Proteomic and immunoproteomic characterization of a DIVA subunit vaccine against Actinobacillus pleuropneumoniae

<p>Abstract</p> <p>Background</p> <p>Protection of pigs by vaccination against <it>Actinobacillus pleuropneumoniae</it>, the causative agent of porcine pleuropneumonia, is hampered by the presence of 15 different serotypes. A DIVA subunit vaccine comprised of detergent-released proteins from <it>A. pleuropneumoniae </it>serotypes 1, 2 and 5 has been developed and shown to protect pigs from clinical symptoms upon homologous and heterologous challenge. This vaccine has not been characterized in-depth so far. Thus we performed i) mass spectrometry in order to identify the exact protein content of the vaccine and ii) cross-serotype 2-D immunoblotting in order to discover cross-reactive antigens. By these approaches we expected to gain results enabling us to argue about the reasons for the efficacy of the analyzed vaccine.</p> <p>Results</p> <p>We identified 75 different proteins in the vaccine. Using the PSORTb algorithm these proteins were classified according to their cellular localization. Highly enriched proteins are outer membrane-associated lipoproteins like OmlA and TbpB, integral outer membrane proteins like FrpB, TbpA, OmpA1, OmpA2, HgbA and OmpP2, and secreted Apx toxins. The subunit vaccine also contained large amounts of the ApxIVA toxin so far thought to be expressed only during infection. Applying two-dimensional difference gel electrophoresis (2-D DIGE) we showed different isoforms and variations in expression levels of several proteins among the strains used for vaccine production. For detection of cross-reactive antigens we used detergent released proteins of serotype 7. Sera of pigs vaccinated with the detergent-released proteins of serotypes 1, 2, and 5 detected seven different proteins of serotype 7, and convalescent sera of pigs surviving experimental infection with serotype 7 reacted with 13 different proteins of the detergent-released proteins of <it>A. pleuropneumoniae </it>serotypes 1, 2, and 5.</p> <p>Conclusions</p> <p>A detergent extraction-based subunit vaccine of <it>A. pleuropneumoniae </it>was characterized by mass spectrometry. It contained a large variety of immunogenic and virulence associated proteins, among them the ApxIVA toxin. The identification of differences in expression as well as isoform variation between the serotypes implied the importance of combining proteins of different serotypes for vaccine generation. This finding was supported by immunoblotting showing the induction of cross-reactive antibodies against several surface associated proteins in immunized animals.</p

The Parallel Persistent Memory Model

We consider a parallel computational model that consists of $P$ processors, each with a fast local ephemeral memory of limited size, and sharing a large persistent memory. The model allows for each processor to fault with bounded probability, and possibly restart. On faulting all processor state and local ephemeral memory are lost, but the persistent memory remains. This model is motivated by upcoming non-volatile memories that are as fast as existing random access memory, are accessible at the granularity of cache lines, and have the capability of surviving power outages. It is further motivated by the observation that in large parallel systems, failure of processors and their caches is not unusual. Within the model we develop a framework for developing locality efficient parallel algorithms that are resilient to failures. There are several challenges, including the need to recover from failures, the desire to do this in an asynchronous setting (i.e., not blocking other processors when one fails), and the need for synchronization primitives that are robust to failures. We describe approaches to solve these challenges based on breaking computations into what we call capsules, which have certain properties, and developing a work-stealing scheduler that functions properly within the context of failures. The scheduler guarantees a time bound of $O(W/P_A + D(P/P_A) \lceil\log_{1/f} W\rceil)$ in expectation, where $W$ and $D$ are the work and depth of the computation (in the absence of failures), $P_A$ is the average number of processors available during the computation, and $f \le 1/2$ is the probability that a capsule fails. Within the model and using the proposed methods, we develop efficient algorithms for parallel sorting and other primitives.Comment: This paper is the full version of a paper at SPAA 2018 with the same nam

Australian women's prediagnostic values and influencing sociodemographic variables relating to treatment choices for early breast cancer treatment

Women are often asked by their doctors to choose their preferred treatment for early breast cancer. Evidence shows that many women are distressed and confused about how to make this treatment decision and frequently seek help from nurses. Very little is known about women's value-centred decision-making in relation to selecting treatment for breast cancer and for nurses it is difficult to know how to assist these women with this process. In this study, 377 women participated prior to undergoing routine mammography screening and the data were collected using the Pre-Decision Portfolio Questionnaire (PDPQ) by Pierce 1. The partipants identified that expected treatment outcomes were the most important factor in choosing early breast cancer treatment. The majority reported that it was very important that a treatment would reduce the chances the cancer would return (95.6%), increase the length of their life (82.1%) and lead them to being healthy (80.4%). In addition, the participants indicated that it was important, or very important, that the emotional consequences of the treatment did "not make you depressed" (88.6%) or "sad" (90.4%) and should "keep you from worrying" (97%) and "give you peace of mind" (98.6%). Other factors, such as treatment's side effects, were identified as less important. Age, employment, education and having a family history of breast cancer were found to be significant influencing variables on the values of the participants. It was concluded that assessing and understanding the treatment values of women can help nurses focus on areas of importance to the woman and lead to informed decision-making when they are choosing treatment for early breast cancer

Does single application of topical chloramphenicol to high risk sutured wounds reduce incidence of wound infection after minor surgery? Prospective randomised placebo controlled double blind trial

Objective To determine the effectiveness of a single application of topical chloramphenicol ointment in preventing wound infection after minor dermatological surgery

Early childhood anaemia more than doubles the risk of developmental vulnerability at school-age among Aboriginal and Torres Strait Islander children of remote Far North Queensland: Findings of a retrospective cohort study

AIMS:Early childhood anaemia, usually attributed to iron deficiency, is associated with persistent detrimental effects on child development. This study investigates the association of anaemia between age six and 23 months with indicators of childhood development at school-age among children of remote Aboriginal and Torres Strait Islander communities of Far North Queensland. METHODS:The triennial Australian Early Development Census (AEDC) encompasses five domains of early childhood development-physical health and wellbeing, social competence, emotional maturity, language and cognitive skills (school-based), communication skills and general knowledge. AEDC 2012 and 2015 assessments were linked with health information for children and their mothers from remote Aboriginal and Torres Strait Islander communities of Far North Queensland. RESULTS:AEDC assessments were available for 250 children who had measurements of haemoglobin recorded at age 6 to 23 months. More children who had had early childhood anaemia (n = 66/143, 46.2%, [37.9%, 54.4%]) were developmentally vulnerable on two or more domains compared to those who had not been anaemic (n = 25/107, 23.4% [15.2%, 31.5%], P < .001). Multivariable analysis confirmed that early childhood anaemia more than doubled the risk of developmental vulnerability (OR 2.2 [1.1, 4.3] P = .020) at school age. CONCLUSIONS:Early childhood anaemia is a risk factor for developmental vulnerability at school-age in this setting. Interventions combining nutrition promotion and multi-micronutrient food fortification, are effective in prevention of early childhood anaemia. Such interventions could also improve early childhood development and subsequent educational achievement.Dympna Leonard, Petra Buettner, Fintan Thompson, Maria Makrides, Robyn McDermot

Measurement of the Luminosity in the ZEUS Experiment at HERA II

The luminosity in the ZEUS detector was measured using photons from electron bremsstrahlung. In 2001 the HERA collider was upgraded for operation at higher luminosity. At the same time the luminosity-measuring system of the ZEUS experiment was modified to tackle the expected higher photon rate and synchrotron radiation. The existing lead-scintillator calorimeter was equipped with radiation hard scintillator tiles and shielded against synchrotron radiation. In addition, a magnetic spectrometer was installed to measure the luminosity independently using photons converted in the beam-pipe exit window. The redundancy provided a reliable and robust luminosity determination with a systematic uncertainty of 1.7%. The experimental setup, the techniques used for luminosity determination and the estimate of the systematic uncertainty are reported.Comment: 25 pages, 11 figure

Arene oxidation with malonoyl peroxides

Malonoyl peroxide 7, prepared in a single step from the commercially available diacid, is an effective reagent for the oxidation of aromatics. Reaction of an arene with peroxide 7 at room temperature leads to the corresponding protected phenol which can be unmasked by aminolysis. An ionic mechanism consistent with the experimental findings and supported by isotopic labeling, Hammett analysis, EPR investigations and reactivity profile studies is proposed