CD155 on HIV-infected cells is not modulated by HIV-1 Vpu and Nef but synergizes with NKG2D ligands to trigger NK cell lysis of autologous primary HIV-infected cells

Activation of primary CD4(+) T cells induces the CD155, but not the CD112 ligands for the natural killer (NK) cell activation receptor (aNKR) CD226 [DNAX accessory molecule-1 (DNAM-1)]. We hypothesize that HIV productively infects activated CD4(+) T cells and makes itself vulnerable to NK cell-mediated lysis when CD155 on infected T cells engages DNAM-1. The primary objective of this study is to determine whether CD155 alone or together with NKG2D ligands triggers autologous NK cell lysis of HIV-infected T cells and whether HIV modulates CD155. To determine whether HIV modulates this activation ligand, we infected “activated” CD4(+) T cells with HIV in the absence or presence of Nef and/or Vpu and determined by flow cytometry whether they modulated CD155. To determine if CD155 alone, or together with NKG2D ligands, triggered NK cell lysis of autologous HIV-infected T cells, we treated purified NK cells with DNAM-1 and/or NKG2D blocking antibodies before the addition of purified autologous HIV-infected cells in cytolytic assays. Finally, we determined whether DNAM-1 works together with NKG2D as an NK cell coactivation receptor (caNKR) or whether they work independently as aNKRs to induce an NK cell lytic response. We demonstrate that HIV and specifically Nef and/or Vpu do not modulate CD155 on infected primary T cells; and both CD155 and NKG2D ligands synergize as aNKRs to trigger NK cell lysis of the infected cell

Calculating error bars for neutrino mixing parameters

One goal of contemporary particle physics is to determine the mixing angles and mass-squared differences that constitute the phenomenological constants that describe neutrino oscillations. Of great interest are not only the best fit values of these constants but also their errors. Some of the neutrino oscillation data is statistically poor and cannot be treated by normal (Gaussian) statistics. To extract confidence intervals when the statistics are not normal, one should not utilize the value for chisquare versus confidence level taken from normal statistics. Instead, we propose that one should use the normalized likelihood function as a probability distribution; the relationship between the correct chisquare and a given confidence level can be computed by integrating over the likelihood function. This allows for a definition of confidence level independent of the functional form of the !2 function; it is particularly useful for cases in which the minimum of the !2 function is near a boundary. We present two pedagogic examples and find that the proposed method yields confidence intervals that can differ significantly from those obtained by using the value of chisquare from normal statistics. For example, we find that for the first data release of the T2K experiment the probability that chisquare is not zero, as defined by the maximum confidence level at which the value of zero is not allowed, is 92%. Using the value of chisquare at zero and assigning a confidence level from normal statistics, a common practice, gives the over estimation of 99.5%.Comment: 9 pages, 6 figure

A history of the Eleventh New Hampshire Regiment, Volunteer Infantry in the rebellion war, 1861-1865

Mode of access: Internet

History of the town of Henniker, Merrimack County, New Hampshire, from the date of the Canada grant by the province of Massachusetts, in 1735, to 1880; with a genealogical register of the families of Henniker.

Mode of access: Internet

Neutrino Oscillations: Hierarchy Question

The only experimentally observed phenomenon that lies outside the standard model of the electroweak interaction is neutrino oscillations. A way to try to unify the extensive neutrino oscillation data is to add a phenomenological mass term to the Lagrangian that is not diagonal in the flavor basis. The goal is then to understand the world's data in terms of the parameters of the mixing matrix and the differences between the squares of the masses of the neutrinos. An outstanding question is what is the correct ordering of the masses, the hierarchy question. We point out a broken symmetry relevant to this question, the symmetry of the simultaneous interchange of hierarchy and the sign of $\theta_{13}$. We first present the results of an analysis of data that well determine the phenomenological parameters but are not sensitive to the hierarchy. We find $\theta_{13} = 0.152\pm 0.014$, $\theta_{23} = 0.25^{+0.03}_{-0.05} \pi$ and $\Delta_{32} = 2.45\pm 0.14 \times 10^{-3}$ eV$^2$, results consistent with others. We then include data that are sensitive to the hierarchy and the sign of $\theta_{13}$. We find, unlike others, four isolated minimum in the $\chi^2$-space as predicted by the symmetry. Now that Daya Bay and RENO have determined $\theta_{13}$ to be surprisingly large, the Super-K atmospheric data produce meaningful symmetry breaking such that the inverse hierarchy is preferred at the 97.2 % level.Comment: to appear in Proceedings of the 5th International Conference on Fission and Neutron Rich Nuclei (ICFN5), (Sanibel Island, Florina, Nov. 4-10, 2012).10 pages, 8 figure

Stereospecific alignment of the X and Y elements is required for major histocompatibility complex class II DRA promoter function.

The regulatory mechanisms controlling expression of the major histocompatibility complex (MHC) class II genes involve several cis-acting DNA elements, including the X and Y boxes. These two elements are conserved within all murine and human class II genes and are required for accurate and efficient transcription from MHC class II promoters. Interestingly, the distance between the X and Y elements is also evolutionarily conserved at 18 to 20 bp. To investigate the function of the invariant spacing in the human MHC class II gene, HLA-DRA, we constructed a series of spacing mutants which alters the distance between the X and Y elements by integral and half-integral turns of the DNA helix. Transient transfection of the spacing constructs into Raji cells revealed that inserting integral turns of the DNA helix (+20 and +10 bp) did not reduce promoter activity, while inserting or deleting half-integral turns of the DNA helix (+15, +5, and -5 bp) drastically reduced promoter activity. The loss of promoter function in these half-integral turn constructs was due neither to the inability of the X and Y elements to bind proteins nor to improper binding of the X- and Y-box-binding proteins. These data indicate that the X and Y elements must be aligned on the same side of the DNA helix to ensure normal function. This requirement for stereospecific alignment strongly suggests that the X- and Y-box-binding proteins either interact directly or are components of a larger transcription complex which assembles on one face of the DNA double helix