Advances in recombinant antibody manufacturing

Since the first use of Chinese hamster ovary (CHO) cells for recombinant protein expression, production processes have steadily improved through numerous advances. In this review, we have highlighted several key milestones that have contributed to the success of CHO cells from the beginning of their use for monoclonal antibody (mAb) expression until today. The main factors influencing the yield of a production process are the time to accumulate a desired amount of biomass, the process duration, and the specific productivity. By comparing maximum cell densities and specific growth rates of various expression systems, we have emphasized the limiting parameters of different cellular systems and comprehensively described scientific approaches and techniques to improve host cell lines. Besides the quantitative evaluation of current systems, the quality-determining properties of a host cell line, namely post-translational modifications, were analyzed and compared to naturally occurring polyclonal immunoglobulin fractions from human plasma. In summary, numerous different expression systems for mAbs are available and also under scientific investigation. However, CHO cells are the most frequently investigated cell lines and remain the workhorse for mAb production until today.(VLID)135204

BMC Proceedings / Benchmarking of commercially available CHO cell culture media for antibody production

Poster presentation from 23rd European Society for Animal Cell Technology (ESACT) Meeting: Better Cells for Better Health, Lille, France. 23-26 June 201

BMC Proceedings / Characterization of recombinant IgA producing CHO cell lines by qPCR

Immunoglobulin A (IgA) mediates a key role in mucosal immunity and is a promising novel immunotherapeutic candidate. However, difficulties in obtaining enough material often hamper in vivo explorations. We have previously generated recombinant Chinese hamster ovary (CHO) cell lines which expressed two different HIV-1 antibodies, 3D6 and 4B3, as IgA1 [1]. One cell line (3D6-IgA) shows high production rates, whereas the other (4B3-IgA) secretes rather low amounts of product. In order to unravel the mystery of productivity bottlenecks we extensively characterized the cell lines regarding growth rate, IgA productivity in long-term culture, immunofluorescence microscopy, flow cytometry and Western blotting of intra- and extracellular product (data not shown). The generated data encouraged us to analyze whether the observed antibody productivities could be explained by gene copy number (GCN) or mRNA levels

The Space Communications and Navigation Testbed aboard International Space Station: Seven Years of Space-based Reconfigurable Software Defined Communications, Navigation, and Networking

The adoption of software defined radios offers space missions a new way to develop and operate space transceivers for communications and navigation.The SCaN Testbed on-board the ISS led groundbreaking efforts to champion use of software defined radios for space communications. The SCaN Testbed has allowed NASA, industry, academia, and international partners to pursue their respective interests in joint collaboration with NASA, and move this technology and it's applications to the space domain. Launched in 2012, The SCaN Testbed has logged over 4000 hours of operation exploring the development, reconfiguration, and operation of software defined radios and their software applications. Over the past seven years, experimenters and organizations from across the United States and around the world, have advanced the applications of software defined radios and networks using the SCaN Tested. Some of SCaN Testbed's successful experiments include the demonstration of the first Ka-band full duplex space transceiver, which became an R&D 100 award winning technology, and was inducted into the Space Technology Hall of Fame, following the launch and space deployment of a successful commercial product line based on the Testbed radios.Experiments have focused on new software development and operations concepts for understanding how to manage and apply this relatively new technology to space to improve communications and navigation for space science and exploration missions. The advanced capabilities of the software radios allow for multiple applications or functions (e.g., communication and navigation) to operate from the same radio platform. Multiple software waveform applications enable software component reuse and improve efficiency for multiple applications operating over different mission phases. The new capabilities of software defined radios such as on-orbit reconfiguration, also present new challenges such as increased operational complexity. Experiments of the SCaN testbed include more intelligent or cognitive applications to improve communications efficiency and manage the complexity of the radios, the communication channels, and the network itself. The software defined radios on the SCaN Testbed are each compliant to NASA's Space Telecommunications Radio System (STRS) Architecture. The STRS Architecture provides commonality among radio developments from different providers and different mission applications, and is designed to reduce the cost, risk, and complexity of unique and custom radio developments. This radio architecture standard defines common waveform software interfaces, methods of instantiation, operation, and documentation. As the SCaN Testbed concludes its operations on ISS, this presentation explores the advancements and accomplishments made to advance software defined radio technology and its applications for exploration. The accomplishments cover a number of experiment areas in Ka-band and S-band communications with TDRS, high rate communications, adaptive waveform operation, navigation using both GPA and Galileo constellations, complex networking and disruptive tolerant link protocols, user initiative service, and initial experiments with intelligent and cognitive applications which demonstrate the significant potential of software defined and cognitive radios

Enabling Future Science and Human Exploration with NASA's Next Generation near Earth and Deep Space Communications and Navigation Architecture

The National Aeronautics and Space Administration (NASA) is studying alternatives for the United States space communications architecture through the 2040 timeframe. This architecture provides communication and navigation services to both human exploration and science missions throughout the solar system. Several of NASA's key space assets are approaching their end of design life and major systems are in need of replacement. The changes envisioned in the relay satellite architecture and capabilities around both Earth and Mars are significant undertakings and occur only once or twice each generation, and therefore is referred to as NASA's next generation space communications architecture. NASA's next generation architecture will benefit from technology and services developed over recent years. These innovations will provide missions with new operations concepts, increased performance, and new business and operating models. Advancements in optical communications will enable high-speed data channels and the use of new and more complex science instruments. Modern multiple beam/multiple access technologies such as those employed on commercial high throughput satellites will enable enhanced capabilities for on-demand service, and with new protocols will help provide Internet-like connectivity for cooperative spacecraft to improve data return and coordinate joint mission objectives. On-board processing with autonomous and cognitive networking will play larger roles to help manage system complexity. Spacecraft and ground systems will coordinate among themselves to establish communications, negotiate link connectivity, and learn to share spectrum to optimize resource allocation. Spacecraft will autonomously navigate, plan trajectories, and handle off-nominal events. NASA intends to leverage the ever-expanding capabilities of the satellite communications industry and foster its continued growth. NASA's technology development will complement and extend commercial capabilities to meet unique space environment requirements and to provide capabilities that are beyond the commercial marketplace. The progress of the communications industry, including the emerging global space internet segment and its planned constellations of 100's of satellites offer additional opportunities for new capability and mission concepts. The opportunities and challenges of a future space architecture require an optimal solution encompassing a global perspective. The concepts and technologies intentionally define an architecture that applies not only to NASA, but to other U.S. government agencies, international space and government agencies, and domestic and international industries to advance the openness, interoperability, and affordability of space communications. Cooperation among the worlds space agencies, their capabilities, standards, operations, and interoperability are key to advancing humankind's understand of the universe and extending human presence into the solar system

Increasing Knowledge and Self-Efficacy in Nurses Orienting to Cardiovascular Surgery Using A New Periop 202 Program

The operating room theater can be intimidating for new nurses, thus leading to a shortage of nurses who are comfortable working in this environment. Evidence supports that 50% of perioperative nurses in 2017 were between the age of 50 and 59. Additionally, no formal didactic courses are being offered in undergraduate programs and the challenging environment related directly to the future shortage of perioperative nurses. This negatively impacts the number of trained perioperative cardiovascular nurses. The project proposed a new didactic educational Perioperative (Periop) 202 program that aimed to increase nurses’ self-efficacy to function on the cardiovascular operating room (CVOR) team and their knowledge of protocols and guidelines of new nurses entering the CVOR with the goal of generating future perioperative nurses to care for of this patient population. The eight actionable items within the Periop 202 program were designed to increase knowledge of CVOR procedures and protocol and the self-efficacy of new perioperative cardiovascular nurses, as evidence supports the use of nurses to complete these essential educational interventions. The Periop 202 program was an evidenced based program that added value and solution to the CVOR market. The program increased nurses’ confidence level of what they already knew about OR nursing with their pre-course percentage scores of 63% to post-course percentage scores of 80% on the OR knowledge questionnaire. The SEIEL self-efficacy questionnaire reported an increase in communication and team collaboration. All nurse participants completed their CVOR competency validated by their preceptors. Through a partnership with the AORN, a CVOR program with online-learning modules, one on one meetings with the primary investigator, clinical experiences and exposure, and team involvement led to a successful training program. The implications of creating and implementing an evidenced based Periop 202 program will have a positive impact on recruitment strategies across the nation. Key words: nurse, education, environment, operating room, readiness to learn

Studying NASA's Transition to Ka-Band Communications for Low Earth Orbit

As the S-band spectrum becomes crowded, future space missions will need to consider moving command and telemetry services to Ka-band. NASA's Space Communications and Navigation (SCaN) Testbed provides a software-defined radio (SDR) platform that is capable of supporting investigation of this service transition. The testbed contains two S-band SDRs and one Ka-band SDR. Over the past year, SCaN Testbed has demonstrated Ka-band communications capabilities with NASAs Tracking and Data Relay Satellite System (TDRSS) using both open- and closed-loop antenna tracking profiles. A number of technical areas need to be addressed for successful transition to Ka-band. The smaller antenna beamwidth at Ka-band increases the criticality of antenna pointing, necessitating closed loop tracking algorithms and new techniques for received power estimation. Additionally, the antenna pointing routines require enhanced knowledge of spacecraft position and attitude for initial acquisition, versus an S-band antenna. Ka-band provides a number of technical advantages for bulk data transfer. Unlike at S-band, a larger bandwidth may be available for space missions, allowing increased data rates. The potential for high rate data transfer can also be extended for direct-to-ground links through use of variable or adaptive coding and modulation. Specific examples of Ka-band research from SCaN Testbeds first year of operation will be cited, such as communications link performance with TDRSS, and the effects of truss flexure on antenna pointing

An application of physical flexibility and software reconfigurability for the automation of battery module assembly

Batteries are a strategic technology to decarbonize conventional automotive powertrains and enable energy policy turnaround from fossil fuels to renewable energy. The demand for battery packs is rising, but they remain unable to compete with conventional technologies, primarily due to higher costs. Major sources of cost remain in manufacturing and assembly. These costs can be attributed to a need for high product quality, material handling complexity, uncertain and fluctuating production volumes, and an unpredictable breadth of product variants. This research paper applies the paradigms of flexibility from a mechanical engineering perspective, and reconfigurability from a software perspective to form a holistic, integrated manufacturing solution to better realize product variants. This allows manufacturers to de-risk investment as there is increased confidence that a facility can meet new requirements with reduced effort, and also shows how part of the vision of Industry 4.0 associated with the integration and exploitation of data can be fulfilled. A functional decomposition of battery packs is used to develop a foundational understanding of how changes in customer requirements can result in physical product changes. A Product, Process, and Resource (PPR) methodology is employed to link physical product characteristics to physical and logical characteristics of resources. This mapping is leveraged to enable the design of a gripper with focused flexibility by the Institute for Machine Tools and Industrial Management (iwb) at the Technical University of Munich, as it is acknowledged that mechanical changes are challenging to realize within industrial manufacturing facilities. Reconfigurability is realised through exploitation of data integration across the PPR domains, through the extension of the capabilities of a non-commercial virtual engineering toolset developed by the Automation Systems Group at the University of Warwick. The work shows an “end-to-end” approach that practically demonstrates the application of the flexibility and reconfigurability paradigms within an industrial engineering context

Microbial ligand costimulation drives neutrophilic steroid-refractory asthma

Funding: The authors thank the Wellcome Trust (102705) and the Universities of Aberdeen and Cape Town for funding. This research was also supported, in part, by National Institutes of Health GM53522 and GM083016 to DLW. KF and BNL are funded by the Fonds Wetenschappelijk Onderzoek, BNL is the recipient of an European Research Commission consolidator grant and participates in the European Union FP7 programs EUBIOPRED and MedALL. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

We Are History: The Outlines of a Quasi-Substantive Philosophy of History

In times of a felt need to justify the value of the humanities, the need to revisit and re-establish the public relevance of the discipline of history cannot come as a surprise. On the following pages I will argue that this need is unappeasable by scholarly proposals. The much desired revitalization of historical writing lies instead in reconciling ourselves with the dual meaning of the word history, in exploring the necessary interconnection between history understood as the course of events and as historical writing. Despite the general tendency of the last decades to forbid philosophizing about history in the former sense (at least in departments of history and philosophy), I think that to a certain extent we already do so without succumbing to substantive thought. We already have the sprouts of a speculative although only quasi-substantive philosophy of history that nevertheless takes seriously the postwar criticism of the substantive enterprise. In this essay I will first try to outline this quasi-substantive philosophy of history that attests to the historical sensibility of our times; and second, I will try to outline its consequences regarding history as historical writing. Finally, in place of a conclusion I will suggest that historical writing is not as much a contribution to public agendas as it is the very arena in which public life is at stake