Insight into stability of CotA laccase from the spore coat of Bacillus subtilis

The axial ligand of the catalytic mononuclear T1 copper site (Met(502)) of the CotA laccase was replaced by a leucine or phenylalanine residue to increase the redox potential of the enzyme. These mutations led to an increase in the redox potential by approx. 100 mV relative to the wild-type enzyme but the catalytic constant k(cat) in the mutant enzymes was severely compromised. This decrease in the catalytic efficiency was unexpected as the X-ray analysis of mutants has shown that replacement of methionine ligand did not lead to major structural changes in the geometry of the T1 Centre or in the overall fold of the enzyme. However, the mutations have a profound impact on the thermodynamic stability of the enzyme. The fold of the enzyme has become unstable especially with the introduction of the larger phenylalanine residue and this instability should be related to the decrease in the catalytic efficiency. The instability of the fold for the mutant proteins resulted in the accumulation of an intermediate state, partly unfolded, in-between native and unfolded states. Quenching of tryptophan fluorescence by acrylamide has further revealed that the intermediate state is partly unfolded.info:eu-repo/semantics/publishedVersio

Changes in Physician Knowledge, Attitudes, Beliefs, and Practices regarding Lung Cancer Screening

More patients die of lung cancer than breast, colorectal, and prostate cancers combined (1). After the National Lung Screening Trial finding of a 20% relative reduction in mortality of lung cancer with lung cancer screening (LCS) by low-dose computed tomography (LDCT) (2), the U.S. Preventive Services Task Force published recommendations for LCS in high-risk patients (current and former heavy smokers aged 55–80 yr) annually with LDCT (3)

Patient preferences for the design of a pharmacy-based colorectal cancer screening program

Purpose: To assess preferences for design of a pharmacy-based colorectal cancer (CRC) screening program (PharmFIT™) among screening-eligible adults in the United States (US) and explore the impact of rurality on pharmacy use patterns (e.g., pharmacy type, prescription pick-up preference, service quality rating). Methods: We conducted a national online survey of non-institutionalized US adults through panels managed by Qualtrics, a survey research company. A total of 1,045 adults (response rate 62%) completed the survey between March and April 2021. Sampling quotas matched respondents to the 2010 US Census and oversampled rural residents. We assessed pharmacy use patterns by rurality and design preferences for learning about PharmFIT™; receiving a FIT kit from a pharmacy; and completing and returning the FIT kit. Results: Pharmacy use patterns varied, with some notable differences across rurality. Rural respondents used local, independently owned pharmacies more than non-rural respondents (20.4%, 6.3%, p < 0.001) and rated pharmacy service quality higher than non-rural respondents. Non-rural respondents preferred digital communication to learn about PharmFIT™ (36% vs 47%; p < 0.001) as well as digital FIT counseling (41% vs 49%; p = 0.02) more frequently than rural participants. Preferences for receiving and returning FITs were associated with pharmacy use patterns: respondents who pick up prescriptions in-person preferred to get their FIT (OR 7.7; 5.3–11.2) and return it in-person at the pharmacy (OR 1.7; 1.1–2.4). Conclusion: Pharmacies are highly accessible and could be useful for expanding access to CRC screening services. Local context and pharmacy use patterns should be considered in the design and implementation of PharmFIT™

Opinions and Practices of Lung Cancer Screening by Physician Specialty

BACKGROUND In response to the National Lung Screening Trial, numerous professional organizations published guidelines recommending annual lung cancer screening with low-dose computed tomography (LDCT) for high-risk patients. Prior studies found that physician attitudes and knowledge about lung cancer screening directly impacts the number of screening exams ordered.METHODS In 2015, we surveyed 34 pulmonologists and 186 primary care providers (PCPs) to evaluate opinions and practices of lung cancer screening in a large academic medical center. We compared PCP and pulmonologist responses using t-tests and χ2 tests.RESULTS The overall survey response rate was 40% (39% for PCPs and 50% for pulmonologists). Pulmonologists were more likely than PCPs to report lung cancer screening as beneficial for patients (88.2% versus 37.7%, P < .0001) and as being cost-effective (47.1% versus 14.3%, P = .02). More pulmonologists (76%) reported ordering a LDCT for screening in the past 12 months compared to PCPs (41%, P = .012). Pulmonologists and PCPs reported similar barriers to referring patients for lung cancer screening, including patient costs (82.4% versus 77.8%), potential for emotional harm (58.8% versus 58.3%), high false positive rate (47.1% versus 69.4%), and likelihood for medical complications (47.1% versus 59.7%).LIMITATIONS Our results are generalizable to academic medical centers and responses may be susceptible to recall bias, non-response bias, and social desirability bias.CONCLUSION We found significant differences in opinions and practices between PCPs and pulmonologists regarding lung cancer screening referrals and perceived benefits. As lung cancer screening continues to emerge in clinical practice, it is important to understand these differences across provider specialty to ensure screening is implemented and offered to patients appropriately

Opinions, practice patterns, and perceived barriers to lung cancer screening among attending and resident primary care physicians

Introduction: The US Preventive Services Task Force recommended annual lung cancer screening with low-dose computed tomography (LDCT) for high-risk patients in December 2013. We compared lung cancer screening-related opinions and practices among attending and resident primary care physicians (PCPs). Methods: In 2015, we conducted a 23-item survey among physicians at a large academic medical center. We surveyed 100 resident PCPs (30% response rate) and 86 attending PCPs (49% response rate) in Family Medicine and Internal Medicine. The questions focused on physicians’ opinions, knowledge of recommendations, self-reported practice patterns, and barriers to lung cancer screening. In 2015 and 2016, we compared responses among attending versus resident PCPs using chi-square/Fisher’s exact tests and 2-samples t-tests. Results: Compared with resident PCPs, attending PCPs were older (mean age =47 vs 30 years) and more likely to be male (54% vs 37%). Over half of both groups concurred that inconsistent recommendations make deciding whether or not to screen difficult. A substantial proportion in both groups indicated that they were undecided about the benefit of lung cancer screening for patients (43% attending PCPs and 55% resident PCPs). The majority of attending and resident PCPs agreed that barriers to screening included limited time during patient visits (62% and 78%, respectively), cost to patients (74% and 83%, respectively), potential for complications (53% and 70%, respectively), and a high false-positive rate (67% and 73%, respectively). Conclusion: There was no evidence to suggest that attending and resident PCPs had differing opinions about lung cancer screening. For population-based implementation of lung cancer screening, physicians and trainees will need resources and time to address the benefits and harms with their patients

Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in √s = 7 TeV pp collisions with the ATLAS detector

A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fb−1 of proton–proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results

Jet size dependence of single jet suppression in lead-lead collisions at sqrt(s(NN)) = 2.76 TeV with the ATLAS detector at the LHC

Measurements of inclusive jet suppression in heavy ion collisions at the LHC provide direct sensitivity to the physics of jet quenching. In a sample of lead-lead collisions at sqrt(s) = 2.76 TeV corresponding to an integrated luminosity of approximately 7 inverse microbarns, ATLAS has measured jets with a calorimeter over the pseudorapidity interval |eta| < 2.1 and over the transverse momentum range 38 < pT < 210 GeV. Jets were reconstructed using the anti-kt algorithm with values for the distance parameter that determines the nominal jet radius of R = 0.2, 0.3, 0.4 and 0.5. The centrality dependence of the jet yield is characterized by the jet "central-to-peripheral ratio," Rcp. Jet production is found to be suppressed by approximately a factor of two in the 10% most central collisions relative to peripheral collisions. Rcp varies smoothly with centrality as characterized by the number of participating nucleons. The observed suppression is only weakly dependent on jet radius and transverse momentum. These results provide the first direct measurement of inclusive jet suppression in heavy ion collisions and complement previous measurements of dijet transverse energy imbalance at the LHC.Comment: 15 pages plus author list (30 pages total), 8 figures, 2 tables, submitted to Physics Letters B. All figures including auxiliary figures are available at http://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/HION-2011-02

Search for displaced vertices arising from decays of new heavy particles in 7 TeV pp collisions at ATLAS

We present the results of a search for new, heavy particles that decay at a significant distance from their production point into a final state containing charged hadrons in association with a high-momentum muon. The search is conducted in a pp-collision data sample with a center-of-mass energy of 7 TeV and an integrated luminosity of 33 pb^-1 collected in 2010 by the ATLAS detector operating at the Large Hadron Collider. Production of such particles is expected in various scenarios of physics beyond the standard model. We observe no signal and place limits on the production cross-section of supersymmetric particles in an R-parity-violating scenario as a function of the neutralino lifetime. Limits are presented for different squark and neutralino masses, enabling extension of the limits to a variety of other models.Comment: 8 pages plus author list (20 pages total), 8 figures, 1 table, final version to appear in Physics Letters

Measurement of the polarisation of W bosons produced with large transverse momentum in pp collisions at sqrt(s) = 7 TeV with the ATLAS experiment

This paper describes an analysis of the angular distribution of W->enu and W->munu decays, using data from pp collisions at sqrt(s) = 7 TeV recorded with the ATLAS detector at the LHC in 2010, corresponding to an integrated luminosity of about 35 pb^-1. Using the decay lepton transverse momentum and the missing transverse energy, the W decay angular distribution projected onto the transverse plane is obtained and analysed in terms of helicity fractions f0, fL and fR over two ranges of W transverse momentum (ptw): 35 < ptw < 50 GeV and ptw > 50 GeV. Good agreement is found with theoretical predictions. For ptw > 50 GeV, the values of f0 and fL-fR, averaged over charge and lepton flavour, are measured to be : f0 = 0.127 +/- 0.030 +/- 0.108 and fL-fR = 0.252 +/- 0.017 +/- 0.030, where the first uncertainties are statistical, and the second include all systematic effects.Comment: 19 pages plus author list (34 pages total), 9 figures, 11 tables, revised author list, matches European Journal of Physics C versio

Observation of a new chi_b state in radiative transitions to Upsilon(1S) and Upsilon(2S) at ATLAS

The chi_b(nP) quarkonium states are produced in proton-proton collisions at the Large Hadron Collider (LHC) at sqrt(s) = 7 TeV and recorded by the ATLAS detector. Using a data sample corresponding to an integrated luminosity of 4.4 fb^-1, these states are reconstructed through their radiative decays to Upsilon(1S,2S) with Upsilon->mu+mu-. In addition to the mass peaks corresponding to the decay modes chi_b(1P,2P)->Upsilon(1S)gamma, a new structure centered at a mass of 10.530+/-0.005 (stat.)+/-0.009 (syst.) GeV is also observed, in both the Upsilon(1S)gamma and Upsilon(2S)gamma decay modes. This is interpreted as the chi_b(3P) system.Comment: 5 pages plus author list (18 pages total), 2 figures, 1 table, corrected author list, matches final version in Physical Review Letter