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1.
Rev Sci Instrum ; 93(1): 013702, 2022 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-35104957

RESUMEN

Multi-tip scanning tunneling microscopy (STM) is a powerful method to perform charge transport measurements at the nanoscale. With four STM tips positioned on the surface of a sample, four-point resistance measurements can be performed in dedicated geometric configurations. Here, we present an alternative to the most often used scanning electron microscope imaging to infer the corresponding tip positions. After the initial coarse positioning is monitored by an optical microscope, STM scanning itself is used to determine the inter-tip distances. A large STM overview scan serves as a reference map. Recognition of the same topographic features in the reference map and in small scale images with the individual tips allows us to identify the tip positions with an accuracy of about 20 nm for a typical tip spacing of ∼1µm. In order to correct for effects such as the non-linearity of the deflection, creep, and hysteresis of the piezoelectric elements of the STM, a careful calibration has to be performed.

2.
Rev Sci Instrum ; 92(6): 063701, 2021 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-34243501

RESUMEN

We present the design and performance of an ultra-high vacuum scanning tunneling microscope (STM) that uses adiabatic demagnetization of electron magnetic moments for controlling its operating temperature ranging between 30 mK and 1 K with an accuracy of up to 7 µK rms. At the same time, high magnetic fields of up to 8 T can be applied perpendicular to the sample surface. The time available for STM experiments at 50 mK is longer than 20 h, at 100 mK about 40 h. The single-shot adiabatic demagnetization refrigerator can be regenerated automatically within 7 h while keeping the STM temperature below 5 K. The whole setup is located in a vibrationally isolated, electromagnetically shielded laboratory with no mechanical pumping lines penetrating its isolation walls. The 1 K pot of the adiabatic demagnetization refrigeration cryostat can be operated silently for more than 20 days in a single-shot mode using a custom-built high-capacity cryopump. A high degree of vibrational decoupling together with the use of a specially designed minimalistic STM head provides outstanding mechanical stability, demonstrated by the tunneling current noise, STM imaging, and scanning tunneling spectroscopy measurements, all performed on an atomically clean Al(100) surface.

3.
Sci Rep ; 10(1): 2816, 2020 Feb 18.
Artículo en Inglés | MEDLINE | ID: mdl-32071388

RESUMEN

One of the hallmarks of topological insulators (TIs), the intrinsic spin polarisation in the topologically protected surface states, is investigated at room temperature in-situ by means of four-probe scanning tunnelling microscopy (STM) for a BiSbTe3 thin film. To achieve the required precision of tip positions for measuring a spin signal, a precise positioning method employing STM scans of the local topography with each individual tip is demonstrated. From the transport measurements, the spin polarisation in the topological surface states (TSS) is estimated as p ~ 0.3 - 0.6, which is close to the theoretical limit.

4.
Sci Rep ; 9(1): 2476, 2019 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-30792428

RESUMEN

The electrical properties of SrTiO3(100) single crystals were investigated in-situ at different stages of thermal reduction by means of a 4-tip STM. Using the tips of the STM as electrical probes, distance-dependent four-point measurements were performed at the surface of the crystal at room temperature after reduction by thermal treatment. For annealing temperatures T ≤ 700 °C, charge transport is confined to a surface region <3 µm below the surface. For reduction at T ≥ 900 °C a transition from a conducting 2D sheet with insulating bulk to a system with dominant 3D bulk conductivity is found. At an intermediate reduction temperature of T = 800 °C, a regime with mixed 2D/3D contributions is observed in the distance-dependent resistance measurements. Describing the depth-dependent conductivity with an analytical N-layer model, this regime of mixed 2D/3D conductivity is evaluated quantitatively under the assumption of an exponentially decaying conductivity profile, correlated with the previously observed depth-dependent dislocation density in the sample. A non-monotonous temperature dependence of the 3D conductivity in the respective conducting layer is found and possible underlying mechanisms are discussed, particularly with regard to non-intrinsic material properties depending on details of the sample preparation.

5.
J Phys Condens Matter ; 31(7): 074004, 2019 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-30524116

RESUMEN

The charge transport through GaAs nanowires, partially p-doped and partially intrinsic, is analyzed by four-point resistance profiling along freestanding nanowires using a multip-STM. The charge transport channel in the undoped segment is assigned to the surface conductivity, while the interior of the nanowire is the conductance channel in the p-doped segment. The convoluted interplay between conduction through the interior of the nanowire and surface state conduction is studied in detail. Measurements of the I-V curves along the nanowires provide the experimental basis for the proposed charge transport model for the transition of the conduction from the interior to the surface of the nanowire. A voltage drop along the surface state conduction channel leads to an upward shift of the band edges at the surface. This results, for higher applied voltages, in the removal of the depletion layer and an opening of a conductance channel between the interior of the nanowire and the surface states.

6.
Rev Sci Instrum ; 89(10): 101101, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-30399776

RESUMEN

In scanning tunneling microscopy, we witness in recent years a paradigm shift from "just imaging" to detailed spectroscopic measurements at the nanoscale and multi-tip scanning tunneling microscope (STM) is a technique following this trend. It is capable of performing nanoscale charge transport measurements like a "multimeter at the nanoscale." Distance-dependent four-point measurements, the acquisition of nanoscale potential maps at current carrying nanostructures and surfaces, as well as the acquisition of I - V curves of nanoelectronic devices are examples of the capabilities of the multi-tip STM technique. In this review, we focus on two aspects: How to perform the multi-tip STM measurements and how to analyze the acquired data in order to gain insight into nanoscale charge transport processes for a variety of samples. We further discuss specifics of the electronics for multi-tip STM and the properties of tips for multi-tip STM, and present methods for a tip approach to nanostructures on insulating substrates. We introduce methods on how to extract the conductivity/resistivity for mixed 2D/3D systems from four-point measurements, how to measure the conductivity of 2D sheets, and how to introduce scanning tunneling potentiometry measurements with a multi-tip setup. For the example of multi-tip measurements at freestanding vapor liquid solid grown nanowires, we discuss contact resistances as well as the influence of the presence of the probing tips on the four point measurements.

8.
J Phys Condens Matter ; 30(5): 054004, 2018 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-29260731

RESUMEN

We present a four-point probe resistance measurement technique which uses four equivalent current measuring units, resulting in minimal hardware requirements and corresponding sources of noise. Local sample potentials are measured by a software feedback loop which adjusts the corresponding tip voltage such that no current flows to the sample. The resulting tip voltage is then equivalent to the sample potential at the tip position. We implement this measurement method into a multi-tip scanning tunneling microscope setup such that potentials can also be measured in tunneling contact, allowing in principle truly non-invasive four-probe measurements. The resulting measurement capabilities are demonstrated for [Formula: see text] and [Formula: see text] samples.

10.
Cardiology ; 138(4): 249-253, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28898876

RESUMEN

BACKGROUND: The US Food and Drug Administration Adverse Event Reporting System (FAERS) is a global passive surveillance database that relies on voluntary reporting by health care professionals and consumers as well as required mandatory reporting by pharmaceutical manufacturers. However, the initial filers and comparative patterns for oral P2Y12 platelet inhibitor reporting are unknown. We assessed who generated original FAERS reports for clopidogrel, prasugrel, and ticagrelor in 2015. METHODS: From the FAERS database we extracted and examined adverse event cases coreported with oral P2Y12 platelet inhibitors. All adverse event filing originating sources were dichotomized into consumers, lawyers, pharmacists, physicians, other health care professionals, and unknown. RESULTS: Overall, 2015 annual adverse events were more commonly coreported with clopidogrel (n = 13,234) with known source filers (n = 12,818, or 96.9%) than with prasugrel (2,896; 98.9% out of 2,927 cases) or ticagrelor (2,163, or 82.3%, out of 2,627 cases, respectively). Overall, most adverse events were filed by consumers (8,336, or 44.4%), followed by physicians (5,290, or 28.2%), other health care professionals (2,997, or 16.0%), pharmacists (1,125, or 6.0%), and finally by lawyers (129, or 0.7%). The origin of 811 (4.7%) initial reports remains unknown. The adverse event filing sources differ among drugs. While adverse events coreported with clopidogrel and prasugrel were commonly originated by patients (40.4 and 84.3%, respectively), most frequently ticagrelor reports (42.5%) were filed by physicians. CONCLUSION: The reporting quality and initial sources differ among oral P2Y12 platelet inhibitors in FAERS. The ticagrelor surveillance in 2015 was inadequate when compared to clopidogrel and prasugrel. Patients filed most adverse events for clopidogrel and prasugrel, while physicians originated most ticagrelor complaints. These differences justify stricter compliance control for ticagrelor manufacturers and may be attributed to the confusion of treating physicians with unexpected fatal, cardiac, and thrombotic adverse events linked to ticagrelor.


Asunto(s)
Sistemas de Registro de Reacción Adversa a Medicamentos , Bases de Datos Factuales/estadística & datos numéricos , Archivo/estadística & datos numéricos , Antagonistas del Receptor Purinérgico P2Y/efectos adversos , Adenosina/efectos adversos , Adenosina/análogos & derivados , Clopidogrel , Humanos , Seguridad del Paciente , Clorhidrato de Prasugrel/efectos adversos , Ticagrelor , Ticlopidina/efectos adversos , Ticlopidina/análogos & derivados , Estados Unidos , United States Food and Drug Administration
11.
Open Heart ; 4(2): e000629, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28761683

RESUMEN

OBJECTIVE: The comparative crude death rates (CDR) among non-vitamin K antagonist oral anticoagulants (NOACs) are unknown. Further, whether NOACs improve survival when compared with warfarin is also unclear. We compared CDR co-reported for four NOACs combined or separately versus warfarin within the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database. METHODS: We selected CDR from the FAERS database linked to four NOACs and warfarin. The primary endpoints were differences in proportional reporting ratios (PRRs), and Chi-Square (χ2)for dabigatran, rivaroxaban, apixaban and edoxaban when compared with warfarin. RESULTS: The FAERS database contains significantly less death reports associated with all NOACs combined (14 917 out of 128 267 reports (11.63%); PRR=1.089; χ2=70.0; p=6.05e-17) than for warfarin (19 493 out of 153 911 reports (12.67%)). The numbers for rivaroxaban (6318 out of 64 512 reports or (9.79%); PRR=1.293; χ2=359.4; p=3.72e-80), apixaban (1693 out of 17 789 reports (9.52%); PRR=1.331; χ2=145.8; p=1.43e-33) and edoxaban (53 out of 755 reports (7.02%); PRR=1.804; χ2=21.18; p=4.18e-06) were favourable as compared with warfarin, while the numbers of fatalities co-reported with dabigatran (6989 out of 46 250 reports (15.11%); PRR=0.838; χ2=185.2; p=3.61e-42) were higher than for warfarin. CONCLUSION: Overall, based on these CDR, NOACs appear to be associated with a mortality benefit over warfarin. Among NOACs, we observed remarkably similar for factor Xa inhibitors (rivaroxiban, apixaban and edoxaban) but unfavourable signal for the direct thrombin inhibitor (dabigatran). However, these data are clearly not sufficient to change the prescription patterns.

12.
Nat Commun ; 8: 15704, 2017 06 12.
Artículo en Inglés | MEDLINE | ID: mdl-28604672

RESUMEN

Three-dimensional topological insulators host surface states with linear dispersion, which manifest as a Dirac cone. Nanoscale transport measurements provide direct access to the transport properties of the Dirac cone in real space and allow the detailed investigation of charge carrier scattering. Here we use scanning tunnelling potentiometry to analyse the resistance of different kinds of defects at the surface of a (Bi0.53Sb0.47)2Te3 topological insulator thin film. We find the largest localized voltage drop to be located at domain boundaries in the topological insulator film, with a resistivity about four times higher than that of a step edge. Furthermore, we resolve resistivity dipoles located around nanoscale voids in the sample surface. The influence of such defects on the resistance of the topological surface state is analysed by means of a resistor network model. The effect resulting from the voids is found to be small compared with the other defects.

13.
Rev Sci Instrum ; 88(2): 023703, 2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-28249528

RESUMEN

The construction and the vibrational performance of a low vibration laboratory for microscopy applications comprising a 100 ton floating foundation supported by passive pneumatic isolators (air springs), which rest themselves on a 200 ton solid base plate, are discussed. The optimization of the air spring system leads to a vibration level on the floating floor below that induced by an acceleration of 10 ng for most frequencies. Additional acoustic and electromagnetic isolation is accomplished by a room-in-room concept.

16.
Thromb Haemost ; 114(6): 1104-12, 2015 Nov 25.
Artículo en Inglés | MEDLINE | ID: mdl-26559427

RESUMEN

The role of anticoagulants and antiplatelet agents in tumour growth and prognosis is not new, and currently under intense investigation. Some randomised data strongly suggest that this association exists, but it is complex, and not necessarily pointed at the same direction. The potential mechanisms responsible for such harmful association include a direct hazard of novel antithrombotics on cancer, indirect promotion of tumour growth, easier metastatic dissemination due to instability of platelet-tumour cell aggregates, or/and inability to keep cancer cells locally in situ are considered. The latest randomised evidence ultimately rejected the drug-specific cancer risks, clearly indicating the class-effect. In lay terms "cancers follow bleeding", which seems to be true for antithrombotic agents in general. Significant excess of solid cancers which was similar after prasugrel in TRITON, and with vorapaxar in TRACER trials was confirmed by the FDA reviews. Later, extra cancer deaths reported following clopidogrel and prasugrel in DAPT, and after ticagrelor in PEGASUS are also of concern. However, there are remaining controversies with regard to published cancer risks after ticagrelor (PLATO), or another vorapaxar trial (TRA2P), while full disclosure of separate clopidogrel and prasugrel cancer data in DAPT is still lacking. In short, if we apply moderate antiplatelet strategies for over two years, or aggressive regimens including triple therapy for much less than one year, the solid cancer risks emerge. Currently, more delicate platelet inhibition, and shorter exposure to dual oral antiplatelet agents should prevail.


Asunto(s)
Neoplasias/inducido químicamente , Inhibidores de Agregación Plaquetaria/efectos adversos , Adenosina/administración & dosificación , Adenosina/efectos adversos , Adenosina/análogos & derivados , Animales , Anticarcinógenos/farmacología , Anticarcinógenos/uso terapéutico , Aspirina/farmacología , Aspirina/uso terapéutico , Plaquetas/fisiología , Pruebas de Carcinogenicidad , Clopidogrel , Neoplasias del Colon/prevención & control , Quimioterapia Combinada , Femenino , Humanos , Lactonas/administración & dosificación , Lactonas/efectos adversos , Masculino , Ratones , Estudios Multicéntricos como Asunto , Metástasis de la Neoplasia , Neoplasias/epidemiología , Neoplasias Experimentales/inducido químicamente , Células Neoplásicas Circulantes , Inhibidores de Agregación Plaquetaria/farmacología , Inhibidores de Agregación Plaquetaria/uso terapéutico , Clorhidrato de Prasugrel/administración & dosificación , Clorhidrato de Prasugrel/efectos adversos , Piridinas/administración & dosificación , Piridinas/efectos adversos , Ensayos Clínicos Controlados Aleatorios como Asunto , Rivaroxabán/administración & dosificación , Rivaroxabán/efectos adversos , Factores Sexuales , Especificidad de la Especie , Ticagrelor , Ticlopidina/administración & dosificación , Ticlopidina/efectos adversos , Ticlopidina/análogos & derivados , Factores de Tiempo
17.
Phys Rev Lett ; 115(6): 066801, 2015 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-26296126

RESUMEN

Four-point measurements using a multitip scanning tunneling microscope are carried out in order to determine surface and step conductivities on Si(111) surfaces. In a first step, distance-dependent four-point measurements in the linear configuration are used in combination with an analytical three-layer model for charge transport to disentangle the 2D surface conductivity from nonsurface contributions. A termination of the Si(111) surface with either Bi or H results in the two limiting cases of a pure 2D or 3D conductance, respectively. In order to further disentangle the surface conductivity of the step-free surface from the contribution due to atomic steps, a square four-probe configuration is applied as a function of the rotation angle. In total, this combined approach leads to an atomic step conductivity of σ(step)=(29±9) Ω(-1) m(-1) and to a step-free surface conductivity of σ(surf)=(9±2)×10(-6) Ω(-1)/□ for the Si(111)-(7×7) surface.

18.
Int J Cardiol ; 195: 104-10, 2015 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-26043353

RESUMEN

BACKGROUND: ST-elevated myocardial infarction (STEMI) holds the highest early mortality among patients with acute coronary syndromes. Despite numerous claims of clinical benefits and superiority over clopidogrel, there are no head-to-head outcome randomized clinical trials (RCTs) directly comparing novel antithrombotic agents in STEMI. Moreover, since most regulatory approvals are based on a single RCT's results, their meta-analyses are rare to compare death rates. We analyzed the 30-day mortality in STEMI patients who underwent percutaneous coronary intervention (PCI) and were treated with antithrombotic agents compared to clopidogrel as a reference. METHODS AND RESULTS: Altogether, 10 RCT's and 1 retrospective study with a total number of 26,658 STEMI patients were included. Random-effects model with Mantel-Heanszel weighting was used to pool outcomes into a meta-analysis. Therapy with clopidogrel was associated with 2.76% 30-day STEMI mortality which was similar to that of ticagrelor (2.6%; OR=0.9395 [CI=0.76 to 1.17; p=0.58]), and for bivalirudin (2.8%; OR=1.02 [CI=0.82 to 1.27; p=0.86]), but was slightly higher for heparin (3.0%; OR=1.08 [CI=0.86 to 1.35; p=0.52]). There was a trend towards lower mortality after tirofiban (2.1%; OR=0.77 [CI=0.52 to 1.13; p=0.20]), and cangrelor (1.7%; OR=0.59 [CI=0.29 to 1.20; p=0.19]), although the sample size for both agents was woefully small. The only agent which offers a significant 30-day mortality benefit in STEMI was prasugrel with significant lowest 1.75% death rate (OR=0.63 [CI=0.46 to 0.86; p=0.03]). CONCLUSIONS: Among antithrombotic agents, prasugrel, but not ticagrelor, offers significant 30-day mortality benefit over clopidogrel in PCI-treated STEMI patients justifying short-term use in such a high-risk population.


Asunto(s)
Adenosina/análogos & derivados , Infarto del Miocardio/tratamiento farmacológico , Clorhidrato de Prasugrel/farmacología , Ticlopidina/análogos & derivados , Adenosina/farmacología , Clopidogrel , Electrocardiografía/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/mortalidad , Infarto del Miocardio/cirugía , Evaluación de Resultado en la Atención de Salud , Intervención Coronaria Percutánea/métodos , Inhibidores de Agregación Plaquetaria/farmacología , Ensayos Clínicos Controlados Aleatorios como Asunto , Análisis de Supervivencia , Ticagrelor , Ticlopidina/farmacología
19.
Cardiology ; 132(2): 74-80, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26111880

RESUMEN

BACKGROUND: The landmark Dual Antiplatelet Therapy (DAPT) trial revealed an impressive reduction of stent thrombosis and myocardial infarction after prolonged 30-month DAPT compared to the conventional 12-month regimen. However, aside from the expected extra bleeding risks, more cancers and noncardiovascular deaths (NCVD) were observed in the 30-month DAPT arm. OBJECTIVE: We aimed to comprehend the totality of DAPT trial evidence in the light of the FDA medical review. RESULTS: A significant excess of solid cancers that was picked up after prasugrel treatment in the TRITON trial (Prasugrel versus Clopidogrel in Patients with Acute Coronary Syndromes) and later observed with vorapaxar treatment in the TRACER trial (Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome) has now been confirmed by the FDA DAPT review for 30-month therapy with prasugrel [hazard ratio (HR) 1.3] and clopidogrel (HR 1.2). The latest randomized evidence with antiplatelet agents rejected the drug-specific cancer risks, clearly indicating the class effect. The NCVD risks were elevated after treatment with both thienopyridines, but were more prominent after clopidogrel treatment (HR 1.91) than prasugrel treatment (HR 1.17). About half of the NCVD were considered to be caused by cancers occurring after the 24 months of extended antiplatelet therapy. Impression: The DAPT trial confirmed that long-term antiplatelet therapy is associated with cancer that contributes to NCVD. Based on the full disclosure of cancer data by the DAPT study, it can be reflected that the optimal duration of antiplatelet therapy with thienopyridines should be limited to no more than 2 years. This duration allows the preservation of most vascular benefits while avoiding additional cancers and NCVD. © 2015 S. Karger AG, Basel.

20.
Thromb Haemost ; 114(1): 7-8, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25947272

RESUMEN

The recently published Administration of Ticagrelor in the Cath Lab or in the Ambulance for New ST Elevation Myocardial Infarction to Open the Coronary Artery (ATLANTIC) trial concluded that prehospital administration of ticagrelor in patients with acute STEMI appeared to be safe but did not improve pre-PCI coronary reperfusion. The ATLANTIC data fully support the PLATO Angiographic Substudy denying early benefit of ticagrelor, and correspond well with lack of immediate clinical benefit including the early PCI "death paradox" in PLATO-USA patients. Finally, there were significantly (p=0.043) more deaths in early ticagrelor ATLANTIC arm (odds ratio 3.18 (1.02-9.90) challenging stent thrombosis reduction. Indeed, ATLANTIC represents an important step for our better understanding of ticagrelor, although the confirmation of the PLATO mortality wonder in an adequately powered PEGASUS (TIMI-54) to be reported in 2015 will be vital for ticagrelor future.


Asunto(s)
Adenosina/análogos & derivados , Ensayos Clínicos como Asunto , Servicios Médicos de Urgencia , Infarto del Miocardio/tratamiento farmacológico , Intervención Coronaria Percutánea , Inhibidores de Agregación Plaquetaria/administración & dosificación , Adenosina/administración & dosificación , Adenosina/efectos adversos , Esquema de Medicación , Humanos , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/mortalidad , Oportunidad Relativa , Intervención Coronaria Percutánea/efectos adversos , Inhibidores de Agregación Plaquetaria/efectos adversos , Medición de Riesgo , Factores de Riesgo , Ticagrelor , Factores de Tiempo , Resultado del Tratamiento
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