The South Pole Telescope

A new 10 meter diameter telescope is being constructed for deployment at the NSF South Pole research station. The telescope is designed for conducting large-area millimeter and sub-millimeter wave surveys of faint, low contrast emission, as required to map primary and secondary anisotropies in the cosmic microwave background. To achieve the required sensitivity and resolution, the telescope design employs an off-axis primary with a 10m diameter clear aperture. The full aperture and the associated optics will have a combined surface accuracy of better than 20 microns rms to allow precision operation in the submillimeter atmospheric windows. The telescope will be surrounded with a large reflecting ground screen to reduce sensitivity to thermal emission from the ground and local interference. The optics of the telescope will support a square degree field of view at 2mm wavelength and will feed a new 1000-element micro-lithographed planar bolometric array with superconducting transition-edge sensors and frequency-multiplexed readouts. The first key project will be to conduct a survey over approximately 4000 degrees for galaxy clusters using the Sunyaev-Zel'dovich Effect. This survey should find many thousands of clusters with a mass selection criteria that is remarkably uniform with redshift. Armed with redshifts obtained from optical and infrared follow-up observations, it is expected that the survey will enable significant constraints to be placed on the equation of state of the dark energy.Comment: Written prior to SPIE conference, June 21-25, 2004. 19 pages, 13 figures. Also available (with higher resolution figures) at http://spt.uchicago.edu

Megastudy testing 25 treatments to reduce antidemocratic attitudes and partisan animosity

Scholars warn that partisan divisions in the mass public threaten the health of American democracy. We conducted a megastudy (n = 32,059 participants) testing 25 treatments designed by academics and practitioners to reduce Americans' partisan animosity and antidemocratic attitudes. We find that many treatments reduced partisan animosity, most strongly by highlighting relatable sympathetic individuals with different political beliefs or by emphasizing common identities shared by rival partisans. We also identify several treatments that reduced support for undemocratic practices-most strongly by correcting misperceptions of rival partisans' views or highlighting the threat of democratic collapse-which shows that antidemocratic attitudes are not intractable. Taken together, the study's findings identify promising general strategies for reducing partisan division and improving democratic attitudes, shedding theoretical light on challenges facing American democracy

Megastudy testing 25 treatments to reduce antidemocratic attitudes and partisan animosity

Scholars warn that partisan divisions in the mass public threaten the health of American democracy. We conducted a megastudy (n = 32,059 participants) testing 25 treatments designed by academics and practitioners to reduce Americans' partisan animosity and antidemocratic attitudes. We find that many treatments reduced partisan animosity, most strongly by highlighting relatable sympathetic individuals with different political beliefs or by emphasizing common identities shared by rival partisans. We also identify several treatments that reduced support for undemocratic practices-most strongly by correcting misperceptions of rival partisans' views or highlighting the threat of democratic collapse-which shows that antidemocratic attitudes are not intractable. Taken together, the study's findings identify promising general strategies for reducing partisan division and improving democratic attitudes, shedding theoretical light on challenges facing American democracy.</p

Site-Specific Incorporation of a ¹⁹F-Amino Acid into Proteins as an NMR Probe for Characterizing Protein Structure and Reactivity

19F NMR is a powerful tool for monitoring protein conformational changes and interactions; however, the inability to site-specifically introduce fluorine labels into proteins of biological interest severely limits its applicability. Using methods for genetically directing incorporation of unnatural amino acids, we have inserted trifluoromethyl-l-phenylalanine (tfm-Phe) into proteins in vivo at TAG nonsense codons with high translational efficiency and fidelity. The binding of substrates, inhibitors, and cofactors, as well as reactions in enzymes, were studied by selective introduction of tfm-Phe and subsequent monitoring of the 19F NMR chemical shifts. Subtle protein conformational changes were detected near the active site and at long distances (25 Å). 19F signal sensitivity and resolution was also sufficient to differentiate protein environments in vivo. Since there has been interest in using 19F-labeled proteins in solid-state membrane protein studies, folding studies, and in vivo studies, this general method for genetically incorporating a 19F-label into proteins of any size in Escherichia coli should have broad application beyond that of monitoring protein conformational changes

Generating Permissive Site-Specific Unnatural Aminoacyl-tRNA Synthetases

Genetically incorporated unnatural amino acid (UAA) technologies are powerful tools that are greatly enhancing our ability to study and engineer biological systems. Using these techniques, researchers can precisely control the position and number of novel chemical moieties in a protein, via introducing the novel R group of UAAs, that are genetically encoded in the protein’s primary structure. The substrate recognition properties of a natural aminoacyl-tRNA synthetase (aaRS) must be modified in order to incorporate UAAs into proteins. Protocols to do so are technically simple but require time and optimization, which has significantly limited the accessibility of this important technology. At present, engineered unnatural aminoacyl-tRNA synthetases (UaaRS) are evaluated on their translational efficiency (the extent to which they allow for incorporation of UAAs into protein) and fidelity (the extent to which they prevent incorporation of natural amino acids). We propose that a third parameter of substrate recognition, permissivity, is equally important. Permissive UaaRSs, whose relaxed substrate recognition properties allow them to incorporate multiple unnatural amino acids (but not natural amino acids), would eliminate the need to generate new UaaRSs for many new UAAs. Here, we outline methods for quickly and easily assessing the permissivity of existing UaaRSs and for generating permissive UaaRSs. In proof of principle experiments, we determined the degree of permissivity of two UaaRSs for a family of structurally related fluorinated UAAs (19F-UAAs). We then increased the permissivity of the initial UaaRSs to allow for incorporation of the family of 19F-UAAs. Finally, we validated the utility of these new 19F-UAAs as probes for fluorine NMR studies of protein structure and dynamics. We expect that results of this work will increase the accessibility of UAA technology and the use of new UAAs in proteins

Probing Protein Folding Using Site-Specifically Encoded Unnatural Amino Acids as FRET Donors with Tryptophan

The experimental study of protein folding is enhanced by the use of nonintrusive probes that are sensitive to local conformational changes in the protein structure. Here, we report the selection of an aminoacyl-tRNA synthetase/tRNA pair for the cotranslational, site-specific incorporation of two unnatural amino acids that can function as fluorescence resonance energy transfer (FRET) donors with Trp to probe the disruption of the hydrophobic core upon protein unfolding. l-4-Cyanophenylalanine (pCNPhe) and 4-ethynylphenylalanine (pENPhe) were incorporated into the hydrophobic core of the 171-residue protein, T4 lysozyme. The FRET donor ability of pCNPhe and pENPhe is evident by the overlap of the emission spectra of pCNPhe and pENPhe with the absorbance spectrum of Trp. The incorporation of both unnatural amino acids in place of a phenylalanine in the hydrophobic core of T4 lysozyme was well tolerated by the protein, due in part to the small size of the cyano and ethynyl groups. The hydrophobic nature of the ethynyl group of pENPhe suggests that this unnatural amino acid is a more conservative substitution into the hydrophobic core of the protein compared to pCNPhe. The urea-induced disruption of the hydrophobic core of the protein was probed by the change in FRET efficiency between either pCNPhe or pENPhe and the Trp residues in T4 lysozyme. The methodology for the study of protein conformational changes using FRET presented here is of general applicability to the study of protein structural changes, since the incorporation of the unnatural amino acids is not inherently limited by the size of the protein