Temperature-independent lasing wavelength of highly stacked InAs quantum dot laser fabricated on InP(311)B substrate with Bi irradiation.

In this study, the effects of bismuth (Bi) irradiation on InAs quantum dot (QD) lasers operating in the telecommunication wavelength band were investigated. Highly stacked InAs QDs were grown on an InP(311)B substrate under Bi irradiation, and a broad-area laser was fabricated. In the lasing operation, the threshold currents were almost the same, regardless of Bi irradiation at room temperature. These QD lasers were operated at temperatures between 20 and 75°C, indicating the possibility of high-temperature operation. In addition, the temperature dependence of the oscillation wavelength changed from 0.531 nm/K to 0.168 nm/K using Bi in the temperature range 20-75°C.

Wavefront superposition method for accurate and efficient mode conversion.

A wavefront superposition (WS) method is proposed for accurate and efficient mode conversion in mode-division multiplexing transmission. The WS method converts an input beam to the WS state, which is composed of the conversion target and radiation modes of a few-mode fiber. The appropriate weighting for the modal component of the WS state enables more efficient conversion than the conventional method in which the output beam consists only of the conversion target. Further, since the components of the radiation modes in the output are eliminated by the mode-filtering property of the few-mode fiber, no modal crosstalk occurs in the WS method. We examine the conversion performance of the WS method by a numerical simulation for the mode-multiplexing numbers 3, 6, 10, and 15. The WS method shows a 2.4 dB higher efficiency than the conventional method, while maintaining an extremely low modal crosstalk (less than -80 dB), even when the number of multiplexed modes is 15.

Center of Gravity Tracker for Operator Fatigue Detection.

Driver fatigue is a cause of serious accidents for heavy machinery operators. Monitoring operator position, as indicated by their Center of Gravity (CoG), may be a means to non-invasively detect driver fatigue. We prototyped a research tool that tracks CoG from four sensors located within the legs of a seat, and validated its accuracy and precision. Our primary contributions are the development of a low-cost integrated CoG detector for seated drivers and the design of a flexure structure to protect load cells from shocks, tensile and shear forces. This system will enable research into CoG as an indicator of fatigue.

Absorption and fluorescence spectroscopic properties of 1- and 1,4-silyl-substituted naphthalene derivatives.

Silyl-substituted naphthalene derivatives at the 1- and 1,4-positions were synthesized and their UV absorption, fluorescence spectroscopic properties, and fluorescence lifetimes were determined. Analysis of the results shows that the introduction of silyl groups at these positions of the naphthalene chromophore/fluorophore causes shifts of the absorption maxima to longer wavelengths and increases in fluorescence intensities. Bathochromic shifts of the absorption maxima and increases in fluorescence intensities are also promoted by the introduction of methoxy and cyano groups at the naphthalene 4- and 5-positions. In addition, the fluorescence of 9,10-dicyanoanthracene is efficiently quenched by these naphthalene derivatives with Stern-Volmer plot calculated rate constants that depend on the steric bulk of the silyl groups.

Permeation enhancement of ascorbic acid by self-dissolving micropile array tip through rat skin.

Ascorbic acid (AA) loaded self-dissolving micropiles (SDMP) were prepared using chondroitin sulfate as the base for the percutaneous administration of AA. AA solution was added to dense solution of chondroitin solution, glue, and array tip, 1.0 cm(2), containing 100 SDMPs of which length was 500 microm and basal diameter was 300 microm, were prepared. Two kinds of AA array tips containing 1344.2+/-1.7 microg (high content ones) and 638.7+/-4.3 microg (low content ones) were used. In vitro dissolution study showed that more than 90% of AA were released from both SDMP array tips within 5 min. Stability experiment showed that 99.2-99.4% of AA was detected in SDMP array tips when stored at 23 degrees C for 1 week. When in vitro permeation experiments were performed after AA SDMP array was inserted to the isolated rat abdominal skin, extremely high amounts of AA, 1285.3+/-369.0 microg (95.3%) for high content SDMP tip and 405.6+/-84.3 microg (65.8%) for low content SDMP tip, were permeated for 6 h into the receptor compartment due to the break down of the skin barrier function. When AA SDMP array tip was administered to the rat skin under anesthetized condition with the different contact times, 10, 20 and 30 min, the permeated amount of AA was dependent on both the AA content in SDMP array tips and the contact time. When AA SDMP was contact to the skin for 30 min, permeated amounts of AA were 146.8+/-22.9 microg (10.9%) for high content-SDMP tip and 61.2+/-18.2 microg (9.6%) for low content SDMP tip. These results suggest the usefulness of SDMP array tip for the percutaneous absorption of AA.

Stimuli-responsive coacervate induced in binary functionalized poly(N-isopropylacrylamide) aqueous system and novel method for preparing semi-ipn microgel using the coacervate.

We describe a novel method for preparing a stimuli-responsive semi-interpenetrating polymer network (semi-IPN) hydrogel microsphere using a thermoresponsive-type coacervation. The coacervate droplets were formed in the two-component nonionic poly(N-isopropylacrylamide-co-2-hydroxyisopropylacrylamide) (poly(NIPAAm-co-HIPAAm)) and ionic poly(NIPAAm-co-2-carboxyisopropylacrylamide) (poly(NIPAAm-co-CIPAAm)) aqueous system by heating the solution above the lower critical solution temperature. The resulting coacervate droplets included both kinds of polymer chains. Divinyl sulfone, which cross-links the hydroxyl groups of the poly(NIPAAm-co-HIPAAm), was added to the coacervate droplets. In this way, the stimuli-responsive semi-IPN hydrogel microsphere consisting of the poly(NIPAAm-co-HIPAAm) gel matrix and the linear poly(NIPAAm-co-CIPAAm) chains could be prepared, and their sizes were relatively homogeneous. That is, by utilizing the thermoresponsive coacervate droplets induced in the binary system, we could successfully prepare the fine stimuli-responsive semi-IPN hydrogel microsphere and it was prepared in a simple and easy method without any additives.

Successful treatment of a patient with severe pulmonary hypertension due to perivalvular leakage at aortic and mitral positions after aortic and mitral valve replacement.

A 33-year-old-man had severe secondary pulmonary hypertension due to perivalvular leakage at the aortic and mitral positions after aortic and mitral valve replacement. Preoperative cardiac catheterization revealed pulmonary artery pressure of 105/45 mmHg and pulmonary vascular resistance of 929 dynes.s.cm(-5) To save the patient, we performed aortic and mitral valve re-replacement, and tricuspid annuloplasty. After surgery, selective pulmonary vasodilators, beraprost sodium, inhaled nitric oxide, and intravenous prostaglandin (PG) I(2) were administered because of persistent severe pulmonary hypertension. Cardiac catheterization on postoperative day 58 showed that the pulmonary artery pressure and pulmonary vascular resistance had decreased to 40/20 mmHg and 87.7 dynes x s x cm(-5), respectively The simultaneous use of inhaled nitric oxide, intravenous PGI(2), and oral beraprost sodium might be useful for treating postoperative persistent pulmonary hypertension.

Evaluation of self-dissolving needles containing low molecular weight heparin (LMWH) in rats.

Feasibility study of self-dissolving needles containing polysaccharide was performed. Low molecular weight heparin (LMWH) was used as a representative polysaccharide. Using chondroitin, dextran and dextrin as the base, self-dissolving needles (SDN) were prepared. The obtained SDNs were evaluated in rat absorption experiment, where pharmacological availability (PA) was calculated by comparing the plasma anti-Xa activity vs. time curves between SDNs and i.v. solution. After the insertion of SDNs to rats skin where the doses of LMWH were 25, 50 and 100 IU/kg, plasma samples were collected for 6h and anti-Xa activity was measured as the pharmacological index of LMWH. The anti-Xa level was maintained above 0.2 IU/ml, the therapeutic level, for about 2h at a dose of 100 IU/kg. Almost the same PAs of LMWH were obtained with dextran and dextrin SDNs, 97.7% and 102.3%, though lower PA was obtained with chondroitin SDN, 81.5%. In vitro dissolution experiment showed that LMWH was released from dextran, dextrin and chondroitin SDNs within 10 min. The T(50%)s were 0.84+/-0.06 min for dextran SDN, 1.07+/-0.12 min for chondroitin SDN and 2.11+/-0.31 min for dextrin SDN, respectively. Plasma anti-Xa activity vs. time profiles showed good dose-dependency in the 25-100 IU/kg range and high PAs were obtained, 90.0% for 25 IU/kg, 95.4% for 50 IU/kg and 97.7% for 100 IU/kg from dextran SDNs. Stability experiment was performed with dextran SDNs for 3 months. Above 97% of LMWH were remained in SDNs under three different conditions, -80, 4 and 40 degrees C. These results suggest the usefulness of SDN to polysaccharide drug.

Importance of bound water in hydration-dehydration behavior of hydroxylated poly(N-isopropylacrylamide).

In this study, a differential scanning calorimetric analysis was performed to investigate the role of water existing around the polymer chains on their thermoresponsive behaviors using the novel functional temperature-sensitive copolymer, poly(N-isopropylacrylamide-co-2-hydroxyisopropylacrylamide) (poly(NIPAAm-co-HIPAAm)). The HIPAAm comonomers were incorporated into the polymeric chains as hydrophilic parameters, and then the hydration states of poly(NIPAAm-co-HIPAAm) with various HIPAAm compositions were examined. Bound water, which is affected by the polymeric chains to some extent, was produced by adding the copolymers to the water, and the temperature due to the melting of the bound water decreased as the HIPAAm content increased. On the basis of this result, we considered that the interaction between the bound water and the polymeric chains is reinforced by the increasing HIPAAm composition. In addition, the cloud points of the copolymers shifted to a higher temperature, and the endothermic enthalpy for the phase transition decreased with increasing the HIPAAm content, suggesting that the number of water molecules disassociated from the polymeric chains decreased. Based on these results, we postulate that the changes in the interaction between the thermosensitive polymer and bound water exert a strong influence on its phase transition and/or separation, such as the cloud point or dehydration behavior.

Analysis of the formation mechanism for thermoresponsive-type coacervate with functional copolymers consisting of N-isopropylacrylamide and 2-hydroxyisopropylacrylamide.

We now report the formation mechanism of the thermoresponsive-type coacervate with the novel functional temperature-sensitive polymer, poly(N-isopropylacrylamide-co-2-hydroxyisopropylacrylamide) (poly(NIPAAm-co-HIPAAm)), synthesized in our laboratory. The effects of introducing the hydrophilic comonomer (HIPAAm) into the copolymer chains and adding salts on the behaviors of the coacervate droplets induced in the poly(NIPAAm-co-HIPAAm) aqueous solutions were investigated. Not only the particle sizes of the coacervate droplets but also the cloud points of the copolymer solutions could be modulated by the HIPAAm content incorporated in the copolymers. Moreover, the particle sizes of the coacervate droplets were also changed by adding salts. Namely, the particle sizes increased with the decreasing HIPAAm composition and increasing NaCl concentration. In addition, the 1H NMR and differential scanning calorimetric measurements suggested that as the HIPAAm content decreased or NaCl concentration increased, dehydration of the copolymers induced in the phase transition and/or separation became much easier. Therefore, on the basis of the findings obtained from these measurements, we determined that the particle sizes of the coacervate droplets induced in the temperature-sensitive polymers increased as the number of the water molecules, which are dissociated from the polymeric chains during the phase transition and/or separation, increased. Besides, to examine the separation of the model solutes, the aqueous two-phase separation with the coacervate droplets of poly(NIPAAm-co-HIPAAm) was carried out. The partitions of Methyl Orange as a model solute under both acidic (pH 2) and basic (pH 12) conditions were performed. The amount of Methyl Orange partitioned into the coacervate droplets at pH 12 is much greater than that at pH 2, which indicated that the coacervate droplets could recognize a slight difference in the polarity or structure between the model solutes.

Hydroxylated poly(N-isopropylacrylamide) as functional thermoresponsive materials.

In this study, we developed a poly(N-isopropylacrylamide)-based thermoresponsive polymeric material with a high content of hydroxyl groups. We newly designed the functional monomer, N-(2-hydroxyisopropyl)acrylamide (HIPAAm), considering maintaining the continuous and repeated structure of the isopropylamide group after copolymerization and the monomer reactivity ratios. The thermoresponsive polymer was derived by conventional radical copolymerization of HIPAAm with N-isopropylacrylamide (NIPAAm) in high yield. Estimation of monomer reactivity ratios, r(1) and r(2), supported the almost random sequence of the comonomers. The obtained copolymers showed a very sensitive phase transition and/or separation in response to temperature in aqueous media although they have many hydrophilic parts, and their thermoresponsive behavior was not affected by the pH. Furthermore, the cloud points of these copolymers closely depended on the HIPAAm content and could be easily controlled by adding salts. HIPAAm is expected to regulate the phase transition and/or separation temperature of the NIPAAm-based copolymers while maintaining their desirable sensitive thermoresponse. Differential scanning calorimetric analysis showed that dehydration of the polymer chains occurring in phase transition became incomplete with increasing HIPAAm content. Moreover, it was found that poly(NIPAAm-co-HIPAAm) having a high content of the HIPAAm unit showed liquid-liquid phase separation involving coacervation. The sizes of the coacervate droplets were relatively monodisperse and very minimal. Poly(NIPAAm-co-HIPAAm) is valuable for use in biomedical fields such as bioseparation.

Alkynylpyrenes as improved pyrene-based biomolecular probes with the advantages of high fluorescence quantum yields and long absorption/emission wavelengths.

The photochemical properties of various alkynylpyrene derivatives have been investigated in detail with a view to developing a new class of pyrene-based biomolecular probes. The absorption maxima of the alkynylpyrenes were seen to be shifted to longer wavelengths compared with those of the unsubstituted parent pyrene. Fluorescence quantum yields of the alkynylpyrenes dramatically increased up to 0.99 in ethanol, and only slight quenching of the fluorescence occurred even under aerated conditions. The alkynylpyrenes have been successfully introduced into representative biomolecules such as peptides, proteins, and DNAs. The detectabilities of the labeled biomolecules were significantly improved, with the unique photochemical characteristics of the pyrene nucleus being maintained.

In vitro and in vivo induction of human LoVo cells into apoptotic process by non-invasive microwave treatment: a potentially novel approach for physical therapy of human colorectal cancer.

The human LoVo and WI-38 cells were exposed to high power non-invasive microwaves. The apoptotic effect of the microwaves on the cells was examined with TUNEL, DNA fragmentation and flow cytometry. The human colon cancer LoVo cells showed pathological change of apoptosis but the normal human WI-38 cells showed no detectable apoptotic response. Exposure of the mice bearing tumor tissue to microwave resulted in a significant regression of the tumor tissue in the animal models. We demonstrate that the LoVo cells can be induced into apoptosis by microwave treatment both in in vitro and in vivo. The data described in this communication implies the possibility that microwave therapy may become a novel approach in human colorectal cancer treatment.

Development of silicone rubber hollow fiber membrane oxygenator for ECMO.

Silicone rubber hollow fiber membrane produces an ideal gas exchange for long-term ECMO due to nonporous characteristics. The extracapillary type silicone rubber ECMO oxygenator having an ultrathin hollow fiber membrane was developed for pediatric application. The test modules were compared to conventional silicone coil-type ECMO modules. In vitro experiments demonstrated a higher O2 and CO2 transfer rate, lower blood flow resistance, and less hemolysis than the conventional silicone coil-type modules. This oxygenator was combined with the Gyro C1E3 centrifugal pump, and three ex vivo experiments were conducted to simulate pediatric V-A ECMO condition. Four day and 6 day experiments were conducted in cases 1 and 2, respectively. Case 3 was a long-term experiment up to 2 weeks. No plasma leakage and stable gas performances were achieved. The plasma free hemoglobin was maintained within a normal range. This compact pump-oxygenator system in conjunction with the Gyro C1E3 centrifugal pump has potential for a hybrid total ECMO system.

Long-term ex vivo bovine experiments with the Gyro C1E3 centrifugal blood pump.

Centrifugal blood pumps are used widely for cardiopulmonary bypass, as ventricular assist devices, and for extracorporeal membrane oxygenation (ECMO). However, there is no centrifugal blood pump that is suitable for long-term ECMO. The authors developed the Gyro C1E3 centrifugal blood pump (Kyocera Corporation, Kyoto, Japan), which has superior antithrombogenic, antitraumatic, and hydraulic features in comparison with the conventional centrifugal blood pumps. Five ex vivo long-term durability tests of the Gyro C1E3 were performed using healthy miniature calves. The ECMO circuit was composed of a prototype hollow fiber silicone membrane oxygenator and a Gyro C1E3 pump. Venous blood was drained from the left jugular vein of a calf, passed through the oxygenator and infused into the left carotid artery using a Gyro C1E3. Ex vivo studies were performed from 7 to 15 days at a blood flow rate of 1 L/min. During this period, the Gyro C1E3 demonstrated a stable performance without exchanging the pump. Bleeding complications were the major reason for termination of each experiment. Rotational speed was maintained around 2,000 rpm. All five calves demonstrated neither abnormal signs nor abnormal blood examination data throughout the experiment. Neither clot nor thrombus formations were found during the necropsy in the cannula or pump nor were infarctions observed in any of the major organs. In conclusion, the Gyro C1E3 showed a stable and reliable performance during long-term ex vivo bovine experiments under the conditions tested.

Hemolytic characteristics of oxygenators during clinical extracorporeal membrane oxygenation.

A connection was previously reported between the hemolytic characteristics associated with oxygenators and the pressure drop measurements in the blood chamber under experimental conditions simulating their use in cardiopulmonary bypass. We examined this association during extracorporeal membrane oxygenation (ECMO) conditions. Three oxygenators for ECMO or pediatric cardiopulmonary bypass (Menox EL4000, Dideco Module 4000, and Mera HPO-15H) were evaluated. Fresh blood from healthy Dexter strain calves anticoagulated with citrate phosphate dextrose adenine solution was used. The blood flow was fixed at 1 L/min, similar to that in ECMO. The Normalized Index of Hemolysis for Oxygenators (NIHO) has been modified according to the American Society of Testing and Materials standards, as was previously reported. The NIHO value was the lowest in the Menox (0.0070+/-0.0009) and increased from Menox to Dideco (0.0113+/-0.0099) to Mera (0.0164+/-0.0043); however, there were no significant differences among the oxygenators. This NIHO value has a close correlation to the pressure drop. In conclusion, this evaluation method is also applicable to comparison of the biocompatibility performance of different types of clinically available oxygenators for ECMO.

Extracorporeal membrane oxygenator compatible with centrifugal blood pumps.

Coil-type silicone membrane oxygenators can only be used with roller blood pumps due to the resistance from the high blood flow. Therefore, during extracorporeal membrane oxygenation (ECMO) treatment, the combination of a roller pump and an oxygenator with a high blood flow resistance will induce severe hemolysis, which is a serious problem. A silicone rubber, hollow fiber membrane oxygenator that has a low blood flow resistance was developed and evaluated with centrifugal pumps. During in vitro tests, sufficient gas transfer was demonstrated with a blood flow less than 3 L/min. Blood flow resistance was 18 mm Hg at 1 L/min blood flow. This oxygenator module was combined with the Gyro C1E3 (Kyocera, Japan), and veno-arterial ECMO was established on a Dexter strain calf. An ex vivo experiment was performed for 3 days with stable gas performance and low blood flow resistance. The combination of this oxygenator and centrifugal pump may be advantageous to enhance biocompatibility and have less blood trauma characteristics.

Feasibility of a new hollow fiber silicone membrane oxygenator for long-term ECMO application.

Currently in United States, there are no clinically-applicable hollow fiber extracorporeal membrane oxygenation (ECMO) oxygenators available. Therefore, our laboratory is in the process of developing a silicone hollow fiber membrane oxygenator for long-term ECMO usage. This oxygenator incorporates an ultrathin silicone hollow fiber. At this time, a specially-modified blood flow distributor (one chamber distributor) is centered in the module to prevent blood stagnation. An ex vivo long-term durability test for ECMO was performed using a healthy miniature calf for 2 weeks. Venous blood was drained from the left jugular vein of a calf, passed through the oxygenator and infused into the left carotid artery using a Gyro C1E3 centrifugal blood pump. A successful 2-week ex vivo experiment was performed. The O2 and CO2 gas transfer rates were maintained at the same value of 40 m/min at a blood flow rate of 1 L/min flow and V/Q=3 (V=gas flow rate; Q=blood flow rate). The plasma free hemoglobin was maintained around 5 mg/dl. After the experiment, no blood clot formation was observed in the module and no abnormal necropsy findings were found. These data suggest that the performance of this newly-improved oxygenator was stable, reliable, and acceptable for long-term ECMO.

Preclinical evaluation of a new hollow fiber silicone membrane oxygenator for pediatric cardiopulmonary bypass: ex-vivo study.

Based on the results of many experimental models, a hollow fiber silicone membrane oxygenator applicable for long-term extracorporeal membrane oxygenation (ECMO) was developed. For further high performance and antithrombogenicity, this preclinical model was modified, and a new improved oxygenator was successfully developed. In addition to ECMO application, the superior biocompatibility of silicone must be advantageous for pediatric cardiopulmonary bypass (CPB). An ex vivo short-term durability test for pediatric CPB was performed using a healthy miniature calf for six hours. Venous blood was drained from the left jugular vein of a calf, passed through the oxygenator and infused into the left carotid artery using a Gyro C1E3 centrifugal pump. For six hours, the O2 and CO2 gas transfer rates were maintained around 90 and 80 ml/min at a blood flow rate of 2 L/min and V/Q=3, respectively. The plasma free hemoglobin was maintained around 5 mg/dl. These data suggest that this newly improved oxygenator has superior efficiency, less blood trauma, and may be suitable for not only long-term ECMO but also pediatric CPB usage.

Inlet port positioning for a miniaturized centrifugal blood pump.

We are developing the Baylor-Kyocera KP implantable centrifugal blood pump for small sized adult and pediatric patients. This pump eccentrically positions the inlet port, which eliminates flow stagnation around the top pivot bearing. The inlet port design is important because it may vary the inlet orifice pressure on the top housing and change hydraulic performance and hemolytic characteristics. The pressure distribution inside the KP pump was assessed by a computational fluid dynamic (CFD) analysis with 2.7 x 10(5) elements and 3.16 x 10(5) nodes. Hydraulic performance and hemolysis were evaluated with 3 different pump housings, which had 3.8, 4.5, and 6.1 mm offset inlet ports from the center in a mock circuit. The CFD analysis revealed that the pressure gradually increased from the center toward the peripheral. The pressure difference between the 3.8 to 6.1 mm offsets was less than 600 Pa. The hydraulic performance did not drastically change at 3.8, 4.5, and 6.1 mm offset from the center. However, the hemolysis increased with the increase of the port offset from 0.0080+/- 0.0048 to 0.054 +/- 0.028 g/100 L. The inlet port positioning is important to attain less blood trauma in this small Gyro centrifugal blood pump. The preferable position of the inlet port is less than 4.5 mm offset from the center.