Mechanical behavior of in-situ alloyed Ti6Al4V(ELI)-3 at.% Cu lattice structures manufactured by laser powder bed fusion and designed for implant applications.

In the present study, cellular lattice structures for implant applications are reported for the first-time incorporating copper directly by in-situ alloying in the laser powder bed fusion process. The aim to incorporate 3 at.% Cu into Ti6Al4V(ELI) is selected for improved antibacterial properties while maintaining appropriate mechanical properties. Previously, topologically optimized Ti6Al4V(ELI) lattice structures were successfully designed, manufactured and studied for implant applications. The development of a new alloy produced by in-situ alloying of elemental powder mixture of Ti6Al4V(ELI) and pure Cu powders was used here for the production of identical lattice structures with improved antibacterial properties. One of the same as-designed CAD models was used for the manufacturing of these lattices compared to previous work on pure Ti6Al4V(ELI) lattices, making direct comparison of mechanical properties possible. Similar manufacturability highlights the applicability of this alloying technique to other lattice designs. Microstructural characterization was performed by optical and electron microscopies, as well as microCT. Mechanical characterization was performed by means of compression tests and hardness measurements. Results showed that in-situ alloying with copper leads to the formation of localized Cu-rich regions, refinement of martensitic phase and the formation of CuTi2 intermetallic precipitates, which increased the hardness and strength of the material. Deviations in wall thickness between the as-designed and as-manufactured lattices led to anisotropy of the mechanical properties of the lattices. Higher compressive strength values were obtained when thicker walls were oriented along the loading direction. Nevertheless, alloying with Cu had a higher impact on the compressive strength of lattice structure than the wall thickness deviations. The direct in-situ alloying of copper in Ti6Al4V(ELI) is a promising route for direct manufacturing of antibacterial implants.

Expression analysis of cellulose synthases that comprise the Type II complex in hybrid aspen.

Gene duplication in plants occurs via several different mechanisms, including whole genome duplication, and the copied genes acquire various forms and types. The cellulose synthase (CesA) family functions in cellulose synthesis complex (CSC) formation, which is involved in the synthesis of primary and secondary cell walls in plants. In the genome of Populus, 17 CesA have been annotated, and some of them appeared through whole genome duplication. The nucleotide sequence of the duplicated genes changed during subsequent evolution, and functional differentiation of genes might have occurred. To gain insight into the evolutionary fate of the duplicated CesA, expression analysis with quantitative reverse transcription polymerase chain reactions and promoter-reporter assays was performed on three duplicated gene pairs whose products have been reported to form a single CSC. Changes in expression of each gene at different developmental stages were detected and divergent expression patterns in different organs and tissues observed between the gene pairs. Among the tested genes, expression of PttCesA3-C was apparently lower than that of its counterpart, PttCesA3-D. The results suggest that the six CesA are approaching sub-functionalisation or non-functionalisation. Furthermore, the level of functionalisation may vary among the three pairs of genes, and functional specialisation of each CesA should have been achieved, at least partially, through differences in expression of genes.

Preterm birth is associated with higher prevalence of wheeze and asthma in a selected population of Japanese children aged three years.

BACKGROUND: The present cross-sectional study investigated the associations between low birthweight (LBW), high birthweight, preterm birth (PTB), postterm birth, small for gestational age (SGA), and large for gestational age (LGA) and the prevalence of wheeze and asthma in Japanese children aged three years (age range, 33-54 months; mean age, 38.7 months). METHODS: Study subjects were 6364 children. A questionnaire was used to collect all data. Wheeze and asthma were defined according to the criteria of the International Study of Asthma and Allergies in Childhood. RESULTS: The prevalence values of wheeze and asthma were 19.5% and 7.7%, respectively. Of the 6364 subjects, 8.8% were classified as LBW (<2500g), 90.4% as normal birthweight, 0.8% as high birthweight (≥4000g), 4.8% as PTB (<37 weeks), 94.8% as term birth, 0.4% as postterm birth (≥42 weeks), 7.8% as SGA (<10th percentile), 82.5% as appropriate for gestational age, and 9.7% as LGA (>90th percentile). Compared with term birth, PTB was independently positively associated with wheeze and asthma: the adjusted ORs (95% CI) were 1.47 (1.11-1.92) and 1.52 (1.02-2.20), respectively. An independent positive association was shown between PTB and wheeze only in boys; the interaction between PTB and sex was significant. Such an interaction between PTB and sex was not seen for asthma. No evident associations were observed between LBW, high birthweight, postterm birth, SGA, or LGA and wheeze or asthma. CONCLUSIONS: This is the first study in Japan to show that PTB, but not LBW or SGA, was significantly positively associated with childhood wheeze and asthma.

Strain-triggered mechanical feedback in self-organizing optic-cup morphogenesis.

Organogenesis is a self-organizing process of multiple cells in three-dimensional (3D) space, where macroscopic tissue deformations are robustly regulated by multicellular autonomy. It is clear that this robust regulation requires cells to sense and modulate 3D tissue formation across different scales, but its underlying mechanisms are still unclear. To address this question, we developed a versatile computational model of 3D multicellular dynamics at single-cell resolution and combined it with the 3D culture system of pluripotent stem cell-derived optic-cup organoid. The complementary approach enabled quantitative prediction of morphogenesis and its corresponding verification and elucidated that the macroscopic 3D tissue deformation is fed back to individual cellular force generations via mechanosensing. We hereby conclude that mechanical force plays a key role as a feedback regulator to establish the robustness of organogenesis.

Adaptive changes of extracellular amino acid concentrations in mouse dorsal striatum by 4-AP-induced cortical seizures.

The striatum is a major target of cerebral cortical output. The cortico-striatal projection has been well described, however, the neurochemical changes that occur in the striatum after prolonged cortical hyperactivation remain to be investigated. In this study, extracellular levels of glutamate, GABA, and alanine levels were measured in the dorsal striatum using microdialysis in anesthetized mice at resting condition and during 4-aminopyridine (4-AP)-induced cortical seizures. After topical application of 4-AP on the primary motor cortex that induced cortical seizures, the extracellular level of striatal GABA increased by 40% in 60 min. By contrast, the extracellular level of striatal glutamate decreased by 20%. Moreover, the surface amounts of striatal glutamate/aspartate transporter (GLAST) and glutamate transporter 1 (GLT-1), the major astrocytic high-affinity glutamate transporters, tended to increase by cortical seizures in 60 min, suggesting a recruitment of the glutamate transporters from internal stores. 4-AP also resulted in a steady increase of alanine levels which are thought to reflect glutamate and pyruvate metabolism in neurons and astrocytes. These observations possibly delineate adaptive changes of striatal metabolism by severe cortical seizures.

Comparison of the NMIJ and the ARPANSA standards for absorbed dose to water in high-energy photon beams.

The authors report the results of an indirect comparison of the standards of absorbed dose to water in high-energy photon beams from a clinical linac and (60)Co radiation beam performed between the National Metrology Institute of Japan (NMIJ) and the Australian Radiation Protection and Nuclear Safety Agency (ARPANSA). Three ionisation chambers were calibrated by the NMIJ in April and June 2013 and by the ARPANSA in May 2013. The average ratios of the calibration coefficients for the three ionisation chambers obtained by the NMIJ to those obtained by the ARPANSA were 0.9994, 1.0040 and 1.0045 for 6-, 10- and 15-MV (18 MV at the ARPANSA) high-energy photon beams, respectively. The relative standard uncertainty of the value was 7.2 × 10(-3). The ratio for (60)Co radiation was 0.9986(66), which is consistent with the results published in the key comparison of BIPM.RI(I)-K4.

Changes in the sensitivity of cutaneous points and the oral mucosa after intraoral vertical ramus osteotomy.

In this study we investigated the changes in the sensitivity of cutaneous points and the oral mucosa that occur after intraoral vertical ramus osteotomy (IVRO). Additionally, postoperative changes in the sensitivity and the relationships between neurosensory disturbance and factors associated with IVRO operations were evaluated. An objective evaluation of the neurosensory status of cutaneous points and the oral mucosa of each patient was completed preoperatively and at 1, 2, 4, 8, 12, and 24 weeks postoperatively. The other variables studied for each patient included sex, age, magnitude of mandibular setback, and the amount of haemorrhage that occurred during surgery. In addition, the relationships between neurosensory disturbance and factors connected with IVRO operations were evaluated. We found that at cutaneous points, contributing factors such as sex, age, the magnitude of mandibular setback, and haemorrhage were associated with an increased risk of neurosensory disturbance after IVRO. However, these factors were not associated with that in the oral mucosa. In conclusion, we demonstrated the changes that occur in the sensitivity of cutaneous points and the oral mucosa after IVRO, the postoperative changes in sensitivity, and the relationships between neurosensory disturbance and factors connected with IVRO operations.

Accumulation and dissipation of positive charges induced on a PMMA build-up cap of an ionisation chamber by (60)Co gamma-ray irradiation.

The signal current from an ionisation chamber with a PMMA build-up cap decreases with irradiation time due to electric fields produced by positive charges induced on the cap. In the present study, it was confirmed that the signal current decreases faster for irradiation using narrower (60)Co gamma-ray beams. This is because the number of secondary electrons that are emitted from surrounding materials and penetrate the build-up cap is smaller in a narrower gamma-ray beam, so that fewer positive charges are neutralised. The ionisation chamber was first subjected to continuous gamma-ray irradiation for 24 h, following which it was irradiated with shorter periodic gamma-ray bursts while measuring the current signal. This allowed the coefficients of positive charge accumulation and dissipation to be determined. It was found that the dissipation coefficient has a large constant value during gamma-ray irradiation and decreases asymptotically to a small value after irradiation is stopped. From the coefficients, the minimum signal current was calculated, which is the value when accumulation and dissipation balance each other under continuous irradiation. The time required for the signal current to recover following irradiation was also calculated.

Results of clot waveform analysis and thrombin generation test for a plasma-derived factor VIIa and X mixture (MC710) in haemophilia patients with inhibitors--phase I trial: 2nd report.

We reported the results of a clinical pharmacological study of MC710 (a mixture of plasma-derived FVIIa and FX) in haemophilia patients with inhibitors during a non-haemorrhagic state. This report provides the results of a clot waveform analysis (CWA) and thrombin generation test (TGT) using blood samples obtained in this study. CWA and TGT were conducted using blood samples obtained from a pharmacokinetic and pharmacodynamic study in which MC710 (five dose rates: 20, 40, 80, 100 and 120 µg kg(-1)) was compared with NovoSeven (120 µg kg(-1)) and FEIBA (two dose rates: 50 and 75 U kg(-1)) as control drugs in 11 haemophilia patients with inhibitors without haemorrhagic symptoms. CWA showed that MC710 provided significantly greater improvement than the control drugs in activated partial thromboplastin time (APTT) at 80 µg kg(-1); maximum clot velocity and maximum clot acceleration were more enhanced by MC710 than by control drugs. TGT revealed that MC710 significantly shortened the initiation time of thrombin generation in comparison to FEIBA and induced greater thrombin generation potency than NovoSeven. It was not clear whether or not MC710 caused significant dose-dependent changes in the two measurements; however, differences between MC710 and the control drugs were clarified. MC710 was confirmed to have superior coagulation activity and thrombin productivity and is expected to have superior bypassing activity.

A standard for absorbed dose rate to water in a 60Co field using a graphite calorimeter at the National Metrology Institute of Japan.

A primary standard for the absorbed dose rate to water in a 6°Co radiation field has been newly established at the National Metrology Institute of Japan. This primary standard combines the calorimetric measurements using a graphite calorimeter with the ionometric measurements using a thick-walled graphite cavity ionisation chamber. The calorimeter is operated in the constant temperature mode using AC Wheatstone bridges. The absorbed dose rate to water was determined to be 12 mGy s⁻¹ at a point of 1 m from the radiation source and at a water depth of 5 g cm⁻². The uncertainty on the calibration coefficient in terms of the absorbed dose to water of an ionisation chamber using this standard was estimated to be 0.39 % (k=1).

Clinical pharmacological study of a plasma-derived factor VIIa and factor X mixture (MC710) in haemophilia patients with inhibitors--phase I trial.

MC710, a combined product of plasma-derived activated factor VII (FVIIa) and factor X (FX) at a protein weight ratio of 1:10, is a novel bypassing agent for haemostasis in haemophilia patients with inhibitors. In this study, pharmacokinetic (PK), pharmacodynamic (PD) parameters and safety of single doses of MC710 were investigated in 11 male haemophilia patients with inhibitors in a non-bleeding state. This was a multi-centre, open-labelled, non-randomized, active controlled crossover, dose-escalation study of five doses (20-120 µg kg(-1) of FVIIa) with re-administration of different MC710 dosages to the same subjects. The active controls were NovoSeven (120 µg kg(-1)) and/or FEIBA (50 and 75 U kg(-1)) which were used to compare PD parameters. The area under the curve (AUC) and maximum plasma concentration (C(max)) of MC710 active ingredients increased dose-dependently within the range of 20 and 120 µg kg(-1). After administration of MC710, activated partial thromboplastin time (APTT) was dose-dependently improved and prothrombin time (PT) was shortened to approximately 6 s at 10 min, and APTT improvement and PT shortening effects were maintained until 12 h after administration of MC710 at all doses. No serious or severe adverse event was observed after administration of MC710; furthermore, several diagnostic marker values and those changes did not indicate any signs of disseminated intravascular coagulation (DIC). These results suggest that MC710 would have haemostatic potential equal to or greater than NovoSeven and FEIBA and was be tolerable when given at doses up to 120 µg kg(-1).

Effect of radiation-induced charge accumulation on build-up cap on the signal current from an ionisation chamber.

The signal current from a thimble ionisation chamber with a build-up cap made of an insulator decreases by about 0.41 % after being irradiated for 17 h at an air kerma rate of 41 Gy h(-1) by a collimated (60)Co gamma-ray beam in air. In contrast, the signal current remains constant when the thimble ionisation chamber is irradiated in a water phantom. During irradiation, positive charge is considered to accumulate near the outer surface of the build-up cap where electron equilibrium is not achieved. Secondary electrons travelling in the build-up cap and the chamber wall toward the ionisation volume are decelerated by the electric field generated by the positive charge. Consequently, the signal current decreases with increasing charge accumulation because some secondary electrons are prevented from entering the ionisation volume. In the water phantom, electron equilibrium is established in and around the ionisation chamber and charge does not accumulate. To confirm this hypothesis, the signal current was measured for an ionisation chamber in air with a build-up cap wrapped with Al foil and covered with PMMA tubes. Electron equilibrium was established over the build-up cap because the tubes were thicker than the secondary electron range. The signal current decreased with increasing positive voltage applied to the Al foil. It was estimated from the results that positive charges equivalent to a voltage of over 6 kV applied to the Al foil accumulated during irradiation. The signal current was also measured for an ionisation chamber with a metal build-up cap and for an ionisation chamber with a wall and build-up cap made of conductive plastic.

Corrections to air kerma and exposure measured with free air ionisation chambers for charge of photoelectrons, Compton electrons and Auger electrons.

The signal charge from a free air ionisation chamber for the measurement of air kerma and exposure consists of not only the charge of ion pairs produced by secondary electrons (i.e. photoelectrons, Compton electrons and Auger electrons), but also the charge of the secondary electrons and single and multiple charged ions formed by the release of the secondary electrons. In the present work, correction factors for air kerma and exposure for the charge of the secondary electrons and ions were calculated for photons with energies in the range from 1 to 400 keV. The effects of an increase in the W value of air for low-energy electrons were also taken into consideration. It was found that the correction factors for air kerma and exposure have a maximum value near a photon energy of 30 keV; in the lower energy region, the correction factor for exposure monotonically decreases with a decrease in photon energy except for a small dip due to K-edge absorption by argon atoms in air. The values of the correction factors were found to be 0.9951 and 0.9892, respectively, for a spectrum with a mean energy of 7.5 keV, the reference X-ray spectrum with the lowest mean energy in ISO 4037-1. The air kerma correction is smaller than that for exposure, because for air kerma the signal due to the charge of secondary electrons and ions is partly compensated by the decrease in the number of ion pairs produced by the secondary electrons due to the increase of the W value of air for lower energy electrons.

Hippocampal synthesis of estrogens and androgens which are paracrine modulators of synaptic plasticity: synaptocrinology.

Hippocampal pyramidal neurons and granule neurons of adult male rats are equipped with a complete machinery for the synthesis of pregnenolone, dehydroepiandrosterone, testosterone, dihydrotestosterone and 17beta-estradiol. Both estrogens and androgens are synthesized in male hippocampus. These brain steroids are synthesized by cytochrome P450s (P450scc, P45017alpha and P450arom), hydroxysteroid dehydrogenases and reductases from endogenous cholesterol. The expression levels of enzymes are as low as 1/300-1/1000 of those in endocrine organs. Synthesis is dependent on the acute Ca(2+) influx upon neuron-neuron communication via NMDA receptors. Estradiol is particularly important because estradiol rapidly modulates neuronal synaptic transmission such as long-term potentiation via synaptic estrogen receptors. Xenoestrogens may also act via estrogen-driven signaling pathways.

Loss of ions in cavity ionization chambers.

Ion losses due to initial recombination, volume recombination, and back diffusion were each determined by measurements and calculations for different size cylindrical ionization chambers and spherical ionization chambers. By measuring signal currents from these ionization chambers irradiated with (60)Co gamma rays, two groups of ion losses were obtained. (Group 1) Ion loss due to initial recombination and diffusion, which changes proportionally to the inverse of the voltage applied to the ionization chambers; (and group 2) ion loss due to volume recombination, which changes proportionally to the inverse of the square of the applied voltage. The diffusion loss was obtained separately by computing electric field distributions in the ionization chambers. It was found that diffusion loss is larger than initial recombination loss for the cylindrical ionization chambers and vise versa for the spherical ionization chambers.

Angle dependence of signal currents from cylindrical ionisation chambers.

A signal current from a cylindrical ionisation chamber with an ionisation volume of 62.7 cm3, 40 mm in diameter and 50 mm long, peaked when the chamber was lixed at 0 degrees and at 90 degrees in 137Cs and 60Co gamma ray fields for source-chamber distances of 1 m and 2 m. A smaller ionisation chamber showed a small peak at 0 degrees in both fields but not at 90 degrees. However, calculations indicated that the signal current from the smaller chamber would also show a peak at 90 degrees in a 137Cs point-source gamma ray field. Peaks occur because gamma rays attenuate along the cylindrical side wall or along the end walls when a chamber is tilted slightly from 0 degrees or 90 degrees and the direction of the gamma ray beam agrees with the plane of one of these walls. These facts suggest the need for care in the common practice of measuring and calculating responses for cylindrical ionisation chambers fixed perpendicular to gamma ray beams.

Neurosteroid synthesis by cytochrome p450-containing systems localized in the rat brain hippocampal neurons: N-methyl-D-aspartate and calcium-dependent synthesis.

Neurosteroidogenesis has not been well elucidated due to the very low level of steroidogenic proteins in the brain. Here we report the first demonstration of the neuronal localization of neurosteroidogenic systems as well as the regulation of neurosteroidogenic activity in the adult rat hippocampus. Significant localization of cytochrome P450scc was observed in pyramidal neurons and granule neurons by means of immunohistochemical staining of slices. We also observed the colocalization, in hippocampal neurons, of P450scc with redox partners, hydroxysteroid sulfotransferase and steroidogenic acute regulatory protein. The distributions of astroglial cells and oligodendroglial cells showed very different patterns from that of the P450scc-containing cells. The expression of P450scc, redox partners, the sulfotransferase, and steroidogenic acute regulatory protein was also confirmed by Western blot analysis. The process of active neurosteroidogenesis was stimulated by exposing neurons to N-methyl-D-aspartate. Upon stimulation with N-methyl-D-aspartate, Ca(2+) influx through the N-methyl-D-aspartate subtype of glutamate receptors occurred, and significant net production of pregnenolone and pregnenolone sulfate was observed in the hippocampus. This neurosteroid production was considerably suppressed by the addition of antagonists of N-methyl-D-aspartate receptors, by Ca(2+) depletion, or by the addition of an inhibitor of P450scc. Upon stimulation with N-methyl-D-aspartate, the processing of full-length steroidogenic acute regulatory protein (37-kDa) to the truncated 30-kDa steroidogenic acute regulatory protein was observed. Taken together, these observations imply that hippocampal neurons synthesize neurosteroids. This synthesis may be stimulated and regulated by glutamate-mediated synaptic communication.

Autoimmune neutropenia in pregnant women causing neonatal neutropenia.

Autoimmune neutropenia (AIN) can occur during pregnancy. However, neonatal neutropenia occurring in an infant born to a mother with AIN has only rarely been documented. Recently, we have experienced two cases of AIN during pregnancy, both of which caused severe yet transient neonatal neutropenia (< 0.3 x 10(9)/l), probably as a result of transplacental maternal anti-neutrophil autoantibodies. The anti-neutrophil antibodies seemed to be against antigens other than NA1/NA2 because the autoantibodies did not bind to neutrophils of specific NA types selectively in the granulocyte indirect immunofluorescence test. Although AIN is a relatively uncommon disease, neonatal neutropenia caused by maternal AIN may not be quite as rare.