Deactivation of TEM-1 beta-Lactamase investigated by isothermal batch and non-isothermal continuous enzyme membrane reactor methods

The thermal deactivation of TEM-1 β-lactamase was examined using two experimental techniques: a series of isothermal batch assays and a single, continuous, non-isothermal assay in an enzyme membrane reactor (EMR). The isothermal batch-mode technique was coupled with the three-state Equilibrium Model of enzyme deactivation, while the results of the EMR experiment were fitted to a four-state molten globule model . The two methods both led to the conclusions that the thermal deactivation of TEM-1 β -lactamase does not follow the Lumry-Eyring model and that the Teq of the enzyme (the point at which active and inactive states are present in equal amounts due to thermodynamic equilibrium) is at least 10 °C from the Tm (melting temperature), contrary to the idea that the true temperature optimum of a biocatalyst is necessarily close to the melting temperature

Research Think Tank: "Complexifying" International Communication and Communication Technology

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66530/2/10.1177_108056999706000413.pd

Internationalism, Technological Innovation, and New Associations: Bringing Change to Business Communication Research and Teaching

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68267/2/10.1177_108056999906200418.pd

Recent Decisions

Comments on recent decisions by John Rogers, Thomas S. Calder, Edward S. Mraz, Cornelius Jerome Smith, Allan C. Schmid, and Ralph R. Blume

High-grade B-Cell lymphoma with MYC and BCL6 rearrangements associated with Richter transformation of chronic lymphocytic leukemia

Richter transformation (RT), or Richter syndrome, is defined as the transformation of chronic lymphocytic leukemia (CLL) to an aggressive B-cell lymphoma. The vast majority, up to 99%, transform into diffuse large B-cell lymphoma (DLBCL), with a small subset (<1%) becoming classical Hodgkin lymphoma. Approximately half of RT cases progress through a pathway involving dysregulation of C-MYC. High-grade B-cell lymphoma (HGBL) is a recent diagnostic category of aggressive B-cell lymphomas set forth in the updated 2017 WHO Classification of Hematopoietic and Lymphoid Tissues. HGBL with MYC and BCL2 and/or BCL6 rearrangements, formerly “double-hit” and “triple-hit” lymphomas, comprise the majority of HGBL cases. Patients with HGBL have a worse prognosis than those with diffuse large B-cell lymphoma. We present a case of RT with rearrangements of MYC and BCL6. To our knowledge, there are no reported cases of RT with a “double-hit” lymphoma genotype

Results from EDGES High-Band: II. Constraints on Parameters of Early Galaxies

We use the sky-average spectrum measured by EDGES High-Band ($90-190$ MHz) to constrain parameters of early galaxies independent of the absorption feature at $78$~MHz reported by Bowman et al. (2018). These parameters represent traditional models of cosmic dawn and the epoch of reionization produced with the 21cmFAST simulation code (Mesinger & Furlanetto 2007, Mesinger et al. 2011). The parameters considered are: (1) the UV ionizing efficiency ($\zeta$), (2) minimum halo virial temperature hosting efficient star-forming galaxies ($T^{\rm min}_{\rm vir}$), (3) integrated soft-band X-ray luminosity ($L_{\rm X\,<\,2\,keV}/{\rm SFR}$), and (4) minimum X-ray energy escaping the first galaxies ($E_{0}$), corresponding to a typical H${\rm \scriptstyle I}$ column density for attenuation through the interstellar medium. The High-Band spectrum disfavors high values of $T^{\rm min}_{\rm vir}$ and $\zeta$, which correspond to signals with late absorption troughs and sharp reionization transitions. It also disfavors intermediate values of $L_{\rm X\,<\,2\,keV}/{\rm SFR}$, which produce relatively deep and narrow troughs within the band. Specifically, we rule out $39.4<\log_{10}\left(L_{\rm X\,<\,2\,keV}/{\rm SFR}\right)<39.8$ ($95\%$ C.L.). We then combine the EDGES High-Band data with constraints on the electron scattering optical depth from Planck and the hydrogen neutral fraction from high-$z$ quasars. This produces a lower degeneracy between $\zeta$ and $T^{\rm min}_{\rm vir}$ than that reported in Greig & Mesinger (2017a) using the Planck and quasar constraints alone. Our main result in this combined analysis is the estimate $4.5$~$\leq \log_{10}\left(T^{\rm min}_{\rm vir}/\rm K\right)\leq$~$5.7$ ($95\%$ C.L.). We leave for future work the evaluation of $21$~cm models using simultaneously data from EDGES Low- and High-Band.Comment: Accepted in Ap

Recent Decisions

Comments on recent decisions by Lawrence A. Kane, Jr., Vernon O. Teofan, Thomas S. Calder, John Rogers, James Carroll Booth, Paul M. Kraus, Jack Economou, and Robert P. Gorman

The First Passage Probability of Intracellular Particle Trafficking

The first passage probability (FPP), of trafficked intracellular particles reaching a displacement L, in a given time t or inverse velocity S = t/L, can be calculated robustly from measured particle tracks, and gives a measure of particle movement in which different types of motion, e.g. diffusion, ballistic motion, and transient run-rest motion, can readily be distinguished in a single graph, and compared with mathematical models. The FPP is attractive in that it offers a means of reducing the data in the measured tracks, without making assumptions about the mechanism of motion: for example, it does not employ smoothing, segementation or arbitrary thresholds to discriminate between different types of motion in a particle track. Taking experimental data from tracked endocytic vesicles, and calculating the FPP, we see how three molecular treatments affect the trafficking. We show the FPP can quantify complicated movement which is neither completely random nor completely deterministic, making it highly applicable to trafficked particles in cell biology.Comment: Article: 13 pages, 8 figure

A novel drug management system in the Febuxostat versus Allopurinol Streamlined Trial:A description of a pharmacy system designed to supply medications directly to patients within a prospective multicenter randomised clinical trial

Background: Trials of investigational medicinal products are required to adhere to strict guidelines with regard to the handling and supply of medication. Information technology offers opportunities to approach clinical trial methodology in new ways. This report summarises a novel pharmacy system designed to supply trial medications directly to patients by post in the Febuxostat versus Allopurinol Streamlined Trial.Method: A bespoke web-based software package was designed to facilitate the direct supply of trial medications to Febuxostat versus Allopurinol Streamlined Trial participants from a pharmacy based in the Medicines Monitoring Unit, University of Dundee.Results: To date, 65,467 packs of medication have been dispensed using the system to 3978 patients. Up to 238 packs per day have been dispensed.Conclusion: The Medicines Monitoring Unit Febuxostat versus Allopurinol Streamlined Trial drug management system is an effective method of administering the complex drug supply requirements of a large-scale clinical trial with advantages over existing arrangements. A low rate of loss to follow-up in the Febuxostat versus Allopurinol Streamlined Trial may be attributable to the drug management system.</p