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Background/Aims Endoscopic ultrasound-guided tissue acquisition (EUS-TA) using Franseen needles is reportedly useful for its high diagnostic yield. This study compared the diagnostic yield and puncturing ability of EUS-TA using 22-gauge cobalt-chromium (CO-Cr) needles with those of stainless-steel Franseen needles in patients with solid pancreatic lesions. Methods Outcomes were compared between the 22-gauge Co-Cr Franseen needle (December 2019 to November 2020; group C) and stainless-steel needle (November 2020 to May 2022; group S). Results A total of 155 patients (group C, 75; group S, 80) were eligible. The diagnostic accuracy was 92.0% in group C and 96.3% in group S with no significant intergroup differences (p=0.32). The rate of change in the operator (from training fellows to experts) was 20.0% (15/75) in group C and 7.5% (6/80) in group S. Stainless-steel Franseen needles showed less inter-operator difference than Co-Cr needles (p=0.03). Conclusions Both Co-Cr and stainless-steel Franseen needles showed high diagnostic ability. Stainless-steel Franseen needles are soft and flexible; therefore, the range of puncture angles can be widely adjusted, making them suitable for training fellows to complete the procedure.

Endoscopic retrograde cholangiopancreatography (ERCP) in patients with surgically altered anatomy is technically challenging. For example, scope insertion, selective cannulation, and intended procedures, such as stone extraction or stent placement, can be difficult. Single-balloon enteroscopy (SBE)-assisted ERCP has been used to effectively and safely address these technical issues in clinical practice. However, the small working channel limits its therapeutic potential. To address this shortcoming, a short-type SBE (short SBE) with a working length of 152 cm and a channel of 3.2 mm diameter has recently been introduced. Short SBE facilitates the use of larger accessories to complete certain procedures, such as stone extraction or self-expandable metallic stent placement. Despite the development in the SBE endoscope, various steps have to be overcome to successfully perform such procedure. To improve success, the challenging factors of each procedure must be identified. At the same time, endoscopists need to be mindful of adverse events, such as perforation, which can arise due to adhesions specific to the surgically altered anatomy. This review discussed technical tips regarding SBE-assisted ERCP in patients with surgically altered anatomy to increase success and reduce the risk of adverse events associated with ERCP.

Abstract Scirrhous gastric cancer (SGC) is diagnosed using endoscopy and/or biopsy; however, SGC diagnosis remains challenging owing to its special growth form and morphologic features. Hence, endoscopic ultrasound‐guided fine‐needle aspiration (EUS‐FNA), which is minimally invasive and has a high proportion of diagnostic tissue, may be an alternative investigative modality for patients with suspected SGC. This systematic review and meta‐analysis aimed to identify and evaluate the evidence for the efficacy and safety of EUS‐FNA in patients with suspected SGC. We conducted a systematic review using the PubMed (MEDLINE) and Ichushi‐Web (NPO Japan Medical Abstracts Society) databases and included all entries in which SGC was evaluated using EUS‐FNA in accordance with the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) statement from the databases′ inception to October 10, 2022. The primary outcome was the proportion of SGC diagnosed using EUS‐FNA. In addition, we analyzed the proportion of adverse events associated with EUS‐FNA. The electronic search identified 1890 studies; overall, four studies met the selection criteria and reported data on EUS‐FNA performed on 114 patients with suspected SGC. The overall diagnostic yield of EUS‐FNA for SGC was 82.6% (95% confidence interval, 74.6–90.6%) and the statistical heterogeneity was 0% (I2 = 0%), indicating a low heterogeneity. Furthermore, the EUS‐FNA diagnostic proportion for SGC lymph node metastasis was 75–100%, indicating a high diagnostic performance. The adverse event rate of EUS‐FNA was 0%. EUS‐FNA may be an alternative investigation mode for SGC patients with negative esophagogastroduodenoscopy‐biopsy results.

Abstract Background Myalgic encephalomyelitis/chronic fatigue syndrome/systemic exertion intolerance disease (ME/CFS/SEID) is a condition diagnosed primarily based on clinical symptoms, including prolonged fatigue and post-exertional malaise; however, there is no specific test for the disease. Additionally, diagnosis can be challenging since healthcare professionals may lack sufficient knowledge about the disease. Prior studies have shown that patients with ME/CFS/SEID have low serum acylcarnitine levels, which may serve as a surrogate test for patients suspected of having this disease. This systematic review and meta-analysis aimed to investigate the differences in serum acylcarnitine levels between patients with ME/CFS/SEID and healthy controls. Methods This systematic review was conducted using PubMed and Ichushi-Web databases. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, we included all studies from the databases’ inception until February 17, 2023, that evaluated blood tests in both patients with ME/CFS/SEID and healthy control groups. The primary endpoint was the difference in serum acylcarnitine levels between the two groups. Results The electronic search identified 276 studies. Among them, seven met the eligibility criteria. The serum acylcarnitine levels were analyzed in 403 patients with ME/CFS/SEID. The patient group had significantly lower serum acylcarnitine levels when compared with the control group, and the statistical heterogeneity was high. Conclusion The patient group had significantly lower serum acylcarnitine levels when compared with the control group. In the future, the measurement of serum acylcarnitine levels, in addition to clinical symptoms, may prove to be a valuable diagnostic tool for this condition.

Abstract Background Some conventional prognostic biomarkers for esophageal squamous cell carcinoma (ESCC) have the disadvantage that they have only been investigated at the level of either mRNA or protein levels or only in individual cohorts. Associations between Syntaxin 3 (STX3) expression and malignancy have been reported in several tumor types but not in ESCC. Here, we investigated the levels of both STX3 mRNA and protein, and its prognostic potential in two independent cohorts of patients with ESCC. Methods STX3 mRNA levels were examined in surgical specimens by quantitative PCR in a cohort that included 176 ESCC patients. STX3 protein levels were investigated in surgically resected ESCC tissues by immunohistochemistry using tissue microarrays in a different cohort of 177 ESCC patients. Correlations were analyzed between the expression of STX3 mRNA and protein with clinicopathological factors and long‐term prognosis. Results Quantitative PCR indicated a significant association between high level of STX3 mRNA expression and lymph node involvement, pathological stage, and poor overall survival. The multivariate analysis demonstrated that high STX3 mRNA expression was independently associated with poor overall survival outcomes. Immunohistochemistry revealed that STX3 protein expression in ESCC tissues and high STX3 protein expression were also significantly correlated with unfavorable overall survival. Conclusions Overexpression of STX3 mRNA and protein may serve as potential prognostic biomarkers for ESCC patients.

Abstract Regulated Ire1-dependent decay (RIDD) is a feedback mechanism in which the endoribonuclease Ire1 cleaves endoplasmic reticulum (ER)-localized mRNAs encoding secretory and membrane proteins in eukaryotic cells under ER stress. RIDD is artificially induced by chemicals that generate ER stress; however, its importance under physiological conditions remains unclear. Here, we demonstrate the occurrence of RIDD in filamentous fungus using Aspergillus oryzae as a model, which secretes copious amounts of amylases. α-Amylase mRNA was rapidly degraded by IreA, an Ire1 ortholog, depending on its ER-associated translation when mycelia were treated with dithiothreitol, an ER-stress inducer. The mRNA encoding maltose permease MalP, a prerequisite for the induction of amylolytic genes, was also identified as an RIDD target. Importantly, RIDD of malP mRNA is triggered by inducing amylase production without any artificial ER stress inducer. Our data provide the evidence that RIDD occurs in eukaryotic microorganisms under physiological ER stress.

Abstract There is a need for serum diagnostic biomarkers to improve the prognosis of solid malignant tumors. Here, we conducted a single-institutional study to evaluate the diagnostic performance of serum stromal cell-derived factor 4 (SDF4) levels in cancer patients. Serum samples were collected from a total of 582 patients with solid cancers including gastric cancer (GC) and 80 healthy volunteers. SDF4 protein levels in sera, and conditioned media or lysates of human GC cell lines were measured by enzyme-linked immunosorbent assay, and those in GC tissue by immunohistochemistry. Serum SDF4 levels were higher in patients with cancer than the healthy control in all cancer type. Regarding GC, serum SDF4 levels distinguished healthy controls from GC patients with the area under the curve value of 0.973, sensitivity of 89%, and specificity of 99%. Serum SDF4 levels were significantly elevated in patient with early stage GC. In immunohistochemistry, the frequency of SDF4-positive GC tumors did not vary significantly between GC stages. The ability of human GC cell lines to both produce and secrete SDF4 was confirmed in vitro. In conclusion, serum SDF4 levels could be a promising candidate for a novel diagnostic biomarker for GC and other malignancies.

Abstract Background Valproic acid (VPA) is a relatively safe drug widely used for the treatment of epileptic seizures and mania in bipolar disorder, as well as the prevention of migraine headaches. Here, we present a case of VPA-induced pancreatitis in a patient with vascular dementia, epileptic seizures, and psychiatric symptoms. He had no distinctive abdominal symptoms. Case presentation A 66-year-old Japanese man was treated with VPA for agitation and violent behavior due to vascular dementia, epileptic seizures, and psychiatric symptoms. During admission, he experienced a sudden decrease in consciousness and blood pressure. Abdominal findings were unremarkable; however, blood tests showed an inflammatory response and elevated amylase levels. Contrast-enhanced abdominal computed tomography showed diffuse pancreatic enlargement and inflammation extending to the subrenal pole. VPA-induced acute pancreatitis was diagnosed, VPA was discontinued, and high-dose infusions were administered. Acute pancreatitis resolved after treatment initiation. Conclusions Clinicians should be aware of this relatively rare side effect of VPA. Diagnosis may be challenging in elderly people and patients with dementia as they may present with non-specific symptoms. Clinicians should consider the risk of acute pancreatitis when using VPA in patients who cannot report spontaneous symptoms. Blood amylase and other parameters should be measured accordingly.

Automatic speech recognition of a target speaker in the presence of interfering speakers remains a challenging issue. One approach to tackle this problem is target-speaker speech recognition, which conditions the recognition process on an embedding that characterizes the voice of the target speaker. This enables recognizing only the speech of the target speaker while ignoring interferences. In this work, we propose an end-to-end target-speaker speech recognition system based on a neural transducer architecture to allow streaming and on-device recognition. Moreover, a target-speaker speech recognition system should be able to detect when the target speaker is inactive and output nothing in such a case. We introduce training and decoding schemes to allow target-speaker activity detection within our proposed recognition system. We confirm experimentally that our proposed end-to-end system performs competitively to conventional cascade approaches of a target speech extraction module and a recognition module while reducing computation costs and allowing streaming decoding.

Gas atomized powder is commonly used for Laser powder bed fusion (L-PBF) additive manufacturing because of its good flowability. On the other hand, water atomized powder is inexpensive and has a great potential for application to middle range manufactured products. In this study, SUS316L water atomized powder was applied to L-PBF additive manufacturing. To solve its poor flowability and excessive spatter, we investigated these problems and modified the additive manufacturing machine. Our test results revealed that a laser energy density of 57.8 J/mm3 is one of the best laser conditions for water atomized powder additive manufacturing. To apply the design for additive manufacturing (DfAM), the mechanical properties and overhang process window were revised. Finally, an extruder die plate with better pellet productivity was designed and produced by using SUS316L water atomized powder. The results showed that, it produced better quality pellets than the original one. From this research, we found that water atomized powder is useful for L-PBF additive manufactured products.

Key Clinical Message Neuronal intranuclear inclusion disease (NIID) is a progressive neurodegenerative disorder characterized by intranuclear inclusions. Kidney injury involvement and successful treatment for NIID have rarely been reported. A NIID patient developed crescentic IgA nephropathy. Steroid therapy resolved digestive symptoms and recovered renal function. Steroids are considered for concomitant symptoms of NIID.

The electron beam current of high-power, long-pulse gyrotrons for fusion devices is typically controlled to remain constant by adjusting the power to the cathode heater by using a pre-programmed waveform. However, this pre-programmed waveform is usually developed through a time-consuming trial and error process and its precision is low. Therefore, a system to automatically control electron beam current was developed and its performance was tested with one of the JADA/QST-manufactured gyrotrons for ITER. The control system automatically adjusted beam current to a target value of 47 A within ±0.5% for 900 s. This high-precision beam current control can maintain an output power of 1 MW and, being automated, it is useful for power on/off modulation operations. If the operation is switched from continuous to modulated, the beam current can be changed to compensate for the decrease in emission cooling of the cathode. This automatic control system demonstrates the quick recovery of a stable beam current in modulation operations.

Abstract Paleotsunami studies along the Pacific coast of Tohoku, northern Japan, have been considerably developed recently, particularly after the massive impact of the 2011 Tohoku-oki tsunami. Nevertheless, in the southernmost Shimokita Peninsula, studies pertaining to paleotsunami are underdeveloped, leading to a vague understanding of the tsunamigenic sources northward of the Tohoku region, along with incomplete hazard evaluation. Paleotsunami deposits in Shimokita can be related not only to the Japan Trench along the Sanriku coast but also to the Kuril trench along the Pacific coast of Hokkaido. In this study, we unveiled the paleotsunami history of Hachinohe in northern Tohoku. Using a combination of sedimentological, geochemical, paleontological, and mineralogical proxies, we characterized seven sand layers that dated from ca. 2700 to ca. 5500 yr BP based on radiocarbon (14C) ages as event deposits of marine origin. Sedimentological and paleontological evidence coupled with ground-penetrating radar imagery revealed a marsh environment comprising successive extinct ponds, controlling the depositional environment. Numerical modeling ruled out the possibility of storms as genetic sources, leading to the conclusion that the presence of event deposits with marine sediments in the study area would be associated with tsunami inundation episodes. Based on 14C dating, the mean frequency of recurrence of tsunamis is estimated as 384 years (320–450 yr, 95% confidence interval) and a coefficient of variation of 0.78 (0.68–0.99, 95% confidence interval). The previously recorded limited paleotsunami evidence and absence of an estimated recurrence interval in the Shimokita Peninsula reaffirm the importance of Hachinohe as a tsunami record site for the activity of both trenches.

Introduction After kidney transplantation, patients should be treated with caution and monitored for surgical complications. Among the possible surgical complications, strangulation ileus after kidney transplantation is rare. Case presentation A 59‐year‐old woman who had undergone kidney transplantation at 41 years of age presented to our hospital with lower abdominal pain. She was diagnosed with strangulation ileus and underwent emergency surgery. In the lower right abdomen, the small intestine was compressed by cord‐like tissue running from the intraperitoneal space to the retroperitoneal space. We confirmed that the cord‐like tissue was the ureter of the transplanted kidney. The necrotic small intestine was resected, and ureter‐ureteral anastomosis of the ureter of the transplanted kidney was performed. Conclusion All surgical procedures, including ureteroneocystostomy, require careful attention. The occurrence of some postoperative surgical complications can be prevented by carefully performing the kidney transplantation procedure.

Abstract Higher cortisol levels due to a hyperactive hypothalamic–pituitary–adrenal axis have been reported in patients with major depressive disorder (MDD). Increased cortisol levels change both the brain morphology and function in MDD patients. The multivariate source-based morphometry (SBM) technique has been applied to investigate neuroanatomical changes in some neuropsychiatric diseases, but not MDD. We aimed to examine the alterations in gray matter (GM) networks and their relationship with serum cortisol levels in first-episode, drug-naïve MDD patients using SBM. Forty-two patients with MDD and 39 controls were recruited via interviews. Morning serum cortisol levels were measured, and high-resolution T1-weighted imaging followed by SBM analysis was performed in all participants. The patients had significantly higher serum cortisol levels than the controls. We found two GM sources, which were significantly different between patients with MDD and controls (prefrontal network, p

High-power (1 MW), long-pulse operations up to 300 s were demonstrated by multi-frequency oscillations at 170 GHz, 137 GHz, and 104 GHz. A multi-frequency gyrotron based on the design of the ITER gyrotron has been developed and studied. By redesigning the built-in mode convertor and internal mirrors of the ITER gyrotron, the internal scattered power of the gyrotron was reduced while maintaining the same output beam size and beam direction for the three frequencies. In addition, the mirrors of a matching optics unit were designed to efficiently couple the RF beam at 170 GHz, 137 GHz, and 104 GHz oscillations to a waveguide 50 mm in diameter, the same size that will be used in ITER. An HE _11 mode content of ∼94% was achieved for the three frequencies. Output powers of 1 MW at 170 GHz and 137 GHz, and 0.9 MW at 104 GHz were demonstrated up to 300 s. These oscillation frequencies can facilitate in a wide range of toroidal magnetic field operations at ITER, including plasma start-up and electron heating and current drive.

Introduction: The frequency that idiopathic focal segmental glomerulosclerosis (FSGS) recurs in renal allografts is reportedly 20-50%, but the epidemiology of secondary FSGS in this setting has scarcely been addressed. Objectives: The aim of this study was to examine the incidence, etiology, and subtypes of FSGS in renal allograft recipients and allograft survival in recipients with FSGS. Patients and Methods: As a retrospective review, we examined medical records of 359 consecutive renal allograft recipients (living donors, 329; cadaveric donors, 30). In 121 of these patients, allograft dysfunction or proteinuria prompted biopsies. We compared allograft survival in recipients with and without FSGS. We then determined histologic subtypes of FSGS using the Columbia classification and categorized FSGS as recurrent or de novo, and idiopathic or secondary. Results: Of 121 subjects who were biopsied, six with inadequate specimens (

The construction of the Linear IFMIF Prototype Accelerator (LIPAc) is in progress in order to demonstrate the feasibility of the low energy section of an IFMIF deuteron accelerator up to 9 MeV with a beam current of 125 mA in CW. The next milestone of the project is the so-called Phase-B beam commissioning, and one of the missions is to demonstrate the acceleration of the proton beam up to 2.5 MeV or the deuteron beam up to 5.0 MeV in pulsed mode with a low duty cycle of 0.1% through RFQ. Most of the components and subsystems necessary for Phase-B were delivered by 2016 under the responsibility of Fusion for Energy (F4E) as in-kind contributions of several European institutes, namely CEA (France), CIEMAT (Spain), INFN (Italy), and SCK-CEN (Belgium), and QST is in charge of the installation of the delivered equipment. The installation and check-out of the RFQ subsystem and the RF power system was completed by July 2017, and the RF conditioning of the RFQ cavity started. Also, the installation and the check-out of the important sub-systems for Phase-B, namely MEBT and beam diagnostics, have been completed. Keywords: IFMIF, LIPAc, RFQ, Accelerator, Deuteron, Neutron source

The Radio Frequency Quadrupole (RFQ) linac and 1.6 MW RF power system of the Linear IFMIF Prototype Accelerator (LIPAc) facility in the International Fusion Energy Research Center (IFERC) in Rokkasho (Japan) has been installed and conditioned. During the assembly and tuning process, the RFQ cavity was protected with a temporary tent from the potential deterioration of performance caused by dust. The vacuum in the cavity was improved through the 100 °C baking process of the cavity. The high power test of the 175 MHz RF systems up to 200 kW in CW for each of the eight RF chains was performed for checking its stable output reproducibility in Japan, before connecting 9–3/16 inch coaxial transmission lines from the RF chains to the RF input couplers of the cavity. It was confirmed that the eight RF chains provided the balanced RF power to the single RFQ cavity in-phase using a feedback loop and a synchronization system. The peak power in the cavity achieved 150 kW in the pulsed mode, which corresponds approximately to the required electric field to accelerate proton beam. Such RF conditioning process is ongoing to achieve 600 kW approximately required for deuteron beam commissioning planned in 2018.

Emergency medical treatment in Japan is subject to jurisdiction by the Fire Department. Triage, by definition, is a dynamic process, as the patient's status can change rapidly. Triage is very important for Japan, where emergency patients are on the rise. The role of triage nurse is also important. That will improve the life-saving rate of emergency patients and improve the reversion to society.

We demonstrate clear self-heating effects (SHEs) of bulk and silicon-on-insulator (SOI) MOSFETs for various SOI/buried oxide (BOX) thicknesses including ultra-thin 6 nm BOX, which was not detected by the ac conductance method, using the four-terminal gate resistance technique. We clarify that the SHE in bulk MOSFETs originates from the degradation of thermal conductivity in a heavily doped well region. The strong chip-temperature dependence of the SHE was observed only in bulk MOSFETs. As results of the chip temperature-dependent SHE of bulk devices and the SHE suppression by BOX thinning, the device temperature of ultra-thin BOX SOI MOSFETs is close to that of bulk MOSFETs at an elevated chip temperature, which suggests the thermal advantage of extremely thin BOX structures.

This paper proposes an identification method for the excitation force of a rigid body vibration source. This is done by constructing a characteristic matrix without a force signal during a preliminary excitation test. In mechanical products, if an abnormal vibration such as excessive vibration occurs after machine assembly, reworking is necessary to rectify the problem. This extends of the development period and increases cost. Therefore, quantitative vibration prediction at the design state is important. In order to predict quantitative vibration, it is necessary to understand the excitation force of the vibration source. The proposed method of excitation force does not use a force signal during the preliminary excitation test. Therefore, there is no restriction on the vibration method in the preliminary vibration test, and it solves the problem in the case where the excitation point cannot be secured. In this method, the modal mass is calculated using a rigid body mode vector of 6 degrees of freedom (acquired during the preliminary vibration test) and the mass of the vibration source. Then, after determining the mass normalized mode vector from the calculated modal mass, the characteristic matrix of the rigid body vibration source is identified. Finally, the excitation force when the machine is running is identified from the equation of motion in the frequency domain. As a result of testing the verify the validity of the method, the proposed method can identify the excitation with the same precision as when using the force signal and has demonstrated its usefulness.

Human-computer interface systems whose input is based on eye movements can serve as a means of communication for patients with locked-in syndrome. Eye-writing is one such system; users can input characters by moving their eyes to follow the lines of the strokes corresponding to characters. Although this input method makes it easy for patients to get started because of their familiarity with handwriting, existing eye-writing systems suffer from slow input rates because they require a pause between input characters to simplify the automatic recognition process. In this paper, we propose a continuous eye-writing recognition system that achieves a rapid input rate because it accepts characters eye-written continuously, with no pauses. For recognition purposes, the proposed system first detects eye movements using electrooculography (EOG), and then a hidden Markov model (HMM) is applied to model the EOG signals and recognize the eye-written characters. Additionally, this paper investigates an EOG adaptation that uses a deep neural network (DNN)-based HMM. Experiments with six participants showed an average input speed of 27.9 character/min using Japanese Katakana as the input target characters. A Katakana character-recognition error rate of only 5.0% was achieved using 13.8 minutes of adaptation data.

This paper proposes identification method of excitation force of rigid body vibration source by physical model identification. If the reworking occurs after the assembly of the prototype in mechanical product, the cost increases due to the retrofit countermeasures and development period extension. Pre-prediction of vibration at the design stage is important to avoid these problems. Prior prediction of vibration needs to grasp the excitation force of the vibration source. As conventional methods, the mount stiffness method and the matrix inversion method have been proposed. However, mount stiffness method calculates the mount transmission force. Therefore, if the development machine changes the structure, preliminary evaluation does not apply. The matrix inversion method can solve this problem. However, when the frequency response function contains a measurement error, the error spreading propagates in inverse matrix calculation. Therefore, in order to avoid the inverse matrix calculation, we propose identification method of excitation force of rigid body vibration source by physical model identification. In this paper, it was investigated features of the inverse matrix method and the identification method of excitation force by physical model identification using the basic experiment. As a result of study, the method by physical model identification showed that the influence of measurement error is smaller than the matrix inversion method. In addition, it showed that it is possible to identify the excitation force with fewer excitation points than the matrix inversion method.

Successful treatment of aspergillosis caused by Aspergillus fumigatus is threatened by an increasing incidence of drug resistance. This situation is further complicated by the finding that strains resistant to azoles, the major antifungal drugs for aspergillosis, have been widely disseminated across the globe. To elucidate mechanisms underlying azole resistance, we identified a novel transcription factor that is required for normal azole resistance in Aspergillus fungi including A. fumigatus, Aspergillus oryzae, and Aspergillus nidulans. This fungal-specific Zn2-Cys6 type transcription factor AtrR was found to regulate expression of the genes related to ergosterol biosynthesis, including cyp51A that encodes a target protein of azoles. The atrR deletion mutant showed impaired growth under hypoxic conditions and attenuation of virulence in murine infection model for aspergillosis. These results were similar to the phenotypes for a mutant strain lacking SrbA that is also a direct regulator for the cyp51A gene. Notably, AtrR was responsible for the expression of cdr1B that encodes an ABC transporter related to azole resistance, whereas SrbA was not involved in the regulation. Chromatin immunoprecipitation assays indicated that AtrR directly bound both the cyp51A and cdr1B promoters. In the clinically isolated itraconazole resistant strain that harbors a mutant Cyp51A (G54E), deletion of the atrR gene resulted in a hypersensitivity to the azole drugs. Together, our results revealed that AtrR plays a pivotal role in a novel azole resistance mechanism by co-regulating the drug target (Cyp51A) and putative drug efflux pump (Cdr1B).

An erbium-doped silicon transistor prepared by ion implantation and co-doped with oxygen is investigated by photocurrent generation in the telecommunication range. The photocurrent is explored at room temperature as a function of the wavelength by using a supercontinuum laser source working in the μW range. The 1-μm2 transistor is tuned to involve in the transport only those electrons lying in the Er-O states. The spectrally resolved photocurrent is characterized by the typical absorption line of erbium and the linear dependence of the signal over the impinging power demonstrates that the Er-doped transistor is operating far from saturation. The relatively small number of estimated photoexcited atoms (≈ 4 × 10 4 ) makes Er-dpoed silicon potentially suitable for designing resonance-based frequency selective single photon detectors at 1550 nm.

The metabolic pathway of purine nucleotides in parasitic protozoa is a potent drug target for treatment of parasitemia. Guanosine 5'-monophosphate reductase (GMPR), which catalyzes the deamination of guanosine 5'-monophosphate (GMP) to inosine 5'-monophosphate (IMP), plays an important role in the interconversion of purine nucleotides to maintain the intracellular balance of their concentration. However, only a few studies on protozoan GMPR have been reported at present. Herein, we identified the GMPR in Trypanosoma brucei, a causative protozoan parasite of African trypanosomiasis, and found that the GMPR proteins were consistently localized to glycosomes in T. brucei bloodstream forms. We characterized its recombinant protein to investigate the enzymatic differences between GMPRs of T. brucei and its host animals. T. brucei GMPR was distinct in having an insertion of a tandem repeat of the cystathionine β-synthase (CBS) domain, which was absent in mammalian and bacterial GMPRs. The recombinant protein of T. brucei GMPR catalyzed the conversion of GMP to IMP in the presence of NADPH, and showed apparent affinities for both GMP and NADPH different from those of its mammalian counterparts. Interestingly, the addition of monovalent cations such as K+ and NH4+ to the enzymatic reaction increased the GMPR activity of T. brucei, whereas none of the mammalian GMPR's was affected by these cations. The monophosphate form of the purine nucleoside analog ribavirin inhibited T. brucei GMPR activity, though mammalian GMPRs showed no or only a little inhibition by it. These results suggest that the mechanism of the GMPR reaction in T. brucei is distinct from that in the host organisms. Finally, we demonstrated the inhibitory effect of ribavirin on the proliferation of trypanosomes in a dose-dependent manner, suggesting the availability of ribavirin to develop a new therapeutic agent against African trypanosomiasis.

We report the successful minimally invasive placement of a pericardial implantable cardioverter-defibrillator (ICD) in a 16-kg child. A transvenous ICD dual coil was advanced through a small subxiphoid incision and screwed into the oblique sinus pericardium under fluoroscopic guidance. An additional sense-pace lead was sutured onto the right ventricular apex, and the generator was placed in the upper abdominal wall through the same incision. Threshold testing demonstrated successful defibrillation at 15 J. After implantation, the patient had two episodes of appropriate shock for ventricular fibrillation. The ICD system continues to show stable impedance at 6 months of follow-up.

The simultaneous control of the number and position of negatively charged nitrogen-vacancy (NV) centers in diamond was achieved. While single near-surface NV centers are known to exhibit outstanding capabilities in external spin sensing, trade-off relationships among the accuracy of the number and position, and the coherence of NV centers have made the use of such engineered NV centers difficult. Namely, low-energy nitrogen implantation with lithographic techniques enables the nanoscale position control but results in degradation of the creation yield and the coherence property. In this paper, we show that low-energy nitrogen ion implantation to a ^12 C (99.95%)-enriched homoepitaxial diamond layer using nanomask is applicable to create shallow NV centers with a sufficiently long coherence time for external spin sensing, at a high creation yield. Furthermore, the NV centers were arranged in a regular array so that 40% lattice sites contain single NV centers. The XY8- k measurements using the individual NV centers reveal that the created NV centers have depths from 2 to 12 nm, which is comparable to the stopping range of nitrogen ions implanted at 2.5 keV. We show that the position-controlled NV centers are capable of external spin sensing with a ultra-high spatial resolution.

The potassium voltage-gated channel KCNH2 is a well-known gene in which mutations induce familial QT interval prolongation. KCNH2 is suggested to be a risk gene for schizophrenia. Additionally, the disturbance of autonomic control, which affects the QT interval, is known in schizophrenia. Therefore, we speculate that schizophrenic patients have characteristic features in terms of the QT interval in addition to the effect of antipsychotic medication. The QT interval of patients with schizophrenia not receiving antipsychotics (n = 85) was compared with that of patients with schizophrenia receiving relatively large doses of antipsychotics (n = 85) and healthy volunteers (n = 85). The QT interval was corrected using four methods (Bazett, Fridericia, Framingham or Hodges method). In ANCOVA with age and heart rate as covariates, patients not receiving antipsychotic treatment had longer QT intervals than did the healthy volunteers, but antipsychotics prolonged the QT interval regardless of the correction method used (P

Diffusion imaging is a unique noninvasive tool to detect brain white matter trajectory and integrity in vivo. However, this technique suffers from spatial distortion and signal pileup or dropout originating from local susceptibility gradients and eddy currents. Although there are several methods to mitigate these problems, most techniques can be applicable either to susceptibility or eddy-current induced distortion alone with a few exceptions. The present study compared the correction efficiency of FSL tools, "eddy_correct" and the combination of "eddy" and "topup" in terms of diffusion-derived fractional anisotropy (FA). The brain diffusion images were acquired from 10 healthy subjects using 30 and 60 directions encoding schemes based on the electrostatic repulsive forces. For the 30 directions encoding, 2 sets of diffusion images were acquired with the same parameters, except for the phase-encode blips which had opposing polarities along the anteroposterior direction. For the 60 directions encoding, non-diffusion-weighted and diffusion-weighted images were obtained with forward phase-encoding blips and non-diffusion-weighted images with the same parameter, except for the phase-encode blips, which had opposing polarities. FA images without and with distortion correction were compared in a voxel-wise manner with tract-based spatial statistics. We showed that images corrected with eddy and topup possessed higher FA values than images uncorrected and corrected with eddy_correct with trilinear (FSL default setting) or spline interpolation in most white matter skeletons, using both encoding schemes. Furthermore, the 60 directions encoding scheme was superior as measured by increased FA values to the 30 directions encoding scheme, despite comparable acquisition time. This study supports the combination of eddy and topup as a superior correction tool in diffusion imaging rather than the eddy_correct tool, especially with trilinear interpolation, using 60 directions encoding scheme.