Suppression of allergic airway inflammation by helminth-induced regulatory T cells

Allergic diseases mediated by T helper type (Th) 2 cell immune responses are rising dramatically in most developed countries. Exaggerated Th2 cell reactivity could result, for example, from diminished exposure to Th1 cell–inducing microbial infections. Epidemiological studies, however, indicate that Th2 cell–stimulating helminth parasites may also counteract allergies, possibly by generating regulatory T cells which suppress both Th1 and Th2 arms of immunity. We therefore tested the ability of the Th2 cell–inducing gastrointestinal nematode Heligmosomoides polygyrus to influence experimentally induced airway allergy to ovalbumin and the house dust mite allergen Der p 1. Inflammatory cell infiltrates in the lung were suppressed in infected mice compared with uninfected controls. Suppression was reversed in mice treated with antibodies to CD25. Most notably, suppression was transferable with mesenteric lymph node cells (MLNC) from infected animals to uninfected sensitized mice, demonstrating that the effector phase was targeted. MLNC from infected animals contained elevated numbers of CD4(+)CD25(+)Foxp3(+) T cells, higher TGF-β expression, and produced strong interleukin (IL)-10 responses to parasite antigen. However, MLNC from IL-10–deficient animals transferred suppression to sensitized hosts, indicating that IL-10 is not the primary modulator of the allergic response. Suppression was associated with CD4(+) T cells from MLNC, with the CD4(+)CD25(+) marker defining the most active population. These data support the contention that helminth infections elicit a regulatory T cell population able to down-regulate allergen induced lung pathology in vivo

The Turing Guide

This volume celebrates the various facets of Alan Turing (1912–1954), the British mathematician and computing pioneer, widely considered as the father of computer science. It is aimed at the general reader, with additional notes and references for those who wish to explore the life and work of Turing more deeply. The book is divided into eight parts, covering different aspects of Turing’s life and work. Part I presents various biographical aspects of Turing, some from a personal point of view. Part II presents Turing’s universal machine (now known as a Turing machine), which provides a theoretical framework for reasoning about computation. His 1936 paper on this subject is widely seen as providing the starting point for the field of theoretical computer science. Part III presents Turing’s working on codebreaking during World War II. While the War was a disastrous interlude for many, for Turing it provided a nationally important outlet for his creative genius. It is not an overstatement to say that without Turing, the War would probably have lasted longer, and may even have been lost by the Allies. The sensitive nature of Turning’s wartime work meant that much of this has been revealed only relatively recently. Part IV presents Turing’s post-War work on computing, both at the National Physical Laboratory and at the University of Manchester. He made contributions to both hardware design, through the ACE computer at the NPL, and software, especially at Manchester. Part V covers Turing’s contribution to machine intelligence (now known as Artificial Intelligence or AI). Although Turing did not coin the term, he can be considered a founder of this field which is still active today, authoring a seminal paper in 1950. Part VI covers morphogenesis, Turing’s last major scientific contribution, on the generation of seemingly random patterns in biology and on the mathematics behind such patterns. Interest in this area has increased rapidly in recent times in the field of bioinformatics, with Turing’s 1952 paper on this subject being frequently cited. Part VII presents some of Turing’s mathematical influences and achievements. Turing was remarkably free of external influences, with few co-authors – Max Newman was an exception and acted as a mathematical mentor in both Cambridge and Manchester. Part VIII considers Turing in a wider context, including his influence and legacy to science and in the public consciousness. Reflecting Turing’s wide influence, the book includes contributions by authors from a wide variety of backgrounds. Contemporaries provide reminiscences, while there are perspectives by philosophers, mathematicians, computer scientists, historians of science, and museum curators. Some of the contributors gave presentations at Turing Centenary meetings in 2012 in Bletchley Park, King’s College Cambridge, and Oxford University, and several of the chapters in this volume are based on those presentations – some through transcription of the original talks, especially for Turing’s contemporaries, now aged in their 90s. Sadly, some contributors died before the publication of this book, hence its dedication to them. For those interested in personal recollections, Chapters 2, 3, 11, 12, 16, 17, and 36 will be of interest. For philosophical aspects of Turing’s work, see Chapters 6, 7, 26–31, and 41. Mathematical perspectives can be found in Chapters 35 and 37–39. Historical perspectives can be found in Chapters 4, 8, 9, 10, 13–15, 18, 19, 21–25, 34, and 40. With respect to Turing’s body of work, the treatment in Parts II–VI is broadly chronological. We have attempted to be comprehensive with respect to all the important aspects of Turing’s achievements, and the book can be read cover to cover, or the chapters can be tackled individually if desired. There are cross-references between chapters where appropriate, and some chapters will inevitably overlap. We hope that you enjoy this volume as part of your library and that you will dip into it whenever you wish to enter the multifaceted world of Alan Turing

Effect of silver content on the structure and antibacterial activity of silver-doped phosphate-based glasses

Staphylococcus aureus can cause a range of diseases, such as osteomyelitis, as well as colonize implanted medical devices. In most instances the organism forms biofilms that not only are resistant to the body's defense mechanisms but also display decreased susceptibilities to antibiotics. In the present study, we have examined the effect of increasing silver contents in phosphate-based glasses to prevent the formation of S. aureus biofilms. Silver was found to be an effective bactericidal agent against S. aureus biofilms, and the rate of silver ion release (0.42 to 1.22 µg·mm–2·h–1) from phosphate-based glass was found to account for the variation in its bactericidal effect. Analysis of biofilms by confocal microscopy indicated that they consisted of an upper layer of viable bacteria together with a layer (20 µm) of nonviable cells on the glass surface. Our results showed that regardless of the silver contents in these glasses (10, 15, or 20 mol%) the silver exists in its +1 oxidation state, which is known to be a highly effective bactericidal agent compared to that of silver in other oxidation states (+2 or +3). Analysis of the glasses by 31P nuclear magnetic resonance imaging and high-energy X-ray diffraction showed that it is the structural rearrangement of the phosphate network that is responsible for the variation in silver ion release and the associated bactericidal effectiveness. Thus, an understanding of the glass structure is important in interpreting the in vitro data and also has important clinical implications for the potential use of the phosphate-based glasses in orthopedic applications to deliver silver ions to combat S. aureus biofilm infections

Development of an antimicrobial blended white LED system containing pulsed 405-nm LEDs for decontamination applications

This study details the design, build and testing of a prototype antimicrobial blended white light unit containing pulsed red, yellow, green and 405nm LEDs. With a push for alternative methods of disinfection, optical methods have become a topic of interest. Ultra-violet (UV) light is widely known for its antimicrobial properties however; 405nm light has demonstrated significant antimicrobial properties against many common hospital acquired pathogens. In this study, a pulsed, blended, white-light prototype with a high content of 405 nm antimicrobial light, was designed, built and tested. Antimicrobial efficacy testing of the prototype was conducted using Staphylococcus aureus and Pseudomonas. aeruginosa, two bacteria which are common causes of hospital acquired infections. These were exposure to 3 different light outputs from the prototype and the surviving bacteria enumerated. Results showed that the mixed light output provided a much better CRI and light output under which to work. Also, the light output containing 405 nm light provided an antimicrobial effect, with decontamination of 103 CFUml-1 populations of both bacterial species. The other light content (red, yellow, green) had no beneficial or adverse effects on the antimicrobial properties of the 405nm light. The results suggest that with further development, it could be possible to produce an antimicrobial blended white light containing pulsed 405nm light that could supplement or even replace standard white lighting in certain environments

Pulsed ultraviolet light decontamination of artificially-generated microbiological aerosols

Airborne transmission of infectious organisms is a major public health concern, particularly within healthcare and communal public environments. Methods of environmental decontamination utilising pulsed ultraviolet (UV) light are currently available, however it is important that germicidal efficacy against airborne contamination is established. This study demonstrates evidence of the dose-response kinetics of airborne bacterial contamination when exposed to pulsed UV-rich (PUV) light. Bacterial aerosols (Staphylococcus epidermidis) were generated using a 6-Jet Collison nebuliser, and introduced into a custom-designed aerosol chamber which enabled prolonged airborne suspension and circulation. Bacterial aerosols were exposed to short duration pulses (~20 µs) of UV-rich light emitted from a xenon-filled flashlamp. The lamp was operated using a 1 kV solid–state pulsed power source, with a pulse frequency of 1 Hz, and output energy of 20 J/pulse. Post-treatment, air samples were extracted from the chamber using a BioSampler liquid impinger, and the surviving fraction was enumerated using standard microbiological culture methods. Results demonstrate successful aerosol inactivation, with a 66.4% reduction achieved with only 10 pulses of UV-rich light (P=<0.0002). Inactivation using continuous UV light was also investigated in order to quantify the comparative efficacy of these antimicrobial light regions. In addition to determining the inactivation kinetics, the spectral outputs of the pulsed and continuous UV sources were captured and compared in order to assess their comparative UV-C content, and subsequently assess how this UV content relates to their germicidal efficiency. Overall, results provide evidence of the dose-response kinetics of bacterial aerosols to PUV-rich light. As with continuous UV light, safety restrictions limit its application to unoccupied environments, or within sealed enclosures such as air handling units, however the reduced treatment times with PUV provides operational advantages over continuous light treatment

Spectroscopic Confirmation of Two Massive Red-Sequence-Selected Galaxy Clusters at z ~ 1.2 in the SpARCS-North Cluster Survey

The Spitzer Adaptation of the Red-sequence Cluster Survey (SpARCS) is a deep z'-band imaging survey covering the Spitzer Wide-Area Infrared Extragalactic Survey (SWIRE) Legacy fields designed to create the first large homogeneously selected sample of massive clusters at z > 1 using an infrared adaptation of the cluster red-sequence method. We present an overview of the northern component of the survey which has been observed with Canada-France-Hawaii Telescope (CFHT)/MegaCam and covers 28.3 deg^2. The southern component of the survey was observed with Cerro Tololo Inter-American Observatory (CTIO)/MOSAICII, covers 13.6 deg^2, and is summarized in a companion paper by Wilson et al. We also present spectroscopic confirmation of two rich cluster candidates at z ~ 1.2. Based on Nod-and-Shuffle spectroscopy from GMOS-N on Gemini, there are 17 and 28 confirmed cluster members in SpARCS J163435+402151 and SpARCS J163852+403843 which have spectroscopic redshifts of 1.1798 and 1.1963, respectively. The clusters have velocity dispersions of 490 ± 140 km s^(–1) and 650 ± 160 km s^(–1), respectively, which imply masses (M_(200)) of (1.0 ± 0.9) × 10^(14) M_⊙ and (2.4 ± 1.8) × 10^(14) M_⊙. Confirmation of these candidates as bonafide massive clusters demonstrates that two-filter imaging is an effective, yet observationally efficient, method for selecting clusters at z > 1

Spectroscopic Confirmation of a Massive Red-Sequence-Selected Galaxy Cluster at z = 1.34 in the SpARCS-South Cluster Survey

The Spitzer Adaptation of the Red-sequence Cluster Survey (SpARCS) is a z'-passband imaging survey, consisting of deep (z' ~ 24 AB) observations made from both hemispheres using the CFHT 3.6m and CTIO 4m telescopes. The survey was designed with the primary aim of detecting galaxy clusters at z >~ 1. In tandem with pre-existing 3.6um observations from the Spitzer Space Telescope SWIRE Legacy Survey, SpARCS detects clusters using an infrared adaptation of the two-filter red-sequence cluster technique. The total effective area of the SpARCS cluster survey is 41.9 deg^2. In this paper, we provide an overview of the 13.6 deg^2 Southern CTIO/MOSAICII observations. The 28.3 deg^2 Northern CFHT/MegaCam observations are summarized in a companion paper by Muzzin et al. (2008). In this paper, we also report spectroscopic confirmation of SpARCS J003550-431224, a very rich galaxy cluster at z = 1.335, discovered in the ELAIS-S1 field. To date, this is the highest spectroscopically confirmed redshift for a galaxy cluster discovered using the red-sequence technique. Based on nine confirmed members, SpARCS J003550-431224 has a preliminary velocity dispersion of 1050 +/- 230 km/s. With its proven capability for efficient cluster detection, SpARCS is a demonstration that we have entered an era of large, homogeneously-selected z > 1 cluster surveys.Comment: 10 pages, 6 Figures, Submitted to the Ap

Human genomic DNA quantitation system, H-Quant: Development and validation for use in forensic casework

The human DNA quantification (H-Quant) system, developed for use in human identification, enables quantitation of human genomic DNA in biological samples. The assay is based on real-time amplification of AluYb8 insertions in hominoid primates. The relatively high copy number of subfamily-specific Alu repeats in the human genome enables quantification of very small amounts of human DNA. The oligonucleotide primers present in H-Quant are specific for human DNA and closely related great apes. During the real-time PCR, the SYBR® Green I dye binds to the DNA that is synthesized by the human-specific AluYb8 oligonucleotide primers. The fluorescence of the bound SYBR® Green I dye is measured at the end of each PCR cycle. The cycle at which the fluorescence crosses the chosen threshold correlates to the quantity of amplifiable DNA in that sample. The minimal sensitivity of the H-Quant system is 7.6 pg/μL of human DNA. The amplicon generated in the H-Quant assay is 216 bp, which is within the same range of the common amplifiable short tandem repeat (STR) amplicons. This size amplicon enables quantitation of amplifiable DNA as opposed to a quantitation of degraded or nonamplifiable DNA of smaller sizes. Development and validation studies were performed on the 7500 real-time PCR system following the Quality Assurance Standards for Forensic DNA Testing Laboratories. Copyright © 2006 by American Academy of Forensic Sciences

Efficacy of Pulsed 405-nm LEDs for antimicrobial photodynamic inactivation : effects of intensity, frequency, and duty cycle

Objective: This study investigates possible advantages in pulsed over continuous 405-nm LED-light for bacterial inactivation and energy efficiency. Background: Alternative non-antibiotic methods of disinfection and infection control have become of significant interest. Recent studies have demonstrated the application of systems using 405-nm light-emitting diodes for continuous disinfection of the clinical environment, and also for potential treatment of contaminated wounds. Methods: Liquid suspensions of 103 CFU/ml populations of Staphylococcus aureus were subject to pulsed 405-nm light of different frequencies, duty cycles and intensities, and for different lengths of time. Results: Pulsed exposures with the same average irradiance of 16 mWcm2 and varying duty cycle (25%, 50%, 75%), showed very similar performance compared with continuous exposures, with 95-98% reduction of S. aureus achieved for all duty cycles. The pulsing frequency was varied in intervals from 100 Hz - 10 kHz and appeared to have little effect on antimicrobial efficacy. However, when comparing pulsed with continuous exposure, an improvement in inactivation per unit optical energy was achieved, with results showing an increase of approximately 83% in optical efficiency. Conclusions: These results suggest that under pulsed conditions a lower energy consumption and lower perceived brightness could be achieved, thus potentially providing improved operating conditions for medical/infection-control applications without compromising antimicrobial efficacy