Continuous Wave Terahertz Systems Based on 1.5 μm Telecom Technologies

Terahertz systems can profit from technologies developed originally for telecom applications. Recent developments on telecom-based key devices are summarized and ways towards CW systems with highest flexibility and excellent performance at reasonable costs are sketched

Early pH Changes in Musculoskeletal Tissues upon Injury-Aerobic Catabolic Pathway Activity Linked to Inter-Individual Differences in Local pH

Local pH is stated to acidify after bone fracture. However, the time course and degree of acidification remain unknown. Whether the acidification pattern within a fracture hematoma is applicable to adjacent muscle hematoma or is exclusive to this regenerative tissue has not been studied to date. Thus, in this study, we aimed to unravel the extent and pattern of acidification in vivo during the early phase post musculoskeletal injury. Local pH changes after fracture and muscle trauma were measured simultaneously in two pre-clinical animal models (sheep/rats) immediately after and up to 48 h post injury. The rat fracture hematoma was further analyzed histologically and metabolomically. In vivo pH measurements in bone and muscle hematoma revealed a local acidification in both animal models, yielding mean pH values in rats of 6.69 and 6.89, with pronounced intra- and inter-individual differences. The metabolomic analysis of the hematomas indicated a link between reduction in tricarboxylic acid cycle activity and pH, thus, metabolic activity within the injured tissues could be causative for the different pH values. The significant acidification within the early musculoskeletal hematoma could enable the employment of the pH for novel, sought-after treatments that allow for spatially and temporally controlled drug release

Comparison between experimental data and thermodynamic predictions

Funding Information: JPO and JS acknowledge Fundação para a Ciência e a Tecnologia (FCT - MCTES) for its financial support via the project UID/00667/2020 (UNIDEMI). JS acknowledges the China Scholarship Council for funding the Ph.D. grant (CSC NO. 201808320394). JPO acknowledges funding by national funds from FCT - Fundação para a Ciência e a Tecnologia, I.P. in the scope of the projects LA/P/0037/2020, UIDP/50025/2020 and UIDB/50025/2020 of the Associate Laboratory Institute of Nanostructures, Nanomodelling and Nanofabrication – i3N. The authors acknowledge DESY (Hamburg, Germany), a member of the Helmholtz Association HGF, for the provision of experimental facilities. Beamtime was allocated for proposal I-20210899 EC. The research leading to this result has been supported by the project CALIPSOplus under the Grant Agreement 730872 from the EU Framework Programme for Research and Innovation HORIZON 2020. CF and ACM gratefully acknowledge partial financial support for this research by the Institute of Materials Research (IMR) at The Ohio State University under a 2017 Exploratory Materials Research Grant, and by the American Welding Society (AWS) under an AWS Graduate Research Fellowship Grant. Electron microscopy was performed at the Center for Electron Microscopy and Analysis (CEMAS) at The Ohio State University. Funding Information: JPO and JS acknowledge Fundação para a Ciência e a Tecnologia (FCT - MCTES) for its financial support via the project UID/00667/2020 (UNIDEMI). JS acknowledges the China Scholarship Council for funding the Ph.D. grant (CSC NO. 201808320394 ). JPO acknowledges funding by national funds from FCT - Fundação para a Ciência e a Tecnologia, I.P., in the scope of the projects LA/P/0037/2020, UIDP/50025/2020 and UIDB/50025/2020 of the Associate Laboratory Institute of Nanostructures, Nanomodelling and Nanofabrication – i3N. The authors acknowledge DESY (Hamburg, Germany), a member of the Helmholtz Association HGF, for the provision of experimental facilities. Beamtime was allocated for proposal I-20210899 EC. The research leading to this result has been supported by the project CALIPSOplus under the Grant Agreement 730872 from the EU Framework Programme for Research and Innovation HORIZON 2020. CF and ACM gratefully acknowledge partial financial support for this research by the Institute of Materials Research (IMR) at The Ohio State University under a 2017 Exploratory Materials Research Grant, and by the American Welding Society (AWS) under an AWS Graduate Research Fellowship Grant. Electron microscopy was performed at the Center for Electron Microscopy and Analysis (CEMAS) at The Ohio State University. Publisher Copyright: © 2022 The AuthorsThe development of multi-principal element alloys is currently on the rise. While there is significant fundamental work being performed to understand microstructure-property relationships, the processability of these novel alloys is yet incipient. In this work, the microstructure evolution in two arc-welded multi-principal element alloys, Al10Co25Cr8Fe15Ni36Ti6 and Al10.87Co21.74Cr21.74Cu2.17Fe21.74Ni21.74, was evaluated by electron microscopy and high energy synchrotron X-ray diffraction coupled with thermodynamic calculations. By correlating microhardness maps across the welds to results from microstructure characterization, it was possible to identify the strengthening phases across the welded materials, which can aid in fine tuning the alloy microstructure to achieve targeted strengths. Moreover, a comparison between the thermodynamically predicted microstructure evolution and that present in the welded joints was performed, highlighting the difficulty of such predictions in complex, scarcely studied multi-principal element systems.publishersversionpublishe

Absorbance-activated-droplet sorting for directed enzyme evolution

The successful creation of custom-made enzymes by directed evolution relies in no small part on screening as many variants as possible. Massive scale-down of assay volumes by compartmentalization of library members in water-in-oil emulsion droplets has recently led to the development of ultrahigh-throughput screening platforms that use small volumes (typically picoliters) and allow sorting of more than 106 variants per hour 1,2. The key technical module to make this possible is a microfluidic droplet sorter that has so far relied exclusively on fluorescent readouts. To extend the range of assays amenable to this approach, we developed a highly efficient microfluidic absorbance-activated droplet sorter (AADS)3. Using this module, microdroplets can be sorted based on absorbance readout at rates of up to more than a million droplets in 3 hours. To validate this device, we implemented a miniaturized coupled assay for an NAD+- dependent amino acid dehydrogenase. The detection limit (10 μM in a coupled assay producing a formazan dye) enables accurate kinetic readouts and sorting experiments showed that the AADS successfully enriched active variants up to 2,800-fold from an overwhelming majority of inactive ones at ≈ 100 Hz. Furthermore, improved variants showing increased solubility (up to 60%) and thermostability (up to 12 °C) were identified after two rounds of directed evolution, thereby demonstrating the usefulness of this sorting module for enzyme engineering. This AADS makes the most widely used optical detection format amenable to screens of unprecedented size, paving the way for the implementation of chromogenic assays in droplet microfluidics workflows. We are currently expanding its range of applications towards the monitoring of cell growth for the development of survival assays and the detection of weak enzymatic reactions. 1. Colin P-Y, Kintses B, Gielen F, et al. Ultrahigh-throughput discovery of promiscuous enzymes by picodroplet functional metagenomics. Nat Commun. 2015; vol: 6, p:1-12. doi:10.1038/ncomms10008. 2. Colin PY, Zinchenko A, Hollfelder F. Enzyme engineering in biomimetic compartments. Curr Opin Struct Biol. 2015; vol: 33, p: 42-51. doi:10.1016/j.sbi.2015.06.001. 3. Gielen F, Hours R, Emond S, Fischlechner M, Schell U, Hollfelder F. Ultrahigh-throughput-directed enzyme evolution by absorbance-activated droplet sorting (AADS). Proc Natl Acad Sci U S A. 2016; vol: 113, p: E7383-E7389. doi:10.1073/pnas.160692711

Early pH changes in musculoskeletal tissues upon injury-aerobic catabolic pathway activity linked to inter-individual differences in local pH

Local pH is stated to acidify after bone fracture. However, the time course and degree of acidification remain unknown. Whether the acidification pattern within a fracture hematoma is applicable to adjacent muscle hematoma or is exclusive to this regenerative tissue has not been studied to date. Thus, in this study, we aimed to unravel the extent and pattern of acidification in vivo during the early phase post musculoskeletal injury. Local pH changes after fracture and muscle trauma were measured simultaneously in two pre-clinical animal models (sheep/rats) immediately after and up to 48 h post injury. The rat fracture hematoma was further analyzed histologically and metabolomically. In vivo pH measurements in bone and muscle hematoma revealed a local acidification in both animal models, yielding mean pH values in rats of 6.69 and 6.89, with pronounced intra- and inter-individual differences. The metabolomic analysis of the hematomas indicated a link between reduction in tricarboxylic acid cycle activity and pH, thus, metabolic activity within the injured tissues could be causative for the different pH values. The significant acidification within the early musculoskeletal hematoma could enable the employment of the pH for novel, sought-after treatments that allow for spatially and temporally controlled drug release

AAPM medical physics practice guideline 10.a.: Scope of practice for clinical medical physics.

The American Association of Physicists in Medicine (AAPM) is a nonprofit professional society whose primary purposes are to advance the science, education, and professional practice of medical physics. The AAPM has more than 8000 members and is the principal organization of medical physicists in the United States. The AAPM will periodically define new practice guidelines for medical physics practice to help advance the science of medical physics and to improve the quality of service to patients throughout the United States. Existing medical physics practice guidelines will be reviewed for the purpose of revision or renewal, as appropriate, on their fifth anniversary or sooner. Each medical physics practice guideline (MPPG) represents a policy statement by the AAPM, has undergone a thorough consensus process in which it has been subjected to extensive review, and requires the approval of the Professional Council. The medical physics practice guidelines recognize that the safe and effective use of diagnostic and therapeutic radiation requires specific training, skills, and techniques as described in each document. As the review of the previous version of AAPM Professional Policy (PP)-17 (Scope of Practice) progressed, the writing group focused on one of the main goals: to have this document accepted by regulatory and accrediting bodies. After much discussion, it was decided that this goal would be better served through a MPPG. To further advance this goal, the text was updated to reflect the rationale and processes by which the activities in the scope of practice were identified and categorized. Lastly, the AAPM Professional Council believes that this document has benefitted from public comment which is part of the MPPG process but not the AAPM Professional Policy approval process. The following terms are used in the AAPM's MPPGs: Must and Must Not: Used to indicate that adherence to the recommendation is considered necessary to conform to this practice guideline. Should and Should Not: Used to indicate a prudent practice to which exceptions may occasionally be made in appropriate circumstances

Evaluation of an MPN test for the rapid enumeration of Pseudomonas aeruginosa in hospital waters.

In this study, the performance of a new most probable number (MPN) test (Pseudalert®/Quanti-Tray®) for the enumeration of Pseudomonas aeruginosa from hospital waters was compared with both international and national membrane filtration-based culture methods for P. aeruginosa: ISO 16266:2006 and UK The Microbiology of Drinking Water – Part 8 (MoDW Part 8), which both use Pseudomonas CN agar. The comparison based on the calculation of mean relative differences between the two methods was conducted according to ISO 17994:2014. Using both routine hospital water samples (80 from six laboratories) and artificially contaminated samples (192 from five laboratories), paired counts from each sample and the enumeration method were analysed. For routine samples, there were insufficient data for a conclusive assessment, but the data do indicate at least equivalent performance of Pseudalert®/Quanti-Tray®. For the artificially contaminated samples, the data revealed higher counts of P. aeruginosa being recorded by Pseudalert®/Quanti-Tray®. The Pseudalert®/Quanti-Tray® method does not require confirmation testing for atypical strains of P. aeruginosa, saving up to 6 days of additional analysis, and has the added advantage of providing confirmed counts within 24–28 hours incubation compared to 40–48 hours or longer for the ISO 16266 and MoDW Part 8 methods

Antigenic diversity is generated by distinct evolutionary mechanisms in African trypanosome species

Antigenic variation enables pathogens to avoid the host immune response by continual switching of surface proteins. The protozoan blood parasite Trypanosoma brucei causes human African trypanosomiasis ("sleeping sickness") across sub-Saharan Africa and is a model system for antigenic variation, surviving by periodically replacing a monolayer of variant surface glycoproteins (VSG) that covers its cell surface. We compared the genome of Trypanosoma brucei with two closely related parasites Trypanosoma congolense and Trypanosoma vivax, to reveal how the variant antigen repertoire has evolved and how it might affect contemporary antigenic diversity. We reconstruct VSG diversification showing that Trypanosoma congolense uses variant antigens derived from multiple ancestral VSG lineages, whereas in Trypanosoma brucei VSG have recent origins, and ancestral gene lineages have been repeatedly co-opted to novel functions. These historical differences are reflected in fundamental differences between species in the scale and mechanism of recombination. Using phylogenetic incompatibility as a metric for genetic exchange, we show that the frequency of recombination is comparable between Trypanosoma congolense and Trypanosoma brucei but is much lower in Trypanosoma vivax. Furthermore, in showing that the C-terminal domain of Trypanosoma brucei VSG plays a crucial role in facilitating exchange, we reveal substantial species differences in the mechanism of VSG diversification. Our results demonstrate how past VSG evolution indirectly determines the ability of contemporary parasites to generate novel variant antigens through recombination and suggest that the current model for antigenic variation in Trypanosoma brucei is only one means by which these parasites maintain chronic infections