Absolute Calibration of a Large-diameter Light Source

A method of absolute calibration for large aperture optical systems is presented, using the example of the Pierre Auger Observatory fluorescence detectors. A 2.5 m diameter light source illuminated by an ultra--violet light emitting diode is calibrated with an overall uncertainty of 2.1 % at a wavelength of 365 nm.Comment: 15 pages, 8 figures. Submitted to JINS

Absolute Calibration of the Auger Fluorescence Detectors

Absolute calibration of the Pierre Auger Observatory fluorescence detectors uses a light source at the telescope aperture. The technique accounts for the ombined effects of all detector components in a single measurement. The calibrated 2.5 m diameter light source fills the aperture, providing uniform illumination to each pixel. The known flux from the light source and the response of the acquisition system give the required calibration for each pixel. In the lab, light source uniformity is studied using CCD images and the intensity is measured relative to NIST-calibrated photodiodes. Overall uncertainties are presently 12%, and are dominated by systematics.Comment: 4 pages, 3 figure. Submitted to the 29th ICRC, Pune, Indi

Multi-wavelength Calibration Procedure for the Pierre Auger Observatory Fluorescence Detectors

We present a method to measure the relative spectral response of the Pierre Auger Observatory Fluorescence Detector. The calibration was done at wavelengths of 320, 337, 355, 380 and 405 nm using an end-to-end technique in which the response of all detector components are combined in a single measurement. A xenon flasher and notch-filters were used as the light source for the calibration device. The overall uncertainty is 5%.Comment: Submitted to Astroparticle Physics. V2: section 5.2 extended; author list change

Class II Transactivator: Mastering the Art of Major Histocompatibility Complex Expression

Great progress in understanding the relative importance of various portions of CIITA for transcriptional activation of class II MHC genes has been made since CIITA's discovery in 1993. Emerging from these studies is a fairly consistent picture where CIITA is expressed, binds GTP, translocates to the nucleus, and interacts with specific DNA-binding transcription factors and basal transcription components, thus opening and activating class II MHC and related promoters. Despite these strides, this model is essentially unchanged from that initially espoused. The observation that class II MHC promoters in some B cells are bound to X and Y box binding proteins and thus open even in the absence of CIITA, whereas these same promoters in non-B cells are closed until CIITA is present, is provocative. One potential explanation is that CIITA possesses two distinct functions, the ability to direct the opening of responsive promoters (presumably through some form of remodeling) and the ability to activate transcription through its activation domain and protein-protein interactions (132, 141). The presence of a locus control region responsive to a B-cell-specific factor is another possibility, yet CIITA must, in some fashion, be directing chromatin remodeling in cells which can be induced to express CIITA. While CBP is an obvious candidate for mediating remodeling, no conclusive experiments have shown that CBP is required for the remodeling of class II MHC promoters. The studies above support interactions between CIITA and transcription factors, but does CIITA merely bind these factors to place the activation domain appropriately? Why has it been difficult to demonstrate a role for CIITA in a transcription complex? Is GTP binding only essential for nuclear import? Is nuclear export of CIITA occurring and is it relevant? What aspect of class II MHC transcription requires that retinoblastoma protein Rb be present? Is CIITA a prototype for a family of transcriptional coactivators? Why is limited class II expression observed in the absence of CIITA? The evolutionary conservation of W-, X-, and Y-containing promoters in mammals, birds (104), amphibians (51), and fish (121) suggests that CIITA may be extremely old; what are its origins? All remaining questions aside, CIITA is truly a remarkable protein. Controlled by up to four separate promoters, CIITA has been imparted a complex pattern of inducible and constitutive expression that can be regulated in developmental pathways. Through exercising specific control over the transcription of every major component of class II MHC antigen presentation pathway, CIITA gains the title of a master regulator. As CIITA appears to be class II MHC specific, it can be thought of as the core transcription factor of which all the remaining components are but cofactors. This is central to the concept of CIITA as a scaffolding protein or integrator and perhaps alters our view of transcriptional control away from promoters and individual factors towards a more unified enhanceosome perspective. The view of CIITA as a master regulator has implications for practical applications that are staggering. Successful engineering of dominant-negative CIITAs may lead to the production of transplant tissues unable to express class II MHC and the associated self peptides which contribute so significantly to graft rejection. A thorough understanding of CIITA's molecular mechanisms may lead to therapeutics which allow temporary enhancement or suppression of class II MHC, thus favorably altering the immune response during critical events in pathogenesis, autoimmune disease, tumorigenesis, and neuroinflammation

The DRIFT Dark Matter Experiments

The current status of the DRIFT (Directional Recoil Identification From Tracks) experiment at Boulby Mine is presented, including the latest limits on the WIMP spin-dependent cross-section from 1.5 kg days of running with a mixture of CS2 and CF4. Planned upgrades to DRIFT IId are detailed, along with ongoing work towards DRIFT III, which aims to be the world's first 10 m3-scale directional Dark Matter detector.Comment: Proceedings of the 3rd International conference on Directional Detection of Dark Matter (CYGNUS 2011), Aussois, France, 8-10 June 201

Downregulation of CIITA Function by Protein Kinase A (PKA)-Mediated Phosphorylation: Mechanism of Prostaglandin E, Cyclic AMP, and PKA Inhibition of Class II Major Histocompatibility Complex Expression in Monocytic Lines

Prostaglandins, pleiotropic immune modulators that induce protein kinase A (PKA), inhibit gamma interferon induction of class II major histocompatibility complex (MHC) genes. We show that phosphorylation of CIITA by PKA accounts for this inhibition. Treatment with prostaglandin E or 8-bromo-cyclic AMP or transfection with PKA inhibits the activity of CIITA in both mouse and human monocytic cell lines. This inhibition is independent of other transcription factors for the class II MHC promoter. These same treatments also greatly reduced the induction of class II MHC mRNA by CIITA. PKA phosphorylation sites were identified using site-directed mutagenesis and phosphoamino acid analysis. Phosphorylation at CIITA serines 834 and 1050 accounts for the inhibitory effects of PKA on CIITA-driven class II MHC transcription. This is the first demonstration that the posttranslational modification of CIITA mediates inhibition of class II MHC transcription