Joint Program Office Research Articles

Exosome‐Encapsulated Persistent Luminescence Nanoparticles Enabled Medicinal Product‐Based Drug Delivery System

IntroductionRecent studies have found that exosome or extracellular vesicles (EVs) are associated with cancer metastasis, disease progression, diagnosis and treatment, making cell research a hot emerging research area. Instead, cells would send them out via exocytosis. This has also been observed for other rigid nanoparticles such as silica and carbon. Relying on the superior targeting function and biocompatibility of cancer exosomes, they were able to deliver the drug to cancer stem cells deep inside the tumor in mouse models.ChallengeDespite significant efforts made in this relatively new field of exosome research, progress has been held back by challenges such as inefficient separation methods, difficulties in characterization, and lack of specific biomarkers. Moreover, the applications of exosome still need more evaluation for the true condition.ActionPersistent luminescence nanoparticles (PLNs) result in their powerful in vivo near‐infrared fluorescence, thus generating remarkable tumors imaging tracking ability in subcutaneous, orthotopic and metastatic tumors. Our study provides an approach for cancer therapy by using exosome‐biomimetic nanoparticles named PLN@tExo exocytosed by the Transwell channel electroporation (TEP) process. The PLN@tExo can be applied for drug carriers to efficiently deliver the anticancer drug into the center of cancer cells.ResolutionThe biocompatible exosome‐sheathed PLNs (Dox‐PLN@tExo) have been synthesized for targeted cancer chemotherapy. Dox‐PLN@tExos are exocytosed from cells after the TEP process. Following intravenous injection, Dox‐PLN@tExos actively accumulate in the tumor site and cross‐reactive cellular uptake by cancer cells, resulting in augmented in vivo DOX enrichment in tumor cells. Our study clearly demonstrates that exosome‐biomimetic nanoparticles have potential as drug carriers to improve anticancer efficacy.Support or Funding InformationThis research was supported by Academia Sinica [AS‐SUMMIT‐108] to MH and Academia Sinica Joint Program Office [AS‐NTU‐108‐01] to MH.The scheme figure shows the exocytotic pathway can generate therapeutic exosome and encapsulate the nanoparticles as a targeting anticancer nanovehicle.Figure 1The confocal image shows the NEP process actively sends the nanoparticles into the cytosol. Moreover, the transport effect is better than incubated‐nanoparticle directly.Figure 2

Upconversion Nanoparticles Induce Lung Inflammatory, Immunologic and Pulmonary Injury in Vivo

IntroductionEngineered nanoparticles which are developed for multiple uses are defined as those in which the one‐dimensional length is in the range of 1 – 100 nm. Nanoparticles enter the exposure pathway of the organism and are now known to enter the path via the respiratory tract, skin penetration, oral ingestion, and via injection. As an emerging optical nanomaterial, the study of the effects of upconversion nanoparticles (UCNP) on organisms has not yet been discussed. Recently, many studies use this UCNP for lung cancer treatment, so it can be detecting the deposition of the lungs, which will lead to the poisoning of lung tissue.ChallengeThe main effects on the lung tissue caused by the entry of the respiratory tract into the organism are cytotoxicity, inflammatory response, early pulmonary fibrosis, oxidative stress, inhibition of the immune system, increased chance of infection by microorganisms, and even cancer. But the toxicity test of nanoparticles. Technically, there is still no standard test method.ActionTo elucidate the UCNP‐induced cytotoxicity at the molecular level, we try to measure the gene expression changes in human THP‐1 derived macrophages exposed to UCNP for 24 h evaluating be affymetrix microarrays. To analyze the complicated genome‐wide gene expression data, we introduced a computational method to decipher the molecular cytotoxic mechanisms induced by UCNP exposure on the macrophages.ResolutionBased on the comprehensive and detailed molecular characterization of UCNP‐induced cytotoxicity, to our knowledge, it has not been achieved previously, and this study provides an important insight into the molecular mechanisms involved in UCNP‐induced lung inflammatory, immunologic and pulmonary Injury.Support or Funding InformationThis research was supported by Academia Sinica [AS‐SUMMIT‐108] to MH and Academia Sinica Joint Program Office [AS‐NTU‐108‐01] to MH.The actual operation of IT.Figure 1(a) The schematic imaging shows the IT drug administration. (b) The PLNs persistent luminescence can achieve an in vivo test that arrived at 6 hr. (c) The truly tumor size evaluation of lung tissue. (d) The luminescence of CL1‐5 cell line and PLN fluorescence signalFigure 2

A model of interior cockpit noise for the F-35A

Characterization of environmental noise is vital to protection of hearing. A measurement campaign to understand the nature of the noise in the cockpit of fifth-generation fighter aircraft has been completed. Measurements during multiple missions for each variant of the F-35 aircraft characterized the cockpit acoustic levels during various stages of flight. Additional data collection defined the aircraft state during the acoustic data collection. An initial model of the F-35A represents the A-weighted overall sound pressure level (LA) within the cockpit by a series of random decision forest models. Sensitivity analysis conducted on these models demonstrates that airspeed and the environmental control system (ECS) flow rate are the two most important parameters determining the interior acoustic levels. However, the measurements cover a subset of the full dynamic envelope of the aircraft. Since machine-learning algorithms are susceptible to greater uncertainty where no acoustic data exists, a curve fit model defines acoustic levels throughout the envelope. This model adds the ECS flow rate to the dynamic pressure calculations and produces a more accurate model of LA within the cockpit of the F-35A. This research is sponsored, in part, by F-35 Joint Program Office.

Megacities and the US Army

ABSTRACT: The urban environment is a known vulnerability for US forces, and grows more acute as megacities increase around the world. This article describes past research and joint experimentation efforts concerning urban environments and identifies critical gaps for further research and experimentation. A more committed Joint Force constituency, led by the US Army, can lead to better readiness in this area. ********** The US Army is currently examining the topic of megacities and how to train, organize, and equip itself for successful operations in them. As a recent report from the Army Chief of Staff's Strategic Studies Group stressed, it is inevitable that at some point the United States Army will be asked to operate in a megacity and currently the Army is ill-prepared to do so. (1) As other authors have noted, Army researchers have determined megacities, urban concentrations exceeding 10 million people, will be the most complex environments for future land Global growth trends also suggest the importance of such complex environments is increasing, ... since the places where people live are getting increasingly crowded, urban, coastal and networked, the wars people fight will take on the same characteristics. (2) Given such trends, the Army is justified in asking whether current urban operating concepts and capabilities will suffice to accomplish future national security objectives. Numerous studies related to urban operations exist, all with different focus areas and outcomes, some of which are inconsistent or incomplete. In fact, as this article maintains, the current Department of Defense (DoD) urban strategy is on an uncertain trajectory and is in need of new leadership. Until its closure in 2011, Joint Forces Command (JFCOM) supported other geographic combatant commands advocating for, and developing, future concepts for joint warfighting. However, the closure of JFCOM and its inability to obtain approval of a Joint Capabilities Document stalled urban concept development. Perhaps JFCOM was never the best choice for this endeavor but merely a pragmatic one, given the Army's preoccupation with the wars in Iraq and Afghanistan. Nevertheless, DoD needs another organization to refresh its dated urban strategy and capitalize on JFCOM's prior work. What organization is best suited for addressing this projected challenge? Establishing yet another ad hoc joint task force is neither optimal or desirable. Giving responsibility to the Joint Staff seems misplaced because is not charged with organizing, training, and equipping the force. Creating a joint program office is an option, but only desirable if one of the military services is willing to lead as the Joint Executive Agent. The Title X statute prescribes that the three services organize, train, and equip their respective forces. It is unlikely the Air Force or Navy would give priority to this effort. The Marine Corps contributes greatly to urban concept development; however, the Marine Corps as an amphibious force does not view urban operations as a core competency. Among the services, the Army provides the largest share of the capability and capacity for operating in urban environments. As the nation's predominant land force, the task of reviving DoD's dormant urban strategy logically falls to the Army. Originating Directives The 2014 Army Operating Concept (AOC) builds a narrative of future warfare describing urban operating environments as likely to have significant impact on land force operations. (3) Clearly, land forces must prepare for all future operating environments and cannot organize, train, and equip exclusively for urban battle-spaces. Forces should be tailored to provide the maximum flexibility to deal with a wide range of operating environments, conflicts, and contingencies. The Army must transform current forces with new capabilities for urban operating environments. …

The Origins of Miniature Global Positioning System-Based Navigation Systems [SP History

For the past decade or so, the Navigation Signal Timing and Ranging Global Positioning System (NAVSTAR GPS) has been synonymous with personal navigation. We find GPS in our smartphones, tablets, cars, aircraft, and boats. But how did it get that way? The U.S. Department of Defense (DoD) established the NAVSTAR GPS Joint Program Office (JPO) (GPS JPO) in 1973 to make the GPS a military and civilian reality [1]?[3]. However, its receivers were large and heavy and not very attractive to military and civilian personnel without vehicles. It wasn?t until the mid-1980s that miniature GPS receiver (GPSR) and inertial navigation system (INS) technologies came into being, whose architectures became the standards for both the military and commercial precise navigation markets after the 1991 Desert Storm military campaign [4].

Mine Resistant Ambush Protected (MRAP) Vehicle

Soldiers in Iraq are dying in increasing numbers from improvised explosive devices planted in roads by insurgents. Up-armored Humvees offer little to no protection. Specialty vehicles with v-shaped bottoms to deflect blasts had been developed in South Africa and Rhodesia in the 1970s.The MRAP Vehicle Joint Program Office's mission is to procure up to 20,000 of these commercial off-the-shelf vehicles and get them to Iraq within 30 months. Yet U.S. production is fewer than 10 vehicles per month because not enough tires, ballistics-grade steel, and other raw materials are available. The daunting task: to undertake the fastest vehicle procurement since the Jeep in World War II, ramping up the industrial base, and overcoming the bureaucratic logjam in Department of Defense procedures.

Mine Resistant Ambush Protected (Mrap) Vehicle

This case is about the strategic-sourcing process: leading a major acquistion program with an unprecedented schedule and an unprepared industrial base. Soldiers in Iraq are dying in increasing numbers from improvised explosive devices planted in roads by insurgents. Up-armored Humvees offer little to no protection. Specialty vehicles with v-shaped bottoms to deflect blasts had been developed in South Africa and Rhodesia in the 1970s. The MRAP Vehicle Joint Program Office's mission was to procure up to 20,000 of these commercial off-the-shelf vehicles and get them to Iraq within 30 months. Yet U.S. production is fewer than 10 vehicles per month because not enough tires, ballistics-grade steel, and other raw materials are available. The daunting task: to undertake the fastest vehicle procuremenet since the Jeep in World War II, ramping up the industrial base, and overcoming the bureaucratic logjam in Departmert of Defense procedures.

KR03 Global Positioning System (GPS) Systems Engineering Case Study

AbstractThe Global Positioning System (GPS) Systems Engineering Case Study (O'Brien & Griffin, 2008) describes the application of systems engineering during the concept validation, system design and development, and production phases of the GPS program. The case examines the applied systems engineering processes, as well as the interactions of the GPS Joint Program Office, the prime contractors, and the plethora of government agencies that were associated with the programs development and fielding. The systems engineering process is traced from the initiation of studies and the development of key technologies that established the vision of a satellite navigation system in the 1960s, through the multi‐phase joint program that resulted in a full operational capability release in 1995. Numerous interviews were conducted with individuals who personally directed, managed and engineered the program, from which the systems engineering story emerged. Results are organized using the Friedman‐Sage Framework

Report Notes Benefits, Costs, and Lessons Learned from ITS Applications

This article describes a report released by the U.S. Department of Transportation (DOT) in which data collected by the DOT’s Intelligent Transportation Systems (ITS) Joint Program Office (JPO) offers a look at the benefits, costs, and lessons learned from ITS The report, an update to the 2003 report, expands the earlier versions by including summaries of the lessons learned from various ITS planning, deployment, operation, maintenance, and evaluation experiences. The report also examines the benefits and costs of different components comprising intelligent infrastructure. This includes technologies such as arterial management systems, freeway and incident management systems, and electronic payment systems. The report also describes a system developed by the authors in which a rating is assigned to a technology based on the findings in the ITS Benefits Database. By using the ratings derived from case studies in the Database, readers may be able to assess the applicability of a particular technology before pursuing actual implementation.

Part 3: Technology: Creating Intelligent, Coordinated Transit: Moving New Mexico the Smart Way

New Mexico is among the first states in the United States to develop, implement, and deploy contactless, smart card technology in a rural area. The Alliance for Transportation Research Institute, working with the New Mexico Department of Transportation's Public Transportation Programs Bureau, developed the Intelligent, Coordinated Transit (ICTransit) smart card technology and the Client, Referral, Ridership, and Financial Tracking (CRRAFT) software. The U.S. Department of Transportation's FTA-FHWA Joint Program Office provided federal funding for the project. The ICTransit smart card functions as a universal use electronic fare card, enabling passengers to transfer between transit providers to access jobs, education, and health care beyond their local rural communities. ICTransit's Global Positioning System receiver and Pocket PC capture the time and location that passengers board and exit the vehicle and the passenger miles traveled on the vehicle. The CRRAFT software system for express scheduling, autom...

Creating Intelligent, Coordinated Transit

New Mexico is among the first states in the United States to develop, implement, and deploy contactless, smart card technology in a rural area. The Alliance for Transportation Research Institute, working with the New Mexico Department of Transportation's Public Transportation Programs Bureau, developed the Intelligent, Coordinated Transit (ICTransit) smart card technology and the Client, Referral, Ridership, and Financial Tracking (CRRAFT) software. The U.S. Department of Transportation's FTA–FHWA Joint Program Office provided federal funding for the project. The ICTransit smart card functions as a universal use electronic fare card, enabling passengers to transfer between transit providers to access jobs, education, and health care beyond their local rural communities. ICTransit's Global Positioning System receiver and Pocket PC capture the time and location that passengers board and exit the vehicle and the passenger miles traveled on the vehicle. The CRRAFT software system for express scheduling, automatic generation of monthly financial reports, and onboard tracking of ridership provides increased efficiency in rural areas. The ICTransit system with CRRAFT can overcome barriers to coordinated interagency transportation and provide increased access and mobility to all, but especially to those underserved by public transportation. ICTransit with CRRAFT can empower states to build coordinated transportation networks that provide safe and seamless movement of people and enhance the quality of life.

Seattle Metropolitan Model Deployment Initiative Evaluation: Results and Key Findings from Modeling

At the request of the Joint Program Office for intelligent transportation systems (ITS) of the FHWA, Mitretek Systems conducted a modeling analysis of ITS impacts in support of the metropolitan model deployment initiative evaluation program. The Mitretek modeling study supports the evaluation of the Seattle model deployment Smart Trek, testing a series of hypotheses that could not be addressed in controlled field studies or survey research. Using both a regional planning model and a subarea simulation, the study includes a series of experiments to quantify impacts from integrating ITS technologies and services both across jurisdictions and between functional components. The analysis addressed ( a) subarea-wide impacts of traffic signal coordination on major arterials, ( b) the impact of integrating arterial data into the current freeway-based advanced traveler information service (ATIS), and ( c) interactions at the corridor and the regional levels from concurrent deployment of signal coordination and the enhanced freeway and arterial ATIS. Results from that study have been summarized, detailing findings for a 300-km2 mixed freeway and arterial subarea network drawn from the roadway system north of downtown Seattle. The coordination of traffic signals along two major arterials resulted in a 7 percent reduction in overall subarea delay and a 3 percent reduction in total stops. More efficient route diversions for ATIS users result from the integration of arterial data into the current web-based service. At currently estimated levels of ATIS usage (6 percent of travelers), this improved diversion efficiency reduces overall subarea delay (users and nonusers) by over 3 percent.

Ada conformity assessments

This paper presents the actual status of Ada Conformity Assessments after the transition of Ada Conformity Assessments from the Ada Joint Program Office to ISO. The principles of Ada Conformity Assessments according to the ISO/IEE Final Committee Draft 18009 are summarized and the commonalties and differences to the previous practices are discussed. In the main part of the work conformity assessments for Ada C, C++, and Java are compared. It is shown that the process as practiced with Ada is unique compared to other programming languages. This can be understood by looking at the special culture of the language Ada and its validation system. Both were sponsored by one single party (the US DoD) and not the IT industry. The paper concludes with an assessment and outlook on the future development on compiler conformity assessments in general.

Open systems ADA technology demonstration program

On 20 March, 1997 McDonnell Douglas Aerospace (now Boeing), and NAWC-China Lake conducted a demonstration flight as part of the Open Systems Ada Technology (OSAT) program, co-sponsored by the Ada Joint Program Office, the Open Systems Joint Task Force, and the Joint Strike Fighter Program Office. The flight, of a specially modified AV-8B Harrier, accomplished several key objectives: first known application of the Ada95 programming language to flight software; application of the POSIX commercial standard in a real-time flight software domain; application of commercial hardware, software and development tools to avionics; demonstration and evaluation of object oriented design and mixed programming languages for real-time flight software; application and evaluation of data error detection/compensation technology developed by Wright Laboratory under the Data Fusion Integrity Process (DFIP) Program. The test aircraft was a two-seat TAV-8. The host mission computer was an improved version of the PowerPC 604 system, which was employed in MDA's Common Operational Flight Program (OFF) demonstration flights in 1996. The test profile entailed six releases of MK-76 practice bombs over China Lake's Baker Range, using different dive angles and release altitudes. Although accuracy was not an explicit test objective, all six drops were scored as hits under standard accuracy criteria. This paper summarizes selected key findings and lessons learned which resulted from this program.

Ada 95 conformity assessment - Phil Brashear

On September 30, 1998, the Ada Resource Association (ARA) accepted responsibility to continue the activities of the Ada Joint Program Office (AIPO), as part of transitioning Ada support from government to private industry. The ARA is promoting Ada in a variety of areas. One primary responsibility is the continuation of the Ada compiler validation process.The ARA considered it necessary to distance the vendors that comprise the ARA from the validation process itself. Consequently, the ARA is supporting the activities of the Ada Working Group (JTC1/SC22/WG9) within the International Organization for Standards (ISO) to standardize the existing validation processes. To become a standard, the Ada validation terminology must be changed to match ISO terminology (for example, validation is replaced with conformance assessment). The actual validation procedures supported by the ARA are largely unchanged from those under the AJPO, with a few minor changes to reduce bureaucracy, improve reproducibility, and more easily integrate language maintenance. A number of independent organizations will work together to perform and oversee validations.The revised procedures are in use while waiting for the actual ISO approval. To date, seven conformity assessments by two vendors have been performed using the new procedures and organization.

Open systems Ada technology demonstration program

On 20 March 1997 McDonnell Douglas Aerospace (now Boeing), and NAWC-China Lake conducted a demonstration flight as part of the Open Systems Ada Technology (OSAT) program, co-sponsored by the Ada Joint Program Office, the Open Systems Joint Task Force, and the Joint Strike Fighter Program Office. The flight, of a specially modified AV-8B Harrier, accomplished several key objectives: (1) first known application of the Ada95 programming language to flight software; (2) application of the POSIX commercial standard in a real-time flight software domain; (3) application of commercial hardware, software and development tools to avionics; (4) demonstration and evaluation of object oriented design and mixed programming languages for real-time flight software; and (5) application and evaluation of data error detection/compensation technology developed by Wright Laboratory under the Data Fusion Integrity Process (DFIP) Program. The test aircraft was a two-seater TAV-8, flown by USMC Maj. Mark Werth. The host mission computer was an improved version of the PowerPC 604 system, which was employed in MDA's Common Operational Flight Program (OFP) demonstration flights in 1996. The test profile entailed six releases of Mk-76 practice bombs over China Lake's Baker Range, using different dive angles and release altitudes. Although accuracy was not an explicit test objective, all six drops were scored as hits under standard accuracy criteria.

Analysis and Recommendation for Reuse of the L1 and L2 GPS Spectrum

This paper documents a year-long (July 1997-1998) scoring process led by the GPS Joint Program Office (JPO) and Space Warfare Center (SWC) to identify the best signal structure for the next 30 years of military and civilian GPS applications. The focus of this analysis was on waveform design for the reuse of the existing L1 and L2 GPS frequency allocations. The requirements for a new signal structure are explained, and the candidate waveform options are introduced. The scoring criteria and decision analysis are developed. The resulting waveform scores are presented by overall ranking and in terms of their scores by major criteria category. Civilian and military user preferences are also addressed. Finally, a waveform recommendation for reuse of both the L1 and L2 GPS frequencies is presented.

Results of the GPS JPO's GPS Performance Baseline Analysis: The GOSPAR Project*

The GPS Operational Control System (OCS) Performance Analysis and Reporting (GOSPAR) project was initiated by the GPS Joint Program Office (JPO) to establish an in-depth definition of current GPS Precise Positioning Service (PPS) performance characteristics. This paper provides a description of the key findings of the GOSPAR project to date. Specifically, the following topics are addressed: project overview, performance metric review, how GPS is doing, why GPS is doing so well, and bottom line to users. The results of the GOSPAR project have established a GPS performance baseline and set the stage for development of the next-generation GPS OCS. The next-generation OCS has as an objective to reduce GPS PPS user range errors (UREs) to 1.5 m root mean square (RMS) or better.

Object-oriented Ada-based development of highly reusable control software

This paper discusses the object-oriented design paradigm versus the traditional applications development model, in the context of software reuse. The features of the Ada 1 1 Ada is a registered trademark of the US DoD — Ada Joint Program Office (AJPO). language are explored, with particular emphasis on the aspects that promote reuse and that make Ada 9X — the successor to Ada 83 — an increasingly sound choice for developing and maintaining large, embedded, object-oriented applications for real-time control.

Testing the precision lightweight GPS receiver

Innovative field testing techniques are employed at Holloman Air Force Base to help the Global Positioning System (GPS) NAVSTAR Joint Program Office (JPO) test the Precision Lightweight GPS Receiver (PLGR). Characterizing the PLGR's accuracy in dynamic environments is of prime importance but testing also prescribes the evaluation of its ability to receive differential GPS corrections, real time, and its Electronic Counter Counter Measures. To meet these goals, the 46th Test Group provides the C-12 cargo aircraft for flight testing, an instrumented test van for mobile testing, the High Speed Test Track for high velocity testing, a UH-1 helicopter for rotor blade modulation testing, and special PC laptops for ground troop testing. All of these test capabilities utilize Holloman's well instrumented test environments with thousands of surveyed sites validated by the Defense Mapping Agency. This paper emphasizes the testing techniques that are helping to define Test & Evaluation methodologies for the changing world where Global Positioning with NAVSTAR is becoming a reality.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>