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We report the random telegraph noise observed in gate-all-around (GAA) PMOS silicon nanowire FETs (SNWFETs) with the radius of 5 nm, at various temperatures (s) down to 4.2 K. From the -dependence of the capture/emission time, we obtain the energy and the charging status of the trap states. The gate bias dependence and the -dependence of the scattering coefficient-mobility product extracted from the relative fluctuation amplitude of the drain current are consistent with the fact that the surface roughness scattering is dominant in GAA PMOS SNWFETs.

We investigate effects of impurity scattering on current–voltage characteristics in a gate-all-around Si nanowire theoretically. Using non-equilibrium Green's function technique, the self-energy for the impurity scattering is incorporated under the self-consistent Born approximation. We show that the impurity scattering changes the electronic structure of the Si nanowire largely and, thus, results in very different current–voltage curves compared to the case of the free-impurity scattering.

Human cathepsin K, a cysteine proteinase of the papain family, has been recognized as a potential drug target for the treatment of osteoporosis. The predominant expression of cathepsin K in osteoclasts has rendered the enzyme into a major target for the development of novel antiresorptive drugs. Now, we report the pharmacological properties of OST-4077 [furan-2-carboxylic acid (1-{1-[4-fluoro-2-(2-oxo-pyrrolidin-1-yl)-phenyl]-3-oxo-piperidin-4-ylcarbamoyl}-cyclohexyl)-amide] as a novel selective cathepsin K inhibitor. Human and rat cathepsin K were inhibited in vitro by OST-4077 with the IC50 values of 11 and 427 nM, respectively. OST-4077 suppressed bone resorption induced by rabbit osteoclasts (IC50, 37 nM) but did not affect bone mineralization or cellular alkaline phosphatase activity in MC3T3-E1 cells. Parathyroid hormone-induced bone resorption was inhibited in a dose-dependent manner in thyroparathyroidectomized rats gavaged with a single dose of OST-4077 (ED50, 69 mg/kg). When given orally twice daily for 4 weeks to 3-month-old ovariectomized (OVX) rats, OST-4077 dose-dependently prevented bone loss, as monitored by bone densitometry, ash content, and urinary excretion of deoxypyridinoline. No change in serum osteocalcin in the OVX rats by OST-4077 suggested that bone formation might not be affected by the agent. In summary, OST-4077 selectively inhibited bone resorbing activities of osteoclasts and prevented bone loss induced by estrogen deficiency but did not affect bone formation. OST-4077, an orally active selective human cathepsin K inhibitor, may have the therapeutic potential for the treatment of diseases characterized by excessive bone loss including osteoporosis.

Background: There has been an increase in allergic diseases as a result of increased air pollution emanating from traffic and various industries. Objective: This study evaluated the association between air pollution and airway hyperresponsiveness in a cross-sectional study of a cohort of 670 children, aged 10–13 years. Methods: We measured spirometry and conducted allergic skin tests and methacholine challenge tests in 670 schoolchildren. The methacholine concentration causing a 20% fall in FEV1 (PC20) was used as the threshold of airway hyperresponsiveness (AHR). Thresholds of 16 mg/dl or less were assumed to indicate AHR. Results: All of the schoolchildren had normal pulmonary function. Of the children, 257 (38.3%) had AHR. There was a significant increase in AHR in schoolchildren living near a chemical factory [45.0% (138/306), 6.50 ± 0.48] compared to those in rural [31.9% (52/163), 9.84 ± 0.83] and coastal [33.3% (67/201), 7.17 ± 0.68] areas. Atopy was significantly more prevalent near the chemical factory vs the coastal and rural areas [35.6% (109/306) vs 27.3% (55/201) and 23.3% (38/163), respectively, P

In this study, we investigated the role of inositol polyphosphate-4-phosphatase, type-II (INPP4B) in acute myeloid leukemia (AML). We observed that AML patients with high levels of INPP4B (INPP4B(high)) had poor response to induction therapy, shorter event-free survival and shorter overall survival. Multivariate analyses demonstrated that INPP4B(high) was an independent predictor of poor prognosis, significantly improving current predictive models, where it outperformed conventional biomarkers including FLT3-ITD and NPM1. Furthermore, INPP4B(high) effectively segregated relative risk in AML patients with normal cytogenetics. The role of INPP4B on the biology of leukemic cells was assessed in vitro. Overexpression of INPP4B in AML cell lines enhanced colony formation potential, recapitulated the chemotherapy resistance observed in AML patients and promoted proliferation in a phosphatase-dependent, and Akt-independent manner. These findings reveal that INPP4B(high) has an unexpected role consistent with oncogenesis in AML, in contrast to its previously reported tumor-suppressive role in epithelial cancers. Overall, we propose that INPP4B is a novel prognostic biomarker in AML that has potential to be translated into clinical practice both as a disease marker and therapeutic target.

A single wall carbon nanotube (SWCNT) network is fabricated and its electronic transport properties are investigated. It shows a typical p-type field-effect-transistor (FET) behavior and nonlinearities in the source current-source bias characteristics. The network also exhibits incomplete turn-off and a small mobility. These characteristics are explained by the fact that the network is a mixture of metallic and semiconducting SWCNTs connecting with one another. Various cross junctions such as SWCNT (semiconducting)-SWCNT (semiconducting), SWCNT (semiconducting)-SWCNT (metallic) are the source of nonlinearities and the small mobility. Incomplete turn-off can be explained by the parallel conduction paths consisting of metallic SWCNTs which are insensitive to the gate bias. (© 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) (© 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

We report on low temperature magnetotunneling measurements through an AlAs/GaAs n-i-n diode incorporating stacked double layers of InAs self-assembled quantum dots (SAQDs). We observe that two strong conductance peaks at zero magnetic field (B) are split into four peaks at high B values. The double conductance peaks are interpreted as due to the conduction through the symmetric and antisymmetric states of coupled SAQDs. The separations between conductance peaks at B=0 and at B=18 T are consistent with the calculated energy separation between the symmetric and the antisymmetric states and with the previously reported Zeeman splitting, respectively.

Success of umbilical cord blood transplantation (UCBT) has been limited by a high rate of graft failure and delayed hematological recovery. It has been postulated that MSCs have hematopoiesis-supportive properties. Therefore, to overcome the limitation of UCBT, third-party UCB-derived MSCs were co-transplanted in recipients receiving unrelated UCBT. Seven patients received UCB and third-party UCB-MSCs. Hematopoietic recovery and transplantation outcomes were compared with historic controls. There was no acute toxicity associated with the infusion of MSCs. The median day to neutrophil engraftment was 19 days in patients, as compared with 24 days in controls (P=0.03). The median day of platelet engraftment was 47 days and 57 days in patients and controls, respectively (P=0.26). In addition, there was no engraftment failure in the MSC group. The incidence of acute and chronic GVHD was comparable between the two groups. However, veno-occlusive disease and TRM did not occur in the MSC group. Third-party UCB-MSCs infusion was safe and feasible. MSCs may also enhance the engraftment of UCBT and prevent rejection. In addition, MSCs may have a role in decreasing TRM. Randomized, controlled trials are required to confirm these results and longer follow-up will determine the effects of MSCs on the risk of relapse.

Capacitance-voltage measurements were carried out to investigate the effects of the doping profile on characteristics of self-assembled InAs quantum dots. Using this technique, we observed features of zero-dimensional electron confinement indicating the presence of quantum dots. However, the number of confined states differed depending on the doping profile, and this fact was confirmed by photoluminescence measurements. The equation in the depletion approximation led us to calculate the distribution of carriers as a function of depth from the sample surface, and the results are in agreement with the depth of the quantum dot layer.

We demonstrate a hybrid process for fabricating one-dimensional wire devices. The process is a combination of an alignment procedure using dielectrophoresis and subsequent contact metal formation utilizing electrochemical deposition with non-toxic organic-based Au electrolytes. Several devices have been successfully made from GaN nanowires or multi-walled carbon nanotubes (MWCNTs) using our hybrid technique. We demonstrate that rapid thermal annealing improves the ohmic characteristics by five orders of magnitude in the case of the GaN devices and ∼300% in the case of the MWCNT devices. One of the reasons for this improvement is enhanced gold wetting due to the reduction of grain size at the annealing temperature.

The quantization of conductance in units of 2e2/h of a quantum point contact (QPC) under low temperature, a narrow way formed in a two‐dimensional electron gas (2DEG), has become a paradigm of mesoscopic physics. Devices defined by electrostatic gates in GaAs/AlGaAs 2DEGs display an extraordinary variety of spin related phenomena. Besides the usual conductance plateaus, QPCs show an extra plateau at ∼0.7 (2e2/h), believed to arise from electron‐electron interactions. These plateaus disappear as temperature rise. We present the experimental results of temperature dependent disappearance. Under magnetic fields plateaus shift due to the Landau level. The numerical results using Green's function approach is also presented.

We report the selective growth of InAs self-assembled quantum dots (SAQDs) on silicon-dioxide/silicon (SiO2/Si) substrates patterned in nanometer scale. The SiO2 thin film is found to be an efficient mask material for prohibiting the growth of InAs SAQDs, while the formation of stable SAQDs is observed on the exposed surface of Si. We have utilized this selectivity to demonstrate almost one-dimensional alignment of InAs SAQDs on Si stripes. The crystallinity of SAQDs is also identified by high-resolution transmission electron microscope observation. Our study opens up a possibility of reliably integrating III–V quantum dot devices with conventional Si circuits.

The application of atomic-force-microscope (AFM) direct patterning to the selective positioning of InAs quantum dots (QDs) on a (100) GaAs substrate has been proposed and experimentally implemented. The AFM direct patterning was used to generate various patterns of several tens of nanometers in size, and InAs QDs were subsequently grown by a metalorganic chemical vapor deposition technique. A nonuniform distribution of the QDs was observed near the patterns. The detailed shape of the QD distribution and the size of the QDs depended on the geometrical properties such as the sidewall angle, the spacing, and the width of the patterns. We have been able to ascertain, through our work, what growth conditions are necessary for QDs’ alignment along the patterns.

Planar-type quantum-dot devices have been fabricated and characterized. Aluminum metal electrodes with interelectrode spacing of 30 nm have been deposited on an InAs self-assembled quantum-dot wafer to form the quantum-dot devices. The current–voltage characteristics measured from the devices, in which a single quantum dot is placed in between the electrodes, exhibit negative differential resistance effects at the temperature above 77 K. They are interpreted as due to three-dimensional–zero-dimensional resonant tunneling through the InAs self-assembled quantum dot.

We report fabrication and characterization of lambda DNA field effect transistors. Our transistor is basically a DNA network formed in between the source and the drain electrode on a SiO2/Si substrate. Measured source‐drain current (ISD) as a function of the source‐drain bias shows nonlinear characteristics. Such non‐linearity is typically a manifestation of the semiconducting behavior and is believed to be caused by the energy gap of the DNA molecules. Our sample shows a field effect behavior and we observe that ISD increases as the gate bias becomes more negative. It suggests that the lambda DNA used in our experiment is a p‐type molecule.

We compared the effects of two different doping methods on electronic states of self-assembled InAs quantum dots using photoluminescence and C-V spectroscopy. Analytical interpretation will be presented in conjunction with the experimental data.

There have been considerable efforts for the growth of InAs self-assembled quantum dots (QDs), and recently, many interesting works of selective growth on patterned substrates are under progress. Most of the works so far have been concentrated on the growth of QDs on GaAs substrates. On the other hand, the growth of InAs QDs on silicon substrates is expected to provide interesting growth mechanisms and new zero-dimensional states. We would like to present that InAs QDs are successfully grown on silicon substrates. The position control of QDs is also shown to be possible by utilizing patterned silicon/silicon dioxide (Si/SiO/sub 2/) substrates.

The mechanisms of cadmium-induced toxicity may include oxidative stress, altered redox homeostasis, and injuries to organelles. The current study was designed to study the effect of decreased cellular glutathione (GSH) content by sulfur amino acid deprivation on cadmium toxicity and to identify the signaling pathways responsible for the cytotoxicity. GSH content was increased by cadmium in H4IIE cells prior to cell death, which was prevented by excess GSH or cysteine. Cell viability, however, was not improved by GSH or cysteine complexation of cadmium. Cadmium-induced cytotoxicity was 40-fold potentiated in cells with decreased GSH by sulfur amino acid deprivation. Cadmium in combination with decreased GSH markedly increased apoptotic cell death. Mitogen-activated protein kinases including extracellular signal-regulated kinase 1/2, p38 kinase and c-Jun N-terminal kinase (JNK) were all activated 1-12 hr after sulfur amino acid deprivation. U0126 (1,4-diamino-2,3-dicyano-1,4-bis[2-aminophenylthio]butadiene), which inhibited activation of extracellular signal-regulated kinase1/2 and p38 kinase in cells under sulfur amino acid deprivation, completely prevented potentiation in Cd-induced cytotoxicity and apoptosis. Potentiation of cadmium toxicity by sulfur amino acid deprivation was prevented in part by either PD98059 or SB203580, or in cells stably expressing dominant negative mutant of JNK1, and to greater extents by PD98059 in combination with either SB203580 or JNK1(-) transfection. These results demonstrated that decreased cellular GSH content potentiated cytotoxicity induced by cadmium at the level of human exposure, and that the potentiation of cytotoxicity resulted from activation of extracellular signal-regulated kinase1/2 in conjunction with p38 kinase or JNK.

Microwave (MW) characteristics of a field effect transistor (FET) incorporating a single silicon nanowire (SiNW) were obtained from S-parameter measurements in the frequency range of 0.05 to 20 GHz. The single SiNW was aligned, using the alternating current (ac) dielectrophoresis alignment method, between the drain and source electrode forming a coplanar waveguide (CPW) structure. Analysis of the FET was performed using equivalent circuit modeling by advanced device system (ADS) simulation. By fitting the measured data with the simulation results, the parameters of the single SiNW FET were obtained and the cutoff frequency was derived.

The time-dependent responses of a single-electron transistor are investigated theoretically by adopting the Green’s function approach. Since the formalism takes non-adiabatic effects of the time-dependent perturbation into account, as well as the many-body interaction, the calculated results provide full expressions for the tunneling current and the noise. For typical experimental parameters, we calculate the first-harmonic responses of the single-electron transistor and discuss static voltage effects on the tunneling current and the noise in a radio-frequency single-electron transistor.

We measured the pseudo-dielectric function of self-assembled InAs/GaAs quantum dots at room temperature using spectroscopic ellipsometry. We observed a strong excitonic peak at 0.9 eV, which was attributed to quantum dot transitions. We also observed a plateau from 1.2 eV to 1.4 eV, which arose from steplike joint density of states originating from an InAs wetting layer. Our room temperature data are very similar to the 1.8 K photoluminescence excitation spectra of InAs/GaAs quantum dots reported in the literature. The higher energy dielectric response of the quantum dots enabled us to estimate the morphology of the quantum dots using effective medium analysis. These results were compared to atomic force microscopy measurement results. Effective medium analysis showed that a GaAs cap layer was preferentially grown on the InAs wetting layer rather than on InAs islands.

Two new local anesthetics, HS 37 and etidocaine, were evaluated in epidural analgesia and compared with bupivacaine. Initially, a dose-response study was conducted in which concentrations of etidocaine of 0.75%, 1% and 1.5% and concentrations of HS 37 of 0.75% and 1% were employed. On the basis of this study, a double-blind study was performed with 1% etidocaine, 1% HS 37 and 0.5% bupivacaine. This latter study indicated no difference in onset time and duration of maximal segmental spread. Bupivacaine possessed a significantly longer total duration of sensory analgesia. The frequency of satisfactory surgical anesthesia and segmental spread of analgesia were similar for etidocaine and bupivacaine. The frequency of anesthetic supplementation was greater for HS 37 due to a more restricted spread of segmental anesthesia in the sacral area. Etidocaine showed a significantly greater depth of motor paralysis than either bupivacaine or HS 37. Side effects or methemoglobinemia were not observed with any of the agents. Venous blood concentrations of etidocaine following the use of 300 mg revealed a peak plasma level of 1.51 μg/ml and a whole blood concentration of 0.82 μg/ml. The results showed HS 37 and etidocaine to be long-acting local anesthetics comparable to bupivacaine. ZUSAMMENFASSUNG Zwei neue Lokalanaesthetika, HS 37 und Etidocain, wurden bei der Epiduralanalgesie erprobt und mit Bupivacain verglichen. Einleitend wurde eine Dosis-Antwort-Studie durchgefiihrt, wobei Konzentrationen von 0,75%, 1% und 1,5% Etidocain und 0,75% und 1% HS 37 verwendet wurden. Auf Grund diaer Untersuchung wurde ein Doppelblindversuch mit 1% Etidocain, 1% HS 37 und 0,5% Bupivacain unternommen. Diese zeigte keinen Unterschied beziiglich Wirkungseintritt und Dauer der maximalen segmentalen Ausbreitung. Bupivacain wies eine signifikant langere Gesamtdauer der sensorischen Analgesie auf. Die Haufigkeit zufriedenstellender Operations-anaesthesie und die segmentale Ausbreitung der Analgesie war fur Etidocain und Bupivacaiu ahnlich. Bei HS 37 war haufiger eine Zusatzanaesthesie erforderlich, bedingt durch beschranktere Ausbreitung der Segmentalanaathesie im Sakralbereich. Bei Etidocain war die motorische Paralyse signifikant ausgepragter als bei Bupivacain oder HS 37. Nebenwirkungen oder Methaemoglobinaemie wurden mit keinem der Mittel beobachtet. Nach Anwendung von 300 mg Etidocain ergab sich eine maximale veniise Plasmakonzentration von 1,5 1 μg/ml und eine maximale Gesamtblutkonzentration im Venenblut von 0,82 μ/ml. Die Ergebnisse zeigten, das HS 37 und Etidocain lang wirkende Lokalanaesthetika sind, vergleichbar dem Bupivacain.

SUMMARY Profound hypothermia is an alternative to the heart-lung machine with oxygenator. The different perfusion techniques, their development and details are described. A total of 27 patients has been operated upon under profound hypothermia. Fourteen of these died. In three cases, the hypothermic technique itself was considered to be the cause of death. In the other cases, the cardiac defects were inoperable for anatomical reasons. With increasing experience of perfusion under both normo- and hypothermia, the indications for the use of profound hypothermia were reduced. The anaesthesia used in these cases was as light as possible with nitrous oxide and a neuromuscular blocking agent. Ventilation was adjusted, so that the patients had an acid-base balance as near to normal as possible. Moderate metabolic acidosis was found in only a few cases apart from the final stages. ZUSAMMENFASSUNG Tiefe Unterkuhlung ist eine Alternativmethode zur Herz-Lungenmaschine mit Oxygenator. Die verschiedenen Perfusionstechniken, ihre Entwicklung und Einzelheiten werden beschrieben. Insgesamt wurden 27 Patienten in tiefer Hypothermie operiert. 14 von diesen starben. In 3 Fallen musste die Unterkuhlungstechnik selbst fur den todlichen Ausgang verantwortlich gemacht werden. In den ubrigen Fallen lagen anatomisch inoperable Defekte vor. Bei zunehmender Erfahrung mit der kunstlichen Perfusion sowohl unter Normo- als auch unter Hypothermie wurden die Indikationen zur tiefen Unterkuhlung eingeschrankt. Die Narkose wurde bei diesen Fallen so oberflachlich wie moglich gehalten und bestand in der Hauptsache aus Stickoxydul und einem neuromuskularen Blocker. Die Beatmung wurde so eingestellt, dass das Saure-Basengleichgewicht so nahe wie moglich der Norm blieb. Eine massige metabolische Acidose wurde—abgesehen von den Endstadien—nur in ganz wenigen Fallen gefunden.

An analysis of local anesthesia in past, present, and future clinical practice indicates that local and regional anesthesia will regain some of its earlier importance. The first era, as you all know, was started by the introduction of cocaine as a topical anesthetic agent in ophthalmology in 1884. This was followed by the synthesis of procaine in 1905 and, later, tetracaine in 1931. The esters of para-aminobenzoic acid marked the beginning of clinical regional anesthesia, as they were less toxic than cocaine. It has been said that the second era in regional anesthesia began with the synthesis of lidocaine in 1944. Lidocaine presented a new chemical class of local anesthetic compounds — the amide derivatives of diethylaminoacetic acid. It possessed distinctive advantages over procaine in terms of its greater potency and over tetracaine because of greater penetrating properties and a larger therapeutic ratio. This made it the drug of choice for various regional anesthetic procedures. Only in subarachnoid anesthesia, where penetration does not represent a problem, where relatively small doses are required and where there is markedly reduced systemic toxicity, did the longer-acting tetracaine maintain its position.

Draper and Whitehead and their co-workers1 have described a phenomenon which they have called ‘diffusion respiration’. In experiments with dogs, they have shown that the blood under certain conditions will be normally oxygenated from the lungs without respiratory movements and without rhythmical changes of pressure in the lungs. They explain this phenomenon as follows. Owing to the affinity of oxygen for haemoglobin, the amount of oxygen removed from the alveoli during apnea exceeds the amount of carbon dioxide that simultaneously enters from the blood. The pressure within the alveoli is therefore reduced below that of the atmosphere, and a continuous inward movement of the dead-space air and the external atmosphere takes place. Essential conditions, however, for diffusion respiration are a high percentage of oxygen in the lungs and in the dead space, a free airway and an adequate circulation. During the first thirty minutes of diffusion respiration the uptake of oxygen is not reduced. After this time the oxygen consumption and the oxygen content of the blood decrease due, probably, to the Bohr effect produced by retention of carbon dioxide, with respiratory acidosis and low blood pH.