Compact, ultrastable, high repetition-rate 2 µm and 3 µm fiber laser for seeding mid-IR OPCPA.

We report a compact and reliable ultrafast fiber laser system optimized for seeding a high energy, 2 µm pumped, 3 µm wavelength optical parametric chirped pulse amplification to drive soft X-ray high harmonics. The system delivers 100 MHz narrowband 2 µm pulses with >1 nJ energy, synchronized with ultra-broadband optical pulses with a ∼1 µm FWHM spectrum centered at 3 µm with 39 pJ pulse energy. The 2 µm and 3 µm pulses are derived from a single 1.5 µm fiber oscillator, fully fiber integrated with free-space downconversion for the 3 µm. The system operates hands-off with power instabilities <0.2% over extended periods of time.

Numerical investigation of gas-filled multipass cells in the enhanced dispersion regime for clean spectral broadening and pulse compression.

We show via numerical simulations that the regime of enhanced frequency chirp can be achieved in gas-filled multipass cells. Our results demonstrate that there exists a region of pulse and cell parameters for which a broad and flat spectrum with a smooth parabolic-like phase can be generated. This spectrum is compatible with clean ultrashort pulses, whose secondary structures are always below the 0.5% of its peak intensity such that the energy ratio (the energy contained within the main peak of the pulse) is above 98%. This regime makes multipass cell post-compression one of the most versatile schemes to sculpt a clean intense ultrashort optical pulse.

Nonlinear post-compression in multi-pass cells in the mid-IR region using bulk materials.

We numerically investigate the regime of nonlinear pulse compression at mid-IR wavelengths in a multi-pass cell (MPC) containing a dielectric plate. This post-compression setup allows for ionization-free spectral broadening and self-compression while mitigating self-focusing effects. We find that self-compression occurs for a wide range of MPC and pulse parameters and derive scaling rules that enable its optimization. We also reveal the solitonic dynamics of the pulse propagation in the MPC and its limitations and show that spatiotemporal/spectral couplings can be mitigated for appropriately chosen parameters. In addition, we reveal the formation of spectral features akin to quasi-phase matched degenerate four-wave mixing. Finally, we present two case studies of self-compression at 3-µm and 6-µm wavelengths using pulse parameters compatible with driving high-field physics experiments. The simulations presented in this paper set a framework for future experimental work using few-cycle pulses at mid-IR wavelengths.

Highly efficient generation of narrowband terahertz radiation driven by a two-spectral-line laser in PPLN.

We demonstrate record ∼0.9% efficiencies for optical conversion to narrowband (<1% relative bandwidth) terahertz (THz) radiation by strongly cascaded difference frequency generation. These results are achieved using a novel, to the best of our knowledge, laser source, customized for high efficiencies, with two narrow spectral lines of variable separation and pulse duration (≥250 ps). THz radiation generation in 5% MgO-doped periodically poled lithium niobate (PPLN) crystals of varying poling period was explored at cryogenic and room temperature operation as well as with different crystal lengths. This work addresses an increasing demand for high-field THz radiation pulses which has, up to now, been largely limited by low optical-to-THz radiation conversion efficiencies.

Cascaded interactions mediated by terahertz radiation.

We investigate a regime of parametric amplification in which the pump and signal waves are spectrally separated by only a few hundreds of GHz frequency - therefore resulting in a sub-THz frequency idler wave. Operating in this regime we find an optical parametric amplifier (OPA) behavior which is highly dissimilar to conventional OPAs. In this regime, we observe multiple three-wave mixing processes occurring simultaneously which results in spectral cascading around the pump and signal wave. Via numerical simulations, we elucidate the processes at work and show that cascaded optical parametric amplification offers a pathway toward THz-wave generation beyond the Manly-Rowe limit and toward the generation of high-energy, sparse frequency-combs.

250 W average power, 100 kHz repetition rate cryogenic Yb:YAG amplifier for OPCPA pumping.

A cryogenically cooled, bulk Yb:YAG, four-pass amplifier delivering up to 250 W average power at 100 kHz repetition rate is reported. The 2.5 mJ amplified optical pulses show a sub-20 ps duration before temporal compression and a spectrum supporting a transform-limited duration of 3.6 ps. The power instabilities were measured to be <0.5% rms over 30 min at full power, and the spatial intensity profile showed a flat-top distribution and near diffraction-limited beam quality. This compact amplifier is an ideal source for pumping either near-IR or mid-IR optical parametric chirped pulse amplifiers.

High power multi-color OPCPA source with simultaneous femtosecond deep-UV to mid-IR outputs.

Many experimental investigations demand synchronized pulses at various wavelengths, ideally with very short pulse duration and high repetition rate. Here we describe a femtosecond multi-color optical parametric chirped pulse amplifier (OPCPA) with simultaneous outputs from the deep-UV to the mid-IR with optical synchronization. The high repetition rate of 160 kHz is well suited to compensate for low interaction probability or low cross section in strong-field interactions. Our source features high peak powers in the tens to hundreds of MW regime with pulse durations below 110 fs, which is ideal for pump-probe experiments of nonlinear and strong-field physics. We demonstrate its utility by strong-field ionization experiments of xenon in the near- to mid-IR.

2-µm wavelength, high-energy Ho:YLF chirped-pulse amplifier for mid-infrared OPCPA.

A 2-µm wavelength laser delivering up to 39-mJ energy, ∼10 ps duration pulses at 100-Hz repetition rate is reported. The system relies on chirped pulse amplification (CPA): a modelocked Er:Tm:Ho fiber-seeder is followed by a Ho:YLF-based regenerative amplifier and a cryogenically cooled Ho:YLF single pass amplifier. Stretching and compressing are performed with large aperture chirped volume Bragg gratings (CVBG). At a peak power of 3.3 GW, the stability was <1% rms over 1 h, confirming high suitability for OPCPA and extreme nonlinear optics applications.

Performance of MgO:PPLN, KTA, and KNbO3 for mid-wave infrared broadband parametric amplification at high average power.

The performance of potassium niobate (KNbO3), MgO-doped periodically poled lithium niobate (MgO:PPLN), and potassium titanyl arsenate (KTA) were experimentally compared for broadband mid-wave infrared parametric amplification at a high repetition rate. The seed pulses, with an energy of 6.5 µJ, were amplified using 410 µJ pump energy at 1064 nm to a maximum pulse energy of 28.9 µJ at 3 µm wavelength and at a 160 kHz repetition rate in MgO:PPLN while supporting a transform limited duration of 73 fs. The high average powers of the interacting beams used in this study revealed average power-induced processes that limit the scaling of optical parametric amplification in MgO:PPLN; the pump peak intensity was limited to 3.8 GW/cm² due to nonpermanent beam reshaping, whereas in KNbO3 an absorption-induced temperature gradient in the crystal led to permanent internal distortions in the crystal structure when operated above a pump peak intensity of 14.4 GW/cm².

High-flux table-top soft x-ray source driven by sub-2-cycle, CEP stable, 1.85-µm 1-kHz pulses for carbon K-edge spectroscopy.

We report on the first table-top high-flux source of coherent soft x-ray radiation up to 400 eV, operating at 1 kHz. This source covers the carbon K-edge with a beam brilliance of (4.3±1.2)×10(15) photons/s/mm(2)/strad/10% bandwidth and a photon flux of (1.85±0.12)×10(7) photons/s/1% bandwidth. We use this source to demonstrate table-top x-ray near-edge fine-structure spectroscopy at the carbon K-edge of a polyimide foil and retrieve the specific absorption features corresponding to the binding orbitals of the carbon atoms in the foil.

Broadband mid-IR frequency comb with CdSiP2 and AgGaS2 from an Er,Tm:Ho fiber laser.

We report on the generation of a 2500 nm bandwidth frequency comb at 6.5 µm central wavelength based on critically phase-matched parametric down-conversion in the nonlinear crystal CdSiP(2) (CSP), driven by a compact Er,Tm:Ho fiber laser. The generated ultra-broadband pulses show a transform-limited duration of 2.3 optical cycles and carry up to 150 pJ of energy at a 100 MHz pulse repetition rate. For comparison, the spectrum generated in AgGaS(2) (AGS) spans from 6.2 to 7.4 µm at full-width at half-maximum (FWHM) with a pulse energy of 3 pJ. A full 3D nonlinear wave propagation code is used for optimization of the noncollinear angle, propagation direction, and crystal thickness.

Impact of a model synovial fluid on supported lipid membranes.

The interaction of a model synovial fluid, here a solution of 3mg/mL hyaluronic acid (HA) in heavy water (D(2)O), with an oligolamellar stack of lipid (DMPC) membranes on silicon support has been studied by neutron reflectometry and infrared spectroscopy on the molecular scale at non-physiological and physiological conditions. The system under investigation represents a simple model for lipid-coated mammalian joints and other artificial implant surfaces. When exposed to pure D(2)O at 21°C, i.e. below the main phase transition of the system, the lipid membranes show a lamellar spacing of 65Å. Heating to 26°C results in detachment of all lipid bilayers except for the innermost lipid lamella directly adsorbed to the surface of the silicon support. On the contrary, when incubated in the solution of HA in D(2)O the oligolamellar lipid system starts swelling. In addition, heating to 39°C does not result in loss of the lipid membranes into the liquid phase. The interfacial lipid coating adopts a new stable lamellar state with an increase in d-spacing by 380% to 247Å measured after 43 days of incubation with the model synovial fluid. Potential consequences for joint lubrication and protective wear functionality are considered.

All-PM coherent 2.05 µm Thulium/Holmium fiber frequency comb source at 100 MHz with up to 0.5 W average power and pulse duration down to 135 fs.

We report on a dual output all-PM fiber laser system running at 100 MHz repetition rate offering coherent broadband and narrowband pulses centered at 2.05 µm with a spectral FWHM bandwidth of 60 nm and 1.5 nm at up to 360 mW and 500 mW, respectively. The broadband pulses are compressed down to 135 fs. The multi-stage double-clad amplifier based on Tm/Ho codoping is seeded by a supercontinuum light source, spanning from around 1 µm up to 2.4 µm.

Sub-250-mrad, passively carrier-envelope-phase-stable mid-infrared OPCPA source at high repetition rate.

An all-optical and passively carrier-to-envelope-phase-stabilized (CEP-stabilized) optical parametric chirped pulse amplification (OPCPA) system is demonstrated with sub-250-mrad CEP stability over 11 min and better than 100 mrad over 11 s. This is achieved without any electronic CEP stabilization loop for 160 kHz pulse repetition rate in the few cycle regime.

Identification of estrogen-responsive vitelline envelope protein fragments from rainbow trout (Oncorhynchus mykiss) plasma using mass spectrometry.

Plasma peptides previously associated with exposure of juvenile male rainbow trout (Oncorhynchus mykiss) to the hormone 17ß-estradiol (E2) were identified using matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS). Specifically, plasma peptides of interest were fractionated and subsequently identified via spectra obtained by MALDI QqTOF MS/MS and LC-MALDI TOFTOF MS/MS analysis, de novo sequencing and database matching. The two peptide masses were identified as significant matches for fragments of the C-terminal propeptides from rainbow trout vitelline envelope protein (VEP)α and VEPγ isoforms. Our findings document the presence of the C-terminal propeptides from rainbow trout VEPα and VEPγ proteins in the bloodstream of juvenile male rainbow trout exposed to E2 via MALDI-TOF-MS detection. We provide three possible explanations for the presence of C-terminal propeptides in the bloodstream, as well as compare previously obtained hepatic transcriptomic results with the plasma proteomic results obtained in the present study.

E47 modulates hepatic glucocorticoid action.

Glucocorticoids (GCs) are effective drugs, but their clinical use is compromised by severe side effects including hyperglycemia, hyperlipidemia and obesity. They bind to the Glucocorticoid Receptor (GR), which acts as a transcription factor. The activation of metabolic genes by GR is thought to underlie these adverse effects. We identify the bHLH factor E47 as a modulator of GR target genes. Using mouse genetics, we find that E47 is required for the regulation of hepatic glucose and lipid metabolism by GR, and that loss of E47 prevents the development of hyperglycemia and hepatic steatosis in response to GCs. Here we show that E47 and GR co-occupy metabolic promoters and enhancers. E47 is needed for the efficient recruitment of GR and coregulators such as Mediator to chromatin. Altogether, our results illustrate how GR and E47 regulate hepatic metabolism, and might provide an entry point for novel therapies with reduced side effects.

Outcomes following autologous hematopoietic stem cell transplant for patients with relapsed Wilms' tumor: a CIBMTR retrospective analysis.

Despite the marked improvement in the overall survival (OS) for patients diagnosed with Wilms' tumor (WT), the outcomes for those who experience relapse have remained disappointing. We describe the outcomes of 253 patients with relapsed WT who received high-dose chemotherapy (HDT) followed by autologous hematopoietic stem cell transplant (HCT) between 1990 and 2013, and were reported to the Center for International Blood and Marrow Transplantation Research. The 5-year estimates for event-free survival (EFS) and OS were 36% (95% confidence interval (CI); 29-43%) and 45% (95 CI; 38-51%), respectively. Relapse of primary disease was the cause of death in 81% of the population. EFS, OS, relapse and transplant-related mortality showed no significant differences when broken down by disease status at transplant, time from diagnosis to transplant, year of transplant or conditioning regimen. Our data suggest that HDT followed by autologous HCT for relapsed WT is well tolerated and outcomes are similar to those reported in the literature. As attempts to conduct a randomized trial comparing maintenance chemotherapy with consolidation versus HDT followed by stem cell transplant have failed, one should balance the potential benefits with the yet unknown long-term risks. As disease recurrence continues to be the most common cause of death, future research should focus on the development of consolidation therapies for those patients achieving complete response to therapy.

GvHD after umbilical cord blood transplantation for acute leukemia: an analysis of risk factors and effect on outcomes.

Using the Center for International Blood and Marrow Transplant Research (CIBMTR) registry, we analyzed 1404 umbilical cord blood transplantation (UCBT) patients (single (<18 years)=810, double (⩾18 years)=594) with acute leukemia to define the incidence of acute GvHD (aGvHD) and chronic GvHD (cGvHD), analyze clinical risk factors and investigate outcomes. After single UCBT, 100-day incidence of grade II-IV aGvHD was 39% (95% confidence interval (CI), 36-43%), grade III-IV aGvHD was 18% (95% CI, 15-20%) and 1-year cGvHD was 27% (95% CI, 24-30%). After double UCBT, 100-day incidence of grade II-IV aGvHD was 45% (95% CI, 41-49%), grade III-IV aGvHD was 22% (95% CI, 19-26%) and 1-year cGvHD was 26% (95% CI, 22-29%). For single UCBT, multivariate analysis showed that absence of antithymocyte globulin (ATG) was associated with aGvHD, whereas prior aGvHD was associated with cGvHD. For double UCBT, absence of ATG and myeloablative conditioning were associated with aGvHD, whereas prior aGvHD predicted for cGvHD. Grade III-IV aGvHD led to worse survival, whereas cGvHD had no significant effect on disease-free or overall survival. GvHD is prevalent after UCBT with severe aGvHD leading to higher mortality. Future research in UCBT should prioritize prevention of GvHD.

0.5-keV Soft X-ray attosecond continua.

Attosecond light pulses in the extreme ultraviolet have drawn a great deal of attention due to their ability to interrogate electronic dynamics in real time. Nevertheless, to follow charge dynamics and excitations in materials, element selectivity is a prerequisite, which demands such pulses in the soft X-ray region, above 200 eV, to simultaneously cover several fundamental absorption edges of the constituents of the materials. Here, we experimentally demonstrate the exploitation of a transient phase matching regime to generate carrier envelope controlled soft X-ray supercontinua with pulse energies up to 2.9±0.1 pJ and a flux of (7.3±0.1) × 10(7) photons per second across the entire water window and attosecond pulses with 13 as transform limit. Our results herald attosecond science at the fundamental absorption edges of matter by bridging the gap between ultrafast temporal resolution and element specific probing.

There goes the neighborhood: Assembly of transcriptional complexes during the regulation of metabolism and inflammation by the glucocorticoid receptor.

Glucocorticoids (GCs), as ligands for the glucocorticoid receptor (GR), represent one of the most effective and frequently used classes of drugs for anti-inflammatory and immunosuppressive therapy. In addition, its role in physiological and pathophysiological processes makes the GR an important research target. The past decades have yielded a wealth of insight into the physiological and pharmacological effects of GCs. Today's era of next generation sequencing techniques is now beginning to elucidate the molecular and genomic circuits underlying GR's cell type-specific actions. This review focuses on the concepts and insights gained from recent studies in two of the most important tissues for GC action: the liver (mediating GR's metabolic effects) and macrophages (as the main target of anti-inflammatory GC therapy). We summarize results obtained from transgenic mouse models, molecular and genome-wide studies to illustrate GR's complex interactions with DNA, chromatin, co-regulators and other transcription factors. Characterizing the cell type-specific transcriptional complexes assembled around GR will pave the road for the development of new anti-inflammatory and metabolic therapies in the future.