Rate of Dissolution of γ-Irradiated Sodium Chloride Single Crystal Studied by Aquoluminescence

1009-101

Accounting Problems Under the Excess Profits Tax

DNA vaccines based on subunits from pathogens have several advantages over other vaccine strategies. DNA vaccines can easily be modified, they show good safety profiles, are stable and inexpensive to produce, and the immune response can be focused to the antigen of interest. However, the immunogenicity of DNA vaccines which is generally quite low needs to be improved. Electroporation and co-delivery of genetically encoded immune adjuvants are two strategies aiming at increasing the efficacy of DNA vaccines. Here, we have examined whether targeting to antigen-presenting cells (APC) could increase the immune response to surface envelope glycoprotein (Env) gp120 from Human Immunodeficiency Virus type 1 (HIV- 1). To target APC, we utilized a homodimeric vaccine format denoted vaccibody, which enables covalent fusion of gp120 to molecules that can target APC. Two molecules were tested for their efficiency as targeting units: the antibody-derived single chain Fragment variable (scFv) specific for the major histocompatilibility complex (MHC) class II I-E molecules, and the CC chemokine ligand 3 (CCL3). The vaccines were delivered as DNA into muscle of mice with or without electroporation. Targeting of gp120 to MHC class II molecules induced antibodies that neutralized HIV-1 and that persisted for more than a year after one single immunization with electroporation. Targeting by CCL3 significantly increased the number of HIV-1 gp120-reactive CD8(+) T cells compared to non-targeted vaccines and gp120 delivered alone in the absence of electroporation. The data suggest that chemokines are promising molecular adjuvants because small amounts can attract immune cells and promote immune responses without advanced equipment such as electroporation.Funding Agencies|Research Council of Norway; Odd Fellow</p

Rasch analysis of the Patient and Observer Scar Assessment Scale (POSAS) in burn scars

The Patient and Observer Scar Assessment Scale (POSAS) is a questionnaire that was developed to assess scar quality. It consists of two separate six-item scales (Observer Scale and Patient Scale), both of which are scored on a 10-point rating scale. After many years of experience with this scale in burn scar assessment, it is appropriate to examine its psychometric properties using Rasch analysis. Cross-sectional data collection from seven clinical trials resulted in a data set of 1,629 observer scores and 1,427 patient scores of burn scars. We examined the person-item map, item fit statistics, reliability, response category ordering, and dimensionality of the POSAS. The POSAS showed an adequate fit to the Rasch model, except for the item surface area. Person reliability of the Observer Scale and Patient Scale was 0.82 and 0.77, respectively. Dimensionality analysis revealed that the unexplained variance by the first contrast of both scales was 1.7 units. Spearman correlation between the Observer Scale Rasch measure and the overall opinion of the clinician was 0.75. The Rasch model demonstrated that the POSAS is a reliable and valid scale that measures the single-construct scar qualit

The Secreted Lipoprotein, MPT83, of Mycobacterium tuberculosis Is Recognized during Human Tuberculosis and Stimulates Protective Immunity in Mice

The long-term control of tuberculosis (TB) will require the development of more effective anti-TB vaccines, as the only licensed vaccine, Mycobacterium bovis bacille Calmette-Guérin (BCG), has limited protective efficacy against infectious pulmonary TB. Subunit vaccines have an improved safety profile over live, attenuated vaccines, such as BCG, and may be used in immuno-compromised individuals. MPT83 (Rv2873) is a secreted mycobacterial lipoprotein expressed on the surface of Mycobacterium tuberculosis. In this study, we examined whether recombinant MPT83 is recognized during human and murine M. tuberculosis infection. We assessed the immunogenicity and protective efficacy of MPT83 as a protein vaccine, with monophosphyl lipid A (MPLA) in dimethyl-dioctadecyl ammonium bromide (DDA) as adjuvant, or as a DNA vaccine in C57BL/6 mice and mapped the T cell epitopes with peptide scanning. We demonstrated that rMPT83 was recognised by strong proliferative and Interferon (IFN)-γ-secreting T cell responses in peripheral blood mononuclear cells (PBMC) from patients with active TB, but not from healthy, tuberculin skin test-negative control subjects. MPT83 also stimulated strong IFN-γ T cell responses during experimental murine M. tuberculosis infection. Immunization with either rMPT83 in MPLA/DDA or DNA-MPT83 stimulated antigen-specific T cell responses, and we identified MPT83127–135 (PTNAAFDKL) as the dominant H-2b-restricted CD8+ T cell epitope within MPT83. Further, immunization of C57BL/6 mice with rMPT83/MPLA/DDA or DNA-MPT83 stimulated significant levels of protection in the lungs and spleens against aerosol challenge with M. tuberculosis. Interestingly, immunization with rMPT83 in MPLA/DDA primed for stronger IFN-γ T cell responses to the whole protein following challenge, while DNA-MPT83 primed for stronger CD8+ T cell responses to MPT83127–135. Therefore MPT83 is a protective T cell antigen commonly recognized during human M. tuberculosis infection and should be considered for inclusion in future TB subunit vaccines

DNA vaccination for prostate cancer: key concepts and considerations

While locally confined prostate cancer is associated with a low five year mortality rate, advanced or metastatic disease remains a major challenge for healthcare professionals to treat and is usually terminal. As such, there is a need for the development of new, efficacious therapies for prostate cancer. Immunotherapy represents a promising approach where the host’s immune system is harnessed to mount an anti-tumour effect, and the licensing of the first prostate cancer specific immunotherapy in 2010 has opened the door for other immunotherapies to gain regulatory approval. Among these strategies DNA vaccines are an attractive option in terms of their ability to elicit a highly specific, potent and wide-sweeping immune response. Several DNA vaccines have been tested for prostate cancer and while they have demonstrated a good safety profile they have faced problems with low efficacy and immunogenicity compared to other immunotherapeutic approaches. This review focuses on the positive aspects of DNA vaccines for prostate cancer that have been assessed in preclinical and clinical trials thus far and examines the key considerations that must be employed to improve the efficacy and immunogenicity of these vaccines

Comparing Recent Pulsar Timing Array Results on the Nanohertz Stochastic Gravitational-wave Background

The Australian, Chinese, European, Indian, and North American pulsar timing array (PTA) collaborations recently reported, at varying levels, evidence for the presence of a nanohertz gravitational-wave background (GWB). Given that each PTA made different choices in modeling their data, we perform a comparison of the GWB and individual pulsar noise parameters across the results reported from the PTAs that constitute the International Pulsar Timing Array (IPTA). We show that despite making different modeling choices, there is no significant difference in the GWB parameters that are measured by the different PTAs, agreeing within 1σ. The pulsar noise parameters are also consistent between different PTAs for the majority of the pulsars included in these analyses. We bridge the differences in modeling choices by adopting a standardized noise model for all pulsars and PTAs, finding that under this model there is a reduction in the tension in the pulsar noise parameters. As part of this reanalysis, we "extended" each PTA's data set by adding extra pulsars that were not timed by that PTA. Under these extensions, we find better constraints on the GWB amplitude and a higher signal-to-noise ratio for the Hellings–Downs correlations. These extensions serve as a prelude to the benefits offered by a full combination of data across all pulsars in the IPTA, i.e., the IPTA's Data Release 3, which will involve not just adding in additional pulsars but also including data from all three PTAs where any given pulsar is timed by more than a single PTA

Comparing recent PTA results on the nanohertz stochastic gravitational wave background

The Australian, Chinese, European, Indian, and North American pulsar timing array (PTA) collaborations recently reported, at varying levels, evidence for the presence of a nanohertz gravitational wave background (GWB). Given that each PTA made different choices in modeling their data, we perform a comparison of the GWB and individual pulsar noise parameters across the results reported from the PTAs that constitute the International Pulsar Timing Array (IPTA). We show that despite making different modeling choices, there is no significant difference in the GWB parameters that are measured by the different PTAs, agreeing within $1\sigma$. The pulsar noise parameters are also consistent between different PTAs for the majority of the pulsars included in these analyses. We bridge the differences in modeling choices by adopting a standardized noise model for all pulsars and PTAs, finding that under this model there is a reduction in the tension in the pulsar noise parameters. As part of this reanalysis, we "extended" each PTA's data set by adding extra pulsars that were not timed by that PTA. Under these extensions, we find better constraints on the GWB amplitude and a higher signal-to-noise ratio for the Hellings and Downs correlations. These extensions serve as a prelude to the benefits offered by a full combination of data across all pulsars in the IPTA, i.e., the IPTA's Data Release 3, which will involve not just adding in additional pulsars, but also including data from all three PTAs where any given pulsar is timed by more than as single PTA.Comment: 21 pages, 9 figures, submitted to Ap

How to Detect an Astrophysical Nanohertz Gravitational Wave Background

\ua9 2023. The Author(s). Published by the American Astronomical Society.Analyses of pulsar timing data have provided evidence for a stochastic gravitational wave background in the nanohertz frequency band. The most plausible source of this background is the superposition of signals from millions of supermassive black hole binaries. The standard statistical techniques used to search for this background and assess its significance make several simplifying assumptions, namely (i) Gaussianity, (ii) isotropy, and most often, (iii) a power-law spectrum. However, a stochastic background from a finite collection of binaries does not exactly satisfy any of these assumptions. To understand the effect of these assumptions, we test standard analysis techniques on a large collection of realistic simulated data sets. The data-set length, observing schedule, and noise levels were chosen to emulate the NANOGrav 15 yr data set. Simulated signals from millions of binaries drawn from models based on the Illustris cosmological hydrodynamical simulation were added to the data. We find that the standard statistical methods perform remarkably well on these simulated data sets, even though their fundamental assumptions are not strictly met. They are able to achieve a confident detection of the background. However, even for a fixed set of astrophysical parameters, different realizations of the universe result in a large variance in the significance and recovered parameters of the background. We also find that the presence of loud individual binaries can bias the spectral recovery of the background if we do not account for them