Enhanced Out-of-plane Emission of K+ Mesons observed in Au+Au Collisions at 1 AGeV

The azimuthal angular distribution of K+ mesons has been measured in Au + Au collisions at 1 AGeV. In peripheral and semi-central collisions, K+ mesons preferentially are emitted perpendicular to the reaction plane. The strength of the azimuthal anisotropy of K+ emission is comparable to the one of pions. No in-plane flow was found for K+ mesons near projectile and target rapidity.Comment: Accepted for publication in Phys. Rev.Let

Medium Effects in Kaon and Antikaon Production in Nuclear Collisions at Subthreshold Beam Energies

Production cross sections of K$^+$ and K$^-$ mesons have been measured in C+C collisions at beam energies per nucleon below and near the nucleon-nucleon threshold. At a given beam energy, the spectral slopes of the K$^-$ mesons are significantly steeper than the ones of the K$^+$ mesons. The excitation functions for K$^+$ and K$^-$ mesons nearly coincide when correcting for the threshold energy. In contrast, the K$^+$ yield exceeds the K$^-$ yield by a factor of about 100 in proton-proton collisions at beam energies near the respective nucleon-nucleon thresholds.Comment: Accepted for publication in Phys. Rev. Let

Predicting the impact of Lynch syndrome-causing missense mutations from structural calculations

Accurate methods to assess the pathogenicity of mutations are needed to fully leverage the possibilities of genome sequencing in diagnosis. Current data-driven and bioinformatics approaches are, however, limited by the large number of new variations found in each newly sequenced genome, and often do not provide direct mechanistic insight. Here we demonstrate, for the first time, that saturation mutagenesis, biophysical modeling and co-variation analysis, performed in silico, can predict the abundance, metabolic stability, and function of proteins inside living cells. As a model system, we selected the human mismatch repair protein, MSH2, where missense variants are known to cause the hereditary cancer predisposition disease, known as Lynch syndrome. We show that the majority of disease-causing MSH2 mutations give rise to folding defects and proteasome-dependent degradation rather than inherent loss of function, and accordingly our in silico modeling data accurately identifies disease-causing mutations and outperforms the traditionally used genetic disease predictors. Thus, in conclusion, in silico biophysical modeling should be considered for making genotype-phenotype predictions and for diagnosis of Lynch syndrome, and perhaps other hereditary diseases

A Chaperone Trap Contributes to the Onset of Cystic Fibrosis

Protein folding is the primary role of proteostasis network (PN) where chaperone interactions with client proteins determine the success or failure of the folding reaction in the cell. We now address how the Phe508 deletion in the NBD1 domain of the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) protein responsible for cystic fibrosis (CF) impacts the binding of CFTR with cellular chaperones. We applied single ion reaction monitoring mass spectrometry (SRM-MS) to quantitatively characterize the stoichiometry of the heat shock proteins (Hsps) in CFTR folding intermediates in vivo and mapped the sites of interaction of the NBD1 domain of CFTR with Hsp90 in vitro. Unlike folding of WT-CFTR, we now demonstrate the presence of ΔF508-CFTR in a stalled folding intermediate in stoichiometric association with the core Hsps 40, 70 and 90, referred to as a ‘chaperone trap’. Culturing cells at 30 C resulted in correction of ΔF508-CFTR trafficking and function, restoring the sub-stoichiometric association of core Hsps observed for WT-CFTR. These results support the interpretation that ΔF508-CFTR is restricted to a chaperone-bound folding intermediate, a state that may contribute to its loss of trafficking and increased targeting for degradation. We propose that stalled folding intermediates could define a critical proteostasis pathway branch-point(s) responsible for the loss of function in misfolding diseases as observed in CF

Azimuthally anisotropic emission of pions in symmetric heavy-ion collisions

Triple differential cross sections d3 sigma /dp3 for charged pions produced in symmetric heavy-ion collisions were measured with the KaoS magnetic spectrometer at the heavy-ion synchrotron facility SIS at GSI. The correlations between the momentum vectors of charged pions and the reaction plane in 197Au+197Au collisions at an incident energy of 1 GeV/nucleon were determined. We observe, for the first time, an azimuthally anisotropic distribution of pions, with enhanced emission perpendicular to the reaction plane. The anisotropy is most pronounced for pions of high transverse momentum in semicentral collisions

Site qualification studies of the UCG-SDB at North Knobs, Wyoming

The site qualification program for the North Knobs UCG site near Rawlins, Wyoming has been completed. This site will be the location for the field tests of Underground Coal Gasification of Steeply Dipping Beds undertaken by Gulf Research and Development Company for DOE in a cost shared contract. Site characterization included a comprehensive geotechnical analysis along with vegetation, historical, and archeological studies. The G coal seam chosen for these tests is a subbituminous B coal with a true seam thickness of 22 feet and has thin coal benches above and below the main seam. The water table is at 90 feet below the surface. Hydrologic studies have defined the seam as an aquiclude (non-aquifer). The site is deemed restorable to regulatory requirements. Evaluation of this site indicates total acceptability for the three-test program planned by GR and DC