Room Temperature Electrically Detected Nuclear Spin Coherence of NV Centres in Diamond.

We demonstrate electrical detection of the 14N nuclear spin coherence of NV centres at room temperature. Nuclear spins are candidates for quantum memories in quantum-information devices and quantum sensors, and hence the electrical detection of nuclear spin coherence is essential to develop and integrate such quantum devices. In the present study, we used a pulsed electrically detected electron-nuclear double resonance technique to measure the Rabi oscillations and coherence time (T2) of 14N nuclear spins in NV centres at room temperature. We observed T2 ≈ 0.9 ms at room temperature, however, this result should be taken as a lower limit due to limitations in the longitudinal relaxation time of the NV electron spins. Our results will pave the way for the development of novel electron- and nuclear-spin-based diamond quantum devices.

Extension of the Coherence Time by Generating MW Dressed States in a Single NV Centre in Diamond.

Nitrogen-vacancy (NV) centres in diamond hold promise in quantum sensing applications. A major interest in them is an enhancement of their sensitivity by the extension of the coherence time (T2). In this report, we experimentally generated more than four dressed states in a single NV centre in diamond based on Autler-Townes splitting (ATS). We also observed the extension of the coherence time to T2 ~ 1.5 ms which is more than two orders of magnitude longer than that of the undressed states. As an example of a quantum application using these results we propose a protocol of quantum sensing, which shows more than an order of magnitude enhancement in the sensitivity.

Ultra-long coherence times amongst room-temperature solid-state spins.

Solid-state single spins are promising resources for quantum sensing, quantum-information processing and quantum networks, because they are compatible with scalable quantum-device engineering. However, the extension of their coherence times proves challenging. Although enrichment of the spin-zero 12C and 28Si isotopes drastically reduces spin-bath decoherence in diamond and silicon, the solid-state environment provides deleterious interactions between the electron spin and the remaining spins of its surrounding. Here we demonstrate, contrary to widespread belief, that an impurity-doped (phosphorus) n-type single-crystal diamond realises remarkably long spin-coherence times. Single electron spins show the longest inhomogeneous spin-dephasing time ([Formula: see text] ms) and Hahn-echo spin-coherence time (T2 ≈ 2.4 ms) ever observed in room-temperature solid-state systems, leading to the best sensitivities. The extension of coherence times in diamond semiconductor may allow for new applications in quantum technology.

Oxidative stress-driven parvalbumin interneuron impairment as a common mechanism in models of schizophrenia.

Parvalbumin inhibitory interneurons (PVIs) are crucial for maintaining proper excitatory/inhibitory balance and high-frequency neuronal synchronization. Their activity supports critical developmental trajectories, sensory and cognitive processing, and social behavior. Despite heterogeneity in the etiology across schizophrenia and autism spectrum disorder, PVI circuits are altered in these psychiatric disorders. Identifying mechanism(s) underlying PVI deficits is essential to establish treatments targeting in particular cognition. On the basis of published and new data, we propose oxidative stress as a common pathological mechanism leading to PVI impairment in schizophrenia and some forms of autism. A series of animal models carrying genetic and/or environmental risks relevant to diverse etiological aspects of these disorders show PVI deficits to be all accompanied by oxidative stress in the anterior cingulate cortex. Specifically, oxidative stress is negatively correlated with the integrity of PVIs and the extracellular perineuronal net enwrapping these interneurons. Oxidative stress may result from dysregulation of systems typically affected in schizophrenia, including glutamatergic, dopaminergic, immune and antioxidant signaling. As convergent end point, redox dysregulation has successfully been targeted to protect PVIs with antioxidants/redox regulators across several animal models. This opens up new perspectives for the use of antioxidant treatments to be applied to at-risk individuals, in close temporal proximity to environmental impacts known to induce oxidative stress.

Optically detected magnetic resonance of high-density ensemble of NV- centers in diamond.

Optically detected magnetic resonance (ODMR) is a way to characterize the ensemble of NV-centers. Recently, a remarkably sharp dip was observed in the ODMR with a high-density ensemble of NV centers. The model (Zhu et al 2014 Nat. Commun. 5 3424) indicated that such a dip was due to the spin-1 properties of the NV- centers. Here, we present many more details of the analysis to show how this model can be applied to investigate the properties of the NV- centers. By using our model, we have reproduced the ODMR with and without applied external magnetic fields. Additionally, we investigate how the ODMR is affected by the typical parameters of the ensemble NV- centers such as strain distributions, inhomogeneous magnetic fields, and homogeneous broadening width. Our model provides a way to characterize the NV- center from the ODMR, which would be crucial to realize diamond-based quantum information processing.

Robust absolute magnetometry with organic thin-film devices.

Magnetic field sensors based on organic thin-film materials have attracted considerable interest in recent years as they can be manufactured at very low cost and on flexible substrates. However, the technological relevance of such magnetoresistive sensors is limited owing to their narrow magnetic field ranges (∼30 mT) and the continuous calibration required to compensate temperature fluctuations and material degradation. Conversely, magnetic resonance (MR)-based sensors, which utilize fundamental physical relationships for extremely precise measurements of fields, are usually large and expensive. Here we demonstrate an organic magnetic resonance-based magnetometer, employing spin-dependent electronic transitions in an organic diode, which combines the low-cost thin-film fabrication and integration properties of organic electronics with the precision of a MR-based sensor. We show that the device never requires calibration, operates over large temperature and magnetic field ranges, is robust against materials degradation and allows for absolute sensitivities of <50 nT Hz(-1/2).

Drug interactions between tacrolimus and phenytoin in Japanese heart transplant recipients: 2 case reports.

OBJECTIVE: The purpose of the study was to demonstrate how the interaction between phenytoin and tacrolimus (FK 506) can be managed clinically and to characterize the change in FK 506 levels after discontinuation of phenytoin in two Japanese heart transplant recipients with different dosing periods ofphenytoin. METHODS: A drug interaction between phenytoin and FK 506 was investigated in 2 patients. The concentration-dose ratios (CDR: trough blood FK 506 level (ng/ml)/FK 506 dose (mg/day) on the previous day) were calculated as an index of the induction of the CYP3A4 enzyme during and after phenytoin therapy. RESULTS: About 2- to 3-fold dosages of FK 506 were required to maintain the required blood level when phenytoin was used concomitantly in the two cases examined. The FK 506 dose was constant within 21 days after discontinuing phenytoin in Patient 1 who had 36 days of phenytoin therapy. In Patient 2 with 21-day phenytoin therapy, the FK 506 doses and CDR varied for 10 days after discontinuing phenytoin, and expected FK 506 C0 levels were achieved within 11 days. CONCLUSIONS: The persistence of CYP induction after discontinuing phenytoin is dependent on the history of administration and, perhaps, on the dosing period in particular.

Successful embolisation of intrahepatic portosystemic venous shunt using coils and n-butyl cyanoacrylate through two approach routes.

Interventional radiological treatment by transcatheter embolisation has been used to treat patients with symptomatic intrahepatic portosystemic venous shunt (IPSVS). We present a case of symptomatic IPSVS treated by both retrograde and antegrade transcatheter embolisation using coils and n-butyl cyanoacrylate.

Genetic variations and haplotype structures of the ABCB1 gene in a Japanese population: an expanded haplotype block covering the distal promoter region, and associated ethnic differences.

As functional ABCB1 haplotypes were recently reported in the promoter region of the gene, we resequenced the ABCB1 distal promoter region, along with other regions (the enhancer and proximal promoter regions, and all 28 exons), in a total of 533 Japanese subjects. Linkage disequilibrium (LD) analysis based on 92 genetic variations revealed 4 LD blocks with the same make up as previously described (Blocks -1, 1, 2 and 3), except that Block 1 was expanded to include the distal promoter region, and that a new linkage between polymorphisms -1,789G>A in the distal promoter region and IVS5 + 123A>G in intron 5 was identified. We re-assigned Block 1 haplotypes, and added novel haplotypes to the other 3 blocks. The reported promoter haplotypes were further classified into several types according to tagging variations within Block 1 coding or intronic regions. Our current data reconfirm the haplotype profiles of the other three blocks, add more detailed information on functionally-important haplotypes in Block 1 and 2 in the Japanese population, and identified differences in haplotype profiles between ethnic groups. Our updated analysis of ABCB1 haplotype blocks will assist pharmacogenetic and disease-association studies carried out using Asian subjects.

Serum amiodarone and desethylamiodarone concentrations following nasogastric versus oral administration.

OBJECTIVE: Hospitalized patients unable to ingest anything by mouth require nutritional support by enteral feeding and administration of drugs through a nasogastric tube inserted into the digestive tract. Nasogastric administration of amiodarone may not always be equivalent to oral administration of amiodarone. METHODS: We collected 162 observations of serum amiodarone and desethylamiodarone metabolite concentrations from 93 patients within 60 days of starting treatment with amiodarone. Eight patients were given the drug nasogastrically and 85 patients, orally. The two groups, were compared in terms of their serum concentration/(dose/weight) (C/D) value. A ratio of serum amiodarone concentration to serum desethylamiodarone concentration (AMD/DEA) was calculated for each sample. In addition, the percentage drug recovery after nasogastric administration of amiodarone was analysed. RESULTS: Significant differences were observed in C/D values of amiodarone and desethylamiodarone and in AMD/DEA values of patients given amiodarone orally when compared with those given the drug nasogastrically. The C/D values of patients who received their medication nasogastrically were approximately 30% of the C/D values of patients who received their medication orally. Approximately 70% of the drug was recovered after it had passed through the nasogastric tube. CONCLUSIONS: To achieve similar concentrations, an approximately 3-fold increase in dosage of amiodarone was required when patients were given the drug nasogastrically rather than orally. This suggests that the absorption of amiodarone following nasogastric administration is poor when compared with oral administration. Therapeutic drug monitoring is necessary to optimize dose particularly during the early stages of amiodarone therapy.

Haplotype structures of the UGT1A gene complex in a Japanese population.

Genetic polymorphisms of UDP-glucuronosyltransferases (UGTs) are involved in individual and ethnic differences in drug metabolism. To reveal co-occurrence of the UGT1A polymorphisms, we first analyzed haplotype structures of the entire UGT1A gene complex using the polymorphisms from 196 Japanese subjects. Based on strong linkage disequilibrium between UGT1A8 and 1A10, among 1A9, 1A7, and 1A6, and between 1A3 and 1A1, the complex was divided into five blocks, Block 8/10, Block 9/6, Block 4, Block 3/1, and Block C, and the haplotypes for each block were subsequently determined/inferred. Second, using pyrosequencing or direct sequencing, additional 105 subjects were genotyped for 41 functionally tagged polymorphisms. The data from 301 subjects confirmed the robustness of block partitioning, but several linkages among the haplotypes with functional changes were found across the blocks. Thus, important haplotypes and their linkages were identified among the UGT1A gene blocks (and segments), which should be considered in pharmacogenetic studies.

Antioxidant activity and hypoglycemic effect of ferulic acid in STZ-induced diabetic mice and KK-Ay mice.

Antioxidant activity and biological properties of ferulic acid (FA) are well recognized. This study was designed to estimate the potential utility of FA administered orally at low dosage for improvement of hyperglycemia in diabetes. With this aim we have evaluated the hypoglycemic effect of FA in two type diabetic animal models: (1) streptozotocin (STZ)-induced diabetic mice, a model of insulin-dependent diabetes mellitus (IDDM); (2) KK-Ay mice, a model of non-insulin dependent diabetes mellitus (NIDDM). In addition, we measured the production of thiobarbituric acid-reactive substances (TBARS) in brown adipose tissues of diabetic mice at the end of FA feeding experiment. FA at 0.01% and 0.1% of basal diet showed to suppress significantly blood glucose levels in STZ-induced diabetic mice. In KK-Ay mice 0.05% FA suppressed effectively blood glucose levels. In addition, FA inhibited the lipid peroxidation in brown adipose tissue of diabetic mice. Taken together, these findings suggest that dietary FA may be useful in alleviating oxidative stress and attenuating the hyperglycemic response associated with diabetes.

Circulating leptin response to feeding and exogenous infusion of insulin in sheep exposed to thermoneutral and cold environments.

Leptin has been shown to regulate feed intake and energy expenditure. Insulin stimulates leptin secretion in rodents, but its action on leptin secretion is still obscure in ruminants. If insulin stimulates leptin secretion in ruminants, circulating leptin concentrations may change during exposure to cold, because of fluctuating insulin secretion and action in the cold environment. The present experiment was designed to determine whether feeding or exogenous administration of insulin affects circulating leptin levels in sheep exposed to thermoneutral and cold environments. Suffolk rams that were shorn and fed a diet once daily were subjected to a thermoneutral (20 degrees C) or cold (0 degrees C) environment for at least 1 week. Overall mean concentrations of plasma leptin in the feeding experiment were lower (P<0.05) in the cold environment than in the thermoneutral environment. Plasma leptin levels remained relatively unchanged after feeding in both environments, though plasma insulin response to feeding in both environments increased (P<0.01). The euglycemic clamps (insulin infusion rate: 4 mUkgBW(-1)min(-1) for 2 h) increased (P<0.01) circulating leptin concentrations in the thermoneutral, but not in the cold environment. These results suggest that lower circulating leptin levels in ruminants exposed to the cold environment could be partly due to the depressed insulin action on leptin secretion.

Deafness due to degeneration of cochlear neurons in caspase-3-deficient mice.

Mice that lack caspase-3, which functions in apoptosis, were generated by gene targeting and shown to undergo hearing loss. The ABR threshold of the caspase-3(-/-) mice was significantly elevated compared to that of caspase-3(+/+) mice at 15 days of age and was progressively elevated further by 30 days. Distortion product otoacoustic emissions were not detectable in caspase-3(-/-) mice at 15 days of age. Caspase-3(-/-) mice exhibited marked degeneration of spiral ganglion neurons and a loss of inner and outer hair cells in the cochlea at 30 days of age, although no such changes were apparent at 15 days. The degenerating neurons manifested features, including cytoplasmic vacuolization, distinct from those characteristic of apoptosis. Spiral ganglion neurons and cochlear hair cells thus appear to require caspase-3 for survival but not for initial development. The mapping of both the human caspase-3 gene and the locus responsible for an autosomal dominant, nonsyndromic form of hearing loss (DFNA24) to chromosome 4q35 suggests that the caspase-3(-/-) mice may represent a model of this human condition.

Twin pregnancy consisting of 46, XY heterozygous complete mole coexisting with a live fetus.

Complete hydatidiform mole and coexistent fetus (CMCF) is a rare occurrence and is associated with an increased risk of persistent gestational trophoblastic diseases. The aim of this study was to reveal a potential risk factor and to determine optimum management of CMCF cases. Molar tissues are cytogenetically divided into two types, homozygous and heterozygous. The molar tissue of our case showed a 46, XY heterozygous complete mole. Genomic DNA was analyzed by the polymerase chain reaction using sets of unlabelled forward and Cy-5-labelled reverse primers for DNA marker loci. The patient developed persistent trophoblastic disease (PTD) with lung metastasis. Since 1980 there have been 13 reports (including our case) that cytogenetically revealed CMCF and clarified the clinical outcome. Nine of the 16 CMCF cases before 21 weeks of gestation and seven of the 12 CMCF cases after 22 weeks of gestation developed PTD. The incidence of PTD from CMCF was not related to the gestational age at termination or delivery. There were 10 case reports that analyzed the zygosity of a mole, heterozygous or homozygous. Two of six homozygous and three of four heterozygous moles in CMCF cases developed PTD. A heterozygous mole is thought to be a high risk factor for the incidence of PTD. Cytogenetic study is clinically useful for the optimum management of CMCF cases.

Microsatellite instability in transforming growth factor-beta 1 type II receptor gene in alveolar lining epithelial cells of idiopathic pulmonary fibrosis.

It has been reported that transforming growth factor (TGF)-beta, which plays an integral role in the pathogenesis of idiopathic pulmonary fibrosis (IPF), suppresses proliferation of alveolar epithelial cells in vitro. Although hyperplastic lesions of alveolar lining epithelial cells (ALECs) are characteristic pathologic features of IPF, the mechanism of their involvement in the pathogenesis has not yet been extensively studied. On the assumption that the hyperplastic ALECs have escaped from the growth-inhibitory effects of TGF-beta, we searched for mutations in the microsatellite of the TGF-beta receptor type II (T beta RII) gene. To detect a deletion in the polyadenine tract in exon 3 of the T beta RII gene, cells were isolated by microdissection from lung sections of IPF patients, and DNA was extracted from these cells and amplified by high-fidelity polymerase chain reaction. A total of 121 sites of hyperplastic ALECs from 11 IPF patients were analyzed, and a one-base-pair deletion was detected in nine sites from five patients. The mutation was also detected in smooth muscle-like cells of the thickened pulmonary artery. In some tissue areas where the deletion was detected, low T beta RII expression was confirmed by immunohistochemical staining. These data suggest that microsatellite instability in the T beta RII gene occurred in some lesions of hyperplastic ALECs in IPF, although at a low incidence, and that this genetic disorder might play a partial role in the pathologic changes of IPF.

Impaired fertility in female mice lacking urinary trypsin inhibitor.

Urinary trypsin inhibitor (UTI) is a serine proteinase inhibitor that is found in blood and urine. To investigate the physiological functions of UTI in vivo, we generated UTI-deficient mice by gene targeting. The mice showed no obvious abnormalities and appeared healthy. However, the females displayed a severe reduction in fertility. Wild-type embryos developed normally when transplanted into UTI-deficient female mice, suggesting that UTI-deficient females have a normal ability to maintain pregnancy. The number of naturally ovulated oocytes from UTI-deficient mice was greatly reduced compared with that from wild-type mice. Histologically, oocytes with disorganized corona radiata were frequently seen in the ovaries of UTI-deficient mice after hormonal stimulation. When ovaries from UTI-deficient mice were transplanted into wild-type mice, pups derived from the transplanted ovaries were obtained, suggesting that the ovary of UTI-deficient mice functions normally if UTI is supplied from the systemic circulation. These results demonstrate that UTI plays an important role in the formation of the stable cumulus-oocyte complex that is essential for oocyte maturation and ovulation.

Improvement of anti-Hu-associated paraneoplastic sensory neuropathy after chemoradiotherapy in a small cell lung cancer patient.

A 66-year-old man developed progressive painful dysesthesia in his hands and feet over 3 months. His vibration sense was impaired and sensory nerve action potentials of the limbs were not evoked. Biopsy of the peroneal nerve revealed sensory neuropathy. Positive anti-Hu antibody facilitated delineation of a right hilar mass and a metastatic lymph node in thoracic CT scan. He was diagnosed as small cell lung cancer associated with paraneoplastic sensory neuropathy. A complete response was achieved through chemotherapy (carboplatin and etoposide) and subsequent radiation therapy. Notably, his neurological conditions, although not changed during the hospitalization, gradually improved afterwards.