System locates randomly placed remote objects

System to locate objects submerged underwater uses active/passive sonar techniques in which a transmitter is attached to the object to be recovered and a receiver is used for search. The system is rugged, has a long term operating life, and furnishes a precise bearing on the object

Implantable acoustic-beacon automatic fish-tracking system

A portable automatic fish tracking system was developed for monitoring the two dimensional movements of small fish within fixed areas of estuarine waters and lakes. By using the miniature pinger previously developed for this application, prototype tests of the system were conducted in the York River near the Virginia Institute of Marine Science with two underwater listening stations. Results from these tests showed that the tracking system could position the miniature pinger signals to within + or - 2.5 deg and + or - 135 m at ranges up to 2.5 km. The pingers were implanted in small fish and were successfully tracked at comparable ranges. No changes in either fish behavior or pinger performance were observed as a result of the implantation. Based on results from these prototype tests, it is concluded that the now commercially available system provides an effective approach to underwater tracking of small fish within a fixed area of interest

Distinguishing cancerous from non-cancerous cells through analysis of electrical noise

Since 1984, electric cell-substrate impedance sensing (ECIS) has been used to monitor cell behavior in tissue culture and has proven sensitive to cell morphological changes and cell motility. We have taken ECIS measurements on several cultures of non-cancerous (HOSE) and cancerous (SKOV) human ovarian surface epithelial cells. By analyzing the noise in real and imaginary electrical impedance, we demonstrate that it is possible to distinguish the two cell types purely from signatures of their electrical noise. Our measures include power-spectral exponents, Hurst and detrended fluctuation analysis, and estimates of correlation time; principal-component analysis combines all the measures. The noise from both cancerous and non-cancerous cultures shows correlations on many time scales, but these correlations are stronger for the non-cancerous cells.Comment: 8 pages, 4 figures; submitted to PR

Next-generation cell line selection methodology leveraging data lakes, natural language generation and advanced data analytics

Cell line development is an essential stage in biopharmaceutical development that often lies on the critical path. Failure to fully characterise the lead clone during initial screening can lead to lengthy project delays during scale-up, which can potentially compromise commercial manufacturing success. In this study, we propose a novel cell line development methodology, referenced as CLD4, which involves four steps enabling autonomous data-driven selection of the lead clone. The first step involves the digitalisation of the process and storage of all available information within a structured data lake. The second step calculates a new metric referenced as the cell line manufacturability index (MICL) quantifying the performance of each clone by considering the selection criteria relevant to productivity, growth and product quality. The third step implements machine learning (ML) to identify any potential risks associated with process operation and relevant critical quality attributes (CQAs). The final step of CLD4 takes into account the available metadata and summaries all relevant statistics generated in steps 1–3 in an automated report utilising a natural language generation (NLG) algorithm. The CLD4 methodology was implemented to select the lead clone of a recombinant Chinese hamster ovary (CHO) cell line producing high levels of an antibody-peptide fusion with a known product quality issue related to end-point trisulfide bond (TSB) concentration. CLD4 identified sub-optimal process conditions leading to increased levels of trisulfide bond that would not be identified through conventional cell line development methodologies. CLD4 embodies the core principles of Industry 4.0 and demonstrates the benefits of increased digitalisation, data lake integration, predictive analytics and autonomous report generation to enable more informed decision making

Geologic technical assessment of the Stratton Ridge salt dome, Texas, for potential expansion of the U.S. strategic petroleum reserve.

The Stratton Ridge salt dome is a large salt diapir located only some ten miles from the currently active Strategic Petroleum Reserve Site at Bryan Mound, Texas. The dome is approximately 15 miles south-southwest of Houston. The Stratton Ridge salt dome has been intensively developed, in the desirable central portions, with caverns for both brine production and product storage. This geologic technical assessment indicates that the Stratton Ridge salt dome may be considered a viable, if less-than-desirable, candidate site for potential expansion of the Strategic Petroleum Reserve (SPR). Past development of underground caverns significantly limits the potential options for use by the SPR. The current conceptual design layout of proposed caverns for such an expansion facility is based upon a decades-old model of salt geometry, and it is unacceptable, according to this reinterpretation of salt dome geology. The easternmost set of conceptual caverns are located within a 300-ft buffer zone of a very major boundary shear zone, fault, or other structural feature of indeterminate origin. This structure transects the salt stock and subdivides it into an shallow western part and a deeper eastern part. In places, the distance from this structural boundary to the design-basis caverns is as little as 150 ft. A 300-ft distance from this boundary is likely to be the minimum acceptable stand-off, from both a geologic and a regulatory perspective. Repositioning of the proposed cavern field is possible, as sufficient currently undeveloped salt acreage appears to be available. However, such reconfiguration would be subject to limitations related to land-parcel boundaries and other existing infrastructure and topographic constraints. More broadly speaking, the past history of cavern operations at the Stratton Ridge salt dome indicates that operation of potential SPR expansion caverns at this site may be difficult, and correspondingly expensive. Although detailed information is difficult to come by, widely accepted industry rumors are that numerous existing caverns have experienced major operational problems, including salt falls, sheared casings, and unintended releases of stored product(s). Many of these difficulties may be related to on-going differential movement of individual salt spines or to lateral movement at the caprock-salt interface. The history of operational problems, only some of which appear to be a matter of public record, combined with the potential for encountering escaped product from other operations, renders the Stratton Ridge salt dome a less-than-desirable site for SPR purposes

Geologic technical assessment of the Chacahoula Salt Dome, Louisiana, for potential expansion of the U.S. strategic petroleum reserve.

The Chacahoula salt dome, located in southern Louisiana, approximately 66 miles southwest of New Orleans, appears to be a suitable site for a 160-million-barrel-capacity expansion facility for the U.S. Strategic Petroleum Reserve, comprising sixteen 10-million barrel underground storage caverns. The overall salt dome appears to cover an area of some 1800 acres, or approximately 2.8 square miles, at a subsea elevation of 2000 ft, which is near the top of the salt stock. The shallowest known salt is present at 1116 ft, subsea. The crest of the salt dome is relatively flatlying, outward to an elevation of -4000 ft. Below this elevation, the flanks of the dome plunge steeply in all directions. The dome appears to comprise two separate spine complexes of quasi-independently moving salt. Two mapped areas of salt overhang, located on the eastern and southeastern flanks of the salt stock, are present below -8000 ft. These regions of overhang should present no particular design issues, as the conceptual design SPR caverns are located in the western portion of the dome. The proposed cavern field may be affected by a boundary shear zone, located between the two salt spines. However, the large size of the Chacahoula salt dome suggests that there is significant design flexibility to deal with such local geologic issues

An automated, low volume, and high-throughput analytical platform for aggregate quantitation from cell culture media

High throughput screening methods have driven a paradigm shift in biopharmaceutical development by reducing the costs of good manufactured (COGM) and accelerate the launch to market of novel drug products. Scale-down cell culture systems such as shaken 24- and 96-deep-well plates (DWPs) are used for initial screening of hundreds of recombinant mammalian clonal cell lines to quickly and efficiently select the best producing strains expressing product quality attributes that fit to industry platform. A common modification monitored from early-stage product development is protein aggregation due to its impact on safety and efficacy. This study aims to integrate high-throughput analysis of aggregation-prone therapeutic proteins with 96-deep well plate screening to rank clones based on the aggregation levels of the expressed proteins. Here we present an automated, small-scale analytical platform workflow combining the purification and subsequent aggregation analysis of protein biopharmaceuticals expressed in 96-DWP cell cultures. Product purification was achieved by small-scale solid-phase extraction using dual flow chromatography (DFC) automated on a robotic liquid handler for the parallel processing of up to 96 samples at a time. At-line coupling of size-exclusion chromatography (SEC) using a 2.1 mm ID column enabled the detection of aggregates with sub-2 µg sensitivity and a 3.5 min run time. The entire workflow was designed as an application to aggregation-prone mAbs and “mAb-like” next generation biopharmaceuticals, such as bispecific antibodies (BsAbs). Application of the high-throughput analytical workflow to a shake plate overgrow (SPOG) screen, enabled the screening of 384 different clonal cell lines in 32 h, requiring < 2 μg of protein per sample. Aggregation levels expressed by the clones varied between 9 and 76%. This high-throughput analytical workflow allowed for the early elimination of clonal cell lines with high aggregation, demonstrating the advantage of integrating analytical testing for critical quality attributes (CQAs) earlier in product development to drive better decision making

Polypeptide-grafted macroporous polyHIPE by surface-initiated N-Carboxyanhydride (NCA) polymerization as a platform for bioconjugation

A new class of functional macroporous monoliths from polymerized high internal phase emulsion (polyHIPE) with tunable surface functional groups was developed by direct polypeptide surface grafting. In the first step, amino-functional polyHIPEs were obtained by the addition of 4-vinylbenzyl or 4-vinylbenzylphthalimide to the styrenic emulsion and thermal radical polymerization. The obtained monoliths present the expected open-cell morphology and a high surface area. The incorporated amino group was successfully utilized to initiate the ring-opening polymer- ization of benzyl-L-glutamate N-carboxyanhydride (BLG NCA) and benzyloxycarbonyl-L-lysine (Lys(Z)) NCA, which resulted in a dense homogeneous coating of polypeptides throughout the internal polyHIPE surfaces as confirmed by SEM and FTIR analysis. The amount of polypeptide grafted to the polyHIPE surfaces could be modulated by varying the initial ratio of amino acid NCA to amino-functional polyHIPE. Subsequent removal of the polypeptide protecting groups yielded highly functional polyHIPE-g-poly(glutamic acid) and polyHIPE-g- poly(lysine). Both types of polypeptide-grafted monoliths responded to pH by changes in their hydrohilicity. The possibility to use the high density of function (−COOH or −NH2) for secondary reaction was demonstrated by the successful bioconjugation of enhanced green fluorescent protein (eGFP) and fluorescein isocyanate (FITC) on the polymer 3D-scaffold surface. The amount of eGFP and FITC conjugated to the polypeptide-grafted polyHIPE was significantly higher than to the amino- functional polyHIPE, signifying the advantage of polypeptide grafting to achieve highly functional polyHIPEs

Preconception Care Between Pregnancies: The Content of Internatal Care

For more than two decades, prenatal care has been a cornerstone of our nation’s strategy for improving pregnancy outcomes. In recent years, however, a growing recognition of the limits of prenatal care and the importance of maternal health before pregnancy has drawn increasing attention to preconception and internatal care. Internatal care refers to a package of healthcare and ancillary services provided to a woman and her family from the birth of one child to the birth of her next child. For healthy mothers, internatal care offers an opportunity for wellness promotion between pregnancies. For high-risk mothers, internatal care provides strategies for risk reduction before their next pregnancy. In this paper we begin to define the contents of internatal care. The core components of internatal care consist of risk assessment, health promotion, clinical and psychosocial interventions. We identified several priority areas, such as FINDS (family violence, infections, nutrition, depression, and stress) for risk assessment or BBEEFF (breastfeeding, back-to-sleep, exercise, exposures, family planning and folate) for health promotion. Women with chronic health conditions such as hypertension, diabetes, or weight problems should receive on-going care per clinical guidelines for their evaluation, treatment, and follow-up during the internatal period. For women with prior adverse outcomes such as preterm delivery, we propose an internatal care model based on known etiologic pathways, with the goal of preventing recurrence by addressing these biobehavioral pathways prior to the next pregnancy. We suggest enhancing service integration for women and families, including possibly care coordination and home visitation for selected high-risk women. The primary aim of this paper is to start a dialogue on the content of internatal care