Cascaded Parametric Amplification for Highly Efficient Terahertz Generation

A highly efficient, practical approach to high-energy terahertz (THz) generation based on spectrally cascaded optical parametric amplification (THz-COPA) is introduced. The THz wave initially generated by difference frequency generation between a strong narrowband optical pump and optical seed (0.1-10% of pump energy) kick-starts a repeated or cascaded energy down-conversion of pump photons. This helps to greatly surpass the quantum-defect efficiency and results in exponential growth of THz energy over crystal length. In cryogenically cooled periodically poled lithium niobate, energy conversion efficiencies >8% for 100 ps pulses are predicted. The calculations account for cascading effects, absorption, dispersion and laser-induced damage. Due to the coupled nonlinear interaction of multiple triplets of waves, THz-COPA exhibits physics distinct from conventional three-wave mixing parametric amplifiers. This in turn governs optimal phase-matching conditions, evolution of optical spectra as well as limitations of the nonlinear process.Comment: 5 pages, double colum

Parametric Waveform Synthesis: a scalable approach to generate sub-cycle optical transients

The availability of electromagnetic pulses with controllable field waveform and extremely short duration, even below a single optical cycle, is imperative to fully harness strong-field processes and to gain insight into ultrafast light-driven mechanisms occurring in the attosecond time-domain. The recently demonstrated parametric waveform synthesis (PWS) introduces an energy-, power- and spectrum-scalable method to generate non-sinusoidal sub-cycle optical waveforms by coherently combining different phase-stable pulses attained via optical parametric amplifiers. Significant technological developments have been addressed to overcome the stability issues related to PWS and to obtain an effective and reliable waveform control system. Here we present the main ingredients enabling PWS technology. The design choices concerning the optical, mechanical and electronic setups are justified by analytical/numerical modeling and benchmarked by experimental observations. In its present incarnation, the PWS technology enables the generation of field-controllable mJ-level few-femtosecond pulses spanning the visible to infrared range.Comment: 34 page

Terahertz Generation in Lithium Niobate Driven by Ti:Sapphire Laser Pulses and its Limitations

We experimentally investigate the limits to 800 nm-to-terahertz (THz) energy conversion in lithium niobate at room temperature driven by amplified Ti:Sapphire laser pulses with tilted-pulse-front. The influence of the pump central wavelength, pulse duration, and fluence on THz generation is studied. We achieved a high peak efficiency of 0.12% using transform limited 150 fs pulses and observed saturation of the optical to THz conversion efficiency at a fluence of 15 mJ/cm2. We experimentally identify two main limitations for the scaling of optical-to-THz conversion efficiencies: (i) the large spectral broadening of the optical pump spectrum in combination with large angular dispersion of the tilted-pulse-front and (ii) free-carrier absorption of THz radiation due to multi-photon absorption of the 800 nm radiation.Comment: 4 pages, 6 figure

Coherent pulse synthesis: Towards sub-cycle optical waveforms

The generation of sub-optical-cycle, carrier–envelope phase-stable light pulses is one of the frontiers of ultrafast optics. The two key ingredients for sub-cycle pulse generation are bandwidths substantially exceeding one octave and accurate control of the spectral phase. These requirements arevery challenging to satisfy with a single laser beam, and thus intense research activity is currently devoted to the coherent synthesis of pulses generated by separate sources. In this review we discuss the conceptual schemes and experimental tools that can be employed for the generation, amplification, control, and combination of separate light pulses. The main techniques for the spectrotemporal characterization of the synthesized fields are also described. We discuss recent implementations of coherent waveform synthesis: from the first demonstration of a single-cycle opticalpulse by the addition of two pulse trains derived from a fiber laser, to the coherent combination of the outputs from optical parametric chirped-pulse amplifiers

Toward Waveform Nonlinear Optics Using Multimillijoule Sub-Cycle Waveform Synthesizers

Waveform nonlinear optics aims to study and control the nonlinear interactions of matter with extremely short optical waveforms custom-tailored within a single cycle of light. Different technological routes to generate such multimillijoule sub-optical-cycle waveforms are currently pursued, opening up unprecedented opportunities in attoscience and strong-field physics. Here, we discuss the experimental schemes, introduce the technological challenges, and present our experimental results on high-energy sub-cycle optical waveform synthesis based on (1) parametric amplification and (2) induced-phase modulation in a two-color-driven gas-filled hollow-core fiber compressor. More specifically, for (1), we demonstrate a carrier-envelope-phase (CEP)-stable, multimillijoule three-channel parametric waveform synthesizer generating a >2-octave-wide spectrum (0.52-2.4 μm). After two amplification stages, the combined 125-μJ output supports 1.9-fs FWHM waveforms; energy scaling to >2 mJ is achieved after three amplification stages. FROG pulse characterization of all three second-stage outputs demonstrates the feasibility to recompress all three channels simultaneously close to the Fourier limit and shows the flexibility of our intricate dispersion management scheme for different experimental situations. For (2), we generate CEP-stable 1.7-mJ waveforms covering 365-930 nm (measured at 1% of the peak intensity) obtained from induced-phase modulation in a two-color-driven gas-filled hollow-core fiber. Using custom-designed double-chirped mirrors and a UV spatial light modulator will permit compression close to the 0.9-fs FWHM transform limit. These novel sources will become versatile tools for controlling strong-field interactions in matter and for attosecond pump-probe spectroscopy using VIS/IR and XUV/soft-X-ray pulses

High-energy sub-cycle optical waveform synthesizer

High-energy sub-cycle optical waveform synthesis is demonstrated with a three-channel OPA pumped by an 18-mJ cryogenically cooled Ti:sapphire laser. The system aims towards multi-mJ, 2-fs, phase-stable pulses covering the wavelength range from 0.52 - 2.4μ

Multimillijoule sub-optical-cycle parametric waveform synthesis for attosecond science

We present a phase-stable, multi-mJ 3-channelparametric synthesizer generating 2-octave-wide waveforms (0.52-2.4 μm). After two amplification stages, the combined 125-μJ output supports 1.9-fs waveforms. The energy is scaled to 2 mJ after three amplification stages

Growth hormone secretagogues modulate inflammation and fibrosis in mdx mouse model of Duchenne muscular dystrophy

IntroductionGrowth hormone secretagogues (GHSs) exert multiple actions, being able to activate GHS-receptor 1a, control inflammation and metabolism, to enhance GH/insulin-like growth factor-1 (IGF-1)-mediated myogenesis, and to inhibit angiotensin-converting enzyme. These mechanisms are of interest for potentially targeting multiple steps of pathogenic cascade in Duchenne muscular dystrophy (DMD).MethodsHere, we aimed to provide preclinical evidence for potential benefits of GHSs in DMD, via a multidisciplinary in vivo and ex vivo comparison in mdx mice, of two ad hoc synthesized compounds (EP80317 and JMV2894), with a wide but different profile. 4-week-old mdx mice were treated for 8 weeks with EP80317 or JMV2894 (320 µg/kg/d, s.c.).ResultsIn vivo, both GHSs increased mice forelimb force (recovery score, RS towards WT: 20% for EP80317 and 32% for JMV2894 at week 8). In parallel, GHSs also reduced diaphragm (DIA) and gastrocnemius (GC) ultrasound echodensity, a fibrosis-related parameter (RS: ranging between 26% and 75%). Ex vivo, both drugs ameliorated DIA isometric force and calcium-related indices (e.g., RS: 40% for tetanic force). Histological analysis highlighted a relevant reduction of fibrosis in GC and DIA muscles of treated mice, paralleled by a decrease in gene expression of TGF-β1 and Col1a1. Also, decreased levels of pro-inflammatory genes (IL-6, CD68), accompanied by an increment in Sirt-1, PGC-1α and MEF2c expression, were observed in response to treatments, suggesting an overall improvement of myofiber metabolism. No detectable transcript levels of GHS receptor-1a, nor an increase of circulating IGF-1 were found, suggesting the presence of a novel receptor-independent mechanism in skeletal muscle. Preliminary docking studies revealed a potential binding capability of JMV2894 on metalloproteases involved in extracellular matrix remodeling and cytokine production, such as ADAMTS-5 and MMP-9, overactivated in DMD.DiscussionOur results support the interest of GHSs as modulators of pathology progression in mdx mice, disclosing a direct anti-fibrotic action that may prove beneficial to contrast pathological remodeling

Introduction to nonlinear optics

Nonlinear optics (NLO) is a branch of physics dealing with electromagnetic fields whose wavelength (frequency, color) is modified by the interaction with a medium. For example, in second harmonic generation an infrared laser beam is converted into a visible beam when going through a crystal. In white light generation, a pulse with narrow spectrum generates a broadband continuum of new frequencies.Due to the high energies needed to observe such phenomena, NLO started in 1961, just one year after the realization of the first laser.With NLO techniques, it is possible to generate optical pulses whose duration is in the order of the femtosecond (10-15 seconds) or even attosecond (10-18 seconds). Such extremely short pulses are routinely used for detecting and even controlling the dynamics of molecules and atoms on the same time scale.I will give a brief introduction to NLO. I will show its importance for science, describe the nonlinear effects that can be observed and some of their applications, with particular focus on those of interest for biology. I will introduce the pump-probe technique for ultrafast spectroscopy, and describe an experiment on the primary step of human vision. Finally, I will describe the applications of NLO to microscopy, showing its advantages in terms of resolution in respect to conventional techniques