TGF-β and IL-10 Production by HIV-Specific CD8+ T Cells Is Regulated by CTLA-4 Signaling on CD4+ T Cells

Immune dysregulation in HIV-1 infection is associated with increased expression of inhibitory molecules such as CTLA-4, TGF-β, and IL-10. In this study we examined one potential mechanism for regulating TGF-β and IL-10 expression by HIV-specific suppressor CD8+ T cells. No overlap between TGF-β, IL-10, and IFN-γ cytokine production by HIV-specific CD8+ T cells was observed. TGF-β positive and IL-10 positive cells were FOXP3 negative, CD25 negative, and displayed a heterogeneous surface expression of CD127. TGF-β and IL-10 positive CD8+ T cells did not express CTLA-4. Nevertheless, CTLA-4 blockade resulted in a significant decrease in HIV-specific TGF-β positive and IL-10 positive CD8+ T cell responses, and a concomitant increase in HIV-specific IFN-γ positive CD8+ T cell responses. Depletion of CD4+ T cells abrogated the impact of CTLA-4 on HIV-specific TGF-β positive and IL-10 positive CD8+ T cells. Our study suggests that CTLA-4 Signaling on CD4+ T cells regulates the inhibitory functions of the HIV-specific suppressor CD8+ T cells

Atmospheric deposition of soluble trace elements along the Atlantic Meridional Transect (AMT)

We briefly review the role of atmospheric deposition measurements within the Atlantic Meridional Transect (AMT) programme and then go on to present new data on the soluble concentrations of a range of trace metals (Fe, Al, Mn, Ti, Zn, V, Ni and Cu) and major ions in aerosols collected along the AMT transect. The results allow us to identify emission sources of the trace metals particularly in terms of the relative importance of anthropogenic versus crustal sources. We identify strong gradients in concentrations and deposition for both crustal and anthropogenically sourced metals with much higher inputs to the North Atlantic compared to the South Atlantic, reflecting stronger land based emission sources in the Northern Hemisphere. We suggest anthropogenic sources of Ni and V may include an important component from shipping. We consider the extent to which these gradients are reflected in surface water concentrations of these metals based on the GEOTRACES water column trace metal data. We find there is a clear difference in the concentrations of surface water dissolved Al and Fe between the north and south Atlantic gyres reflecting atmospheric inputs. However for Mn, V or Ni, higher inputs to the North Atlantic compared to the South Atlantic are not clearly reflected in their water column concentrations

Does shade improve light interception efficiency? A comparison among seedlings from shade-tolerant and -intolerant temperate deciduous tree species

• Here, we tested two hypotheses: shading increases light interception efficiency (LIE) of broadleaved tree seedlings, and shade-tolerant species exhibit larger LIEs than do shade-intolerant ones. The impact of seedling size was taken into account to detect potential size-independent effects on LIE. LIE was defined as the ratio of mean light intercepted by leaves to light intercepted by a horizontal surface of equal area. • Seedlings from five species differing in shade tolerance (Acer saccharum, Betula alleghaniensis, A. pseudoplatanus, B. pendula, Fagus sylvatica) were grown under neutral shading nets providing 36, 16 and 4% of external irradiance. Seedlings (1- and 2-year-old) were three-dimensionally digitized, allowing calculation of LIE. • Shading induced dramatic reduction in total leaf area, which was lowest in shade-tolerant species in all irradiance regimes. Irradiance reduced LIE through increasing leaf overlap with increasing leaf area. There was very little evidence of significant size-independent plasticity of LIE. • No relationship was found between the known shade tolerance of species and LIE at equivalent size and irradiance

Forward Neutron Production at the Fermilab Main Injector

We have measured cross sections for forward neutron production from a variety of targets using proton beams from the Fermilab Main Injector. Measurements were performed for proton beam momenta of 58 GeV/c, 84 GeV/c, and 120 GeV/c. The cross section dependence on the atomic weight (A) of the targets was found to vary as $A^(alpha)$ where $\alpha$ is $0.46\pm0.06$ for a beam momentum of 58 GeV/c and 0.54$\pm$0.05 for 120 GeV/c. The cross sections show reasonable agreement with FLUKA and DPMJET Monte Carlos. Comparisons have also been made with the LAQGSM Monte Carlo.Comment: Accepted for publication in Physical Review D. This version incorporates small changes suggested by referee and small corrections in the neutron production cross sections predicted by FLUK

Measurement of Charged Pion Production Yields off the NuMI Target

The fixed-target MIPP experiment, Fermilab E907, was designed to measure the production of hadrons from the collisions of hadrons of momenta ranging from 5 to 120 GeV/c on a variety of nuclei. These data will generally improve the simulation of particle detectors and predictions of particle beam fluxes at accelerators. The spectrometer momentum resolution is between 3 and 4%, and particle identification is performed for particles ranging between 0.3 and 80 GeV/c using $dE/dx$, time-of-flight and Cherenkov radiation measurements. MIPP collected $1.42 \times10^6$ events of 120 GeV Main Injector protons striking a target used in the NuMI facility at Fermilab. The data have been analyzed and we present here charged pion yields per proton-on-target determined in bins of longitudinal and transverse momentum between 0.5 and 80 GeV/c, with combined statistical and systematic relative uncertainties between 5 and 10%.Comment: 15 pages, 13 figure

Interpreting the results of patient reported outcome measures in clinical trials: The clinician's perspective

This article deals with the problem of interpreting health-related quality of life (HRQL) outcomes in clinical trials. First, we will briefly describe how dichotomization and item response theory can facilitate interpretation. Based on examples from the medical literature for the interpretation of HRQL scores we will show that dichotomies may help clinicians understand information provided by HRQL instruments in RCTs. They can choose thresholds to calculate proportions of patients benefiting based on absolute scores or change scores. For example, clinicians interpreting clinical trial results could consider the difference in the proportion of patients who achieve a mean score of 50 before and after an intervention on a scale from 1 to 100. For the change score approach, they could consider the proportion of patients who have changed by a score of 5 or more. Finally, they can calculate the proportion of patients benefiting and transform these numbers into a number needed to treat or natural frequencies. Second, we will describe in more detail an approach to the interpretation of HRQL scores based on the minimal important difference (MID) and proportions. The MID is the smallest difference in score in the outcome of interest that informed patients or informed proxies perceive as important, either beneficial or harmful, and that would lead the patient or clinician to consider a change in the management. Any change in management will depend on the downsides, including cost and inconvenience, associated with the intervention. Investigators can help with the interpretation of HRQL scores by determining the MID of an HRQL instrument and provide mean differences in relation to the MID. For instance, for an MID of 0.5 on a seven point scale investigators could provide the mean change on the instrument as well as the proportion of patients with scores greater than the MID. Thus, there are several steps investigators can take to facilitate this process to help bringing HRQL information closer to the bedside