La2SrSc2O7: A-Site Cation Disorder Induces Ferroelectricity in Ruddlesden-Popper Layered Perovskite Oxide.

Rational design of ferroelectrics in layered perovskites, like n = 2 Ruddlesden-Popper (RP) phase A3B2O7, has been achieved by the hybrid-improper ferroelectric (HIF) mechanism, in which an electric polarization is induced via a trilinear coupling to nonpolar BO6 octahedral rotation and tilt distortions around crystallographic axes. In the present work, hybrid improper ferroelectricity in n = 2 RP-type La2SrSc2O7 induced by the disordering of Sr2+/La3+ cations on the A-sites in rocksalt ([Sr/La]Rs = 25/75) and perovskite ([Sr/La]Pv = 50/50) layers is demonstrated through experimental and theoretical investigations. The ferroelectric A21am structure (a-a-c+ in Glazer notation) at room temperature and the second-order phase transition to paraelectric Amam structure (a-a-c0) at TC ∼ 600 K are determined by a combination of X-ray and neutron diffraction and optical second harmonic generation. The ferroelectric hysteresis loop measurements prove the switchable electric polarization indicative of ferroelectricity. These results represent an unprecedented example of ferroelectricity in the n = 2 RP family of Ln2AB2O7 with inequivalent Ln3+ and A2+ cations. Combining the abovementioned experimental results with the first-principles calculations, we verify the role of Sr/La distributions in regulating the interlayer rumpling, which, in addition to the structural tolerance factor, is key to controlling the structural distortions of RP phases. The stabilization of the ferroelectric, a-a-c+ distorted structure is a consequence of the disordered Sr/La distribution on the A-sites, which suppresses the rumpling-induced octahedral deformations in competition with the octahedral rotations and thus enables the concurrence of a0a0c+ rotations and a-a-c0 tilts required for the HIF mechanism. This work demonstrates the possibility of altering the crystal symmetry of RP phases through the A-site cation disorder and provides a complementary approach to the rational design of new HIF materials.

The Efficacy of Denosumab in Treating Spinal Aneurysmal Bone Cyst: A Case Report.

The optimal treatment for aneurysmal bone cysts (ABCs) of the spine remains controversial. No treatment guidelines exist for the use of denosumab in aneurysmal bone cysts. In this report, we describe the results from a representative case and compare our experience with those of previously published reports. A 38-year-old male was referred for pain in the lower back and left leg. Radiographs and a needle biopsy specimen revealed a lumbar aneurysmal bone cyst, which was treated with denosumab chemotherapy. The pain in the lower back and left leg gradually improved, and at 16 weeks, the symptoms had resolved. Once a satisfactory local effect was achieved, denosumab therapy was discontinued. However, the erosive lesion subsequently expanded. After re-initiation of treatment, there was no subsequent evidence of recurrence. Single-therapy denosumab is an option for aneurysmal bone cysts. However, recurrences have been documented after denosumab termination, and the timing for cessation of denosumab is controversial.

Synthesis of Boron Nitride Nanotubes Using Plasma-Assisted CVD Catalyzed by Cu Nanoparticles and Oxygen.

We found that oxidized Cu nanoparticles can catalyze the growth of boron nitride nanotubes from borazine via plasma-assisted chemical vapor deposition. The Raman spectra suggest that the formation of thin-walled nanotubes show a radial breathing mode vibration. The presence of oxygen in the plasma environment was necessary for the growth of the nanotubes, and a part of the nanotubes had a core shell structure with a cupper species inside it. In atomic resolution transmission electron microscope (TEM) images, Cu2O was found at the interface between the Cu-core and turbostratic BN-shell. The growth mechanism seemed different from that of carbon nanotube core-shell structures. Therefore, we pointed out the important role of the dynamic morphological change in the Cu2O-Cu system.

Three-dimensional ultrastructure reconstruction of tendinous components at the bifurcation of the bovine superficial digital flexor tendon using array and STEM tomographies.

Tendons transmit force from muscle to bone for joint movement. Tenocytes are a specialized type of fibroblast that produces collagen fibrils in tendons. Their cytoplasmic processes form a network surrounding collagen fibrils to define a collagen fibre. Glycosaminoglycan (GAG) chains link collagen fibrils and adhere at the D-band of the collagen fibril. In this study, we used array and scanning transmission electron microscope (STEM) tomographies to reconstruct the three-dimensional ultrastructure of tenocytes, collagen fibres, collagen fibrils and GAG chains at the bifurcation of the bovine hindlimb superficial digital flexor tendon (SDFT). Collagen fibrils comprising a collagen fibre were not aligned uniformly and had at least two running directions. Spindle-shaped tenocytes were arranged along the long axis of a plurality of collagen fibres, where two groups of collagen fibrils with oblique directions to each other exhibited an oblique overlap of the two collagen fibril layers. Collagen fibrils with different running directions were observed in separating layers of about 300 nm in thickness and had diameters of 0-200 nm. About 40% of all collagen fibrils had a peak in the range of 20-40 nm. STEM analysis of the same site where the crossing of collagen fibres was observed by transmission electron microscopy demonstrated the outline of collagen fibrils with a clear D-banding pattern at a regular interval. Collagen fibrils were reconstructed three-dimensionally using continuous images acquired by STEM tomography, which confirmed that the collagen fibrils at the crossing sites did not orientate in layers, but were woven one by one. Higher magnification observation of GAG chains attached between the crossing collagen fibrils revealed numerous GAG chains arranged either vertically or obliquely on collagen fibrils. Furthermore, GAG chains at the cross of collagen fibrils connected the closest D-bands. GAG chains are thought to be universally present between collagen fibrils of the tendon. These observations by array and STEM tomographies increase our knowledge of the anatomy in the bifurcation of the bovine hindlimb SDFT and demonstrate the utility of these new imaging technologies.

Sandwich-type detection of nucleic acids by bioorthogonal SERS probes.

Nucleic acids in body fluids, such as circulating cell-free nucleic acids, viral DNA, and RNA have received much attention for their great potential as biomarkers in liquid biopsies of serious diseases. Although quantitative polymerase chain reaction (qPCR) has been traditionally used as a laboratory-based assay for measuring nucleic acids, there is a strong demand for techniques to qualitatively, rapidly, and simply measure the extremely low-abundance nucleic acids in order to realize the nucleic acid-based liquid biopsies. With this aim in mind, we developed a simple and highly sensitive sandwich-type assay for nucleic acids using a combination of surface-enhanced Raman scattering (SERS), which enhances Raman scattering by 108- to 1010-fold, and bioorthogonal Raman tags, which generate signals in the biologically silent region (1800-2800 cm-1). Using gold nanorods having approximately 240 strands of oligonucleotides and 4-cyano-N-(2-mercaptoethyl)benzamide (4CMB) as the bioorthogonal Raman tag, we successfully detected target nucleic acids in a sequence-selective manner.

Chemo-enzymatic synthesis of p-nitrophenyl ß-D-galactofuranosyl disaccharides from Aspergillus sp. fungal-type galactomannan.

ß-d-Galactofuranose (Galf) is a component of polysaccharides and glycoconjugates. There are few reports about the involvement of galactofuranosyltransferases and galactofuranosidases (Galf-ases) in the synthesis and degradation of galactofuranose-containing glycans. The cell walls of filamentous fungi in the genus Aspergillus include galactofuranose-containing polysaccharides and glycoconjugates, such as O-glycans, N-glycans, and fungal-type galactomannan, which are important for cell wall integrity. In this study, we investigated the synthesis of p-nitrophenyl ß-d-galactofuranoside and its disaccharides by chemo-enzymatic methods including use of galactosidase. The key step was selective removal of the concomitant pyranoside by enzymatic hydrolysis to purify p-nitrophenyl ß-d-galactofuranoside, a promising substrate for ß-d-galactofuranosidase from Streptomyces species.

Product Selectivity of Esterification of L-Aspartic Acid and L-Glutamic Acid Using Chlorotrimethylsilane.

TMSCI works as an acid catalyst precursor for selective esterification of L-aspartic and L-glutamic acids in the presence of primary, secondary and tertiary alcohols. Although excess TMSCI was required for the completion of esterification, the resulting alkyl TMS ether could be azeotropically removed by simple evaporation with alcohol.

[Malignant Leydig Cell Tumor of the Testis : A Case Report].

A 69-year-old Japanese man was referred to our hospital for a left inguinal testicular tumor and paraaortic lymph node swelling and pleural dissemination. A left orchiectomy was performed in October 2013. Histologically, this testicular tumor was a malignant Leydig cell tumor. The antineoplastic agent mitotan was administered after the orchiectomy. Two months later, although his plasma level of testosterone had de-escalated, the para-aortic lymph node did not decrease in size. A retroperitoneal lymph node dissection was performed in January 2014. Unfortunately, three days after the surgery, the patient died due to disseminated intravascular coagulation and gastrointestinal hemorrhage of unknown cause.

Acceptable range of speech level in noisy sound fields for young adults and elderly persons.

The acceptable range of speech level as a function of background noise level was investigated on the basis of word intelligibility scores and listening difficulty ratings. In the present study, the acceptable range is defined as the range that maximizes word intelligibility scores and simultaneously does not cause a significant increase in listening difficulty ratings from the minimum ratings. Listening tests with young adult and elderly listeners demonstrated the following. (1) The acceptable range of speech level for elderly listeners overlapped that for young listeners. (2) The lower limit of the acceptable speech level for both young and elderly listeners was 65 dB (A-weighted) for noise levels of 40 and 45 dB (A-weighted), a level with a speech-to-noise ratio of +15 dB for noise levels of 50 and 55 dB, and a level with a speech-to-noise ratio of +10 dB for noise levels from 60 to 70 dB. (3) The upper limit of the acceptable speech level for both young and elderly listeners was 80 dB for noise levels from 40 to 55 dB and 85 dB or above for noise levels from 55 to 70 dB.

GPR35 is a novel lysophosphatidic acid receptor.

GPR35 is a rhodopsin-like G protein-coupled receptor identified in 1998. It has been reported that kynurenic acid, a tryptophan metabolite, may act as an endogenous ligand for GPR35. However, the concentrations of kynurenic acid required to elicit the cellular responses are usually high, raising the possibility that another endogenous ligand may exist. In this study, we searched for another endogenous ligand for GPR35. Finally, we found that the magnitude of the Ca(2+) response induced by 2-acyl lysophosphatidic acid in the GPR35-expressing HEK293 cells was markedly greater than that in the vector-transfected control cells. Such a difference was not apparent in the case of 1-acyl lysophosphatidic acid. 2-Acyl lysophosphatidic acid also caused the sustained activation of RhoA and the phosphorylation of extracellular signal-regulated kinase, and triggered the internalization of the GPR35 molecule. These results strongly suggest that 2-acyl lysophosphatidic acid is an endogenous ligand for GPR35.

Carbachol injection into the pontine reticular formation depresses laryngeal muscle activities and airway reflexes in decerebrate cats.

To understand the role of cholinoceptive, medial pontine reticular formation (mPRF) neurons in the control of upper airway, pharyngolaryngeal reflexes, we measured activities of intrinsic laryngeal muscles (posterior cricoarytenoid, PCA; thyroarytenoid, TA), diaphragm (DIA), genioglossus (GG) and a neck muscle (trapezius) in unanesthetized, decerebrated, spontaneously breathing cats with and without mPRF carbachol injections. The ethimoidal nerve was electrically stimulated to evoke sneezing, and the superior laryngeal nerve to evoke the laryngeal reflex, swallowing, and coughing. Carbachol reduced the amplitudes of the spontaneous electromyographic activities in the neck, TA, PCA, GG, and DIA to 7%, 30%, 54%, 45% and 71% of control, respectively, reduced the respiratory rate to 53% without changes in expiratory CO(2) concentration; the magnitude of the laryngeal reflex in the TA muscle to 56%; increased its latency by 13%; and reduced the probability of stimulus-induced sneezing, swallowing, and coughing to less than 40%. These changes lasted more than 1h. These data demonstrate that important upper airway reflexes are suppressed by increasing cholinergic neurotransmission in the mPRF. Because acetylcholine release in the mPRF changes in accordance with sleep-wake cycles, the present findings are relevant to the control of upper airway reflexes during various vigilance states.

Lysophosphatidylinositol induces rapid phosphorylation of p38 mitogen-activated protein kinase and activating transcription factor 2 in HEK293 cells expressing GPR55 and IM-9 lymphoblastoid cells.

Lysophosphatidylinositol (LPI) is an endogenous ligand for GPR55, a putative novel type of cannabinoid receptor. In this study, we first examined the effects of LPI on p38 mitogen-activated protein kinase in HEK293 cells expressing GPR55. LPI induced the rapid phosphorylation of p38 mitogen-activated protein kinase in GPR55-expressing cells. No apparent effect was observed in the vector-transfected cells. The exposure of GPR55-expressing cells to LPI also triggered the phosphorylation of activating transcription factor 2 downstream of the p38 mitogen-activated protein kinase. Treatment of the cells with Y-27632 [a Rho-associated kinase (ROCK) inhibitor] blocked the LPI-induced phosphorylation of p38 mitogen-activated protein kinase and activating transcription factor 2, suggesting that the Rho-ROCK pathway is involved in these cellular responses. Notably, GPR55 was found to be abundantly expressed in lymphoid organs such as the spleen and thymus. We obtained evidence that rapid phosphorylation of p38 mitogen-activated protein kinase and activating transcription factor 2 also takes place in IM-9 lymphoblastoid cells, which naturally express GPR55, after stimulation with LPI. These results suggest that GPR55 and its endogenous ligand LPI play essential roles in the homoeostatic responses to stress signals in several mammalian tissues and cells including certain types of immune cells.

A case of invasive paranasal aspergillosis that developed from a non-invasive form during 5-year follow-up.

Invasive paranasal aspergillosis has been previously reported, but there have been no case reports of non-invasive paranasal aspergillosis that progressed to the invasive form during follow-up. A case of non-invasive aspergillosis of the maxillary sinus that appeared to become invasive during 5-year follow-up is reported. The patient was diagnosed as having non-invasive aspergillosis at the first visit because CT images revealed only mucosal thickening and calcifications in the right maxillary sinus. Five years later, CT images showed an invasive mass lesion in the orbit and large bone destruction of the posterior wall of the maxillary sinus. The patient was rescued by total removal of the orbital contents with zygomatic ostectomy followed by appropriate antifungal chemotherapy irrespective of residual tissue invasion. We would propose that appropriate surgical treatment and antifungal agents are necessary to improve the prognosis of invasive aspergillosis.

Roles of matrix metalloproteinases in flow-induced outward vascular remodeling.

Sustained hemodynamic stresses, especially high blood flow, result in flow-induced outward vascular remodeling. Our previous study showed that macrophage depletion reduced flow-induced outward remodeling of the rat common carotid artery, indicating that macrophages are critical in flow-induced outward vascular remodeling. Macrophage is known to release proteinases, including matrix metalloproteinases (MMPs). Degradation and loosening of extracellular matrix by MMPs may facilitate vascular remodeling. Therefore, we assessed the functions of MMPs in flow-induced outward vascular remodeling by using the flow-augmented common carotid artery model in mice. We validated that ligation of the left common carotid artery increased blood flow and luminal diameter of the right common carotid artery without significant change in blood pressure of mice. To assess the functions of MMPs in flow-induced outward vascular remodeling, we used doxycycline (broad-spectrum MMP inhibitor), SB-3CT (selective MMP inhibitor), MMP-9 knockout mice, and MMP-12 knockout mice. Although there was only a trend for doxycycline treatment to reduce flow-induced outward vascular remodeling, SB-3CT treatment significantly reduced flow-induced outward vascular remodeling. In addition, flow-induced outward vascular remodeling was significantly reduced in MMP-9 knockout mice, but not in MMP-12 knockout mice. These data revealed that MMPs, especially MMP-9, are critical in flow-induced outward vascular remodeling.

Evaluation of the insertion efficiencies of tapered silicon nanoneedles and invasiveness of diamond nanoneedles in manipulations of living single cells.

We have been developing a low invasive cell manipulation technology based on inserting an ultra-thin needle--"nanoneedle"--into a living cell by using an atomic force microscope (AFM). The nanoneedle, made from a silicon AFM tip by focused-ion-beam etching, has a diameter of several hundred nanometers and a length of about 10 microns. Successful insertion of the nanoneedle into the cell can be confirmed by the appearance of a steep relaxation of repulsive force in the force-distance curve as monitored by the AFM system. This technology, termed "cell surgery", can be applied for the detection of intracellular proteins in a living cell or for highly efficient gene transfer. The present study shows that the durability of a tapered nanoneedle is superior to that of a cylindrical nanoneedle, and that a proper aspect ratio for the tapered nanoneedle must be chosen to maintain sufficient insertion efficiency for a particular target cell: tapered nanoneedles of an aspect ratio over 20 showed high insertion efficiency for various kinds of mammalian cells. We then used diamond for the material of the nanoneedle because its specific properties, such as high stiffness, heat conductivity, and electrical conductivity capacitated by boron doping, were deemed useful for the analysis and manipulation of intracellular phenomena. We compared the capability of the diamond nanoneedle in cell manipulation with that of the silicon nanoneedle. Evaluation of the effect of the former on transcription efficiency and localization analysis of p53 expression revealed the low invasiveness for cell manipulation as was also the case for the silicon nanoneedle. We also succeeded in achieving highly efficient plasmid DNA delivery into a mouse fibroblast C3H10T1/2 using the diamond nanoneedle. The diamond nanoneedle is expected to contribute to the versatility of "cell surgery" technology.

Acceptable range of speech level for both young and aged listeners in reverberant and quiet sound fields.

The speech level of verbal information in public spaces should be determined to make it acceptable to as many listeners as possible, while simultaneously maintaining maximum intelligibility and considering the variation in the hearing levels of listeners. In the present study, the universally acceptable range of speech level in reverberant and quiet sound fields for both young listeners with normal hearing and aged listeners with hearing loss due to aging was investigated. Word intelligibility scores and listening difficulty ratings as a function of speech level were obtained by listening tests. The results of the listening tests clarified that (1) the universally acceptable ranges of speech level are from 60 to 70 dBA, from 56 to 61 dBA, from 52 to 67 dBA and from 58 to 63 dBA for the test sound fields with the reverberation times of 0.0, 0.5, 1.0 and 2.0 s, respectively, and (2) there is a speech level that falls within all of the universally acceptable ranges of speech level obtained in the present study; that speech level is around 60 dBA.