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

Assessment of Multi-Scale Approaches for Computing UV-Vis Spectra in Condensed Phases: Toward an Effective yet Reliable Integration of Variational and Perturbative QM/MM Approaches

Computational simulation of UV/vis spectra in condensed phases can be performed starting from converged molecular dynamics (MD) simulations and then performing quantum mechanical/molecular mechanical (QM/MM) computations for a statistically significant number of snapshots. However, the need of variational solutions (e.g., ONIOM/EE) for a huge number of snapshots makes unpractical the use of state-of-the-art QM Hamiltonians. On the other hand, the effectivity of perturbative approaches (e.g., perturbed matrix method, PMM) comes at the price of poor convergence for configurations strongly different from the reference one. In this paper we introduce an integrated strategy based on a cluster analysis of the MD snapshots. Next, a representative configuration for each cluster is treated at the ONIOM/EE level, whereas local fluctuations within each cluster are described at the PMM level. Some representative systems (uracil in dimethylformamide and in water and tyrosine zwitterion in water) are analyzed to show the effectivity and flexibility of the proposed strategy

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

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

Quality improvement of medical records in a teaching hospital

Introduction. The aim of this study was to evaluate the quality of the MR compilation in some Operative Units of the ?Azienda Ospedaliera Universitaria - II Università di Napoli? (AOU- SUN) - Italy, before and after an intervention of quality improve- ment, underlining the potential differences in the behaviour of dif- ferent specialists (physicians vs. surgeons). Methods. Two random samples of 660 MRs were reviewed. A four-step program was developed: 1) first assessment of the MR; 2) implementation of the MR quality, sending a letter with the purpose of the study, the results obtained in the first step from that ward, the guidelines to correctly fill out the MR; 3) follow-up step four months later; 4) comparison of the data before and after the distribution of the guidelines using indicators of completeness of all sections of MR, clarity of handwriting and presence and clar- ity of signature. Results. The main concerns were related to the signature of the duty physician (present in 2.0% and legible in only 15.4%), the presence of the letter of discharge (18.0%) and the clarity of the days of hospital stay (32.0%). After the intervention the improvement of the quality of compilation was modest and regarded mainly medical rather than surgical wards. Discussion and conclusions. The improvement was not satisfying since from a medical and a legal point of view the indicators should reach 100% of clarity and completeness. A further study is being carried out to improve the involvement of health care professional, so that such requirements will be perceived as a common goal, not as mere bureaucratic initiatives

Silencing of caveolin-1 in fibroblasts as opposed to epithelial tumor cells results in increased tumor growth rate and chemoresistance in a human pancreatic cancer model

Caveolin‑1 (Cav‑1) expression has been shown to be associated with tumor growth and resistance to chemotherapy in pancreatic cancer. The primary aim of this study was to explore the significance of Cav‑1 expression in pancreatic cancer cells as compared to fibroblasts in relation to cancer cell proliferation and chemoresistance, both in vitro and in vivo, in an immunodeficient mouse model. We also aimed to evaluate the immunohistochemical expression of Cav‑1 in the epithelial and stromal component of pancreatic cancer tissue specimens. The immunohistochemical staining of poorly differentiated tissue sections revealed a strong and weak Cav‑1 expression in the epithelial tumor cells and stromal fibroblasts, respectively. Conversely, the well‑differentiated areas were characterized by a weak epithelial Cav‑1 expression. Cav‑1 downregulation in cancer cells resulted in an increased proliferation in vitro; however, it had no effect on chemoresistance and growth gain in vivo. By contrast, the decreased expression of Cav‑1 in fibroblasts resulted in a growth advantage and the chemoresistance of cancer cells when they were co‑injected into immunodeficient mice to develop mixed fibroblast/cancer cell xenografts. On the whole, the findings of this study suggest that the downregulation of Cav‑1 in fibroblasts is associated with an increased tumor proliferation rate in vivo and chemoresistance. Further studies are warranted to explore whether the targeting of Cav‑1 in the stroma may represent a novel therapeutic approach in pancreatic cancer

New reference ranges for interpreting forced expiratory manoeuvres in infants and implications for clinical interpretation: a multicentre collaboration

The raised volume rapid thoracoabdominal compression (RVRTC) technique is commonly used to obtain full forced expiratory manoeuvres from infants, but reference equations derived from 'in-house' equipment have been shown to be inappropriate for current commercially available devices