Decoupling Frequencies, Amplitudes and Phases in Nonlinear Optics

In linear optics, light fields do not mutually interact in a medium. However, they do mix when their field strength becomes comparable to electron binding energies in the so-called nonlinear optical regime. Such high fields are typically achieved with ultra-short laser pulses containing very broad frequency spectra where their amplitudes and phases are mutually coupled in a convolution process. Here, we describe a regime of nonlinear interactions without mixing of different frequencies. We demonstrate both in theory and experiment how frequency domain nonlinear optics overcomes the shortcomings arising from the convolution in conventional time domain interactions. We generate light fields with previously inaccessible properties by avoiding these uncontrolled couplings. Consequently, arbitrary phase functions are transferred linearly to other frequencies while preserving the general shape of the input spectrum. As a powerful application, we introduce deep UV phase control at 207 nm by using a conventional NIR pulse shaper

Efecto terapéutico del alprostadil en pacientes con isquemia crítica terminal de los miembros inferiores

Objetivo: El manejo de la isquemia crítica de los miembros inferiores representa un reto para el cirujano vascular debido a la alta tasa de amputaciones y mortalidad. Las opciones de manejo actuales: puente femorodistal, angioplastia con o sin la colocación de Stents y la resección de la placa con láser o de manera mecánica, presentan a largo plazo una tasa de éxito muy baja y un número de amputaciones supracondíleas que continúa siendo elevado. Métodos: Para este estudio prospectivo se reclutaron 173 pacientes con diagnóstico de estadio avanzado, con isquemia crítica de miembro inferior quienes fueron tratados con alprostadil (60 – 120 mcgr/día) por vía intravenosa sistémica por 28 días. La respuesta se midió clínicamente por mejoría del llenado capilar y con el uso de la escala análoga visual del dolor. Resultados: Al momento del alta hospitalaria el 94.3% de los pacientes mejoró el puntaje en la escala análoga visual del dolor (p < 0.0001). El seguimiento a más de un año del tratamiento con alprostadil mostró que el 97% de los pacientes mejoró significativamente su estadio de isquemia, evitándose así una amputación mayor. No se observó respuesta al tratamiento en pacientes previamente intervenidos por vía endovascular (5 pacientes). Conclusiones: El tratamiento de pacientes con isquemia crítica de miembro inferior con alpostadil por infusión intravenosa, con bolos diarios de entre 60 y 120 mcg durante 28 días, este medicamento es seguro y presenta mínimos efectos secundarios. Esta terapia mejora sustancialmente el estadio funcional de Rutherford en estos pacientes y evita amputaciones mayores

Phase-matching-free pulse retrieval based on transient absorption in solids

In this paper, we introduce a pulse characterization technique that is free of phase-matching constraints, exploiting transient absorption in solids as an ultrafast optical switch. Based on a pump-probe setup, this technique uses pump pulses of sufficient intensity to induce the switch, while the pulses to characterize are probing the transmissivity drop of the photoexcited material. This enables the characterization of low-intensity ultra-broadband pulses at the detection limit of the spectrometer, and within the transparency range of the solid. For example, by using zinc selenide (ZnSe), pulses with wavelengths from 0.5 to 20 µm can be characterized, denoting five octaves of spectral range. Using ptychography, we retrieve the temporal profiles of both the probe pulse and the switch. To demonstrate this approach, we measure ultrashort pulses from a titanium-sapphire (Ti-Sa) amplifier which are compressed using a hollow core fiber setup, as well as infrared to mid-infrared pulses generated from an optical parametric amplifier (OPA). The characterized pulses are centered at wavelengths of 0.77, 1.53, 1.75, 4, and 10 µm, down to sub-two optical cycles duration, exceeding an octave of bandwidth, and with energy as low as a few nanojoules

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

BackgroundWe previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in similar to 80% of cases.MethodsWe report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded.ResultsNo gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5-528.7, P=1.1x10(-4)) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70[95%CI 1.3-8.2], P=2.1x10(-4)). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR=19.65[95%CI 2.1-2635.4], P=3.4x10(-3)), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR=4.40[9%CI 2.3-8.4], P=7.7x10(-8)). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years; P=1.68x10(-5)).ConclusionsRare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old