Designing and Rightsizing the Information System Architecture

Information system design and sizing constitute a complex, top-down process that tailors the technology architecture to application requirements. Practitioners usually tackle this top-down process by focusing on individual design aspects, such as data or specific applications, and by relying on their previous experiences to compare alternative architectural solutions. Acquisition costs are usually accounted for, but related operating and maintenance costs are often neglected or underestimated. The complexity of optimizing individual design problems leads researchers to avoid a global optimization perspective and, thus, the IS architecture is usually a result of the juxtaposition of multiple local optima.This paper takes an overall perspective on the cost minimization problem of information system design to achieve a better trade-off between cost and performance over the whole expected life of the technology architecture. A comprehensive design methodology is discussed as an integrating framework that accounts for all categories of costs, including design, implementation, maintenance, and operation, to achieve a globally cost-minimizing solution.     

Pharmacogenetics Biomarkers and Their Specific Role in Neoadjuvant Chemoradiotherapy Treatments: An Exploratory Study on Rectal Cancer Patients

Background: Pathological complete response (pCR) to neoadjuvant chemoradiotherapy (CRT) in locally advanced rectal cancer (LARC) is still ascribed to a minority of patients. A pathway based-approach could highlight the predictive role of germline single nucleotide polymorphisms (SNPs). The primary aim of this study was to define new predictive biomarkers considering treatment specificities. Secondary aim was to determine new potential predictive biomarkers independent from radiotherapy (RT) dosage and cotreatment with oxaliplatin. Methods: Thirty germ-line SNPs in twenty-one genes were selected according to a pathway-based approach. Genetic analyses were performed on 280 LARC patients who underwent fluoropyrimidine-based CRT. The potential predictive role of these SNPs in determining pathological tumor response was tested in Group 1 (94 patients undergoing also oxaliplatin), Group 2 (73 patients treated with high RT dosage), Group 3 (113 patients treated with standard RT dosage), and in the pooled population (280 patients). Results: Nine new predictive biomarkers were identified in the three groups. The most promising one was rs3136228-MSH6 (p = 0.004) arising from Group 3. In the pooled population, rs1801133-MTHFR showed only a trend (p = 0.073). Conclusion: This exploratory study highlighted new potential predictive biomarkers of neoadjuvant CRT and underlined the importance to strictly define treatment peculiarities in pharmacogenetic analyses.     

Anisotropic molecular packing of soluble C60 fullerenes in hexagonal nanocrystals obtained by solvent vapor annealing

We describe the self-assembly of soluble, chemically modified fullerene [6,6]-phenyl C₆₁ butyric acid methyl ester (PCBM) into a new crystalline phase where the C₆₀ moieties are arranged in parallel layers. Minimum C₆₀ center-to-center distance is 10 Å within the layers, and up to 15 Å perpendicular to the layers. Highly anisotropic, mesoscopic hexagonal crystals of this material, with a lateral size of many microns and a thickness below 1 μm, are obtained from chloroform solution by solvent vapor annealing, and characterized by optical microscopy and X-ray diffraction. The crystalline structure is deduced combining experimental data with molecular modeling and ab initio calculations. The large difference in C₆₀–C₆₀ spacing indicates a high anisotropy in electrical and charge transport properties of this new phase.     

Corticosteroids in liver and urine in Sicilian cattle by a LC-MS/MS method

The presence of corticosteroid residues was assessed in urine and liver samples from livestock of Sicily. A total of 630 bovine samples were collected from farms and slaughterhouses. The samples were analysed using solid-phase extraction (SPE) coupled with ultra-performance liquid chromatography tandem mass spectrometry (UHPLC–MS/MS). All the corticosteroids found were under the maximum residue limit imposed by Commission Regulation (EC) 37/2010. About 4% of liver samples showed dexamethasone levels above the limit of detection (LOD), with a mean of 1.5 ± 0.2 µg kg^?1. Betamethasone was found only in seven liver samples, with a mean of 1.6 ± 0.1 µg kg^?1. Furthermore, prednisolone and prednisone were found only in urine and liver samples from slaughterhouse, probably related to the high rate of stress for bovines. These results suggest good control practices adopted by Sicilian farms, able to ensure the quality of food products.     

Assessment of intradialysis calcium mass balance by a single pool variable‐volume calcium kinetic model

Introduction: A reliable method of intradialysis calcium mass balance quantification is far from been established. We herein investigated the use of a single‐pool variable‐volume Calcium kinetic model to assess calcium mass balance in chronic and stable dialysis patients. Methods: Thirty‐four patients on thrice‐weekly HD were studied during 240 dialysis sessions. All patients were dialyzed with a nominal total calcium concentration of 1.50 mmol/L. The main assumption of the model is that the calcium distribution volume is equal to the extracellular volume during dialysis. This hypothesis is assumed valid if measured and predicted end dialysis plasma water ionized calcium concentrations are equal. A difference between predicted and measured end‐dialysis ionized plasma water calcium concentration is a deviation on our main hypothesis, meaning that a substantial amount of calcium is exchanged between the extracellular volume and a nonmodeled compartment. Findings: The difference between predicted and measured values was 0.02 mmol/L (range ?0.08:0.16 mmol/L). With a mean ionized dialysate calcium concentration of 1.25 mmol/L, calcium mass balance was on average negative (mean ± SD ?0.84 ± 1.33 mmol, range ?5.42:2.75). Predialysis ionized plasma water concentration and total ultrafiltrate were the most important predictors of calcium mass balance. A significant mobilization of calcium from the extracellular pool to a nonmodeled pool was calculated in a group of patients. Discussion: The proposed single pool variable‐volume Calcium kinetic model is adequate for prediction and quantification of intradialysis calcium mass balance, it can evaluate the eventual calcium transfer outside the extracellular pool in clinical practice.     

A Phenylacetamide Resveratrol Derivative Exerts Inhibitory Effects on Breast Cancer Cell Growth

Resveratrol (RSV) is a natural compound that displays several pharmacological properties, including anti-cancer actions. However, its clinical application is limited because of its low solubility and bioavailability. Here, the antiproliferative and anti-inflammatory activity of a series of phenylacetamide RSV derivatives has been evaluated in several cancer cell lines. These derivatives contain a monosubstituted aromatic ring that could mimic the RSV phenolic nucleus and a longer flexible chain that could confer a better stability and bioavailability than RSV. Using MTT assay, we demonstrated that most derivatives exerted antiproliferative effects in almost all of the cancer cell lines tested. Among them, derivative 2, that showed greater bioavailability than RSV, was the most active, particularly against estrogen receptor positive (ER+) MCF7 and estrogen receptor negative (ER-) MDA-MB231 breast cancer cell lines. Moreover, we demonstrated that these derivatives, particularly derivative 2, were able to inhibit NO and ROS synthesis and PGE2 secretion in lipopolysaccharide (LPS)-activated U937 human monocytic cells (derived from a histiocytoma). In order to define the molecular mechanisms underlying the antiproliferative effects of derivative 2, we found that it determined cell cycle arrest at the G1 phase, modified the expression of cell cycle regulatory proteins, and ultimately triggered apoptotic cell death in both breast cancer cell lines. Taken together, these results highlight the studied RSV derivatives, particularly derivative 2, as promising tools for the development of new and more bioavailable derivatives useful in the treatment of breast cancer.