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The total synthesis of alcyonolide, an antitumor xenicn diterpenoid, has been achieved. The inverse electron demand hetero-Diels-Alder reaction using a dienophile possessing an electron-withdrawing group provided the endo adduct which included a condensed lactone and dihydropyran rings with the desired three stereogenic centers. After introduction of the side chain by the Negishi coupling, the lactone ring was opened to form a Weinreb amide. The sequential transformation including conversion of Weinreb amide to aldehyde, PMB to acetate, and allylation of the aldehyde gave a mixture of separable four diastereomers. The desired stereoisomer was submitted to the 2,2,6,6-tetramethylpiperidine 1-oxyl oxidation, which afforded the δ-lactone and the methyl ketone side chain. Finally, the olefin metathesis of the desired isomer gave racemic alcyonolide.

Magnetic gears can change output-torque and -speed without any mechanical contacts. Therefore, they have a low acoustic noise and vibration, and their maintainability and reliability are high. Especially, a flux-modulated type magnetic gear is expected to be put into practical use because its torque density is higher than that of other magnetic gears. For the practical use, further improvement of torque and losses is important, especially, reduction of eddy current loss in permanent magnets (PMs) due to asynchronous harmonic magnetic fluxes is necessary. This paper investigates an interior permanent magnet (IPM) structure to improve the efficiency by reducing the eddy current loss in PMs. In addition, this paper presents a method for increasing torque of the IPM magnetic gear by changing a position of magnetic-bridge.

The conventional planar culture of adherent cells is inefficient for large‐scale manufacturing of cell and gene therapy products. We developed a facile and efficient bead‐to‐bead cell‐transfer method for serial subculture and large‐scale expansion of human mesenchymal stem cells (hMSCs) with microcarriers in bioreactors. We first compared culture medium with and without nucleosides and found the former maintained the expression of surface markers of hMSCs during their prolonged culture and enabled faster cell proliferation. Subsequently, we developed our bead‐to‐bead cell transfer method to subculture hMSCs and found that intermittent agitation after adding fresh microcarriers to cell‐populated microcarriers could promote spontaneous cell migration to fresh microcarriers, reduce microcarrier aggregation, and improve cell yield. This method enabled serial subculture of hMSCs in spinner flasks from passage 4 to passage 9 without using proteolytic enzymes, which showed faster cell proliferation than the serial planar cultures undergoing multiple enzyme treatment. Finally, we used the medium containing nucleosides and our bead‐to‐bead cell transfer method for cell culture scale‐up from 4‐ to 50‐L cultures in single‐use bioreactors. We achieved a 242‐fold increase in the number of cells to 1.45 × 1010 after 27‐day culture and found that the cells harvested from the bioreactors maintained proliferation ability, expression of their surface markers, tri‐lineage differentiation potential and immunomodulatory property. This study shows the promotive effect of nucleosides on hMSC expansion and the potential of using our bead‐to‐bead transfer method for larger‐scale manufacturing of hMSCs for cell therapy., The expansion of human mesenchymal stem cells (hMSCs) was promoted using a culture medium with nucleosides. Intermittent agitation was performed to facilitate bead‐to‐bead cell transfer to expand hMSCs in bioreactors without proteolytic enzymes. By using this culture medium and our bead‐to‐bead cell‐transfer method, hMSC cultures were scaled up from 4‐ to 50‐L in bioreactors, resulting in a 242‐fold increase in cell number to 1.45 × 1010.

Paragonimiasis is an important food-borne zoonosis caused by Paragonimus flukes and is endemic to western Japan. However, there have been few epidemiological studies in the Tohoku district of northeastern Japan. In this study, Paragonimus metacercariae (mc) was detected in Geothelphusa dehaani (Japanese freshwater crab or Sawagani) in Iwate Prefecture. Out of the 207 Sawagani collected from 35 localities, 12 individuals from six localities were infected with Paragonimus mc. The mc were identified as P. skrjabini miyazakii based on the sequences of nuclear ribosomal internal transcribed spacer 2 and mitochondrial cytochrome c oxidase I. This is the first report of P. s. miyazakii mc infection in Sawagani in Iwate Prefecture.

Vertically aligned carbon nanotubes (VACNTs or CNTs) were synthetized by thermal chemical vapor deposition method on the Si/SiO2 substrates, using Al/Fe as catalyst. In the present study, the influence of the annealing duration and synthesis time on the length, grow rate and quality of the VACNTs according to 9 different regimes was investigated. The outcomes of the study was observed using scanning electron microscope, atomic force microscopy and Raman spectroscopy analysis was utilized in order to evaluate the quality of the obtained nanotubes. Results have shown that the length of the VACNTs increases with the rise of annealing time, however only to a certain degree, after which the deterioration of the nanotubes occurs and the reduction of their length is noticeable.

For high sensitivity and rapid reaction of enzyme-linked immunosorbent assay (ELISA), the film-stack reaction field with micro-pillars array was designed and developed. The film-stack reaction field was fabricated by a nanoimprint process and an automatic punch-press process. The films with different gaps between micro-pillars (5, 10 and 50 μm) were prepared. These reaction fields were evaluated by IgA ELISA using 96-well microtitre plates and the computational simulation analysis of the fluid flow and the particle trajectory. Compared with ELISA using only the microtitre plate, higher detection sensitivity and shorter incubation time were achieved using the film-stack reaction field due to the increased surface area and the circulating flow through the space between films in a well by the rotation of the film-stack reaction field. Furthermore, in the ELISA results obtained using the film-stack reaction fields, the fluorescence intensities in 10-μm and 50-μm pillar gaps were the minimum and maximum values, respectively. This trend was due to the flow rate between micro-pillars, and the number and the diffusion distance of supplied biomolecules to the inertial space in the film-stack reaction field. In simulation results, the trend of the number of adsorbed biomolecule particles with different gaps between micro-pillars was in agreement with the trend in the ELISA results. Hence, these simulation analyses were validated in the quantitative evaluation of this reaction field and could be applied in the design of this reaction field as an effective design tool.

Elaborately programmed silver nanowire arrays can be prepared using a tapered push-pull nozzle system (TPPNS), which is used to directly write micro-nano wires on a substrate via a two-reagent reaction in the diffusion mixing region. The wires could be precisely positioned on the substrate and their width could be freely controlled from the micro to the nano scale, indicating an advance in the methodologies of controlling and fabricating nanowires. The as-prepared silver three-electrode device can serve as a three-electrode sensor.

Monohydrocalcite (MHC: CaCO 3 ·H 2 O), a rare carbonate mineral formed under surface conditions, is usually observed in nature as containing a variable amount of Mg, with a 0.007–0.45 Mg/Ca mole ratio. The variable Mg composition in MHC is anticipated as a promising proxy to assess paleo-hydrochemistry especially in saline lakes. Although the roles of Mg on the formation and stability of MHC have been studied intensively, the Mg speciation in MHC has remained unclear and controversial. This study examined Mg speciation in MHC using X-ray absorption near edge structure (XANES), ab initio molecular simulation, and geochemical modeling. Mg-XANES spectra of MHC with different Mg/Ca ratios prepared from mixing solutions of Na 2 CO 3 , CaCl 2 and MgCl 2 revealed that the Mg in MHC is a mixture of amorphous Mg carbonate (AMC) and other Mg containing phase. The contribution of AMC to total Mg is negatively correlated to the crystallinity of MHC. Results show that AMC might play a protective role in the crystallization and the transformation to stable calcium carbonates. Ab initio calculation of Mg 2+ substitution into MHC showed that a limited amount of Mg 2+ can be incorporated into the MHC structure. Six-fold coordination of Mg 2+ is substituted for eight-fold coordination of Ca 2+ in the MHC structure. The other type of Mg in MHC revealed from the XANES analyses most likely corresponds to the structural Mg in MHC. The contribution of the structural Mg is almost constant at 0.06 in Mg/Ca, representing the limit of solid solubility of Mg in MHC. The solubility products of the MHC with the limit of solid solubility of Mg and the AMC associated with MHC were estimated from the reacted solution compositions. Prediction of the Mg/Ca ratio as a function of the initial solution conditions using solubility reasonably reproduces the observed apparent Mg/Ca ratios in MHC from the present study and earlier studies. The apparent Mg/Ca ratio of MHC is useful to elucidate water chemistry, especially for CO 3 /Ca and Mg concentrations during MHC formation.

Background The quantitative evaluation of the biomolecules transport with multi-physics in nano/micro scale is demanded in order to optimize the design of microfluidics device for the biomolecules detection with high detection sensitivity and rapid diagnosis. Objective This paper aimed to investigate the effectivity of the computational simulation using the numerical model of the biomolecules transport with multi-physics near a microchannel surface on the development of biomolecules-detection devices. Methods The biomolecules transport with fluid drag force, electric double layer (EDL) force, and van der Waals force was modeled by Newtonian Equation of motion. The model validity was verified in the influence of ion strength and flow velocity on biomolecules distribution near the surface compared with experimental results of previous studies. The influence of acting forces on its distribution near the surface was investigated by the simulation. Results The trend of its distribution to ion strength and flow velocity was agreement with the experimental result by the combination of all acting forces. Furthermore, EDL force dominantly influenced its distribution near its surface compared with fluid drag force except for the case of high velocity and low ion strength. Conclusions The knowledges from the simulation might be useful for the design of biomolecules-detection devices and the simulation can be expected to be applied on its development as the design tool for high detection sensitivity and rapid diagnosis in the future.

In the early developmental stages, infants learn to control complex and redundant body movements using sensory inputs. Reaching with the arm and hand position control are fundamental features of motor development. However, it remains unclear how infants aquire such kind ofmotor control. In the current study, we propose a network model that learns the relationship between motor commands and visual and proprioceptive sensory input using predictive learning to perform reaching based on infantile musculoskeletal body. Based on assumption that human motion is generated from combinations of muscle activation patterns deiňĄned as a motor primitive, we examine the contribution of motor primitive to sensorimotor development. The results of this predictive learning model revealed that acquisition of motor primitives promoted sensorimotor learning of reaching.

Paragonimiasis is an important food-borne zoonosis caused by Paragonimus flukes and is endemic to western Japan. However, there have been few epidemiological studies in the Tohoku district of northeastern Japan. In this study, Paragonimus metacercariae (mc) was detected in Geothelphusa dehaani (Japanese freshwater crab or Sawagani) in Iwate Prefecture. Out of the 207 Sawagani collected from 35 localities, 12 individuals from six localities were infected with Paragonimus mc. The mc were identified as P. skrjabini miyazakii based on the sequences of nuclear ribosomal internal transcribed spacer 2 and mitochondrial cytochrome c oxidase I. This is the first report of P. s. miyazakii mc infection in Sawagani in Iwate Prefecture.

Cilnidipine is a dihydropyridine derivative that inhibits N-type and L-type voltage-gated Ca2+ channels (VDCCs). We recently reported that a selective N-type VDCC blocker attenuated the spinal long-term potentiation (LTP) of C-fiber-evoked field potentials recorded in the spinal dorsal horn of rats, which served as a model for examining synaptic function during central pain sensitization. In this study, we investigated the effects of cilnidipine on the changes related to neuropathic pain induced by nerve injury. Mechanical allodynia and hyperalgesia were evaluated by von Frey test and pin prick test, respectively. Spinal LTP of C-fiber-evoked field potentials were evaluated by in vivo electrophysiology. Intrathecally administrated cilnidipine attenuated mechanical allodynia and hyperalgesia in the spared nerve injury mouse model. Using in vivo electrophysiology in rats, cilnidipine (10µm) administered spinally inhibited the induction and maintenance of high-frequency stimulation-induced LTP of C-fiber-evoked field potentials, while basal C-fiber-evoked field potentials in naive rats were unaffected. The basal C-fiber-evoked field potentials in nerve-injured rats were strongly inhibited by cilnidipine. Treatment with a specific N-type VDCC blocker, ω-conotoxin GVIA, which reportedly attenuates C-fiber-evoked field potentials both before and after the induction of LTP, attenuated mechanical allodynia and hyperalgesia in nerve-injured mice. By contrast, an L-type VDCC blocker, nicardipine attenuated only mechanical hyperalgesia, but not mechanical allodynia in nerve-injured mice, and also attenuated the established LTP of C-fiber-evoked field potentials in rats. These results suggested that N-type and L-type VDCC blockers may effectively alleviate the hyperalgesia and allodynia associated with neuropathic pain without affecting normal pain perception.

Various micro surface-modification approaches including photolithography, dip-pen lithography and ink-jet systems have been developed and used to extend the functionalities of solid surfaces. While those approaches work in the "open space", push-pull systems which work in solutions have recently drawn considerable attention. However, the confining flows performed by push-pull systems have realized only the dispense process, while microscale, region-selective chemical reactions have remained unattainable. This study reports a microchemical pen that enables region-selective chemical reactions for the micro surface modification/patterning. The chemical pen is based on the principle of microfluidic laminar flows and the resulting mixing of reagents by the mutual diffusion. The tiny diffusion layer performs as the working region. This report represents the first demonstration of an open microreactor in which two different reagents react on a real solid sample. The multifunctional characteristics of the microchemical pen are confirmed by different types of reactions in many research areas, including inorganic chemistry, polymer science, electrochemistry and biological sample treatment.

Background Enzyme-linked immunosorbent assays (ELISA) are considered the gold standard in the demonstration of various immunological reactions with an application in the detection of infectious diseases such as during outbreaks or in patient care. Objective This study aimed to produce an ELISA-based diagnostic with an increased sensitivity of detection compared to the standard 96-well method in the immunologic diagnosis of infectious diseases. Methods A '3DStack' was developed using readily available, low cost fabrication technologies namely nanoimprinting and press stamping with an increased surface area of 4 to 6 times more compared to 96-well plates. This was achieved by stacking multiple nanoimprinted polymer sheets. The flow of analytes between the sheets was enhanced by rotating the 3DStack and confirmed by Finite-Element (FE) simulation. An Immunoglobulin G (IgG) ELISA for the detection of antibodies in human serum raised against Rubella virus was performed for validation. Results An improved sensitivity of up to 1.9 folds higher was observed using the 3DStack compared to the standard method. Conclusions The increased surface area of the 3DStack developed using nanoimprinting and press stamping technologies, and the flow pattern between sheets generated by rotating the 3DStack were potential contributors to a more sensitive ELISA-based diagnostic device.

Apple pomace is one of the major agricultural residues in Aomori prefecture, Japan, and it would be useful to develop effective applications for it. As apple pomace contains easily fermentable sugars such as glucose, fructose and sucrose, it can be used as a feedstock for the fermentation of fuels and chemicals. We previously isolated a new hydrogen-producing bacterium, Clostridium beijerinckii HU-1, which could produce H2 at a production rate of 14.5 mmol of H2/L/h in a fed-batch culture at 37 °C, pH 6.0. In this work we found that the HU-1 strain produces H2 at an approximately 20% greater rate when the fermentation medium contains the water-insoluble material from apple pomace. The water-insoluble material from apple pomace caused a metabolic shift that stimulated H2 production. HU-1 showed a decrease of lactate production, which consumes NADH, accompanied by an increase of the intracellular pyrophosphate content, which is an inhibitor of lactate dehydrogenase. The intracellular NAD(+)/NADH ratios of HU-1 during H2 fermentation were maintained in a more reductive state than those observed without the addition of the water insoluble material. To correct the abnormal intracellular redox balance, caused by the repression of lactate production, H2 production with NADH oxidation must be stimulated.