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1.
Opt Express ; 32(3): 4072-4080, 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38297615

RESUMO

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.

2.
Opt Express ; 31(12): 18898-18906, 2023 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-37381320

RESUMO

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.

3.
Opt Lett ; 47(20): 5289-5292, 2022 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-36240345

RESUMO

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.

4.
Opt Lett ; 47(10): 2374-2377, 2022 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-35561354

RESUMO

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.

5.
Nat Commun ; 10(1): 306, 2019 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-30659202

RESUMO

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.


Assuntos
Glucocorticoides/farmacologia , Fígado/efeitos dos fármacos , Receptores de Glucocorticoides/genética , Fator 3 de Transcrição/genética , Animais , Imunoprecipitação da Cromatina/métodos , Fígado Gorduroso/metabolismo , Perfilação da Expressão Gênica , Glucocorticoides/efeitos adversos , Glucose/genética , Glucose/metabolismo , Metabolismo dos Lipídeos/genética , Fígado/metabolismo , Masculino , Camundongos Knockout , Fator 3 de Transcrição/metabolismo
6.
Opt Express ; 26(10): 12536-12546, 2018 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-29801292

RESUMO

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.

7.
Bone Marrow Transplant ; 52(11): 1549-1555, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28869618

RESUMO

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.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Tumor de Wilms/terapia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Lactente , Masculino , Recidiva , Estudos Retrospectivos , Terapia de Salvação/métodos , Terapia de Salvação/mortalidade , Análise de Sobrevida , Transplante Autólogo , Resultado do Tratamento , Tumor de Wilms/mortalidade , Adulto Jovem
8.
Bone Marrow Transplant ; 52(3): 400-408, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27941764

RESUMO

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.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Doença Enxerto-Hospedeiro/mortalidade , Doença Enxerto-Hospedeiro/prevenção & controle , Leucemia/mortalidade , Leucemia/terapia , Doença Aguda , Adolescente , Soro Antilinfocitário/administração & dosagem , Criança , Pré-Escolar , Doença Crônica , Intervalo Livre de Doença , Feminino , Doença Enxerto-Hospedeiro/etiologia , Humanos , Lactente , Recém-Nascido , Masculino , Sistema de Registros , Taxa de Sobrevida , Condicionamento Pré-Transplante
9.
Science ; 354(6310): 308-312, 2016 10 21.
Artigo em Inglês | MEDLINE | ID: mdl-27846561

RESUMO

Visualizing chemical reactions as they occur requires atomic spatial and femtosecond temporal resolution. Here, we report imaging of the molecular structure of acetylene (C2H2) 9 femtoseconds after ionization. Using mid-infrared laser-induced electron diffraction (LIED), we obtained snapshots as a proton departs the [C2H2]2+ ion. By introducing an additional laser field, we also demonstrate control over the ultrafast dissociation process and resolve different bond dynamics for molecules oriented parallel versus perpendicular to the LIED field. These measurements are in excellent agreement with a quantum chemical description of field-dressed molecular dynamics.

10.
Opt Lett ; 41(15): 3583-6, 2016 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-27472624

RESUMO

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.

11.
Nat Commun ; 7: 11493, 2016 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-27167525

RESUMO

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.

12.
Steroids ; 114: 7-15, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27192428

RESUMO

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.


Assuntos
Inflamação/metabolismo , Receptores de Glucocorticoides/metabolismo , Animais , Glucocorticoides/metabolismo , Humanos , Inflamação/genética , Camundongos , Camundongos Transgênicos , Ligação Proteica , Receptores de Glucocorticoides/genética
13.
Opt Lett ; 41(3): 492-5, 2016 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-26907405

RESUMO

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.

14.
Nucl Instrum Methods Phys Res A ; 829: 24-29, 2016 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-28706325

RESUMO

X-ray crystallography is one of the main methods to determine atomic-resolution 3D images of the whole spectrum of molecules ranging from small inorganic clusters to large protein complexes consisting of hundred-thousands of atoms that constitute the macromolecular machinery of life. Life is not static, and unravelling the structure and dynamics of the most important reactions in chemistry and biology is essential to uncover their mechanism. Many of these reactions, including photosynthesis which drives our biosphere, are light induced and occur on ultrafast timescales. These have been studied with high time resolution primarily by optical spectroscopy, enabled by ultrafast laser technology, but they reduce the vast complexity of the process to a few reaction coordinates. In the AXSIS project at CFEL in Hamburg, funded by the European Research Council, we develop the new method of attosecond serial X-ray crystallography and spectroscopy, to give a full description of ultrafast processes atomically resolved in real space and on the electronic energy landscape, from co-measurement of X-ray and optical spectra, and X-ray diffraction. This technique will revolutionize our understanding of structure and function at the atomic and molecular level and thereby unravel fundamental processes in chemistry and biology like energy conversion processes. For that purpose, we develop a compact, fully coherent, THz-driven atto-second X-ray source based on coherent inverse Compton scattering off a free-electron crystal, to outrun radiation damage effects due to the necessary high X-ray irradiance required to acquire diffraction signals. This highly synergistic project starts from a completely clean slate rather than conforming to the specifications of a large free-electron laser (FEL) user facility, to optimize the entire instrumentation towards fundamental measurements of the mechanism of light absorption and excitation energy transfer. A multidisciplinary team formed by laser-, accelerator,- X-ray scientists as well as spectroscopists and biochemists optimizes X-ray pulse parameters, in tandem with sample delivery, crystal size, and advanced X-ray detectors. Ultimately, the new capability, attosecond serial X-ray crystallography and spectroscopy, will be applied to one of the most important problems in structural biology, which is to elucidate the dynamics of light reactions, electron transfer and protein structure in photosynthesis.

15.
Opt Lett ; 40(4): 451-4, 2015 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-25680122

RESUMO

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.

16.
Opt Lett ; 39(24): 6883-6, 2014 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-25503021

RESUMO

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.

17.
Opt Lett ; 39(20): 5802-5, 2014 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-25361089

RESUMO

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.

18.
Reprod Toxicol ; 48: 51-61, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24907688

RESUMO

Proper formation of the vascular system is necessary for embryogenesis, and chemical disruption of vascular development may be a key event driving developmental toxicity. In order to test the effect of environmental chemicals on this critical process, we evaluated a quantitative assay in transgenic zebrafish using angiogenesis inhibitors that target VEGFR2 (PTK787) or EGFR (AG1478). Both PTK787 and AG1478 exposure impaired intersegmental vessel (ISV) sprouting, while AG1478 also produced caudal and pectoral fin defects at concentrations below those necessary to blunt ISV morphogenesis. The functional consequences of vessel toxicity during early development included decreased body length and survival in juvenile cohorts developmentally exposed to inhibitor concentrations sufficient to completely block ISV sprouting angiogenesis. These data show that concentration-dependent disruption of the presumed targets for these inhibitors produce adverse outcomes at advanced life stages.


Assuntos
Vasos Sanguíneos/embriologia , Embrião não Mamífero/embriologia , Receptores ErbB/antagonistas & inibidores , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Peixe-Zebra/embriologia , Inibidores da Angiogênese/farmacologia , Animais , Animais Geneticamente Modificados , Vasos Sanguíneos/efeitos dos fármacos , Embrião não Mamífero/efeitos dos fármacos , Desenvolvimento Embrionário/efeitos dos fármacos , Desenvolvimento Embrionário/fisiologia , Ftalazinas/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Piridinas/farmacologia , Quinazolinas/farmacologia , Tirfostinas/farmacologia
19.
Opt Lett ; 39(18): 5383-6, 2014 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-26466278

RESUMO

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.

20.
Sci Rep ; 3: 2675, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24043222

RESUMO

Strong-field ionisation surprises with richness beyond current understanding despite decade long investigations. Ionisation with mid-IR light has promptly revealed unexpected kinetic energy structures that seem related to unanticipated quantum trajectories of the electrons. We measure first 3D momentum distributions in the deep tunneling regime (γ = 0.3) and observe surprising new electron dynamics of near-zero momentum electrons and extremely low momentum structures, below the eV, despite very high quiver energies of 95 eV. Such level of high-precision measurements at only 1 meV above the threshold, despite 5 orders higher ponderomotive energies, has now become possible with a specifically developed ultrafast mid-IR light source in combination with a reaction microscope, thereby permitting a new level of investigations into mid-IR recollision physics.

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