48 research outputs found
Time Domain Mapping of Spin Torque Oscillator Effective Energy
Stochastic dynamics of spin torque oscillators (STOs) can be described in
terms of magnetization drift and diffusion over a current-dependent effective
energy surface given by the Fokker-Planck equation. Here we present a method
that directly probes this effective energy surface via time-resolved
measurements of the microwave voltage generated by a STO. We show that the
effective energy approach provides a simple recipe for predicting spectral line
widths and line shapes near the generation threshold. Our time domain technique
also accurately measures the field-like component of spin torque in a wide
range of the voltage bias values.Comment: 5 pages, 3 figures. Supplement included: 7 pages, 6 figure
Characterizing the transition from diffuse atomic to dense molecular clouds in the Magellanic clouds with [CII], [CI], and CO
We present and analyze deep Herschel/HIFI observations of the [CII] 158um,
[CI] 609um, and [CI] 370um lines towards 54 lines-of-sight (LOS) in the Large
and Small Magellanic clouds. These observations are used to determine the
physical conditions of the line--emitting gas, which we use to study the
transition from atomic to molecular gas and from C^+ to C^0 to CO in their low
metallicity environments. We trace gas with molecular fractions in the range
0.1<f(H2)<1, between those in the diffuse H2 gas detected by UV absorption
(f(H2)<0.2) and well shielded regions in which hydrogen is essentially
completely molecular. The C^0 and CO column densities are only measurable in
regions with molecular fractions f(H2)>0.45 in both the LMC and SMC. Ionized
carbon is the dominant gas-phase form of this element that is associated with
molecular gas, with C^0 and CO representing a small fraction, implying that
most (89% in the LMC and 77% in the SMC) of the molecular gas in our sample is
CO-dark H2. The mean X_CO conversion factors in our LMC and SMC sample are
larger than the value typically found in the Milky Way. When applying a
correction based on the filling factor of the CO emission, we find that the
values of X_CO in the LMC and SMC are closer to that in the Milky Way. The
observed [CII] intensity in our sample represents about 1% of the total
far-infrared intensity from the LOSs observed in both Magellanic Clouds.Comment: 32 pages, 21 figures, Accepted to Ap
Nucleofection: A New Method for Cutaneous Gene Transfer?
Background. Transfection efficacy after nonviral gene transfer in primary epithelial cells is limited. The aim of this study was to compare transfection efficacy of the recently available method of nucleofection with the established transfection reagent FuGENE6. Methods. Primary human keratinocytes (HKC), primary human fibroblasts (HFB), and a human keratinocyte cell line (HaCaT) were transfected with reporter gene construct by FuGENE6 or Amaxa Nucleofector device. At corresponding time points, β-galactosidase expression, cell proliferation (MTT-Test), transduction efficiency (X-gal staining), cell morphology, and cytotoxicity (CASY) were determined. Results. Transgene expression after nucleofection was significantly higher in HKC and HFB and detected earlier (3 h vs. 24 h) than in FuGENE6. After lipofection 80%–90% of the cells remained proliferative without any influence on cell morphology. In contrast, nucleofection led to a decrease in keratinocyte cell size, with only 20%–42% proliferative cells. Conclusion. Related to the method-dependent increase of cytotoxicity, transgene expression after nucleofection was earlier and higher than after lipofection
Ultralow-current-density and bias-field-free spin-transfer nano-oscillator
The spin-transfer nano-oscillator (STNO) offers the possibility of using the
transfer of spin angular momentum via spin-polarized currents to generate
microwave signals. However, at present STNO microwave emission mainly relies on
both large drive currents and external magnetic fields. These issues hinder the
implementation of STNOs for practical applications in terms of power
dissipation and size. Here, we report microwave measurements on STNOs built
with MgO-based magnetic tunnel junctions having a planar polarizer and a
perpendicular free layer, where microwave emission with large output power,
excited at ultralow current densities, and in the absence of any bias magnetic
fields is observed. The measured critical current density is over one order of
magnitude smaller than previously reported. These results suggest the
possibility of improved integration of STNOs with complementary
metal-oxide-semiconductor technology, and could represent a new route for the
development of the next-generation of on-chip oscillators.Comment: 18 pages, 4 figure
Voltage-Induced Ferromagnetic Resonance in Magnetic Tunnel Junctions
We demonstrate excitation of ferromagnetic resonance in CoFeB/MgO/CoFeB
magnetic tunnel junctions (MTJs) by the combined action of voltage-controlled
magnetic anisotropy (VCMA) and spin transfer torque (ST). Our measurements
reveal that GHz-frequency VCMA torque and ST in low-resistance MTJs have
similar magnitudes, and thus that both torques are equally important for
understanding high-frequency voltage-driven magnetization dynamics in MTJs. As
an example, we show that VCMA can increase the sensitivity of an MTJ-based
microwave signal detector to the sensitivity level of semiconductor Schottky
diodes.Comment: 5 pages; supplementary material adde
Effect of natalizumab on disease progression in secondary progressive multiple sclerosis (ASCEND). a phase 3, randomised, double-blind, placebo-controlled trial with an open-label extension
Background: Although several disease-modifying treatments are available for relapsing multiple sclerosis, treatment effects have been more modest in progressive multiple sclerosis and have been observed particularly in actively relapsing subgroups or those with lesion activity on imaging. We sought to assess whether natalizumab slows disease progression in secondary progressive multiple sclerosis, independent of relapses. Methods: ASCEND was a phase 3, randomised, double-blind, placebo-controlled trial (part 1) with an optional 2 year open-label extension (part 2). Enrolled patients aged 18–58 years were natalizumab-naive and had secondary progressive multiple sclerosis for 2 years or more, disability progression unrelated to relapses in the previous year, and Expanded Disability Status Scale (EDSS) scores of 3·0–6·5. In part 1, patients from 163 sites in 17 countries were randomly assigned (1:1) to receive 300 mg intravenous natalizumab or placebo every 4 weeks for 2 years. Patients were stratified by site and by EDSS score (3·0–5·5 vs 6·0–6·5). Patients completing part 1 could enrol in part 2, in which all patients received natalizumab every 4 weeks until the end of the study. Throughout both parts, patients and staff were masked to the treatment received in part 1. The primary outcome in part 1 was the proportion of patients with sustained disability progression, assessed by one or more of three measures: the EDSS, Timed 25-Foot Walk (T25FW), and 9-Hole Peg Test (9HPT). The primary outcome in part 2 was the incidence of adverse events and serious adverse events. Efficacy and safety analyses were done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01416181. Findings: Between Sept 13, 2011, and July 16, 2015, 889 patients were randomly assigned (n=440 to the natalizumab group, n=449 to the placebo group). In part 1, 195 (44%) of 439 natalizumab-treated patients and 214 (48%) of 448 placebo-treated patients had confirmed disability progression (odds ratio [OR] 0·86; 95% CI 0·66–1·13; p=0·287). No treatment effect was observed on the EDSS (OR 1·06, 95% CI 0·74–1·53; nominal p=0·753) or the T25FW (0·98, 0·74–1·30; nominal p=0·914) components of the primary outcome. However, natalizumab treatment reduced 9HPT progression (OR 0·56, 95% CI 0·40–0·80; nominal p=0·001). In part 1, 100 (22%) placebo-treated and 90 (20%) natalizumab-treated patients had serious adverse events. In part 2, 291 natalizumab-continuing patients and 274 natalizumab-naive patients received natalizumab (median follow-up 160 weeks [range 108–221]). Serious adverse events occurred in 39 (13%) patients continuing natalizumab and in 24 (9%) patients initiating natalizumab. Two deaths occurred in part 1, neither of which was considered related to study treatment. No progressive multifocal leukoencephalopathy occurred. Interpretation: Natalizumab treatment for secondary progressive multiple sclerosis did not reduce progression on the primary multicomponent disability endpoint in part 1, but it did reduce progression on its upper-limb component. Longer-term trials are needed to assess whether treatment of secondary progressive multiple sclerosis might produce benefits on additional disability components. Funding: Biogen
Expression and clinical significance of Glucose Regulated Proteins GRP78 (BiP) and GRP94 (GP96) in human adenocarcinomas of the esophagus
<p>Abstract</p> <p>Background</p> <p>Glucose regulated proteins (GRPs) are main regulators of cellular homeostasis due to their role as molecular chaperones. Moreover, the functions of GRPs suggest that they also may play important roles in cancer biology. In this study we investigated the glucose regulated proteins GRP78 (BiP) and GRP94 (GP96) in a series of human esophageal adenocarcinomas to determine their implications in cancer progression and prognosis.</p> <p>Methods</p> <p>Formalin-fixed, paraffin-embedded tissues of primary resected esophageal (Barrett) adenocarcinomas (n = 137) and corresponding normal tissue were investigated. mRNA-gene expression levels of GRP78 and GRP94 were determined by quantitative real-time RT-PCR after mRNA extraction. Protein expression analysis was performed with immunohistochemical staining of the cases, assembled on a tissue micorarray. The results were correlated with pathologic features (pT, pN, G) and overall survival.</p> <p>Results</p> <p>GRP78 and GRP94 mRNA were expressed in all tumors. The relative gene expression of GRP78 was significantly higher in early cancers (pT1m and pT1sm) as compared to more advanced stages (pT2 and pT3) and normal tissue (p = 0.031). Highly differentiated tumors showed also higher GRP78 mRNA levels compared to moderate and low differentiated tumors (p = 0.035). In addition, patients with higher GRP78 levels tended to show a survival benefit (p = 0.07). GRP94 mRNA-levels showed no association to pathological features or clinical outcome.</p> <p>GRP78 and GRP94 protein expression was detectable by immunohistochemistry in all tumors. There was a significant correlation between a strong GRP78 protein expression and early tumor stages (pT1m and pT1sm, p = 0.038). For GRP94 low to moderate protein expression was significantly associated with earlier tumor stage (p = 0.001) and less lymph node involvement (p = 0.036). Interestingly, the patients with combined strong GRP78 and GRP94 protein expression exclusively showed either early (pT1m or pT1sm) or advanced (pT3) tumor stages and no pT2 stage (p = 0.031).</p> <p>Conclusion</p> <p>We could demonstrate an association of GRP78 and GRP94 mRNA and protein expression with tumor stage and behaviour in esophageal adenocarcinomas. Increased expression of GRP78 may be responsible for controlling local tumor growth in early tumor stages, while high expression of GRP78 and GRP94 in advanced stages may be dependent from other factors like cellular stress reactions due to glucose deprivation, hypoxia or the hosts' immune response.</p
Present and Future of Surface-Enhanced Raman Scattering.
The discovery of the enhancement of Raman scattering by molecules adsorbed on nanostructured metal surfaces is a landmark in the history of spectroscopic and analytical techniques. Significant experimental and theoretical effort has been directed toward understanding the surface-enhanced Raman scattering (SERS) effect and demonstrating its potential in various types of ultrasensitive sensing applications in a wide variety of fields. In the 45 years since its discovery, SERS has blossomed into a rich area of research and technology, but additional efforts are still needed before it can be routinely used analytically and in commercial products. In this Review, prominent authors from around the world joined together to summarize the state of the art in understanding and using SERS and to predict what can be expected in the near future in terms of research, applications, and technological development. This Review is dedicated to SERS pioneer and our coauthor, the late Prof. Richard Van Duyne, whom we lost during the preparation of this article