The aggregation of cytochrome C may be linked to its flexibility during refolding

Large-scale expression of biopharmaceutical proteins in cellular hosts results in production of large insoluble mass aggregates. In order to generate functional product, these aggregates require further processing through refolding with denaturant, a process in itself that can result in aggregation. Using a model folding protein, cytochrome C, we show how an increase in final denaturant concentration decreases the propensity of the protein to aggregate during refolding. Using polarised fluorescence anisotropy, we show how reduced levels of aggregation can be achieved by increasing the period of time the protein remains flexible during refolding, mediated through dilution ratios. This highlights the relationship between the flexibility of a protein and its propensity to aggregate. We attribute this behaviour to the preferential urea-residue interaction, over self-association between molecules

Efficacy of the Localized Aviation MOS Program in Ceiling Flight Category Forecasts

(1) Background: Flying in instrument meteorological conditions (IMC) carries an elevated risk of fatal outcome for general aviation (GA) pilots. For the typical GA flight, aerodrome-specific forecasts (Terminal Aerodrome Forecast (TAF), Localized Aviation Model Output Statistics Program (LAMP)) assist the airman in pre-determining whether a flight can be safely undertaken. While LAMP forecasts are more prevalent at GA-frequented aerodromes, the Federal Aviation Administration (FAA) recommends that this tool be used as supplementary to the TAF only. Herein, the predictive accuracy of LAMP for ceiling flight categories of visual flight rules (VFR) and instrument flight rules (IFR) was determined. (2) Methods: LAMP accuracy was evaluated for the period of July–December 2018 using aviation-specific probability of detection (PODA), false alarm ratio (FARA) and critical success scores (CSSA). Statistical differences were determined using Chi-Square tests. (3) Results: LAMP forecasts (n = 823) across 39 states were accrued. LAMP PODA for VFR (0.67) and IFR (0.78) exceeded (p \u3c 0.031) the corresponding TAF scores (0.57 and 0.56). For VFR, the LAMP showed a non-significant (p = 0.243) higher FARA (0.25) than the TAF (0.19). For IFR forecasts, the LAMP FARA was lower (p \u3c 0.001) (0.48 and 0.81, respectively). LAMP CSSA scores exceeded the TAF for VFR (p = 0.012) and IFR forecasts (p \u3c 0.001). (4) Conclusion: These findings support the greater integration of LAMP into pre-flight weather briefings

Analogue peptides for the immunotherapy of human acute myeloid leukemia

Accepted manuscript. The final publication is available at: http://link.springer.com/article/10.1007%2Fs00262-015-1762-9The use of peptide vaccines, enhanced by adjuvants, has shown some efficacy in clinical trials. However, responses are often short-lived and rarely induce notable memory responses. The reason is that self-antigens have already been presented to the immune system as the tumor develops, leading to tolerance or some degree of host tumor cell destruction. To try to break tolerance against self-antigens, one of the methods employed has been to modify peptides at the anchor residues to enhance their ability to bind major histocompatibility complex molecules, extending their exposure to the T-cell receptor. These modified or analogue peptides have been investigated as stimulators of the immune system in patients with different cancers with variable but sometimes notable success. In this review we describe the background and recent developments in the use of analogue peptides for the immunotherapy of acute myeloid leukemia describing knowledge useful for the application of analogue peptide treatments for other malignancies

Black Hole Decay and Quantum Instantons

We study the analytic structure of the S-matrix which is obtained from the reduced Wheeler-DeWitt wave function describing spherically symmetric gravitational collapse of massless scalar fields. The complex simple poles in the S-matrix lead to the wave functions that satisfy the same boundary condition as quasi-normal modes of a black hole, and correspond to the bounded states of the Euclidean Wheeler-DeWitt equation. These wave function are interpreted as quantum instantons.Comment: RevTex, 7 pages, no figure; The wave functions of gr-qc/9912115 are newly interpreted as quantum instantons describing a black hole decay. Replaced by the version to be published in Phys. Rev. D, in which the boundary condition on the apparent horizon is clarifie

Contamination Control and Assay Results for the Majorana Demonstrator Ultra Clean Components

The MAJORANA DEMONSTRATOR is a neutrinoless double beta decay experiment utilizing enriched Ge-76 detectors in 2 separate modules inside of a common solid shield at the Sanford Underground Research Facility. The DEMONSTRATOR has utilized world leading assay sensitivities to develop clean materials and processes for producing ultra-pure copper and plastic components. This experiment is now operating, and initial data provide new insights into the success of cleaning and processing. Post production copper assays after the completion of Module 1 showed an increase in U and Th contamination in finished parts compared to starting bulk material. A revised cleaning method and additional round of surface contamination studies prior to Module 2 construction have provided evidence that more rigorous process control can reduce surface contamination. This article describes the assay results and discuss further studies to take advantage of assay capabilities for the purpose of maintaining ultra clean fabrication and process design.Comment: Proceedings of Low Radioactivity Techniques (LRT May 2017, Seoul

Low Background Materials and Fabrication Techniques for Cables and Connectors in the Majorana Demonstrator

The MAJORANA Collaboration is searching for the neutrinoless double-beta decay of the nucleus Ge-76. The MAJORANA DEMONSTRATOR is an array of germanium detectors deployed with the aim of implementing background reduction techniques suitable for a tonne scale Ge-76-based search (the LEGEND collaboration). In the DEMONSTRATOR, germanium detectors operate in an ultra-pure vacuum cryostat at 80 K. One special challenge of an ultra-pure environment is to develop reliable cables, connectors, and electronics that do not significantly contribute to the radioactive background of the experiment. This paper highlights the experimental requirements and how these requirements were met for the MAJORANA DEMONSTRATOR, including plans to upgrade the wiring for higher reliability in the summer of 2018. Also described are requirements for LEGEND R&D efforts underway to meet these additional requirements.Comment: Proceedings of LRT 201

A Comparison of the Localized Aviation MOS Program (LAMP) and Terminal Aerodrome Forecast (TAF) Accuracy for General Aviation

Background. For general aviation (GA) pilots, operations in instrument meteorological conditions (IMC) carry an elevated risk of a fatal accident. As to whether a general aviation flight can be safely undertaken, aerodrome-specific forecasts (TAF, LAMP) provide guidance. Although LAMP forecasts are more common for GA-frequented aerodromes, nevertheless, the FAA recommends that for such aerodromes (and for which a TAF is not issued) the airman uses the TAF generated for the geographically closest airport for pre-flight weather evaluation. Herein, for non-TAF-issuing airports, the LAMP (sLAMP) predictive accuracy for visual (VFR) and instrument (IFR) flight rules flight category was determined. Method. sLAMP accuracy was evaluated over 12 months using the fractions of forecasts which were correct or false alarms. Statistical differences employed Chi-Square/Fisher Exact tests. Results. sLAMP forecasts (n=570) across 43 states were accrued. The fraction of correct sLAMP forecasts for VFR (0.53) and IFR (0.68) exceeded (p Conclusion. Our findings indicate the forecast superiority of the satellite-LAMP at non-TAF-issuing airports compared with the TAF generated at a proximate aerodrome. Practical Application. For non-TAF-issuing sLAMP airports, these findings argue for greater integration of the latter tool in pre-flight weather briefings for general aviation operations