Generic high-capacity protein capture and release by pH control

Techniques for immobilization and release of proteins are of general interest but challenging to develop. Here we show a new method for high-capacity (several \ub5g cm-2) immobilization of proteins in polyelectrolyte brushes by multivalent hydrogen bonds. Upon increasing pH, the proteins are fully released with preserved structure and activity

Predicting the number of oocytes retrieved from controlled ovarian hyperstimulation with machine learning

STUDY QUESTION: Can machine learning predict the number of oocytes retrieved from controlled ovarian hyperstimulation (COH)? SUMMARY ANSWER: Three machine-learning models were successfully trained to predict the number of oocytes retrieved from COH. WHAT IS KNOWN ALREADY: A number of previous studies have identified and built predictive models on factors that influence the number of oocytes retrieved during COH. Many of these studies are, however, limited in the fact that they only consider a small number of variables in isolation. STUDY DESIGN, SIZE, DURATION: This study was a retrospective analysis of a dataset of 11,286 cycles performed at a single centre in France between 2009 and 2020 with the aim of building a predictive model for the number of oocytes retrieved from ovarian stimulation. The analysis was carried out by a data analysis team external to the centre using the Substra framework. The Substra framework enabled the data analysis team to send computer code to run securely on the centre's on-premises server. In this way, a high level of data security was achieved as the data analysis team did not have direct access to the data, nor did the data leave the centre at any point during the study. PARTICIPANTS/MATERIALS, SETTING, METHODS: The Light Gradient Boosting Machine algorithm was used to produce three predictive models: one that directly predicted the number of oocytes retrieved and two that predicted which of a set of bins provided by two clinicians the number of oocytes retrieved fell into. The resulting models were evaluated on a held-out test set and compared to linear and logistic regression baselines. In addition, the models themselves were analysed to identify the parameters that had the biggest impact on their predictions. MAIN RESULTS AND THE ROLE OF CHANCE: On average, the model that directly predicted the number of oocytes retrieved deviated from the ground truth by 4.21 oocytes. The model that predicted the first clinician's bins deviated by 0.73 bins whereas the model for the second clinician deviated by 0.62 bins. For all models, performance was best within the first and third quartiles of the target variable, with the model underpredicting extreme values of the target variable (no oocytes and large numbers of oocytes retrieved). Nevertheless, the erroneous predictions made for these extreme cases were still within the vicinity of the true value. Overall, all three models agreed on the importance of each feature which was estimated using Shapley Additive Explanation (SHAP) values. The feature with the highest mean absolute SHAP value (and thus the highest importance) was the antral follicle count, followed by basal AMH and FSH. Of the other hormonal features, basal TSH, LH, and testosterone levels were similarly important and baseline LH was the least important. The treatment characteristic with the highest SHAP value was the initial dose of gonadotropins. LIMITATIONS, REASONS FOR CAUTION: The models produced in this study were trained on a cohort from a single centre. They should thus not be used in clinical practice until trained and evaluated on a larger cohort more representative of the general population. WIDER IMPLICATIONS OF FINDINGS: These predictive models for the number of oocytes retrieved from COH may be useful in clinical practice, assisting clinicians in optimizing COH protocols for individual patients. Our work also demonstrates the promise of using the Substra framework for allowing external researchers to provide clinically relevant insights on sensitive fertility data in a fully secure, trustworthy manner and opens a number of exciting avenues for accelerating future research. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the French Public Bank of Investment as part of the Healthchain Consortium. T.Fe., C.He., J.C., C.J., C.-A.P., and C.Hi. are employed by Apricity. C.Hi. has received consulting fees and honoraria from Vitrolife, Merck Serono, Ferring, Cooper Surgical, Dibimed, Apricity, and Fairtility and travel support from Fairtility and Vitrolife, participates on an advisory board for Merck Serono, was the founder and organizer of the AI Fertility conference, has stock in Aria Fertility, TMRW, Fairtility, Apricity, and IVF Professionals, and received free equipment from Planar in exchange for first user feedback. C.J. has received a grant from BPI. J.C. has also received a grant from BPI, is a member of the Merck AI advisory board, and is a board member of Labelia Labs. C.He has a contract for medical writing of this manuscript by CHU Nantes and has received travel support from Apricity. A.R. haș received honoraria from Ferring and Organon. T.Fe. has received a grant from BPI. TRIAL REGISTRATION NUMBER: N/A

Detecting Selective Protein Binding Inside Plasmonic Nanopores: Toward a Mimic of the Nuclear Pore Complex

Biosensors based on plasmonic nanostructures offer label-free and real-time monitoring of biomolecular interactions. However, so do many other surface sensitive techniques with equal or better resolution in terms of surface coverage. Yet, plasmonic nanostructures offer unique possibilities to study effects associated with nanoscale geometry. In this work we use plasmonic nanopores with double gold films and detect binding of proteins inside them. By thiol and trietoxysilane chemistry, receptors are selectively positioned on the silicon nitride interior walls. Larger (similar to 150 nm) nanopores are used detect binding of averaged sized proteins (similar to 60 kg/mol) with high signal to noise (>100). Further, we fabricate pores that approach the size of the nuclear pore complex (diameter down to 50 nm) and graft disordered phenylalanine-glycine nucleoporin domains to the walls, followed by titration of karyopherin beta 1 transport receptors. The interactions are shown to occur with similar affinity as determined by conventional surface plasmon resonance on planar surfaces. Our work illustrates another unique application of plasmonic nanostructures, namely the possibility to mimic the geometry of a biological nanomachine with integrated optical sensing capabilities

Prime Focus Spectrograph (PFS) for the Subaru Telescope: Overview, recent progress, and future perspectives

PFS (Prime Focus Spectrograph), a next generation facility instrument on the 8.2-meter Subaru Telescope, is a very wide-field, massively multiplexed, optical and near-infrared spectrograph. Exploiting the Subaru prime focus, 2394 reconfigurable fibers will be distributed over the 1.3 deg field of view. The spectrograph has been designed with 3 arms of blue, red, and near-infrared cameras to simultaneously observe spectra from 380nm to 1260nm in one exposure at a resolution of ~1.6-2.7A. An international collaboration is developing this instrument under the initiative of Kavli IPMU. The project is now going into the construction phase aiming at undertaking system integration in 2017-2018 and subsequently carrying out engineering operations in 2018-2019. This article gives an overview of the instrument, current project status and future paths forward.Comment: 17 pages, 10 figures. Proceeding of SPIE Astronomical Telescopes and Instrumentation 201

Progress with the Prime Focus Spectrograph for the Subaru Telescope: a massively multiplexed optical and near-infrared fiber spectrograph

The Prime Focus Spectrograph (PFS) is an optical/near-infrared multi-fiber spectrograph with 2394 science fibers, which are distributed in 1.3 degree diameter field of view at Subaru 8.2-meter telescope. The simultaneous wide wavelength coverage from 0.38 um to 1.26 um, with the resolving power of 3000, strengthens its ability to target three main survey programs: cosmology, Galactic archaeology, and galaxy/AGN evolution. A medium resolution mode with resolving power of 5000 for 0.71 um to 0.89 um also will be available by simply exchanging dispersers. PFS takes the role for the spectroscopic part of the Subaru Measurement of Images and Redshifts project, while Hyper Suprime-Cam works on the imaging part. To transform the telescope plus WFC focal ratio, a 3-mm thick broad-band coated glass-molded microlens is glued to each fiber tip. A higher transmission fiber is selected for the longest part of cable system, while one with a better FRD performance is selected for the fiber-positioner and fiber-slit components, given the more frequent fiber movements and tightly curved structure. Each Fiber positioner consists of two stages of piezo-electric rotary motors. Its engineering model has been produced and tested. Fiber positioning will be performed iteratively by taking an image of artificially back-illuminated fibers with the Metrology camera located in the Cassegrain container. The camera is carefully designed so that fiber position measurements are unaffected by small amounts of high special-frequency inaccuracies in WFC lens surface shapes. Target light carried through the fiber system reaches one of four identical fast-Schmidt spectrograph modules, each with three arms. Prototype VPH gratings have been optically tested. CCD production is complete, with standard fully-depleted CCDs for red arms and more-challenging thinner fully-depleted CCDs with blue-optimized coating for blue arms.Comment: 14 pages, 12 figures, submitted to "Ground-based and Airborne Instrumentation for Astronomy V, Suzanne K. Ramsay, Ian S. McLean, Hideki Takami, Editors, Proc. SPIE 9147 (2014)

The Nature and Necessity of Operational Flexibility in the Emergency Department

Hospital-based emergency departments (EDs), given their high cost and major role in allocating care resources, are at the center of the debate about how to maximize value in delivering health care in the United States. To operate effectively and create value, EDs must be flexible, having the ability to rapidly adapt to the highly variable needs of patients. The concept of flexibility has not been well described in the ED literature. We introduce the concept, outline its potential benefits, and provide some illustrative examples to facilitate incorporating flexibility into ED management. We draw on operations research and organizational theory to identify and describe 5 forms of flexibility: physical, human resource, volume, behavioral, and conceptual. Each form of flexibility may be useful individually or in combination with other forms in improving ED performance and enhancing value. We also offer suggestions for measuring operational flexibility in the ED. A better understanding of operational flexibility and its application to the ED may help us move away from reactive approaches of managing variable demand to a more systematic approach. We also address the tension between cost and flexibility and outline how "partial flexibility" may help resolve some challenges. Applying concepts of flexibility from other disciplines may help clinicians and administrators think differently about their workflow and provide new insights into managing issues of cost, flow, and quality in the ED