Characterization of a novel weak cation-exchange hydrogel membrane through the separation of lysozyme from egg white

Membrane chromatography was investigated as an alternative method to packed-bed chromatography for protein recovery. The purification of lysozyme from egg white with Natrix adseptTM weak cation-exchange membranes was investigated under two different binding configurations: (1) a non-flow, static set-up with variable pH and sodium chloride (NaCl) concentrations during the binding and elution steps, and (2) a dynamic, cross-flow set-up with recycle at pH 7.5 and no NaCl addition during binding. The weak cation-exchange membrane consisted of a carboxylic acid-based, environmentally-responsive hydrogel layer bonded to a polymer matrix. Lysozyme was chosen to illustrate protein-membrane binding interactions due to its well-characterized nature and positive surface charge over a large pH range. For the static binding set-up, two sources of lysozyme were studied: pure lysozyme and egg whites treated with 60 % (v/v) ethanol (ESEW). Elution of bound protein was performed with 1 M NaCl under two pH strategies: binding and elution at a constant pH, and binding at pH 4.5 and variable elution pH. The highest maximum total protein binding capacity for pure lysozyme and ESEW was observed at pH 4.5 with no NaCl addition; however, poor total protein and lysozyme activity recovery were achieved during separation. As well, other egg white proteins, such as ovomucoid, were observed to bind to the membrane surface at pH 4.5, despite possessing similar charge polarity to the anionic membrane surface, indicating a non-electrostatic binding mechanism during operation below the membrane’s pKa (4.7). Based on the conditions tested, the highest total protein and lysozyme activity recovery was demonstrated for the separation of lysozyme from ESEW at pH 7.5 binding and elution and no NaCl addition. In the dynamic binding study, very high pure lysozyme dynamic binding capacity was achieved at 10 % breakthrough (167.3 mg/ml membrane for a 0.35 mg/ml lysozyme solution). The lysozyme dynamic binding capacity was 2.2 times greater than the static binding capacity under similar conditions, significantly higher than published results for other cation-exchange membranes. The separation of lysozyme from four lysozyme sources was tested: pure lysozyme, ESEW, and aqueous egg whites with (ASEW) and without (AEW) 100 mM NaCl. The highest lysozyme activity recovery during separation and lysozyme purity was achieved from the ESEW feed. Lysozyme separation from aqueous egg whites was not as effective, likely due to a high concentration of negatively-charged protein impurities fouling the surface of the membrane. Competitive binding to the membrane limited lysozyme binding and reduced the purity of the recovery elution stream. The application of feed-side pressure during the separation of ESEW produced a high purity, high recovery lysozyme elution stream with a significant reduction in processing time; however, protein aggregates were observed to form on the membrane surface, limiting the applicability of high-pressure operation and reducing protein functionality in the elution stream. The weak cation-exchange membrane system was shown to successfully separate out a target protein from a low concentration protein mixture through electrostatic interactions, and may be further applied to other protein systems

Exposure to Kynurenic Acid during Adolescence Increases Sign-Tracking and Impairs Long-Term Potentiation in Adulthood

Changes in brain reward systems are thought to contribute significantly to the cognitive and behavioral impairments of schizophrenia, as well as the propensity to develop co-occurring substance abuse disorders. Presently, there are few treatments for persons with a dual diagnosis and little is known about the neural substrates that underlie co-occurring schizophrenia and substance abuse. One goal of the present study was to determine if a change in the concentration of kynurenic acid (KYNA), a tryptophan metabolite that is increased in the brains of people with schizophrenia, affects reward-related behavior. KYNA is an endogenous antagonist of NMDA glutamate receptors and α7 nicotinic acetylcholine receptors, both of which are critically involved in neurodevelopment, plasticity, and behavior. In Experiment 1, rats were treated throughout adolescence with L-kynurenine (L-KYN), the precursor of KYNA. As adults, the rats were tested drug-free in an autoshaping procedure in which a lever was paired with food. Rats treated with L-KYN during adolescence exhibited increased sign-tracking behavior (lever pressing) when they were tested as adults. Sign-tracking is thought to reflect the lever acquiring incentive salience (motivational value) as a result of its pairing with reward. Thus, KYNA exposure may increase the incentive salience of cues associated with reward, perhaps contributing to an increase in sensitivity to drug-related cues in persons with schizophrenia. In Experiment 2, we tested the effects of exposure to KYNA during adolescence on hippocampal long-term potentiation (LTP). Rats treated with L-KYN exhibited no LTP after a burst of high-frequency stimulation that was sufficient to produce robust LTP in vehicle-treated rats. This finding represents the first demonstrated consequence of elevated KYNA concentration during development and provides insight into the basis for cognitive and behavioral deficits that result from exposure to KYNA during adolescence

Future Foam

We study pocket universes which have zero cosmological constant and non-trivial boundary topology. These arise from bubble collisions in eternal inflation. Using a simplified dust model of collisions we find that boundaries of any genus can occur. Using a radiation shell model we perform analytic studies in the thin wall limit to show the existence of geometries with a single toroidal boundary. We give plausibility arguments that higher genus boundaries can also occur. In geometries with one boundary of any genus a timelike observer can see the entire boundary. Geometries with multiple disconnected boundaries can also occur. In the spherical case with two boundaries the boundaries are separated by a horizon. Our results suggest that the holographic dual description for eternal inflation, proposed by Freivogel, Sekino, Susskind and Yeh, should include summation over the genus of the base space of the dual conformal field theory. We point out peculiarities of this genus expansion compared to the string perturbation series.Comment: 23 pages, 6 figure

Associations between quality indicators of internal medicine residency training programs

<p>Abstract</p> <p>Background</p> <p>Several residency program characteristics have been suggested as measures of program quality, but associations between these measures are unknown. We set out to determine associations between these potential measures of program quality.</p> <p>Methods</p> <p>Survey of internal medicine residency programs that shared an online ambulatory curriculum on hospital type, faculty size, number of trainees, proportion of international medical graduate (IMG) trainees, Internal Medicine In-Training Examination (IM-ITE) scores, three-year American Board of Internal Medicine Certifying Examination (ABIM-CE) first-try pass rates, Residency Review Committee-Internal Medicine (RRC-IM) certification length, program director clinical duties, and use of pharmaceutical funding to support education. Associations assessed using Chi-square, Spearman rank correlation, univariate and multivariable linear regression.</p> <p>Results</p> <p>Fifty one of 67 programs responded (response rate 76.1%), including 29 (56.9%) community teaching and 17 (33.3%) university hospitals, with a mean of 68 trainees and 101 faculty. Forty four percent of trainees were IMGs. The average post-graduate year (PGY)-2 IM-ITE raw score was 63.1, which was 66.8 for PGY3s. Average 3-year ABIM-CE pass rate was 95.8%; average RRC-IM certification was 4.3 years. ABIM-CE results, IM-ITE results, and length of RRC-IM certification were strongly associated with each other (p < 0.05). PGY3 IM-ITE scores were higher in programs with more IMGs and in programs that accepted pharmaceutical support (p < 0.05). RRC-IM certification was shorter in programs with higher numbers of IMGs. In multivariable analysis, a higher proportion of IMGs was associated with 1.17 years shorter RRC accreditation.</p> <p>Conclusions</p> <p>Associations between quality indicators are complex, but suggest that the presence of IMGs is associated with better performance on standardized tests but decreased duration of RRC-IM certification.</p

The continuing evolution of Energy Policy

As the world confronts the Covid-19 pandemic, we hope that all of you are doing well. We know that many lives have been greatly disrupted, and that world economic activity is slowing and maybe declining in some places. We have read reports that energy consumption has been greatly affected by the slowdown in world economic activity—likely contributing to the sharp plunge in oil prices earlier this year. We do not know how long this pandemic may last. As we look forward to the end of the pandemic and a recovering world economy, however, we wonder if and how energy systems may have to be transformed, and whether new energy policy needs and approaches will emerge. Will we see any change in the trajectory of adopting sustainable energy systems and reducing carbon emissions?In the academic world, many of us are now teleworking and teaching our courses online. This transition has proved time consuming—so we want to thank our many reviewers who are staying on or close to schedule. So far, Energy Policy has been mostly unaffected by the pandemic, but we must recognize that the Elsevier employees who are responsible for the operations side of the journal may at some time be affected by Covid-19.In the meantime, we want to keep you informed about some recent developments regarding Energy Policy, including a little about its history and our editorial priorities

Twin-Free GaAs Nanosheets by Selective Area Growth: Implications for Defect-Free Nanostructures

Highly perfect, twin-free GaAs nanosheets grown on (111)B surfaces by selective area growth (SAG) are demonstrated. In contrast to GaAs nanowires grown by (SAG) in which rotational twins and stacking faults are almost universally observed, twin formation is either suppressed or eliminated within properly oriented nanosheets are grown under a range of growth conditions. A morphology transition in the nanosheets due to twinning results in surface energy reduction, which may also explain the high twin-defect density that occurs within some III–V semiconductor nanostructures, such as GaAs nanowires. Calculations suggest that the surface energy is significantly reduced by the formation of {111}-plane bounded tetrahedra after the morphology transition of nanowire structures. By contrast, owing to the formation of two vertical {11̅0} planes which comprise the majority of the total surface energy of nanosheet structures, the energy reduction effect due to the morphology transition is not as dramatic as that for nanowire structures. Furthermore, the surface energy reduction effect is mitigated in longer nanosheets which, in turn, suppresses twinning

Association Between Public Reporting of Outcomes With Procedural Management and Mortality for Patients With Acute Myocardial Infarction

AbstractBackgroundPublic reporting of procedural outcomes may create disincentives to provide percutaneous coronary intervention (PCI) for critically ill patients.ObjectivesThis study evaluated the association between public reporting with procedural management and outcomes among patients with acute myocardial infarction (AMI).MethodsUsing the Nationwide Inpatient Sample, we identified all patients with a primary diagnosis of AMI in states with public reporting (Massachusetts and New York) and regionally comparable states without public reporting (Connecticut, Maine, Maryland, New Hampshire, Rhode Island, and Vermont) between 2005 and 2011. Procedural management and in-hospital outcomes were stratified by public reporting.ResultsAmong 84,121 patients hospitalized with AMI, 57,629 (69%) underwent treatment in a public reporting state. After multivariate adjustment, percutaneous revascularization was performed less often in public reporting states than in nonreporting states (odds ratio [OR]: 0.81, 95% confidence interval [CI]: 0.67 to 0.96), especially among older patients (OR: 0.75, 95% CI: 0.62 to 0.91), those with Medicare insurance (OR: 0.75, 95% CI: 0.62 to 0.91), and those presenting with ST-segment elevation myocardial infarction (OR: 0.63, 95% CI: 0.56 to 0.71) or concomitant cardiac arrest or cardiogenic shock (OR: 0.58, 95% CI: 0.47 to 0.70). Overall, patients with AMI in public reporting states had higher adjusted in-hospital mortality rates (OR: 1.21, 95% CI: 1.06 to 1.37) than those in nonreporting states. This was observed predominantly in patients who did not receive percutaneous revascularization in public reporting states (adjusted OR: 1.30, 95% CI: 1.13 to 1.50), whereas those undergoing the procedure had lower mortality (OR: 0.71, 95% CI: 0.62 to 0.83).ConclusionsPublic reporting is associated with reduced percutaneous revascularization and increased in-hospital mortality among patients with AMI, particularly among patients not selected for PCI

Association between diagnosis code expansion and changes in 30-day risk-adjusted outcomes for cardiovascular diseases

BACKGROUND In January 2011, Centers for Medicare and Medicaid Services expanded the number of inpatient diagnosis codes from 9 to 25, which may influence comorbidity counts and risk-adjusted outcome rates for studies spanning January 2011. This study examines the association between (1) limiting versus not limiting diagnosis codes after 2011, (2) using inpatient-only versus inpatient and outpatient data, and (3) using logistic regression versus the Centers for Medicare and Medicaid Services risk-standardized methodology and changes in risk-adjusted outcomes. METHODS AND RESULTS Using 100% Medicare inpatient and outpatient files between January 2009 and December 2013, we created 2 cohorts of fee-for-service beneficiaries aged ≥65 years. The acute myocardial infarction cohort and the heart failure cohort had 578 728 and 1 595 069 hospitalizations, respectively. We calculate comorbidities using (1) inpatient-only limited diagnoses, (2) inpatient-only unlimited diagnoses, (3) inpatient and outpatient limited diagnoses, and (4) inpatient and outpatient unlimited diagnoses. Across both cohorts