Huisgen-based conjugation of water-soluble porphyrins to deprotected sugars: Towards mild strategies for the labelling of glycans

Fully deprotected alkynyl-functionalised mono- and oligosaccharides undergo CuAAC-based conjugation with water-soluble porphyrin azides in aqueous environments. The mild reaction conditions are fully compatible with the presence of labile glycosidic bonds. This approach provides an ideal strategy to conjugate tetrapyrroles to complex carbohydrates

Efficacy of nisin A and nisin V semi-purified preparations alone and in combination with plant essential oils to control Listeria monocytogenes

peer-reviewedThe foodborne pathogenic bacterium Listeria is known for relatively low morbidity and high mortality rates reaching up to 25-30%. Listeria is a hardy organism and its control in foods represents a significant challenge. Many naturally occurring compounds, including the bacteriocin nisin and a number of plant essential oils, have been widely studied and are reported to be effective as antimicrobial agents against spoilage and pathogenic microorganisms. The aim of this study was to investigate the ability of semi-purified preparations (spp) containing either nisin A or an enhanced bioengineered derivative nisin V, alone and in combination with low concentrations of the essential oils thymol, carvacrol and trans-cinnamaldehyde, to control L. monocytogenes in both laboratory media and model food systems. Combinations of nisin V-containing spp (25 μg/ml) with thymol (0.02%), carvacrol (0.02%) or cinnamaldehyde (0.02%) produced a significantly longer lag phase than any of the essential oil/nisin A combinations. In addition, the log reduction in cell counts achieved by the nisin V + carvacrol or nisin V + cinnamaldehyde combinations was twice that of the equivalent nisin A + essential oil treatment. Significantly, this enhanced activity was validated in model food systems against L. monocytogenes strains of food origin. We conclude that the fermentate form of nisin V in combination with carvacrol and cinnamaldehyde offers significant advantages as a novel, natural and effective means to enhance food safety by inhibiting foodborne pathogens such as L. monocytogenes.This work was supported by the Irish Government under the National Development Plan, through Science Foundation Ireland Investigator awards to C.H. and R.P.R. (10/IN.1/B3027), and C.H., R.P.R. and P.D.C. (06/IN.1/B98)

Atypical Listeria innocua strains possess an intact LIPI-3

peer-reviewedBackground: Listeria monocytogenes is a food-borne pathogen which is the causative agent of listeriosis and can be divided into three evolutionary lineages I, II and III. While all strains possess the well established virulence factors associated with the Listeria pathogenicity island I (LIPI-1), lineage I strains also possess an additional pathogenicity island designated LIPI-3 which encodes listeriolysin S (LLS), a post-translationally modified cytolytic peptide. Up until now, this pathogenicity island has been identified exclusively in a subset of lineage I isolates of the pathogen Listeria monocytogenes. Results: In total 64 L. innocua strains were screened for the presence of LIPI-3. Here we report the identification of an intact LIPI-3 in 11 isolates of L. innocua and the remnants of the cluster in several others. Significantly, we can reveal that placing the L. innocua lls genes under the control of a constitutive promoter results in a haemolytic phenotype, confirming that the cluster is capable of encoding a functional haemolysin. Conclusions: Although the presence of the LIPI-3 gene cluster is confined to lineage I isolates of L. monocytogenes, a corresponding gene cluster or its remnants have been identified in many L. innocua strains.This work was funded by the Enterprise Ireland Commercialisation fund, a programme which is co-financed by the EU through the ERDF. This work was also supported by the Irish Government under the National Development Plan, through Science Foundation Ireland Investigator awards; (06/IN.1/B98) and (10/IN.1/B3027)

RowHammer: Reliability Analysis and Security Implications

As process technology scales down to smaller dimensions, DRAM chips become more vulnerable to disturbance, a phenomenon in which different DRAM cells interfere with each other's operation. For the first time in academic literature, our ISCA paper exposes the existence of disturbance errors in commodity DRAM chips that are sold and used today. We show that repeatedly reading from the same address could corrupt data in nearby addresses. More specifically: When a DRAM row is opened (i.e., activated) and closed (i.e., precharged) repeatedly (i.e., hammered), it can induce disturbance errors in adjacent DRAM rows. This failure mode is popularly called RowHammer. We tested 129 DRAM modules manufactured within the past six years (2008-2014) and found 110 of them to exhibit RowHammer disturbance errors, the earliest of which dates back to 2010. In particular, all modules from the past two years (2012-2013) were vulnerable, which implies that the errors are a recent phenomenon affecting more advanced generations of process technology. Importantly, disturbance errors pose an easily-exploitable security threat since they are a breach of memory protection, wherein accesses to one page (mapped to one row) modifies the data stored in another page (mapped to an adjacent row).Comment: This is the summary of the paper titled "Flipping Bits in Memory Without Accessing Them: An Experimental Study of DRAM Disturbance Errors" which appeared in ISCA in June 201

Bioengineered Nisin A Derivatives with Enhanced Activity against Both Gram Positive and Gram Negative Pathogens

peer-reviewedNisin is a bacteriocin widely utilized in more than 50 countries as a safe and natural antibacterial food preservative. It is the most extensively studied bacteriocin, having undergone decades of bioengineering with a view to improving function and physicochemical properties. The discovery of novel nisin variants with enhanced activity against clinical and foodborne pathogens has recently been described. We screened a randomized bank of nisin A producers and identified a variant with a serine to glycine change at position 29 (S29G), with enhanced efficacy against S. aureus SA113. Using a site-saturation mutagenesis approach we generated three more derivatives (S29A, S29D and S29E) with enhanced activity against a range of Gram positive drug resistant clinical, veterinary and food pathogens. In addition, a number of the nisin S29 derivatives displayed superior antimicrobial activity to nisin A when assessed against a range of Gram negative food-associated pathogens, including E. coli, Salmonella enterica serovar Typhimurium and Cronobacter sakazakii. This is the first report of derivatives of nisin, or indeed any lantibiotic, with enhanced antimicrobial activity against both Gram positive and Gram negative bacteria.This work was supported by the Irish Government under the National Development Plan, through Science Foundation Ireland Investigator awards (10/IN.1/B3027) and (06/IN.1/B98) (http://www.sfi.ie)

Listeriolysin S, a Novel Peptide Haemolysin Associated with a Subset of Lineage I Listeria monocytogenes

peer-reviewedStreptolysin S (SLS) is a bacteriocin-like haemolytic and cytotoxic virulence factor that plays a key role in the virulence of Group A Streptococcus (GAS), the causative agent of pharyngitis, impetigo, necrotizing fasciitis and streptococcal toxic shock syndrome. Although it has long been thought that SLS and related peptides are produced by GAS and related streptococci only, there is evidence to suggest that a number of the most notorious Gram-positive pathogenic bacteria, including Listeria monocytogenes, Clostridium botulinum and Staphylococcus aureus, produce related peptides. The distribution of the L. monocytogenes cluster is particularly noteworthy in that it is found exclusively among a subset of lineage I strains; i.e., those responsible for the majority of outbreaks of listeriosis. Expression of these genes results in the production of a haemolytic and cytotoxic factor, designated Listeriolysin S, which contributes to virulence of the pathogen as assessed by murine- and human polymorphonuclear neutrophil–based studies. Thus, in the process of establishing the existence of an extended family of SLS-like modified virulence peptides (MVPs), the genetic basis for the enhanced virulence of a proportion of lineage I L. monocytogenes may have been revealed.Work is funded by the Irish Government under the National Development Plan, through a Science Foundation Ireland Investigator award to CH, PR and PC (06/IN.1/B98)

PEak: A Single Source of Truth for Hardware Design and Verification

Domain-specific languages for hardware can significantly enhance designer productivity, but sometimes at the cost of ease of verification. On the other hand, ISA specification languages are too static to be used during early stage design space exploration. We present PEak, an open-source hardware design and specification language, which aims to improve both design productivity and verification capability. PEak does this by providing a single source of truth for functional models, formal specifications, and RTL. PEak has been used in several academic projects, and PEak-generated RTL has been included in three fabricated hardware accelerators. In these projects, the formal capabilities of PEak were crucial for enabling both novel design space exploration techniques and automated compiler synthesis

Comparison of the prognostic value of ECOG-PS, MGPS and BMI/WL: Implications for a clinically important framework in the assessment and treatment of advanced cancer

BACKGROUND AND AIMS:The systemic inflammatory response is associated with the loss of lean tissue, anorexia, weakness, fatigue and reduced survival in patients with advanced cancer and therefore is important in the definition of cancer cachexia. The aim of the present study was to carry out a direct comparison of the prognostic value of Eastern Cooperative Oncology Group Performance Status (ECOG-PS), modified Glasgow Prognostic Score (mGPS) and Body Mass Index/Weight Loss Grade (BMI/WL grade) in patients with advanced cancer. METHOD:All data were collected prospectively across 18 sites in the UK and Ireland. Patient's age, sex, ECOG-PS, mGPS and BMI/WL grade were recorded, as were details of underlying disease including metastases. Survival data were analysed using univariate and multivariate Cox regression. RESULTS:A total of 730 patients were assessed. The majority of patients were male (53%), over 65 years of age (56%), had an ECOG-PS>0/1 (56%), mGPS≥1 (56%), BMI≥25 (51%), <2.5% weight loss (57%) and had metastatic disease (86%). On multivariate cox regression analysis ECOG-PS (HR 1.61 95%CI 1.42-1.83, p < 0.001), mGPS (HR 1.53, 95%CI 1.39-1.69, p < 0.001) and BMI/WL grade (HR 1.41, 95%CI 1.25-1.60, p < 0.001) remained independently associated with overall survival. In patients with a BMI/WL grade 0/1 both ECOG and mGPS remained independently associated with overall survival. CONCLUSION:The ECOG/mGPS framework may form the basis of risk stratification of survival in patients with advanced cancer

The benefits and enjoyment of a swimming intervention for youth with cerebral palsy:An RCT Study

To investigate enjoyment and specific benefits of a swimming intervention for youth with cerebral palsy (CP).status: publishe