to that for antiparallel-stranded (aps) B-form DNA. While the strand orientations of ps and aps duplexes are quite different, metallo-BLMs still bind to ps DNA duplex and cause DNA degradation. These results indicate that metallo-BLMs productively interact with the degradable strand of both ps and aps DNA duplexes.

A tri-gate bulk MOSFET design utilizing a low-aspect-ratio channel is proposed to provide an evolutionary pathway for CMOS scaling to the end of the roadmap. 3-D device simulations indicate that this design offers the advantages of a multi-gate FET (reduced variability in performance and improved scalability) together with the advantages of a conventional planar MOSFET (low substrate cost and capability for dynamic threshold-voltage control).

Once considered mature and commodity technology, CMOS Si technology keeps revamping itself as a collection of most innovative technologies known to humanity at this given time. Beyond conventional vanilla scale of SiON/Poly planar bulk Si technology, lab-level experiments constantly become manufacturing reality, such as high- k , metal gate, FDSOI, FinFET, and many exotic patterning technologies. This rapid pace of new technology introduction to CMOS technology, however, requires much more sophisticated optimization of process, device, and circuit design, in order to maximize return on investment. Careful optimization of process technology, device structure, layout, and circuit design in a holistic manner enables significant performance improvement while reducing overall power consumption with the least amount of area penalty.

A facile method for the synthesis of puromycin-tethered oligonucleotides at the 3′-end is described. The method utilizes a novel CPG support derived from commercially available puromycin. Puromycin-tethered DNA and RNA oligomers were synthesized using a puromycin-tethered CPG support by the usual protocol for automated DNA and RNA synthesis.

Summary: A 47-year-old woman was admitted to the hospital for evaluation of proteinuria. Bilateral sensorineural deafness had been diagnosed previously at age 35. She had a positive family history of deafness going back three generations. A renal biopsy showed the presence of highly organized fibrillary deposits in the subendothelial mesangial areas. the microfibrils had a diameter of 11-16 nm, larger than the diameter of amyloid fibrils, and did not have a microtubular appearance. the renal specimen was negative for Congored staining. There was no clinical or serologic evidence of paraproteinaemia, cryoglobulinaemia, light-chain disease, or systemic lupus erythematosus. the diagnosis was fibrillary glomerulonephritis. This is the first known case of fibrillary glomerulonephritis in a patient with familial sensorineural deafness.

Fluorescent probes for the detection of a double-stranded DNA were prepared by labeling a triplex-forming DNA oligonucleotide with a thiazole orange (TO) dimer unit. They belong to ECHO (exciton-controlled hybridization-sensitive fluorescent oligonucleotide) probes which we have previously reported. The excitonic interaction between the two TO molecules was expected to effectively suppress the background fluorescence of the probes. The applicability of the ECHO probes for the detection of double-stranded DNA was confirmed by examining the thermal stability and photophysical and kinetic properties of the DNA triplexes formed by the ECHO probes.