Contributions to three problems relevant to cavity quantum optics

En la primera parte, el tema de estudio son las fluctuaciones cuánticas en el Oscilador Óptico Paramétrico (OPO) de tipo II. En esencia, los OPOs son cavidades ópticas que contienen un cristal con una no linealidad de segundo orden. Cuando bombeamos con un laser de frecuencia 2w0, el OPO es capaz de generar frecuencias ws (señal) y wi (vago) de tal forma que ws+wi=2w0. Que el dispositivo sea de Tipo II hace referencia a que estos haces tienen polarizaciones ortogonales. En una descripción clásica, la generación de frecuencias requiere que el OPO sea bombeado por encima de un cierto valor umbral; sin embargo, cuánticamente las parejas de fotones señal-vago pueden ser generadas incluso por debajo de ese umbral, lo cual les confiere propiedades cuánticas muy interesantes. En particular, los OPOs de tipo I, en los cuales señal y vago tienen la misma polarización, mantienen el record de reducción de ruido en cuadraturas ("single-mode squeezing"), lo que se manifiesta en el modo degenerado de frecuencia ws=wi=w0; consistiendo el "squeezing" en reducir el ruido cuántico en un observable a costa de incrementarlo en su par canónico, preservando así el principio de incertidumbre, lo que permite, por ejemplo, realizar medidas ultraprecisas virtualmente libres de ruido cuántico. Por otro lado, los OPOs de tipo II además de proporcionar "squeezing" en la suma de fases de señal y vago (lo que no resulta detectable puesto que se trata de una cuadratura "mixta" que implica a dos modos de frecuencias y polarizaciones diferentes), tiene reducción completa de ruido en la resta de intensidades, lo cual quiere decir que sus amplitudes están perfectamente correlacionadas y los haces ¿entrelazados¿. Cuando dos sistemas están entrelazados, presentan correlaciones cuánticas no-locales que pueden explotarse para muchas aplicaciones impensables en el dominio clásico. Sin embargo, para la manipulación y detección de estos estados es muy conveniente que los campos generados estén degenerados en frecuencia ("locking"). Hasta ahora, las técnicas conocidas que consiguen "locking" deterioran los niveles de "squeezing" y entrelazamiento. La primera vez que fue propuesta una técnica de "locking" fue por Fabre y colaboradores. En esta parte de la tesis, nosotros proponemos una alternativa de conseguir degeneración a frecuencia w0. Mostramos que el "locking" puede ser conseguido en el OPO tipo II preservando buenos niveles de entrelazamiento. En la segunda parte de la tesis nos centramos en el estudio de simuladores cuánticos de la física de sistemas de muchos cuerpos. En particular, nos centramos en el estudio de colecciones ("arrays") de cavidades ópticas, cada una interactuando fuertemente con un emisor de dos niveles. Este tipo de sistemas han recibido una atención considerable en los últimos años. Se han descubierto fases coherentes fuertemente correlacionadas y se ha discutido sobre analogías con el efecto hall cuántico y con estados cuánticos topológicamente protegidos. En investigaciones anteriores el mecanismo de bombeo utilizado ha sido un bombeo coherente para cada cavidad, con lo que la relación de fase entre los campos de cavidades distantes podía ser atribuida, al menos en parte, a la relación de fase entre los campos coherentes bombeados. En este trabajo mostramos que la coherencia entre cavidades distantes puede construirse espontáneamente, provocada solo por los procesos físicos dentro del "array". De esta forma nos preguntamos si en estas estructuras se pueden desarrollar superfluidos fuera del equilibrio o condensados de Bose Einstein. Por este motivo, consideramos que el "array" de cavidades esta bombeado sólo de forma incoherente. Para una sola cavidad el sistema se reduce al láser de un solo emisor ("one- emitter laser"), ampliamente estudiado en trabajos anteriores. En nuestro análisis nos concentramos en las correlaciones en cavidades distantes, típicamente consideradas para investigar efectos de rango lejano y la emergencia de superfluidez. De hecho encontramos correlaciones colectivas cuando las cavidades se encuentran en régimen de emisión láser. Estas correlaciones decaen más rápido que ninguna potencia de la distancia cuando la distancia entre cavidades tiende a infinito para cualquier dimensión del "array". Como es de esperar, la longitud de correlación asociada aumenta al aumentar el acoplo entre cavidades. También encontramos propiedades intrínsecas del laser, como el típico espectro de fotoluminiscencia, el triplete de Mollow, el cual puede ser observado lejos de la resonancia entre emisor y cavidad debido a la aparición de modos fotónicos colectivos. La tercera parte de la tesis se centra en el estudio de cavidades optomecánicas, que son resonadores ópticos (dos espejos enfrentados, por ejemplo) iluminados por un láser, en los que se produce una interacción entre la luz y uno o varios sistemas mecánicos. Estos dispositivos pueden implementarse de varias formas, siendo la más sencilla la que asume que la luz ejerce una presión de radiación que puede modificar la posición de un espejo móvil. El uso de resonadores ópticos permite aumentar en varios órdenes de magnitud la intensidad de la luz en el interior de la cavidad, lo cual conduce a una mejora impresionante de la interacción. Las cavidades optomecánicas han sido implementadas usando diferentes osciladores mecánicos (OMs) como, por ejemplo, resonadores microtoroidales o membranas suspendidas en una cavidad. Desde el punto de vista cuántico, estos dispositivos también pueden proporcionar estados cuánticos de la luz como "squeezed" o entrelazados, así como enfriamiento del OM ("laser cooling"). El laser "cooling" es una técnica para enfriar el OM hasta su estado fundamental (el de mínima energía), punto de partida para estudiar la transición microscópica-macroscópica de las leyes mecano-cuánticas. El modelo propuesto en esta parte de la tesis, permite la coexistencia de muchos modos tanto mecánicos como ópticos (estamos entonces en presencia de un sistema intrínsecamente multimodo). A través del estudio de la estabilidad del sistema hemos obtenido que pueden coexistir dos soluciones homogéneas (biestabilidad) y que no solo existen inestabilidades temporales, sino que también pueden formarse estructuras espaciales disipativas. Por ejemplo, partiendo de una inyección plana (invariante bajo traslaciones) encontramos patrones hexagonales (que rompen espontáneamente la simetría espacial), y, en la zona de biestabilidad, donde los patrones coexisten con una solución homogénea, encontramos solitones de cavidad

Dissipative structures in optomechanical cavities

Motivated by the increasing interest in the properties of multimode optomechanical devices, here we study a system in which a driven mode of a large-area optical cavity is despersively coupled to a deformable mechanical element. Two different models naturally appear in such scenario, for which we predict the formation of periodic patterns, localized structures (cavity solitons), and domain walls, among other complex nonlinear phenomena. Further, we propose a realistic design based on intracavity membranes where our models can be studied experimentally. Apart from its relevance to the field of nonlinear optics, the results put forward here are a necessary step towards understanding the quantum properties of optomechanical systems in the multimode regime of both the optical and mechanical degrees of freedom.Comment: Updated version with a more general model and a specific implementation proposal. Comments and (constructive) criticism are welcom

Active locking and entanglement in type II optical parametric oscillators

Type II optical parametric oscillators are amongst the highest-quality sources of quantum-correlated light. In particular, when pumped above threshold, such devices generate a pair of bright orthogonally-polarized beams with strong continuous-variable entanglement. However, these sources are of limited practical use, because the entangled beams emerge with different frequencies and a diffusing phase difference. It has been proven that the use of an internal wave-plate coupling the modes with orthogonal polarization is capable of locking the frequencies of the emerging beams to half the pump frequency, as well as reducing the phase-difference diffusion, at the expense of reducing the entanglement levels. In this work we characterize theoretically an alternative locking mechanism: the injection of a laser at half the pump frequency. Apart from being less invasive, this method should allow for an easier real-time experimental control. We show that such an injection is capable of generating the desired phase locking between the emerging beams, while still allowing for large levels of entanglement. Moreover, we find an additional region of the parameter space (at relatively large injections) where a mode with well defined polarization is in a highly amplitude-squeezed state

Spatial localization and pattern formation in discrete optomechanical cavities and arrays

We investigate theoretically the generation of nonlinear dissipative structures in optomechanical (OM) systems containing discrete arrays of mechanical resonators. We consider both hybrid models in which the optical system is a continuous multimode field, as it would happen in an OM cavity containing an array of micro-mirrors, and also fully discrete models in which each mechanical resonator interacts with a single optical mode, making contact with Ludwig and Marquardt (2013 Phys. Rev. Lett. 101, 073603). Also, we study the connections between both types of models and continuous OM models. While all three types of models merge naturally in the limit of a large number of densely distributed mechanical resonators, we show that the spatial localization and the pattern formation found in continuous OM models can still be observed for a small number of mechanical elements, even in the presence of finite-size effects, which we discuss. This opens new venues for experimental approaches to the subject

Física, Matemáticas y Música

Esta documento corresponde a la memoria final de ejecución del proyecto de innovación docente número 210 de la convocatoria 2020/2021 que lleva por título "Física, Matemáticos y Música"

Melatonin's role as a co-adjuvant treatment in colonic diseases: a review

Melatonin is produced in the pineal gland as well as many other organs, including the enterochromaffin cells of the digestive mucosa. Melatonin is a powerful antioxidant that resists oxidative stress due to its capacity to directly scavenge reactive species, to modulate the antioxidant defense system by increasing the activities of antioxidant enzymes, and to stimulate the innate immune response through its direct and indirect actions. In addition, the dysregulation of the circadian system is observed to be related with alterations in colonic motility and cell disruptions due to the modifications of clock genes expression. In the gastrointestinal tract, the activities of melatonin are mediated by melatonin receptors (MT2), serotonin (5-HT), and cholecystokinin B (CCK2) receptors and via receptor-independent processes. The levels of melatonin in the gastrointestinal tract exceed by 10–100 times the blood concentrations. Also, there is an estimated 400 times more melatonin in the gut than in the pineal gland. Gut melatonin secretion is suggested to be influenced by the food intake. Low dose melatonin treatment accelerates intestinal transit time whereas high doses may decrease gut motility. Melatonin has been studied as a co-adjuvant treatment in several gastrointestinal diseases including irritable bowel syndrome (IBS), constipation-predominant IBS (IBS-C), diarrhea-predominant IBS (IBS-D), Crohn''s disease, ulcerative colitis, and necrotizing enterocolitis. The purpose of this review is to provide information regarding the potential benefits of melatonin as a co-adjuvant treatment in gastrointestinal diseases, especially IBS, Crohn''s disease, ulcerative colitis, and necrotizing enterocolitis

Mutations in TP53 and JAK2 are independent prognostic biomarkers in B-cell precursor acute lymphoblastic leukaemia

[EN]Background: In B-cell precursor acute lymphoblastic leukaemia (B-ALL), the identification of additional genetic alterations associated with poor prognosis is still of importance. We determined the frequency and prognostic impact of somatic mutations in children and adult cases with B-ALL treated with Spanish PETHEMA and SEHOP protocols. Methods: Mutational status of hotspot regions of TP53, JAK2, PAX5, LEF1, CRLF2 and IL7R genes was determined by next-generation deep sequencing in 340 B-ALL patients (211 children and 129 adults). The associations between mutation status and clinicopathological features at the time of diagnosis, treatment outcome and survival were assessed. Univariate and multivariate survival analyses were performed to identify independent prognostic factors associated with overall survival (OS), event-free survival (EFS) and relapse rate (RR). Results: A mutation rate of 12.4% was identified. The frequency of adult mutations was higher (20.2% vs 7.6%, P=0.001). TP53 was the most frequently mutated gene (4.1%), followed by JAK2 (3.8%), CRLF2 (2.9%), PAX5 (2.4%), LEF1 (0.6%) and IL7R (0.3%). All mutations were observed in B-ALL without ETV6-RUNX1 (P=0.047) or BCR-ABL1 fusions (P<0.0001). In children, TP53mut was associated with lower OS (5-year OS: 50% vs 86%, P=0.002) and EFS rates (5-year EFS: 50% vs 78.3%, P=0.009) and higher RR (5-year RR: 33.3% vs 18.6% P=0.037), and was independently associated with higher RR (hazard ratio (HR)=4.5; P=0.04). In adults, TP53mut was associated with a lower OS (5-year OS: 0% vs 43.3%, P=0.019) and a higher RR (5-year RR: 100% vs 61.4%, P=0.029), whereas JAK2mut was associated with a lower EFS (5-year EFS: 0% vs 30.6%, P=0.035) and a higher RR (5-year RR: 100% vs 60.4%, P=0.002). TP53mut was an independent risk factor for shorter OS (HR=2.3; P=0.035) and, together with JAK2mut, also were independent markers of poor prognosis for RR (TP53mut: HR=5.9; P=0.027 and JAK2mut: HR=5.6; P=0.036). Conclusions: TP53mut and JAK2mut are potential biomarkers associated with poor prognosis in B-ALL patients.European Commision (EC). Funding FP7/SP1/HEALTH. Project Code: 30624

Detection of kinase domain mutations in BCR::ABL1 leukemia by ultra-deep sequencing of genomic DNA

The screening of the BCR::ABL1 kinase domain (KD) mutation has become a routine analysis in case of warning/failure for chronic myeloid leukemia (CML) and B-cell precursor acute lymphoblastic leukemia (ALL) Philadelphia (Ph)-positive patients. In this study, we present a novel DNA-based next-generation sequencing (NGS) methodology for KD ABL1 mutation detection and monitoring with a 1.0E−4 sensitivity. This approach was validated with a well-stablished RNA-based nested NGS method. The correlation of both techniques for the quantification of ABL1 mutations was high (Pearson r = 0.858, p < 0.001), offering DNA-DeepNGS a sensitivity of 92% and specificity of 82%. The clinical impact was studied in a cohort of 129 patients (n = 67 for CML and n = 62 for B-ALL patients). A total of 162 samples (n = 86 CML and n = 76 B-ALL) were studied. Of them, 27 out of 86 harbored mutations (6 in warning and 21 in failure) for CML, and 13 out of 76 (2 diagnostic and 11 relapse samples) did in B-ALL patients. In addition, in four cases were detected mutation despite BCR::ABL1 < 1%. In conclusion, we were able to detect KD ABL1 mutations with a 1.0E−4 sensitivity by NGS using DNA as starting material even in patients with low levels of disease.Tis project was funded in part by CRIS CANCER FOUNDATION

COVID-19 Severity and Survival over Time in Patients with Hematologic Malignancies: A Population-Based Registry Study

Mortality rates for COVID-19 have declined over time in the general population, but data in patients with hematologic malignancies are contradictory. We identified independent prognostic factors for COVID-19 severity and survival in unvaccinated patients with hematologic malignancies, compared mortality rates over time and versus non-cancer inpatients, and investigated post COVID-19 condition. Data were analyzed from 1166 consecutive, eligible patients with hematologic malignancies from the population-based HEMATO-MADRID registry, Spain, with COVID-19 prior to vaccination roll-out, stratified into early (February–June 2020; n = 769 (66%)) and later (July 2020–February 2021; n = 397 (34%)) cohorts. Propensity-score matched non-cancer patients were identified from the SEMI-COVID registry. A lower proportion of patients were hospitalized in the later waves (54.2%) compared to the earlier (88.6%), OR 0.15, 95%CI 0.11–0.20. The proportion of hospitalized patients admitted to the ICU was higher in the later cohort (103/215, 47.9%) compared with the early cohort (170/681, 25.0%, 2.77; 2.01–3.82). The reduced 30-day mortality between early and later cohorts of non-cancer inpatients (29.6% vs. 12.6%, OR 0.34; 0.22–0.53) was not paralleled in inpatients with hematologic malignancies (32.3% vs. 34.8%, OR 1.12; 0.81–1.5). Among evaluable patients, 27.3% had post COVID-19 condition. These findings will help inform evidence-based preventive and therapeutic strategies for patients with hematologic malignancies and COVID-19 diagnosis.Depto. de MedicinaFac. de MedicinaTRUEFundación Madrileña de Hematología y HemoterapiaFundación Leucemia y LinfomaAsociación Madrileña de Hematología y Hemoterapiapu

Association Between Preexisting Versus Newly Identified Atrial Fibrillation and Outcomes of Patients With Acute Pulmonary Embolism

Background Atrial fibrillation (AF) may exist before or occur early in the course of pulmonary embolism (PE). We determined the PE outcomes based on the presence and timing of AF. Methods and Results Using the data from a multicenter PE registry, we identified 3 groups: (1) those with preexisting AF, (2) patients with new AF within 2 days from acute PE (incident AF), and (3) patients without AF. We assessed the 90-day and 1-year risk of mortality and stroke in patients with AF, compared with those without AF (reference group). Among 16 497 patients with PE, 792 had preexisting AF. These patients had increased odds of 90-day all-cause (odds ratio [OR], 2.81; 95% CI, 2.33-3.38) and PE-related mortality (OR, 2.38; 95% CI, 1.37-4.14) and increased 1-year hazard for ischemic stroke (hazard ratio, 5.48; 95% CI, 3.10-9.69) compared with those without AF. After multivariable adjustment, preexisting AF was associated with significantly increased odds of all-cause mortality (OR, 1.91; 95% CI, 1.57-2.32) but not PE-related mortality (OR, 1.50; 95% CI, 0.85-2.66). Among 16 497 patients with PE, 445 developed new incident AF within 2 days of acute PE. Incident AF was associated with increased odds of 90-day all-cause (OR, 2.28; 95% CI, 1.75-2.97) and PE-related (OR, 3.64; 95% CI, 2.01-6.59) mortality but not stroke. Findings were similar in multivariable analyses. Conclusions In patients with acute symptomatic PE, both preexisting AF and incident AF predict adverse clinical outcomes. The type of adverse outcomes may differ depending on the timing of AF onset.info:eu-repo/semantics/publishedVersio