Physicochemical insights into semiconductor properties of a semitransparent tantalum nitride photoanode for solar water splitting.

The self-conductivity of tantalum nitride (Ta3N5) thin film-based semitransparent photoanodes was found to promote the current originating from the photoelectrochemical oxygen evolution reaction (PEC OER) without a conducting substrate. With surface modification by the NiFeOx-electrocatalyst, an optimized Ta3N5 thin film fabricated directly on a transparent insulating quartz substrate generated a photocurrent density of ∼5.9 ± 0.1 mA cm-2 at 1.23 V vs. the reversible hydrogen electrode under simulated AM 1.5G solar illumination. The correlation between the PEC OER performance of NiFeOx-modified Ta3N5 photoanodes and the electrical properties of Ta3N5 thin films was investigated based on the Hall effect measurements. By changing the nitridation conditions, these properties can be tuned so that the higher the Hall mobility (0.2 to 1.7 cm2 V-1 s-1) and the lower the carrier concentration (1020 to 1019 cm-3). The surface chemical states of Ta3N5 thin films were investigated using X-ray photoelectron spectroscopy as a means of evaluating surface oxygen impurities and nitrogen vacancies, which may correlate with the PEC OER performance and the electrical properties of the material.

Direct Observation of Group-V Dopant Substitutional Defects in CdTe Single Crystals.

Point defect chemistry strongly affects the fundamental properties of materials and has a decisive impact on device performance. The Group-V dopant is prominent acceptor species with high hole concentration in CdTe; however, its local atomic structure is still not clear owing to difficulties in definitive measurements and discrepancies between experimental observations and theoretical models. Herein, we report on direct observation of the local structure for the As dopant in CdTe single crystals by the X-ray fluorescence holography (XFH) technique, which is a powerful tool to visualize three-dimensional atomic configurations around a specific element. The XFH result shows the As substituting on both Cd (AsCd) and Te (AsTe) sites. Although AsTe has been well known as a shallow acceptor, AsCd has not attracted much attention and been discussed so far. Our results provide new insights into point defects by expanding the experimental XFH study in combination with theoretical first-principles studies in II-VI semiconductors.

Effect of Extracellular Signal-Regulated Protein Kinase 5 Inhibition in Clear Cell Renal Cell Carcinoma.

(1) Background: Extracellular signal-regulating kinase 5 (ERK5) has been implicated in many cellular functions, including survival, proliferation, and vascularization. Our objectives were to examine the expression and effect of ERK5 in clear cell renal cell carcinoma (ccRCC). (2) Methods: The expressions of ERK5 and its regulating micro-RNA miR-143 were investigated using immunohistochemistry and quantitative reverse transcriptase PCR in surgical specimens of ccRCC patients. With invitro and in vivo studies, we used pharmacologic ERK5 inhibitor XMD8-92, RNA interference, pre-miR-143 transduction, Western blotting, MTS assay, apoptosis assay, and subcutaneous xenograft model. (3) Results: A strong ERK5 expression in surgical specimen was associated with high-grade (p = 0.01), high-recurrence free rate (p = 0.02), and high cancer-specific survival (p = 0.03). Expression levels of ERK5 and miR-143 expression level were correlated (p = 0.049). Pre-miR-143 transduction into ccRCC cell A498 suppressed ERK5 expression. ERK5 inhibition enhanced cyclin-dependent kinase inhibitor p21 expression and decreased anti-apoptotic molecules BCL2, resulting in decreased cell proliferation and survival both in ccRCC and endothelial cells. In the xenograft model, ERK5 inhibitor XMD8-92 suppressed tumor growth. (4) Conclusions: ERK5 is regulated by miR-143, and ERK5 inhibition is a promising target for ccRCC treatment.

Association between Hyposensitivity of C-fiber Afferents at The Proximal Urethra and Storage/voiding Dysfunction in Female Patients with Detrusor Overactivity.

PURPOSE: We examined the associations between urethral sensation and storage/voiding function in female patients with detrusor overactivity (DO) by measuring urethral current perception threshold (CPT). MATERIALS AND METHODS: We retrospectively investigated the medical records of 27 consecutive patients with lower urinary tract symptoms who underwent cystometry, uroflowmetry (UFM), and urethral CPT tests from 2000 to 2015. Patients were classified into 2 groups: with/without DO. Seven DO-negative cases were selected as normal controls on cystometrogram (CMG) matching the inclusion criteria: bladder compliance ?12.5 mL/cmH2O, volume <275 mL at first sensation, and no comorbidities possibly influencing micturition. Finally, 17 patients were included. Urethral CPT was evaluated with intraurethral square-wave impulses at 3 Hz to stimulate C-fibers. Urethral loss coefficient (LC), reflecting urethral resistance during voiding, was calculated by curve-fitting a mathematical model to a UFM waveform. RESULTS: Urge incontinence (UI) was observed in 7 DO-positive patients, but not in those with normal CMG. Urethral CPT and LC were significantly higher in patients with DO than in those with normal CMG. Median urethral CPT significantly increased in patients with both DO and UI than in those without these symptoms (p<0.005). CPT values were correlated with the volume at first sensation (?=0.53, p<0.05) and LC (?=0.59, p<0.05). LC was not calculated in 3 cases due to poor curve-fitting. CONCLUSIONS: In females, urethral C-fiber afferents may become hyposensitive as the detrusor becomes overactive with UI in the storage phase. During voiding, C-fiber hyposensitivity may relate to increased functional resistance of the urethra to urine outflow.

Bidirectional in vivo structural dendritic spine plasticity revealed by two-photon glutamate uncaging in the mouse neocortex.

Most excitatory synapses in the brain form on dendritic spines. Two-photon uncaging of glutamate is widely utilized to characterize the structural plasticity of dendritic spines in brain slice preparations in vitro. In the present study, glutamate uncaging was used to investigate spine plasticity, for the first time, in vivo. A caged glutamate compound was applied to the surface of the mouse visual cortex in vivo, revealing the successful induction of spine enlargement by repetitive two-photon uncaging in a magnesium free solution. Notably, this induction occurred in a smaller fraction of spines in the neocortex in vivo (22%) than in hippocampal slices (95%). Once induced, the time course and mean long-term enlargement amplitudes were similar to those found in hippocampal slices. However, low-frequency (1-2 Hz) glutamate uncaging in the presence of magnesium caused spine shrinkage in a similar fraction (35%) of spines as in hippocampal slices, though spread to neighboring spines occurred less frequently than it did in hippocampal slices. Thus, the structural plasticity may occur similarly in the neocortex in vivo as in hippocampal slices, although it happened less frequently in our experimental conditions.

Possible role of hyposensitivity of C-fiber afferents at the proximal urethra in the development of urge urinary incontinence in patients with detrusor overactivity.

OBJECTIVE: The aim of the present study was to investigate associations between urethral sensation and urge urinary incontinence (UUI) in patients with and without detrusor overactivity (DO). METHODS: The medical records of 80 consecutive patients who underwent filling cystometry and urethral current perception threshold (CPT) tests were examined retrospectively. Following the exclusion of 4 patients not eligible for analysis, patients were classified into neurogenic DO, idiopathic DO, or DO-negative groups based on neurological and cystometric findings (n = 30, 12, and 34, respectively). Eleven DO-negative patients were defined as normal controls on cystometrograms (CMG) using the following exclusion criteria: bladder compliance <12.5 mL/cmH2 O, volume >275 mL at first filling sensation, and comorbidities possibly affecting lower urinary tract function. Thus, 53 patients were finally included in the study. Proximal urethral CPT was evaluated with intraurethral square-wave stimulation at 3 Hz to activate C-fiber afferents. RESULTS: Median CPT was higher in neurogenic and idiopathic DO than in the normal CMG group (11.3 and 9.0 vs. 2.8 mA, respectively; P < .05), as well as in patients with UUI (n = 19) compared with non-UUI patients (n = 34; 12.5 vs. 5.4 mA, respectively; P < .05). The proportion of UUI patients was significantly greater in the DO-positive groups than in the normal CMG group (P < .05). CPTs were not associated with bladder capacity at the first filling sensation (r = 0.11). CONCLUSION: Hyposensitive C-fibers of the proximal urethra may contribute to the development of urodynamic DO as well as UUI in patients complaining of lower urinary tract symptoms.

[AN EXPERIENCE OF PARTIAL NEPHRECTOMY IN A PATIENT WITH VON WILLEBRAND DISEASE].

A 28-year-old male visited a nearby hospital with chief complaint of bilateral back pain and fever. He was diagnosed with a right complex renal cyst (Bosniak classification, IIF) with a kidney stone and was referred to our hospital. We first suspected an incarcerated kidney stone and performed flexible transurethral lithotomy; however, his symptoms did not improve. Blood examination revealed prolonged APTT; subsequently, he was diagnosed with von Willebrand disease (VWD). Because he experienced pain due to the hemorrhagic renal cyst, we performed partial nephrectomy. Preoperatively, we supplemented the von Willebrand factor (VWF) based on the VWF activity in the patient. Although intraoperative bleeding was well controlled, he developed bleeding from pseudoaneurysms on the postoperative day (POD) 6. We immediately performed transarterial embolization along with VWF replenishment. VWF supplementation was discontinued on POD 14, and the patient was discharged on POD 23. Since then, he has not experienced a bleeding recurrence or pain. In patients with VWD, the perioperative administration of desmopressin or VWF is recommended. Although several reports showed that surgeries involving these treatments are safe, only three cases with VWD, including the present case where the patient underwent partial nephrectomy, have been reported. In the present case, postoperative bleeding occurred despite exhibiting adequate perioperative VWF activity. Thus, bleeding complications in patients with VWD undergoing partial nephrectomy must be considered and should be carefully followed up.

Topological Insulator-Based van der Waals Heterostructures for Effective Control of Massless and Massive Dirac Fermions.

Three dimensional (3D) topological insulators (TIs) are an important class of materials with applications in electronics, spintronics and quantum computing. With the recent development of truly bulk insulating 3D TIs, it has become possible to realize surface dominated phenomena in electrical transport measurements e.g. the quantum Hall (QH) effect of massless Dirac fermions in topological surface states (TSS). However, to realize more advanced devices and phenomena, there is a need for a platform to tune the TSS or modify them e.g. gap them by proximity with magnetic insulators, in a clean manner. Here we introduce van der Waals (vdW) heterostructures in the form of topological insulator/insulator/graphite to effectively control chemical potential of the TSS. Two types of gate dielectrics, normal insulator hexagonal boron nitride (hBN) and ferromagnetic insulator Cr2Ge2Te6 (CGT) are utilized to tune charge density of TSS in the quaternary TI BiSbTeSe2. hBN/graphite gating in the QH regime shows improved quantization of TSS by suppression of magnetoconductivity of massless Dirac fermions. CGT/graphite gating of massive Dirac fermions in the QH regime yields half-quantized Hall conductance steps and a measure of the Dirac gap. Our work shows the promise of the vdW platform in creating advanced high-quality TI-based devices.

Enhancement in surface mobility and quantum transport of Bi2-xSbxTe3-ySey topological insulator by controlling the crystal growth conditions.

Despite numerous studies on three-dimensional topological insulators (3D TIs), the controlled growth of high quality (bulk-insulating and high mobility) TIs remains a challenging subject. This study investigates the role of growth methods on the synthesis of single crystal stoichiometric BiSbTeSe2 (BSTS). Three types of BSTS samples are prepared using three different methods, namely melting growth (MG), Bridgman growth (BG) and two-step melting-Bridgman growth (MBG). Our results show that the crystal quality of the BSTS depend strongly on the growth method. Crystal structure and composition analyses suggest a better homogeneity and highly-ordered crystal structure in BSTS grown by MBG method. This correlates well to sample electrical transport properties, where a substantial improvement in surface mobility is observed in MBG BSTS devices. The enhancement in crystal quality and mobility allow the observation of well-developed quantum Hall effect at low magnetic field.

In Vivo Volume Dynamics of Dendritic Spines in the Neocortex of Wild-Type and Fmr1 KO Mice.

Excitatory synapses are often formed at small protrusions of dendrite, called dendritic spines, in most projection neurons, and the spine-head volumes show strong correlations with synaptic connectivity. We examined the dynamics of spine volume in the adult mouse visual cortex using time-lapse in vivo two-photon imaging with a resonant Galvano scanner. Contrary to expectations, we found that the spines in the adult neocortex showed fluctuations to a similar degree as that observed in young hippocampal preparations, but there were systematic differences in how the dynamics were dependent on spine volumes, thus allowing for fewer fluctuations in small spines, which could account for the relatively low turnover rates of neocortical spines in vivo. We found that spine volumes fluctuated to a greater extent in a mouse model (Fmr1 knockout) of fragile X mental retardation than in wild-type mice, and the spine turnover rates were also higher in Fmr1 knock-out mice. Such features of spine dynamics in Fmr1 knock-out mice could be represented by a single slope factor in our model. Our data and model indicate a small but significant change in the average spine volume and more eminent differences in the statistical distribution in Fmr1 knock-out mice even in adulthood, which reflects the abnormal in vivo dynamics of spine volumes.

Calcineurin knockout mice show a selective loss of small spines.

Calcineurin is required for long-term depression and activity-dependent spine shrinkage, and calcineurin mutations have been identified in patients with schizophrenia. Moreover, mice with conditional knockout of calcineurin B (CNB-KO) exhibit behavioral abnormalities suggestive of schizophrenia. Changes in the dendritic spines of these mice, however, have not been investigated. We therefore examined the dendritic spines of CNB-KO mice, and observed a significant reduction in small spines and an increase in large spines in the prefrontal and visual cortices. The effect of CNB-KO on the spine sizes was relatively moderate, possibly due to the presence of spontaneous fluctuations (dynamics) in the dendritic spines themselves. Thus, CNB-KO mice showed a spine phenotype similar to those recently reported in patients with schizophrenia.

[Spontaneous Remission of Everolimus-Induced Interstitial Lung Disease in Metastatic Renal Cell Carcinoma : An Autopsy Case Report].

Interstitial lung disease (ILD) is a common side effect of the mechanistic target of rapamycin inhibitor everolimus. Most cases of everolimus-induced ILD are mild and reversible. As per guidelines, even if Common Terminology Criteria for Adverse Events grade 1 or 2 everolimus-induced ILD occurs, either continuation of everolimus without dose reduction or readministration at a low dose is possible. However, the pathophysiology of everolimus-induced ILD is unknown. We present a case of everolimus-induced ILD with spontaneous remission during treatment in a patient with metastatic renal cell carcinoma. At autopsy, there was no evidence of remodeling or chronic inflammation in the lungs. Cryptogenic interstitual pneumonia and broncholitis obliterans with organizing pneumonia can be suspected as a pattern of mild everolimus-induced ILD. This case report provides evidence that everolimus-induced ILD is reversible fromthe pathological perspective.

Renoprotective Procedures with a Cold Ischemia Time of <60 min Minimize the Deterioration of Kidney Function in Open Nephron-Sparing Surgery for Renal Cell Carcinoma.

INTRODUCTION: We evaluated whether nephron sparing surgery (NSS) combined with meticulous suturing of the cut stump under clamping with cooling is beneficial for oncological outcomes and also assessed the relationship between cold ischemia time and deterioration of renal function. METHODS: One hundred and six patients with renal cell carcinoma (RCC) were subjected to this procedure. Oncological outcomes and renal function according to the estimated glomerular filtration rate (eGFR) and the tubular excretion rate on renoscintigraphy before and at 12 months after surgery were evaluated. RESULTS: Cancer recurrences were observed in 2 patients with past history of RCC; however, no patient died of cancer. Renal function was evaluated depending on 4 different ischemia times. All groups did not show a remarkable decrease of renal function in terms of eGFR. Renoscintigraphy revealed the deterioration of the affected kidney in patients with >60 min ischemia. CONCLUSION: The renoprotective procedure of NSS provided maximum preservation of renal function until 60 min of cold ischemia time.

Rise in ambient temperature predisposes aging, male Japanese patients to renal colic episodes due to upper urolithiasis.

OBJECTIVE: Urolithiasis is a common urological problem, and its incidence has been increasing worldwide, including in Japan. Relationships between stone etiology and rise in ambient temperature have been reported, but it remains unclear how age and gender affect these relationships. MATERIALS AND METHODS: A retrospective examination was conducted of the medical archives of 1005 patients (aged ≥15 years) with acute renal colic diagnosed with urolithiasis upon image examination who consecutively visited emergency departments in three hospitals. The patients were categorized into six groups according to age: younger than 30, 30-39, 40-49, 50-59, 60-69, and 70 years and older. The net difference and fold increase in the number of patients in summer (July to September) versus in winter (December to February) were calculated. RESULTS: Overall, the actual number of the patients varied according to the temperature rise throughout the year and among the age groups. Net increases in the number of patients were observed in all age groups for both genders, apart from 30-39-year-old women. The age group of 50-59 years considerably outnumbered all other groups. A significant statistical correlation was detected between the fold increase and male aging using Spearman's rank correlation analysis (ρ = 0.94, p = 0.017), but not in females (ρ = -0.03, p = 1). CONCLUSIONS: These results support a positive association between ambient temperature rise and increase in the incidence of renal colic due to urolithiasis in Japan, and indicate that aging and gender affect the association differently.

[CEREBRAL VENOUS SINUS THROMBOSIS IN PATIENTS WITH METASTATIC TESTICULAR CANCER DURING CHEMOTHERAPY: REPORTS OF TWO CASES].

Cerebral venous sinus thrombosis (CVT) is rare but sometimes develops in association with malignant neoplasm. We report two cases of CVT that occurred during cisplatin-based chemotherapy for testicular cancer. A 46-year-old man with stage IIA non-seminomatous germ cell tumour was treated with conventional doses of etoposide and cisplatin (EP). On day 11 of the third treatment course, he developed a systemic seizure. Brain computed tomography (CT) and magnetic resonance (MR) imaging could not detect the cause. Enhanced chest-pelvic CT revealed pelvic thrombosis. Administration of phenytoin for epilepsy of unknown cause and heparin for thrombosis was started. He had completed 4 courses of EP therapy without seizure recurrence. After re-evaluating the brain CT images retrospectively, we found high density of superior sagittal sinus (SSS) and strongly suspected CVT. Another patient was a 47-year-old man with stage IIIB seminomatous germ cell tumour treated with bleomycin, etoposide, and cisplatin (BEP) therapy. On day 11 of the second treatment course, he developed a systemic seizure. Brain CT revealed subarachnoid haemorrhage localised in the right parietal lobe. CT venography revealed a filling defect in the superior sagittal sinus (SSS). MR venography revealed a SSS stenosis. We diagnosed the cause of the seizure as CVT and started administration of anticoagulant therapy. After the thrombus had diminished, chemotherapy was restarted and another 2 courses of BEP therapy was completed.

Expression of Extracellular Signal-regulated Kinase 5 and Ankyrin Repeat Domain 1 in Composite Pheochromocytoma and Ganglioneuroblastoma Detected Incidentally in the Adult Adrenal Gland.

Composite pheochromocytoma (cPC) is extremely rare, arising in the adrenal medulla as a mixture of PC and other tumors of neural origin. We herein report on a case of adrenal incidentaloma post-operatively diagnosed as cPC with ganglioneuroblastoma (GNBL). The PC component had 7 points on the PASS, a Ki-67 index of 5.1%, a focal absence of sustentacular cells, and no genetic aberrations in succinate dehydrogenase subunit B. The GNBL component exhibited no N-myc amplification. Tumor cells of both components were stained positively for extracellular signal-regulated kinase 5 and ankyrin repeat domain 1. The aberrant activation of growth signaling may play a role in the marginal malignancy of cPC.

GSK-3 directly regulates phospho-4EBP1 in renal cell carcinoma cell-line: an intrinsic subcellular mechanism for resistance to mTORC1 inhibition.

BACKGROUND: The phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin 1 (mTORC1) signaling pathway is aberrantly activated in renal cell carcinoma (RCC). We previously demonstrated glycogen synthase kinase-3ß (GSK-3ß) positively regulated RCC proliferation. The aim of this study was to evaluate the role of GSK-3 in the PI3K/Akt/mTORC1 pathway and regulation of the downstream substrates, eukaryotic translation initiation factor 4E-binding protein 1 (4EBP1), ribosomal protein S6 kinase (S6K), and ribosomal protein S6 (S6RP). METHODS: We used human RCC cell lines (ACHN, Caki1, and A498) and, as normal controls, human renal proximal tubular epithelial cell (HRPTEpC) and non-tumorous kidney tissues that were obtained surgically for treatment of RCC patients. Rapamycin-resistant ACHN (ACHN/RR) cells were generated with chronic exposure of ACHN to rapamycin ranging from 1nM finally to 1 µM. Cell viability, cell cycling and direct interaction between GSK-3ß and 4EBP1 were evaluated with MTS assay, flowcytometry and in vitro kinase assay with recombinant GSK-3ß and 4EBP1products, respectively. Protein expression and phosphorylation of molecules associated with the PI3K/Akt/mTORC1 pathway were examined by immunoblotting. Effects of drug combination were determined as the combination index with CompuSyn software. RESULTS: Overexpression and phosphorylation of 4EBP1 and S6RP together with GSK-3 activation were observed in RCC cell lines, but not in human normal kidney cells and tissues. Cell proliferation, p4EBP1 and pS6RP were strongly suppressed by GSK-3 inhibition. Rapamycin and LY294002 sufficiently decreased pS6RP, but only moderately p4EBP1. In vitro kinase assays showed that recombinant GSK-3ß phosphorylated recombinant 4EBP1, and the effect was blocked by GSK-3 inhibitors. Different from rapamycin, AR- A014418 remarkably inhibited cell proliferation, and rapidly suppressed p4EBP1 and pS6RP in ACHN and ACHN/RR (in 30 min to 1 h). AR- A014418 and rapamycin combination showed additivity at lower concentrations, but antagonism at higher concentrations. CONCLUSIONS: GSK-3ß could directly phosphorylate 4EBP1 and activate the mTORC1 downstream signaling cascades to enhance protein biosynthesis and cell proliferation in RCC cell lines independent of rapamycin sensitivity. The direct GSK-3ß/4EBP1 pathway might be an important subcellular mechanism as an inherent equipment for RCC cells to acquire clinical chemoresistance to mTORC1 inhibitors.

Abnormal intrinsic dynamics of dendritic spines in a fragile X syndrome mouse model in vivo.

Dendritic spine generation and elimination play an important role in learning and memory, the dynamics of which have been examined within the neocortex in vivo. Spine turnover has also been detected in the absence of specific learning tasks, and is frequently exaggerated in animal models of autistic spectrum disorder (ASD). The present study aimed to examine whether the baseline rate of spine turnover was activity-dependent. This was achieved using a microfluidic brain interface and open-dura surgery, with the goal of abolishing neuronal Ca(2+) signaling in the visual cortex of wild-type mice and rodent models of fragile X syndrome (Fmr1 knockout [KO]). In wild-type and Fmr1 KO mice, the majority of baseline turnover was found to be activity-independent. Accordingly, the application of matrix metalloproteinase-9 inhibitors selectively restored the abnormal spine dynamics observed in Fmr1 KO mice, without affecting the intrinsic dynamics of spine turnover in wild-type mice. Such findings indicate that the baseline turnover of dendritic spines is mediated by activity-independent intrinsic dynamics. Furthermore, these results suggest that the targeting of abnormal intrinsic dynamics might pose a novel therapy for ASD.

[Asynchronous Bilateral Testicular Infarction with Suspected Polyarteritis Nodosa : A Case Report].

This report documents a case of asynchronous bilateral testicular infarction. The patient was a 42- year-old man who presented with left testicular pain and swelling. He had a past history of right idiopathic testicular infarction and underwent a right orchiectomy 6 years ago. He also had received treatment for 5 years for suspected polyarteritis nodosa (PAN). The left scrotal pain persisted for a week and left orchiectomy was performed. Pathological evaluations demonstrated a benign testis with testicular hemorrhage and chronic vasculopathy. There was no fibrinoid necrosis of medium-size vessel walls which characterizes PAN. In this report, we review the pathogenesis, risk of contralateral testicular infarction, and management of testicular infarction.