Toward Synthesizing a Selective Dopamine Binding Magnetic Resonance Contrast Agent

Magnetic resonance imaging (MRI) is a non-invasive diagnostic methodology used to provide a two-dimensional view of an internal organ or structure, especially the brain and spinal cord. Magnetic resonance contrast agents are usually injected into necessary parts of the body prior to imaging to increase the differences between different tissues or between normal and abnormal tissue, making it easier for a radiologist or doctor to interpret the image that is taken. The development of new and more efficient, effective, and selective contrast agents for various biological processes or chemicals is a growing field of research and study. My project allowed me to engage in undergraduate chemistry research in an academic setting under the supervision of an organic chemistry professor, Dr. DeBoef. He designed a molecule that will be developed further to be a magnetic resonance contrast agent, also referred to as an MRI probe. Reactions were carried out that were the beginning steps of the multi-step synthesis, or recipe, if you will, to make the target molecule which also binds gadolinium, making it MRI active (Figure 1). The entire multi-step synthesis is not included in this paper. The purpose of his design is for the molecule to selectively bind dopamine (Figure 2), a neurotransmitter that has been found to be associated with Parkinson’s Disease in humans. His molecule’s design is based on existing contrast agent structures published in chemical literature but is a new molecule after changes and additions were made. It can be years later before it will be tested for use in MRI as a contrast agent that is safe for use in humans

Developmental Effects of Perfluorononanoic Acid in the Mouse Are Dependent on Peroxisome Proliferator-Activated Receptor-Alpha

Perfluorononanoic acid (PFNA) is one of the perfluoroalkyl acids found in the environment and in tissues of humans and wildlife. Prenatal exposure to PFNA negatively impacts survival and development of mice and activates the mouse and human peroxisome proliferator-activated receptor-alpha (PPARα). In the current study, we used PPARα knockout (KO) and 129S1/SvlmJ wild-type (WT) mice to investigate the role of PPARα in mediating PFNA-induced in vivo effects. Pregnant KO and WT mice were dosed orally with water (vehicle control: 10 ml/kg), 0.83, 1.1, 1.5, or 2 mg/kg PFNA on gestational days (GDs) 1–18 (day of sperm plug = GD 0). Maternal weight gain, implantation, litter size, and pup weight at birth were unaffected in either strain. PFNA exposure reduced the number of live pups at birth and survival of offspring to weaning in the 1.1 and 2 mg/kg groups in WT. Eye opening was delayed (mean delay 2.1 days) and pup weight at weaning was reduced in WT pups at 2 mg/kg. These developmental endpoints were not affected in the KO. Relative liver weight was increased in a dose-dependent manner in dams and pups of the WT strain at all dose levels but only slightly increased in the highest dose group in the KO strain. In summary, PFNA altered liver weight of dams and pups, pup survival, body weight, and development in the WT, while only inducing a slight increase in relative liver weight of dams and pups at 2 mg/kg in KO mice. These results suggest that PPARα is an essential mediator of PFNA-induced developmental toxicity in the mouse

Live birth following double-factor pre-implantation genetic diagnosis for both reciprocal translocation and alpha-thalassaemia

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Development of a 150-GHz MMIC Module Prototype for Large-Scale CMB Radiation

HEMT-based receiver arrays with excellent noise and scalability are already starting to be manufactured at 100 GHz, but the advances in technology should make it possible to develop receiver modules with even greater operation frequency up to 200 GHz. A prototype heterodyne amplifier module has been developed for operation from 140 to 170 GHz using monolithic millimeter-wave integrated circuit (MMIC) low-noise InP high electron mobility transistor (HEMT) amplifiers. The compact, scalable module is centered on the 150-GHz atmospheric window using components known to operate well at these frequencies. Arrays equipped with hundreds of these modules can be optimized for many different astrophysical measurement techniques, including spectroscopy and interferometry. This module is a heterodyne receiver module that is extremely compact, and makes use of 35-nm InP HEMT technology, and which has been shown to have excellent noise temperatures when cooled cryogenically to 30 K. This reduction in system noise over prior art has been demonstrated in commercial mixers (uncooled) at frequencies of 160-180 GHz. The module is expected to achieve a system noise temperature of 60 K when cooled. An MMIC amplifier module has been designed to demonstrate the feasibility of expanding heterodyne amplifier technology to the 140 to 170-GHz frequency range for astronomical observations. The miniaturization of many standard components and the refinement of RF interconnect technology have cleared the way to mass-production of heterodyne amplifier receivers, making it a feasible technology for many large-population arrays. This work furthers the recent research efforts in compact coherent receiver modules, including the development of the Q/U Imaging ExperimenT (QUIET) modules centered at 40 and 90 GHz, and the production of heterodyne module prototypes at 90 GHz

Cryogenic MMIC Low Noise Amplifiers for W-Band and Beyond

We discuss results of low noise amplifier Monolithic Millimeter-wave Integrated Circuits (MMICs), which were designed for specific frequencies in the range of 70-200 GHz. We report on room temperature and cryogenic noise performance for a variety of circuits. The designs utilize Northrop Grumman Corporation’s (NGC) 35 nm gate length InP HEMT technology. Some of the lowest reported noise figures to date have been observed with this process at cryogenic temperatures

Cryogenic 160-GHz MMIC Heterodyne Receiver Module

A cryogenic 160-GHz MMIC heterodyne receiver module has demonstrated a system noise temperature of 100 K or less at 166 GHz. This module builds upon work previously described in Development of a 150-GHz MMIC Module Prototype for Large-Scale CMB Radiation (NPO-47664), NASA Tech Briefs, Vol. 35, No. 8 (August 2011), p. 27. In the original module, the local oscillator signal was saturating the MMIC low-noise amplifiers (LNAs) with power. In order to suppress the local oscillator signal from reaching the MMIC LNAs, the W-band (75 110 GHz) signal had to be filtered out before reaching 140 170 GHz. A bandpass filter was developed to cover 120 170 GHz, using microstrip parallel-coupled lines to achieve the desired filter bandwidth, and ensure that the unwanted W-band local oscillator signal would be sufficiently suppressed. With the new bandpass filter, the entire receiver can work over the 140 180-GHz band, with a minimum system noise temperature of 460 K at 166 GHz. The module was tested cryogenically at 20 K ambient temperature, and it was found that the receiver had a noise temperature of 100 K over an 8-GHz bandwidth. The receiver module now includes a microstrip bandpass filter, which was designed to have a 3-dB bandwidth of approximately 120-170 GHz. The filter was fabricated on a 3-mil-thick alumina substrate. The filter design was based on a W-band filter design made at JPL and used in the QUIET (Q/U Imaging ExperimenT) radiometer modules. The W-band filter was scaled for a new center frequency of 150 GHz, and the microstrip segments were changed accordingly. Also, to decrease the bandwidth of the resulting scaled design, the center gaps between the microstrip lines were increased (by four micrometers in length) compared to the gaps near the edges. The use of the 150-GHz bandpass filter has enabled the receiver module to function well at room temperature. The system noise temperature was measured to be less than 600 K (at room temperature) from 154 to 168 GHz. Additionally, the use of a W-band isolator between the receiver module and the local oscillator source also improved the noise temperature substantially. This may be because the mixer was presented with a better impedance match with the use of the isolator. Cryogenic testing indicates a system noise temperature of 100 K or less at 166 GHz. Prior tests of the MMIC amplifiers alone have resulted in a system noise temperature of 65.70 K in the same frequency range (.160 GHz) when cooled to an ambient temperature of 20 K. While other detector systems may be slightly more sensitive (such as SIS mixers), they require more cooling (to 4 K ambient) and are not as easily scalable to build a large array, due to the need for large magnets and other equipment. When cooled to 20 K, this receiver module achieves approximately 100 K system noise temperature, which is slightly higher than single-amplifier module results obtained at JPL (65.70 K when an amplifier is corrected for back-end noise contributions). If this performance can be realized in practice, and a scalable array can be produced, the impact on cosmic microwave background experiments, astronomical and Earth spectroscopy, interferometry, and radio astronomy in general will be dramatic

Technology developments for a large-format heterodyne MMIC array at W-band

We report on the development of W-band (75–110 GHz) heterodyne receiver technology for large-format astronomical arrays. The receiver system is designed to be both mass producible, so that the designs could be scaled to thousands of receiver elements, and modular. Most of the receiver functionality is integrated into compact monolithic microwave integrated circuit (MMIC) amplifier-based multichip modules. The MMIC modules include a chain of InP MMIC low-noise amplifiers, coupled-line bandpass filters, and sub-harmonic Schottky diode mixers. The receiver signals will be routed to and from the MMIC modules on a multilayer high-frequency laminate, which includes splitters, amplifiers, and frequency triplers. A prototype MMIC module has exhibited a band-averaged noise temperature of 41 K from 82 to 100 GHz and a gain of 29 dB at 15 K, which is the state-of-the-art for heterodyne multichip modules

Organic over-the-horizon targeting for the 2025 surface fleet

Please note that this activity was not conducted in accordance with Federal, DOD, and Navy Human Research Protection RegulationsAdversarial advances in the proliferation of anti-access/area-denial (A2/AD) techniques requires an innovative approach to the design of a maritime system of systems capable of detecting, classifying, and engaging targets in support of organic over-the-horizon (OTH) tactical offensive operations in the 2025–2030 timeframe. Using a systems engineering approach, this study considers manned and unmanned systems in an effort to develop an organic OTH targeting capability for U.S. Navy surface force structures of the future. Key attributes of this study include overall system requirements, limitations, operating area considerations, and issues of interoperability and compatibility. Multiple alternative system architectures are considered and analyzed for feasibility. The candidate architectures include such systems as unmanned aerial vehicles (UAVs), as well as prepositioned undersea and low-observable surface sensor and communication networks. These unmanned systems are expected to operate with high levels of autonomy and should be designed to provide or enhance surface warfare OTH targeting capabilities using emerging extended-range surface-to-surface weapons. This report presents the progress and results of the SEA-21A capstone project with the recommendation that the U.S. Navy explore the use of modestly-sized, network-centric UAVs to enhance the U.S. Navy’s ability to conduct surface-based OTH tactical offensive operations by 2025.http://archive.org/details/organicovertheho1094545933Approved for public release; distribution is unlimited