Optimized synthesis of O-carboxymethyl-N,N,N-trimethyl chitosan.

We present here the synthesis of a highly O-carboxymethylated chitosan derivative. First, an improved protocol for the two-step synthesis of N-trimethyl chitosan (TMC) from chitosan was developed, yielding a maximum degree of quaternization (DQ) of up to 46.6%. Successively, the chitosan derivative O-carboxymethyl-N-trimethyl chitosan (CMTMC) was synthesized from the TMC obtained by applying an optimized synthesis pathway. In contrast to previous reports, the optimized protocol was shown to yield very high rates (>85%) of O-carboxymethylation of CMTMC, as shown by (1)H NMR and heteronuclear single quantum correlation ((1)H-(13)C HSQC). Finally, in vitro cytocompatibility (viability >80%) of the polymer was demonstrated using human fibroblasts.

Toward on-the-fly quantum mechanical/molecular mechanical (QM/MM) docking: development and benchmark of a scoring function.

We address the challenges of treating polarization and covalent interactions in docking by developing a hybrid quantum mechanical/molecular mechanical (QM/MM) scoring function based on the semiempirical self-consistent charge density functional tight-binding (SCC-DFTB) method and the CHARMM force field. To benchmark this scoring function within the EADock DSS docking algorithm, we created a publicly available dataset of high-quality X-ray structures of zinc metalloproteins ( http://www.molecular-modelling.ch/resources.php ). For zinc-bound ligands (226 complexes), the QM/MM scoring yielded a substantially improved success rate compared to the classical scoring function (77.0% vs 61.5%), while, for allosteric ligands (55 complexes), the success rate remained constant (49.1%). The QM/MM scoring significantly improved the detection of correct zinc-binding geometries and improved the docking success rate by more than 20% for several important drug targets. The performance of both the classical and the QM/MM scoring functions compare favorably to the performance of AutoDock4, AutoDock4Zn, and AutoDock Vina.

Diagnosis of endocrine disease: High-yield thyroid fine-needle aspiration cytology: an update focused on ancillary techniques improving its accuracy.

Thyroid fine-needle aspiration (FNA) cytology is a fast growing field. One of the most developing areas is represented by molecular tests applied to cytological material. Patients that could benefit the most from these tests are those that have been diagnosed as 'indeterminate' on FNA. They could be better stratified in terms of malignancy risk and thus oriented with more confidence to the appropriate management. Taking in to consideration the need to improve and keep high the yield of thyroid FNA, professionals from various fields (i.e. molecular biologists, endocrinologists, nuclear medicine physicians and radiologists) are refining and fine-tuning their diagnostic instruments. In particular, all these developments aim at increasing the negative predictive value of FNA to improve the selection of patients for diagnostic surgery. These advances involve terminology, the application of next-generation sequencing to thyroid FNA, the use of immunocyto- and histo-chemistry, the development of new sampling techniques and the increasing use of nuclear medicine as well as molecular imaging in the management of patients with a thyroid nodule. Herein, we review the recent advances in thyroid FNA cytology that could be of interest to the 'thyroid-care' community, with particular focus on the indeterminate diagnostic category.

A comprehensive model for quantum noise characterization in digital mammography.

NlmCategory="UNASSIGNED">A version of cascaded systems analysis was developed specifically with the aim of studying quantum noise propagation in x-ray detectors. Signal and quantum noise propagation was then modelled in four types of x-ray detectors used for digital mammography: four flat panel systems, one computed radiography and one slot-scan silicon wafer based photon counting device. As required inputs to the model, the two dimensional (2D) modulation transfer function (MTF), noise power spectra (NPS) and detective quantum efficiency (DQE) were measured for six mammography systems that utilized these different detectors. A new method to reconstruct anisotropic 2D presampling MTF matrices from 1D radial MTFs measured along different angular directions across the detector is described; an image of a sharp, circular disc was used for this purpose. The effective pixel fill factor for the FP systems was determined from the axial 1D presampling MTFs measured with a square sharp edge along the two orthogonal directions of the pixel lattice. Expectation MTFs were then calculated by averaging the radial MTFs over all possible phases and the 2D EMTF formed with the same reconstruction technique used for the 2D presampling MTF. The quantum NPS was then established by noise decomposition from homogenous images acquired as a function of detector air kerma. This was further decomposed into the correlated and uncorrelated quantum components by fitting the radially averaged quantum NPS with the radially averaged EMTF(2). This whole procedure allowed a detailed analysis of the influence of aliasing, signal and noise decorrelation, x-ray capture efficiency and global secondary gain on NPS and detector DQE. The influence of noise statistics, pixel fill factor and additional electronic and fixed pattern noises on the DQE was also studied. The 2D cascaded model and decompositions performed on the acquired images also enlightened the observed quantum NPS and DQE anisotropy.