Longueur de diffusion de spin et magnétisme de structures nanotubes de carbone / matériaux ferromagnétiques

The aim of this thesis work is to study the spin-dependent transport in multiwalled carbon nanotubes (MWNT). To do so, the electrical resistance of MWNT contacted between ferromagnetic electrodes has been measured, as a function of the contacts magnetic configuration and temperature. An original sample fabrication process to contact MWNT has been developed. The MWNT growth is achieved via chemical vapour deposition in the pores of an alumina template, with electrodeposited nickel or cobalt nanowires as catalyst. The pores are 1,5 µm, in length, and 40 nm in diameter. The second electrical contact is sputter deposited or evaporated over the membrane surface. This geometry allows us to contact MWNT between ferromagnetic electrodes, which magnetisation states versus the applied magnetic field are known. Furthermore, the electrical current flows perpendicularly to the plane of the contacts layers. Finally, it enables us to tune the length of the MWNT between the electrodes. The features of the measured spin-dependent magnetoresistance (SD-MR) signals cannot be correctly interpreted with common tunnel or giant magnetoresistance approaches. Every MWNT which is less than 300 nm long between nickel contacts destroys the spin polarisation of the current. MWNT longer than 300 nm featured spin-dependent magnetoresistance signals, with a small amplitude and depending on the direction of the current. One 500 nm long MWNT between cobalt contacts shows 25% SD-MR signals at 2,5 K, at zero applied current. This signal is caused by a thermopower effect, and not by a spin polarised current. Another signal, from a 700 nm long between cobalt contacts is more similar to usual signals shown by magnetic tunnel junctions. In order to understand spin-dependent transport in MWNT, it is therefore necessary to determine first the electrical transport mechanisms, independent of the spin. Nowadays, it is still poorly understood. Therefore, besides spin-dependent transport measurements, we measured the conductance versus the temperature and the bias voltage. At temperatures below 50 K, the conductance diminishes as the temperature and the bias voltage decrease. This effect, called Zero-Bias Anomaly (ZBA), is a consequence of disorder and electron-electron interactions in our systems. 46 samples out of 113 have shown power law scaling laws of the ZBA. From these scaling-laws, we get the power law coefficient α. Such scaling laws have been observed many times for carbon nanotubes. However, none of these studies has such a large spectra for the values of α as we have : for our samples, α ranges between 0 and 1,7. With samples contacted via cobalt cobalt electrodes, α is usually larger than nickel contacted samples. Therefore, a single parameter α enables us to describe and characterise the electrical transport in our samples. The large number of measured samples allows us to correlate this coefficient α with other experimental parameters, such as the MWNT length, or the metallic or structural nature of the contact electrodes. We also have established the linear relation : ln G0 ~ A · α, with G0 the extrapolated conductance at 1 K. To our knowledge, this relation has not yet been predicted nor observed. The physical interpretation of this relation is interpreted in the Coulomb blockade formalism. Finally, a link between the weak localisation amplitude et the value of α has been displayed. In this case, the weak localisation amplitude not only depends on α, but also on the metallic nature of the electrodes

CdTe semiconductor nanowires and NiFe ferro-magnetic metal nanowires electrodeposited into cylindrical nano-pores on the surface of anodized aluminum

Cylindrical nano-pores of an anodized aluminum oxide layer on the surface of bulk aluminum were used as templates for the electrochemical growth of semiconductor and magnetic nanowires. The electrodeposition of CdTe and NiFe was investigated to determine the optimum conditions for each nanowire growth over a wide range of cathode potentials. The desired composition of Cd50Te50 and Ni80Fe20 was achieved by controlling the cathode potential during electrodeposition. Temperature dependences of resistance for CdTe nanowires confirmed the semiconductor character with amorphous behavior at low temperature, while those of NiFe nanowires showed metallic character. The anisotropic magnetoresistance (AMR) of NiFe nanowires reached 1.9% at 300

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

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

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.For complete list of authors see http://dx.doi.org/10.1093/eurheartj/ehz299</p

Effect of alirocumab on mortality after acute coronary syndromes. An analysis of the ODYSSEY OUTCOMES randomized clinical trial

Background: Previous trials of PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitors demonstrated reductions in major adverse cardiovascular events, but not death. We assessed the effects of alirocumab on death after index acute coronary syndrome. Methods: ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was a double-blind, randomized comparison of alirocumab or placebo in 18 924 patients who had an ACS 1 to 12 months previously and elevated atherogenic lipoproteins despite intensive statin therapy. Alirocumab dose was blindly titrated to target achieved low-density lipoprotein cholesterol (LDL-C) between 25 and 50 mg/dL. We examined the effects of treatment on all-cause death and its components, cardiovascular and noncardiovascular death, with log-rank testing. Joint semiparametric models tested associations between nonfatal cardiovascular events and cardiovascular or noncardiovascular death. Results: Median follow-up was 2.8 years. Death occurred in 334 (3.5%) and 392 (4.1%) patients, respectively, in the alirocumab and placebo groups (hazard ratio [HR], 0.85; 95% CI, 0.73 to 0.98; P=0.03, nominal P value). This resulted from nonsignificantly fewer cardiovascular (240 [2.5%] vs 271 [2.9%]; HR, 0.88; 95% CI, 0.74 to 1.05; P=0.15) and noncardiovascular (94 [1.0%] vs 121 [1.3%]; HR, 0.77; 95% CI, 0.59 to 1.01; P=0.06) deaths with alirocumab. In a prespecified analysis of 8242 patients eligible for ≥3 years follow-up, alirocumab reduced death (HR, 0.78; 95% CI, 0.65 to 0.94; P=0.01). Patients with nonfatal cardiovascular events were at increased risk for cardiovascular and noncardiovascular deaths (P<0.0001 for the associations). Alirocumab reduced total nonfatal cardiovascular events (P<0.001) and thereby may have attenuated the number of cardiovascular and noncardiovascular deaths. A post hoc analysis found that, compared to patients with lower LDL-C, patients with baseline LDL-C ≥100 mg/dL (2.59 mmol/L) had a greater absolute risk of death and a larger mortality benefit from alirocumab (HR, 0.71; 95% CI, 0.56 to 0.90; Pinteraction=0.007). In the alirocumab group, all-cause death declined wit h achieved LDL-C at 4 months of treatment, to a level of approximately 30 mg/dL (adjusted P=0.017 for linear trend). Conclusions: Alirocumab added to intensive statin therapy has the potential to reduce death after acute coronary syndrome, particularly if treatment is maintained for ≥3 years, if baseline LDL-C is ≥100 mg/dL, or if achieved LDL-C is low. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01663402

Rational Design of PDZ Domain Inhibitors: Discovery of Small Organic Compounds Targeting PDZ Domains

International audiencePDZ domains, which belong to protein–protein interaction networks, are critical for regulating important biological processes such as scaffolding, trafficking, and signaling cascades. Interfering with PDZ-mediated interactions could affect these numerous biological processes. Thus, PDZ domains have emerged as promising targets to decipher biological phenomena and potentially treat cancer and neurological diseases. In this minireview, we focus on the discovery and design of small molecule inhibitors to modulate PDZ domains. These compounds interfere with endogenous protein partners from the PDZ domain by binding at the protein–protein interface. While peptides or peptidomimetic ligands were described to modulate PDZ domains, the focus of this review is on small organic compounds

Chemistry-driven Hit-to-lead Optimization Guided by Structure-based Approaches

International audienc

CdTe semiconductor nanowires and NiFe ferro-magnetic metal nanowires electrodeposited into cylindrical nano-pores on the surface of anodized aluminum

Cylindrical nano-pores of an anodized aluminum oxide layer on the surface of bulk aluminum were used as templates for the electrochemical growth of semiconductor and magnetic nanowires. The electrodeposition of CdTe and NiFe was investigated to determine the optimum conditions for each nanowire growth over a wide range of cathode potentials. The desired composition of Cd50Te50 and Ni80Fe20 was achieved by controlling the cathode potential during electrodeposition. Temperature dependences of resistance for CdTe nanowires confirmed the semiconductor character with amorphous behavior at low temperature, while those of NiFe nanowires showed metallic character. The anisotropic magnetoresistance (AMR) of NiFe nanowires reached 1.9% at 300 K