Trends and Challenges in Experimental Macromolecular Crystallography

Macromolecular X-ray crystallography underpins the vigorous field of structural molecular biology having yielded many protein, nucleic acid and virus structures in fine detail. The understanding of the recognition by these macromolecules, as receptors, of their cognate ligands involves the detailed study of the structural chemistry of their molecular interactions. Also these structural details underpin the rational design of novel inhibitors in modern drug discovery in the pharmaceutical industry. Moreover, from such structures the functional details can be inferred, such as the biological chemistry of enzyme reactivity. There is then a vast number and range of types of biological macromolecules that potentially could be studied. The completion of the protein primary sequencing of the yeast genome, and the human genome sequencing project comprising some 105 proteins that is underway, raises expectations for equivalent three dimensional structural database

Uprighting impacted mandibular second molar using a skeletal anchorage: a case report

The aim of this case report is to present an innovative combined orthodontic-surgical technique to disimpact mandibular second molar (MM2) using an orthodontic miniscrew and an elastic chain. The impact on the Oral health-related quality of life (OHRQoL) was also evaluated. Using the present techinique, it is possible to expose the impacted tooth, insert a self-drilling miniscrew in the retromolar area, and remove the bud of third mandibular molar. At the same time the orthodontic force is applied with the use of an elastomeric chain that connects the head of miniscrew and vestibular and oral buttons bonded on MM2. A close traction is performed for the whole treatment time without the reactivation of the elastic force. The use of skeletal anchorage allowed the disimpaction of impacted MM2 in a short treatment time (about three months) avoiding the typical biomechanical side effects of traditional orthodontic appliance and increasing the effectiveness of the treatment. Further studies are necessary to evaluate the real advantages and disadvantages of this combined orthodontic-surgical approach

Effect of the crystal structure on the optical properties and Ag sensitization of Tb3+/Yb3+ ions in silica-zirconia glasses and glass-ceramics

The role of the material structure in the energy transfer between Ag and Tb3+/Yb3+ ions is studied in silica-soda-zirconia sol-gel glasses and glass-ceramics. The preparation of Tb3+ and Yb3+ doped silica-soda-zirconia layers was carried out by sol-gel and dip-coating, followed by thermal annealing. The precipitation of zirconia nanocrystals was obtained by controlling the annealing temperature: from a full amorphous glass at 700 °C into a glass-ceramic at 1000 °C. A different crystalline structure of zirconia nanocrystals, tetragonal or cubic, was controlled by the rare-earth doping and investigated in relation to the Tb3+/Yb3+ optical properties. Moreover, Ag codoping was introduced by ion-exchange, obtaining a significant photoluminescence enhancement, both in the intensity and in the broadness of the excitation band, covering the whole UV region and part of the violet-blue region. Ag-sensitized Tb3+/Yb3+ doped silica-soda-zirconia glass-ceramics were attested to be potential candidates for energy-related applications, such as spectral conversion layers for solar cells, lasers and light-emitting devices (LEDs) in the visible and NIR spectral regions

Comparision of profile macro-estethic perception among orthodontists, dentistry students, orthodontic patients and surgical orthodontic patients

Background: The patient's needs should guide the orthodontist in choosing the most appropriate therapy. The purpose of the present survey was to compare the esthetic perception of the facial profile by orthodontists (O), dentistry students (DS), orthodontic patients (OP) and surgical-orthodontic patients (SOP) and to evaluate the influence of gender, age and level of study. Material and Methods: A facial profile photograph of a young female was taken and twelve modified images were made, altering the position of the jaws in protrusion and in retrusion. Two hundred caucasian examiners, divided into four groups (O, DS, OP, SOP), were selected. Each examiner was asked to complete the questionnaire with an approval rating from 1 to 10. An ordinary least square OLS model was applied. Significant levels were set at P ≤ 0.05. Results: All examiners considered a straight profile or a slight retrusion of the maxilla as the most attractive profile. Slight discrepancies (up to 2 mm) in jaw protrusion were barely perceived by patients. Mandibular retrusion (2 and 4 mm) was one of the least appreciated condition by all examiners. Surgical-orthodontic patients assigned lower ratings compared to orthodontic patients. Female subjects assigned lower ratings than males. Patients with secondary school education assigned higher statistically significant values compared to other levels of study. The lowest values were attributed by the sample of age > = 17 years. Conclusions: The choice of the most appropriate therapy is based not only on a correct diagnosis, but on the evaluation of esthetic and psychological aspects

Pharmacokinetic study of gemcitabine, given as prolonged infusion at fixed dose rate, in combination with cisplatin in patients with advanced non-small-cell lung cancer.

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Viscosity, Boson Peak and Elastic Moduli in the Na2O-SiO2 System

The temperature and chemical dependence of the melt viscosity are ubiquitous in the model development of the volcanic dynamics, as well as in the glass production and design. We focussed on the yet-explored relationship between the bulk and shear moduli ratio and boson peak with the melt fragility of their parental glasses. Here, we explored the extension of the observed trend by testing the conventional binary system Na2O-SiO2, thus providing new evidence supporting the link between the flow of melts and supercooled liquids and the vibrational dynamics of their parental glasses. This was accomplished by integrating new low-frequency Raman measurements and integrating data from the literature on Brillouin light scattering and viscometry. This approach allows us to feed the MYEGA equation with reliable input parameters to quantitatively predict the viscosity of the Na2O-SiO2 system from the liquid up to the glass transition

Prospective phase II single-center study of the safety of a single very high dose of liposomal amphotericin B for antifungal prophylaxis in patients with acute myeloid leukemia.

Some preclinical and pharmacokinetic studies suggested the variable safety and the potential efficacy of an antifungal prophylaxis with a single high dose of liposomal amphotericin B (L-AmB) in high-risk patients. An open-label, prospective study was conducted with 48 adults receiving induction chemotherapy for acute myeloid leukemia (AML). Patients received a single infusion of 15 mg/kg of body weight L-AmB and, eventually, a second dose after 15 days of persistent neutropenia. The primary objective was tolerability and safety. Efficacy was also evaluated as a secondary endpoint. A pharmacokinetic study was performed with 34 patients in order to evaluate any association of plasma L-AmB levels with toxicity and efficacy. Overall, only 6 patients (12.5%) reported Common Toxicity Criteria (CTC) grade 3 hypokalemia, which was corrected with potassium supplementation in all cases, and no patient developed clinically relevant nephrotoxicity. Mild infusion-related adverse events occurred after 6 of 53 (11.3%) total infusions, with permanent drug discontinuation in only one case. Proven invasive fungal disease (IFD) was diagnosed in 4 (8.3%) patients. The mean AmB plasma levels at 6 h, 24 h, and 7 days after L-AmB administration were 160, 49.5, and 1 mg/liter, respectively. The plasma AmB levels were higher than the mean values of the overall population in 3 patients who developed CTC grade 3 hypokalemia and did not significantly differ from the mean values of the overall population in 3 patients who developed IFD. Our experience demonstrates the feasibility and safety of a single 15-mg/kg L-AmB dose as antifungal prophylaxis in AML patients undergoing induction chemotherapy

Investigating Macrophages Plasticity Following Tumour–Immune Interactions During Oncolytic Therapies

Over the last few years, oncolytic virus therapy has been recognised as a promising approach in cancer treatment, due to the potential of these viruses to induce systemic anti-tumour immunity and selectively killing tumour cells. However, the effectiveness of these viruses depends significantly on their interactions with the host immune responses, both innate (e.g., macrophages, which accumulate in high numbers inside solid tumours) and adaptive (e.g., CD8+ T cells). In this article, we consider a mathematical approach to investigate the possible outcomes of the complex interactions between two extreme types of macrophages (M1 and M2 cells), effector CD8+ T cells and an oncolytic Vesicular Stomatitis Virus (VSV), on the growth/elimination of B16F10 melanoma. We discuss, in terms of VSV, CD8+ and macrophages levels, two different types of immune responses which could ensure tumour control and eventual elimination. We show that both innate and adaptive anti-tumour immune responses, as well as the oncolytic virus, could be very important in delaying tumour relapse and eventually eliminating the tumour. Overall this study supports the use mathematical modelling to increase our understanding of the complex immune interaction following oncolytic virotherapies. However, the complexity of the model combined with a lack of sufficient data for model parametrisation has an impact on the possibility of making quantitative predictions

From SiO1.5CH3 to vitreous SiO2: A structural evolution study

The conversion of SiO1.5CH3 into SiO2 glass by pyrolysis in air has been studied by combining density measurements, vibrational spectroscopy, positron annihilation spectroscopy, and nuclear magnetic resonance. The results show that a critical transition takes place between 400 and 500 degrees C and at 600 degrees C the organic features are completely removed. The conversion of the hybrid structure into a fully inorganic network takes place through the formation of metastable 3-membered rings that progressively evolve into more stable 5+ rings as the pyrolysis temperature increases. The evolution of the organic moieties is coupled with the formation of Si-OH and molecular water trapped in the network which are well visible between 500 and 800 degrees C. In such temperature regions, a clear evolution of the network density can be detected, though the amount of free volume is nearly constant (due to the presence of trapped H2O). Only at 1250 degrees C, the network is comparable with a melt-derived glass