Studies on processing, particle formation, and immunogenicity of the HIV-1 gag gene product: a possible component of a HIV vaccine

Antigens in a particulate conformation were shown to be highly immunogenic in mammals. For this reason, the particle forming capacity of derivatives of the HIV-1 group specific core antigen p55 gag was assayed and compared dependent on various expression systems: recombinant bacteria, vaccinia- and baculoviruses were established encoding the entire core protein p55 either in its authentic sequence or lacking the myristylation consensus signal. Moreover, p55 gag was expressed in combination with the protease (p55-PR) or with the entire polymerase (p55-pol), respectively. Budding of 100-160 nm p55 core particles, resembling immature HIV-virions, was observed in the eucaryotic expression systems only. In comparison to the vaccinia virus driven expression of p55 in mammalian cells, considerably higher yields of particulate core antigen were obtained by infection of Spodoptera frugiperda (Sf9) insect cells with the recombinant Autographa californica nuclear polyhedrosis (AcMNPV) baculovirus. Mutation of the NH2-terminal myristylation signal sequence prevented budding of the immature core particles. Expression of the HIV p55-PR gene construct by recombinant baculovirus resulted in complete processing of the p55 gag precursor molecule in this system. The introduction of an artificial frameshift near the natural frameshift site resulted in constitutive expression of the viral protease and complete processing of p55, both in Escherichia coli and in vaccinia virus infected cells. Interestingly, significant processing of p55 resembling that of HIV infected H9 cells could also be achieved in the vaccinia system by fusing the entire pol gene to the gag gene. Moreover, processing was not found to be dependent on amino-terminal myristylation of the gag procursor molecule, which is in contrast to observations with type C and type D retrovirus. However, complete processing of p55 into p24, p17, p9 and p6 abolished particle formation. Purified immature HIV-virus like particles were highly immunogenic in rabbits, leading to a strong humoral immune response after immunization. Empty immature p55 gag particles represent a noninfectious and attractive candidate for a basic vaccine component

Immunological reactivity of a human immunodeficiency virus type I derived peptide representing a consensus sequence of the GP120 major neutralizing region V3

To reduce the opportunities for human immunodeficiency virus type 1 (HIV-1) to evade vaccine induced immunity, the development of subunit vaccines must focus on the characterization of immunogenic epitopes, which are major targets for the immune system. The most dominant site for elicitation of neutralising immune response is located on the external envelope glycoprotein gp120 within the third variable domain (V3). To overcome virus type specificity of antibodies directed to the V3-domain we designed a 36 amino acids long gp120/V3-consensus peptide (V3-C36) based on published biological data and sequence comparisons of various HIV-1 virus isolates. This peptide contains a conserved core sequence which is suggested to form a surface-exposed beta-turn. This peptide also includes T-cell epitopes defined in mice and humans, an ADCC-epitope and two highly conserved cysteine residues which were oxidized to form a cystine derivate, thus allowing correct peptide folding. In ELISA-tests, this peptide reacts with at least 90% of randomly selected sera of European and African patients infected with HIV-1 and is recognized by three different HIV-1/V3 "type-specific" antisera (MN, RF, IIIB-strain). Using this peptide as immunogen in rabbits, antisera could be raised with highly cross-reactive and HIV-1/IIIB strain neutralizing properties. Moreover, HTLV/HIV-1/IIIB specific cytotoxic T-lymphocytes (CTLs) of BALB/c mice infected with a gp120 recombinant vaccinia virus recognized the central 16- and 12-mer peptides of the V3-C36 consensus peptide in cytolytic assays, indicating perfect compatibility of the consensus peptide with the IIIB-primed CTLs. The DNA-sequence encoding the V3-consensus loop region might be an important component in newly designed recombinant subunit vaccines. In addition, due to its broad serological reactivity, the V3-consensus peptide might play an important role in special diagnostic purposes

Temporal Oscillation of Conductances in Quantum Hall Effect of Bloch Electrons

We study a nonadiabatic effect on the conductances in the quantum Hall effect of two-dimensional electrons with a periodic potential. We found that the Hall and longitudinal conductances oscillate in time with a very large frequencies due to quantum fluctuation.Comment: 8 pages, 4 figure

Gender differences in self-reported family history of cancer A review and secondary data analysis in Cancer Medicine has the following publication status: Published as Early View

Background: Assessment of family history of cancer (FHC) mostly relies on self‐report. Our goal was to find out whether there is a systematic gender difference in self‐reported FHC. Methods: We identified nine population‐based studies which provided statistics of FHC in men and women (N1 = 404 541). Furthermore, we analyzed data (N2 = 167 154) from several iterations of the US‐based Health Information National Trends Survey (HINTS) and the National Health Interview Survey (NHIS). We calculated the proportion of positive FHC, odds ratios (OR M/F), 95% confidence intervals, and aggregated statistics. We additionally analyzed in‐depth questions about FHC from HINTS 5 Cycle 2. Results: In the reviewed studies the odds of men reporting a FHC were lower compared with the odds of women with an average OR of 0.84 [0.71; 1.00] across all studies and an OR of 0.75 [0.70; 0.80] for the six studies from the US and Europe. The gender gap was replicated in our own analyses of HINTS and NHIS with an average OR of 0.75 [0.71; 0.79]. In HINTS 5 Cycle 2 men described themselves as less familiar with their FHC and less confident answering questions regarding FHC. They were also less likely to discuss FHC with family members. Conclusions: Men— at least in the US and Europe—were consistently less likely to report FHC compared with women. Future research should investigate how the assessment of FHC can be improved to reduce these differences. Health care professionals should also consider the potential for biased reporting by gender when assessing FHC

Patient-reported outcomes following flexible sigmoidoscopy screening for colorectal cancer in a demonstration screening programme in the UK

<p>OBJECTIVES: Flexible sigmoidoscopy (FS) screening for colorectal cancer will be introduced into the National Cancer Screening Programmes in England in 2013. Patient-reported outcome measures (PROMs) from trial participants indicate high acceptability and no adverse physical or psychological consequences, but this may not generalize to routine screening in the community. This study examined PROMs in a community-based FS screening programme.</p> <p>METHODS: Eligible adults aged 58-59 (n = 2016) registered at 34 London general practices were mailed a National Health Service-endorsed invitation to attend FS screening. Pain and side-effects were assessed in a 'morning-after' questionnaire, and satisfaction was assessed in a three-month follow-up questionnaire. Anxiety, self-rated health and colorectal symptoms were assessed at prescreening and follow-up.</p> <p>RESULTS: In total, 1020 people attended screening and were included in the current analyses, of whom 913 (90%) returned the morning-after questionnaire, and 674 (66%) the follow-up questionnaire. The prescreening questionnaire had been completed by 751 (74%) of those who attended. The majority (87%) of respondents reported no pain or mild pain, and the most frequent side-effect (wind) was only experienced more than mildly by 16%. Satisfaction was extremely high, with 98% glad they had the test; 97% would encourage a friend to have it. From prescreening to follow-up there were no changes in anxiety or self-rated health, and the number of colorectal symptoms declined. Satisfaction and changes in wellbeing were not moderated by gender, deprivation, ethnicity or screening outcome.</p> <p>CONCLUSIONS: PROMs indicate high acceptability of FS screening in 58-59 year olds, with no adverse effects on colorectal symptoms, health status or psychological wellbeing.</p&gt

A Mean-Field Theory for Coarsening Faceted Surfaces

A mean-field theory is developed for the scale-invariant length distributions observed during the coarsening of one-dimensional faceted surfaces. This theory closely follows the Lifshitz-Slyozov-Wagner theory of Ostwald ripening in two-phase systems [1-3], but the mechanism of coarsening in faceted surfaces requires the addition of convolution terms recalling the work of Smoluchowski [4] and Schumann [5] on coalescence. The model is solved by the exponential distribution, but agreement with experiment is limited by the assumption that neighboring facet lengths are uncorrelated. However, the method concisely describes the essential processes operating in the scaling state, illuminates a clear path for future refinement, and offers a framework for the investigation of faceted surfaces evolving under arbitrary dynamics. [1] I. Lifshitz, V. Slezov, Soviet Physics JETP 38 (1959) 331-339. [2] I. Lifshitz, V. Slyozov, J. Phys. Chem. Solids 19 (1961) 35-50. [3] C. Wagner, Elektrochemie 65 (1961) 581-591. [4] M. von Smoluchowski, Physikalische Zeitschrift 17 (1916) 557-571. [5] T. Schumann, J. Roy. Met. Soc. 66 (1940) 195-207

How to measure patent thickets – a novel approach

The existing literature identifies patent thickets indirectly. In this paper we propose a novel measure based on patent citations which allows us to measure the density of patent thickets directly. We discuss the algorithm which generates the measure and present descriptive results validating it. Moreover, we identify technology areas which are particularly impacted by patent thickets

Maternal serum interleukin-1β, -6 and -8 levels and potential determinants in pregnancy and peripartum

Aims: To measure maternal serum interleukins (IL) in pregnancy, delivery and early puerperium, and to identify their potential determinants. Methods: Prospective longitudinal measures of serum IL-1β, IL-6 and IL-8 in 38 healthy pregnant women at antenatal visits, through labor and delivery, with clinical correlates (infection, vaginal hemorrhage and anemia) recorded by questionnaire. Results: Pregnancy IL levels remained consistently low. IL-1β increased shortly before delivery, then returned to pregnant levels, except where blood loss exceeded 500 ml. IL-6 and IL-8 rose at labor onset and exceeded pregnancy levels through postpartum day three. Postpartum IL-6 was higher after non-elective cesarean section than after spontaneous delivery (P < 0.0001), and where blood loss exceeded 500 ml. IL-6 and IL-8 were higher with systemic infection during delivery (P < 0.0001) and on postpartum day one (P < 0.05); IL-8 was higher in anemia (delivery: P < 0.005; postpartum day 1: P < 0.05). Differences due to delivery mode and systemic infection remained significant after correction for other conditions. Conclusions: Labor-dependent inflammation increases all IL levels at delivery. Further studies with larger sample sizes are required to establish reference values differentiating physiology from pathology as an aid to peripartum managemen

Offering disinclined people the choice between different screening appointments: a randomised online survey

Objectives: An invitation to cancer screening with a single (fixed) appointment time has been shown to be a more effective way at increasing uptake compared with an invitation with an open (unscheduled) appointment. The present study tested whether offering more than one fixed appointment could further enhance this effect or be detrimental to people’s intention. / Design: Experimental online hypothetical vignette survey. / Methods: 1,908 respondents who stated that they did not intend to participate in Bowel Scope Screening (BSS) were offered either one, two, four or six hypothetical fixed BSS appointments (all of which covered the same time of day to control for individual preferences). / Results: Participants who were given more than one appointment to choose from were less likely to intend to book an appointment despite multiple appointments being perceived as more convenient. / Conclusions: These results suggest that when it comes to offering people appointments for cancer screening, less (choice) is more, at least if alternatives fail to serve an inherent preference