Modular detergents tailor the purification and structural analysis of membrane proteins including G-protein coupled receptors

Detergents enable the purification of membrane proteins and are indispensable reagents instructural biology. Even though a large variety of detergents have been developed in the lastcentury, the challenge remains to identify guidelines that allowfine-tuning of detergents forindividual applications in membrane protein research. Addressing this challenge, here weintroduce the family of oligoglycerol detergents (OGDs). Native mass spectrometry (MS)reveals that the modular OGD architecture offers the ability to control protein purificationand to preserve interactions with native membrane lipids during purification. In addition to abroad range of bacterial membrane proteins, OGDs also enable the purification and analysisof a functional G-protein coupled receptor (GPCR). Moreover, given the modular design ofthese detergents, we anticipatefine-tuning of their properties for specific applications instructural biology. Seen from a broader perspective, this represents a significant advance forthe investigation of membrane proteins and their interactions with lipids

Modular detergents tailor the purification and structural analysis of membrane proteins including G-protein coupled receptors

Detergents enable the purification of membrane proteins and are indispensable reagents in structural biology. Even though a large variety of detergents have been developed in the last century, the challenge remains to identify guidelines that allow fine-tuning of detergents for individual applications in membrane protein research. Addressing this challenge, here we introduce the family of oligoglycerol detergents (OGDs). Native mass spectrometry (MS) reveals that the modular OGD architecture offers the ability to control protein purification and to preserve interactions with native membrane lipids during purification. In addition to a broad range of bacterial membrane proteins, OGDs also enable the purification and analysis of a functional G-protein coupled receptor (GPCR). Moreover, given the modular design of these detergents, we anticipate fine-tuning of their properties for specific applications in structural biology. Seen from a broader perspective, this represents a significant advance for the investigation of membrane proteins and their interactions with lipids

Cognitive performance profiles by latent classes of drug use

Background and Objectives: The relationship between substance use and cognitive deficits is complex and requires innovative methods to enhance understanding. The present study is the first to use LCA to examine associations of drug use patterns with cognitive performance. Methods: Cocaine/heroin users (N = 552) completed questionnaires, and cognitive measures. LCA identified classes based on past-month drug use and adjusted for probabilities of group membership when examining cognitive performance. Latent indicators were: alcohol (ALC), cigarettes (CIG), marijuana (MJ), crack smoking (CS), nasal heroin (NH), injection cocaine (IC), injection heroin (IH), and injection speedball (IS). Age and education were included as covariates in model creation. Results: Bootstrap likelihood ratio test (BLRT) supported a 5-class model. Prevalent indicators (estimated probability of over 50%) for each class are as follows: “Older Nasal Heroin/Crack Smokers” (ONH/CS, n = 166.9): ALC, CIG, NH, CS; “Older, Less Educated Polysubstance” (OLEP, n = 54.8): ALC, CIG, CS, IH, IC, and IS; “Younger Multi-Injectors” (MI, n = 128.7): ALC, CIG, MJ, IH, IC, and IS; “Less Educated Heroin Injectors” (LEHI, n = 87.4): CIG, IH; and “More Educated Nasal Heroin” users (MENH, n = ALC, CIG, NH. In general, all classes performed worse than established norms and older, less educated classes performed worse, with the exception that MENH demonstrated worse cognitive flexibility than YMI. Discussion and Conclusions: This study demonstrated novel applications of a methodology for examining complicated relationships between polysubstance use and cognitive performance. Scientific Significance: Education and/or nasal heroin use are associated with reduced cognitive flexibility in this sample of inner city drug users

Testbeam and Laboratory Characterization of CMS 3D Pixel Sensors

The pixel detector is the innermost tracking device in CMS, reconstructing interaction vertices and charged particle trajectories. The sensors located in the innermost layers of the pixel detector must be upgraded for the ten-fold increase in luminosity expected with the High- Luminosity LHC (HL-LHC) phase. As a possible replacement for planar sensors, 3D silicon technology is under consideration due to its good performance after high radiation fluence. In this paper, we report on pre- and post- irradiation measurements for CMS 3D pixel sensors with different electrode configurations. The effects of irradiation on electrical properties, charge collection efficiency, and position resolution of 3D sensors are discussed. Measurements of various test structures for monitoring the fabrication process and studying the bulk and surface properties, such as MOS capacitors, planar and gate-controlled diodes are also presented.Comment: 14 page

Operational experience, improvements, and performance of the CDF Run II silicon vertex detector

The Collider Detector at Fermilab (CDF) pursues a broad physics program at Fermilab's Tevatron collider. Between Run II commissioning in early 2001 and the end of operations in September 2011, the Tevatron delivered 12 fb-1 of integrated luminosity of p-pbar collisions at sqrt(s)=1.96 TeV. Many physics analyses undertaken by CDF require heavy flavor tagging with large charged particle tracking acceptance. To realize these goals, in 2001 CDF installed eight layers of silicon microstrip detectors around its interaction region. These detectors were designed for 2--5 years of operation, radiation doses up to 2 Mrad (0.02 Gy), and were expected to be replaced in 2004. The sensors were not replaced, and the Tevatron run was extended for several years beyond its design, exposing the sensors and electronics to much higher radiation doses than anticipated. In this paper we describe the operational challenges encountered over the past 10 years of running the CDF silicon detectors, the preventive measures undertaken, and the improvements made along the way to ensure their optimal performance for collecting high quality physics data. In addition, we describe the quantities and methods used to monitor radiation damage in the sensors for optimal performance and summarize the detector performance quantities important to CDF's physics program, including vertex resolution, heavy flavor tagging, and silicon vertex trigger performance.Comment: Preprint accepted for publication in Nuclear Instruments and Methods A (07/31/2013

FGF receptor genes and breast cancer susceptibility: results from the Breast Cancer Association Consortium

Background:Breast cancer is one of the most common malignancies in women. Genome-wide association studies have identified FGFR2 as a breast cancer susceptibility gene. Common variation in other fibroblast growth factor (FGF) receptors might also modify risk. We tested this hypothesis by studying genotyped single-nucleotide polymorphisms (SNPs) and imputed SNPs in FGFR1, FGFR3, FGFR4 and FGFRL1 in the Breast Cancer Association Consortium. Methods:Data were combined from 49 studies, including 53 835 cases and 50 156 controls, of which 89 050 (46 450 cases and 42 600 controls) were of European ancestry, 12 893 (6269 cases and 6624 controls) of Asian and 2048 (1116 cases and 932 controls) of African ancestry. Associations with risk of breast cancer, overall and by disease sub-type, were assessed using unconditional logistic regression. Results:Little evidence of association with breast cancer risk was observed for SNPs in the FGF receptor genes. The strongest evidence in European women was for rs743682 in FGFR3; the estimated per-allele odds ratio was 1.05 (95 confidence interval=1.02-1.09, P=0.0020), which is substantially lower than that observed for SNPs in FGFR2. Conclusion:Our results suggest that common variants in the other FGF receptors are not associated with risk of breast cancer to the degree observed for FGFR2. © 2014 Cancer Research UK

Measurement of WγW\gamma and ZγZ\gamma Production in ppˉp\bar{p} Collisions at s\sqrt{s} = 1.96 TeV

The Standard Model predictions for $W\gamma$ and $Z\gamma$ production are tested using an integrated luminosity of 200 pb$^{-1}$ of \ppbar collision data collected at the Collider Detector at Fermilab. The cross sections are measured selecting leptonic decays of the $W$ and $Z$ bosons, and photons with transverse energy $E_T>7$ GeV that are well separated from leptons. The production cross sections and kinematic distributions for the $W\gamma$ and $Z\gamma$ are compared to SM predictions.Comment: 7 pages, 4 figures, submitted to PR

Measurement of the Lifetime Difference Between B_s Mass Eigenstates

We present measurements of the lifetimes and polarization amplitudes for B_s --> J/psi phi and B_d --> J/psi K*0 decays. Lifetimes of the heavy (H) and light (L) mass eigenstates in the B_s system are separately measured for the first time by determining the relative contributions of amplitudes with definite CP as a function of the decay time. Using 203 +/- 15 B_s decays, we obtain tau_L = (1.05 +{0.16}/-{0.13} +/- 0.02) ps and tau_H = (2.07 +{0.58}/-{0.46} +/- 0.03) ps. Expressed in terms of the difference DeltaGamma_s and average Gamma_s, of the decay rates of the two eigenstates, the results are DeltaGamma_s/Gamma_s = (65 +{25}/-{33} +/- 1)%, and DeltaGamma_s = (0.47 +{0.19}/-{0.24} +/- 0.01) inverse ps.Comment: 8 pages, 3 figures, 2 tables; as published in Physical Review Letters on 16 March 2005; revisions are for length and typesetting only, no changes in results or conclusion

Evidence for the exclusive decay Bc+- to J/psi pi+- and measurement of the mass of the Bc meson

We report first evidence for a fully reconstructed decay mode of the B_c^{\pm} meson in the channel B_c^{\pm} \to J/psi \pi^{\pm}, with J/psi \to mu^+mu^-. The analysis is based on an integrated luminosity of 360 pb$^{-1} in p\bar{p} collisions at 1.96 TeV center of mass energy collected by the Collider Detector at Fermilab. We observe 14.6 \pm 4.6 signal events with a background of 7.1 \pm 0.9 events, and a fit to the J/psi pi^{\pm} mass spectrum yields a B_c^{\pm} mass of 6285.7 \pm 5.3(stat) \pm 1.2(syst) MeV/c^2. The probability of a peak of this magnitude occurring by random fluctuation in the search region is estimated as 0.012%.Comment: 7 pages, 3 figures. Version 3, accepted by PR