Biodegradable hollow microfibres to produce bioactive scaffolds

Biodegradable hollow microfibres containing particles loaded with specific active agents can be potentially employed to produce a special kind of substrate for tissue engineering, able to function as a scaffold and at the same time to act as a drug‐releasing system. Biodegradable hollow microfibres based on poly(lactic acid) were produced by a dry–wet spinning procedure. Drug‐loaded microparticles were prepared by a simple oil‐in‐water emulsion and entrapped inside the fibres. The morphology of both fibres and particles was investigated by scanning electron microscopy. The mechanical and thermal properties of the fibres were investigated by tensile tests and differential scanning calorimetry. In vitro tests were performed to evaluate the release of the drug from the fibres loaded with the particles Copyright © 2004 Society of Chemical Industry     

Direct Methods Optimised for Solving Crystal Structure by Powder Diffraction Data: Limits,Strategies, and Prospects

The ab-initio crystal structure solution by powder diffraction data requires great efforts because of the collapse of the experimental information onto the one dimensional 2θ axis of the pattern. Different strategies will be described aiming at improving the process of extraction of the integrated intensities from the experimental pattern in order to make more straightforward the structure solution process by direct methods. Particular attention will be devoted to the EXPO program. Some of its performance will be analysed and results will be shown.     

The Histidine Phosphocarrier Kinase/Phosphorylase from Bacillus Subtilis Is an Oligomer in Solution with a High Thermal Stability

The histidine phosphocarrier protein (HPr) kinase/phosphorylase (HPrK/P) modulates the phosphorylation state of the HPr protein, and it is involved in the use of carbon sources by Gram-positive bacteria. Its X-ray structure, as concluded from crystals of proteins from several species, is a hexamer; however, there are no studies about its conformational stability, and how its structure is modified by the pH. We have embarked on the conformational characterization of HPrK/P of Bacillus subtilis (bsHPrK/P) in solution by using several spectroscopic (namely, fluorescence and circular dichroism (CD)) and biophysical techniques (namely, small-angle X-ray-scattering (SAXS) and dynamic light-scattering (DLS)). bsHPrK/P was mainly a hexamer in solution at pH 7.0, in the presence of phosphate. The protein had a high conformational stability, with an apparent thermal denaturation midpoint of ~70 °C, at pH 7.0, as monitored by fluorescence and CD. The protein was very pH-sensitive, precipitated between pH 3.5 and 6.5; below pH 3.5, it had a molten-globule-like conformation; and it acquired a native-like structure in a narrow pH range (between pH 7.0 and 8.0). Guanidinium hydrochloride (GdmCl) denaturation occurred through an oligomeric intermediate. On the other hand, urea denaturation occurred as a single transition, in the range of concentrations between 1.8 and 18 µM, as detected by far-UV CD and fluorescence.     

BRAF Gene and Melanoma: Back to the Future

As widely acknowledged, 40–50% of all melanoma patients harbour an activating BRAF mutation (mostly BRAF V600E). The identification of the RAS–RAF–MEK–ERK (MAP kinase) signalling pathway and its targeting has represented a valuable milestone for the advanced and, more recently, for the completely resected stage III and IV melanoma therapy management. However, despite progress in BRAF-mutant melanoma treatment, the two different approaches approved so far for metastatic disease, immunotherapy and BRAF+MEK inhibitors, allow a 5-year survival of no more than 60%, and most patients relapse during treatment due to acquired mechanisms of resistance. Deep insight into BRAF gene biology is fundamental to describe the acquired resistance mechanisms (primary and secondary) and to understand the molecular pathways that are now being investigated in preclinical and clinical studies with the aim of improving outcomes in BRAF-mutant patients.     

The undirected capacitated arc routing problem with profits

A profit and a demand are associated with each edge of a set of profitable edges of a given graph. A travel time is associated with each edge of the graph. A fleet of capacitated vehicles is given to serve the profitable edges. A maximum duration of the route of each vehicle is also given. The profit of an edge can be collected by one vehicle only that also serves the demand of the edge. The objective of this problem, which is called the undirected capacitated arc routing problem with profits (UCARPP), is to find a set of routes that satisfy the constraints on the duration of the route and on the capacity of the vehicle and maximize the total collected profit. We propose a branch-and-price algorithm and several heuristics. We can solve exactly instances with up to 97 profitable edges. The best heuristics find the optimal solution on most of instances where it is available.     

Analysis of the maximum level policy in a production-distribution system

We consider a production-distribution system, where a facility produces one commodity which is distributed to a set of retailers by a fleet of vehicles. Each retailer defines a maximum level of the inventory. The production policy, the retailers replenishment policies and the transportation policy have to be determined so as to minimize the total system cost. The overall cost is composed by fixed and variable production costs at the facility, inventory costs at both facility and retailers and routing costs. We study two different types of replenishment policies. The well-known order-up to level (OU) policy, where the quantity shipped to each retailer is such that the level of its inventory reaches the maximum level, and the maximum level (ML) policy, where the quantity shipped to each retailer is such that the inventory is not greater than the maximum level. We first show that when the transportation is outsourced, the problem with OU policy is NP-hard, whereas there exists a class of instances where the problem with ML policy can be solved in polynomial time. We also show the worst-case performance of the OU policy with respect to the more flexible ML policy. Then, we focus on the ML policy and the design of a hybrid heuristic. We also present an exact algorithm for the solution of the problem with one vehicle. Results of computational experiments carried out on small size instances show that the heuristic can produce high quality solutions in a very short amount of time. Results obtained on a large set of randomly generated problem instances are also shown, aimed at comparing the two policies.     

Matrix-Based Discrete Event Control for Surveillance Mobile Robotics

This paper focuses on the control system for an autonomous robot for the surveillance of indoor environments. Our approach proposes a matrix-based formalism which allows us to merge in a single framework discrete-event supervisory control, conflict resolution and reactive control. As a consequence, the robot is able to autonomously handle high level tasks as well as low-level behaviors, solving control and decision-making issues simultaneously. Moreover, the matrix-based controller is modular and can be easily reconfigured if mission characteristics or robot hardware configuration change. An illustrative example and a report on experimental investigations are provided to illustrate the main features of the proposed approach.     

An exact approach for portfolio selection with transaction costs and rounds

We consider a single-period mean-safety portfolio selection problem with transaction costs and integer constraints on the quantities selected for the securities (rounds). We propose an exact approach based on the partition of the initial problem into two subproblems and the use of a simple local search heuristic to obtain an initial solution. To the best of our knowledge, no optimal algorithms have been proposed in the literature for this problem. The proposed approach is simple, general and easily adaptable to other problems. An extensive experimental analysis based on real data from the main international Stock Exchange Markets is performed. The results show, on average, an impressive improvement with respect to the computational time and space memory required by CPLEX 7.0. We also show that the solution of the first subproblem can be used on its own as an extremely effective heuristic.     

Accuracy of FIB-4 to Detect Elevated Liver Stiffness Measurements in Patients with Non-Alcoholic Fatty Liver Disease: A Cross-Sectional Study in Referral Centers

The identification of advanced fibrosis by applying noninvasive tests is still a key component of the diagnostic algorithm of NAFLD. The aim of this study is to assess the concordance between the FIB-4 and liver stiffness measurement (LSM) in patients referred to two liver centers for the ultrasound-based diagnosis of NAFLD. Fibrosis 4 Index for Liver Fibrosis (FIB-4) and LSM were assessed in 1338 patients. A total of 428 (32%) had an LSM ≥ 8 kPa, whereas 699 (52%) and 113 (9%) patients had an FIB-4 < 1.3 and >3.25, respectively. Among 699 patients with an FIB-4 < 1.3, 118 (17%) had an LSM ≥ 8 kPa (false-negative FIB-4). This proportion was higher in patients ≥60 years, with diabetes mellitus (DM), arterial hypertension or a body mass index (BMI) ≥ 27 kg/m². In multiple adjusted models, age ≥ 60 years (odds ratio (OR) = 1.96, 95% confidence interval (CI) 1.19–3.23)), DM (OR = 2.59, 95% CI 1.63–4.13), body mass index (BMI) ≥ 27 kg/m² (OR = 2.17, 95% CI 1.33–3.56) and gamma-glutamyltransferase ≥ 25 UI/L (OR = 2.68, 95% CI 1.49–4.84) were associated with false-negative FIB-4. The proportion of false-negative FIB-4 was 6% in patients with none or one of these risk factors and increased to 16, 31 and 46% among those with two, three and four concomitant risk factors, respectively. FIB-4 is suboptimal to identify patients to refer to liver centers, because about one-fifth may be false negative at FIB-4, having instead an LSM ≥ 8 KPa.     

Formulations for an inventory routing problem

In this paper, we present and compare formulations for the inventory routing problem (IRP) where the demand of customers has to be served, over a discrete time horizon, by capacitated vehicles starting and ending their routes at a depot. The objective of the IRP is the minimization of the sum of inventory and transportation costs. The formulations include known and new mathematical programming formulations. Valid inequalities are also presented. The formulations are tested on a large set of benchmark instances. One of the most significant conclusions is that the formulations that use vehicle‐indexed variables are superior to the more compact, aggregate formulations.