Differential expression of complement receptors CR1/2 and CR4 by murine M1 and M2 macrophages.

Macrophages polarize into functionally divergent phenotypes - M1 and M2 - which express distinct receptors. These cells are known to express complement receptors, including CR1, CR3, and CR4. However, whether these complement receptors are differentially expressed on M1 and M2 macrophages is not yet known.

Imputing radiobiological parameters of the linear-quadratic dose-response model from a radiotherapy fractionation plan.

The objective in cancer radiotherapy is to maximize tumor-kill while limiting toxic effects of radiation dose on nearby organs-at-risk (OAR). Given a fixed number of treatment sessions, planners thus face the problem of finding a dosing sequence that achieves this goal. This is called the fractionation problem, and has received steady attention over a long history in the clinical literature.

Optimal modality selection in external beam radiotherapy.

The goal in external beam radiotherapy (EBRT) for cancer is to maximize damage to the tumour while limiting toxic effects on the organs-at-risk. EBRT can be delivered via different modalities such as photons, protons and neutrons. The choice of an optimal modality depends on the anatomy of the irradiated area and the relative physical and biological properties of the modalities under consideration.

Adaptive treatment-length optimization in spatiobiologically integrated radiotherapy.

Recent theoretical research on spatiobiologically integrated radiotherapy has focused on optimization models that adapt fluence-maps to the evolution of tumor state, for example, cell densities, as observed in quantitative functional images acquired over the treatment course. We propose an optimization model that adapts the length of the treatment course as well as the fluence-maps to such imaged tumor state. Specifically, after observing the tumor cell densities at the beginning of a session, the treatment planner solves a group of convex optimization problems to determine an optimal number of remaining treatment sessions, and a corresponding optimal fluence-map for each of these sessions.

Traumatic dissociation of aspects of the feminine: an Asian cultural perspective.

The paper explores the impact of the dissociated feminine principle resulting from the trauma of cultural displacement in a young Chinese woman keen to embrace a modern Western identity. A case study illustrates the outcome of the client both consciously and unconsciously rejecting the traditional stereotypical Chinese feminine identity and instead embracing the distorted, yet seductive, image of the Western (Caucasian) woman as independent, intellectual and confident. Her defensive denial of the traditional feminine was dealt with by intellectualising both personal and professional relationships.

Selective recruitment of nucleoporins on vaccinia virus factories and the role of Nup358 in viral infection.

Vaccinia virus (VACV), a member of the Poxviridae family, uses cytoplasmic factories for its replication. Recent studies indicated that VACV infection requires a set of nucleoporins. However, how the nucleoporins contribute to viral life cycle remains unclear.

A theoretical stochastic control framework for adapting radiotherapy to hypoxia.

Hypoxia, that is, insufficient oxygen partial pressure, is a known cause of reduced radiosensitivity in solid tumors, and especially in head-and-neck tumors. It is thus believed to adversely affect the outcome of fractionated radiotherapy. Oxygen partial pressure varies spatially and temporally over the treatment course and exhibits inter-patient and intra-tumor variation.

Optimal fractionation in radiotherapy with multiple normal tissues.

The goal in radiotherapy is to maximize the biological effect (BE) of radiation on the tumour while limiting its toxic effects on healthy anatomies. Treatment is administered over several sessions to give the normal tissue time to recover as it has better damage-repair capabilities than tumour cells. This is termed fractionation.

A Markov decision process approach to multi-category patient scheduling in a diagnostic facility.

Objectives: To develop a mathematical model for multi-category patient scheduling decisions in computed tomography (CT), and to investigate associated tradeoffs from economic and operational perspectives.

Methods: We modeled this decision-problem as a finite-horizon Markov decision process (MDP) with expected net CT revenue as the performance metric. The performance of optimal policies was compared with five heuristics using data from an urban hospital.

Evaluation of intralesional injection of verapamil in treatment of Peyronie's disease.

Objective: To evaluate the effect of intralesional injection of verapamil in Peyronie's plaque with confirmed lesion.

Methods: This randomized clinical trial was carried out between March 2005 and March 2006 on 16 patients with Peyronie's disease who were referred to the Urology Clinic of Shohadaye Ashayer Hospital in Khorram Abad, Iran. Performing a comprehensive physical exam, the genitalia of the patients were checked to confirm the diagnosis and reject other sexual disorders.

A Markov decision process approach to temporal modulation of dose fractions in radiation therapy planning.

The current state of the art in cancer treatment by radiation optimizes beam intensity spatially such that tumors receive high dose radiation whereas damage to nearby healthy tissues is minimized. It is common practice to deliver the radiation over several weeks, where the daily dose is a small constant fraction of the total planned. Such a 'fractionation schedule' is based on traditional models of radiobiological response where normal tissue cells possess the ability to repair sublethal damage done by radiation.

Transcriptome analysis identifies genes with enriched expression in the mouse central extended amygdala.

The central extended amygdala (EAc) is an ensemble of highly interconnected limbic structures of the anterior brain, and forms a cellular continuum including the bed nucleus of the stria terminalis (BNST), the central nucleus of the amygdala (CeA) and the nucleus accumbens shell (AcbSh). This neural network is a key site for interactions between brain reward and stress systems, and has been implicated in several aspects of drug abuse. In order to increase our understanding of EAc function at the molecular level, we undertook a genome-wide screen (Affymetrix) to identify genes whose expression is enriched in the mouse EAc.

Gene expression is altered in the lateral hypothalamus upon activation of the mu opioid receptor.

The lateral hypothalamus (LH) is a brain structure that controls hedonic properties of both natural rewards and drugs of abuse. Mu opioid receptors are known to mediate drug reward, but whether overstimulation of these receptors impacts on LH function has not been studied. Here we have used a genome-wide microarray approach to identify LH responses to chronic mu opioid receptor activation at the transcriptional level.

Mu-opioid receptor activation induces transcriptional plasticity in the central extended amygdala.

Addiction develops from the gradual adaptation of the brain to chronic drug exposure, and involves genetic reprogramming of neuronal function. The central extended amygdala (EAc) is a network formed by the central amygdala and the bed nucleus of the stria terminalis. This key site controls drug craving and seeking behaviors, and has not been investigated at the gene regulation level.

Characterization of antibody-binding sites on proteins: development of a knowledgebase and its applications in improving epitope prediction.

Immunoinformatics provides tools for reverse vaccinology and encompasses development of knowledge bases and algorithms for prediction of epitopes. AgAbDb, a database archiving molecular interactions of antigen-antibody co-crystal structures, has been developed (http://202.41.

Identification of novel striatal genes by expression profiling in adult mouse brain.

Large-scale transcriptome analysis in the brain is a powerful approach to identify novel genes of potential interest toward understanding cerebral organization and function. We utilized the microarray technology to measure expression levels of about 24,000 genes and expressed sequence tags in mouse hippocampus, frontal cortex and striatum. Using expression profile obtained from whole brain as a reference, we categorized the genes into groups of genes either enriched in, or restricted to, one of the three areas of interest.

Influenza type B neuraminidase can replace the function of type A neuraminidase.

Influenza A and B viruses do not form reassortants with each other, presumably due to selection at either the RNA or protein level. Although differences in the promoter sequences of type A and B viruses have been studied, selection at the protein level has not been addressed. In this paper we describe experiments to determine whether differences in structure and/or function of the neuraminidase (NA) protein preclude formation of A/B NA reassortants.

In search of novel water soluble forskolin analogues for positive inotropic activity.

Using the novel lead from hydroxy acetyl substituted forskolin analogues, such as 7 beta-hydroxyacetyl-7 beta-deacetyl forskolin or 6 beta-hydroxyacetyl forskolin, a number of water soluble omega-amino acyl derivatives were synthesized. Two such compounds 6 and 18 showed better in vitro activity but failed to show in vivo activity.

Hydroxyacyl derivatives of forskolin--their positive inotropic activity.

Using appropriate protection and deprotection sequence novel hydroxyacyl chains of the type CO(CH2)nOH are synthesized and are utilized to develop new analogues of forskolin. Several compounds showed good positive inotropic activity. Compound 12 is almost 10 times more active than forskolin (EC50 = 0.

Site-directed mutagenesis of catalytic residues of influenza virus neuraminidase as an aid to drug design.

The neuraminidase of influenza virus is a surface glycoprotein that catalyzes the hydrolysis of glycosidic linkages between terminal sialic acids and adjacent sugar moieties. Neuraminidase function is critical for the spread of virus to new cells, and if the enzyme activity is inhibited, then virus infection is abrogated. The neuraminidase active site is conserved in all influenza type-A and type-B isolates, which makes it an excellent target for drug design.

Generation and characterization of a mutant of influenza A virus selected with the neuraminidase inhibitor BCX-140.

Influenza neuraminidase (NA) plays an important role in viral replication, and characterization of viruses resistant to NA inhibitors will help elucidate the role of active-site residues. This information will assist in designing better inhibitors targeted to essential active-site residues that cannot generate drug-resistant mutations. In the present study we used the benzoic acid-based inhibitor BCX-140 to select and characterize resistant viruses.

HL 752: a potent and long-acting antispasmodic agent.

Ester analogues of methyl-2-(4-(2-piperidinoethoxy)benzoyl)-benzoate hydrochloride (pitofenone) (2) were prepared with an aim to find a more potent and metabolically stable antispasmodic compound. The compounds were evaluated for their in vitro and in vivo antispasmodic activity, and stability to in vitro enzymatic hydrolysis. Of the compounds synthesised, HL 752 (21) showed the most potent and long-lasting antispasmodic activity and was selected as the candidate for clinical development.

Editing of the mitochondrial small subunit rRNA in Physarum polycephalum.

Post-transcriptional insertion, substitution or deletion of nucleotides in RNA (RNA editing) has been observed in RNAs from a number of organisms but always in messenger RNA or transfer RNA. We report here that the 17S rRNA of the mitochondrial ribosome of Physarum polycephalum is edited at 40 sites with single cytidine insertions. The locations of the editing sites are fairly evenly distributed throughout the RNA and do not correspond to any obvious feature of the primary sequence or secondary structure.