We introduce a general theoretical description of non resonant impulsive femtosecond stimulated Raman spectroscopy in a multimode harmonic model. In this technique an ultrashort actinic pulse creates ...coherences of low frequency modes and is followed by a paired narrowband Raman pulse and a broadband probe pulse. Using closed-time-path-loop (CTPL) diagrams, the response on both the red and the blue sides of the broadband pulse with respect to the narrowband Raman pulse is calculated, the process couples high and low frequency modes, which share the same ground state. The transmitted intensity oscillates between the red and the blue side, while the total number of photons is conserved. The total energy of the probe signal is periodically modulated in time by the coherence created in the low frequency modes.
Spontaneous Raman spectroscopy is a formidable tool to probe molecular vibrations. Under electronic resonance conditions, the cross section can be selectively enhanced enabling structural sensitivity ...to specific chromophores and reaction centers. The addition of an ultrashort, broadband femtosecond pulse to the excitation field allows for coherent stimulation of diverse molecular vibrations. Within such a scheme, vibrational spectra are engraved onto a highly directional field, and can be heterodyne detected overwhelming fluorescence and other incoherent signals. At variance with spontaneous resonance Raman, however, interpreting the spectral information is not straightforward, due to the manifold of field interactions concurring to the third order nonlinear response. Taking as an example vibrational spectra of heme proteins excited in the Soret band, we introduce a general approach to extract the stimulated Raman excitation profiles from complex spectral lineshapes. Specifically, by a quantum treatment of the matter through density matrix description of the third order nonlinear polarization, we identify the contributions which generate the Raman bands, by taking into account for the cross section of each process.
Spontaneous Raman is a well‐established tool to probe molecular vibrations. Under resonant conditions, it is a largely used method for characterizing the structure of heme‐proteins. In recent years, ...advances in pulsed laser sources allowed to explore vibrational features with complex techniques based on nonlinear optical interactions, among which is stimulated Raman scattering (SRS). Building on its combined spectral–temporal resolutions and high chemical sensitivities, SRS has been largely applied as a probe for ultrafast, time‐resolved studies, as well as an imaging technique in biological systems. By using a frequency tunable, narrowband pump pulse jointly with a femtosecond white light continuum to initiate the SRS process, here we measure the Raman spectrum of a prototypical heme‐protein, namely deoxy myoglobin, under two different electronic resonances. The SRS results are compared with the spontaneous Raman spectra, and the relative advantages, such as the capability of our experimental approach to provide an accurate mapping of Raman excitation profiles, are discussed.
Combining a frequency tunable, narrowband pump pulse, and a femtosecond white light continuum, the stimulated Raman spectrum of a prototypical heme‐protein, namely, deoxymyoglobin, is measured under two different resonance conditions. Comparison with spontaneous resonant Raman is discussed.
We present the full diagrammatic description of non-resonant impulsive femtosecond stimulated Raman spectroscopy in a multimode model system. In this technique the pump-probe scheme is exploited to ...study the vibrational structure of the sample via stimulated Raman scattering. We apply closed-time-path-loop diagrams to calculate the complete response of the system at the relevant perturbation order. We show that, in presence of low-frequency modes, coherences created by the impulsive pump modify the resulting Raman signal, which oscillates from gain to loss features, depending on the time delay between the pump and probe pulses. This leads to a redistribution of photons among the fields involved in the process and, consequently, the energy flows between fields and matter. Moreover, through this formalism, we address the case of extremely short delays in which the pump and probe fields overlap in time. We find that, even in absence of photo-induced dynamics due to absorption of the pump pulse, the overlap condition can generate time dependent features, arising from additional diagrams, which offer no contribution for well separated pulses.
El presente artículo es resultado de una investigación documental enmarcada en el paradigma cualitativo donde pretendemos plantear algunas reflexiones sobre la ética compleja de Morín en el contexto ...educativo. Utilizamos la metodología hermenéutica. Analizamos e interpretamos bajo nuestra perspectiva subjetiva los diferentes elementos de la ética compleja en el contexto educativo. Finalmente, concluimos que la ética compleja también llamada de resistencia y de religación; es indispensable en la educación porque permite al hombre alejarse de la noción del mal elevando su dimensión altruista. Esta última, necesaria durante la formación educativa de todo ser humano, debido al acompañamiento que recibe de otros seres semejantes a él con los que debe compartir sus conocimientos, habilidades y valores como parte del orden social y planetario.
El presente artículo es resultado de una investigación documental enmarcada en el paradigma cualitativo donde pretendemos plantear algunas reflexiones sobre la ética compleja de Morín en el contexto ...educativo. Utilizamos la metodología hermenéutica. Analizamos e interpretamos bajo nuestra perspectiva subjetiva los diferentes elementos de la ética compleja en el contexto educativo. Finalmente, concluimos que la ética compleja también llamada de resistencia y de religación; es indispensable en la educación porque permite al hombre alejarse de la noción del mal elevando su dimensión altruista. Esta última, necesaria durante la formación educativa de todo ser humano, debido al acompañamiento que recibe de otros seres semejantes a él con los que debe compartir sus conocimientos, habilidades y valores como parte del orden social y planetario.
A reliable, quantitative assessment of humidification performances of passive heat and moisture exchangers in mechanically-ventilated patients is still to be achieved, although relevant efforts have ...been made to date. One of the major problems to tackle consists in the difficulty of humidity measurements, both in vivo (during either anaesthesia or intensive care unit treatments) and in vitro set-ups. In this paper a review of the basic operation principles of humidity sensors as well as an analysis of their usagewithin in vivo and in vitro tests are presented. Particular attention is devoted to the limitations arising from the specific measurement set-up, as they may affect the results notably.
Heart failure (HF) is a leading cause of mortality. Inflammation is implicated in HF, yet clinical trials targeting pro-inflammatory cytokines in HF were unsuccessful, possibly due to redundant ...functions of individual cytokines. Searching for better cardiac inflammation targets, here we link T cells with HF development in a mouse model of pathological cardiac hypertrophy and in human HF patients. T cell costimulation blockade, through FDA-approved rheumatoid arthritis drug abatacept, leads to highly significant delay in progression and decreased severity of cardiac dysfunction in the mouse HF model. The therapeutic effect occurs via inhibition of activation and cardiac infiltration of T cells and macrophages, leading to reduced cardiomyocyte death. Abatacept treatment also induces production of anti-inflammatory cytokine interleukin-10 (IL-10). IL-10-deficient mice are refractive to treatment, while protection could be rescued by transfer of IL-10-sufficient B cells. These results suggest that T cell costimulation blockade might be therapeutically exploited to treat HF.
Background
As treatment interruptions occur during psoriasis management in clinical practice, it is important to know the duration of clinical response after treatment withdrawal.
Objectives
To ...report time to and predictors of relapse in patients who were tildrakizumab 100 and 200 mg responders (≥75% improvement in Psoriasis Area and Severity Index, PASI 75) at week 28 re‐randomized to placebo from reSURFACE 1 trial.
Methods
Post hoc analysis of adult patients with moderate‐to‐severe plaque psoriasis from a 64‐week phase 3 trial. Relapse was primarily defined as loss of PASI 75 response. Both relapses defined as loss of PASI 90 and loss of absolute PASI < 2 response were included as sensitivity analyses. PASI 75, PASI 90 and PASI < 2 responders re‐randomized to placebo at week 28 and followed up until week 64 were included. The Kaplan–Meier (KM) estimates of the 64‐week relapse rate were calculated. The log‐rank test to compare KM curves from responders to tildrakizumab 100 and 200 mg was used. Independent predictors of relapse were explored.
Results
Median time to loss of PASI 75/PASI 90/PASI < 2 response from week 28 was 142/111/112 days with tildrakizumab 100 mg and 172/140/113 days with tildrakizumab 200 mg, respectively (all not significant). Around 20% of patients did not relapse (either maintained a PASI 75 response or were lost to follow‐up) during the 36‐week period. Increase in body mass index (BMI) (hazard ratio, HR 95% confidence interval, CI for loss of PASI 75 response: 1.0345 1.0112–1.0582) and increase in disease duration (HR 95% CI: 1.0151 1.0028–1.0275 for loss of PASI 75 response) were associated with an increased risk of relapse, regardless of the relapse definition.
Conclusions
When treatment is interrupted, tildrakizumab provides durable maintenance of efficacy with a median time to loss of PASI 75 response of 5–6 months, irrespective of the dose. Interventions on modifiable risk factors for relapse, such as BMI, may improve personalized long‐term psoriasis management.
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