Isolation of monocytes from human peripheral blood using immuno-affinity expanded-bed adsorption

A novel technique for the separation of monocytes from human peripheral blood preparations has been developed. The technique is based on the use of expanded-bed adsorption and a solid perfluorocarbon derivatized with avidin or streptavidin for the indirect positive or negative capture of cells labeled with biotinylated monoclonal antibodies. The perfluorocarbon support was prepared and characterized and the contactor design and operating conditions, that enable cells to be selectively isolated, were investigated. Experiments consisted of applying an immunolabeled pulse of 1 x 10(8) peripheral blood mononuclear cells (PBMCs), isolated by density gradient centrifugation, directly onto a refrigerated expanded bed. The major cell types remaining were T-lymphocytes, B-lymphocytes, and monocytes. Monocytes could be positively adsorbed, following labeling with anti-CD14 mAb, with a clearance of up to 89% and a depletion factor of 7.6. They could also be

Interaction of normal and expanded CAG repeat sizes influences age at onset of Huntington disease

Huntington disease (HD) is a neurodegenerative disorder caused by the abnormal expansion of CAG repeats in the HD gene on chromosome 4p16.3. Past studies have shown that the size of expanded CAG repeat is inversely associated with age at onset (AO) of HD. It is not known whether the normal Huntington allele size influences the relation between the expanded repeat and AO of HD. Data collected from two independent cohorts were used to test the hypothesis that the unexpanded CAG repeat interacts with the expanded CAG repeat to influence AO of HD. In the New England Huntington Disease Center Without Walls (NEHD) cohort of 221 HD affected persons and in the HD-MAPS cohort of 533 HD affected persons, we found evidence supporting an interaction between the expanded and unexpanded CAG repeat sizes which influences AO of HD (P = 0.08 and 0.07, respectively). The association was statistically significant when both cohorts were combined (P=0.012). The estimated heritability of the AO residual was 0.56 after adjustment for normal and expanded repeats and their interaction. An analysis of tertiles of repeats sizes revealed that the effect of the normal allele is seen among persons with large HD repeat sizes (47-83). These findings suggest that an increase in the size of the normal repeat may mitigate the expression of the disease among HD affected persons with large expanded CAG repeats. (C) 2003 Wiley-Liss, Inc.

An Expanded Multilocus Sequence Typing Scheme for Propionibacterium acnes: Investigation of ‘Pathogenic’, ‘Commensal’ and Antibiotic Resistant Strains

The Gram-positive bacterium Propionibacterium acnes is a member of the normal human skin microbiota and is associated with various infections and clinical conditions. There is tentative evidence to suggest that certain lineages may be associated with disease and others with health. We recently described a multilocus sequence typing scheme (MLST) for P. acnes based on seven housekeeping genes (http://pubmlst.org/pacnes). We now describe an expanded eight gene version based on six housekeeping genes and two ‘putative virulence’ genes (eMLST) that provides improved high resolution
typing (91eSTs from 285 isolates), and generates phylogenies congruent with those based on whole genome analysis. When compared with the nine gene MLST scheme developed at the University of Bath, UK, and utilised by researchers at Aarhus University, Denmark, the eMLST method offers greater resolution. Using the scheme, we examined 208 isolates from disparate clinical sources, and 77 isolates from healthy skin. Acne was predominately associated with type IA₁ clonal complexes CC1, CC3 and CC4; with eST1 and eST3 lineages being highly represented. In contrast, type IA₂ strains were recovered at a rate similar to type IB and II organisms. Ophthalmic infections were predominately associated with type IA₁ and IA₂ strains, while type IB and II were more frequently recovered from soft tissue and retrieved medical devices. Strains with rRNA mutations conferring resistance to antibiotics used in acne treatment were dominated by eST3, with some evidence for intercontinental spread. In contrast, despite its high association with acne, only a small number of resistant CC1 eSTs were identified. A number of eSTs were only recovered from healthy skin, particularly eSTs representing CC72 (type II) and CC77 (type III). Collectively our data lends support to the view that pathogenic versus truly commensal lineages of P. acnes may exist. This is likely to have important therapeutic and diagnostic implications.

Addressing Selective Polypharmacology of Antipsychotic Drugs Targeting the Bioaminergic Receptors through the Receptor Dynamic Conformational Ensembles

Selective polypharmacology, where a drug acts on multiple rather than single molecular targets involved in a disease, emerges to develop a structure-based system biology approach to design drugs selectively targeting a disease-active protein network. We focus on the bioaminergic receptors that belong to the group of integral membrane signalling proteins coupled to the G protein and represent targets for therapeutic agents against schizophrenia and depression. Among them, it has been shown that the serotonin (5-HT2A and 5-HT6), dopamine (D2 and D3) receptors induce a cognition-enhancing effect (group 1), while the histamine (H1) and serotonin (5-HT2C) receptors lead to metabolic side effects and the 5-HT2B serotonin receptor causes pulmonary hypertension (group 2). Thus, the problem arises to develop an approach that allows identifying drugs targeting only the disease-active receptors, i.e. group 1. The recent release of several crystal structures of the bioaminergic receptors, involving the D3 and H1 receptors provides the possibility to model the structures of all receptors and initiate a study of the structural and dynamic context of selective polypharmacology. In this work, we use molecular dynamics simulations to generate a conformational space of the receptors and subsequently characterize its binding properties applying molecular probe mapping. All-against-all comparison of the generated probe maps of the selected diverse conformations of all receptors with the Tanimoto similarity coefficient (Tc) enable to separate the receptors of group 1 from group 2. The pharmacophore built based on the Tc-selected receptor conformations, using the multiple probe maps discovers structural features that can be used to design molecules selective towards the receptors of group 1. The importance of several predicted residues to ligand selectivity is supported by the available mutagenesis and ligand structure-activity relationships studies. In addition, the Tc-selected conformations of the receptors for group 1 show good performance in isolation of known ligands from a random decoy. Our computational structure-based protocol to tackle selective polypharmacology of antipsychotic drugs could be applied for other diseases involving multiple drug targets, such as oncologic and infectious disorders.

Unveiling Fairness for the Consumer:The Law, Economics and Justice of Expanded Arbitration

In recent years, the US Supreme Court has rather controversially extended the ambit of the Federal Arbitration Act to extend arbitration’s reach into, inter alia¸ consumer matters, with the consequence that consumers are often (and unbeknownst to them) denied remedies which would otherwise be available. Such denied remedies include recourse to class action proceedings, effective denial of punitive damages, access to discovery and the ability to resolve the matter in a convenient forum.

The court’s extension of arbitration’s ambit is controversial. Attempts to overturn this extension have been made in Congress, but to no avail. In contrast to American law, European consumer law looks at pre-dispute agreements to arbitrate directed at consumers with extreme suspicion, and does so on the grounds of fairness. In contrast, some argue that pre-dispute agreements in consumer (and employment) matters are consumer welfare enhancing: they decrease the costs of doing business, which is then passed on to the consumer. This Article examines these latter claims from both an economic and normative perspective.

The economic analysis of these arguments shows that their assumptions do not hold. Rather than being productive of consumer surplus, the use of arbitration is likely to have the opposite effect. The industries from which the recent Supreme Court cases originated not only do not exhibit the industrial structure assumed by the proponents of expanded arbitration, but are also industries which exhibit features that facilitate consumer welfare reducing collusion.

The normative analysis addresses the fairness concerns. It is explicitly based upon John Rawls’ notion of “justice as fairness,” which can provide a lens to evaluate social institutions. This Rawlsian analysis considers the use of extended arbitration in consumer matters in the light of the earlier economic results. It suggests that the asymmetries present in the contractual allocation of rights serve as prima facie evidence that such arbitration–induced exclusions are prima facie unjust/unfair. However, as asymmetry is only a prima facie test, a generalized criticism of the arbitration exclusions (of the sort found in Congress and underlying the European regime) is overbroad.

Expanded iron uta spectra - Probing the thermal stability limits in AGN clouds

The Fe unresolved transition arrays (UTAs) produce prominent features in the 15-17 Å wavelength range in the spectra of active galactic nuclei (AGNs). Here, we present new calculations of the energies and oscillator strengths of inner-shell lines from Fe XIV, Fe XV, and Fe XVI. These are crucial ions since they are dominant at inflection points in the gas thermal stability curve, and UTA excitation followed by autoionization is an important ionization mechanism for these species. We incorporate these, and data reported in previous papers, into the plasma simulation code Cloudy. This updated physics is subsequently employed to reconsider the thermally stable phases in absorbing media in AGNs. We show how the absorption profile of the Fe XIV UTA depends on density, due to the changing populations of levels within the ground configuration. © 2013. The American Astronomical Society. All rights reserved.

Islamic fundamentalism since 1945:2nd revised and expanded edition

Featuring a brand new examination of Islamic fundamentalism in the wake of the Arab Spring, this fully revised and updated second edition of Islamic Fundamentalism since 1945 analyzes the roots and emergence of Islamic movements in the modern world and the main thinkers that inspired them.

Providing a much-needed historical overview of a fast-changing socio-political landscape, the main facets of Islamic fundamentalism are put in a global context, with a thematic debate of issues such as:

- the effects of colonialism on Islam

- secularism and the Islamic reaction

- Islam and violence in the 9/11 era

- globalization and transnational Islamist movements

- Islam in the wake of the Arab Awakening

Islamic Fundamentalism since 1945 provides an authoritative account of the causes and diversity of Islamic fundamentalism, a modern phenomenon which has grabbed the headlines as a grave threat to the West and a potentially revolutionary trend in the Middle East. It is a valuable resource for students and those interested in the history, effects and consequences of these Islamic movements

Homogenization and analysis of an expanded long-term monthly rainfall network for the Island of Ireland (1850–2010)

Long-term precipitation series are critical for understanding emerging changes to the hydrological cycle. To this end we construct a homogenized Island of Ireland Precipitation (IIP) network comprising 25 stations and a composite series covering the period 1850–2010, providing the second-longest regional precipitation archive in the British-Irish Isles. We expand the existing catalogue of long-term precipitation records for the island by recovering archived data for an additional eight stations. Following bridging and updating of stations HOMogenisation softwarE in R (HOMER) homogenization software is used to detect breaks using pairwise and joint detection. A total of 25 breakpoints are detected across 14 stations, and the majority (20) are corroborated by metadata. Assessment of variability and change in homogenized and extended precipitation records reveal positive (winter) and negative (summer) trends. Trends in records covering the typical period of digitization (1941 onwards) are not always representative of longer records. Furthermore, trends in post-homogenization series change magnitude and even direction at some stations. While cautionary flags are raised for some series, confidence in the derived network is high given attention paid to metadata, coherence of behaviour across the network and consistency of findings with other long-term climatic series such as England and Wales precipitation. As far as we are aware, this work represents the first application of HOMER to a long-term precipitation network and bodes well for use in other regions. It is expected that the homogenized IIP network will find wider utility in benchmarking and supporting climate services across the Island of Ireland, a sentinel location in the North Atlantic.

Face Recognition in the Scrambled Domain via Salience-Aware Ensembles of Many Kernels

With the rapid development of internet-of-things (IoT), face scrambling has been proposed for privacy protection during IoT-targeted image/video distribution. Consequently in these IoT applications, biometric verification needs to be carried out in the scrambled domain, presenting significant challenges in face recognition. Since face models become chaotic signals after scrambling/encryption, a typical solution is to utilize traditional data-driven face recognition algorithms. While chaotic pattern recognition is still a challenging task, in this paper we propose a new ensemble approach – Many-Kernel Random Discriminant Analysis (MK-RDA) to discover discriminative patterns from chaotic signals. We also incorporate a salience-aware strategy into the proposed ensemble method to handle chaotic facial patterns in the scrambled domain, where random selections of features are made on semantic components via salience modelling. In our experiments, the proposed MK-RDA was tested rigorously on three human face datasets: the ORL face dataset, the PIE face dataset and the PUBFIG wild face dataset. The experimental results successfully demonstrate that the proposed scheme can effectively handle chaotic signals and significantly improve the recognition accuracy, making our method a promising candidate for secure biometric verification in emerging IoT applications.

Expanded porphyrins and their evaluation as anion chemosensors

Expanded porphyrins are synthetic analogues of porphyrins, differing from the last ones and other naturally occurring tetrapyrrolic macrocycles by containing a larger central core, with a minimum of 17 atoms, while retaining the extended conjugation features that are a tremendous feature of these biological pigments. The core expansion results in various systems with novel spectral and electronic features, often uniques. Most of these systems can also coordinate cations and/or anions, and in some cases they can bind more than one of these species. In many cases, these molecules display structural features, such as non-planar structures, that have no antecedents in the chemistry of porphyrins or related macrocyclic compounds. This work will discuss several synthetic approaches for the synthesis of expanded porphyrins, namely the construction of new building blocks by Michael addition, as well as potential synthetic routes towards expanded porphyrins. The synthesis of smaller oligopyrrolic compounds namely, bipyrroles and dipyrromethanes, not only were developed for the synthesis of expanded porphyrins as they were also used in Knoevenagel condensations furnishing chromogenic compounds able to recognize different anions in solution. Also, an approach to the synthesis of novel expanded porphyrins namely sapphyrins has been done by aza-Michael additions. Several synthetic routes towards the synthesis of pyridyl and pyridinium N-Fused pentaphyrins and hexaphyrins have been explored in order to achieve compounds with potential applications in catalysis and PDI, respectively. Studies on the synthesis of compounds with potential anion binding properties, led to the structural characterization and NMR anion binding studies of [28]hexaphyrins functionalized with several diamines in the para position of their pentafluorophenyl groups. These compounds allow NH hydrogen bond interactions with various anions. All synthesized compounds were fully characterized by modern spectroscopic techniques.

Fuzzy Ensembles for Embedding Adaptive Behaviours in Semi-Autonomous Avatars in 3D Virtual Worlds

Semi-autonomous avatars should be both realistic and believable. The goal is to learn from and reproduce the behaviours of the user-controlled input to enable semi-autonomous avatars to plausibly interact with their human-controlled counterparts. A powerful tool for embedding autonomous behaviour is learning by imitation. Hence, in this paper an ensemble of fuzzy inference systems cluster the user input data to identify natural groupings within the data to describe the users movement and actions in a more abstract way. Multiple clustering algorithms are investigated along with a neuro-fuzzy classifier; and an ensemble of fuzzy systems are evaluated.

U.W. Percussion and Steel Drum Ensembles, June 2, 2005

Concert Program for U.W. Percussion and Steel Drum Ensembles

Electroanalysis of urinary L-dopa using tyrosinase immobilized on gold nanoelectrode ensembles

The performance of an amperometric biosensor constructed by associating tyrosinase (Tyr) enzyme with the advantages of a 3D gold nanoelectrode ensemble (GNEE) is evaluated in a flow-injection analysis (FIA) system for the analysis of l-dopa. GNEEs were fabricated by electroless deposition of the metal within the pores of polycarbonate track-etched membranes. A simple solvent etching procedure based on the solubility of polycarbonate membranes is adopted for the fabrication of the 3D GNEE. Afterward, enzyme was immobilized onto preformed self-assembled monolayers of cysteamine on the 3D GNEEs (GNEE-Tyr) via cross-linking with glutaraldehyde. The experimental conditions of the FIA system, such as the detection potential (−0.200 V vs. Ag/AgCl) and flow rates (1.0 mL min−1) were optimized. Analytical responses for l-dopa were obtained in a wide concentration range between 1 × 10−8 mol L−1 and 1 × 10−2 mol L−1. The limit of quantification was found to be 1 × 10−8 mol L−1 with a resultant % RSD of 7.23% (n = 5). The limit of detection was found to be 1 × 10−9 mol L−1 (S/N = 3). The common interfering compounds, namely glucose (10 mmol L−1), ascorbic acid (10 mmol L−1), and urea (10 mmol L−1), were studied. The recovery of l-dopa (1 × 10−7 mol L−1) from spiked urine samples was found to be 96%. Therefore, the developed method is adequate to be applied in the clinical analysis.