Commercial Launch Research Articles

Proteomic and N-glycomic comparison of synthetic and bovine whey proteins and their effect on human gut microbiomes.

Advances in food production systems and customer acceptance have led to the commercial launch of dietary proteins produced via modern biotechnological approaches as alternatives to traditional agricultural sources. At the same time, a deeper understanding of how dietary components interact with the gut microbiome has highlighted the importance of understanding the nuances underpinning diet-microbiome interactions. Novel food proteins with distinct post-translational modifications resulting from their respective production systems have not been characterized, nor how they may differ from their traditionally produced counterparts. To address this, we have characterized the protein composition and N-glycome of a yeast-synthesized whey protein ingredient isolated from commercially available ice cream and compared this novel ingredient to whey protein powder isolate derived from bovine milk. We found that despite strong similarities in protein composition, the N-glycome significantly differs between these protein sources, reflecting the biosynthetic machinery of the production systems. Further, the composition profile and diversity of proteins found in the synthetic whey protein were lower relative to bovine whey protein, despite both being predominantly composed of β-lactoglobulin. Finally, to understand whether these differences in N-glycome profiles affected the human gut microbiome, we tested these proteins in an in vitro fecal fermentation model. We found that the two whey protein sources generated significant differences among three distinct microbial compositions, which we hypothesize is a product of differences in N-glycan composition and degradation by these representative microbial communities. This work highlights the need to understand how differences in novel biotechnological systems affect the bioactivity of these proteins, and how these differences impact the human gut microbiome.

Quality risk management and data integrity in R&D laboratories supporting CMC lifecycle of biological products

The development of pharmaceutical products is the critical bridge that moves a potential new medicine from academic discovery to applied treatment of patients. It translates an idea for a new drug to bench-level research on how it can be manufactured, formulated, characterized and controlled for use in non-clinical and early clinical trials.From pre-clinical R&D discovery work through the commercial launch, substantial R&D CMC data is generated to develop and optimize cGMP manufacturing and testing operations, while also supporting product comparability, elucidating product / impurity structures, assessing critical quality attributes, developing the drug delivery mode, and developing the product formulation for long-term stability. Significant R&D CMC work continues post-approval to support continuous improvement and market expansion of the commercial product. These activities are crucial elements of Product Lifecycle Management, and taken together, they comprise Pharmaceutical Quality or Chemistry, Manufacturing and Controls (CMC). The objective of this paper is to mitigate the regulatory ambiguity of R&D quality systems with practical, risk-based examples and recommendations when conducting supportive CMC studies for biological products.Making sound strategic CMC decisions under any circumstances assumes data from R&D studies are reliable, traceable, and complete. While there are specific regulatory guidelines on phase-appropriate cGMP activities, none exist for quality practices in R&D CMC laboratories conducting non-cGMP studies. Hindsight is not the time to discover that R&D studies lack key elements that would otherwise have allowed the data to be directly presented to regulators, if needed. There is a strong prospective business interest in protecting considerable investments made for CMC R&D studies. Therefore, establishment of a robust and stage-appropriate R&D laboratory quality system is essential for companies seeking to capitalize on prior knowledge, protect investments, and be prepared for accelerated approval pathways.

Experior: Development History, Commercial Launch, and Research Plans

Experior: Development History, Commercial Launch, and Research Plans

Risk management for viral clearance: A case study on adoption of platform validation approach and risk management of process changes

Viral clearance (VC) studies are routinely required prior to entering clinical trials or for commercial launch of biopharmaceuticals. With increasing prior knowledge and experience, platform validation can be used to eliminate some VC studies and such strategy has been updated into industry guidelines, such as ICH Q5A (R2). In addition, process changes can happen during life-cycle management of a product. In these circumstances, high-risk process parameters need to be identified and corresponding control strategies need to be defined to ensure viral safety of the product. This work describes the design of a science-based risk management tool and how this tool is employed for platform validation and process change scenarios.

Exploring the Feasibility of Kuiper Belt Missions Supported by Centrifugal Nuclear Thermal Propulsion

Missions to the Kuiper belt have previously been carried out only as flybys and with very small payloads. Investigating launch windows for Kuiper belt missions supported by centrifugal nuclear thermal propulsion (CNTP) contributes to defining its operational use case. Results indicate that CNTP enables rendezvous missions to the Kuiper belt, both with direct transfer trajectories or planetary gravity assist trajectories, although there are many challenges to making these mission architectures feasible. The direct trajectories have transfer times of roughly 14 to 16 years while combining CNTP with gravity assists from Jupiter could lower transfer time to as low as 10 to 12 years to Kuiper belt objects such as Pluto and Quaoar. These missions are then shown to inform the architecture of the CNTP injection stage vehicle, which can be supported by heavy and super-heavy commercial launch vehicles with a single launch. Last, drawbacks of the mission and vehicle architectures are given that impose limits on the use case for CNTP on these missions.

Brazil’s First Steps in the Commercial Space Launch Sector: What Has Been Done in the Past Two Years?

Brazil’s First Steps in the Commercial Space Launch Sector: What Has Been Done in the Past Two Years?

Government Policy or Market Mechanism, Which Is Better for Chinese Private Rocket Enterprises

In 2015, Chinese Government issued the<i> Notice on the National Civil Space Infrastructure Medium - and Long-Term Development Plan (2015-2025)</i>, announcing that it would support and guide social capitals to participate in the application and development of national civil space infrastructure construction. Later, Chinese private companies are allowed to apply for launch licenses, breaking the traditional model of allocating funds from the state budget and developing rockets only by the "national teams". Many Chinese private rocket companies were registered and established afterwards, and some of them have successfully launched rockets several times in recent years. At the same time, Chinese private rocket enterprises are also facing with many problems, including the low success rate of rockets, the risk of rocket debris falling, high space insurance rates, space junk, talent competition, and corporate survival, etc. In 2023, the Chinese Government issued <i>Notice on Strengthening the License Management for Civil Space Launch Projects</i>, which requires the third-party liability insurance policy and space debris mitigation plan for launch licenses application, meanwhile the last sub-stage of the launch vehicle should de-orbit according to the regulations after taking measures such as passivation, using government policy tools to regulate and guide the development of private rockets. In conclusion, in order to promote the healthy development of commercial launch service industry, the market mechanism should play a leading role, while appropriately regulation and adjustment from the government policy are also needed. In addition, this paper also suggested that the Chinese government should carry out overall planning for the division of labor and product models of state-owned and private rocket companies.

Public–Private Partnering in Nuclear Reactor Development—Historical Review and Implications for Today

Abstract The dominant nuclear reactor technologies that comprise the current global operating fleet were developed and deployed over a relatively short, midtwentieth century, period spanning the 1950s and 60 s. Four of these technologies were deployed at fleet scales and commercially exported. The historical record indicates a remarkably consistent process of phased technology development that enabled the commercialization of designs that would define the global nuclear marketplace, beginning with research and development (R&D) and advancing through test reactors, small and large demonstration reactors, and first commercial-scale units. Following proof-of-principle R&D, historical commercialization lead times (from decision to construction of a demonstration reactor to first commercial launch) ranged from 12 to16 years for these four commercial technologies. Key factors contributing to successful commercialization included durable government support for early R&D and varying degrees of public–private partnering through commercial launch. This partnering included arrangements for technical support, siting, facility ownership, nuclear material provision, and cost sharing. The policy environment was characterized by unambiguous government support; stabile, effective and informed government program management and oversight; and flexibility in the public–private partnership arrangements to promote technology development and demonstration. Government advocacy was structured to support progressively increasing industry independence and self-sufficiency. This experience is documented and analyzed in this paper to provide salient lessons and example program elements for contemporary efforts to stimulate development and commercialization of a new generation of advanced nuclear technologies through collaboration and public–private partnerships.

Between Sea and Sky: Understanding Liability for Private and Commercial Space Operations

The legal framework for commercial space activities has been an emerging issue in recent decades. Understanding and addressing liability in space activities is crucial for the sustainable and responsible development of the commercial space industry, analogous to laying the foundation for a sturdy structure that can withstand the challenges of the ever-evolving space frontier. This article explores the concept of liability for private and commercial space launches and its importance in ensuring the safe and responsible operation of activities in space. Examining liability in lex maritima and commercial space law involves drawing parallels between the regulations governing both domains and uncovering potential opportunities for learning from existing legal frameworks. The analysis considers liability in various maritime zones, such as the territorial sea, high sea, and deep-sea bed, and draws comparisons to liability in the territory, space, and celestial body. It discusses the challenges and implications of addressing liability in space activities, including the allocation of liability, the protection of public safety, and the preservation of space as a shared resource.

Digestive kinetics of sorghum silages grown in the Amazon Biome

The objective of this work was to evaluate the digestibility and kinetic parameters of silages of commercial and experimental sorghum genotypes grown in a crop in amazon biome to identify materials that present the best performance. The experiment was carried out in Sinop/MT with silages from 15 genotypes to evaluate gas production and in vitro digestibility and energy estimation, including BRS 658, BRS 659, Volumax, BRS Ponta Negra, 15F30005, 15F30006, BRS 511, CMSXS 5027, 5030, 5043, 5045, BRS 716, AGRI-002E, 201934B008 and CMSXS 7501. Gas production, pH, ammonia-N, and in vitro digestibility analyses were carried out, in addition to energy estimation using equations. The silages of materials with the highest gas production and digestibility were forage because they have a greater amount of digestible carbohydrates. On the other hand, the biomass and saccharine standard biomass presented lower performance because they have a higher concentration of lignin and structural carbohydrates in their composition. For pH and ammonium-N, there was no difference between treatments. The greatest digestibility and energy potential come from the genotypes BRS 658, BRS 659 Volumax, 15F30006, CMSXS 5027, and CMSXS 5030, making the last three capable of commercial launch and use in the production of silage in animal feed.

High-speed scientific spacecraft launches with commercial launch vehicles

Reaching the outer solar system and interstellar space beyond has always been challenging due to the long distances and long travel times. Initial work on planetary gravity assists in the early 1960s by Minovitch and Flandro laid the basis for expanding reachable space with then-existing launch vehicles. Such gravity assists have been key enablers for orbital exploration missions to Mercury (MESSENGER), Jupiter (Galileo, Juno), and Saturn (Cassini-Huygens) by trading higher mass for lower launch energy from Earth (C3). They have also enabled close passes to the Sun (Parker Solar Probe) and moderately rapid solar system escape, coupled with fast flybys of various planetary-sized bodies: Mariner 10 (Mercury via Venus), Pioneer 10 (escape via Jupiter), Pioneer 11 and Voyager 1 (escape via Jupiter and Saturn), Voyager 2 (escape via Jupiter, Saturn, Uranus, and Neptune: the “Grand Tour”), and New Horizons (escape via Jupiter and Pluto). Two of these missions hold the first and second places for the most energetic launches (New Horizons: C3 = 157.7502 km2/s2; Parker Solar Probe: C3 = 152.222 km2/s2). Disadvantages in using Earth and Venus gravity assists to increase spacecraft injected mass to Jupiter and beyond include the time penalty and the need for a customized propulsion system to provide a deep-space maneuver (DSM). For “timely” transits to Neptune with a large orbiter or rapid solar system escape with an Interstellar Probe, more capable launch vehicles can be enabling by pushing the injected mass versus C3 curves “to the right.” While the most extreme speeds asymptotically away from the Sun (7–8 au/yr) can be achieved with fast Jupiter gravity assists and super heavy lift-launch vehicles (SHLLV) such as the Space Launch System (SLS) surmounted by multiple upper stages, solar system escape speeds larger than those achieved by Voyager 1 are possible with existing and upcoming large commercial launch vehicles. Such vehicles include the Falcon-Heavy, New Glenn, and Vulcan Centaur. Better performance accrues with the fully expendable versions of these vehicles and/or with “refilling” in a low-Earth orbit, with performance versus launch cost as a central trade. Even better performance can be projected with SHLLVs in development, such as the Starship Super Heavy and Long March 9. We discuss some of the possibilities and trades such newer vehicles can enable in the near term for continued – and more distant – exploration of the solar system and beyond.

Rice cultivar tolerance to florpyrauxifen-benzyl spray-applied vs. coated on urea

Abstract Complaints regarding the sensitivity of rice to florpyrauxifen-benzyl and off-target movement of the herbicide occurred following its commercial launch in 2018 in the midsouthern United States. These two concerns encouraged the exploration of an alternative application method for florpyrauxifen-benzyl in rice. A field study was conducted in 2020 and 2021 to determine if coating florpyrauxifen-benzyl on urea would reduce negative impacts of the herbicide to rice. Five commercial rice lines were evaluated: ‘Diamond’, ‘Titan’, ‘RT7321 FP’, ‘RT7521 FP’, and ‘XP753’. Florpyrauxifen-benzyl coated on urea at a 2× rate (60 g ai ha–1) reduced rice injury in one of five commercial rice lines in 2020 and four of five commercial rice lines in 2021, compared to spray applications at the same rate. In 2020, ‘RT7521 FP’ exhibited a 17-percentage point injury reduction when coating florpyrauxifen-benzyl on urea at a 2× rate vs. the same rate sprayed. In 2021, rice injury was reduced by 26, 10, and 27 percentage points in the commercial rice lines ‘Diamond’, ‘Titan’, and ‘XP753’, respectively, following coated urea vs. spray applications at 4 wk after treatment (WAT). ‘XP753’ exhibited reduced injury (15 percentage points) by coating florpyrauxifen-benzyl at a 1× rate (30 g ai ha–1) 4 WAT in 2021, and another, ‘Diamond’, had comparable groundcover to nontreated plots when florpyrauxifen-benzyl was coated on urea at a 1× rate rather than the reductions observed from the spray application at a 2× rate. Yield differences were a function of urea rate rather than application method, where in six out of ten instances greater rough rice grain yield occurred at the higher rate. Findings from this experiment indicate that coating florpyrauxifen-benzyl on urea can reduce the amount of injury observed, especially in areas of overlap where you would have a 2× rate.

Flood timing and flood loss impact on effectiveness of florpyrauxifen-benzyl coated on urea in rice

Abstract Florpyrauxifen-benzyl has generated complaints and concerns around rice injury and off-target movement to soybean since its commercial launch in 2018. Developing a precise method for applying florpyrauxifen-benzyl was imperative for its continued use. Experiments were conducted in 2020 and 2021 to evaluate rice weed control as influenced by preflood application interval and flood loss following florpyrauxifen-benzyl at 30 g ai ha−1 applied as a spray or coated on urea. In a preflood application experiment, coating florpyrauxifen-benzyl on urea and applying it the day of flood establishment and 5 and 10 d prior to flooding (DPTF) resulted in lower yellow nutsedge, broadleaf signalgrass, and barnyardgrass control than when the herbicide was spray at 3 and 5 wk after final treatment (WAFT). Coating florpyrauxifen-benzyl onto urea provided only 61% to 63% yellow nutsedge control at 3 and 5 WAFT, which was 35 to 37 percentage points lower than when the spray was applied at 5 or 10 DPTF. Likewise, rice yields following applications of florpyrauxifen-benzyl coated onto urea were 1,200 kg ha−1 less than yields following spray applications. Florpyrauxifen-benzyl coated onto urea and clomazone provided lower levels of weed control than spraying the herbicide alone, suggesting an explanation for the yield losses. The timing of flood loss experiment suggested that when florpyrauxifen-benzyl coated onto urea at 30 g ai ha−1 was applied preflood and flood was relinquished at 2 h, 24 h, and 7 d after flood establishment, hemp sesbania and yellow nutsedge control were not affected. However, loss of floodwater 2 h after flood establishment resulted in lower barnyardgrass control than when the flood was lost 24 h and 7 d after flooding. Generally, the period between a herbicide application and flooding completion should be minimized to aid in weed control. These results indicate the importance of maintaining a flood for weed control and nutrient management.

Research on the status quo and future forecast of 6G

The commercial launch of 5G has already begun globally, in the meantime, academia and industry have carried out research on 6G as planned. 6G will bring a new perspective of communication technology, incredible technological innovation, fulfilling coverage technology application, and massive scale of in-depth technology integration. This paper describes technological vision on 6G based on the current situation of mobile communication technological development, and then considers the future directions of technological development from the perspective of 6G, this paper introduces new value offered in the 6G era to support the potential use cases put forward in Chapter 4. Requirements of 6G reveal the goals of mobile developmentsmarter, faster and greener, which provide reference for industry and society in the 2030s.

The Atacama Rover Astrobiology Drilling Studies (ARADS) Project.

With advances in commercial space launch capabilities and reduced costs to orbit, humans may arrive on Mars within a decade. Both to preserve any signs of past (and extant) martian life and to protect the health of human crews (and Earth's biosphere), it will be necessary to assess the risk of cross-contamination on the surface, in blown dust, and into the near-subsurface (where exploration and resource-harvesting can be reasonably anticipated). Thus, evaluating for the presence of life and biosignatures may become a critical-path Mars exploration precursor in the not-so-far future, circa 2030. This Special Collection of papers from the Atacama Rover Astrobiology Drilling Studies (ARADS) project describes many of the scientific, technological, and operational issues associated with searching for and identifying biosignatures in an extreme hyperarid region in Chile's Atacama Desert, a well-studied terrestrial Mars analog environment. This paper provides an overview of the ARADS project and discusses in context the five other papers in the ARADS Special Collection, as well as prior ARADS project results.

HTA304 The Impact of Different HTA Frameworks on Time to Patient Access: A Case Study Assessing the First Commercial Launch Indications for Lynparza, Tagrisso, Imfinzi, Calquence and Enhertu

HTA304 The Impact of Different HTA Frameworks on Time to Patient Access: A Case Study Assessing the First Commercial Launch Indications for Lynparza, Tagrisso, Imfinzi, Calquence and Enhertu

Interoperable data exchange for safe and efficient launch and re-entry operations in an international environment

The frequency of commercial space launch and re-entry operations is increasing worldwide. Current regulations and procedures ensure safe operations by temporarily closing large volumes of airspace where risks to aircraft would exist in case of non-nominal events during launch or re-entry operations. To maintain the safety of air traffic as the number of space operations rises, effectively providing the right information to the right stakeholders at the right time is key. Through a cooperative agreement, the FAA and DLR are sharing their unique capabilities using the Commercial Space Integration Lab and Air Traffic Validation Center, located in the USA and Germany respectively, to improve situational awareness through real-time data exchange. The project seeks to answer whether U.S. and European ANSPs can respond adequately to a non-nominal event during a launch or re-entry operation that presents a hazard to the airspace system. It leverages existing international data standards and infrastructures by using a data exchange approach based on System Wide Information Management (SWIM). Within the project an initial assessment of the processes, roles and responsibilities for implementing launch and re-entry events in the air traffic systems on both sides of the Atlantic, as well as the requirements for basic functions and performance parameters of a SWIM-based integration, have been completed. The project developed a demonstration model across all system levels as far down as to the ANSPs, namely to the air traffic controllers. Through a series of demonstrations, covering launch scenarios from the U.S. with possible effects on European airspace and vice versa, the project evaluated the technical and operational feasibility of the concept. The key data parameters identified during the analyses shall enable information sharing among various users within the U.S. and European global airspace system. It has been shown, that the systems on both sides of the Atlantic could be connected via standardized protocols und used successfully for exercises in different scenarios. Further research on the best integration of the processes in international Air Traffic Management (ATM) networks and domains will be the follow-on.

Field test and sensitivity of Onchocerciasis rapid test in Ogun State, Nigeria

Objective: This study, conducted between March 2015 and July 2016, investigated the sensitivity and specificity of the OV-16 RDT and Dried Blood Spot (DBS) Enzyme-Linked Immunosorbent Assay (ELISA) for skin snip microfilaria (MF) detection in Ogun State.
 Methods: Five hundred and eighty-eight (588) members of 16 first-line communities in 8 endemic Local Government Areas (LGAs) provided fingerstick whole blood specimens examined for IgG4 antibodies against the O. volvulus antigen OV-16, using DBS OV-16 ELISA and OV-16 RDT. In consort with these specimens, 162 study participants consented to be evaluated by skin snip.
 Results: Results showed a seroprevalence of 106(18.0%) using ELISA and 102(17.3%) by RDT, with 92.2% agreement. The OV-16 RDT demonstrated a positive and negative agreement of 76.4 (95% CI 67.2 to 84.1%) and 95.6% (95% CI: 93.4 to 97.3), respectively, to the OV-16 ELISA results from the concordant dataset. Against the 64 positive skin snips microscopy results, sensitivity of the RDT was 79.7% (95% CI 73.43% to 85.27) and the ELISA was 70.3% (95% CI 64.72% to 75.37%).
 Conclusion: The results of this study provided information on the performance of the OV-16 RDT. This information will contribute data for comparison to studies in other areas where treatment is ongoing. In conclusion, the commercial launch of the OV-16 RDT has made available a point-of-care diagnostic tool that could serve to help local and country onchocerciasis elimination programs to measure changes and progress in onchocerciasis intervention.

Normative Behavior Incentives for Space Activities: Sustaining Momentum

ABSTRACT The preponderance of space activity is no longer dictated by governments; the commercial sector has grown more than 250% in the last decade. With the proliferation of commercial constellations and launches, there is an imperative to determine how best to shape normative behavior in space that works to increase the overall sustainability and security of space. This work aims to answer how the U.S. government can best incentivize widespread compliance with best practices in space that will eventually become norms for states and commercial entities alike. These incentives range from compensatory to punitive, and include a financial component. Without widespread adaptation to a set of norms, the increasing congestion of strategically important space geography will continue to threaten both states and private companies and potentially render these near-Earth orbits useless to future generations.

Real world safety of methoxyflurane analgesia in the emergency setting: a comparative hybrid prospective-retrospective post-authorisation safety study

BackgroundLow-dose analgesic methoxyflurane (Penthrox®) was approved in Europe for emergency relief of moderate to severe pain in conscious adults with trauma in 2015. A comparative post-authorisation safety study (PASS) was conducted to assess the risk of hepatotoxicity and nephrotoxicity with methoxyflurane during routine clinical practice.MethodsThis was a comparative hybrid prospective-retrospective cohort study. The comparative cohorts consisted of adults who were given methoxyflurane (methoxyflurane cohort) or another analgesic (concurrent cohort) routinely used for moderate to severe trauma and associated pain in the emergency setting (ambulance and Emergency Department) in the UK between December 2016 and November 2018. Hepatic and renal events were captured in the ensuing 12 weeks. A blinded clinical adjudication committee assessed events. A historical comparator cohort (non-concurrent cohort) was identified from patients with fractures in the English Hospital Episode Statistics (HES) accident and emergency database from November 2013 and November 2015 (before commercial launch of methoxyflurane). Hepatic and renal events were captured in the ensuing 12 weeks via linkage with the Clinical Practice Research Datalink (CPRD) and HES hospital admissions databases.ResultsOverall, 1,236, 1,101 and 45,112 patients were analysed in the methoxyflurane, concurrent and non-concurrent comparator cohorts respectively. There was no significant difference in hepatic events between the methoxyflurane and concurrent cohorts (1.9% vs. 3.0%, P = 0.079) or between the methoxyflurane and non-concurrent cohorts (1.9% vs. 2.5%, P = 0.192). Renal events were significantly less common in the methoxyflurane cohort than in the concurrent cohort (2.3% vs. 5.6%, P < 0.001). For methoxyflurane versus non-concurrent cohort the lower occurrence of renal events (2.3% vs. 3.2%, P = 0.070) was not statistically significant. Multivariable adjustment did not change these associations.ConclusionsMethoxyflurane administration was not associated with an increased risk of hepatotoxicity or nephrotoxicity compared with other routinely administered analgesics and was associated with a reduced risk of nephrotoxicity compared with other routinely administered analgesics.Trial registrationStudy registered in the EU PAS Register (ENCEPP/SDPP/13040).