431 research outputs found

    Harvey Miller Follow Up From Wendy Edelberg

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    Hundredfold Enhancement of Light Emission via Defect Control in Monolayer Transition-Metal Dichalcogenides

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    Two dimensional (2D) transition-metal dichalcogenide (TMD) based semiconductors have generated intense recent interest due to their novel optical and electronic properties, and potential for applications. In this work, we characterize the atomic and electronic nature of intrinsic point defects found in single crystals of these materials synthesized by two different methods - chemical vapor transport and self-flux growth. Using a combination of scanning tunneling microscopy (STM) and scanning transmission electron microscopy (STEM), we show that the two major intrinsic defects in these materials are metal vacancies and chalcogen antisites. We show that by control of the synthetic conditions, we can reduce the defect concentration from above 1013/cm210^{13} /cm^2 to below 1011/cm210^{11} /cm^2. Because these point defects act as centers for non-radiative recombination of excitons, this improvement in material quality leads to a hundred-fold increase in the radiative recombination efficiency

    Magnetism in Semiconducting Molybdenum Dichalcogenides

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    Transition metal dichalcogenides (TMDs) are interesting for understanding fundamental physics of two-dimensional materials (2D) as well as for many emerging technologies, including spin electronics. Here, we report the discovery of long-range magnetic order below TM = 40 K and 100 K in bulk semiconducting TMDs 2H-MoTe2 and 2H-MoSe2, respectively, by means of muon spin-rotation (muSR), scanning tunneling microscopy (STM), as well as density functional theory (DFT) calculations. The muon spin rotation measurements show the presence of a large and homogeneous internal magnetic fields at low temperatures in both compounds indicative of long-range magnetic order. DFT calculations show that this magnetism is promoted by the presence of defects in the crystal. The STM measurements show that the vast majority of defects in these materials are metal vacancies and chalcogen-metal antisites which are randomly distributed in the lattice at the sub-percent level. DFT indicates that the antisite defects are magnetic with a magnetic moment in the range of 0.9-2.8 mu_B. Further, we find that the magnetic order stabilized in 2H-MoTe2 and 2H-MoSe2 is highly sensitive to hydrostatic pressure. These observations establish 2H-MoTe2 and 2H-MoSe2 as a new class of magnetic semiconductors and opens a path to studying the interplay of 2D physics and magnetism in these interesting semiconductors.Comment: 13 pages, 10 Figure

    High-Level Expression of Various Apolipoprotein (a) Isoforms by "Transferrinfection". The Role of Kringle IV Sequences in the Extracellular Association with Low-Density Lipoprotein

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    Characterization of the assembly of lipoprotein(a) [Lp(a)] is of fundamental importance to understanding the biosynthesis and metabolism of this atherogenic lipoprotein. Since no established cell lines exist that express Lp(a) or apolipoprotein(a) [apo(a)], a "transferrinfection" system for apo(a) was developed utilizing adenovirus receptor- and transferrin receptor-mediated DNA uptake into cells. Using this method, different apo(a) cDNA constructions of variable length, due to the presence of 3, 5, 7, 9, 15, or 18 internal kringle IV sequences, were expressed in cos-7 cells or CHO cells. All constructions contained kringle IV-36, which includes the only unpaired cysteine residue (Cys-4057) in apo(a). r-Apo(a) was synthesized as a precursor and secreted as mature apolipoprotein into the medium. When medium containing r-apo(a) with 9, 15, or 18 kringle IV repeats was mixed with normal human plasma LDL, stable complexes formed that had a bouyant density typical of Lp(a). Association was substantially decreased if Cys-4057 on r-apo(a) was replaced by Arg by site-directed mutagenesis or if Cys-4057 was chemically modified. Lack of association was also observed with r-apo(a) containing only 3, 5, or 7 kringle IV repeats without "unique kringle IV sequences", although Cys-4057 was present in all of these constructions. Synthesis and secretion of r-apo(a) was not dependent on its sialic acid content. r-Apo(a) was expressed even more efficiently in sialylation-defective CHO cells than in wild-type CHO cells. In transfected CHO cells defective in the addition of N-acetylglucosamine, apo(a) secretion was found to be decreased by 50%. Extracellular association with LDL was not affected by the carbohydrate moiety of r-apo(a), indicating a protein-protein interaction between r-apo(a) and apoB. These results show that, besides kringle IV-36, other kringle IV sequences are necessary for the extracellular association of r-apo(a) with LDL. Changes in the carbohydrate moiety of apo(a), however, do not affect complex formation

    Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome

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    Patients who have had an acute coronary syndrome are at high risk for recurrent ischemic cardiovascular events. We sought to determine whether alirocumab, a human monoclonal antibody to proprotein convertase subtilisin-kexin type 9 (PCSK9), would improve cardiovascular outcomes after an acute coronary syndrome in patients receiving high-intensity statin therapy.We conducted a multicenter, randomized, double-blind, placebo-controlled trial involving 18,924 patients who had an acute coronary syndrome 1 to 12 months earlier, had a low-density lipoprotein (LDL) cholesterol level of at least 70 mg per deciliter (1.8 mmol per liter), a non-high-density lipoprotein cholesterol level of at least 100 mg per deciliter (2.6 mmol per liter), or an apolipoprotein B level of at least 80 mg per deciliter, and were receiving statin therapy at a high-intensity dose or at the maximum tolerated dose. Patients were randomly assigned to receive alirocumab subcutaneously at a dose of 75 mg (9462 patients) or matching placebo (9462 patients) every 2 weeks. The dose of alirocumab was adjusted under blinded conditions to target an LDL cholesterol level of 25 to 50 mg per deciliter (0.6 to 1.3 mmol per liter). The primary end point was a composite of death from coronary heart disease, nonfatal myocardial infarction, fatal or nonfatal ischemic stroke, or unstable angina requiring hospitalization.The median duration of follow-up was 2.8 years. A composite primary end-point event occurred in 903 patients (9.5%) in the alirocumab group and in 1052 patients (11.1%) in the placebo group (hazard ratio, 0.85; 95% confidence interval [CI], 0.78 to 0.93; P<0.001). A total of 334 patients (3.5%) in the alirocumab group and 392 patients (4.1%) in the placebo group died (hazard ratio, 0.85; 95% CI, 0.73 to 0.98). The absolute benefit of alirocumab with respect to the composite primary end point was greater among patients who had a baseline LDL cholesterol level of 100 mg or more per deciliter than among patients who had a lower baseline level. The incidence of adverse events was similar in the two groups, with the exception of local injection-site reactions (3.8% in the alirocumab group vs. 2.1% in the placebo group).Among patients who had a previous acute coronary syndrome and who were receiving high-intensity statin therapy, the risk of recurrent ischemic cardiovascular events was lower among those who received alirocumab than among those who received placebo. (Funded by Sanofi and Regeneron Pharmaceuticals; ODYSSEY OUTCOMES ClinicalTrials.gov number, NCT01663402 .)

    FCIC memo of staff interview with Institute for International Economics (IIE)

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    Additional IIE staff were also present during this interview

    Effects of alirocumab on types of myocardial infarction: insights from the ODYSSEY OUTCOMES trial

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    AIMS: The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin-kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (>/=1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI. METHODS AND RESULTS: Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77-0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77-0.99; P = 0.032) and Type 2 (0.77, 0.61-0.97; P = 0.025), but not Type 4 MI. CONCLUSION: After ACS, alirocumab added to intensive statin therapy favourably impacted on Type 1 and 2 MIs. The data indicate for the first time that a lipid-lowering therapy can attenuate the risk of Type 2 MI. Low-density lipoprotein cholesterol reduction below levels achievable with statins is an effective preventive strategy for both MI types

    Alirocumab Reduces Total Nonfatal Cardiovascular and Fatal Events : The ODYSSEY OUTCOMES Trial

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    The ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) trial compared alirocumab with placebo, added to high-intensity or maximum-tolerated statin treatment, after acute coronary syndrome (ACS) in 18,924 patients. Alirocumab reduced the first occurrence of the primary composite endpoint and was associated with fewer all-cause deaths. This pre-specified analysis determined the extent to which alirocumab reduced total (first and subsequent) nonfatal cardiovascular events and all-cause deaths in ODYSSEY OUTCOMES. Hazard functions for total nonfatal cardiovascular events (myocardial infarction, stroke, ischemia-driven coronary revascularization, and hospitalization for unstable angina or heart failure) and death were jointly estimated, linked by a shared frailty accounting for patient risk heterogeneity and correlated within-patient nonfatal events. An association parameter also quantified the strength of the linkage between risk of nonfatal events and death. The model provides accurate relative estimates of nonfatal event risk if nonfatal events are associated with increased risk for death. With 3,064 first and 5,425 total events, 190 fewer first and 385 fewer total nonfatal cardiovascular events or deaths were observed with alirocumab compared with placebo. Alirocumab reduced total nonfatal cardiovascular events (hazard ratio: 0.87; 95% confidence interval: 0.82 to 0.93) and death (hazard ratio: 0.83; 95% confidence interval: 0.71 to 0.97) in the presence of a strong association between nonfatal and fatal event risk. In patients with ACS, the total number of nonfatal cardiovascular events and deaths prevented with alirocumab was twice the number of first events prevented. Consequently, total event reduction is a more comprehensive metric to capture the totality of alirocumab clinical efficacy after ACS

    Impacts of selected stimulation patterns on the perception threshold in electrocutaneous stimulation

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    <p>Abstract</p> <p>Background</p> <p>Consistency is one of the most important concerns to convey stable artificially induced sensory feedback. However, the constancy of perceived sensations cannot be guaranteed, as the artificially evoked sensation is a function of the interaction of stimulation parameters. The hypothesis of this study is that the selected stimulation parameters in multi-electrode cutaneous stimulation have significant impacts on the perception threshold.</p> <p>Methods</p> <p>The investigated parameters included the stimulated location, the number of active electrodes, the number of pulses, and the interleaved time between a pair of electrodes. Biphasic, rectangular pulses were applied via five surface electrodes placed on the forearm of 12 healthy subjects.</p> <p>Results</p> <p>Our main findings were: 1) the perception thresholds at the five stimulated locations were significantly different (p < 0.0001), 2) dual-channel simultaneous stimulation lowered the perception thresholds and led to smaller variance in perception thresholds compared to single-channel stimulation, 3) the perception threshold was inversely related to the number of pulses, and 4) the perception threshold increased with increasing interleaved time when the interleaved time between two electrodes was below 500 μs.</p> <p>Conclusions</p> <p>To maintain a consistent perception threshold, our findings indicate that dual-channel simultaneous stimulation with at least five pulses should be used, and that the interleaved time between two electrodes should be longer than 500 μs. We believe that these findings have implications for design of reliable sensory feedback codes.</p

    Effects of Picture Size Reduction and Blurring on Emotional Engagement

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    The activity of basic motivational systems is reflected in emotional responses to arousing stimuli, such as natural pictures. The manipulation of picture properties such as size or detail allows for investigation into the extent to which separate emotional reactions are similarly modulated by perceptual changes, or, rather, may subserve different functions. Pursuing this line of research, the present study examined the effects of two types of perceptual degradation, namely picture size reduction and blurring, on emotional responses. Both manipulations reduced picture relevance and dampened affective modulation of skin conductance, possibly because of a reduced action preparation in response to degraded or remote pictures. However, the affective modulation of the startle reflex did not vary with picture degradation, suggesting that the identification of these degraded affective cues activated the neural circuits mediating appetitive or defensive motivation
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