The ONIOM/PMM Model for Effective Yet Accurate Simulation of Optical and Chiroptical Spectra in Solution: Camphorquinone in Methanol as a Case Study

This paper deals with the development and first validation of a composite approach for the simulation of chiroptical spectra in solution aimed to strongly reduce the number of full QM computations without any significant accuracy loss. The approach starts from the quantum mechanical computation of reference spectra including vibrational averaging effects and taking average solvent effects into account by means of the polarizable continuum model. Next, the snapshots of classical molecular dynamics computations are clusterized and one reference configuration from each cluster is used to compute a reference spectrum. Local fluctuation effects within each cluster are then taken into account by means of the perturbed matrix model. The performance of the proposed approach is tested on the challenging case of the optical and chiroptical spectra of camphorquinone in methanol solution. Although further validations are surely needed, the results of this first study are quite promising also taking into account that agreement with experimental data is reached by just a couple of full quantum mechanical geometry optimizations and frequency computations

CPL Spectra of Camphor Derivatives in Solution by an Integrated QM/MD Approach

We extend a recently proposed computational strategy for the simulation of absorption spectra of semi-rigid molecular systems in condensed phases to the emission spectra of flexible chromophores. As a case study, we have chosen the CPL spectrum of camphor in methanol solution, which shows a well-defined bisignate shape. The first step of our approach is the quantum mechanical computation of reference spectra including vibrational averaging effects and taking bulk solvent effects into account by means of the polarizable continuum model. In the present case, the large amplitude inversion mode is explicitly treated by a numerical approach, whereas the other small-amplitude vibrational modes are taken into account within the harmonic approximation. Next, the snapshots of classical molecular dynamics computations are clusterized and one representative configuration from each cluster is used to compute a reference spectrum. In the present case, different clusters correspond to the two stable conformers of camphor in the S1 excited electronic state and, for each of them, to different numbers of strong solute-solvent hydrogen bonds. Finally, local fluctuation effects within each cluster are taken into account by means of the perturbed matrix model. The overall procedure leads to good agreement with experiment for absorption and emission spectra together with their chiral counterparts, thus allowing to analyze the role of different effects (stereo-electronic, vibrational, environmental) in tuning the overall experimental spectra

The role of allograft inflammatory factor 1 in systemic sclerosis

Purpose of review: The aim of this article is to review studies which support the hypothesis that allograft inflammatory factor-1, a protein initially identified in chronically rejected cardiac allografts, may be involved in the pathogenesis of the progressive fibroproliferative vasculopathy which is a hallmark of systemic sclerosis. Recent findings: Recent findings demonstrated elevated allograft inflammatory factor-1 expression both in systemic sclerosis affected tissues and peripheral blood mononuclear cells. A detailed immunohistopathologic study examined the tissue and cellular localization of the protein in affected systemic sclerosis tissues and demonstrated its expression in the endothelium of dermal and pulmonary vessels, in the pulmonary parenchyma, and in relevant inflammatory cells including T cells and macrophages. Furthermore, functional studies showed specific allograft inflammatory factor-1 isoform expression stimulation by transforming growth factor-[beta]. Summary: This review summarizes recent findings suggesting that allograft inflammatory factor-1 may play an important role in systemic sclerosis vasculopathy and provides supporting evidence to consider the molecule as a novel therapeutic target

Computational Spectroscopy in Solution by Integration of Variational and Perturbative Approaches on Top of Clusterized Molecular Dynamics

Multiscale QM/MM approaches have become the most suitable and effective methods for the investigation of spectroscopic properties of medium-or large-size chromophores in condensed phases. On these grounds, we are developing a novel workflow aimed at improving the generality, reliability, and ease of use of the available tools. In the present paper, we report the latest developments of such an approach with specific reference to a general workplan starting with the addition of acetonitrile to the panel of solvents already available in the General Liquid Optimized Boundary (GLOB) model enforcing nonperiodic boundary conditions (NPBC). Next, the solvatochromic shifts induced by acetonitrile on both rigid (uracil and thymine) and flexible (thyrosine) chromophores have been studied introducing in our software a number of new features ranging from rigid-geometry NPBC molecular dynamics based on the quaternion formalism to a full integration of variational (ONIOM) and perturbative (perturbed matrix method (PMM)) approaches for describing different solute-solvent topologies and local fluctuations, respectively. Finally, thymine and uracil have been studied also in methanol to point out the generality of the computational strategy. While further developments are surely needed, the strengths of our integrated approach even in its present version are demonstrated by the accuracy of the results obtained by an unsupervised approach and coupled to a computational cost strongly reduced with respect to that of conventional QM/MM models without any appreciable accuracy deterioration

Expression of allograft inflammatory factor 1 in tissues from patients with systemic sclerosis and in vitro differential expression of its isoforms in response to transforming growth factor beta

OBJECTIVE: Allograft inflammatory factor 1 (AIF-1), a protein initially identified in chronically rejected rat cardiac allografts, is involved in the immune response and proliferative vasculopathy that occurs during allograft rejection. Three well-characterized isoforms of AIF-1 result from alternative messenger RNA (mRNA) splicing. We previously identified a strong association of systemic sclerosis (SSc) with a polymorphism in AIF-1 isoform 2. The purpose of this study was to investigate AIF-1 expression in affected tissues from patients with SSc and to examine the regulation of its isoforms by transforming growth factor beta (TGFbeta). METHODS: AIF-1 in the skin and lung tissues of patients with SSc was analyzed by immunochemistry. AIF-1 isoform expression in response to TGFbeta and interferon-gamma stimulation was examined by quantitative polymerase chain reaction (PCR). RESULTS: AIF-1 protein was present in affected vessels of the lung and skin lesions of patients with SSc. Quantitative PCR showed an average of 14-fold higher mRNA levels in affected SSc skin than in normal skin. Double-label immunofluorescence staining demonstrated that T cells, macrophages, and endothelial cells in affected tissues expressed AIF-1. Stimulation of peripheral blood mononuclear cells with TGFbeta caused a specific and significant increase in the expression of AIF-1 isoform 2 transcripts (P \u3c 0.005), which was due to stabilization of AIF-1 isoform 2 mRNA. CONCLUSION: These data suggest that AIF-1 plays an important role in the pathogenesis of SSc owing to its increased expression in affected tissues and to the specific stimulation of AIF-1 isoform 2 by TGFbeta

Blends of wood chips from oak and cherry: impact on the general phenolic parameters and sensory profile of a white wine during the aging process

Today, there is a restricted knowledge about the potential impact of the use of different wood chip species on the white wine aging process. This lack of knowledge is even greater when wood species are used in blends of different species. Thus, the aim was to carry out a comparative analysis of the impact of different blends of wood chip species, involving oak and cherry wood, on different phenolic and color parameters, browning potential index and sensory profile of a white wine during the aging process. During the aging time studied, the use of wood chips induced an increase of wine phenolic content and color intensity, particularly in wines aged in contact with cherry wood chips alone or in blends with oak wood chips. A similar tendency was also detected for browning potential index. Regarding the sensorial results, the use of different wood chip species has an impact on the increase of "woody aroma" for the wines aged with oak wood chip species and also an increase of "body" and "astringency" descriptors for the wines aged with oak chips alone or blended with cherry chips. This work advances our understanding of the impact of different wood chip species separately or by the use of blends on white wine quality

Calcificaciones heterotópicas en cirugía protésica de cadera: Prótesis bicénctricas vs híbridas

Realizamos el seguimiento clínico y radiológico de 202 pacientes a los que se implantó una Prótesis Total de Cadera cementada (PTC). Analizamos la presencia de calcificaciones heterotópicas (CH) y su graduación, estudiando separadamente prótesis híbridas y bicéntricas. Valoramos los factores de riesgo relacionados con la aparición de CH, tamaño de implantes, alineación final, lado intervenido y relación con la presencia de complicaciones locales y sistemáticas. La prevalencia de CH fue de 35.5% (grado I, 19%; grado II, 10%; grado III, 5% y grado IV 1,5%); 9,9 % sintomáticas. Una mayor proporción de CH fue observada en varones (p=0,005); vástagos de mayor tamaño (p=0,001). No existen diferencias significativas (p=0,059) entre pacientes con prótesis híbridas frente a aquellos con prótesis bicéntricas. La valoración de Harris mostró diferencias en el seguimiento del parámetro dolor a los 24 meses entre los grupos con y sin CH.The clinical and radiological follow-up of 202 patients with a cemented Hip Artrhoplasty (HA) was reviewed. The presence of periarticular heterotopic ossifications (PHO) and its gradation was compared i9n hybrid and bipolar arthroplasties. Risk factors related to the appearance of PHO, implants size, final alignment, operated side and relationship to the postoperative local and systemic complications were several of the parameter analyzed. The presence of PHO was 35,5% (degree I, 19%; degree II, 10%; degree III, 5% and degree IV, 1,5%); 9,9% symptomatic. A greater proportion of PHO was observed in males (p=0,005) greater zie stems (p=0,001) and patients with postoperative local complications (p=0,001). There were no statistical differences between patients with hybrid hip arthoplasties as compared to those with bipolar his arthroplasties. The Harris score showed differences as regards pain at 24 months follow-up between the groups whit an without PHO