Strain-induced high-temperature perovskite ferromagnetic insulator.

Ferromagnetic insulators are required for many new magnetic devices, such as dissipationless quantum-spintronic devices, magnetic tunneling junctions, etc. Ferromagnetic insulators with a high Curie temperature and a high-symmetry structure are critical integration with common single-crystalline oxide films or substrates. So far, the commonly used ferromagnetic insulators mostly possess low-symmetry structures associated with a poor growth quality and widespread properties. The few known high-symmetry materials either have extremely low Curie temperatures (≤16 K), or require chemical doping of an otherwise antiferromagnetic matrix. Here we present compelling evidence that the LaCoO3 single-crystalline thin film under tensile strain is a rare undoped perovskite ferromagnetic insulator with a remarkably high TC of up to 90 K. Both experiments and first-principles calculations demonstrate tensile-strain-induced ferromagnetism which does not exist in bulk LaCoO3 The ferromagnetism is strongest within a nearly stoichiometric structure, disappearing when the Co2+ defect concentration reaches about 10%. Significant impact of the research includes demonstration of a strain-induced high-temperature ferromagnetic insulator, successful elevation of the transition over the liquid-nitrogen temperature, and high potential for integration into large-area device fabrication processes.

Two-Dimensional Nanoparticle Cluster Formation in Supercritical Fluid CO2.

Supercritical fluid carbon dioxide (sc-CO2) is capable of depositing nanoparticles in small structures of silicon substrates because of its gas-like penetration, liquid-like solvation abilities, and near-zero surface tension. In nanometer-sized shallow wells on silicon surface, formation of two-dimensional (2D) monolayer metal nanoparticle (NP) clusters can be achieved using the sc-CO2 deposition method. Nanoparticles tend to fill nanostructured holes first, and then, if sufficient nanoparticles are available, they will continue to cover the flat areas nearby, unless defects or other surface imperfections are available. In addition, SEM images of two-dimensional gold (Au) nanoparticle clusters formed on a flat silicon surface with two to a dozen or more of the nanoparticles are provided to illustrate the patterns of nanoparticle cluster formation in sc-CO2.

A phase 2 randomized multicenter study of 2 extended dosing schedules of oral ezatiostat in low to intermediate-1 risk myelodysplastic syndrome.

BACKGROUND: Ezatiostat is a glutathione analog prodrug glutathione S-transferase P1-1 (GSTP1-1) inhibitor. This study evaluated 2 extended dose schedules of oral ezatiostat in 89 heavily pretreated patients with low to intermediate-1 risk myelodysplastic syndrome (MDS). METHODS: Patients were randomized by 1 stratification factor-baseline cytopenia (anemia only vs anemia with additional cytopenias)-to 1 of 2 extended dosing schedules. Multilineage hematologic improvement (HI) responses were assessed by International Working Group 2006 criteria. RESULTS: Overall, 11 of 38 (29%) red blood cell (RBC) transfusion-dependent patients had HI-Erythroid (HI-E) response. The median duration of HI-E response was 34 weeks. Multilineage responses were observed. There was 1 cytogenetic complete response in a del (5q) MDS patient. An important trend was the effect of prior therapy on response. A 40% HI-E rate (6 of 15 patients) was observed in patients who had prior lenalidomide and no prior hypomethylating agents (HMAs), with 5 of 11 (45%) patients achieving significant RBC transfusion reduction and 3 of 11 (27%) achieving transfusion independence. A 28% HI-E rate (5 of 18 patients) was observed in patients who were both lenalidomide and HMA naive, with 4 of 8 (50%) patients achieving clinically significant RBC transfusion reductions. Most common ezatiostat-related adverse events were grade 1 and 2 gastrointestinal including: nausea (45%, 17%), diarrhea (26%, 7%), and vomiting (30%, 12%). CONCLUSIONS: Ezatiostat is the first GSTP1-1 inhibitor shown to cause clinically significant and sustained reduction in RBC transfusions, transfusion independence, and multilineage responses in MDS patients. The tolerability and activity profile of ezatiostat may offer a new treatment option for patients with MDS.

Supercritical fluid deposition of uniform PbS nanoparticle films for energy-transfer studies.

Using supercritical fluid CO(2) (Sc-CO(2)) as a medium, PbS nanoparticles can be uniformly deposited on surfaces of various substrates. Sc-CO(2) deposition of PbS nanoparticles on carbon-coated copper grids, into small holes in silicon, and formation of uniform PbS nanoparticle films on glass are described. Fluorescence spectra of PbS nanoparticles obtained from the films prepared by the Sc-CO(2) method indicate effective energy transfer between PbS nanoparticles of different sizes.

Free-standing arrays of isolated TiO2 nanotubes through supercritical fluid drying.

A common complication in fabricating arrays of TiO(2) nanotubes is that they agglomerate into tightly packed bundles during the inevitable solvent evaporation step. This problem is particularly acute for template-fabricated TiO(2) nanotubes, as the geometric tunability of this technique enables relatively large inter-pore spacings or, from another perspective, more space for lateral displacement. Our work showed that agglomeration results from the surface tension forces that are present as the ambient solvent is evaporated from the nanotube film. Herein, we report a processing and fabrication approach that utilizes supercritical fluid drying (CO(2)) to prepare arrays of template-fabricated TiO(2) nanotubes that are free-standing and spatially isolated. This approach could be beneficial to many emerging technologies, such as solid-state dye-sensitized solar cells and vertically-oriented carbon nanotube electrodes.

Phase 1 multicenter dose-escalation study of ezatiostat hydrochloride (TLK199 tablets), a novel glutathione analog prodrug, in patients with myelodysplastic syndrome.

Phase 1 testing of ezatiostat, a glutathione S-transferase P1-1 inhibitor, for the treatment of myelodysplastic syndrome was conducted in a multidose-escalation study. Patients received 10 dose levels (200, 400, 1000, 1400, 2000, 2400, 3000, 4000, 5000, and 6000 mg) of ezatiostat tablets in divided doses on days 1 to 7 of a 21-day cycle for a maximum of 8 cycles. The safety and pharmacokinetics of ezatiostat were evaluated. Forty-five patients with low to intermediate-2 International Prognostic Scoring System risk myelodysplastic syndrome were enrolled. No dose-limiting toxicities were observed. The most common grade 1 or 2, respectively, treatment-related adverse events were nonhematologic: nausea (56%, 9%), diarrhea (36%, 7%), vomiting (24%, 7%), abdominal pain (9%, 0%), constipation (4%, 9%), anorexia (3%, 7%), and dyspepsia (3%, 7%). Concentration of the primary active metabolite, TLK236, increased proportionate to ezatiostat dosage. Seventeen hematologic improvement (HI) responses by International Working Group criteria were observed at dose levels of 200 to 6000 mg/day with 11 HI responses at doses of 4000 to 6000 mg/day. HI responses occurred in all lineages including 3 bilineage and 1 complete cytogenetic response. Decreased number of red blood cell and platelet transfusions and in some cases transfusion independence were attained. Extended dose schedules of ezatiostat tablets are under investigation.

Mid-wavelength infrared avalanche photodetector with AlAsSb/GaSb superlattice.

In this work, a mid-wavelength infrared separate absorption and multiplication avalanche photodiode (SAM-APD) with 100% cut-off wavelength of ~ 5.0 µm at 200 K grown by molecular beam epitaxy was demonstrated. The InAsSb-based SAM-APD device was designed to have electron dominated avalanche mechanism via the band structure engineered multi-quantum well structure based on AlAsSb/GaSb H-structure superlattice and InAsSb material in the multiplication region. The device exhibits a maximum multiplication gain of 29 at 200 K under -14.7 bias voltage. The maximum multiplication gain value for the MWIR SAM-APD increases from 29 at 200 K to 121 at 150 K. The electron and hole impact ionization coefficients were derived and the large difference between their value was observed. The carrier ionization ratio for the MWIR SAM-APD device was calculated to be ~ 0.097 at 200 K.

Depositing ordered arrays of metal sulfide nanoparticles in nanostructures using supercritical fluid carbon dioxide.

Silver sulfide and cadmium sulfide nanoparticles of controllable sizes are synthesized using a water-in-hexane microemulsion method and stabilized by dodecanethiol. The stabilized metal sulfide nanoparticles can be deposited homogenously on flat substrates forming ordered 2-D arrays in supercritical fluid carbon dioxide (Sc-CO(2)). The use of Sc-CO(2) leaves the particles unaffected by dewetting effects caused by traditional solvents and produces uniform arrays. The Sc-CO(2) deposition technique is capable of filling nanoparticles in nanostructures of silicon wafers which is difficult to accomplish by conventional solvent evaporation methods.

Randomized phase III study of canfosfamide in combination with pegylated liposomal doxorubicin compared with pegylated liposomal doxorubicin alone in platinum-resistant ovarian cancer.

OBJECTIVE: To evaluate the safety and efficacy of canfosfamide in combination with pegylated liposomal doxorubicin (PLD) in platinum-resistant ovarian cancer (OC). METHODS: Patients with platinum-refractory or -resistant (primary or secondary) OC were randomized to receive canfosfamide at 1000 mg/m² and PLD at 50 mg/m² intravenously or PLD alone at 50 mg/m2 intravenously on day 1 every 28 days until tumor progression or unacceptable toxicity. The primary end point was progression-free survival (PFS). Other end points were objective response rate and safety. The study was originally planned for 244 patients. The trial was temporarily placed on hold after 125 patients were randomized while the results of another trial were being reviewed and the sponsor decided not to resume enrollment. The interim analysis became the final analysis. RESULTS: The median PFS was 5.6 months for canfosfamide + PLD (n = 65) versus 3.7 months for PLD (n = 60) (hazards ratio, 0.92; P = 0.7243). A preplanned subgroup analysis showed that 75 patients with platinum-refractory or primary platinum-resistant OC had a median PFS of 5.6 months for canfosfamide + PLD versus 2.9 months for PLD (hazards ratio, 0.55; P = 0.0425). Hematologic adverse events were 66% on the canfosfamide + PLD arm versus 44% on the PLD arm, manageable with dose reductions. Nonhematologic adverse events were similar for both arms. The incidence of palmar-plantar erythrodysesthesia and stomatitiswas lower on canfosfamide + PLD(23%, 31%, respectively) versus (39%, 49%, respectively) on PLD. CONCLUSIONS: Overall median PFS showed a positive trend but was not statistically significant. The median PFS in the platinum-refractory and primary platinum-resistant OC patients was significantly longer for canfosfamide + PLD versus PLD. Canfosfamide may ameliorate the palmar-plantar erythrodysesthesia and stomatitis known to be associated with PLD. Further study of this active well-tolerated regimen in platinum-refractory and primary platinum-resistant OC is planned. This study was registered at www.clinicaltrials.gov: NCT00350948.

Acoustically actuated ultra-compact NEMS magnetoelectric antennas.

State-of-the-art compact antennas rely on electromagnetic wave resonance, which leads to antenna sizes that are comparable to the electromagnetic wavelength. As a result, antennas typically have a size greater than one-tenth of the wavelength, and further miniaturization of antennas has been an open challenge for decades. Here we report on acoustically actuated nanomechanical magnetoelectric (ME) antennas with a suspended ferromagnetic/piezoelectric thin-film heterostructure. These ME antennas receive and transmit electromagnetic waves through the ME effect at their acoustic resonance frequencies. The bulk acoustic waves in ME antennas stimulate magnetization oscillations of the ferromagnetic thin film, which results in the radiation of electromagnetic waves. Vice versa, these antennas sense the magnetic fields of electromagnetic waves, giving a piezoelectric voltage output. The ME antennas (with sizes as small as one-thousandth of a wavelength) demonstrates 1-2 orders of magnitude miniaturization over state-of-the-art compact antennas without performance degradation. These ME antennas have potential implications for portable wireless communication systems.The miniaturization of antennas beyond a wavelength is limited by designs which rely on electromagnetic resonances. Here, Nan et al. have developed acoustically actuated antennas that couple the acoustic resonance of the antenna with the electromagnetic wave, reducing the antenna footprint by up to 100.

Non-Volatile Ferroelectric Switching of Ferromagnetic Resonance in NiFe/PLZT Multiferroic Thin Film Heterostructures.

Magnetoelectric effect, arising from the interfacial coupling between magnetic and electrical order parameters, has recently emerged as a robust means to electrically manipulate the magnetic properties in multiferroic heterostructures. Challenge remains as finding an energy efficient way to modify the distinct magnetic states in a reliable, reversible, and non-volatile manner. Here we report ferroelectric switching of ferromagnetic resonance in multiferroic bilayers consisting of ultrathin ferromagnetic NiFe and ferroelectric Pb0.92La0.08Zr0.52Ti0.48O3 (PLZT) films, where the magnetic anisotropy of NiFe can be electrically modified by low voltages. Ferromagnetic resonance measurements confirm that the interfacial charge-mediated magnetoelectric effect is dominant in NiFe/PLZT heterostructures. Non-volatile modification of ferromagnetic resonance field is demonstrated by applying voltage pulses. The ferroelectric switching of magnetic anisotropy exhibits extensive applications in energy-efficient electronic devices such as magnetoelectric random access memories, magnetic field sensors, and tunable radio frequency (RF)/microwave devices.

Phase 1 study of TLK286 (Telcyta) administered weekly in advanced malignancies.

PURPOSE: To determine the dose-limiting toxicities, maximum tolerated dose, and pharmacokinetics of TLK286, a novel cancer prodrug, administered weekly. PATIENTS AND METHODS: Patients with advanced malignancies were treated with TLK286 administered weekly by i.v. infusion over 30 min in escalating doses 60-960 mg/m(2). A treatment cycle was defined as 3 weekly treatments. Patients underwent tumor assessments on day 43, and those patients receiving clinical benefit continued on treatment until disease progression or unacceptable toxicity. Safety was assessed by the WHO criteria. RESULTS: Thirty-seven patients received 111 cycles of TLK286 at eight dose levels (median, 3 cycles; range, 1-16 cycles). In this study, TLK286 given weekly at 960 mg/m(2) was well tolerated without dose-limiting toxicities. TLK286-related toxicities included grade 1-2 nausea and vomiting, fatigue and anemia. Nine of 31 evaluable patients continued therapy beyond day 43 and received a median of 5 cycles (range of 3-16 cycles) and experienced durable stable disease or minor tumor regression. Pharmacokinetic characteristics of TLK286 are described by an optimized two-compartment model. Mild to moderate renal or hepatic organ dysfunction did not impact the elimination of TLK286. CONCLUSIONS: TLK286 administered weekly at doses up to 960 mg/m(2) were well tolerated. The safety and antitumor activity observed in a broad range of cancer types supports Phase 2 disease-specific investigations of TLK286 given weekly at 960 mg/m(2).

Phase I study of TLK286 (glutathione S-transferase P1-1 activated glutathione analogue) in advanced refractory solid malignancies.

PURPOSE: The purpose of this study was to determine the dose-limiting toxicities (DLTs), the maximum tolerated dose, and the pharmacokinetics of the novel glutathione analog TLK286 administered by i.v. infusion. EXPERIMENTAL DESIGN: Patients with advanced malignancies received i.v. TLK286 administered as a 30-min constant rate infusion once every 3 weeks in escalating doses from 60 to 1280 mg/m(2). Patients underwent tumor assessment on day 43 and continued on treatment until disease progression or unacceptable toxicity. RESULTS: A total of 35 patients were treated with 109 cycles of TLK286. At 1280 mg/m(2), 3 of 5 patients developed one of two observed dose limiting toxicities (DLTs). The DLTs were: mild pancreatitis (1 of 5) and bladder symptoms (2 of 5) consisting of hematuria, dysuria, and urinary frequency. All of the patients with DLTs continued on TLK286 treatment at 960 mg/m(2) (one dose below maximum tolerated dose) without recurrence of DLTs. DLTs were transient, resolved without sequelae, and noncumulative. TLK286-related toxicities included grade 1-2 nausea, vomiting, fatigue, transient microscopic hematuria, and anemia. Of 31 evaluable patients, 10 patients continued therapy (median six cycles; range, four to nine cycles). Pharmacokinetic studies of TLK286 on cycle 1 revealed a mean elimination half-life of 18 min (95% confidence interval, 16.1-19.9). Dose-proportional increases in both maximum blood concentrations and area under the blood-concentration-time curve were observed over the dose range of 60-960 mg/m(2). CONCLUSION: TLK286 was well tolerated in this study. TLK286 safety and pharmacokinetics support disease-specific evaluations of TLK286 at doses <1280 mg/m(2) administered once every three weeks in the treatment of patients with advanced malignancies.

Interfacial charge-mediated non-volatile magnetoelectric coupling in Co0.3Fe0.7/Ba0.6Sr0.4TiO3/Nb:SrTiO3 multiferroic heterostructures.

The central challenge in realizing non-volatile, E-field manipulation of magnetism lies in finding an energy efficient means to switch between the distinct magnetic states in a stable and reversible manner. In this work, we demonstrate using electrical polarization-induced charge screening to change the ground state of magnetic ordering in order to non-volatilely tune magnetic properties in ultra-thin Co0.3Fe0.7/Ba0.6Sr0.4TiO3/Nb:SrTiO3 (001) multiferroic heterostructures. A robust, voltage-induced, non-volatile manipulation of out-of-plane magnetic anisotropy up to 40 Oe is demonstrated and confirmed by ferromagnetic resonance measurements. This discovery provides a framework for realizing charge-sensitive order parameter tuning in ultra-thin multiferroic heterostructures, demonstrating great potential for delivering compact, lightweight, reconfigurable, and energy-efficient electronic devices.

Probing electric field control of magnetism using ferromagnetic resonance.

Exchange coupled CoFe/BiFeO3 thin-film heterostructures show great promise for power-efficient electric field-induced 180° magnetization switching. However, the coupling mechanism and precise qualification of the exchange coupling in CoFe/BiFeO3 heterostructures have been elusive. Here we show direct evidence for electric field control of the magnetic state in exchange coupled CoFe/BiFeO3 through electric field-dependent ferromagnetic resonance spectroscopy and nanoscale spatially resolved magnetic imaging. Scanning electron microscopy with polarization analysis images reveal the coupling of the magnetization in the CoFe layer to the canted moment in the BiFeO3 layer. Electric field-dependent ferromagnetic resonance measurements quantify the exchange coupling strength and reveal that the CoFe magnetization is directly and reversibly modulated by the applied electric field through a ~180° switching of the canted moment in BiFeO3. This constitutes an important step towards robust repeatable and non-volatile voltage-induced 180° magnetization switching in thin-film multiferroic heterostructures and tunable RF/microwave devices.

Increased NO-mediated and reduced TxA2-dependent responses in skeletal muscle arterioles in pregnancy.

The contribution of skeletal muscle microvessels to pregnancy-induced decrease in peripheral vascular resistance and its underlying mechanisms are not fully understood. We aimed to test the hypothesis that pregnancy enhances arteriolar dilation and reduces constriction by increasing NO-mediation and decreasing reactivity to TxA2. Thus, changes in diameter of isolated, pressurized gracilis muscle arterioles (d: approximately 180 microm) of non-pregnant (NP) and pregnant (P) rabbits to vasoactive agents were measured by videomicroscopy. Acetylcholine (ACh) elicited significantly greater dilations in P than in NP arterioles that could be inhibited by L-NAME, a NO synthase blocker. Dilations to the NO donor SNP did not differ between P and NP arterioles. Constrictions to norepinephrine and the TxA2 receptor agonist U46619 were significantly attenuated in P as compared to NP arterioles. L-NAME increased norepinephrine-induced arteriolar constrictions eliminating the difference between responses of NP and P arterioles. L-NAME enhanced constrictions to U46619 in P and NP arterioles, but the constrictions were still greater in NP vessels. The number of vascular TxA2 receptors-characterized by the TxA2 analog [125I]-BOP in aortic membrane preparations-was significantly less in P as compared to NP rabbits (NP: 284 +/- 83, P: 62 +/- 14 fmol/mg protein, p<0.01). Thus, pregnancy up-regulates endothelial NO- and down regulates TxA2-mediation of responses of skeletal muscle arterioles. These changes in the local regulation of microvascular tone are likely to favor a dilated state of skeletal muscle arterioles, which may contribute to the decreased peripheral vascular resistance during normal pregnancy.

Quantification of strain and charge co-mediated magnetoelectric coupling on ultra-thin Permalloy/PMN-PT interface.

Strain and charge co-mediated magnetoelectric coupling are expected in ultra-thin ferromagnetic/ferroelectric multiferroic heterostructures, which could lead to significantly enhanced magnetoelectric coupling. It is however challenging to observe the combined strain charge mediated magnetoelectric coupling, and difficult in quantitatively distinguish these two magnetoelectric coupling mechanisms. We demonstrated in this work, the quantification of the coexistence of strain and surface charge mediated magnetoelectric coupling on ultra-thin Ni0.79Fe0.21/PMN-PT interface by using a Ni0.79Fe0.21/Cu/PMN-PT heterostructure with only strain-mediated magnetoelectric coupling as a control. The NiFe/PMN-PT heterostructure exhibited a high voltage induced effective magnetic field change of 375 Oe enhanced by the surface charge at the PMN-PT interface. Without the enhancement of the charge-mediated magnetoelectric effect by inserting a Cu layer at the PMN-PT interface, the electric field modification of effective magnetic field was 202 Oe. By distinguishing the magnetoelectric coupling mechanisms, a pure surface charge modification of magnetism shows a strong correlation to polarization of PMN-PT. A non-volatile effective magnetic field change of 104 Oe was observed at zero electric field originates from the different remnant polarization state of PMN-PT. The strain and charge co-mediated magnetoelectric coupling in ultra-thin magnetic/ferroelectric heterostructures could lead to power efficient and non-volatile magnetoelectric devices with enhanced magnetoelectric coupling.

Collaborative hospital orientation: simulation as a teaching strategy.

For nurses, the stress caused by entering a new place of employment may give rise to insecurity and a lack of confidence. Lack of confidence in one's nursing skills can affect performance and, ultimately, patient care and safety. In healthcare, growing fiscal constraints have resulted in lost resources, and support for new nursing staff is limited by both time and cost considerations. Clinical educators therefore must find innovative ways to provide education and support, including creative learning modalities that facilitate nurses' transition into a new role and work environment.