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Exploitation of X-ray circular polarized beams to study forbidden Bragg reflections and new information that could be obtained in these experiments are discussed. It is shown that the intensities of such reflections can be different for the right- and left-circular polarizations (i.e. exhibiting circular dichroism) even for the dipole-dipole resonant transitions involved in the scattering process. This difference can be observed only in crystals having no center of inversion. Here, this approach is used to study helicity-dependent resonant diffraction in copper metaborate CuB2O4 single crystal, which is non-centrosymmetric but achiral. Nonetheless, a strong circular dichroism has been observed for hh0 forbidden reflections in the vicinity of the Cu K-edge. This effect is shown to originate from dipolar transitions in Cu atoms occupying the 8(d) Wyckoff position only.
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Background: Endovascular venous stenting with dedicated venous stents for the treatment of chronic venous outflow obstruction is developing as efficacious alternative to conservative therapy or open surgery. However, so far, mid- and long-term evidence on effectiveness and safety is poor. Patients and methods: The prospective, single-center, observational study enrolled consecutive patients with chronic non-thrombotic iliac vein lesions (NIVL) or post-thrombotic iliofemoral obstructions (PTO). From February 2016 to April 2017, patients underwent implantation of open cell, self-expandable dedicated venous stents. Short-term symptomatic improvement, patency, and complication rate were favorable. Evaluation at 2-years included improvement in the revised venous clinical severity score (rVCSS), patency, stent migration, major target limb events, clinically important pulmonary embolism, major bleeding, and all-cause mortality. Results: A total of 79 patients (57 ± 16 years, 44 female) were evaluated. At 2 years, rVCCS improved by 4.3 ± 2.7 (p < 0.001). Substantial clinical improvement of ≥ 2 score points was achieved in 86.4% (38 of 44) of patients. Improvement was not associated with thrombotic pathogenesis (regression coefficient [B] with PTO = 0.6 [95%CI: -1.1 to 2.3], p = 0.48). At 2 years, all ulcers (in 8 of 79 patients) were healed and none recurred. Two-year primary patency was 95.5% (95%CI: 86.5 to 98.5) with no difference between NIVL- and PTO-patients (log-rank p = 0.83). Target vessel revascularization was conducted in two PTO- and one NIVL-patients in the period of 34 days to 156 days from index procedure, resulting in a secondary patency of 100%. No stent migration, target limb deep vein thrombosis, major amputation, pulmonary embolism, or death occurred. Conclusions: Venovo venous open cell self-expanding stent implantation for chronic outflow obstruction was efficacious and provided a sufficient level of safety throughout 2 years.
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Procedimientos Endovasculares/métodos , Vena Ilíaca/cirugía , Síndrome de May-Thurner/cirugía , Stents , Adulto , Anciano , Enfermedad Crónica , Femenino , Alemania , Humanos , Vena Ilíaca/diagnóstico por imagen , Síndrome de May-Thurner/diagnóstico por imagen , Persona de Mediana Edad , Estudios Prospectivos , Sistema de Registros , Resultado del Tratamiento , Grado de Desobstrucción VascularRESUMEN
The magnitude of the orbital magnetic moment and its role as a trigger of the Verwey transition in the prototypical Mott insulator, magnetite, remain contentious. Using 1s2p resonant inelastic x-ray scattering angle distribution (RIXS-AD), we prove the existence of noncollinear orbital magnetic ordering and infer the presence of dynamical distortion creating a polaronic precursor for the metal to insulator transition. These conclusions are based on a subtle angular shift of the RIXS-AD spectral intensity as a function of the magnetic field orientation. Theoretical simulations show that these results are only consistent with noncollinear magnetic orbital ordering. To further support these claims we perform Fe K-edge x-ray magnetic circular dichroism in order to quantify the Fe average orbital magnetic moment.
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Magnetic materials are usually classified into a distinct category such as diamagnets, paramagnets or ferromagnets. The enormous progress in materials science allows one nowadays, however, to change the magnetic nature of an element in a material. Gold, in bulk form, is traditionally a diamagnet. But in a ferromagnetic environment, it can adopt an induced ferromagnetic moment. Moreover, the growth of gold under certain conditions may lead to a spontaneous ferromagnetic or paramagnetic response. Here, we report on paramagnetic gold in a highly disordered Au-Ni-O alloy and focus on the unusual magnetic response. Such materials are mainly considered for plasmonic applications. Thin films containing Au, Ni and NiO are fabricated by co-deposition of Ni and Au in a medium vacuum of 2 × 10-2 mbar. As a result, Au is in a fully disordered state forming in some cases isolated nanocrystallites of up to 4 nm in diameter as revealed by high resolution transmission electron microscopy. The disorder and the environment, which is rich in oxygen, lead to remarkable magnetic properties of Au: an induced ferromagnetic and a paramagnetic state. This can be proven by measuring the x-ray magnetic circular dichroism. Our experiments show a way to establish and monitor Au paramagnetism in alloys.
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This is a report on the early years of combinatorial materials science and technology. High-throughput technologies (HTTs) are found in life- and materials-science laboratories. Although HTTs have long been the standard in life sciences in academia as well as in industry, HTTs in materials science have become the standard in industry but not in academia. In life science, successful drugs developed with HTTs have been reported, but there is no information on successful materials developed with HTTs that have made it to the market. Some initial development of HTTs in materials science is summarized, especially early applications of artificial intelligence. This outlook attempts to summarize the development of combinatorial materials sciences from the early years to today.
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Ensayos Analíticos de Alto Rendimiento , Ciencia de los Materiales , Catálisis , Evaluación Preclínica de Medicamentos/historia , Evaluación Preclínica de Medicamentos/métodos , Evaluación Preclínica de Medicamentos/normas , Ensayos Analíticos de Alto Rendimiento/historia , Ensayos Analíticos de Alto Rendimiento/métodos , Ensayos Analíticos de Alto Rendimiento/normas , Historia del Siglo XX , Historia del Siglo XXI , Industrias/historia , Industrias/métodos , Ciencia de los Materiales/historia , Ciencia de los Materiales/métodos , Ciencia de los Materiales/normasRESUMEN
Background: We sought to determine the patency and clinical symptom relief following the usage of the sinus-Obliquus venous stent in the endovascular treatment of venous obstruction of the ilio-femoral track in short-term. Patients and methods: 48 patients (62 % female, mean age 57 years) with chronic unilateral post-thrombotic obstruction (PTO) and non-thrombotic iliac vein obstructive lesions (NIVL) without involvement of inferior vena cava receiving a sinus-Obliquus venous stent was included in the analysis. Clinical improvement determined by the revised venous clinical severity score (rVCSS) as well as the clinical, etiologic, anatomic and pathophysiologic score (CEAP), safety, and stent patency rates were determined at baseline and at 1, 6 and 12 months after stent placement. Ten of the 48 included patients had a venous ulceration. Results: Primary patency rates were 98 % at FU1, 94 % at FU2 and 94 % at FU3, respectively. Secondary patency was 100 % at FU1, 96 % at FU2 and remained 96 % at FU3. At 12 months, the mean rVCSS dropped from 9.0 to 4.8 points (p < 0.001) whereas the mean CEAP improved from 3.45 to 2.96 (p < 0.001). A substantial healing of ulcerations was observed in 8 of 10 patients with initial venous ulceration. There were no relevant safety concerns noticed. Conclusions: Even though long-term studies are missing, the sinus-Obliquus venous stent already showed very promising patency rates at short term, associated with substantial clinical improvement and low device-related complications in both NIVL and PTS.
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Stents , Femenino , Humanos , Vena Ilíaca , Masculino , Persona de Mediana Edad , Flebografía , Síndrome Postrombótico , Sistema de Registros , Estudios Retrospectivos , Resultado del Tratamiento , Grado de Desobstrucción VascularRESUMEN
BACKGROUND: We sought to determine the patency and clinical symptom relief of the Venovo venous stent in the endovascular treatment of non-thrombotic (NIVL) or post-thrombotic venous obstruction (PTO) of the iliofemoral track over a period of 6 months. PATIENTS AND METHODS: A total of 80 patients (45 female, mean age 57 years) treated in 2016 and 2017 were included in the Arnsberg venous registry. Clinical improvement was determined by the revised venous clinical severity score (rVCSS) as well as the clinical, etiologic, anatomic and pathophysiologic (CEAP) score. Primary and secondary stent patency was evaluated using duplex ultrasound. RESULTS: Overall 6-months patency rates were 98 % for primary and 100 % for secondary patency. For NIVL primary patency was 97 %, whereas for PTO primary patency was 96 %. Early stent re-occlusion occurred in 3 patients within 34, 59 and 156 days after intervention. Two of these patients were successfully treated by endovascular mechanical thrombectomy and stent in stent implantation. Clinical improvement with a gain of ≥ 2 rVCSS levels was observed in 51 %. CEAP scores decreased from 4.3 to 2.7. CONCLUSIONS: In this first time report the novel Venovo venous stent showed adequate patency rates associated with reasonable clinical improvement and low device-related complications throughout a 6-months-follow-up in both NIVL and PTO.
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Síndrome Postrombótico , Stents , Trombosis de la Vena , Femenino , Vena Femoral , Humanos , Vena Ilíaca , Persona de Mediana Edad , Flebografía , Sistema de Registros , Resultado del Tratamiento , Grado de Desobstrucción VascularRESUMEN
First-order magnetic transitions (FOMTs) with a large discontinuity in magnetization are highly sought in the development of advanced functional magnetic materials. Isosymmetric magnetoelastic FOMTs that do not perturb crystal symmetry are especially rare, and only a handful of material families, almost exclusively transition metal-based, are known to exhibit them. Yet, here we report a surprising isosymmetric FOMT in a rare-earth intermetallic, Eu2In. What makes this transition in Eu2In even more remarkable is that it is associated with a large latent heat and an exceptionally high magnetocaloric effect in low magnetic fields, but with tiny lattice discontinuities and negligible hysteresis. An active role of the Eu-5d and In-4p states and a rather unique electronic structure borne by In to Eu charge transfer, altogether result in an unusual exchange mechanism that both sets the transition in motion and unveils an approach toward developing specific magnetic functionalities ad libitum.
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USA100 strains are significant contributors to the overall burden of health care-associated methicillin-resistant Staphylococcus aureus (MRSA) infections. Strain 209 is a representative MRSA isolate that serves as a model organism for agr type II studies and USA100 virulence assessments. We present a draft genome sequence of this strain.
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We develop a generalized framework for constructing many-body-interaction operations either in linear time or in logarithmic time with a linear number of ancilla qubits. Exact gate decompositions are given for Pauli strings, many-control Toffoli gates, number- and parity-conserving interactions, unitary coupled cluster operations, and sparse matrix generators. We provide a linear time protocol that works by creating a superposition of exponentially many different possible operator strings and then uses dynamical decoupling methodology to undo all the unwanted terms. A logarithmic time protocol overcomes the speed limit of the first by using ancilla registers to condition evolution to the support of the desired many-body interaction before using parallel chaining operations to expand the string length. The two techniques improve substantially on current strategies (reductions in time and space ranging from linear to exponential), are applicable to different physical interaction mechanisms such as cnot, XX, and XX+YY, and generalize to a wide range of many-body operators.
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We measure x-ray magnetic circular dichroism (XMCD) spectra at the Pu M_{4,5} absorption edges from a newly prepared high-quality single crystal of the heavy-fermion superconductor ^{242}PuCoGa_{5}, exhibiting a critical temperature T_{c}=18.7 K. The experiment probes the vortex phase below T_{c} and shows that an external magnetic field induces a Pu 5f magnetic moment at 2 K equal to the temperature-independent moment measured in the normal phase up to 300 K by a superconducting quantum interference device. This observation is in agreement with theoretical models claiming that the Pu atoms in PuCoGa_{5} have a nonmagnetic singlet ground state resulting from the hybridization of the conduction electrons with the intermediate-valence 5f electronic shell. Unexpectedly, XMCD spectra show that the orbital component of the 5f magnetic moment increases significantly between 30 and 2 K; the antiparallel spin component increases as well, leaving the total moment practically constant. We suggest that this indicates a low-temperature breakdown of the complete Kondo-like screening of the local 5f moment.
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Research on eating behavior is limited by an overreliance on self-report. It is well known that actual food intake is frequently underreported, and it is likely that this problem is overrepresented in vulnerable populations. The present research tested a chewing detection method that could assist self-report methods. A trained sample of 15 participants (usable data of 14 participants) kept detailed eating records during one day and one night while carrying a recording device. Signals recorded from electromyography sensors unobtrusively placed behind the right ear were used to develop a chewing detection algorithm. Results showed that eating could be detected with high accuracy (sensitivity, specificity >90%) compared to trained self-report. Thus, electromyography-based eating detection might usefully complement future food intake studies in healthy and vulnerable populations.
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Ingestión de Alimentos , Electromiografía , Monitoreo Ambulatorio/métodos , Adolescente , Adulto , Algoritmos , Índice de Masa Corporal , Femenino , Humanos , Masculino , Masticación , Evaluación Nutricional , Autoinforme , Sensibilidad y Especificidad , Adulto JovenRESUMEN
Microbial pathogens have developed several mechanisms to modulate and interfere with host cell cycle progression. In this study, we analyzed the effect of the human pathogen Neisseria meningitidis on the cell cycle of epithelial cells. Two pathogenic isolates, as well as two carrier isolates, were tested for their ability to adhere to and invade into the epithelial cell lines Detroit 562 and NP69 and to modulate the cell cycle. We found that all isolates adhered equally well to both Detroit 562 and NP69 cells, whereas the carrier isolates were significantly less invasive. Using propidium iodide staining and 5-ethynyl-2'-deoxyuridine pulse-labeling, we provide evidence that meningococcal infection arrested cells in the G1 phase of the cell cycle at 24 h postinfection. In parallel, a significant decrease of cells in the S phase was observed. Interestingly, G1-phase arrest was only induced after infection with live bacteria but not with heat-killed bacteria. By Western blotting we demonstrate that bacterial infection resulted in a decreased protein level of the cell cycle regulator cyclin D1, whereas cyclin E expression levels were increased. Furthermore, N. meningitidis infection induced an accumulation of the cyclin-dependent kinase inhibitor (CKI) p21(WAF1/CIP1) that was accompanied by a redistribution of this CKI to the cell nucleus, as shown by immunofluorescence analysis. Moreover, the p27(CIP1) CKI was redistributed and showed punctate foci in infected cells. In summary, we present data that N. meningitidis can interfere with the processes of host cell cycle regulation.
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Puntos de Control del Ciclo Celular , Células Epiteliales/microbiología , Interacciones Huésped-Patógeno , Infecciones Meningocócicas/microbiología , Neisseria meningitidis/fisiología , Adhesión Bacteriana/fisiología , Western Blotting , Núcleo Celular/metabolismo , Ciclina D1/metabolismo , Ciclina E/metabolismo , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/metabolismo , Células Epiteliales/fisiología , Humanos , Infecciones Meningocócicas/metabolismo , Neisseria meningitidis/metabolismoRESUMEN
Present-day environments are replete with tempting foods and the current obesity pandemic speaks to humans' inability to adjust to this. Pavlovian processes may be fundamental to such hedonic overeating. However, a lack of naturalistic Pavlovian paradigms in humans makes translational research difficult and important parameters such as implicitness and acquisition speed are unknown. Here we present a novel naturalistic conditioning task: an image of a neutral object was conditioned to marzipan taste in a single trial procedure by asking the participant to eat the 'object' (made from marzipan). Relative to control objects, results demonstrate robust pre- to post-conditioning changes of both subjective ratings and early as well as late event related brain potentials, suggesting contributions of implicit (attentional) and explicit (motivational) processes. Naturalistic single-trial taste-appetitive conditioning is potent in humans and shapes attentional and motivational neural processes that might challenge self-regulation during exposure to tempting foods. Thus, appetitive conditioning processes might contribute to overweight and obesity.
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Conducta Apetitiva/fisiología , Encéfalo/fisiología , Condicionamiento Clásico/fisiología , Potenciales Evocados/fisiología , Alimentos , Motivación/fisiología , Adulto , Análisis de Varianza , Electroencefalografía , Femenino , Humanos , Psicometría , Autoinforme , Estadística como Asunto , Factores de Tiempo , Adulto JovenRESUMEN
Posttraumatic stress disorder (PTSD) is a highly debilitating and prevalent psychological disorder. It is characterized by highly distressing intrusive trauma memories that are partly explained by fear conditioning. Despite efficient therapeutic approaches, a subset of PTSD patients displays spontaneous recurrence of traumatic memories after successful treatment. The development of animal behavioral models mimicking the individual variability in treatment outcome for PTSD patients represent therefore an important challenge as it allows for the identification of predicting factors of resilience or susceptibility to relapse. However, to date, only few animal behavioral models of long-lasting fear recovery have been developed and their predictive validity has not been tested directly. The objectives of this study were twofold. First we aimed to develop a simple animal behavioral model of long-lasting fear recovery based on auditory cued fear conditioning and extinction learning, which recapitulates the heterogeneity of fear responses observed in PTSD patients after successful treatment. Second we aimed at testing the predictive validity of our behavioral model and used to this purpose a translational approach based (i) on the demonstration of the efficiency of Eye Movement Desensitization and Reprocessing (EMDR) therapy to reduce conditioned fear responses in PTSD patients and (ii) on the implementation in our behavioral model of an electrical bilateral alternating stimulation of the eyelid which mimics the core feature of EMDR. Our data indicate that electrical bilateral alternating stimulation of the eyelid during extinction learning alleviates long-lasting fear recovery of conditioned fear responses and dramatically reduces inter-individual variability. These results demonstrate the face and predictive validity of our animal behavioral model and provide an interesting tool to understand the neurobiological underpinnings of long-lasting fear recovery.
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Miedo , Trastornos por Estrés Postraumático/psicología , Estimulación Acústica , Adulto , Animales , Condicionamiento Psicológico , Estimulación Eléctrica , Extinción Psicológica , Desensibilización y Reprocesamiento del Movimiento Ocular , Párpados/fisiopatología , Femenino , Humanos , Masculino , Ratones Endogámicos C57BL , Persona de Mediana Edad , Trastornos por Estrés Postraumático/fisiopatología , Trastornos por Estrés Postraumático/terapiaRESUMEN
Microbial pathogens have developed several mechanisms to modulate and interfere with host cell cycle progression. In this study, we analysed the effect of the human pathogen Neisseria meningitidis on cell cycle in a brain endothelial cell line as well as in primary brain endothelial cells. We found that N. Meningitidis causes an accumulation of cells in the S phase early at 3 and at 24 h post-infection that was paralleled by a decrease of cells in G2/M phase. Importantly, the outer membrane proteins of the colony opacity-associated (Opa) protein family as well as the Opc protein proved to trigger the accumulation of cells in the S phase. A focused cell cycle reverse transcription quantitative polymerase chain reaction-based array and integrated network analysis revealed changes in the abundance of several cell cycle regulatory mRNAs, including the cell cycle inhibitors p21(WAF1/CIP1) and cyclin G2. These alterations were reflected in changes in protein expression levels and/or relocalization in N. meningitidis-infected cells. Moreover, an increase in p21(WAF1/CIP1) expression was found to be p53 independent. Genetic ablation of p21(WAF1/CIP1) and cyclin G2 abrogated N. meningitidis-induced S phase accumulation. Finally, by measuring the levels of the biomarker 8-hydroxydeoxyguanosine and phosphorylation of the histone variant H2AX, we provide evidence that N. meningitidis induces oxidative DNA damage in infected cells.
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Puntos de Control del Ciclo Celular , Ciclina G2/metabolismo , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/metabolismo , Células Endoteliales/microbiología , Interacciones Huésped-Patógeno , Neisseria meningitidis/patogenicidad , Fase S , Proteínas de la Membrana Bacteriana Externa/metabolismo , Encéfalo , Células Cultivadas , Células Endoteliales/fisiología , Perfilación de la Expresión Génica , Humanos , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
BACKGROUND: Rigosertib (ON 01910.Na), a first-in-class Ras mimetic and small-molecule inhibitor of multiple signaling pathways including polo-like kinase 1 (PLK1) and phosphoinositide 3-kinase (PI3K), has shown efficacy in preclinical pancreatic cancer models. In this study, rigosertib was assessed in combination with gemcitabine in patients with treatment-naïve metastatic pancreatic adenocarcinoma. MATERIALS AND METHODS: Patients with metastatic pancreatic adenocarcinoma were randomized in a 2:1 fashion to gemcitabine 1000 mg/m(2) weekly for 3 weeks of a 4-week cycle plus rigosertib 1800 mg/m(2) via 2-h continuous IV infusions given twice weekly for 3 weeks of a 4-week cycle (RIG + GEM) versus gemcitabine 1000 mg/m(2) weekly for 3 weeks in a 4-week cycle (GEM). RESULTS: A total of 160 patients were enrolled globally and randomly assigned to RIG + GEM (106 patients) or GEM (54). The most common grade 3 or higher adverse events were neutropenia (8% in the RIG + GEM group versus 6% in the GEM group), hyponatremia (17% versus 4%), and anemia (8% versus 4%). The median overall survival was 6.1 months for RIG + GEM versus 6.4 months for GEM [hazard ratio (HR), 1.24; 95% confidence interval (CI) 0.85-1.81]. The median progression-free survival was 3.4 months for both groups (HR = 0.96; 95% CI 0.68-1.36). The partial response rate was 19% versus 13% for RIG + GEM versus GEM, respectively. Of 64 tumor samples sent for molecular analysis, 47 were adequate for multiplex genetic testing and 41 were positive for mutations. The majority of cases had KRAS gene mutations (40 cases). Other mutations detected included TP53 (13 cases) and PIK3CA (1 case). No correlation between mutational status and efficacy was detected. CONCLUSIONS: The combination of RIG + GEM failed to demonstrate an improvement in survival or response compared with GEM in patients with metastatic pancreatic adenocarcinoma. Rigosertib showed a similar safety profile to that seen in previous trials using the IV formulation.
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Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Desoxicitidina/análogos & derivados , Glicina/análogos & derivados , Neoplasias Pancreáticas/tratamiento farmacológico , Sulfonas/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Antimetabolitos Antineoplásicos/uso terapéutico , Proteínas de Ciclo Celular/antagonistas & inhibidores , Fosfatidilinositol 3-Quinasa Clase I , Desoxicitidina/efectos adversos , Desoxicitidina/uso terapéutico , Supervivencia sin Enfermedad , Esquema de Medicación , Femenino , Glicina/efectos adversos , Glicina/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Fosfatidilinositol 3-Quinasas/genética , Inhibidores de las Quinasa Fosfoinosítidos-3 , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Proteínas Proto-Oncogénicas/antagonistas & inhibidores , Proteínas Proto-Oncogénicas p21(ras)/genética , Sulfonas/efectos adversos , Proteína p53 Supresora de Tumor/genética , Gemcitabina , Quinasa Tipo Polo 1 , Neoplasias PancreáticasRESUMEN
Trivalent americium has a nonmagnetic (J=0) ground state arising from the cancellation of the orbital and spin moments. However, magnetism can be induced by a large molecular field if Am^{3+} is embedded in a ferromagnetic matrix. Using the technique of x-ray magnetic circular dichroism, we show that this is the case in AmFe_{2}. Since ⟨J_{z}⟩=0, the spin component is exactly twice as large as the orbital one, the total Am moment is opposite to that of Fe, and the magnetic dipole operator ⟨T_{z}⟩ can be determined directly; we discuss the progression of the latter across the actinide series.