A novel hybrid evolutionary algorithm based on ACO and SA for distribution feeder reconfiguration with regard to DGs

This paper presents an efficient hybrid evolutionary optimization algorithm based on combining Ant Colony Optimization (ACO) and Simulated Annealing (SA), called ACO-SA, for distribution feeder reconfiguration (DFR) considering Distributed Generators (DGs). Due to private ownership of DGs, a cost based compensation method is used to encourage DGs in active and reactive power generation. The objective function is summation of electrical energy generated by DGs and substation bus (main bus) in the next day. The approach is tested on a real distribution feeder. The simulation results show that the proposed evolutionary optimization algorithm is robust and suitable for solving DFR problem.

A novel, automated nutrition screening system as a predictor of nutritional risk in an oncology day treatment unit (ODTU)

Purpose Paper-based nutrition screening tools can be challenging to implement in the ambulatory oncology setting. The aim of this study was to determine the validity of the Malnutrition Screening Tool (MST) and a novel, automated nutrition screening system compared to a ‘gold standard’ full nutrition assessment using the Patient-Generated Subjective Global Assessment (PG-SGA). Methods An observational, cross-sectional study was conducted in an outpatient oncology day treatment unit (ODTU) within an Australian tertiary health service. Eligibility criteria were as follows: ≥18 years, receiving outpatient anticancer treatment and English literate. Patients self-administered the MST. A dietitian assessed nutritional status using the PGSGA, blinded to the MST score. Automated screening system data were extracted from an electronic oncology prescribing system. This system used weight loss over 3 to 6 weeks prior to the most recent weight record or age-categorised body mass index (BMI) to identify nutritional risk. Sensitivity and specificity against PG-SGA (malnutrition) were calculated using contingency tables and receiver operating curves. Results There were a total of 300 oncology outpatients (51.7 % male, 58.6±13.3 years). The area under the curve (AUC) for weight loss alone was 0.69 with a cut-off value of ≥1 % weight loss yielding 63 % sensitivity and 76.7 % specificity. MST (score ≥2) resulted in 70.6 % sensitivity and 69.5 % specificity, AUC 0.77. Conclusions Both the MST and the automated method fell short of the accepted professional standard for sensitivity (~≥80 %) derived from the PG-SGA. Further investigation into other automated nutrition screening options and the most appropriate parameters available electronically is warranted to support targeted service provision.

A novel process of group-oriented question reduction for rule-based recommendation websites

Several websites utilise a rule-base recommendation system, which generates choices based on a series of questionnaires, for recommending products to users. This approach has a high risk of customer attrition and the bottleneck is the questionnaire set. If the questioning process is too long, complex or tedious; users are most likely to quit the questionnaire before a product is recommended to them. If the questioning process is short; the user intensions cannot be gathered. The commonly used feature selection methods do not provide a satisfactory solution. We propose a novel process combining clustering, decisions tree and association rule mining for a group-oriented question reduction process. The question set is reduced according to common properties that are shared by a specific group of users. When applied on a real-world website, the proposed combined method outperforms the methods where the reduction of question is done only by using association rule mining or only by observing distribution within the group.

Novel sequential methods in dose-finding designs : extensions of the continual reassessment method

Dose-finding trials are a form of clinical data collection process in which the primary objective is to estimate an optimum dose of an investigational new drug when given to a patient. This thesis develops and explores three novel dose-finding design methodologies. All design methodologies presented in this thesis are pragmatic. They use statistical models, incorporate clinicians' prior knowledge efficiently, and prematurely stop a trial for safety or futility reasons. Designing actual dose-finding trials using these methodologies will minimize practical difficulties, improve efficiency of dose estimation, be flexible to stop early and reduce possible patient discomfort or harm.

Xanthones from fungi, lichens, and bacteria : the natural products and their synthesis

Many fungi, lichens, and bacteria produce xanthones (derivatives of 9H-xanthen-9-one, “xanthone” from the Greek “xanthos”, for “yellow”) as secondary metabolites. Xanthones are typically polysubstituted and occur as either fully aromatized, dihydro-, tetrahydro-, or, more rarely, hexahydro-derivatives. This family of compounds appeals to medicinal chemists because of their pronounced biological activity within a notably broad spectrum of disease states, a result of their interaction with a correspondingly diverse range of target biomolecules. This has led to the description of xanthones as “privileged structures”.(1) Historically, the total synthesis of the natural products has mostly been limited to fully aromatized targets. Syntheses of the more challenging partially saturated xanthones have less frequently been reported, although the development in recent times of novel and reliable methods for the construction of the (polysubstituted) unsaturated xanthone core holds promise for future endeavors. In particular, the fascinating structural and biological properties of xanthone dimers and heterodimers may excite the synthetic or natural product chemist.

Synthesis of novel inhibitors blocking Wnt signaling downstream of β-Catenin

Large scale screening of libraries consisting of natural and small molecules led to the identification of many small molecule inhibitors repressing Wnt/β-Catenin signaling. However, targeted synthesis of novel Wnt pathway inhibitors has been rarely described. We developed a modular and expedient way to create the aromatic ring system with an aliphatic ring in between. Our synthesis opens up the possibility, in principle, to substitute all positions at the ring system with any desired substituent. Here, we tested five different haloquinone analogs carrying methoxy- and hydroxy-groups at different positions. Bona fide Wnt activity assays in cell culture and in Xenopus embryos revealed that two of these compounds act as potent inhibitors of aberrant activated Wnt/β-Catenin signaling.

A novel route in bone tissue engineering : magnetic biomimetic scaffolds

In recent years, interest in tissue engineering and its solutions has increased considerably. In particular, scaffolds have become fundamental tools in bone graft substitution and are used in combination with a variety of bio-agents. However, a long-standing problem in the use of these conventional scaffolds lies in the impossibility of re-loading the scaffold with the bio-agents after implantation. This work introduces the magnetic scaffold as a conceptually new solution. The magnetic scaffold is able, via magnetic driving, to attract and take up in vivo growth factors, stem cells or other bio-agents bound to magnetic particles. The authors succeeded in developing a simple and inexpensive technique able to transform standard commercial scaffolds made of hydroxyapatite and collagen in magnetic scaffolds. This innovative process involves dip-coating of the scaffolds in aqueous ferrofluids containing iron oxide nanoparticles coated with various biopolymers. After dip-coating, the nanoparticles are integrated into the structure of the scaffolds, providing the latter with magnetization values as high as 15 emu g�1 at 10 kOe. These values are suitable for generating magnetic gradients, enabling magnetic guiding in the vicinity and inside the scaffold. The magnetic scaffolds do not suffer from any structural damage during the process, maintaining their specific porosity and shape. Moreover, they do not release magnetic particles under a constant flow of simulated body fluids over a period of 8 days. Finally, preliminary studies indicate the ability of the magnetic scaffolds to support adhesion and proliferation of human bone marrow stem cells in vitro. Hence, this new type of scaffold is a valuable candidate for tissue engineering applications, featuring a novel magnetic guiding option.

Fluid-structure interaction analysis by coupled FE-SPH model based on a novel searching algorithm

Fluid–Structure Interaction (FSI) problem is significant in science and engineering, which leads to challenges for computational mechanics. The coupled model of Finite Element and Smoothed Particle Hydrodynamics (FE-SPH) is a robust technique for simulation of FSI problems. However, two important steps of neighbor searching and contact searching in the coupled FE-SPH model are extremely time-consuming. Point-In-Box (PIB) searching algorithm has been developed by Swegle to improve the efficiency of searching. However, it has a shortcoming that efficiency of searching can be significantly affected by the distribution of points (nodes in FEM and particles in SPH). In this paper, in order to improve the efficiency of searching, a novel Striped-PIB (S-PIB) searching algorithm is proposed to overcome the shortcoming of PIB algorithm that caused by points distribution, and the two time-consuming steps of neighbor searching and contact searching are integrated into one searching step. The accuracy and efficiency of the newly developed searching algorithm is studied on by efficiency test and FSI problems. It has been found that the newly developed model can significantly improve the computational efficiency and it is believed to be a powerful tool for the FSI analysis.

Sphingosine-1-phosphate, a novel second messenger involved in cell growth regulation and signal transduction, affects growth and invasiveness of human breast cancer cells

This review will focus on the role of sphingosine and its phosphorylated derivative sphingosine-1-phosphate (SPP) in cell growth regulation and signal transduction. We will show that many of the effects attributed to sphingosine in quiescent Swiss 3T3 fibroblasts are mediated via its conversion to SPP. We propose that SPP has appropriate properties to function as an intracellular second messenger based on the following: it elicits diverse cellular responses; it is rapidly produced from sphingosine by a specific kinase and rapidly degraded by a specific lyase; its concentration is low in quiescent cells but increases rapidly and transiently in response to the growth factors, fetal calf serum (FCS) and platelet derived growth factor (PDGF); it releases Ca2+ from internal sources in an InsP3-independent manner; and finally, it may link sphingolipid signaling pathways to cellular ras-mediated signaling pathways by elevating phosphatidic acid levels. The effects of this novel second messenger on growth, differentiation and invasion of human breast cancer cells will be discussed. © 1994 Kluwer Academic Publishers.

Myogel, a novel, basement membrane-rich, extracellular matrix derived from skeletal muscle, is highly adipogenic in vivo and in vitro

Background/Aims Biological and synthetic scaffolds play important roles in tissue engineering and are being developed towards human clinical applications. Based on previous work from our laboratory, we propose that extracellular matrices from skeletal muscle could be developed for adipose tissue engineering. Methods Extracellular matrices (Myogels) extracted from skeletal muscle of various species were assessed using biochemical assays including ELISA and Western blotting. Biofunctionality was assessed using an in vitro differentiation assay and a tissue engineering construct model in the rat. Results Myogels were successfully extracted from mice, rats, pigs and humans. Myogels contained significant levels of laminin α4- and α2-subunits and collagen I compared to Matrigel™, which contains laminin 1 (α1β1γ1) and collagen IV. Levels of growth factors such as fibroblast growth factor 2 were significantly higher than Matrigel, vascular endothelial growth factor-A levels were significantly lower and all other growth factors were comparable. Myogels reproducibly stimulated adipogenic differentiation of preadipocytes in vitro and the growth of adipose tissue in the rat. Conclusions We found Myogel induces adipocyte differentiation in vitroand shows strong adipogenic potential in vivo, inducing the growth of well-vascularised adipose tissue. Myogel offers an alternative for current support scaffolds in adipose tissue engineering, allowing the scaling up of animal models towards clinical adipose tissue engineering applications.

Characterization and novel activation of 72-kDa metalloproteinase in retinal interphotoreceptor matrix and Y-79 cell culture medium

Analysis of bovine interphotoreceptor matrix and conditioned medium from human Y-79 retinoblastoma cells by gelatin SDS-PAGE zymography reveals abundant activity of a 72-kDa M(r) gelatinase. The 72-kDa gelatinase from either source is inhibited by EDTA but not aprotinin or NEM, indicating that it is a metalloproteinase (MMP). The 72-kDa MMP is converted to a 62-kDa species with APMA treatment after gelatin sepharose affinity purification typical of previously described gelatinase MMP-2. The latent 72-kDa gelatinase from either bovine IPM or Y-79 media autoactivates without APMA in the presence of calcium and zinc after 72 hr at 37°C, producing a fully active mixture of proteinase species, 50 (48 in Y-79 medium), 38 and 35 kDa in size. The presence of inhibitory activity was examined in both whole bovine IPM and IPM fractions separated by SDS-PAGE. Whole IPM inhibited gelatinolytic activity of autoactivated Y-79-derived MMP in a dose-dependent manner. Inhibitory activities are observed in two protein fractions of 27-42 and 20-25 kDa. Western blots using antibodies to human tissue inhibitor of metalloproteinase 1 and 2 (TIMP-1 and -2) reveal the presence of two TIMP-1-like proteins at 21 and 29 kDa in inhibitory fractions of the bovine IPM. TIMP-2 was not detected in the inhibitory IPM fractions, consistent with the observed autoactivation of bovine IPM 72-kDa gelatinase. Potential roles for this IPM MMP-TIMP system include physiologic remodelling of the neural retina-RPE cell interface and digestion of shed rod outer segment as well as pathological processes such as retinal detachment, PE cell migration, neovascularization and tumor progression. Cultured Y-79 cells appear to be a good model for studying the production and regulation of this proteinase system.

Modeling and analysis of a novel variable-speed cage induction generator

This paper introduces a novel cage induction generator and presents a mathematical model, through which its behavior can be accurately predicted. The proposed generator system employs a three-phase cage induction machine and generates single-phase and constant-frequency electricity at varying rotor speeds without an intermediate inverter stage. The technique uses any one of the three stator phases of the machine as the excitation winding and the remaining two phases, which are connected in series, as the power winding. The two-series-connected-and-one-isolated (TSCAOI) phase winding configuration magnetically decouples the two sets of windings, enabling independent control. Electricity is generated through the power winding at both sub- and super-synchronous speeds with appropriate excitation to the isolated single winding at any frequency of generation. A dynamic mathematical model, which accurately predicts the behavior of the proposed generator, is also presented and implemented in MATLAB/Simulink. Experimental results of a 2-kW prototype generator under various operating conditions are presented, together with theoretical results, to demonstrate the viability of the TSCAOI power generation. The proposed generator is simple and capable of both storage and retrieval of energy through its excitation winding and is expected to be suitable for applications, such as small wind turbines and microhydro systems.

BM18 : a novel androgen-dependent human prostate cancer xenograft model derived from a bone metastasis

BACKGROUND Androgen-dependent prostate cancer (PrCa) xenograft models are required to study PrCa biology in the clinically relevant in vivo environment. METHODS Human PrCa tissue from a femoral bone metastasis biopsy (BM18) was grown and passaged subcutaneously through male severe combined immune-deficient (SCID) mice. Human mitochondria (hMt), prostate specific antigen (PSA), androgen receptor (AR), cytokeratin-18 (CK-18), pan-cytokeratin, and high molecular weight-cytokeratin (HMW-CK) were assessed using immunohistochemistry (IHC). Surgical castration was performed to examine androgen dependence. Serum was collected pre- and post-castration for monitoring of PSA levels. RESULTS: BM18 stained positively for hMt, PSA, AR, CK-18, pan keratin, and negatively for HMW-CK, consistent with the staining observed in the original patient material. Androgen-deprivation induced tumor regression in 10/10 castrated male SCID mice. Serum PSA levels positively correlated with BM18 tumor size. CONCLUSIONS BM18 expresses PSA and AR, and rapidly regresses in response to androgen withdrawal. This provides a new clinically significant PrCa model for the study of androgen-dependent growth.